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1
Tuttle, Denis, Jiranan Griffiths, and Anuchart Kaunnil. "Predictors of caregiver burden in caregivers of older people with physical disabilities in a rural community." PLOS ONE 17, no. 11 (November 4, 2022): e0277177. http://dx.doi.org/10.1371/journal.pone.0277177.
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Caring for an aging society is a problem facing many countries including Thailand. This cross-sectional study investigated caregiver burden and related predictive factors among 69 caregivers who had older family members with physical disabilities. Burden Scale, World Health Organization Quality of Life-Bref Thai (QOL), Patient Health Questionnaire-9 (PHQ), Barthel Activity of Daily Living Index (ADL), and Lawton-Brody Instrumental Activities of Daily Living Scale (IADL) assessments were used in addition to demographic data. Thirteen caregivers (18.8%) reported no caregiver burden, 30 (43.5%) reported low-moderate burden, 21 (30.4%) reported moderate-high burden and 5 (7.2%) reported high burden. Using Fisher’s Exact Test the factors found to be significantly associated to caregiver burden were: categorical age of the caregiver (p = .000), education level of the caregiver (p = .002), relationship to the care recipient (p = .009), categorical income level of the caregiver (p = .041), QOL of the caregiver (p = .001) and ADL status of the care recipient (p = .003). Forward stepwise linear regression model revealed three factors which were PHQ score (β = .543, p < .000), ADL score (β = -.341, p = .001) and hours of care/week (β = .227, p = .017). Future studies should focus on interventions that impact depression levels, independence with activities of living and hours of care per week.
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Meagher, Katherine A., David I. Thurnham, Stephen Beatty, Alan N. Howard, Eithne Connolly, Wayne Cummins, and John M. Nolan. "Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration." British Journal of Nutrition 110, no. 2 (December 5, 2012): 289–300. http://dx.doi.org/10.1017/s0007114512004837.
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Macular pigment (MP) is composed of lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ). The present study reports on serum response to three different MP supplements in normal subjects (n 27) and in subjects with age-related macular degeneration (AMD) (n 27). Subjects were randomly assigned to: Group 1 (20 mg L and 2 mg Z), Group 2 (10 mg L, 2 mg Z and 10 mg MZ) or Group 3 (3 mg L, 2 mg Z and 17 mg MZ). Serum carotenoids were quantified at baseline, and at 4 and 8 weeks using HPLC. Response data for normal and AMD subjects were comparable and therefore combined for analysis. We report response as the average of the 4- and 8-week concentrations (saturation plateau). Serum L increased significantly in Group 1 (0·036 μmol/l per mg (269 %); P< 0·001) and Group 2 (0·079 μmol/l per mg (340 %); P< 0·001), with no significant change in Group 3 (0·006 μmol/l per mg (7 %); P= 0·466). Serum Z increased significantly in Group 1 (0·037 μmol/l per mg (69 %); P= 0·001) and Group 2 (0·015 μmol/l per mg (75 %); P< 0·001), with no significant change in Group 3 ( − 0·0002 μmol/l per mg ( − 6 %); P= 0·384). Serum MZ increased significantly in Group 1 (0·0094 μmol/l (absolute value); P= 0·015), Group 2 (0·005 μmol/l per mg; P< 0·001) and Group 3 (0·004 μmol/l per mg; P< 0·001). The formulation containing all three macular carotenoids (Group 2 supplement) was the most efficacious in terms of achieving the highest combined concentration of the three MP constituent carotenoids in serum, thereby potentially optimising the bioavailability of these compounds for capture by the target tissue (retina).
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Visconte, Valeria, Ali Tabarroki, Edy Hasrouni, Yang Liu, Betty K. Hamilton, Craig A. Portell, Edward A. Copelan, Anjali Advani, Mikkael A. Sekeres, and Ramon V. Tiu. "Patients with SF3B1 Mutation Have Good Prognosis Even in the Presence of Other Poor Prognostic MDS Features and Have Better Outcomes During Treatment with Low Intensity Chemotherapy." Blood 120, no. 21 (November 16, 2012): 3831. http://dx.doi.org/10.1182/blood.v120.21.3831.3831.
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Abstract Abstract 3831 The discovery of mutations in components of the RNA splicing machinery has underlined the importance of this pathogenetic mechanism in MDS biology. We and others reported that mutations in SF3B1 are frequent in refractory anemia with ring sideroblasts (RARS) and RARS associated with thrombocytosis (RARS-T). We recently reported good survival outcomes in a large cohort of SF3B1 mutant patients similar to the findings of Papaemmanuil et al, NEJM< 2011. Here, we aimed to evaluate the correlation between SF3B1 mutations in association with other poor prognostic clinical and pathologic factors in MDS. We focused on a large cohort of patients with several myeloid malignancies (n=340). Patients were grouped in MDS (n=176), MDS/MPN (n=88) and secondary AML (sAML) from a previous MDS (n=76). Diseases were classified according to the 2008 WHO classification. Survival outcomes (overall survival [OS], progression free survival [PFS] and event free survival [EFS]) were defined according to MDS IWG criteria. We studied a total of 340 patients with myeloid malignancies. median age, 69 years old (range 19–92), sex (Male, n=222; females, n=118). We performed direct sequencing for SF3B1 (exon 13–16) on a large cohort of MDS, MDS/MPN and sAML patients and found 11.8% SF3B1 mutants. The outcomes of SF3B1 mutant vs WT patients were compared based on the presence of poor clinicopathologic factors associated with MDS like RBC transfusion dependence, presence of SNP-A lesions, presence of acquired somatic uniparental disomy (AS-UPD), Age ≥ 60 years, presence of reticulin fibrosis in the bone marrow. We also assessed the effects of therapies in the prognostic effect of SF3B1 mutations. We previously reported that the presence of new SNP-A lesions in myeloid malignancies including MDS and AML are associated with poor prognostic outcomes. However, the good prognostic effects of SF3B1 mutation is still apparent even in the patients with new SNP-A abnormalities (OS: 40 vs 16 mos, p=.003; PFS: 40 vs 10 mos, p=.003, 40 vs 10 mos, p=.0007. However, when analysis is limited to acquired somatic uniparental disomy defects which we recently reported as the worst lesion among SNP-A abnormalities, the good prognostic effect of SF3B1 is lost (OS: 19 vs 9 mos, p=.29, PFS: 18 vs 7 mos, p=.20, EFS: 19 vs 8 mos, p=.17). Age is an important predictor of outcomes in MDS with higher age associated with worse outcomes. SF3B1 remained predictive of good outcomes in patients ≥ 60 years of age (OS: 40 vs 16, p=.002; PFS: 40 vs 11 mos, p=.003; EFS: 40 vs 10 mos, p=.0005). Persistent RBC transfusions are also associated with inferior survival in MDS, yet SF3B1 mutant patients continued to have good outcomes (OS 34 vs 13, p=.002; PFS: 27 vs 8 mos, p=.004; EFS: 14 vs 9 mos, p=.001). Reticulin fibrosis in the bone marrow is a characteristic feature of myeloproliferative neoplasms but their presence in MDS is associated with unfavorable results, SF3B1 mutant retain their good outcomes even in the presence of reticulin fibrosis in the BM (OS: 40 vs 15 mos, p=.09; PFS: 47 vs 12 mos, p=.04; EFS: 75 vs 13 mos, p=.008). Patients screened for SF3B1 were also further stratified according to treatments received. No patients with SF3B1 mutations underwent allogeneic hematopoietic stem cell transplantation and high intensity chemotherapy specifically induction chemotherapy or high dose cytarabine. However based on treatment with LIC, SF3B1 mutant patients have better survival outcomes compared to WT patients (OS: 61 vs 17 mos, p=.004; PFS: not reached [NR] vs 7 mos; p=.009; EFS: 61 vs 10 mos, p=.001). These observed survival outcomes remain significant when patients were stratified according to disease subtypes. MDS and MDS/MPN patients treated with LIC have better outcomes if they have SF3B1 mutation (OS: 61 vs 23 mos, p=.005; PFS: NR vs 16 mos, p=.01; EFS: 61 vs 16 mos, p=.001). A high number of TET2/DNMT3A mutations are found in SF3B1 mutants. TET2/DNMT3A mutations have been previously association with improved response to hypomethylating agents which is one of the possible reasons why SF3B1 mutants treated with LIC did better than their WT counterpart. In conclusion, SF3B1 retains its favorable prognostic effect even in the face of poor prognostic factors such as RBC transfusion dependence, presence of SNP-A lesions, Age ≥ 60 years, presence of reticulin fibrosis in the bone marrow except in the presence of AS-UPD. SF3B1 mutants treated with LIC also have better outcomes. Disclosures: No relevant conflicts of interest to declare.
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Hasrouni, Edy, Valeria Visconte, Ali Tabarroki, Heesun J. Rogers, Fabiola Traina, Anna Jankowska, Yang Liu, et al. "Pathway Analysis of Molecular Mutations Can Modify Morphologic, Cytogenetic and Prognostic Risk Stratification Schemes in Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN), and Secondary Acute Myeloid Leukemia (AML)." Blood 120, no. 21 (November 16, 2012): 3791. http://dx.doi.org/10.1182/blood.v120.21.3791.3791.
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Abstract Abstract 3791 Molecular mutations of genes important in MDS pathogenesis have been identified using next generation sequencing technologies. These mutations have variable effects on prognosis: results from individual studies are conflicting, and the impact of combining mutations based on pathogenetic pathways has not been explored. Furthermore, most studies do not take into account the types of therapies received by patients (pts). We hypothesized that analyses of mutations incorporating pathways would yield more meaningful results, especially if studied in the context of therapies. We studied 340 pts with MDS (N=176), MDS/MPN (N=88) and sAML (N=76). Median age was 69 years (range, 19–92), 118 (35%) were female. Direct sequencing of 14 genes important in MDS pathogenesis originally identified using whole exome sequencing and involved in methylation (TET2/IDH1/2/DNMT3A), histone modification (ASXL1/EZH2/UTX), signaling (CBL/KRAS, NRAS, JAK2), transcription (RUNX1/TP53) and RNA splicing (SRSF2/U2AF1) was performed. Pts were classified by 2008 WHO criteria. Prognosis was assigned by IPSS (low=67, Int-1=85, Int-2=56, high=64). Karyotypes by metaphase cytogenetics (MC) and SNP-A were stratified by IPSS cytogenetic risk group (Low=82, intermediate=87, poor=106). Treatment received included high intensity (cytarabine+ anthracycline, high dose ARA-C,) (N=75), low intensity (N=124) (hypomethylating therapy, IMiDs, low dose ARA-C), and supportive therapy (N=141) (growth factors, hydroxyurea). Categorical variables were analyzed using X2 or Fischer-exact test. Overall survival (OS) and progression-free survival (PFS) were defined using IWG criteria and analyzed by Kaplan-Meier and log-rank statistics. P-values0.05 were considered statistically significant. Univariate and multivariate analyses were performed by Cox Proportional Hazards, covariates included were age, BM blasts, cytopenias, karyotype, jointly with molecular pathway data. A total of 258 mutations were detected in 158 pts. Mutations involving genes key to methylation (41 vs 37%, p=.01), and histone modification (52 vs 25%, p=.008) were more common in MDS/MPN compared to MDS pts. Mutations in methylation (37 vs 23%, p=.05), transcription (38 vs 14%, p=.01) and splicing (38 vs 17%, p=.007) were more common in MDS compared to sAML pts, and mutations of genes involved in methylation (41 vs 23%, p=.02), signaling (60 vs 7%, p=.005), histone modification (52 vs 23%, p=.004), transcription (49 vs 13%, p=.001) and splicing (45 vs 17%, p=.0005) were more frequent in MDS/MPN compared to sAML pts. Worse outcomes were noted in pts with mutations in histone modification (OS: 17 vs 21 mos, p=.04), transcription (PFS: 7 vs 13 mos, p=.02) and splicing (OS: 11 vs 23 mos, p=.01) genes. This was evident in pts with MDS who had transcription factor-related gene mutations (OS: 9 vs 30 mos, p=<.0001), splicing (PFS: 8 vs 21 mos, p=.008) and in MDS/MPN and MDS pts with histone pathway (27 vs 31 mos, p=.04) and splicing mutations (7 vs 21 mos, p=.0001). Of note, this was clearly mentioned in WHO lower-risk MDS pts with histone pathway (OS: 30 vs 39 mos, p=.01; PFS: 21 vs 32 mos, p=.05) and splicing mutations (PFS: 15 vs 28 mos, p=.003). Pts with good-risk karyotype defects had poor survival if they had histone mutations (OS: 17 vs 35 mos, p=.005; PFS: 11 vs 20 mos, p=.002) while those with intermediate-risk karyotype had worse outcomes if they had splicing mutations (OS: 10 vs 35 mos, p=.001; PFS: 7 vs 35 mos, p=.0001). The survival effects were retained even after accounting for presence of new SNP-A lesions. By IPSS, lower-risk pts had worse outcomes if they had mutations in methylation (OS: 36 vs 18 mos, p=.02), histone modification (28 vs 37 mos, p=0.02) or splicing (OS: 7 vs 17 mos, p=.04; PFS: 14 vs 28 mos, p=.04). Therapeutically, LIC treated pts had better OS if they had methylation mutations (23 vs 8 mos, p=.0009) but worse outcomes if they had transcription factor (7 vs 11 mos, p=.02) or splicing (8 vs 13 mos, p=.05) mutations. Mutations in transcription factors (OS: HR=2.9 CI: 1.58–5.13, p=.0007; PFS: HR=3.3 CI: 1.87–5.63, p=<.0001) and splicing (OS: HR=2.1, CI=1.22–3.76, p=.008; PFS: HR=2.1, CI=1.27–3.71, p=.005) remained independent predictors of poor outcomes in MDS by multivariate analysis. In conclusion, the presence of molecular pathway mutations can modify morphologic, cytogenetic and prognostic scoring schemes in MDS, MPN, AML and other hematological cancers. Disclosures: No relevant conflicts of interest to declare.
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Sasaki, Koji, Elias Jabbour, Hagop M. Kantarjian, Jorge E. Cortes, Guillermo Garcia-Manero, Gautam Borthakur, Sherry R. Pierce, Naveen Pemmaraju, Susan O'Brien, and Farhad Ravandi. "Outcome of Patients (pts) with Therapy-Related De Novo Acute Myeloid Leukemia (t-de novo AML): Single Institution Experience." Blood 124, no. 21 (December 6, 2014): 2273. http://dx.doi.org/10.1182/blood.v124.21.2273.2273.
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Abstract Background: Therapy-related myeloid neoplasms develop after cytotoxic chemotherapy or radiation therapy. The available data on the outcome of pts with t-de novo AML without antecedent history of myelodysplastic syndrome (MDS) is limited. Methods: We reviewed the records of pts with newly diagnosed AML who presented to our tertiary care center from 1/2000 to 1/2014. t-de novo AML was defined as having at least 20% blasts in bone marrow with a history of any previous cytotoxic chemotherapy or radiation therapy, and without an antecedent history of MDS. Leukemia-free survival (LFS) was defined as time from achieving complete response (CR) to relapse or death. The overall survival (OS) and LFS in pts with t-de novo AML were compared to those of with de novo AML with normal karyotype (NK) and complex karyotype (CK). Results: Among 1677 pts with newly diagnosed AML, 383 had de novo NK-AML, 218 had de novo CK-AML, and 187 had t-de novo AML. The median follow-up was 9.3 months (range; 0.2-161.0). Pt characteristics and outcomes are described in Table 1. Among the 187 pts, 69 had a history of lymphoma; 63 pts breast cancer (Ca); 10 pts colon Ca; 10 pts sarcoma; 8 pts prostate; 7 pts bladder Ca; 6 pts uterine Ca; 5 pts lung Ca; 5 pts head and neck Ca; 30 pts other type of Ca. Among the pts with t-de novo AML, 15 pts (8%) had a favorable-risk karyotype by WHO, 53 pts (28%) intermediate-risk karyotype, and 119 pts (64%) poor-risk karyotype. The median LFS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% confidence interval [CI]; 5.1-8.7), 19 months (95% CI; 13.0-25.2), and 6 months (95% CI; 9.0-13.5) (p<.001), respectively. The median OS duration in t-de novo AML, NK-AML, and CK-AML were 7 months (95% CI; 5.9-8.9), 21 months (95% CI; 16.2-25.5), and 12 months (95%CI; 10.6-13.5) (p<.001), respectively. The results of univariate (UVA) and multivariate analysis (MVA) associated with OS were summarize in Table 1. MVA identified age over 60, white blood cell count (WBC) over 10 x103/µL, thrombocytopenia below 30 x103/µL, non-favorable cytogenetic abnormalities, positive RAS mutation, and the absence of CR or CR with incomplete platelet recovery (CRp) as poor prognostic features related to OS. Conclusion: LFS and OS were shorter in patients with t-de novo AML than in those with NK-AML but did not differ significantly from patients with CK-AML. Abstract 2273. Table 1. Patient Characteristics and Outcomes t-de novo AML [n= 187] de novo AML with NK [n= 383] de novo AML with CK [n= 218] P Age at diagnosis, median (years) 64 (21-89] 63 (17-90) 67 (18-87) Prior radiation therapy, No. (%) 101 (54) 0 0 Prior chemotherapy, No. (%) 186 (99) 0 0 White blood cell count at diagnosis, median (x103/µL) 3.2 (0.2-191) 4.3 (0.2-390.0) 2.9 (0.5-278.2) Hemoglobin at diagnosis, median (g/dL) 9.1 (4.5-12.9) 9.1 (4-14.6) 9.0 (2.5-14.2) Platelet count at diagnosis, median (x103/µL) 34 (4-454) 51 (3-469) 42 (2-319) LDH at diagnosis, median (IU/L) 1359 (210-22090) 1189 (200-42000) 1274 (231-20572) Peripheral blood blast percent at diagnosis, median (%) 8 (0-98) 9.5 (0-98) 10 (0-98) Bone marrow blast percent at diagnosis, median (%) 41 (0-96) 44 (0-96) 33 (0-97) Molecular genetic abnormalities at diagnosis, No. (%) FLT3-ITD 17 (9) 96 (25) 5 (2) FLT3-D835 6 (3) 23 (6) 1 (1) NPM1 7 (4) 104 (27) 4 (2) JAK2 3 (2) 6 (2) 8 (4) RAS 17 (9) 50 (13) 8 (4) RUNX1-RUNX1T1 4 (2) 0 0 CBFb-MYH 6 (3) 0 0 Response, No. (%) <0.001 Complete response 89 (48) 237 (62) 76 (35) Complete response without platelet recovery 15 (8) 1 (0) 15 (7) 1-year LFS, (%) 33 60 27 <0.001 2-year LFS, (%) 33 52 20 <0.001 1-year OS, (%) 34 68 30 <0.001 2-year OS, (%) 24 46 13 <0.001 UVA and MVA of OS in t-de novo AML UVA MVA Hazard ratio 95% CI Age at diagnosis Age =< 60 years - Age >60 years < .001 .001 2.238 1.417-3.534 White blood cell count (WBC) (x103/µL) WBC =< 10.0 - WBC > 10.0 .002 .037 1.617 1.030-2.540 Hemoglobin (Hgb) (g/dL) Hgb >= 8 - Hgb < 8 .749 Platelet count (Plt) (x103/µL) Plt >= 30 - Plt < 30 .008 .004 1.852 1.224-2.803 LDH (IU/L) LDH =<1000 - LDH > 1000 .640 Peripheral blood blast percent (PB blast)(%) PB blast =< 10% - PB blast >10% .178 Bone marrow blast percent (BM blast) (%) BM blast =<40% - BM blast >40% .393 Cytogenetic abnormality Favorable - Non-Favorable .002 .019 5.836 1.342-25.370 FLT3-ITD Negative - Positive .768 RAS Negative - Positive .047 .003 2.576 1.367-4.856 Response CR or CRp - Non-CR or CRp <.001 .009 .331 0.145-0.757 CR - Non-CR <.001 0.903 .950 0.418-2.160 Figure 1. LFS and OS Figure 1. LFS and OS Disclosures Kantarjian: ARIAD, Pfizer, Amgen: Research Funding.
