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Durbecq, V., S. Majjaj, J. Nogaret, N. Sirtaine, J. Schobbens, D. Noterman, D. Hertens, V. Filipov, D. Larsimont, and I. Veys. "Use of quantitative RT-PCR assay to predict metastases size of sentinel node from breast cancer patients." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 621. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.621.
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621 Background: A RT-PCR Assay (GeneSearch, Veridex, LLC), FDA approved and CE marked to detect metastases > 0.2 mm in sentinel lymph nodes (SLNs) of breast cancer patients, has been in clinical use in our institute for 25 months. The assay gives qualitative (negative/positive) results by applying cutoff values to cycle times (Cts) of mammaglobin (MG) and cytokeratin 19 (CK19) (cutoff values = 30 / 31 Cts). This study evaluates if quantitative Ct values can be used to estimate the probable size of nodal metastases. Methods: To date 384 patients have been clinically tested with the BLN Assay at Institut Jules Bordet. An additional 74 patients were tested in a pilot study. Both sets had SLNs of breast cancer patients divided in ∼2 mm pieces. Alternating pieces were homogenized and intra-operatively processed by the assay. The remaining pieces were used for histological analysis (positive when > 0.2 mm). During clinical use, same-surgery complete axillary dissection was performed when the assay was positive (n=59). Results: Performance of the assay's qualitative results against permanent section H&E was similar for both groups (total N = 458), for a total sensitivity 89% (68/76), specificity 95% (364/382) and overall agreement 94%. The marker Ct values are correlated with metastases size as determined by H&E on adjacent node pieces (r = -0.74 for MG and -0.77 for CK19, p < 0.001). Lower Ct values indicate increased likelihood of macrometastases reported by H&E, as described in the table. Additionally, Assay Ct values in the SLN were predictive of metastases in non-SLN nodes. For example when CK19 and MG < 24 Cts, the non-SLN positivity rate jumps from 29% to 58%. Conclusions: The BLN Assay's high intra- operative qualitative performance minimizes the need for second surgeries for complete axillary dissections. Results from this investigational study examining the marker Ct values suggest that the assay may provide valuable individual tumor volume data intra- operatively or post-operatively. [Table: see text] [Table: see text]
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Uslu, S., G. Kabadayi, P. Teke Kisa, T. Yüce İnel, Z. Arslan, N. Arslan, S. Akar, F. Onen, and İ. Sari. "SAT0543 PREVALENCE OF FABRY’S DISEASE IN MILD AND SEVERE FMF PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1228.2–1229. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5903.
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Background:Fabry disease (FD) is a rare metabolic disorder caused by the mutations in the α-galactosidase A (GLA) gene. FD patients present with heterogeneous clinical manifestations, which may overlap with systemic diseases including familial Mediterranean fever (FMF). Recurrent episodes of fever, abdominal pain, and arthralgias can be observed in both disorders and this may lead to misdiagnosis.Objectives:To investigate FD prevalence in mild and severe FMF patients.Methods:A total of 66 FMF patients, according to the Tel-Hashomer criteria, were included in the study. Patients were grouped into mild (Group 1) and severe (Group 2) subsets according to the severity score. α-GLA enzyme activity and mutations in the GLA gene were performed. Demographic features, clinical findings, MEFV mutations and treatments were recorded.Results:The clinical and demographical characteristics of the patients were given in Table 1. In severe form, 27 patients were using biological drug and 40.7% had amyloidosis. Symptoms related to FD including hypohidrosis, acroparesthesias, and painful neuropathies, were not different between the groups. Only one patient in group 1 had a low GLA enzyme activity (0.1 nmol/h/ml;Normal >2.5) which also had mutations in the GLA gene but MEFV mutation test was negative. (Table 2). This patient was a 39-year-old female with recurrent abdominal pain, distal extremity pain and the presence of fever during the attacks. She was heterozygous for R301Q. In detailed history, she reported mild acroparesthesias, hypohidrosis, and tinnitus.Table 1.Demographic and clinical findingsAll patientsn: 66Group 1n: 32Group 2n: 34p-valueAge, median (min./max.)34 (17/64)27 (17/59)36 (18/64)0.192Male, n (%)36 (54.5)14 (43.8)22 (64.7)0.137Disease duration, median (min./max.)20.5 (1/57)12.5 (2/50)25 (1/57)0.006Family history of FMF, n (%)41 (62.1)22 (68.8)19 (57.6)0.443Alpha-galactosidase A (nmol/h/ml), median (min./max.)5.9 (0.1/16)5.6 (0.1/9.6)6 (3.1/16)0.330Abdominal pain, n (%)58 (87.9)31 (96.9)27 (79.4)0.030Fever, n (%)54 (81.8)25 (78.1)29 (85.3)0.532Arthritis, n (%)34 (51.5)10 (31.3)24 (70.6)0.003Pleuritis, n (%)31 (47)19 (59.4)12 (35.3)0.083Painful neuropathy, n (%)23 (34.8)13 (40.6)10 (29.4)0.440Acroparesthesias, n (%)9 (13.6)6 (18.8)3 (8.8)0.240Angiokeratomas, n (%)0 (0)0 (0)0 (0)-Cardiac abnormalities1 (1.5)1 (3,1)0 (0)0.485Tinnitus, n (%)4 (6.1)3 (9.4)1 (2.9)0.274Hearing loss, n (%)2 (3)2 (6.2)00.086Hypohydrozis, n (%)2 (3)1 (3.1)1 (2.9)0.965Cornea verticillata, n (%)0 (0)0 (0)0 (0)-Proteinüria, n (%)13 (19.7)2 (6.3)11 (32.4)0.012Colchine dosing (mg/day), median (min./max.)2 (1/3)1 (1/2)2 (1/3)<0.001Table 2.MEFV mutant alleles and GLA mutationsAll patientsn: 66Group 1n: 32Group 2n: 34Alpha -galactosidase A (GLA) gene mutations, n (%)1 (1.5)1 (3.1)0 (0)M694V mutations, n (%)47 (35.6)17 (26.5)30 (44.1)Non-M694V mutations, n(%)36(27.2)20 (31.2)16 (23.5)Conclusion:In this study, we showed the following: 1) the FD rate in the total FMF group was 1.5% (3.1% in group 1), 2) none of the patients in the severe FMF subset had abnormal enzyme activity or mutations related with FD, 3) symptoms related with FD such as hearing loss, hypohidrosis, acroparesthesias, and painful neuropathies also noted in FMF patients particularly in the milder group. Based on our results, FD should be considered in the differential diagnosis of FMF particularly in patients with atypical symptoms.Disclosure of Interests:None declared
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Volkov, Vyacheslav V., Vasil I. Sidey, Alexander V. Naumov, Ivan N. Nekrylov, Nikolay Yu Brezhnev, Ekaterina N. Malygina, and Alexander Yu Zavrazhnov. "Высокотемпературная кубическая модификация сульфида галлия (хs = 59 мол %) и Т, х-диаграмма системы Ga – S." Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 21, no. 1 (March 6, 2019): 37–50. http://dx.doi.org/10.17308/kcmf.2019.21/715.
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Уточнена фазовая диаграмма системы Ga – S в области составов от 30.0 до 60.7 mol % серы и в области температур от комнатной до 1220 °С. Выделена и структурно охарактеризована фаза s-Ga2S3, имеющая сфалеритоподобную структуру (пр. гр. , параметр решетки 5.21 Å) с дефицитом атомов в подрешетке галлия, существование которой подтверждено также термическими методами анализа. Определены температурные зависимости параметров решеток моноклинной фазы a-Ga2S3 (Cc) и гексагональной слоистой фазы b-GaS (P63/mmc), причем показано, что параметр c последней существенно зависит от температуры вследствие увеличения ван-дер-ваальсовой щели.
ИСТОЧНИК ФИНАНСИРОВАНИЯ
Работа выполнена при финансовой поддержке РФФИ, проект 18-33-00900-мол-а.
ЛИТЕРАТУРА
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Hindler, Katja, Andrew D. Shaw, Joshua Samuels, Stephanie Fulton, Charles D. Collard, Bernhard Riedel, and David C. Warltier. "Improved Postoperative Outcomes Associated with Preoperative Statin Therapy." Anesthesiology 105, no. 6 (December 1, 2006): 1260–72. http://dx.doi.org/10.1097/00000542-200612000-00027.
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Statin therapy is well established for prevention of cardiovascular disease. Statins may also reduce postoperative mortality and morbidity via a pleiotropic (non-lipid-lowering) effect. The authors conducted a meta-analysis to determine the influence of statin treatment on adverse postoperative outcomes in patients undergoing cardiac, vascular, or noncardiovascular surgery. Two independent authors abstracted data from 12 retrospective and 3 prospective trials (n = 223,010 patients). A meta-analysis was performed to evaluate the overall effect of preoperative statin therapy on postoperative outcomes. Preoperative statin therapy was associated with 38% and 59% reduction in the risk of mortality after cardiac (1.9% vs. 3.1%; P = 0.0001) and vascular (1.7% vs. 6.1%; P = 0.0001) surgery, respectively. When including noncardiac surgery, a 44% reduction in mortality (2.2% vs. 3.2%; P = 0.0001) was observed. Preoperative statin therapy may reduce postoperative mortality in patients undergoing surgical procedures. However, the statin associated effects on postoperative cardiovascular morbidity are too variable to draw any conclusion.
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Antipov, S. A., A. A. Klenina, and I. V. Doronin. "Morphological characteristics of the populations of Coronella austriaca Laurenti, 1768 (Colubridae, Reptilia) on the northern border of its habitat in Russia." Current Studies in Herpetology 21, no. 1/2 (June 21, 2021): 3–17. http://dx.doi.org/10.18500/1814-6090-2021-21-1-2-3-17.
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Detailed morphological characteristics of the populations of Coronella austriaca on the northern border of its range, in the Vladimir and Nizhny Novgorod regions, are presented. L.corp. of males and females reaches 543 mm and 601 mm, respectively. Ventr. is 166–175 and 175–189, respectively, Scd. Is 50–59 and 32–56, Lab. left/right is usually 7/7 (89.7%), Sublab. is 9/9 (72.4%), respectively. A high incidence of asymmetry (44.4%) was noted for Temp. I and II rows; of 23 combinations, the most common is the symmetric one 2+3/2+3 (25.9%). L.corp./L.cd. limits overlap in 3.1% of underyearlings and yearlings, and in 1.8% of adults. Same-sex individuals statistically significantly differ in their meristic characteristics within the studied regions: the females from a locality near the Chucha river differ from the rest ones in Scd. and Sublab.left., males differ in Scd. and Ventr.+Scd.; males also significantly differ in their metric characteristics L.corp., L.cd., L.total.