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Thomas, Jolene, Billingsley Kaambwa, Christopher Delaney, and Michelle Miller. "An evaluation of the validity of nutrition screening and assessment tools in patients admitted to a vascular surgery unit." British Journal of Nutrition 122, no. 6 (July 1, 2019): 689–97. http://dx.doi.org/10.1017/s0007114519001442.
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AbstractVascular surgery patients are nutritionally vulnerable. Various malnutrition screening and assessment tools are available; however, none has been developed or validated in vascular patients. The present study aimed to: (1) investigate the validity of four commonly administered malnutrition screening tools (Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Nutrition Risk Screen-2002 (NRS-2002) and the Mini-Nutritional Assessment – Short Form (MNA-SF) and an assessment tool (the Patient-Generated Subjective Global Assessment (PG-SGA)) compared against a comprehensive dietitian’s assessment and (2) evaluate the ability of the instruments to predict outcomes. Vascular inpatients were screened using the four malnutrition screening tools and assessed using the PG-SGA. Each was assessed by a dietitian incorporating nutritional biochemistry, anthropometry and changes in dietary intake. Diagnostic accuracy, consistency and predictive ability were determined. A total of 322 (69·3 % male) patients participated, with 75 % having at least one parameter indicating nutritional deficits. No instrument achieved the a priori levels for sensitivity (14·9–52·5 %). Neither tool predicted EuroQoL 5-dimension 5-level score. All tools except the MNA-SF were associated with length of stay (LOS); however, the direction varied with increased risk of malnutrition on the MUST and NRS-2002 being associated with shorter LOS (P=0·029 and 0·045) and the reverse with the MST and PG-SGA (P=0·005 and <0·001). The NRS-2002 was associated with increased risk of complications (P=0·039). The MST, NRS-2002 and PG-SGA were predictive of discharge to an institution (P=0·004, 0·005 and 0·003). The tools studied were unable to identify the high prevalence of undernutrition; hence, vascular disease-specific screening and/or assessment tools are warranted.
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Willasch, Andre Manfred, Christina Peters, Petr Sedlacek, Jean-Hugues Dalle, Stelios Graphakos, Akif Yesilipek, Jacek Wachowiak, et al. "Myeloablative Conditioning for First Allogeneic Hematopoietic Stem Cell Transplantation in Children with ALL: Total Body Irradiation or Chemotherapy? - a Multicenter EBMT-PDWP Study." Blood 130, Suppl_1 (December 7, 2017): 911. http://dx.doi.org/10.1182/blood.v130.suppl_1.911.911.
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Abstract Introduction: Most pediatric patients (pts) with ALL receive total body irradiation (TBI) for myeloablative conditioning of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unproven whether TBI can be replaced by chemotherapy (CHT). Methods: To compare the outcomes of TBI- versus (vs.) CHT-based conditioning, we performed a retrospective EBMT-registry based study. Children between 2 and 18 years of age (y.) after myeloablative conditioning for first allo-HSCT of bone marrow (BM) or peripheral blood SC (PBSC) from matched sibling (MSD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to consider the covariate "distribution of TBI recipients" for pts who did not receive TBI. Results: In total 3071 pts (CR1: 1504 (49%), CR2: 1567 (51%)) were included. CR1: 1045 pts (69%) received BM and 459 pts (31%) PBSC from MSD (760 (51%)) or UD (744 (49%)). CR2: 1067 pts (68%) received BM and 500 pts (32%) PBSC from MSD (675 (43%)) or UD (892 (57%)). Overall, conditioning was TBI- in 2647 (86%) and CHT-based in 424 pts (14%). Busulfan/Cyclophosphamide (Bu/Cy) and Bu/Cy/Etoposide (Bu/Cy/Eto) were the two most frequently applied CHT combinations in CR1 (68 (32%), 66 (31%)) and CR2 (68 (32%), 52 (25%)). The remaining conditionings included 5 different combinations of chemotherapeutics (other chemo). 1504 pts in CR1 were conditioned with TBI (1291), Bu/Cy/Eto (66) or other chemo (147) with a median follow-up of 4.4, 3.4 and 2.4 y. In weighted univariate analysis no significant differences were detected for LFS (5-y.-LFS, range: 62.4 to 67.5%) and relapse incidence (5-y.-RI, range: 24.0 to 29.0%). In pairwise testing, OS after Bu/Cy/Eto was significantly better compared with TBI (5-y.-OS, 78.7 vs. 66.8%, P=.006). Non-relapse mortality was significantly higher after other chemo (5-y.-NRM, 12.7%, P <.001) and TBI (12.5%, P <.001) compared with Bu/Cy/Eto (3.5%). Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 65.8 vs. 12-18 y. 58.0%, P=.009), y. of HSCT (2008-2012 65.9 vs. 2000-2007 59.6%, P=.035) and donor type (MSD 64.9 vs. UD 59.5%, P=.007). RI was influenced by y. of HSCT (5-y.-RI, 2008-2012 21.7 vs. 2000-2007 26.8%. P=.026). OS was influenced by age (5-y.-OS, 2-11 y. 72.7 vs. 12-18 y. 61.7%, P <.001) and donor type (MSD 70.1 vs. UD 65.0%, P=.002). NRM was influenced by age (5-y.-NRM, 2-11 y. 9.0 vs. 12-18 y. 18.0%, P <.001), donor sex (male 10.9 vs. female 16.6%, P=.007) and donor type (MSD 8.5 vs. UD 17.8%, P <.001). In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR1 was associated with lower RI (HR 0.70, P=.047), lower OS (HR 1.54, P=.017) and higher NRM (HR 3.97, P <.001). 1567 pts in CR2 were conditioned with TBI (1356), Bu/Cy (68) or other chemo (143) with a median follow-up of 3.9, 3.2 and 3.1 y. In weighted univariate analysis highly significant differences of survival were detected. TBI-based conditioning resulted in highest 5-y.-LFS of 52.2% (Bu/Cy 41.0%, other chemo 18.4%, P <.001), lowest 5-y.-RI of 33.2% (Bu/Cy 38.3%, other chemo 55.3%, P <.001), highest 5-y.-OS of 56.1% (Bu/Cy 43.6%, other chemo 23.6%, P <.001) and lowest 5-y.-NRM of 14.6% (Bu/Cy 20.8%, other chemo 26.2%, P <.001). Other significant influencing factors on LFS were age (5-y.-LFS, 2-11 y. 53.5 vs. 12-18 y. 43.0%, P <.001), y. of HSCT (2008-2012 53.3 vs. 2000-2007 47.3%, P=.009) and SC source (BM 53.3 vs. PBSC 42.5%, P <.001). RI was influenced by SC source (5-y.-RI, BM 33.1 vs. PBSC 36.6%, P=.024). OS was influenced by age (5-y.-OS, 2-11 y. 59.3 vs. 12-18 y. 46.8%, P <.001), y. of HSCT (2008-2012 58.6 vs. 2000-2007 52.0%, P=.005), donor type (MSD 58.5 vs. UD 52.6%, P <.024) and SC source (BM 58.4 vs. PBSC 47.5%, P <.001). NRM was influenced by age (5-y.-NRM, 2-11 y. 12.5 vs. 12-18 y. 22.3%, P <.001), donor type (MSD 10.2 vs. UD 19.8%, P <.001) and SC source (BM 13.6 vs. PBSC 20.8%, P <.001). In weighted multivariable Cox model clustered on EBMT centers, TBI-based conditioning in CR2 was associated with higher LFS (HR 0.48, P <.001), lower RI (HR 0.48, P <.001) and higher OS (HR 0.51, P <.001). Conclusion: Conditioning by TBI demonstrated clear superiority in comparison to CHT for children with ALL undergoing HSCT in CR2. For pts in CR1, TBI- and CHT-based conditioning showed similar results. This retrospective data is currently re-evaluated in a prospective, randomized, international trial (ALL SCTped 2012 FORUM). Disclosures Büchner: Novartis Pharmaceuticals Corporation: Consultancy; Pfizer: Consultancy. Veys: Bellicum: Research Funding; Servier: Research Funding. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.
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Pham, Hien Van, Nhat Van Tran, Truc Thanh Thai, and Huong Thi Bich Tran. "Gender and age differences in KDIGO treatment targets among people on maintenance hemodialysis: Findings from a tertiary hospital in Vietnam." Medicine 103, no. 4 (January 26, 2024): e37088. http://dx.doi.org/10.1097/md.0000000000037088.
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Age and gender are 2 important factors in the treatment of end-stage chronic kidney disease with hemodialysis. Understanding the influence of these 2 factors can help optimize treatment for this population. This study evaluated gender and age differences in achievement of Kidney Disease Improving Global Outcomes (KDIGO) treatment targets. A cross-sectional study was conducted on 324 chronic hemodialysis patients at a tertiary referral hospital in Ho Chi Minh City, Vietnam. KDIGO treatment targets included treatment time, prescribed Qb, treated blood volume, urea reduction ratio, spKt/V, hemoglobin, albumin, phosphorus, calcium, and parathyroid hormone. Men had significantly higher treatment time (P = .003), prescribed Qb (P = .037) and hemoglobin (P = .031) than women. However, women had significantly higher treated blood volume (P < .001), spKt/V (P < .001) and URR (P < .001). No significant difference between men and women was found in albumin, calcium, phosphorus, and parathyroid hormone. Based on KDIGO treatment targets, women had a significantly higher rate of achievement of spKt/V > 1.2 (91.4% vs 80.7%, P = .005) and URR ≥ 70% (77.0% vs 54.7%, P < .001) than men. A significantly higher rate of treated volume of ≥ 1 L/kg/BW, and phosphorus 2.5 to 4.6 mg/dL was found in women (90.0% and 40.2%) compared to men (68.7% and 27.3%). In contrast, men had a significantly higher rate of prescribed Qb ≥ 300 mL/min (26.7% vs 12.6%, P = .001), albumin ≥ 40 g/L (36.7% vs 26.4%, P = .047), and Hb > 12 g/dL (22.0% vs 11.5%, P = .011) than women. There was no significant difference between men and women in the rate of calcium 8.4 to 10.4 mg/dL, and parathyroid hormone 150 to 600 pg/mL. These differences were not the same across 4 age categories (<60, 60–69, 70–79, and ≥ 80). Most of the differences above were among patients aged < 60 and 60 to 69 years. Although men had higher satisfactory treatment parameters than women, based on KDIGO treatment targets, women received hemodialysis more effectively than men. Treatment targets for patients on hemodialysis should consider gender and age differences.
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Höbaus, Clemens, Gerfried Pesau, Bernhard Zierfuss, Renate Koppensteiner, and Gerit-Holger Schernthaner. "Angiogenin—A Proposed Biomarker for Cardiovascular Disease—Is Not Associated With Long-Term Survival in Patients With Peripheral Artery Disease." Angiology 72, no. 9 (March 29, 2021): 855–60. http://dx.doi.org/10.1177/00033197211004393.
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We evaluated angiogenin as a prospective biomarker in peripheral artery disease (PAD) patients with and without claudication symptoms. A pilot study suggested an elevation of angiogenin in critical limb ischemia. However, in PAD patients, the predictive value of angiogenin has not yet been evaluated. For this purpose, 342 patients with PAD (age: 69 ± 10 years, 34.5% women) were followed-up for 7 years in a cross-sectional study. Angiogenin was measured by enzyme-linked immunosorbent assay. All-cause and cardiovascular mortality were analyzed by Cox regression. Angiogenin levels were higher in men ( P = .001) and were associated with patient waist-to-hip ratio ( P < .001), fasting triglycerides ( P = .011), and inversely with estimated glomerular filtration rate ( P = .009). However, angiogenin showed no association with age, characteristics of diabetes, markers of lipid metabolism, or C-reactive protein. Angiogenin did not correlate with markers of angiogenesis such as vascular endothelial growth factor, angiopoietin-2, or tie-2. Furthermore, angiogenin was not associated with PAD Fontaine stages or with patient ankle-brachial index in addition to all-cause mortality (hazard ratio [HR] = 1.09 [95% CI: 0.89-1.34]) or cardiovascular morality (HR = 1.05 [0.82-1.35]). These results suggest that angiogenin does not provide further information regarding outcome prediction in patients with PAD.
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Guglielmelli, Paola, Chiara Maccari, Manjola Balliu, Giuseppe Gaetano Loscocco, Naseema Gangat, Alessandro Atanasio, Paolo Cicogna, et al. "Homozygosity of the JAK2 46/1 or GGCC Haplotype Contributes to Phenotype and Outcome Diversity Among Patients with Polycythemia Vera." Blood 144, Supplement 1 (November 5, 2024): 1795. https://doi.org/10.1182/blood-2024-198891.
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Background: The JAK2 46/1, also referred to as the GGCC, haplotype, is represented by 4 main SNPs spanning a region of 250kb in chr9 including the JAK2 gene, that are in complete linkage disequilibrium. The GGCC haplo was found to confer susceptibility to JAK2 mutated myeloproliferative neoplasms (MPN) (Jones AV, 2009; Olcaydu D, 2009; Kilpivaara O, 2009) while association with JAK2-wildtype MPN remains controversial (Pardanani A, 2010; Jones AV, 2010; Guglielmelli P, 2010; Trifa A, 2016). The GGCC haplo was also found enriched in MPN pts with splancnic vein thrombosis (SVT) (Smalberg JH, 2011), and to correlate with higher JAK2V617F variant allele frequency (VAF) (Alvarez-Larran, A, 2012). Nullizigosity for GGCC haplo was associated with reduced survival (OS) in pts with myelofibrosis (MF) (Tefferi A, 2019), but no information on the impact of GGCC haplo status with phenotype and outcome in PV is available. Aim: To assess the clinical correlates and the prognostic significance of GGCC haplo status in a large cohort of pts with PV. Pts and Methods: A total of 399 PV pts, all JAK2V617F mutated, diagnosis revised according to 2022 ICC criteria, were genotyped for 46/1 haplotype by PCR allele discrimination with rs12343867 (with the “C” allele standing for 46/1 haplotype). Results: A total of 301 pts (75.4%) had the C allele, of which 143 (47.5%) were CC homo and 158 (52.5%) CT hetero; 98 (24.6%) were nullizygous for GGCC (TT). Since preliminary analysis disclosed no significant difference between CT and TT haplotype for all variables considered, homozygous CC pts were compared to TT+CT. The CC haplotype was associated with higher leukocytes (median 11.3x10e9/L vs 9.6, p<.001), higher hemoglobin (18.4 g/dL vs 17.5, p<.001), lower platelets (441x10e9/L vs 514, p=.002) more aquagenic pruritus (51.8% vs 33.2%, p=.001), and higher JAK2VAF (60.8+-24.8% vs 36.8+-19.7%, p<.001) at diagnosis. Pts with a VAF >50% were 69% in CC versus 24.1% in TT+CT pts (p<.001). ASXL1 mutations were enriched among CC pts (20.3% vs 9.4%, p=0.04), otherwise no difference regarding additional myeloid mutations was noted. All above differences remained significant when considering CC versus TT and CT separately. More pts with CC haplotype suffered from venous thrombosis (VT) during the FU (16.1% vs 4.3%, p<.001), no difference was noted for arterial thrombosis nor for splancnic vein thrombosis. VT-FS by Kaplan Meyer was significantly shorter (p<.001) in CC pts; the rate of VT at 5, 10, 15y after diagnosis, was 5.5%, 12%, 20.2% for CC versus 2.6%, 3.4%, 6.4% for TT+CT, respectively (all p<.001). In multivariable analysis, including JAK2VAF >50%, age >60y, history of VT, WBC >15x10e9/L, only CC haplo remained significant (HR 3.6, 95%CI 1.4-9.5, p=.009). Progression to post-PV MF occurred in 81 pts (20.3%), significantly more among CC (n=45, 31.5%) than TT+CT (n=36; 14.1%; p<.001). Myelofibrosis-FS was significantly shorter in CC vs other genotypes (p=.02). However, in multivariable analysis, only BM fibrosis G1 remained significant (HR 3.2, 1.7-5.9; p<.001). Evolution to blast-phase occurred in 13 pts (3.2%), 9 (6.3%) with CC haplo vs 4 TT+CT (1.6%; p=.01). During the follow-up, 102 pts (25.5%) died, 50 (35%) CC and 52 TT+CT (20.3%; p=.001). In multivariable analysis, including MIPSS-PV variables (Tefferi A 2020), the CC haplo remained significant (HR 1.8, 1.04-3.2, p=.03) together with age (HR 3.0, 1.6-5.7; p<.001), WBC (HR 2.6, 1.3-4.8; p=.004), and thrombosis history (HR 1.9, 1.0-3.7; p=.03). Conclusions. Homozygosity for the 46/1 or CC haplotype contributes to the phenotype diversity of PV, in part possibly mediated by associated higher JAK2V67F VAF, and predicts for incident VT and shorter OS. Supported by AIRC, 21267; MIUR,2022F4WMR3; IHM, PNRR-MAD-2022-12376695
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Sasaki, Koji, Ildefonso Ismael Rodriguez-Rivera, Hagop M. Kantarjian, Susan O'Brien, Elias Jabbour, Gautam Borthakur, Farhad Ravandi, Michael J. Burke, Patrick A. Zweidler-McKay, and Jorge E. Cortes. "Correlation of Lymphocyte Count with Treatment Response to Tyrosine Kinase Inhibitors in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase." Blood 124, no. 21 (December 6, 2014): 4538. http://dx.doi.org/10.1182/blood.v124.21.4538.4538.
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Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.
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Kurochkin, Andrii, and Yuliia Moskalenko. "ANALYSIS OF THYROID CANCER INCIDENCE AND MORTALITY TRENDS AMONG THE RESIDENTS OF THE SUMY REGION." Eastern Ukrainian Medical Journal 10, no. 4 (2022): 322–32. http://dx.doi.org/10.21272/eumj.2022;10(4):322-332.
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Introduction. Thyroid cancer ranks ninth in the structure of malignant neoplasms. Since the 1980s, most countries in the world have seen a rapid increase in the incidence rate and a relatively stable or even decreasing mortality rate. The objective of our study was to analyze the thyroid cancer morbidity and mortality trends in the Sumy region during 2014–2021, to study the prevalence of histological variants and sex-age-specific characteristics, and to compare them with all-Ukrainian and global data. Study results. According to the National Cancer Registry of Ukraine, 24,626 people were diagnosed with thyroid cancer between 2014 and 2021, including 4,556 men (18.5%) and 2,0070 women (81.5%). On average, 3078.25 ± 136.15 people were diagnosed per year. The incidence rate among women is 3.8 times higher than among men. The average incidence rate in Ukraine in 2014–2021 was 6.5 per 100,000 population, while in the Sumy region – 8.9 per 100,000 population. The average mortality rates among residents of the Sumy region and Ukraine did not differ and amounted to 0.4 per 100,000 population. A distinctive feature was represented by the lower male and higher female mortality rates in the Sumy region compared to all-Ukrainian indicators (0.2 versus 0.3 per 100,000 population and 0.6 versus 0.4 per 100,000 population, respectively). The study of histological types of thyroid malignancies demonstrated that papillary variant was most common (70.5 to 81.9%). The specific share of follicular cancer ranged from 12.8 to 19.2%. The medullary variant occured much less often – in 1.5 to 4.6% of cases, while undifferentiated and squamous cell cancer was extremely rare (0.2 to 3.3% of cases). In Buryn district, Velyka Pysarivka district, Konotop district, Krasnopillia district, Krolevets district, Lebedyn district, Nedrygailiv district, Putyvl district, Sumy district, Trostyanets district and the city of Sumy, a significantly higher incidence rate was observed. Women aged 50–64 and men aged 55–69 are most often affected in Ukraine. The highest mortality rate is reported for the age range of 70–84 years for both males and females. Conclusions. During 2014–2021, the incidence and mortality rates among the population of Ukraine remained at a stable level and were lower compared to global indicators. Since 2017, the Sumy region has been presenting with a decrease in the incidence rate, which corresponds to European trends. In the Sumy region, papillary thyroid cancer remains the most common histological variant. In general, the shares of papillary, follicular, medullary, and anaplastic cancers are consistent with the European figures. In general, the age trends in Ukraine and other countries of the world are similar.
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Chaves, Fernando, Bethany Tierno, and Dongsheng Xu. "Neutrophil Volume Distribution Width: A New Automated Hematologic Parameter for Acute Infection." Archives of Pathology & Laboratory Medicine 130, no. 3 (March 1, 2006): 378–80. http://dx.doi.org/10.5858/2006-130-378-nvdwan.
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Abstract Context.—The number of band forms and immature neutrophils increases during acute bacterial infection. However, the determination of band counts and other neutrophil morphologic changes, such as the presence of toxic granulation, toxic vacuolization, and Dohle bodies in the cytoplasm, is labor intensive and time consuming, as it requires manual examination by an experienced medical technologist. Objective.—To investigate the value of the neutrophil volume distribution width (NDW), generated by VCS technology of the Coulter LH 750 hematology analyzer, as an additional predictor of acute infection. Design.—Total white blood cell count, percentage of neutrophils, and NDW data from 70 patients with positive blood cultures for bacteria and from 35 age-matched control subjects were retrospectively analyzed. Results.—A significant increase in the NDW was observed in the bacteremic patients compared with the controls (24.7 ± 4.5 vs 19.0 ± 1.5; P < .001). Such increase was observed even in patients with white blood cell counts less than 11 000/μL (23.0 ± 5.6 vs 19.0 ± 1.5; P < .001) or with percentages of neutrophils less than 85% (24.0 ± 4.9 vs 19.0 ± 1.5; P < .001). The more dramatic increases were seen in patients with leukocytosis (25.7 ± 3.2, P < .001) or with neutrophilia (25.9 ± 3.4, P < .001). Using an NDW cutoff of 23, a 100% specificity and a 69% sensitivity were achieved. Conclusions.—As a quantitative parameter, the NDW has potential for use as an additional indicator for diagnosing acute infection.
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Yalniz, Fevzi F., Rima M. Saliba, Orhan K. Yucel, Guillermo Garcia-Manero, Jeremy Ramdial, Uday Popat, Stefan O. Ciurea, et al. "Somatic Mutations Improve Risk Classification By Cytogenetic Abnormalities in Patients with Myelodysplastic Syndrome after Hematopoietic Stem Cell Transplantation." Blood 134, Supplement_1 (November 13, 2019): 512. http://dx.doi.org/10.1182/blood-2019-125937.
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Background: Hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for patients with myelodysplastic syndrome (MDS) but disease progression after HSCT remains a major reason for failure after transplant. Identification of risk factors for progression of MDS after HSCT would allow to identify target population for early initiation of preventive treatments to improve outcomes. Methods: Patients with a diagnosis of MDS who received first HSCT between 2013 and 2018 with available pre-transplant genetic profile obtained from next generation sequencing of genes were included for the retrospective analysis. Cytogenetic findings were categorized by the revised International Prognostic Scoring System (R-IPSS). Primary outcome of interest was risk of disease progression. Classification and regression tree (CART) analysis was performed to evaluate independent predictors on multivariate analysis using standard methods. Results: Of 378 MDS patients transplanted within the study period, 225 were eligible to be included in this analyses. As shown in the table 1, the study cohort was high risk; cytogenetic risk groups were very-poor and poor in 50 (23%) and 32 (15%) patients, respectively. At least one pathogenic mutation was identified in 215 (91%) of patients prior to transplant. Most frequently mutated genes included, TP53 (24%, 54/225), RAS pathway genes (NRAS, KRAS, FLT3, PTPN11 and KIT) (20%, 44/225), TET2 (16%, 37/172), ASXL1 (12%, 27/172) and DNMT3A (11%, 25/200). In our cohort, patients with very-poor cytogenetics had a high frequency of TP53 mutations (73%), and TP53 mutations occurred almost exclusively in patients with very-poor cytogenetics (76% v 7%; P < .001). That makes those two groups almost inseparable from each other. The median follow-up in 121 (54%) survivors was 24 months (range, 1.8 to 74 months). Of the 225 patients, 65 (29%) had disease progression after HSCT, with a median of 154 days to progression (range, 28 to 1196). By univariate analyses, presence of TP53 (HR, 3.2; CI, 1.9-5.4; P<.001), DNMT3A (HR, 2.6; CI, 1.5-4.7; P=.001), RAS pathway mutations (HR, 2.01; CI, 1.2-3.4; P=.01), therapy related MDS (HR, 2.05; CI, 1.2-3.5; P=.008), very poor risk cytogenetics (HR, 3.4; CI, 1.9-6.3; P<.002), and use of post-transplant cyclophosphamide (PTCy) (HR, 0.5; CI, 0.3-0.96; P=.003) were significant predictors of progression rate. As previously mentioned, we used CART analysis to evaluate independent predictors of progression. The results demonstrated that given the significant overlap with TP53 and very poor cytogenetics, when both variables were forced into the model, only very poor cytogenetics remained significant for progression. Based on CART analysis, 4 mutually exclusive risk groups for progression were identified (Figure 1): high risk (very poor risk cytogenetics or DNMT3Amut), intermediate risk (good, intermediate or poor risk cytogenetics/RAS-pathmut/DNMT3Awt), low risk (poor risk cytogenetics/RAS-pathwt /DNMT3Awt) and a very low risk group (very good, good or intermediate risk cytogenetics/RAS-pathwt /DNMT3Awt). The correlation between R-IPSS based cytogenetic risk and our identified risk groups is shown in table 2. This illustrates how the addition of molecular data upstaged 25% of the patients to a higher risk category as well as downstaged 23% of the patients to a lower risk category for disease progression when compared to the original R-IPSS classification. The cumulative incidence of disease progression at 2 years was 6% (reference), 26% (P=.005), 42% (P<.001) and 56% (P<.001) in very-low, low, intermediate and high risk groups, respectively (Figure 2). Within the risk groups identified, progression incidence was comparable by conditioning intensity and the use of PTCy. The actuarial 2-year progression-free survival for the defined 4 risk groups was, 69% (reference), 48% (HR, 2; P=.04), 38% (HR, 2.2; P=.009), 22% (HR, 3.2; P<.001) and 14% (HR, 4.8; P<.001), in very-low, low, intermediate and high-risk groups, respectively. Non-relapse mortality was similar across the identified risk groups. Conclusion: The proposed model, by incorporating DNMT3A and RAS pathway molecular mutation status to cytogenetic risk per R-IPSS, improves upon the classification of risk groups and enables the physician to better risk stratify and predict likelihood of progression after transplantation. Disclosures Garcia-Manero: Amphivena: Consultancy, Research Funding; Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding. Popat:Bayer: Research Funding; Incyte: Research Funding; Jazz: Consultancy. Ciurea:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees, Other: stock holder; Spectrum: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; MolMed: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Jazz: Consultancy; Pfizer: Honoraria; Kite: Honoraria; Amgen: Research Funding. Bashir:Imbrium: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; StemLine: Research Funding; Acrotech: Research Funding; Celgene: Research Funding. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; Sanofi-Genzyme: Research Funding. Oran:Astex pharmaceuticals: Research Funding; AROG pharmaceuticals: Research Funding.
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Sada, Fatos, Paola Chivers, Sokol Cecelia, Sejdi Statovci, Kujtim Ukperaj, Jeffery Hughes, and Kreshnik Hoti. "Parental Assessment of Postsurgical Pain in Infants at Home Using Artificial Intelligence–Enabled and Observer-Based Tools: Construct Validity and Clinical Utility Evaluation Study." JMIR Pediatrics and Parenting 7 (December 3, 2024): e64669. https://doi.org/10.2196/64669.
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Background Pain assessment in the infant population is challenging owing to their inability to verbalize and hence self-report pain. Currently, there is a paucity of data on how parents identify and manage this pain at home using standardized pain assessment tools. Objective This study aimed to explore parents’ assessment and intervention of pain in their infants at home following same-day surgery, using standardized pain assessment tools. Methods This prospective study initially recruited 109 infant boys undergoing circumcision (same-day surgery). To assess pain at home over 3 days after surgery, parents using iOS devices were assigned to use the PainChek Infant tool, which is a point-of-care artificial intelligence–enabled tool, while parents using Android devices were assigned to use the Observer-Administered Visual Analog Scale (ObsVAS) tool. Chi-square analysis compared the intervention undertaken and pain presence. Generalized estimating equations were used to evaluate outcomes related to construct validity and clinical utility. Receiver operating characteristic analysis assessed pain score cutoffs in relation to the intervention used. Results A total of 69 parents completed postsurgery pain assessments at home and returned their pain diaries. Of these 69 parents, 24 used ObsVAS and 45 used PainChek Infant. Feeding alone and feeding with medication were the most common pain interventions. Pain presence over time reduced. In the presence of pain, an intervention was likely to be administered (χ22=21.4; P<.001), with a medicinal intervention being 12.6 (95% CI 4.3-37.0; P<.001) times more likely and a nonmedicinal intervention being 5.2 (95% CI 1.8-14.6; P=.002) times more likely than no intervention. In the presence of intervention, score cutoff values were ≥2 for PainChek Infant and ≥20 for ObsVAS. A significant effect between the use of the pain instrument (χ21=7.2, P=.007) and intervention (χ22=43.4, P<.001) was found, supporting the construct validity of both instruments. Standardized pain scores were the highest when a medicinal intervention was undertaken (estimated marginal mean [EMM]=34.2%), followed by a nonmedicinal intervention (EMM=23.5%) and no intervention (EMM=11.2%). Similar trends were seen for both pain instruments. Pain was reduced in 94.5% (224/237) of assessments where parents undertook an intervention. In 75.1% (178/237) of assessments indicative of pain, the score changed from pain to no pain, with PainChek Infant assessments more likely to report this change (odds ratio 4.1, 95% CI 1.4-12.3) compared with ObsVAS assessments. Conclusions The use of standardized pain assessment instruments by parents at home to assess pain in their infants can inform their decision-making regarding pain identification and management, including determining the effectiveness of the chosen intervention. In addition to the construct validity and clinical utility of PainChek Infant and ObsVAS in this setting, feeding alone and a combination of feeding with medication use were the key pain intervention strategies used by parents.
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Arun, Banu, Soley Bayraktar, Diane D. Liu, Angelica M. Gutierrez Barrera, Deann Atchley, Lajos Pusztai, Jennifer Keating Litton, et al. "Response to Neoadjuvant Systemic Therapy for Breast Cancer in BRCA Mutation Carriers and Noncarriers: A Single-Institution Experience." Journal of Clinical Oncology 29, no. 28 (October 1, 2011): 3739–46. http://dx.doi.org/10.1200/jco.2011.35.2682.
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Purpose To compare the pathologic complete response (pCR) rate and relapse-free survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2 mutations. Patients and Methods A total of 317 women who underwent BRCA genetic testing and were treated with NST for breast cancer between 1997 and 2009 were included in the study. The Kaplan-Meier product-limit method was used to estimate RFS and OS rates. Logistic regression models were fit to determine the associations between BRCA status, pCR, and survival. Results Fifty-seven (18%) and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2 carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P = .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P = .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001) remained as independent significant predictors for a pCR. At a median follow-up of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No significant differences were noted in survival outcomes with respect to BRCA status and type of NST received. However, among BRCA1 carriers, patients who achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than patients who did not. Conclusion BRCA1 status and ER negativity are independently associated with higher pCR rates in patients with breast cancer. Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast cancers.
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Riechelmann, Rachel P., Lisa Wang, Aoife O'Carroll, and Monika K. Krzyzanowska. "Disclosure of Conflicts of Interest by Authors of Clinical Trials and Editorials in Oncology." Journal of Clinical Oncology 25, no. 29 (October 10, 2007): 4642–47. http://dx.doi.org/10.1200/jco.2007.11.2482.
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Purpose There is concern that financial relationships between sponsors and investigators may bias research results. Our objective was to evaluate the epidemiology of conflicts of interest (COIs) among authors of clinical trials and editorials in oncology and the relationship between COI disclosure and source of funding. Methods We did a cross-sectional survey of clinical trials and editorials of anticancer agents and supportive care medications published in the Journal of Clinical Oncology (JCO) during a 1-year period. Results Of 1,533 articles published in JCO between January 1, 2005, and January 31, 2006, 332 met our inclusion criteria; 289 (87%) were clinical trials, and 43 (13%) were editorials. The pharmaceutical industry entirely or partially funded 44% of the clinical trials. At least one COI was disclosed in 69% of clinical trials and 51% of editorials. The most common types of COI reported by authors were consultancy fees, honoraria, and research funds. The highest monetary levels of interest reported by authors were for research grants, but the majority of authors with COIs received less than US$10,000. In multivariable analysis, authors of clinical trials conducted in North America (North America v Europe: odds ratio [OR] = 2.9, P = .002) and authors of trials funded entirely (industry only v nonprofit: OR = 13.8, P < .001) or partially (both industry and nonprofit v nonprofit only: OR = 5.8, P < .001) by industry were more likely to report personal COIs. Conclusion COIs are common in clinical cancer research and usually take the form of consultancy fees, honoraria, and research funds. Source of study funding was significantly associated with COI disclosure.