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Mulaw, Getahun Fentaw, Bizunesh Fantahun Kase, Adebabay Dessie Manchilo, Bereket Lopiso Lombebo, and Begna Melkamu Tollosa. "Severe Acute Malnutrition and Feeding Practice of Children Aged 6-59 Months in Pastoral Community, Afar, Ethiopia: Descriptive Cross-Sectional Study." International Journal of Child Health and Nutrition 9, no. 4 (November 18, 2020): 156–63. http://dx.doi.org/10.6000/1929-4247.2020.09.04.2.
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Background: Severe acute malnutrition remains one of the most common causes of morbidity and mortality among children in developing countries, including Ethiopia. Knowing the local burden of SAM has huge importance for public health interventions. Therefore this study aimed to assess the level of severe acute malnutrition and feeding practice of children aged 6–59 months in Abaa’la district, Afar, Northeast, Ethiopia. Methods: Community-based descriptive cross-sectional study was conducted on 422 mother-child pairs of children aged 6–59 months. Kebeles were selected randomly after stratifying the district in to urban and rural, and study participants were selected using a cluster sampling technique. Data were collected using an interviewer-administered questionnaire, and child nutritional status was measured using WHO Mid upper arm circumference measuring tape. Data were entered into Epi data version 3.1 and exported to SPSS version 22 for analysis. The result was presented using Descriptive statistics. Results: The prevalence of severe acute malnutrition (SAM) was found to be 4.3% (95% CI, 2.3-6.1%) and that of moderate acute malnutrition (MAM) was 21.1 %. Almost all (98.8%) of children were ever breastfed. Prelacteal feeding and bottle feeding was practiced by 31% and 33.9% of children, respectively. Only 68.5% of children were feed colostrum. Around 45.5% of children were exclusively breastfed for the first six months, and 70.4% of children wean breastfeeding before the age of two years. Conclusion: The prevalence of severe acute malnutrition in the study area was lower than the regional figures, but still, it is a public health priority. There are improper child care and feeding practices. Therefore, public health interventions that can improve those practices should be strengthened.
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Vaidya, Karishma Malla, Gehanath Baral, and Bigya Shrestha. "Two Years Trend of Cervical Screening and Precancerous and Cancerous Lesion in Cervical Biopsy in Paropakar Maternity and Women's Hospital." Nepal Journal of Obstetrics and Gynaecology 13, no. 3 (December 31, 2018): 48–50. http://dx.doi.org/10.3126/njog.v13i3.23430.
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Aims: To determine the detection rate of cervical lesion by cervical Pap test and to see the ongoing trend of Pap testing in the hospital.
Methods: The retrospective study was conducted in department of pathology, Paropakar Maternity and Women's Hospital, Thapathali, Kathmandu, Nepal from 2016 to 2018. Pap testing sample received in the department were included in the study. All the data were retrieved from computers and registers at record section and histopathology unit.
Results: There were 5.49% (1688 out of 30725) and 6.12% (1779 out of 29062) of gynecology out-patients had Pap test in first and second year respectively. Epithelial cells abnormalities were seen in 6.1% (104) and 4.83% (86) in first and second year respectively. Cervical biopsy sample in first year and second year had precancer and cancerous lesion in 29.55% (94 out of 318) and 22.01% (59 out of 268) in second year.
Conclusions: Epithelial abnormalities seen in Pap test could detect quite a good proportion of abnormal cervical lesion in biopsy specimen of cervix.
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Brown, Elizabeth R., Anna Bershteyn, Helen C. Stankiewicz Karita, Christine Johnston, Lorna Thorpe, Angelica Kottkamp, Kathleen Neuzil, et al. "LB-17. Efficacy of Hydroxychloroquine (HCQ) for Post-exposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Blinded, Randomized, Controlled Trial." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S851—S852. http://dx.doi.org/10.1093/ofid/ofaa515.1914.