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Sidiqi, M. Hasib, Mohammed A. Aljama, Francis K. Buadi, Rahma M. Warsame, Martha Q. Lacy, Angela Dispenzieri, David Dingli, et al. "Stem Cell Transplantation for Light Chain Amyloidosis: Decreased Early Mortality Over Time." Journal of Clinical Oncology 36, no. 13 (May 1, 2018): 1323–29. http://dx.doi.org/10.1200/jco.2017.76.9554.
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Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.
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Vardanyan, A. V., M. V. Shapina, A. V. Poletova, and S. I. Achkasov. "Risk factors for postoperative complications after surgery in complicated Crohn’s disease." Hirurg (Surgeon), no. 2 (February 1, 2021): 44–52. http://dx.doi.org/10.33920/med-15-2102-06.
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Aim: to improve results of the surgical treatment of Crohn’s disease. Patients and Methods: 162 patients were included. 69 (42,6 %) — received preoperative conservative treatment. Ileocecal resection was performed in 148 (91,4 %), in 5 (3,1 %) cases — part of jejunum resection, ileum resection — in 3 (1,8 %) patients and right hemicolectomy — 6 (3,7 %). Stoma formation was in 104 (64,2 %) patients. Complications were registered in 25 (15,4 %) cases. Results: in univariant analysis it was found that young age up to 40 years, male gender and short operative time ( 150 min) are the predictors (р = 0,03, р = 0,03 и р = 0,02, respectively) to noncomplicated postoperative period (reduce risk in 10, 5 и 10 fold, respectively). The absence of conservative treatment before surgery increased the complications’ rate more than 3 times comparing to patients who received therapy (OR 3,2 CI 95 % 0,1–11,45; р = 0,06), but we failed to get significance, that is why multivariant analysis was carried out to see the influence of all clinical factors on non-treated patients. Significance was found in all models. Conclusion: male gender (OR 0,2 CI 95 % 0,01–2,02; р = 0,02), the age younger than 40 (OR 0,1 CI 95 % 0,02–0,9; р = 0,03) and the duration of the operation less than 150 minutes (OR 0,1 CI 95 % 0,01–2,02; р = 0,03) is associated with the reduction of complications in the postoperative period. Preoperative conservative treatment during 3 months allows to decrease the rate of complications to 3,5 times (OR 3,5 CI 95 % 1,2–9,8; р = 0,01) and risk of the stoma formation — to 7 times (χ2 = 7,56; р = 0,006).
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Payne, Nancy, Norman Gledhill, Peter T. Katzmarzyk, Veronica Jamnik, and Steven Ferguson. "Health Implications of Musculoskeletal fitness." Canadian Journal of Applied Physiology 25, no. 2 (April 1, 2000): 114–26. http://dx.doi.org/10.1139/h00-008.
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Although it is well documented that physical activity participation can bring about improvements in musculoskeletal fitness, related health implications have only been substantiated in the elderly. Currently, interpretations of the results of musculoskeletal fitness appraisals for the general population are based largely on an intuitive belief that enhanced musculoskeletal fitness is associated with higher levels of health throughout adulthood. Musculoskeletal fitness was measured in 312 females and 259 males aged 15-69 years. Health levels were determined using two previously validated questionnaires and expressed as composite health scores derived from principal components analysis. Grip strength, push strength, pull strength, push-ups, and trunk forward flexion were significant predictors of health scores after controlling for the potentially confounding effects of gender, age, aerobic fitness, waist circumference, and smoking status. These findings indicate that musculoskeletal fitness is related to health in males and females aged 15 to 69 years. Key Words: health-related fitness, fitness assessment, muscular strength, muscular endurance, trunk flexibility
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Levi, Amelia R., Marine Coste, Ethan Warshowsky, Neil V. Shah, Nishant Suneja, Jeffrey M. Schwartz, and Valery Roudnitsky. "Cracking the Hip: Does Protocol Matter? A Retrospective Cohort Study Investigating the Effect of Protocol Implementation." Geriatric Orthopaedic Surgery & Rehabilitation 13 (January 2022): 215145932210766. http://dx.doi.org/10.1177/21514593221076614.
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Introduction Approximately 300 000 hip fractures occur annually in the USA in patients >65 years old. Early intervention is key in reducing morbidity and mortality. Our institution implemented a collaborative hip fracture protocol, streamlining existing processes to reduce time to OR (TTO) and hospital length of stay (LOS). Our aim was to determine if this protocol improved these outcomes. Study Design We conducted a retrospective cohort study using our level-1 trauma center’s trauma registry, comparing outcomes for patients >60 years old with isolated hip fractures pre-and post-hip protocol implementation in May 2018. Our primary outcomes were TTO and in-hospital mortality. Secondary outcomes included LOS and postoperative complications. Univariate analysis was done using chi-square and T-test. Results We identified 176 patients with isolated hip fractures: 69 post- and 107 pre-protocol. Comparing post- to pre-protocol, TTO decreased by 18hrs (39 vs 57h; P = .013) and patients had fewer postoperative complications (9 vs 23%; P = .016) despite post-protocol patients being more likely to have diabetes (42 vs 27%, P < .05), elevated BMI (22 vs 25; P < .001), and to be current smokers (9 vs 2%; P < .05). LOS and in-hospital mortality also decreased (11 vs 20d; P = .312, 4.3 vs 7.5%; P = .402). Post-protocol patients were more likely to go to the OR within 24hrs of presentation (39 vs 16%; P < .001) and to go straight from ED to OR (32 vs 4%; P < .001). Conclusion TTO, LOS, and postoperative complications for isolated hip fracture patients were lower post-protocol. Though not all statistically significant, this trend indicates that the protocol was helpful in improving hip fracture outcomes but may require further improvement and institution-wide education.
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Henry, David H., Naomi V. Dahl, Michael Auerbach, Simon Tchekmedyian, and Leslie R. Laufman. "Intravenous Ferric Gluconate (FG) for Increasing Response to Epoetin (EPO) in Patients with Anemia of Cancer Chemotherapy - Results of a Multicenter, Randomized Trial." Blood 104, no. 11 (November 16, 2004): 3696. http://dx.doi.org/10.1182/blood.v104.11.3696.3696.
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Abstract A significant proportion of cancer patients receiving chemorx will present with or develop anemia. The cause of this anemia is often the inflammatory cytokine-mediated anemia of chronic disease associated with cancer and/or chemorx. We conducted a prospective randomized controlled multicenter trial in anemic cancer patients on chemorx to see if no iron, oral iron, or IV iron, affects Hb response to EPO. Major inclusion criteria: pt about to start cycle of chemorx, eligible for EPO therapy, Hb <11 g/dL, with ferritin > 100 ng/mL and/or transferrin saturation (TSAT) >15%. Major exclusion criteria: recent transfusion, EPO or IV iron use, active infection, anemia from other causes. All pts received 40,000 U epoetin alfa SQ/Wk for first 4 wks, after which dose adjustments permitted for remainder of study period. All pts received cytotoxic chemorx. Pts returned weekly for 8-week treatment period with follow-up visits at wks 10 and 12. Safety population includes all pts exposed to study drug (n=187). Intent-to-treat (ITT) population is pts with at least 1 post-baseline Hgb evaluation prior to transfusion (n=180). Evaluable population consists of ITT pts with no major protocol deviations, who completed ≥7 weeks of the study, received at least 4 doses of EPO, and according to group, ≥ 7 doses of FG, or ≥67% of oral Fe (n=129). Treatment groups compared using ANCOVA model with multiple comparison adjustment. 187 Pts (69% female, mean age 64.4 yrs) were randomized to: no Fe, PO FeSO4 325 mg tid, or FG 125 mg iv weekly for 8 wks. Most common cancers were lung (29.9%) and breast (18.2%). There were no significant differences between groups in mean baseline Hb (10.2g/dL), TSAT (31.3%), serum ferritin (421 ng/mL), reticulocyte hemoglobin content (CHr, 34.2 pg). 95% of pts had baseline ferritin >100ng/mL. Efficacy results are presented for the Evaluable population. Oral iron compliance was excellent at 93.3% of tablets dispensed. 73% of the FG group achieved a Hb increase ≥2g/dL vs 46% for oral iron (p=.0099) and 41% for no iron groups (p=.0029). This difference was most pronounced in patients with baseline TSAT <20% (94% of whom had baseline serum ferritin >100ng/mL). Among these pts, FG group had 81% response rate vs oral iron 37% (p=.0091) and no iron pts 27% (p=.0027). Change from Baseline - Evaluable Population IV FG Oral Iron No Iron p values in comparison to FG group Hb g/dL +2.4 +1.6 p=.009 +1.5 p=.004 TSAT % −1.8 −2.7 −13.7 Ferritin ng/mL +344 −14 p<.0001 −96 p<.0001 CHr pg +2.1 +1.4 +0.3 Overall 93.6% of pts experienced at least 1 adverse event, evenly distributed among all 3 treatment groups. 19 pts (31.1%) in the oral iron group experienced a drug related adverse event, 4 leading to study discontinuation. 8 pts (12.7%) in the FG group experienced a drug related adverse event, 2 leading to discontinuation. In this study of anemic cancer patients on chemorx, all 3 groups responded to EPO therapy, but responses were significantly better in evaluable patients who received IV FG versus oral iron or no iron. Our data indicate FG allows the least iron restricted hematopoiesis and the best Hb responses, especially in patients with TSAT <20% and ferritin > 100, typical of anemia of chronic disease. IV FG was well tolerated.
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Reeder, C. B., T. E. Witzig, P. L. Zinzani, J. M. Vose, R. Buckstein, C. Haioun, R. Bouabdallah, J. Polikoff, D. Pietronigro, and M. S. Czuczman. "Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory mantle-cell lymphoma: Results from an international study (NHL-003)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 8569. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8569.
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8569 Introduction: Relapsed or refractory MCL patients demonstrated a promising overall response rate (ORR) of 53% with a median duration of response (DR) of 13.7 months to single-agent lenalidomide when analyzed as a subset in a recent a phase II study (NHL-002). A supporting international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed or refractory aggressive NHL. In this report, we analyze the current results from the MCL patients enrolled in this trial. Methods: Patients with relapsed or refractory MCL and measurable disease 2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Patients continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: Fifty-four MCL patients were enrolled and were evaluable for response assessment. Median age was 69 years (33–82) and 40 patients (74%) were male. Median time from diagnosis was 3.2 years (0.4–10.4), patients had received a median of 3 prior treatments (1–8), 17 of the patients (32%) had received prior bortezomib therapy (MCL-bortezomib), and 14 (26%) had received a prior stem cell transplant (MCL-stem cell). Response rates are shown in the Table. The most common grade 3 or 4 adverse events were neutropenia (43%), thrombocytopenia (22%) and anemia (11%). Conclusions: This is the second study to demonstrate that lenalidomide oral monotherapy is effective in the treatment of patients with relapsed or refractory MCL, with manageable side effects. [Table: see text] [Table: see text]
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Brezis, M., K. Spokes, P. Silva, and F. H. Epstein. "Lactate increases potassium secretion by perfused rat kidney." American Journal of Physiology-Renal Physiology 251, no. 5 (November 1, 1986): F873—F878. http://dx.doi.org/10.1152/ajprenal.1986.251.5.f873.
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The effect of exogenous metabolic substrates on K+ secretion was evaluated in the isolated perfused rat kidney in the presence of 2-deoxyglucose and 2-tetradecylglycidic acid to inhibit utilization of glucose and fatty acids from endogenous sources. L-Lactate (15 mM) added to the perfusion medium enhanced renal oxygen consumption (4.0 +/- 1.1 mumol X min-1 X g-1 vs. 2.0 +/- 1.0 without lactate) while decreasing fractional excretion of sodium (19.3 +/- 2.4% vs. 47.3 +/- 1.8). L-Lactate markedly increased the fractional excretion of K+ to 181 +/- 29% compared with 68 +/- 12% without lactate (P less than 0.001). The poorly metabolized isomer D-lactate did not alter these parameters. The addition of alpha-ketoglutarate only slightly increased K+ excretion. In the absence of metabolic inhibitors and in the presence of glucose (5 mM), L-lactate also increased K+ excretion significantly more than did D-lactate (108 +/- 19% vs. 69 +/- 11, P less than 0.02). At the end of 90 min of perfusion with L-lactate medium, K+ concentration in the perfusate dropped from 4.7 +/- 0.05 to 3.2 +/- 0.2 meq/liter (vs. 3.8 +/- 0.1 meq/liter with D-lactate, P less than 0.005) without differences in glomerular filtration rate or sodium excretion. L-Lactate appears to increase K+ secretion by preferential metabolic stimulation of the distal tubule, a process that may help in vivo to prevent hyperkalemia in lactic acidosis.
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Baskar, Suriya, Anuj Sharma, Davin Turku, Chaula Desai, and Anush Vasikaran. "Comparing outcomes for early and late drainage of malignant ascites." Journal of Clinical Oncology 43, no. 4_suppl (February 2025): 842. https://doi.org/10.1200/jco.2025.43.4_suppl.842.
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842 Background: Malignant ascites (MA) is a common sequela of peritoneal carcinomatosis resulting in significant morbidity and poses substantial management challenges for clinicians. Large volume paracentesis remains the gold standard treatment. The impact of time to drainage of MA is poorly studied. The purpose of this study was to compare clinical outcomes of hospitalized patients with MA that had drainage performed within 48 hours of admission and after 48 hours of admission. Methods: The NIS was queried between the years 2016 and 2020 to identify all adult patients hospitalized with malignant ascites (ICD-10 code R18.0) and had a drainage procedure performed (ICD-10 Procedure code 0W9Gx). These patients were then stratified into an early cohort (<48 hours after admission) and late cohort (>48 hours after admission). Baseline characteristics and clinical outcomes were collected and analyzed using chi squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). Adjusted Odds ratios (aOR) are presented with 95% Confidence intervals (CI). Results: A total of 129,040 patients were analyzed, with 89,905 (69.7%) hospitalizations in the early cohort and 39,135 (30.3%) in the late cohort. Baseline characteristics were similar between the groups, with no significant differences in age (63.8 vs 63.6, p = .06) or gender distribution (63.6% vs 63.1%, p = .09). However, patients in the early paracentesis group exhibited a lower CCI (9.8 vs 10.2, p<.001). Notably, early paracentesis was associated with significantly improved outcomes, including lower mortality (aOR 0.67, 95% CI 0.64–0.69), reduced incidence of sepsis (aOR 0.67, 95% CI 0.65–0.69), decreased need for transfusions (aOR 0.69, 95% CI 0.66–0.71), lower rates of mechanical ventilation (aOR 0.44, 95% CI 0.42–0.47) and vasopressor use (aOR 0.79, 95% CI 0.73–0.87). Conclusions: Early paracentesis in patients with malignant ascites was found to be associated with significantly improved clinical outcomes, independent of comorbidity burden. These findings underscore the importance of timely intervention to mitigate complications and enhance quality of life. Late ParacentesisN=39,135 EarlyN=89,905 p-value Age (years) 63.6 ± 13.1 63.8 ± 13.0 .06 Gender (% female) 24665 (63.1%) 57120 (63.6%) .09 CCI 10.2 ± 3.1 9.8 ± 3.2 <.001 Mortality 5720 (14.6%) 9030 (10.0%)aOR .67 (.64 - .69) <.001 Sepsis 7675 (19.6%) 12525 (13.9%)aOR .67 (.65 - .69) <.001 Transfusion 5275 (13.5%) 8605 (9.6%)aOR .69 (.66 - .71) <.001 Ventilation 2130 (5.4%) 2190 (2.4%)aOR .44 (.42 - .47) <.001 Vasopressor 770 (2.0%) 1385 (1.5%)aOR .79 (.73 - .87) <.001
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Alipour, Abbas, Mehran Zarghami, Sajjad Rahimi Pordanjani, Ardeshir Khosravi, Mehdi Saberi, and Masoudeh Babakhanian. "Spatial distribution and temporal trend of drug-related deaths in the Islamic Republic of Iran during 2014–2017." Eastern Mediterranean Health Journal 28, no. 10 (October 31, 2022): 758–67. http://dx.doi.org/10.26719/emhj.22.079.
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Background: Research suggests that there is an increasing trend in drug-related deaths worldwide: an estimated 69 000 individuals lose their lives due to substance abuse annually. Aims: To determine the geographical pathology of drug-related deaths in the Islamic Republic of Iran and to evaluate incidence trends, with a focus on identifying high- and low-risk regions. Methods: For this ecological study, we collected data from the 2 main sources (the Legal Medicine Organization and the Ministry of Health and Medical Education) responsible for registering substance-related deaths during 2014–2017. Data analysis was conducted using Joinpoint regression analysis, Global Moran’s I and Anselin Local Moran’s I. Results: Of the 12 386 drug-related deaths in 2014–2017, most occurred during the summer months; 7162 of these were among middle-aged individuals. The mean age of children and adolescents who died of substance abuse was 5.2 [standard deviation (SD) 4.6] years. In the young adult group, mean age at death was 20.7 (SD 2.5) years; it was 34.2 (SD 5.4) years for adults and 55.6 (SD 9.8) years for older adults. Changes in mortality rate peaked in 2017 (annual percentage change = 0.52); in the last months of the study period there was a nonsignificant decrease (annual percentage change = –6.99) in the incidence (average annual percentage change = –0.5; 95% confidence interval: –3.2, 2.3). Conclusion: Deaths due to substance abuse will remain a huge public health problem unless policy- and decision-makers determine why this problem continues to increase despite the extensive efforts on regulation and find ways to mitigate it.
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Foran, Ian M., Nasima Mehraban, Stephen K. Jacobsen, Daniel D. Bohl, Johnny Lin, Kamran S. Hamid, and Simon Lee. "Impact of Coleman Block Test on Adult Hindfoot Alignment Assessed by Clinical Examination, Radiography, and Weight-Bearing Computed Tomography." Foot & Ankle Orthopaedics 5, no. 3 (July 1, 2020): 247301142093326. http://dx.doi.org/10.1177/2473011420933264.
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Background: Cavovarus foot constitutes a complex 3-dimensional deformity. The Coleman block test has traditionally been used to distinguish between forefoot- and hindfoot-driven deformity. However, there has been no objective evaluation of the Coleman block test using radiographs or weightbearing computed tomography (WBCT). The purpose of this study was to compare hindfoot alignment in adult cavovarus feet with and without the Coleman block using clinical examination, radiography, and WBCT. Methods: Six feet in 6 patients with a clinical diagnosis of cavovarus foot deformity were prospectively enrolled. All feet underwent clinical photography with the camera positioned at 0 degrees to the heel, hindfoot alignment view radiography with the beam positioned 20 degrees off the ground, and WBCT, both with and without the Coleman block in place. Clinical photos were characterized using the standing talocalcaneal angle (STCA), radiographs were characterized using the hindfoot alignment angle (HAA), and WBCTs were characterized using manual and automated hindfoot alignment angle (HAA) and foot and ankle offset (FAO). Using paired analyses, measurements taken with the Coleman block in place were compared to those taken without the Coleman block. Finally, the different methods of measuring hindfoot alignment were tested for correlation with each other. Mean age was 56 years (range 38-69). Results: On clinical photography, the STCA decreased by 3.8 degrees with addition of the block (from 10.0±6.6 degrees varus without block to 6.2±7.1 degrees varus with block; P = .001). On radiograph, HAA decreased by 9.0 degrees with addition of the block (from 16.8±8.4 degrees varus without block to 7.5±6.3 degrees varus with block; P = .07). On WBCT, hindfoot alignment angle changed an average of 3.2 degrees (33.4 degrees varus without block, 30.2 degrees varus with block; P = .008). On WBCT, FAO decreased by 1.4% (from 11.3% varus without block to 10.1% varus with block; P = .003). Clinical examination and automated WBCT measurements were strongly correlated with each other. Conclusion: Clinical examination, radiograph, and WBCT demonstrated improvements in hindfoot varus using the Coleman block test in adults, but no patient demonstrated complete resolution of deformity regardless of the measurement modality. Clinical examination correlated strongly with automated WBCT measurements. Level of Evidence: Level IV, retrospective case review.
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Marincowitz, Carl, Omar Bouamra, Tim Coates, Dhushy Kumar, David Lockey, Virginia Newcombe, Lyndon Mason, David Yates, Julian Thompson, and Fiona Lecky. "1427 The effect of the COVID-19 pandemic on major trauma presentations and patient outcomes in English hospitals." Emergency Medicine Journal 39, no. 12 (November 22, 2022): A960.2—A964. http://dx.doi.org/10.1136/emermed-2022-rcem2.2.
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Aims, Objectives and BackgroundThere is evidence that COVID-19 ‘lockdowns’ may have contributed to increased non-accidental injury, domestic violence and self-harm related to deteriorating mental health. Internationally, there is also evidence that the diversion of health care resources may led to worse outcomes for patients presenting with major trauma. There has been no previous national evaluation of ‘lockdown’ measures impact on the characteristics, treatment pathways and outcomes of trauma patients in EnglandWe aimed to assess the impact of successive lockdowns on the volume, demographics, injury mechanism, severity, treatment and outcomes of major trauma in England.Method and DesignDemographic characteristics and clinical pathways of TARN eligible patients in the first lockdown (24th March to 3rd July 2020 inclusive) and second lock down (1st November 2020 to 16th May 2021 inclusive) were compared to equivalent pre-COVID-19 periods in 2018–2019.A segmented regression model predicting the weekly risk adjusted survival was estimated and a discontinuity in the gradient (trend) or intercept (level) of the fitted model was tested for at the weekly time point of implementation of each lockdown.Abstract 1427 Figure 1Strobe diagram for inclusion of study populationAbstract 1427 Figure 2Interrupted time series analysis assessing the impact of COVID restrictions on likelihood of survival (red horizontal lines indicate introduction and relaxation of ‘lockdown’ measures)Abstract 1427 Table 1Comparison of demographics ‘lockdown’ and pre-COVID periodsPeriodPeriod24Mar19 – 03Jul19 (comparator)24Mar20 – 03Jul20 (lockdown 1)Absolute change [percentage point change (95%CI)] p-value01Nov18 – 16May19 (comparator)01Nov20 – 16May21 (lockdown 1)Absolute change [percentage point change (95%CI)] p-valueTotal2224317510-4733 (-21%)p<0.0001‡41016382622754 (–6.7%)p<0.0001‡Age (years), Median (IQR)67.6 (46.5–83.1)70.9 (50.3–84.2)3.3 (2.4 to 4.2)p<0.000169.1 (48.7–83.6)73.1 (53.3–85.1)4 (3.5 to 4.2)<0.0001Age bands, n(%)Age< 1138 (0.6%)130 (0.7%)-8 [0.1(-0.04 to 0.030)] p=0.14281 (0.7%)234 (0.6%)-47 [0.1 (-0.2 to 0.04)]p=0.1979Age <16942 (4.2%)674 (3.8%)-268 [-0.4 (-0.8 to 0]p=0.05311444 (3.5%)1218 (3.2%)-226 [-0.3(-0.6 to – 0.1)p=0.0084Age 16 – 649561 (43%)6974 (39.8%)-2587 [-3.2(-4.1 to -2.2)P<0.000117173 (41.9%)13980 (36.5%)-3193 [-5.3(-6 to -5)]p<0.0001Age 65 and over11740 (52.8%)9862 (56.3%)-1878 [3.5 (2.5 to 4.5)]p<0.000122399 (54.6%)23064 (60.3%)665 [5.7(5 to 6.3)]P<0.0001Age 85 and over4610 (20.7%)4047 (23.1%)-563 [2.4(1.6 to 3.2)]p<0.00018903 (21.7%)9731 (25.4%)828 [3.7 (3.1 to 4.3)]p<0.0001Male, n(%)12316 (55.4%)9512 (54.3%)-2804 [-1 (-2 to -0.6)]p=0.037322146 (54%)19769 (51.7%)-2377 [-2.3 (-3 to -1.6)]<0.0001CCI*, n(%)CCI 09359 (42.1%)6220 (35.5%)-3139 [ -6.5 (-7.5 to -5.6)] p<0.000116665 (40.6%)12806 (33.5%)-3859 [-7.1(-7.8 to -6.5)]p<0.0001CCI 1 – 58538 (38.4%)6896 (39.4%)-1642 [1 (0.3 to 2)]p=0.042615899 (38.8%)15667 (40.9%)-232 [2.2 (1.5 to 2.9)]p<0.0001CCI 6 – 103032 (13.6%)3061 (17.5%)29 [3.8 (3.2 to 4.6)]p<0.00015987 (14.6%)6863 (17.9%)876 [3.3(2.8 to 3.8)]p<0.0001CCI > 10927 (4.2%)1024 (5.8%)97 [1.7(1.2 to 2.1)]p<0.00011648 (4%)2410 (6.3%)762 [2.3(2 to 2.6)]p<0.0001Not recorded387 (1.7%)309 (1.8%)-88 [0.2 (-0.2 to 0.3)]p=0.8513817 (2%)516 (1.3%)-301 [-0.6(-0.8 to -0.5)]p<0.0001MOI**: RTC, n(%)Car occupant1247 (30.7%)551 (20.4%)-696 [-10.4(-12.4 to -8.2)]p<0.00012485 (35.2%)1551 (31.3%)-934 [-3.9(-5.6 to -2.2)]p<0.0001Pedestrian661 (16.3%)288 (10.6%)-373 [-5.6 (-7.2 to -4)]p<0.00011629 (23.1%)962 (19.4%)-667 [-3.7(-5.1 to -2.2)]p<0.0001Motorcycles1196 (29.4%)711 (26.3%)-485 [-3.2(-5.3 to -1)]p<0.00011524 (21.6%)976 (19.7%)-548[ -1.9(-3.3 to -0.4)]p<0.0001Cyclist912 (22.4%)1139 (42.1%)227 [19.6(17.4 to 21.9)]p<0.00011315 (18.6%)1396 (28.2%)81 [9.5(8 to 11.1)]p<0.0001Other11 (0.3%)<9 ()-10 [ -0.2(-0.4 to -0.06)p=0.025131 (0.4%)10 (0.2%)-21 [-0.23(-0.4 to -0.04)]p=0.0281MOI: Intentional, n(%)Intentional assault130 (0.6%)88 (0.5%)-42 [-0.08 (-0.2 to 0.06)]p=0.2724227 (0.6%)175 (0.5%)-52 [-0.1(-0.2 to 0.002)]P=0.0570Self harm276 (1.2%)284 (1.6%)8 [0.4 (0.1 to 0.6)]p=0.0014525 (1.3%)562 (1.5%)37 [0.2 (0.02 to 0.3)]p=0.0223NAI63 (0.3%)27 (0.2%)-36 [-0.1(-0.2 to -0.03)]p=0.007297 (0.2%)90 (0.2%)-7 [-0.001(-0.07 to 0.07)]p=0.9701Shooting34 (0.2%)40 (0.2%)6 [0.08(-0.01 to 0.2)]p=0.082680 (0.2%)56 (0.1%)-24 [ -0.05(-0.1 to 0.001)]p=0.0979Stabbing450 (2%)312 (1.8%)-138 [-0.2(-0.5 to 0.03)]p=0.0816791 (1.9%)589 (1.5%)-202 [-0.4 (-0.6 to -0.2)]p<0.0001Blows1174 (5.3%)647 (3.7%)-527 [-1.6(-1.9 to -1.2)]p<0.00012059 (5%)1299 (3.4%)-760 [-1.6(-1.9 to -1.3)]p<0.0001Unintentional, n(%)Falls>2m2055 (9.2%)1757 (10%)-298 [0.8(0.2 to 1.4)]P=0.00753740 (9,1%)3528 (9.2%)-212 [0.1(-0.3 to 0.5)]p=0.6181Falls<2m13384 (60.2%)11314 (64.6%)-2070 [4.4 (3.5 to 5.4)]p<0.000125505 (62.2%)26203 (65.8%)698 [6.3 (5.6 to 6.9)]p<0.0001Sport449 (2%)320 (1.8%)-129 [-0.2 (-0.5 to 0.01]p=0.1697615 (1.5%)489 (1.3%)-126 [-0.2 (-0.4 to -0.006)]p=0.0079GCS bands , n(%)Mild19609 (88.2%)15449 (88.2%)4160 [0.1 (-0.6 to 0.7)]p=0.826435831 (87.4%)34051 (89%)-1780 [1.6 (1.2 to 2.1)]p<0.0001Moderate689 (3.1%)625 (3.6%)-64 [0.5(0.1 to 0.8)]p=0.00901333 (3.2%)1127 (2.9%)-206 [-0.3 (-0.5 to -0.06)]p=0.0135Severe955 (4.3%)765 (4.4%)-190 [0.1 (-0.3 to 0.5)]p=0.71361886 (4.6%)1464 (3.8%)-422 [-0.8(-1 to -0.5)]p<0.0001Not recorded990 (4.5%)671 (3.8%)-319 [ -0.6(-1 to -0.2)]p=0.00221966 (4.8%)1620 (4.2%)-346 [-0.6(-0.8 to -0.3)]p=0.0002ISS***, median (IQR)9 (9–18)9 (9–18)09 (9–18)9 (9–17)0ISS bands, n(%)ISS 1 – 84545 (20.4%)3062 (17.5%)-1483 [-3 (-4 to -2)]p=<0.00018266 (20.2%)7838 (20.5%)-428 [0.3(-0.2 to 0.9)]p=0.2457ISS 9 – 159290 (41.8%)7728 (44.1%)-1562 [2.4(1.4 to 3.3)]p<0.000117207 (42%)16969 (44.3%)-233 [2.4(1.7 to 3.1)]p<0.0001ISS >158408 (37.8%)6720 (38.4%)-1688 [5.6(-0.4 to 1.5)]p=0.239115543 (37.9%)13455 (35.2%)-2088 [-2.7 (-3.4 to -2)]p<0.0001ISS >253995 (18%)3127 (17.9%)-868 [-0.1(-0.9 to 0.7 )]p=0.79217521 (18.3%)6201 (16.2%)-1320 [-2.1(-2.6 to -1.6)]p<0.0001Body regions, n(%)Head AIS 3+5911 (26.6%)4670 (26.7%)-1241 [0.1 (-0.8 to 1)]p=0.830111128 (27.1%)9629 (25.2%)-1499 [ -2(-2.6 to -1.3)]p<0.0001Face AIS 3+63 (0.3%)41 (0.2%)-22 [-0.05 (-0.1 to 0.05)]p=0.341699 (0.2%)69 (0.2%)-30 [-0.06 (-0.1 to 0)]p=0.0618Chest AIS 3+4787 (21.5%)3915 (22.4%)-872 [8.3 (0.2 to 1.6)]<0.04508515 (20.8%)8075 (21.1%)-440 [0.3 (-0.2 to 0.9)]p=0.2337Abdomen AIS 3+872 (3.9%)690 (3.9%)-182 [0.02 (-0.3 to 0.4)]p=0.91771465 (3.6%)1179 (3.1%)-286 [-0.5 (-0.7 to -0.2)]p=0.0001Spine AIS 3+1985 (8.9%)1561 (8.9%)-424 [-0.01(-0.6 to 0.5)]p=0.97443784 (9.2%)3459 (9%)-325 [-0.2(-0.6 to 0.2)]p=0.3654Pelvis AIS 3+758 (3.4%)600 (3.4%)-158 [0.02(-0.3 to 0.4)]p=0.91841501 (3.7%)1386 (3.6%)-115 [-0.04(-0.3 to 0.2)]p=0.7802Limb AIS 3+5707 (25.7%)4892 (27.9%)-815 [2.3 (1.4 to 3.2)]p<0.000110719 (26.1%)10122 (26.5%)-597 [0.3(-0.3 to 0.9)]p=0.3053Other AIS 3+217 (1%)199 (1.1%)-18 [0.2 (-0.04 to 0.3)]p=0.1176375 (0.9%)396 (1%)21 [0.1 (-0.01 to 0.2]p=0.0836Polytrauma1622 (7.3%)1350 (7.7%)-272 [0.4 (-0.1 to 0.9)]p=0.11602984 (7.3%)2429 (6.3%)-555 [-0.9(-1.2 to 0.6)]p<0.0001*CCI Charlson Comorbidity Index**MOI Mechanism of injury***ISS Injury Severity Score‡chi square test for uniform distributionAbstract 1427 Table 2Comparison care pathways ‘lockdown’ and pre-COVID periodsPeriodPeriod24Mar19 – 03Jul19 (comparator)24Mar20 – 03Jul20 (lockdown 1)Absolute Change01Nov18 – 16May19 (comparator)01Nov20 – 16May21 (lockdown 2)Absolute Change1stHospital MTC9908 (44.5%)7376 (42.1%)-2532 [-2.4 (-3.4 to -1.4)]p<0.000118099 (44.1%)15928 (41.6%)-2171 [-2.5 (-3.2 to -1.8)]p<0.0001Treated at MTC11176 (50.2%)8256 (47.2%)-2920 [-3 (-4 to -2)]p<0.000120395 (49.7%)17852 (46.7%)-2543[-3 (-4 to -2.4)]p<0.0001Consultant ED8140 (36.6%)5562 (31.8%)-2578 [-4.8(-5.8 to -3.9)]p<0.000114779 (36%)12577 (32.9%)-2202 [-3.2 (-3.8 to -2.5)]p<0.0001CT within 1 hr5062 (31.9%)3992 (30.9%)-1070 [-0.9(-2 to 0.1)]p=0.09449203 (31.6%)7776 (27.1%)-1427 [-4(-5 to -3.7)]p<0.0001Whole body CT3348 (15.1%)3210 (18.3%)-138 [3 (2 to 4)]p<0.00016040 (14.7%)6417 (16.8%)377 [2 (1.5 to 2.5)]p<0.0001ICU stay3092 (13.9%)2208 (12.6%)-884 [-1.3(-1.9 to -0.6) ]p=0.00025591 (13.6%)3850 (10.1%)-1741 [-3.6(-4 to -3)]p<0.0001Mortality*1417 (7.1%)1316 (8.3%)-101 [1.2 (0.6 to 1.7)]p<0.00012916 (7.9%)2858 (8.1%)-58 [0.2 (-0.1 to 0.6)] p=0.2040Discharge destination, n(%)Home (own)13800 (62%)10484 (59.9%)-3316 [-2(-3.1 to -1.2)]p<0.000124961 (60.9%)23368 (61.1%)-1593 [-0.7 (-1.4 to -0.05)]p=0.0340Home (relative/carer)473 (2.1%)372 (2.1%)-101 [0 (-0.3 to 0.3)]p=0.9890974 (2.4%)852 (2.2%)-122 [-0.1(-0.4 to 0.06)]p=0.1653Mortuary*1501 (6.7%)1323 (7.6%)-178 [0.8(0.3 to 1.3)]p=0.00193086 (7.5%)2977 (7.8%)-109 [0.1 (-0.3 to 0.5)]p=0.5113No fixed abode75 (0.3%)47 (0.3%)-28 (-37.3%)107 (0.3%)87 (0.2%)-20 (-18.7%)Not Known87 (0.4%)39 (0.2%)-48 (-55.2%)101 (0.2%)95 (0.2%)-6 (-5.9%)Nursing Home1190 (5.3%)1063 (6.1%)-127 [0.7(0.3 to 1.2)]p=0.00202448 (6%)2231 (5.8%)-217 [-0.2(-0.6 to 0.1)]p=0.1620Other Acute hospital2425 (10.9%)1736 (9.9%)-689 [-0.1(-1.6 to -0.4)]p=0.00144346 (10.6%)3313 (8.7%)-1033 [-0.1(-0.5 to 0.2)]p=0.4115Other institution526 (2.4%)516 (2.9%)-10 [0.6 (0.3 to 0.9)]p=0.0003980 (2.4%)870 (2.3%)-110 [-0.1 (-0.3 to 0.1)]p=0.2817Rehabilitation2077 (9.3%)1871 (10.7%)-206 [1.3(0.7 to 1.9)]p<0.00013851 (9.4%)4274 (11.2%)423 [ 1.7(1.3 to 2.2)]p<0.0001Social care63 (0.3%)50 (0.3%)-13 [0 (-0.1 to 0.1)]p=0.9657121 (0.3%)103 (0.3%)-18 [-0.2(-0.1 to 0.5)]p=0.4939*These totals do not correspond as mortality includes deaths in the community and is censored at 30 daysResults and ConclusionThe first ‘lockdown’ had a larger associated reduction in total trauma volume (-21%) compared to the pre-COVID period than the second ‘lockdown’ (-6.7%). Trauma volume increased for those 65 and over (3%) and 85 and over (9.3%) during the second ‘lockdown’.There was a reduction in likelihood of survival (-1.71; 95% CI:-2.76 to -0.66) associated with the immediate introduction of the first ‘lockdown’. However, this was followed by a trend of improving survival (0.25; 95% CI: 0.14 to 0.35) and likelihood of survival returned to pre-pandemic levels by the end of the first ‘lockdown’ period.Future research is needed understand the initial reduction in likelihood of survival after major trauma observed with the implementation of the first ‘lockdown’ to prevent this occurring if measures re-introduced.