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Abstract Background Prevention interventions for coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are currently limited to non-pharmaceutical strategies. Observational and laboratory data suggested that hydroxychloroquine (HCQ) had biologic activity against SARS-CoV-2. A blinded trial of HCQ in persons with confirmed exposure and virologic and clinical endpoints is needed. Methods We conducted a national, householdrandomized, double-blind, controlled trial of HCQ post-exposure prophylaxis, with entirely remote study procedures. We enrolled close contacts exposed to persons with SARS-CoV-2 infection in the past 96 hours. Participants were randomized to either HCQ (400 mg daily for three days followed by 200 mg daily for eleven days) or ascorbic acid (500 mg followed by 250 mg daily), as a placebo-equivalent control. Participants self-collected mid-turbinate swabs daily (days 1–14) for SARS-CoV-2 PCR testing. The primary outcome was PCR-confirmed, incident SARS-CoV-2 infection among persons SARS-CoV-2 negative at enrollment. Symptoms were assessed using criteria from the US CDC. Results From March-August 2020, 623 households were randomized; 311 households (381 participants) to the HCQ group and 312 households (400 participants) to the control group. Ninety- one percent of participants were retained up to day 14 and 9,595 of 10,588 (91%) of swabs were tested. Among participants who were SARS-CoV-2 negative at baseline (n=626/781, 80%), the cumulative incidence of SARS-CoV-2 was 14.5% (95% CI: 11.6–17.4) and the cumulative incidence of COVID-19 symptoms was 11.6% (95% CI: 8.9–14.2) at day 14. By day 14, there was no difference between the HCQ group and control group in SARS-CoV-2 acquisition (46 vs. 43 events, aHR= 0.99, 95% CI 0.64–1.52, p=0.95) or symptomatic disease (40 vs. 32 events, aHR= 1.23, 95% CI: 0.76–1.99, p=0.40). The adverse event frequency was similar between groups (59 [15.5%] participants in the HCQ and 45 [11.3%] in the control group, p=0.092). Cumulative incidence of RT-PCR-confirmed SARS-CoV-2 infection among close contacts of diagnosed cases, by study group Conclusion This randomized, double-blind, controlled trial among persons with recent exposure and high incidence of SAR-CoV2 provides strong evidence that HCQ post-exposure prophylaxis did not prevent SARS-CoV-2 infection or modify clinical disease. Disclosures Anna Bershteyn, PhD, Bill and Melinda Gates Foundation (Grant/Research Support)Gates Ventures (Consultant)National Institutes of Health (Grant/Research Support) Kristopher M. Paolino, MD, MTM&H, Nothing to disclose Raphael J. Landovitz, MD, MSc, Gilead (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Other Financial or Material Support, Speaker Honoraria) Anna Wald, MD, MPH, Aicuris (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): DSMB participation; provision of vaccine for a study, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Scientific Research Study Investigator; X-Vax (Individual(s) Involved: Self): Consultant Helen Y. Chu, MD MPH, Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support)
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Semenenko, S. I., A. I. Semenenko, and O. O. Yakovleva. "Efficacy of ademol in experimental cranial injury on the effect of oxidative stress." Infusion & Chemotherapy, no. 3.1 (October 11, 2020): 71–72. http://dx.doi.org/10.32902/2663-0338-2020-3.1-59.
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Objective. To evaluate the effectiveness and safety of ademol for oxidative stress in the brain of rats with traumatic brain injury (TBI).
Materials and methods. In 260 male-rats weighing 160-180 g, the preclinical efficacy of ademol was studied against the background of the actual developed TBI model. Several groups of animals were formed: pseudo-operated (TBI + 0.9 % NaCl intravenously), control pathology (TBI + 0.9 % NaCl intravenously), TBI + ademol 2 mg/kg intravenously, comparison drug (TBI + amantadine sulfate). The experimental model was induced by the action of a stream of carbon dioxide under pressure using a gas-balloon air pistol “Baikal MR-654K”, evaluated only severe trauma (the air pistol hole is close to the center of the trepanation hole in rats). Ademol (Ademol-Darnytsia, Ukraine) was administered in several doses to determine the conditionally effective dose, and the reference drug amantadine sulfate (PC-Merz, Switzerland) was administered slowly with infusomate for 2 h after 12 h for 8 days, 60 min after injury. Biochemical processes in traumatically damaged brain (in homogenates and postnuclear supernatant) were studied on the 8th day, oxidative stress parameters were evaluated by the content of malonic dialdehyde (MDA) by reaction with thiobarbituric acid, carbonyl groups of proteins (CGP) – by reaction with dinitrophenylhydrazine, activity of antioxidant enzymes – by reaction with superoxide dismutase (SOD), glutathione peroxidase (GPO) and catalase. Statistical processing was performed according to StatPlus programs, by parametric and nonparametric criteria, the differences were considered significant at p<0.05.
Results and discussion. Hyperactivation of free radical oxidation of biomembrane lipids is registered in the brain structures of injured rats. In the group of pseudooperated animals, the median content of the secondary metabolite of lipoperoxidation MDA in the brain was 13.2 (95 % confidence interval (CI) 12.8-14.2) μmol/g of dry tissue. In the control pathology group, the MDA index is 2.28 times (p<0.05) higher than in pseudooperated animals, the median is 30.8 (95 % CI 28.6-33.3) μmol/g of dry tissue. The use of the studied drugs reduces the activation of lipid peroxidation processes in brain tissues. Ademol had the most active influence. In the group of animals treated with this drug, the content of MDA in the brain was lower by 58.3 % (p<0.05) than in the control pathology group, the median was 14.6 (95 % CI 12.6-15.5) μmol/g of dry tissue. Amantadine sulfate was inferior to ademol: the content of MDA in the brain was lower by 48.4 % (p<0.05), the median was 16.1 (95 % CI 14.9-16.7) μmol/g of dry tissue.