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Sieiro Santos, C., C. Moriano, I. González Fernández, X. E. Larco Rojas, C. Álvarez Castro, and E. Diez Alvarez. "AB0647 Clinical phenotype in scleroderma patients with limited and diffuse cutaneous disease based on autoimmunity." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1450. http://dx.doi.org/10.1136/annrheumdis-2022-eular.345.
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BackgroundClassically, anti-centromere antibodies (ACA) are associated with limited cutaneous involvement (lcSSc) and pulmonary hypertension, whereas anti-topoisomerase I (Sc70) are associated with diffuse skin involvement (dcSSc) and pulmonary fibrosis (ILD). Patients with lcSSc and Sc70 antibodies draw particular attention, which is why characterization of clinical phenotypes can help distinguish patient subgroups and assessing the prognosis of the disease.ObjectivesWe aimed to characterize the clinical phenotype of patients with SSc based on autoantibodies.MethodsWe included patients with SSc, fulfilling the 2013 ACR/EULAR criteria, with disease duration ≤10 years. We have compared different subgroups of patients with lcSSc: Scl70-lcSSc (group1), ACA-lcSSc (group 2) and ANA-lcSSc (group 3), (Table 1). Next, we compared patients with Scl70-lcSSc (group 1) to Scl70-dcSSc (group 4) and ANA-lcSSC (group 3) to ANA-dcSSC (group 5). In the ANA subgroup we included patients with negative Scl70 and ACA antibodies. We have assessed the risk of ILD, myositis, scleroderma renal crisis, cardiac and gastrointestinal involvement, myositis, pulmonary hypertension (systolic pulmonary arterial pressure sPAP>45 mmHg at transthoracic echocardiography or sPAP>25 mmHg at right heart catheterization), cancer and all-cause-mortality.Table 1.Clinical characteristics of patients with lcSScScl70-lcSScP valueACA-lcSScP valueANA-lcSScFemale9 (56.3%)0.0336 (83.7%)0.8012 (52%)Time from RP to SSc (years)1.28 (0.25-3.5)0.026.23 (3-9)0.0024.91 (2-5)Age at SSc onset56.5 (48-66)0.0462.5 (54-73)0.7659.2 (44-66)CRP elevation30 (22-39)0.0222 (16-29)0.2110 (6-19)mRSS4 (2-4.2)0.033.2 (2.1-4.0)0.923.9 (2.5-4.2)Joint synovitis6 (37.5%)0.4712 (28%)0.7110 (43%)Tendon friction rubs2 (12.5%)0.503 (7%)0.190Myositis4 (25%)0.042 (5%)0.815 (21.7%)Gastrointestinal involvement6 (37.5%)0.1927 (63%)0.0416 (69%)Renal crisis4 (25%)0.042 (5%)0.182 (9%)ILD10 (63%)0.0017 (16%)0.047 (30%)Pulmonary hypertension4 (25%)0.477 (16%)3 (13%)Arrythmia5 (21.7%)0.086 (14%)0.357 (30%)Conduction defects1 (6.3%)0.595 (11.6%)0.791 (4%)Diastolic disfunction7 (43.8%)0.3617 (39.5%)0.779 (39%)Immunosuppressants10 (63%)0.0113 (30.2%)0.5212 (52%)Steroids9 (56%)0.0412 (28%)0.9813 (56.6%)Cancer8 (50%)0.0410 (23.2%)0.227 (30%)Mortality3 (18.8%)0.046 (14%)0.825 (21.7%)Results103 SSc patients were included: 72 (69%) females, 82 (79%) lcSSc and 21 (20%) dcSSc. Among lcSSc patients, 43 (52%) had ACA, 16 (19%) Scl70 and 23 (28%) ANA. Among dcSSC patients, 9 (43%) had Scl70 and 12 (57%) had ANA. Scl70-lcSSc patients had significantly shorter time from Raynaud’s phenomenon (RP) to SSc diagnosis (p=0.02), younger age at SSc onset (p=0.04), higher mRSS (p=0.03), higher rate of myositis (p=0.04) and renal scleroderma crisis (p=0.04) than ACA-lcSSc patients. The risk of ILD in Scl70-lcSSC compared to ACA-lcSSC is 3.8 higher (95% IC 1.2-14.5) and 1.5 higher (95% IC 1.05-5.61) than ANA-lcSSC. All-cause mortality was higher in Scl70-lcSSC (p=0.04) compared to ACA-lcSSC. Scl70-dcSSC patients had a shorter time from RP to SSc diagnosis (p=0.02), higher CRP (p=0.04), mRSS (p=0.001), higher rate of myositis (p<0.05) and ILD (p=0.04) and all-cause mortality (p=0.04) than Scl70-lcSSc patients, while renal and cardiac involvement was similar. ANA-dcSSC patients also had a shorter time from RP to SSc diagnosis (p=0.03), higher mRSS (p=0.02) and higher rate of ILD (p=0.02).ConclusionScl70-lcSSc patients show the major organ involvement, followed by ANA-lcSSc and ACA-lcSSc. Scl70-dcSSc and ANA-dcSSC patients exhibit more cutaneous involvement and ILD than Scl70-lcSSc and ANA-lcSSc. These results may provide new ways to help in early diagnosis, management and assessing the prognosis of the disease.References[1]Zanatta E et al. POS0318 CLINICAL PHENOTYPE IN SCLERODERMA PATIENTS WITH ANTI-TOPOISOMERASE I POSITIVITY AND LIMITED CUTANEOUS FORM: DATA FROM THE EUSTAR DATABASE. Annals of the Rheumatic Diseases 2021;80:386-387.Disclosure of InterestsNone declared
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Iliadou, Anastasia, Harold Snieder, Xiaoling Wang, Frank A. Treiber, and Catherine L. Davis. "Heritabilities of Lipids in Young European American and African American Twins." Twin Research and Human Genetics 8, no. 5 (October 1, 2005): 492–98. http://dx.doi.org/10.1375/twin.8.5.492.
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AbstractTwin studies of lipids have almost exclusively involved Caucasians. People of African descent are known to show a healthier lipid profile, but relatively little is known about ethnic differences in genetic and environmental influences on lipids. One hundred and six African American (AA) and 106 European American (EA) twins (30 singletons and 91 complete pairs: 49 monozygotic, 21 dizygotic and 21 opposite-sex) from the south-eastern United States were studied (mean age 17.9 ± 3.2 years; 79% fasting). Lipids were assayed with the Cholestech LDX system. Analyses were adjusted for fasting status. Generalized estimating equations were used to test for the effects of sex and ethnicity on means, controlling for the dependence within twin pairs. Structural equation modeling was used to estimate genetic and environmental effects on each lipid variable. Females showed higher high-density lipoprotein (HDL) values than males (p< .001) and AAs showed higher HDL values than EAs (p< .001). EA males had higher triglyceride values than other groups (p= .02). All parameter estimates could be set equal across sex. Parameter estimates for total cholesterol, triglycerides and HDL could be set equal across ethnicity. The best fitting model for low- density lipoprotein (LDL) showed higher heritability in AAs (.92) than EAs (.69). Heritabilities ranged from 69% to 92%, with remaining variation explained by nonshared environmental effects. Adjustment for body mass index had virtually no effect on the heritability estimates. In this first twin study on lipids to include AAs, no ethnic differences in heritability were found except for LDL, where AAs exhibited higher estimates.
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Le Deley, Marie-Cécile, Alfred Reiter, Denise Williams, Georges Delsol, Ilske Oschlies, Keith McCarthy, Martin Zimmermann, and Laurence Brugières. "Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study." Blood 111, no. 3 (February 1, 2008): 1560–66. http://dx.doi.org/10.1182/blood-2007-07-100958.
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Abstract To study prognostic factors of progression/relapse, data concerning 225 children enrolled between 1987 and 1997 in Berlin-Frankfurt-Münster, Société Française d'Oncologie Pédiatrique and United Kingdom Children's Cancer Study Group prospective studies for the treatment of anaplastic large cell lymphoma (ALCL) were merged. Median follow-up was 9.3 years. Five-year overall survival and event-free survival of the whole population was 81% (95% confidence interval, 76%-86%) and 69% (63%-74%), respectively. B symptoms, mediastinal involvement, skin lesions, visceral involvement, St Jude stage 3-4, Ann Arbor stage 3-4, and elevated lactate dehydrogenase increased the risk of progression/relapse in the univariate analysis. In the multivariate analysis, 3 factors remained significant: mediastinal involvement (relative risk [RR] = 2.1 [1.2-3.5]), visceral involvement defined as lung, liver, or spleen involvement (RR = 2.1 [1.3-3.6]), and skin lesions (RR = 1.9 [1.1-3.2]). Five-year progression-free survival (PFS) of the 81 patients with none of these risk factors was 89% [82%-96%], contrasting with a 5-year PFS of 61% [53%-69%] in the 144 patients with at least 1 risk factor (RR = 4.4 [2.2-8.9; P < .001). In conclusion, 3 factors associated with an increased risk of failure in childhood ALCL have been defined: mediastinal involvement, visceral involvement, and skin lesions.
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Postmus, Pieter E., Hanny Haaxma-Reiche, Egbert F. Smit, Harry J. M. Groen, Hanna Karnicka, Tadeusz Lewinski, Jan van Meerbeeck, et al. "Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group." Journal of Clinical Oncology 18, no. 19 (October 19, 2000): 3400–3408. http://dx.doi.org/10.1200/jco.2000.18.19.3400.
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PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m2 was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.
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Uchendu, Obiora Jude, and Obahiagbon Ikponmwosa. "Epidemiological and Pathologic Characteristics of Cancer Morbidity in Elderly Nigerians: A Call for Action." Asian Pacific Journal of Cancer Care 5, no. 4 (February 16, 2021): 295–302. http://dx.doi.org/10.31557/apjcc.2020.5.4.295-302.
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Objective: Geriatric cancer is a major public health problem with increasing incidence due to population growth and ageing.This study hopes to analyze the epidemiology and pathology of geriatric cancer in a Nigerian tertiary healthcare center. Method: The study is a ten-year (2010-2019) descriptive retrospective study of histopathologically confirmed geriatric cancer cases in the University of Benin Teaching Hospital, Nigeria. The age, gender, anatomic site and histological diagnosis were used for the study. Analysis was with Microsoft Excel spreadsheet and results summarized in tables and figures. Result: Geriatric cancer accounted for 33.7% of all cancers, affecting 871 males and 593 females with mean age and age range of 70.4 and 60-101 years respectively. Cases in 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018 and 2019 were 7.9%, 10.5%, 10.7%, 11.3%, 7.0%, 8.5%, 8.55%, 10.5%, 11.8% and 12.4% respectively. Exactly 26.0%, 25.4%, 19.1%, 15.0%, 9.0%, 3.2%, 1.3%, 0.8%, and 0.2% of cancer cases were encountered among the 60-64, 65-69, 70-74, 80-84, 85-89, 90-94, 95-99 and 100-104 years age groups respectively. Prostate, cervical, breast, colorectal and gastric cancer accounted for 41.3%, 12.3%, 12.3%, 5.8% and 3.1% of the cases respectively. Conclusion: Geriatric cancer incidence is on the increase with male predominance and a peak at 60-64 years. About 75% of geriatric cancer affected the prostate, uterine cervix, breast, stomach and colorectum. Geriatric cancer care is still a low priority in Nigeria. A stronger health and social system is desirable for the worsening geriatric cancer burden in this region.
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Dombret, Hervé, Alexandra Coelho, Laurène Fenwarth, Jean-Baptiste Micol, Lionel Ades, Thomas Cluzeau, Emmanuel Raffoux, et al. "Treatments and Outcomes of Adult Patients with AML in the Real-Life - First Report of the French Observational ALFA-PPP Study." Blood 144, Supplement 1 (November 5, 2024): 2424. https://doi.org/10.1182/blood-2024-207226.
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Introduction. AML treatment options have been recently enriched. New agents like gemtuzumab ozogamicin (GO), FLT3 or IDH inhibitors, or CPX-351 have been approved for some patient subsets. Less-intensive options, like the AZA-VEN combination, are used in older/unfit patients. However, while treatments and indications are standardized, their choice is not, depending on often-subjective factors. This makes observational studies so important to describe the real-life management and outcomes of AML patients. Methods. In 2022, the ALFA group initiated a 2-cohort (newly diagnosed, relapsed/refractory) prospective observational study (ALFA-PPP, NCT04777916) aiming to collect clinical data and bio-samples in all AML patients aged ≥18y referred to 27 ALFA centers. Data/sample collection was structured by approved therapies including best supportive care (BSC). Patients treated on a compassionate basis or included in a clinical trial are also registered. Treatment decision-making criteria are prospectively collected. All patients should have a centralized genomic diagnosis (50-gene NGS panel) and molecular/flow MRD follow-up. We report here the initial observations made in the first 648 patients included between April 2022 and September 2023 in the newly diagnosed cohort. The current patient recruitment rate is around 650 new patients per year. Results. There were 340 males and 308 females (median age, 65y [range, 18-100]; ECOG-PS 0/1/2/3/4/NA, 195/295/97/33/8/19; HCT-CI comorbidity index 0/1/2/3+/NA, 54/269/106/216/3; median WBC, 6.9 G/L [IQR, 2.4-26]; median marrow blast percentage, 53% [IQR, 29-79]). The numbers of patients with de novo, post-MDS, post-MPN and therapy-related AML (tAML) were 467 (72%), 54 (8%), 58 (9%) and 69 (11%), respectively. ELN-2022 risk was favorable in 136 (21%), intermediate in 129 (20%), adverse in 340 (52.5%), and not available in 43 (6.5%) patients. In the 595 patients tested, incidences of NPM1, FLT3-ITD, IDH1/2, TP53 and secondary AML (sAML)-like gene mutations were 27%, 19%, 22%, 12% and 48%, respectively. A minority of 172 (26.5%) patients were included into a clinical trial frontline (investigator/company-sponsored trial, 140/32 patients; intensive/less intensive/two-option trial, 142/20/10 patients). They were significantly younger than the 476 (73.5%) patients treated outside any clinical trial (median age, 55 vs 69y, p<.001). In these 476 patients, treatment decision was intensive in 266 (median age, 62y [18-79]; 210 7+3 ± GO or midostaurin, 54 CPX-351, 2 others), less intensive in 185 (median age, 76y [36-100]; 149 AZA-VEN, 18 AZA or low-dose cytarabine alone, 13 AZA-ivosidenib, 5 others), and BSC in 21 patients, while the 4 remaining patients early died before any treatment decision. By investigator declaration, the main reason for selecting a less intensive treatment was advanced age (n=138), AML characteristics/risk (n=19), concomitant diseases (n=16), patient's choice (n=1), or other (n=11), with good statistical correlations with objective data. The objective factors independently associated with the choice of a less intensive option were age ≥65y (p<.001), higher ECOG-PS (p<.001) or comorbidity index (p=.001), but also post-MDS (p=.001) or post-MPN (p<.001) AML, lower WBC (p=.022), poor cytogenetics (p=0.046), and TP53 (p=.003) or IDH1/2 (p=.003) mutation. A total of 89/476 (18.5%) patients received an allogeneic SCT during the first 6 months of follow-up, including 81 intensively and only 8 less-intensively treated patients. In the 185 less-intensively treated patients with a median follow-up of 15 months, median overall survival (OS) was 10.3 months (95% CI, 7.2-12.9) with a 12-month estimate at 45.3% (95% CI, 37.7-52.5). In these patients, multivariate stepwise Cox model evidenced higher ECOG-PS (p=.038), concomitant diseases (p=.003), tAML (p=.046), higher marrow blast percentage (p=.024), sAML-like (p=.048) and TP53 (p<.001) mutation as bad-prognosis factors for OS, while IDH1/2 mutations (p=.001) were associated with longer OS. Conclusions. Awaiting the ELN-2024 recommendations for less-intensive AML therapies, this prospective real-life study confirms their rising place in a European context. Rather than age by itself, survival after less-intensive treatment is governed by multiple independent clinical and genomic factors. Future reports will update these observations on an annual basis.
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Samson, S., J. P. Fagot, J. Merlière, P. Gabach, and A. Fagot-Campagna. "Une prise en charge fréquente de la population adulte pour troubles psychiatriques ou traitements psychotropes, à travers les données de l’Assurance Maladie." European Psychiatry 28, S2 (November 2013): 86–87. http://dx.doi.org/10.1016/j.eurpsy.2013.09.232.
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Introduction.Utiliser les bases de l’Assurance Maladie (Sniiram et PMSI) pour estimer la fréquence des prises en charge liées à la psychiatrie chez l’adulte en France.Méthodes.Parmi les bénéficiaires du régime général en 2010 de plus de 18 ans (45 millions), ceux ayant une prise en charge liée à la psychiatrie ont été identifiés à partir :– des diagnostics liés aux hospitalisations (PMSI-MCO, RIM-P, SSR), aux affections de longue durée, aux arrêts de travail ou invalidité ;– du remboursement de consultation avec un psychiatre ou à des soins ambulatoires psychiatriques ;– d’au moins trois remboursements de médicaments de la dépendance ou neuroleptiques, antidépresseurs, anxiolytiques, hypnotiques [1].Résultats.Près de 8,2 millions des adultes (18 %) ont reçu des soins liés à la psychiatrie, dont 5,6 millions (69 %) ont eu uniquement des délivrances médicamenteuses sans diagnostic identifié dans les bases. Les pathologies les plus fréquemment retrouvées étaient les épisodes dépressifs/troubles de l’humeur (889 000), les troubles anxieux (464 000), les addictions (383 000), les troubles de la personnalité et du comportement (340 000). Schizophrénie, autres troubles psychotiques, troubles bipolaires et anorexie mentale étaient retrouvés chez respectivement 181 000, 224 000, 164 000 et 23 000 adultes. L’âge moyen variait de 42 (anorexie mentale) à 58 ans (patients identifiés seulement par les médicaments). Le pourcentage de femmes (65 %) s’élevait de 28 % (addictions) à 68 % (épisodes dépressifs/troubles de l’humeur, ou patients identifiés seulement par psychotropes) et 87 % (anorexie mentale). Le pourcentage de bénéficiaires de la CMU-C (11,5 %) variait de 11 % (troubles bipolaires) à 26 % (addictions).Discussion.Dix-huit pour cent de la population adulte a eu recours à des soins liés à la psychiatrie en 2010. Un diagnostic spécifique est retrouvé dans les bases chez plus d’un quart de ces patients, avec une forte proportion d’épisodes dépressifs et autres troubles de l’humeur.
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Gazizova, I. R., and V. E. Korelina. "Brimonidine as an additional treatment for moderate glaucoma." Russian Journal of Clinical Ophthalmology 21, no. 2 (2021): 69–71. http://dx.doi.org/10.32364/2311-7729-2021-21-2-69-71.
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Aim: to assess the utility of brimonidine 0.2% as an additional IOP-lowering treatment for moderate glaucoma. Patients and Methods: 99 patients (121 eyes) aged 62–73 years with moderate glaucoma were enrolled. All patients were divided into four groups based on IOP-lowering medications. In group 1, prostaglandin analogues (latanoprost) and beta blockers (timolol) were prescribed. In group 2, carbonic anhydrase inhibitors (dorzolamide) and beta blockers (timolol) were prescribed. In group 3, brimonidine 0.2% was added to prostaglandin analogues and beta blockers. In group 4, brimonidine 0.2% was added to carbonic anhydrase inhibitors and beta blockers. All patients underwent IOP measurements and static automated perimetry (SAP) at baseline and after 6 and 12 months. Results: additional treatment (brimonidine) gradually reduced IOP levels in groups 3 and 4, while in groups 1 and 2 IOP levels were stable. In group 1, mean deviation (MD) increased from -10.7±4.5dB to -10.8±3.8 dB after 6 months but reduced to -10.5±3.4 dB after 12 months. In group 2, MD increased from -11.7±5.1 dB to -12.0±3.2 dB after 6 months and -12.5±2.9 dB after 12 months. In group 3, MD reduced from -13.5±4.1 dB to -12.9±3.6 dB after 6 months and -12.7±3.0 dB after 12 months. In group 4, MD reduced from -13.9±4.6 dB to -13.0±4.1 dB after 6 months and increased to -13.1±3.5 dB after 12 months. Pattern standard deviation (PSD) was stable in all four groups. Conclusion: brimonidine as an additional treatment for moderate and advanced glaucoma results in stable IOP reduction. Combined therapy which includes brimonidine preserves visual functions even in moderate-to-advanced glaucoma. The neuroprotective effect of brimonidine is illustrated by SAP. This medication is well tolerated. Keywords: glaucoma, IOP, visual field, perimetry, tonometry, neuroprotection. For citation: Gazizova I.R., Korelina V.E. Brimonidine as an additional treatment for moderate glaucoma. Russian Journal of Clinical Ophthalmology. 2021;21(2):69–71. DOI: 10.32364/2311-7729-2021-21-2-69-71.
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Artico, Jessica, Hunain Shiwani, James C. Moon, Miroslawa Gorecka, Gerry P. McCann, Giles Roditi, Andrew Morrow, et al. "Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study." Circulation 147, no. 5 (January 31, 2023): 364–74. http://dx.doi.org/10.1161/circulationaha.122.060632.
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Background: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. Methods: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID−/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. Results: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin−] versus 31% [COVID−/comorbidity+]; P <0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P <0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P <0.01) or microinfarction (9% versus 0% and 1%; P <0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P =0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 ( P =0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P =0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12–4.57]; P =0.02). Conclusions: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. Registration: URL: https://www.isrctn.com ; Unique identifier: 58667920.
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Kang, Junho, Changhoon Yoo, Sang Hyun Shin, Kyu-Pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Sang Soo Lee, et al. "Neoadjuvant chemotherapy followed by surgery versus upfront surgery in patients with borderline resectable and locally advanced unresectable pancreatic adenocarcinoma." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 312. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.312.
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312 Background: Although neoadjuvant chemotherapy (NACT) has been widely investigated, the magnitude of the clinical benefit and the potential risk of NACT followed by surgery compared with upfront surgery remains unclear for patients with locally advanced pancreatic cancer (LAPC). Methods: This retrospective, prospective cohort-based analysis included 135 patients who underwent NACT followed by surgery and 359 patients who received upfront surgery for LAPC between October 2005 and April 2017. Disease-free survival (DFS) and overall survival (OS) from surgery were compared between the two groups. Results: There were no significant differences in gender (male, 53% vs 56%) and age (median 60 vs 61 years) between the NACT followed by surgery group and upfront surgery group. As NACT, gemcitabine-based regimens and FOLFIRINOX were used in 69 (51%) and 66 (49%) patients, respectively. The NACT followed by surgery group showed significantly less advanced T stage (T3–4, 93% vs 99%, p = 0.001) and N stage (N+, 49% vs 71%, p < 0.001) than the upfront surgery group. NACT followed by surgery was significantly associated with better OS (median, 25.4 [18.6–32.2] vs 17.1 [15.5–18.7] months, p = 0.001) and DFS (median, 9.0 [95% CI, 6.8–11.2] vs 7.1 [6.4–7.8] months, p = 0.005) than upfront surgery. These results were consistent in the multivariate analysis for OS (adjusted hazard ratio [aHR], 0.73 [95% CI, 0.56–0.96], p = 0.02) and DFS (aHR, 0.72 [95% CI, 0.56–0.93], p = 0.01). There was no difference in length of hospital stay (median 13 vs 17 days, p = 0.14) for surgery between the two groups, and the NACT followed by surgery group showed a significantly lower incidence of postoperative complication than the upfront surgery group (38% vs 27%, p = 0.03). Conclusions: The present study revealed that NACT followed by surgery may provide survival benefit compared with upfront surgery in LAPC without causing significant safety issues.
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Mccready, J., V. Deary, T. Collins, D. Lendrem, and K. Hackett. "POS0043-HPR DO COPING STRATEGIES, ILLNESS PERCEPTIONS AND RELATIONSHIP DYNAMICS CONTRIBUTE TO SEXUAL DYSFUNCTION FOR WOMEN WITH SJÖGREN’S SYNDROME?" Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 237.1–237. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1358.
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BackgroundWomen with Sjögren’s syndrome (SS) are more likely to experience vaginal dryness, dyspareunia and reduced sexual function than healthy controls1. There is limited data investigating relationships with psychosocial influences, such as coping mechanisms, illness perceptions, partners behaviours and relationship satisfaction.ObjectivesTo investigate associations between sexual function and psychosocial parameters in women with SS.MethodsCisgender women aged 18+, diagnosed with SS, were invited to participate in a cross-sectional online survey. Ethical approval and informed consent were obtained. Participants completed the Female Sexual Function Index (FSFI), EULAR Sjӧgren’s Syndrome Patient Reported Index (ESSPRI), NRS scale for vaginal dryness (0-10), Profile of Fatigue and Discomfort (ProFaD), Cognitive Emotion Regulation Questionnaire (CERQ), Brief Illness Perceptions Questionnaire (BIPQ), West-Haven Yale Multidimensional Pain Inventory (WHYMPI – Part II) and Maudsley Marital Questionnaire (MMQ – Marital subscale). Associations between the FSFI and the outcome measures were assessed using Spearman’s correlations. Variables that significantly correlated with FSFI total score were entered into a backward stepwise multiple regression.ResultsThe survey was completed by 98 women (M = 48.13, SD = 13.26), 70.4% were diagnosed as having primary SS (disease duration range = 3 – 348 months); 43.8% were premenopausal and 48% were postmenopausal. Vaginal dryness was reported by 92.9% of participants, and sexual dysfunction was identified in 85.2% (n = 69/81) of cases (<26.55). Participants who were not sexually active in the previous three-month period (n = 17) were excluded from analyses as inactivity may cause a low FSFI score which may be incorrectly construed as sexual dysfunction. Reduced sexual function was significantly associated with increases in age, vaginal dryness, mental fatigue (ProFaD), self-blame, rumination and catastrophising (CERQ), consequences and identity (BIPQ), negative partner responses (WHYMPI) and relationship dissatisfaction (MMQ). Reduced sexual function was also significantly associated with decreases in positive reappraisal and perspective (CERQ), personal control (BIPQ), solicitous responses and distracting responses (WHYMPI) (Table 1). No significant associations were found for disease duration, relationship duration or ESSPRI total. Results from regression analyses indicated that vaginal dryness (β = -.278, p = .004), CERQ positive reappraisal (β = .322, p = .003) and CERQ catastrophising (β = -.277, p = .009) were significantly related to sexual function and explained 42.0% of the variance in total FSFI scores (F(3,72) = 17.394, p < .001).Table 1.Associations between sexual function and psychosocial parametersFSFI totalrsp95% CI (LB, UB)Age (years)-.270.015-.467-.049Disease duration (months)-.030.793-.253.196Relationship duration (months)-.180.119-.396.054VAS Vaginal dryness-.350.001-.533-.136ESSPRI total-.165.141-.376.062ProFaD Mental Fatigue-.294.008-.486-.074CERQ Self-Blame-.264.017-.461-.042CERQ Rumination-.296.007-.488-.077CERQ Positive Reappraisal.469.000.273.628CERQ Perspective.341.002.126.525CERQ Catastrophising-.499.000-.651-.310BIPQ Consequences-.237.033-.438-.013BIPQ Personal Control-.288.009-.481-.068BIPQ Identity-.294.008-.487-.075MMQ-.282.013-.483-.054WHYMPI Negative Responses-.252.028-.457-.021WHYMPI Solicitous Responses.267.020.037.470WHYMPI Distracting Responses.311.006.085.506Note. N = 81. Associations that were not significant are not shown.ConclusionWomen with SS using positive coping strategies have better sexual function than those with negative coping strategies. Learning positive coping strategies may be an important line of approach for managing sexual dysfunction in SS.References[1]Priori R, et al. Quality of sexual life in women with primary Sjögren syndrome. J Rheumatol. 2015;42(8): 1427-31.Disclosure of InterestsNone declared
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Bergström, J., R. R. Eady, and R. N. F. Thorneley. "The vanadium- and molybdenum-containing nitrogenases of Azotobacter chroococcum. Comparison of mid-point potentials and kinetics of reduction by sodium dithionite of the iron proteins with bound magnesium adenosine 5′-diphosphate." Biochemical Journal 251, no. 1 (April 1, 1988): 165–69. http://dx.doi.org/10.1042/bj2510165.
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The mid-point potentials of the Fe protein components (Ac2 and Ac2* respectively) of the Mo nitrogenase and V nitrogenase from Azotobacter chroococcum were determined in the presence of MgADP to be −450 mV (NHE) [Ac2(MgADP)2-Ac2*ox.(MgADP)2 couple] and −463 mV (NHE) [Ac2* (MgADP)2-Ac2*ox.(ADP)2 couple] at 23 degrees C at pH 7.2. These values are consistent with a flavodoxin characterized by Deistung & Thorneley [(1986) Biochem. J. 239, 69-75] with Em = −522 mV (NHE) being an effective electron donor to both the Mo nitrogenase and the V nitrogenase in vivo. Ac2*ox.(MgADP)2 and Ac2*ox.(MgADP)2 were reduced by SO2.- (formed by the predissociation of dithionite ion, S2O4(2-)) at similar rates, k = 4.7 × 10(6) +/- 0.5 × 10(6) M-1.s-1 and 3.2 × 10(6) +/- 0.2 × 10(6) M-1.s-1 respectively, indicating structural homology at the electron-transfer site associated with the [4Fe-4S] centre in these proteins.
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Weisenburger, Dennis D., Kerry J. Savage, Nancy Lee Harris, Randy D. Gascoyne, Elaine S. Jaffe, Kenneth A. MacLennan, Thomas Rüdiger, et al. "Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project." Blood 117, no. 12 (March 24, 2011): 3402–8. http://dx.doi.org/10.1182/blood-2010-09-310342.
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Abstract The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 109/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.
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Le Deley, Marie Cécile, Laurence Brugières, Denise Williams, and Alfred Reiter. "Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma (ALCL): Results of the European Intergroup Study." Blood 108, no. 11 (November 1, 2006): 2050. http://dx.doi.org/10.1182/blood.v108.11.2050.2050.
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Abstract Purpose and methods In order to study prognostic factors of disease progression and relapse, the data of 235 children enrolled for an ALCL between 1987 and 1997 in the BFM (93 patients, pts), SFOP (82 pts) and UKCCSG (60 pts) studies have been merged in 1998. All these children have been treated according to protocols designed to treat childhood ALCL with a short and intensive chemotherapy treatment, similar to those used for B-cell. Slides had been reviewed by the national pathologist panel for 226 patients (96%). Hodgkin-like ALCL were excluded from this series. Follow-up has been updated in April 2006. Results Among the 235 pts included in the study, 206 pts (88%) achieved a CR. With a median follow-up of 7.4 years, 77 events were observed (13 early progressions, 55 relapses, 3 secondary leukaemias, 6 toxic deaths) and 46 patients died. The 5-year overall survival and event-free survival of the whole population is 81% [95%CI, 76–86%] and 69% [63–75%] respectively. Event-free survival differs significantly according to the treatment (p=.01) : the risks of failure of children treated in the SFOP studies and in the UKCCSG studies are multiplied by 1.8 [1.05–3.2] and 2.3 [1.3–4.1] respectively, as compared to pts treated in the BFM studies. Several factors seem to be prognostic of the risk of early progression or relapse in univariate analysis: B-symptoms, mediastinal involvement, skin lesions, visceral involvement, St Jude stage 3–4 or Ann Arbor stage 3–4 or elevated LDH. Patients with bone lesions seem to have a better prognosis than others. Soft tissue masses do not worsen the prognosis. In multivariate analysis, three factors are found to be associated to the risk of progression/relapse : * mediastinal involvement (hazard ratio of progression/relapse, HR=2.2 [1.3–3.6], p=.003), * visceral involvement defined as lung, liver or spleen involvement (HR=2.1 [1.3–3.5], p=.005), * skin lesions (HR = 1.9 [1.2–3.2], p=.01). Based on the results of this Cox model, it is possible to define: * a good prognosis group (85 patients without skin, mediastinal or visceral involvement) with 89% pts [82–96%] free of progression/relapse at 5 year * a poor prognosis group (150 patients with skin and/or mediastinal and/or visceral involvement) with 61% pts [53–69%] free of progression/relapse at 5 year This risk group classification appears significant in each of the three treatment groups. Conclusion : Results obtained with BFM-studies are significantly better than those obtained with the French and British pediatric studies. Pts with mediastinal involvement, visceral involvement and/or skin lesions are at a higher risk of disease failure. These results was the basis of ALCL99 aiming to improve EFS of high risk pts by adding vinblastine to BFM protocol.
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Lei, Tuo, Hai Bai, and Lei Li. "Research on the Resistance Performance and Damage Deterioration Model of Fiber-Reinforced Gobi Aggregate Concrete." Materials 17, no. 10 (May 12, 2024): 2291. http://dx.doi.org/10.3390/ma17102291.