The development of TBI was associated with the activation of oxidative modification of CGP. In pseudooperated animals, the median content of CGP in the brain was 4.73 (95 % CI 4.29-5.01) μmol/g of dry tissue, the level of CGP is 1.77 times higher (p<0.05) in control pathology group. The active preventive drug was ademol: the content of CGP in the brain decreased by 40.1 % (p<0,05) than in animals of the control pathology group, the median was 4.90 (95 % CI 4.62-5.54) μmol/g of dry cloth. Amantadine was slightly inferior to ademol in this effect: the content of CGP in the brain was lower by 39.1 % (p<0.05), against control pathology, the median was 4.99 (95 % CI 4.65-5.59) μmol/g of dry cloth. Oxidative stress occurred against the background of decreasing the rate of inactivation of the superoxide anion radical: the median activity with the participation of SOD in the brains of pseudooperated animals was 2.68 (95 % CI 2.23-3.05) um. od/mg protein; there was also a decrease in the activity of SOD in the brain by 51.7 % (p<0.05) in the control pathology group, the median activity of the enzyme was 1.31 (95 % CI 0.97-1.57) um. od/mg protein. Pharmacotherapy prevented a drop in the reaction rate of SOD: on the background of ademol, it was 105 % higher than the control pathology group, the median of its activity was 2.69 (95 % CI 2.17-3.16) um. od/mg protein. Amantadine sulfate was slightly inferior to ademol: the activity of SOD in the brain was less by 101 %, the median of its activity was 2.53 (95 % CI 2.09-3.11) um. od/mg of protein. TBI is also accompanied by inhibition of hydrogen peroxide inactivation by the enzymes GPO and catalase: a decrease in brain tissues activity of GPO by 55.3 % and catalase by 53.0 %. When corrected with ademol, the activity of GPO in brain was higher by 70.9 %, as well as the activity of catalase – by 89.5 % (ranged from 6.39 to 7.45 μcatal/mg protein), against levels in the control pathology group. Amantadine sulfate contributed to an increase in the activity of GPO by 44.5 % (from 55.5 to 61.2 μmol/min per 1 mg of protein), an increase in catalase – by 79.0 % (from 6.21 to 6.75 μcatal/mg of protein) than indicators in the control pathology group.
Conclusions. The use of ademol in rats with TBI contributes to the probable restraint of oxidative stress: reducing the prooxidative effect of trauma and activation of antioxidant enzymes.
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Lavie, O., O. Barnett-Griness, S. A. Narod, and G. Rennert. "The risk of developing uterine sarcoma after tamoxifen use." International Journal of Gynecologic Cancer 18, no. 2 (2008): 352–56. http://dx.doi.org/10.1111/j.1525-1438.2007.01025.x.
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The treatment of breast cancer with tamoxifen results in an increased risk of uterine cancer. The objective of this study was to evaluate the association between tamoxifen use and the risk of developing uterine sarcomas and endometrial carcinomas in a historical cohort of women diagnosed with breast cancer in 1987–1988. The medical records of all women diagnosed in Israel with breast cancer in the years 1987–1988 were sought. Clinical data, including use of hormone therapy, were extracted from oncology records. In 2004, patient identifiers were linked to the Israel Cancer Registry database to identify all uterine cancers that occurred within 15 years of the diagnosis of breast cancer. The records for 1507 breast cancer cases (84%) were retrieved. Among these cases, 32 uterine malignancies were identified; 11 occurred prior to the diagnosis of breast cancer and 21 occurred during the follow-up period. Eight hundred seventy-five women in the cohort had used tamoxifen (59%). There were 17 uterine cancers observed among the 875 exposed to tamoxifen (1.9%), compared to 4 uterine cancers among the 621 women (0.6%) who did not use tamoxifen (odds ratio = 3.1; 95% CI: 1.0–9.1; P = 0.04). There were four uterine sarcomas among the tamoxifen users, but none among nonusers (P = 0.15). Five of the 875 tamoxifen users (0.6%) died of uterine cancer, compared to no deaths among nonusers (P = 0.08). We conclude that in this national breast cancer cohort, tamoxifen use was associated with elevated risks of uterine cancer incidence and mortality. Uterine sarcomas appear to be overrepresented among women who use tamoxifen.
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Schaefer, M., P. Herzer, C. Kühne, H. Kellner, A. Zink, and A. Strangfeld. "OP0020 IMPACT OF BDMARDS WITH DIFFERENT MODES OF ACTION ON FATIGUE IN RA PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 15–16. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1498.