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Concrete prepared using Gobi sand and gravel instead of ordinary sand and gravel is referred to as Gobi concrete. In order to explore the effect of fibers on the frost resistance of Gobi concrete, as well as to enhance the service life of Gobi aggregate concrete in Northwest China, experiments were conducted with fiber types (polypropylene fibers, basalt fibers, polypropylene–basalt fibers) and fiber volume fractions (0%, 0.1%, 0.2%, 0.3%) as variable parameters. This study investigated the surface morphology, mass loss rate, and relative dynamic elastic modulus of fiber-reinforced Gobi concrete after different freeze–thaw cycles (0, 25, 50, 75, 100). Corresponding frost damage deterioration models were proposed. The results indicate that fibers have a favorable effect on the anti-peeling performance, mass loss rate, and dynamic elastic modulus of Gobi aggregate concrete. The improvement levels of different fiber types are in the following order: 0.1% basalt-polypropylene fibers, 0.2% polypropylene fibers, and 0.3% basalt fibers. Compared to Gobi concrete exposed to natural environmental conditions, the freeze–thaw cycle numbers increased by 343, 79, and 69 times, respectively. A quadratic polynomial damage model for fiber-reinforced Gobi concrete, using relative dynamic elastic modulus as the damage variable, was established and demonstrated good predictive performance.
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Guzel, A., M. Yilmaz, O. Demirhan, A. Pazarbasi, S. Kocaturk-Sel, M. Erkoc, N. Inandiklioglu, F. Ozgunen, and C. Sariturk. "Rapid Detection of Fetal Aneuploidies by Quantitative Fluorescent-Polymerase Chain Reaction for Prenatal Diagnosis in the Turkish Population." Balkan Journal of Medical Genetics 15, no. 1 (January 1, 2012): 11–17. http://dx.doi.org/10.2478/v10034-012-0002-2.
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Rapid Detection of Fetal Aneuploidies by Quantitative Fluorescent-Polymerase Chain Reaction for Prenatal Diagnosis in the Turkish PopulationPrenatal diagnosis is testing for diseases or conditions in a fetus or embryo before it is born. It employs a variety of techniques to determine the health and condition of an unborn fetus. The main goal of this process is to perform prenatal diagnosis at the earliest possible stage of gestation. In this regard, quantitative fluorescent-polymerase chain reaction (QF-PCR), a novel technique that is fast and reliable, was employed to detect aneuploidies (13, 18, 21, X and Y) without the need of the time-consuming culturing process. The QF-PCR method can detect five different chromosome aneuploidies with 98.6% accuracy. In this study, 1874 amniotic fluid samples of pregnant subjects, who were referred to the Department of Medical Biology and Genetics, Adana, Turkey (molecular biology section), were analyzed with the QF-PCR technique by employing 27 short tandem repeat (STR) markers to detect chromosomes 13, 18, 21, X and Y aneuploidies. We detected 31 subjects (1.7%) with aneuploidies or euploidies out of the 1874 subjects. The average age of the pregnant subjects was 32 (range: 14-49). Abnormal karyotypes detected were as follows: 47, XX,+21 (19.4%, 6/31), 47, XY,+21 (48.4%, 15/31), 48, XXX,+21 (3.2%, 1/31), 69, XXX (3.2%, 1/31), 47, XY,+13 (3.2%, 1/31), 47, XXY (9.6%, 3/31), 47, XXX (9.6%, 3/31) and 45, X (3.2%, 1/31). Moreover, some STR markers were found to be more specific to the Turkish population. In conclusion, QF-PCR can be regarded as an alternative method of conventional cytogenetic analysis as it is a rapid and reliable method; however, in most cases it is required to be supported or validated with conventional cytogenetic karyotyping and some STR markers employed for QF-PCR can be more informative for a given population.
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Park, Juyoung, and Yuri Jang. "CLIMATE CHANGE, AIR POLLUTION, AND MENTAL HEALTH AMONG OLDER KOREAN AMERICAN RESIDENTS IN LOW-INCOME SENIOR HOUSING." Innovation in Aging 7, Supplement_1 (December 1, 2023): 1004. http://dx.doi.org/10.1093/geroni/igad104.3227.
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Abstract Given the impact of climate change and air pollution on human health, the present study examined how older individuals’ perceived disruption by extreme weather and air pollution would be linked with mental health. We focused on older Korean Americans living in low-income senior housing and selected anxiety as an indicator of mental health. Data came from surveys with Korean American residents in five low-income senior housing facilities located in the Greater Los Angeles area (n=343, Mean age = 78.4). Anxiety, measured with the GAD-7, averaged 3.38 (SD = 3.77). Perceived levels of disruption caused by extreme weather and air pollution averaged 1.71 (SD = .69) and 1.75 (SD = .72), respectively, out of a range from 1 (not at all) and 4 (very much). Individuals who reported greater disruptions by extreme weather and air pollution had a higher level of anxiety. Given the high correlation between the two types of disruption (r = .56, p < .001), we tested separate regression models of anxiety. Each variable of the perceived disruption by extreme weather (β = .18, p < .001) and air pollution (β = .18, p < .001) was found to have a significant impact on anxiety. Although limited by the use of a small sample of convenience restricted to one ethnic group in one geographic location, our findings suggest the potential mental health impact of climate change and air pollution and call attention to intervention strategies.
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Bormann, Caroline, Catharina Busch, Matus Rehak, Manuela Schmidt, Christian Scharenberg, Focke Ziemssen, and Jan Darius Unterlauft. "Two Year Functional and Structural Changes—A Comparison between Trabeculectomy and XEN Microstent Implantation Using Spectral Domain Optical Coherence Tomography." Journal of Clinical Medicine 11, no. 19 (October 1, 2022): 5840. http://dx.doi.org/10.3390/jcm11195840.
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The aim of this study was to analyze retinal nerve fiber layer (RNFL) thickness after trabeculectomy (TE) versus XEN microstent implantation (XEN) in primary open-angle glaucoma (POAG) cases naïve to prior incisional glaucoma surgery. We examined 119 consecutive glaucoma patients retrospectively, who received a TE or XEN for medically uncontrolled POAG. Intraocular pressure (IOP), amount of IOP-lowering medication, mean deviation of standard automated perimetry and peripapillary RNFL thickness were evaluated during the first 24 months after surgery. Fifty eyes were treated with TE and 69 eyes with XEN. Mean IOP decreased from 25.1 ± 0.8 to 13.3 ± 0.6 mm Hg (p < 0.01) and mean number of IOP-lowering eye drops from 3.2 ± 0.2 to 0.4 ± 0.1 (p < 0.01) 24 months after TE. In 69 eyes undergoing XEN, mean IOP dropped from 24.8 ± 0.6 to 15.0 ± 0.4 mm Hg (p < 0.01) and medication from 3.0 ± 0.1 to 0.6 ± 0.1 (p < 0.01) during the 24 months follow-up. Mean deviation of standard automated perimetry remained stable in TE (8.5 ± 0.7 to 8.1 ± 0.8 dB; p = 0.54) and XEN group (11,0 ± 0.5 to 11.5 ± 0.5 dB; p = 0.12) after 24 months, while mean RNFL thickness further deteriorated in the TE (−2.28 ± 0.65 µm/year) and XEN (−0.68 ± 0.34 µm/year) group. Postoperative RNFL loss develops after TE and XEN despite effective and significant lowering of IOP and amount of IOP-lowering medication. RNFL loss was more pronounced in the first year after glaucoma surgery.
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Tozuka, Takehiro, Hisashi Tanaka, Tomonori Makiguchi, Yosuke Kawashima, Tomohiro Oba, Ryosuke Tsugitomi, Junji Koyama, et al. "Comparison of ICI plus chemotherapy or ipilimumab plus nivolumab based therapy for patients with NSCLC with TPS (1-49%): TOPGAN2023-01." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): 8550. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.8550.
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8550 Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.
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Pulte, Dianne, Lina Jansen, Felipe Castro, and Hermann Brenner. "Changes in Survival of Older Patients with Hematologic Malignancies in the Early 21st Century." Blood 126, no. 23 (December 3, 2015): 3288. http://dx.doi.org/10.1182/blood.v126.23.3288.3288.
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Abstract Background: Survival expectations for patients with hematologic malignancies have improved in the early 21st century. However, survival for older patients remains low and prior studies have not demonstrated as robust an improvement for older patients as for younger patients. Newer, less toxic treatments for several hematologic malignancies have allowed improved survival in older patients in clinical trials. Here, we examine survival for older patients with hematologic malignancies in the early 21st century to determine whether survival has changed over this time period. Methods: Patients over age 65 with a common hematologic malignancy were identified from the Surveillance, Epidemiology, and End Results (SEER) 13 database for the periods 1997-2000, 2001-2004, 2005-2008, and 2009-2012. Malignancies examined included acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelocytic leukemia (CML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and myeloma. Five-year relative survival for each malignancy was calculated using period analysis. For comparison, 5-year relative survival for patients age 50-59 was evaluated as well. Results: Survival expectations were lower for patients age 65 and older than for younger patients with a given hematologic malignancy and survival expectations decreased with age. Five year relative survival increased between 1997-2000 and 2009-12 for all hematologic malignancies. However, for AML and ALL, the increase was limited to patients age 65-74. Five year relative survival estimates increased for all age groups, including 85+, for HL, CML, NHL, CML, and myeloma (Table 1). Five-year relative survival for patients age 85+ increased by 39.6, 11.6 and 31.5 percent units for CLL, myeloma, and NHL, respectively between 1997-2002 and 2009-12. Conclusions: Survival for older patients with hematologic malignancies remains low compared to survival for younger patients. However, survival for older patients has increased in the early 21st century, possibly due to less toxic therapeutic options and improved supportive care, with the greatest improvement observed for NHL , CLL, and CML. Survival remains poor for older patients with acute leukemia, especially in the "oldest old" age group. Table 1. Cancer site Age at diagnosis 5-year relative survival (standard error) 1997-2000 2009-2012 Difference (% units) AML 50-59 21.4 (1.7) 35.0 (1.7) +13.6 65-69 6.6 (1.1) 15.6 (1.7) +9.0 70-74 4.1 (0.8) 8.1 (1.2) +4.0 75-79 3.2 (0.8) 3.4 (0.8) +0.2 80-84 0.4 (0.3) 0.4 (0.4) 0.0 85+ 0.6 (0.4) 0.4 (0.4) -0.2 CML 50-59 46.7 (2.9) 80.4 (2.1) +33.7 65-69 35.2 (3.1) 56.7 (3.5) +21.5 70-74 16.8 (2.2) 48.2 (3.6) +31.4 75-79 13.6 (2.1) 38.4 (3.4) +24.8 80-84 6.4 (1.5) 28.7 (3.6) +22.3 85+ 5.7 (1.7) 18.7 (3.9) +13.0 ALL 50-59 24.5 (4.2) 30.2 (3.8) +5.7 65-74 5.5 (2.0) 19.1 (3.8) +13.6 75+ 2.8 (1.9) 10.6 (3.6) +7.8 CLL 50-59 80.8 (1.4) 92.0 (1.0) +11.2 65-69 67.0 (1.7) 84.7 (1.5) +17.7 70-74 60.9 (1.6) 83.1 (1.6) +22.2 75-79 49.1 (1.7) 80.5 (1.9) +31.4 80-84 35.9 (1.9) 71.3 (2.4) +35.4 85+ 17.6 (1.5) 57.2 (3.2) +39.6 Myeloma 50-59 42.2 (1.6) 58.9 (1.3) +16.7 65-69 27.8 (1.4) 54.7 (1.6) +26.9 70-74 24.6 (1.3) 39.8 (1.5) +15.2 75-79 20.4 (1.2) 41.5 (1.8) +21.1 80-84 13.4 (1.2) 28.5 (1.7) +15.1 85+ 5.5 (0.9) 17.1 (2.0) +11.6 NHL 50-59 63.7 (0.8) 78.1 (0.6) +14.4 65-69 50.8 (0.9) 73.0 (0.9) +22.2 70-74 45.8 (0.9) 68.6 (1.0) +22.8 75-79 35.8 (0.9) 62.7 (1.1) +26.9 80-84 27.2 (0.9) 55.1 (1.3) +27.9 85+ 13.3 (0.8) 44.8 (1.6) +31.5 HL 50-59 71.3 (2.3) 80.7 (1.9) +9.4 65-74 49.8 (2.9) 66.2 (2.9) +16.4 75+ 23.0 (2.5) 45.9 (3.5) +22.9 Disclosures Pulte: ApoPharma: Research Funding; EBSCO: Consultancy; Selexys: Research Funding.
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Lilleby, Wolfgang, Anne Merete Tryggestad, Iris Bigalke, Bjørn Brennhovd, Karol Axcrona, Dag Josefsen, Ulrika Axcrona, Gunnar Kvalheim, and Svein Dueland. "Biochemical relapse in very high-risk prostate cancer after radical prostatectomy and DC-vaccine loaded with tumor RNA, hTERT, and survivin." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 324. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.324.
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324 Background: Patients with very high-risk prostate cancer (VHR-PC) features experience worse outcome after radical prostatectomy. This study was designed to assess biochemical failure and toxicity of adjuvant dendritic cells vaccine (DCV) in prostate cancer patients who are at greatest risk for cancer progression. Methods: Twenty patients with pathological stage pT2 - pT3b and Gleason score 7B-10, pN0, pN+ or pNx were enrolled into the approved study DC-005. The primary end point was clinical failure. Ten patients were tested for disseminated tumor cells (DTCs) to the bone marrow before inclusion to the study. Three patients out of 10 patients had positive DTCs detection in bone marrow. The mean age of the cohort was 63 years (SD 6.9 years), and three patients had postsurgical pN1 status. Eighteen patients had two or more high-risk factors (ISUP grade 5, T3- stage and or PSA > 20 ng/mL). Autologous dendritic cells were transfected with mRNA for hTERT, survivin and tumor mRNA. The DCV product was applied intradermally after curative intended surgery once per week the first months, then once per months the first year, thereafter every 3 months for two years or until biochemical progression (PSA relapse cut-off ≥ 0.3). Results: After 5 years follow-up (FU) 62% (12/20 patients) had not biochemically progressed and with a median FU of 69 months all patients included in the study are alive. Five patients were treated with salvage and one patient with adjuvant radiation treatment, three patients received limited ADT, and three patients are on first line ADT, none of those eight patients have experienced castration resistant prostate cancer. The toxicity was mild with no serious adverse event related to DCV. Conclusions: Adjuvant DCV mitigates the time to biochemical progression. These results appear favorably compared to historical controls in VHR-PC. The clinical outcomes of this study warrants a future enlarged clinical trial. Clinical trial information: NCT01197625.
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koren-Michowitz, Maya, Carsten Müller-Tidow, Aiko Matsubara, Stefanie Göllner, Wolfgang E. Berdel, Arnon Nagler, Seishi Ogawa, and H. Phillip Koeffler. "Older Patients with Normal Cytogenetics AML Have a Higher Rate of Genomic Changes Compared to Young Patients as Determined by SNP Chip Analysis." Blood 116, no. 21 (November 19, 2010): 2479. http://dx.doi.org/10.1182/blood.v116.21.2479.2479.
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Abstract Abstract 2479 Older patients with AML have a worse prognosis compared to young patients. This is partly due to increased incidence of high risk cytogenetic changes and prior hematological disorders; however, the outcome of de novo, normal cytogenetics AML is still worse in older patients, implying distinct pathogenic mechanisms. In order to elucidate further this pathogenesis we used 250K single nucleotide polymorphisms (SNP) Chip arrays to study genomic changes in 49 normal cytogenetics AML patients: 24 old (360 years old) and 25 young (<60 years old). SNP Chip data was analyzed using the CNAG 2.0 software and genomic changes allocated with the UCSC genome browser. Overall, older patients had more genomic changes, (1.83±0.23 per patient) compared to young patients (1.12±0.2 per patient), p=0.02. Chromosomal changes in old and young patients included: losses in 11 and 12, gains in 11 and 7 and CNN-LOH in 11 and 5, respectively (p=1.0, 0.24 and 0.07). Recurrent changes included CNN-LOH of chromosomes 13q (young-2, old-2), 1p (young-1, old-2), 6p (old-2) and 11q (young-1, old-1). While most patients with recurrent CNN-LOH harbored recognized molecular changes including FLT3-ITD in 13q and CBL mutations in 11q, the smallest common region of LOH in 1p and 6p cases did not contain known recurrent molecular lesions. Selected gene targets in the 1p CNN-LOH common region include FGR, RUNX3 and PINK1 and in the 6p CNN-LOH common region DDR1 and RREB1. A higher rate of CNN-LOH occurred in patients with FLT3-ITD; 69% of patients with FLT3-ITD had CNN-LOH compared with 35% of patients without FLT3-ITD, p=0.05. This was mainly explained by a higher rate of CNN-LOH in young patients with FLT3-ITD (100%) compared to young patients without FLT3-ITD (40%), p=0.039. Other molecular changes including FLT3-TKD, NPM and CEBPA mutations and MLL-PTD were not significantly associated with specific genomic changes. The median overall survival (OS) of young patients was not reached compared with 324 days in older patients (p=0.05) and the median EFS was 807 and 324 days in young and older patients, respectively (p=0.2). OS and EFS rates were worse in patients with CNN-LOH compared to patients without CNN-LOH, p=0.025 and 0.037, respectively. CNN-LOH remained an adverse factor for OS and EFS in young patients (p=0.02 for both) but not in older patients (p=0.6 and 0.7). 1p CNN-LOH was found in 6% patients in our cohort compared with a lower incidence of approximately 1% in prior reports that analyzed only young AML patients (Bullinger et al, Leukemia 2010;24:438–449). Although case number was low, a trend was noted for a worse OS of patients with 1p UPD (p=0.059). In summary, we found a higher rate of genomic changes in old compared with young patients with AML, in particular CNN-LOH. This may suggest an underlying genomic instability that is more prevalent in old patients and may contribute to their worse outcome. Disclosures: No relevant conflicts of interest to declare.