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Background:Fatigue is an important patient-reported outcome. It has been reported to be potentially targetable by DMARDs with specific modes of action, particularly IL-6 inhibition [1].Objectives:To assess to which extent patients on DMARDs with different modes of action reach fatigue levels of 2 or less on a 0 (no fatigue) to 10 (high fatigue) scale after 6 months of treatment.Methods:The German register RABBIT is a prospective longitudinally followed cohort of RA patients enrolled with a new start of a DMARD after at least one csDMARD failure. This analysis comprises bionaive patients who were enrolled with start of a b/tsDMARD between 01/2009 and 04/2019, who had at least 1 follow-up, did not switch during the first 3 months and afterwards only within the same substance, and presented fatigue levels of > 2 at baseline.Poisson regression models with a robust error variance were used to calculate risk ratios (RRs) for reaching fatigue values ≤ 2, for all DMARD modes of action. Propensity score weighting was used to adjust for confounding by indication. Multiple imputation of missing values was performed.Results:Baseline fatigue levels were 5.1 overall and 6.1 among patients with a fatigue level of > 2 points on average. They were comparable among different DMARD modes of action. csDMARD patients had lower values than others regarding disease duration, disease activity, or joint erosions (Table 1).Table 1.Patient characteristics for different DMARD modes of actionParametercsDMARDsTNFiRTXABAIL-6JAKiN23762772115166357110Fatigue at baseline5.9 (2)6.1 (2)5.9 (2)5.9 (1.9)6.1 (2)6.3 (1.9)Age [years]58.5 (12.7)56.3 (12.4)62.7 (10.9)59.7 (12.6)57.9 (12.5)61.5 (11.5)Female sex1809 (76.1)2060 (74.3)82 (71.2)118 (71)272 (76.3)79 (70.1)Disease duration [years]6.2 (7.2)8.7 (8.1)10.8 (9.7)9.8 (9.2)7.9 (7.6)8.5 (10)Joint erosions634 (28.4)1358 (50.5)62 (56.8)91 (55.4)158 (46.4)45 (41.3)Prior csDMARD therapies1.3 (0.6)2.3 (1)2.5 (1.1)2.2 (1)2.2 (0.9)1.8 (0.8)DAS28-ESR4.6 (1.2)5 (1.2)5.3 (1.3)5.3 (1.2)5.2 (1.3)4.9 (1.3)% of full physical capacity67.4 (21.6)64.6 (22)57 (23.5)59.5 (21.3)63.8 (20.9)61.6 (23)Glucocorticoid therapy (last 6 months)1161 (48.9)1747 (63)76 (66.4)93 (56)198 (55.5)42 (38.1)Fibromyalgia73 (3.1)111 (4)6 (5.2)7 (4.2)11 (3.1)1 (0.9)Depression180 (7.6)218 (7.9)10 (8.7)14 (8.4)26 (7.3)16 (14.6)Ever smoker1252 (52.7)1497 (54)68 (59)84 (50.7)200 (56)59 (53.5)Results are presented as mean ± SD or number (percentage). Absolute numbers may be rounded due to multiple imputation.The RR of IL-6 inhibitors for achieving a fatigue level of ≤ 2 was 1.34 (95% CI: 1.09 – 1.64) compared to csDMARDs. Among other factors, current smoking, prevalent fibromyalgia and depression had a negative impact on achieving a low fatigue level (Table 2).Table 2.Risk ratios for achieving fatigue levels ≤2Parameter (at baseline)RR95% confidence intervalFatigue (1 point higher)0.83(0.80;0.86)TNF inhibitor (vs. csDMARDs)1.11(0.99;1.24)Rituximab (vs. csDMARDs)1.10(0.71;1.68)Abatacept (vs. csDMARDs)1.13(0.82;1.54)IL-6 inhibitor (vs. csDMARDs)1.34(1.09;1.64)JAK inhibitor (vs. csDMARDs)1.19(0.81;1.75)Age (5 years more)0.97(0.95;0.99)Female sex0.83(0.74;0.92)Patient global health (1 point higher)0.97(0.94;0.997)Joint erosions1.19(1.07;1.32)Current smoking0.86(0.76;0.98)Former smoking0.92(0.82;1.04)Fibromyalgia0.56(0.35;0.90)Depression0.75(0.59;0.95)Conclusion:Treatment with IL-6 inhibitors significantly increases the chance of reaching low fatigue levels within half a year in RA patients, while current smoking reduces it.References:[1]Choy E.H.S. and Calabrese L. H Rheumatology 2018;57:1885-95.Acknowledgments:RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Fresenius Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB.Disclosure of Interests:Martin Schaefer: None declared, Peter Herzer Speakers bureau: AbbVie, Novartis, Sanofi, Janssen, Cornelia Kühne Grant/research support from: Novartis, Amgen, Roche/Chugai, Pfizer, Celgene, AbbVie, Sanofi, Herbert Kellner Grant/research support from: Biogen, Consultant of: Biogen, Speakers bureau: Biogen, Angela Zink Speakers bureau: AbbVie, Amgen, BMS, Gilead, Hexal, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi Aventis, UCB, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis
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Lynch, Julie Ann, Michael J. Kelley, Kyung Min Lee, Anna Hung, Yanhong Li, Bradley J. Hintze, Trudy Pendergraft, et al. "An NLP tool to identify molecular diagnostic testing in veterans with stage IV NSCLC." Journal of Clinical Oncology 37, no. 27_suppl (September 20, 2019): 318. http://dx.doi.org/10.1200/jco.2019.37.27_suppl.318.
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318 Background: ASCO Quality Oncology Practice Initiative (QOPI) encourages hospitals to determine if patients (pts) with stage IV NSCLC adenocarcinoma have activating EGFR mutations. Guidelines recommend tumor testing to identify ALK, BRAF, EGFR, ROS1 and other gene alterations before treatment. Studies have shown EGFR testing underutilization. We developed and tested a tool to identify EGFR tests in Veterans Affairs (VA) electronic health record (EHR). We examined whether Veterans with newly diagnosed NSCLC-IV underwent EGFR testing. We measured EGFR testing trends and analyzed differences by patient, VA Medical Center (VAMC) and region. Methods: VA EHR data identified Veterans with NSCLC-IV diagnosed 2013-2017, who survived 45+ days and had 2+ visits with a VA oncologist within 120 days of diagnosis. All NSCLC histologies were included. Demographics and VAMC were obtained from VA Corporate Data Warehouse. EGFR testing results performed outside VA were from commercial laboratory data. We deployed a natural language processing (NLP) tool to identify EGFR tests in VA EHR clinical notes. Testing rates and characteristics associated with testing were examined by descriptive analysis. Results: Of 3484 pts, 623 (18%) had evidence of EGFR testing. There was a 244% rise in testing. 54 (9%) pts diagnosed in 2013 were tested vs 186 (25%) diagnosed in 2017 ( χ2 82.3, p-value 0.00). No statistically significant differences by sex, race, or urban/rural address existed. Testing decreased as pts aged ( χ2 27, p-value 0.00). 35% of pts age ≤49 and 12% of pts age ≥80 were tested. Testing varied widely by VAMC and region (VAMC χ2 795.6, p-value 0.00; region χ2 90.3, p-value 0.00). 28% of pts in the Pacific were tested vs 10% of pts in the Southeast. The main contributor to regional variation was VAMC differences. VAMCs that conducted EGFR testing within their own laboratories (64% and 53%), or were co-located with the national precision oncology program (NPOP, 59%) tested the most pts. NPOP was temporally associated with increased testing nationally. 9% of pts diagnosed in 2017 were tested using NPOP. Conclusions: EGFR testing underutilization in the VA persists. QOPI and the NLP tool for this initiative will help system-wide quality improvement initiatives.
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Meyers, Stephen L., Katherine M. Jennings, David W. Monks, James R. Ballington, and David L. Jordan. "POST Control of Carolina Redroot (Lachnanthes caroliniana)." Weed Technology 27, no. 3 (September 2013): 534–37. http://dx.doi.org/10.1614/wt-d-12-00164.1.
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Greenhouse studies were conducted in 2012 in Raleigh, NC to determine Carolina redroot control by ten POST herbicides. Paraquat and glufosinate provided the greatest control 14 (73 and 64%, respectively) and 25 d (82 and 68%, respectively) after treatment (DAT), but control declined between 25 and 63 DAT (72 and 59%, respectively). Glyphosate provided minimal control 14 DAT (18%), and control increased from 14 to 25 DAT (46%) and 25 to 63 DAT (69%). Control of Carolina redroot roots and rhizomes (roots/rhizomes) was greatest in plants treated with paraquat (91%), glyphosate (88%), glufosinate (73%), hexazinone (62%), diuron (60%). Nontreated Carolina redroot shoot and root/rhizome dry weight were 8.3 and 7.6 g, respectively. Paraquat, glufosinate, glyphosate, and diuron reduced both shoot and root/rhizome dry weight (3.1 and 0.7 g, 5.1 and 2.7 g, 5.4 and 1.0, 5.7 and 1.6 g, respectively). Hexazinone reduced root/rhizome dry weight (2.7 g). Fomesafen reduced shoot dry weight (6.1 g), but did not reduce root/rhizome dry weight. Paraquat, glufosinate, glyphosate, hexazinone, diuron, and clopyralid treatments resulted in reduced incidence of Carolina redroot flowering and anthesis.
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Miranda, Vanessa Costa, Luiza Dib Faria, Maria Ignez Freitas Melro Braghiroli, Monica Jacobs, Jorge Sabbaga, Paulo Marcelo Hoff, and Rachel Pimenta Riechelmann. "A phase II trial of metformin and fluorouracil (MetFU) for patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard treatment." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 601. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.601.
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601 Background: Pts with mCRC whose disease progressed after 5-FU, oxaliplatin, irinotecan and monoclonal antibodies have an unmet medical need. There is growing evidence suggesting an antitumoral effect of metformin in several tumor types, including CRC. Methods: Our primary objective was to evaluate the efficacy and safety of MetFU in heavily pretreated CRC pts with current progressive disease Last dose of 5-FU was administred at least 4 months prior to enrollment. Efficacy was defined as disease control rate at 8 weeks, using RECIST 1.1. Secondary endpoints were progression free survival, overall survival and tolerability. Single-arm Simon two-stage phase II trial was used. The treatment consisted of metformin 850 mg bid continuously plus 5-FU 425mg/m2 + Leucovorin (LV) 50 mg weekly for 4 weeks until disease progression, unacceptable toxicity or consent withdrawn in pts with mCRC who had progressed to conventional lines of treatment. Results: In the first stage, 22 pts were included: 12 pts (54%) were men, median age was 55 years and 59% were classified as an ECOG 1.14 pts faced treatment adverse events and 4 pts were excluded due to toxicity G3/4 - 2 pts had thrombocytopenia and 2 had limiting fatigue. Median time on treatment was 3.8 months, and 17 pts were evaluable for response: 6 pts (27%) had stable disease at 8 weeks as best response, with a median progression free survival (PFS) of 8.1 months. For the whole cohort, median overall survival was 5.6 months (IC95%: 3.1-8.2) and PFS was 2.0 months (IC95%: 1.8-2.3). Conclusions: Our results suggest that metformin may have antitumor activity when combined with 5-FU/LV in a subgroup of mCRC pts, with acceptable toxicity. It is unlikely that 5-FU alone had activity in these heavily treated pts. Clinical trial information: NCT01941953.
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Hehlmann, Rüdiger, Michael Lauseker, Susanne Jung-Munkwitz, Armin Leitner, Martin C. Müller, Nadine Pletsch, Ulrike Proetel, et al. "Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia." Journal of Clinical Oncology 29, no. 12 (April 20, 2011): 1634–42. http://dx.doi.org/10.1200/jco.2010.32.0598.
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Purpose Treatment of chronic-phase (CP) chronic myeloid leukemia (CML) with imatinib 400 mg/d can be unsatisfactory. Optimization of treatment is warranted. Patients and Methods In all, 1,014 newly diagnosed CP-CML patients were randomly assigned to imatinib 800 mg/d (n = 338), imatinib 400 mg/d (n = 325), or imatinib 400 mg/d plus interferon alfa (IFN-α; n = 351). Dose adaptation to avoid higher-grade toxicity was recommended. First primary end point was major molecular remission (MMR) at 12 months. Results A higher rate of MMR at 12 months occurred with tolerability-adapted imatinib 800 mg/d than with imatinib 400 mg/d (59% [95% CI, 53% to 65%] v 44% [95% CI, 37% to 50%]; P < .001) or imatinib 400 mg/d plus IFN-α (59% v 46% [95% CI, 40% to 52%]; P = .002). Median dose in the 800-mg/d arm was 628 mg/d with a maximum dose of 737 mg/d during months 4 to 6 and a maintenance dose of 600 mg/d. All three treatment approaches were well tolerated with similar grade 3 and 4 adverse events. Independent of treatment approach, MMR at 12 months showed better progression-free survival (99% v 94%; P = .0023) and overall survival (99% v 93%; P = .0011) at 3 years when compared with > 1% on the international scale or no MMR but showed no difference in 0.1% to < 1% on the international scale, which closely correlates with complete cytogenetic remission. Conclusion Treatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival.
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Khanam, Fahmida, Ashees Kumar Saha, and China Rani Mittra. "Infection control practices in a district hospital." Asian Journal of Medical and Biological Research 6, no. 2 (July 7, 2020): 321–27. http://dx.doi.org/10.3329/ajmbr.v6i2.48079.
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Infection control practice is one of the major task performed by health care worker to reduce health care-associated infections (HACIs) in hospital. Health care-associated infections (HACIs) are common causes of illness and mortality among hospitalized patients including healthcare workers. The study aimed to identify the infection control practices in a district hospital. A cross sectional study was conducted from January to December, 2019 in a district hospital, Jashore, Bangladesh. Two hundred and twelve (212) Healthcare workers were selected purposively from this hospital and interviewed with a pre-tested semi-structured questionnaire. An observational check list was also used to observe the practices of that hospital. Among the healthcare workers 21 (9.9%) were doctor, 143 (67.5%) were nurse, 8 (3.8%) were technologist, 7 (3.3%) were aya, 13 (6.1%), were ward boy and 20 (9.4%) were cleaner. Collected data were checked, coded and transferred in to SPSS version 25 for analysis. Frequency, Percentage, Mean, SD, chi-square and other statistics were calculated. P-value less than 0.05 were set as statistically significant. The practices scores were categorized into good (≥80%), fair (59-79%), and poor (≤59%). The study found that overall of the respondents had fair practices regarding infection control. Among the doctors, nurse 7.3% had good practice, 51.8% had fair practice and 40.9% had poor practice. Among the supporting staffs 54.20% had Fair practice and 45.80% had Poor practice regarding infection control practices. Association between use of PPE with gender (p-.000) and with designation (p-.000) was evaluated and found highly significant relationship. Study findings suggest that in the existing infection control practices are often neglected and failed to protect healthcare workers and patients from hospital acquired infection.
Asian J. Med. Biol. Res. June 2020, 6(2): 321-327
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Buda, Gabriele, Alessandro Martino, Daniele Campa, Juan Sainz, Rui Manuel Vieira Reis, Ramón García-Sanz, Krzysztof Jamroziak, et al. "Polymorphisms in Regulators of Xenobiotic Transport and Metabolism Genes NR1I2 and NR1I3 and Multiple Myeloma Risk: A Case-Control Study in the Context of IMMEnSE Consortium." Blood 118, no. 21 (November 18, 2011): 5014. http://dx.doi.org/10.1182/blood.v118.21.5014.5014.
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Abstract Abstract 5014 Exposure to toxic compounds and pesticides leads to an increased risk to develop Multiple Myeloma (MM). The metabolism and the excretion of xenobiotics are mediated by the enzymes and transporters acting in the detoxifying/elimination process. The nuclear receptors NR1I2 (or PXR) and NR1I3 (or CAR) act as xenosensor activating the detoxifying/elimination process in response to the intracellular levels of xenobiotics. It has been hypothesized that part of the individual variability in drug metabolism efficiency could be due to the genetic variations within these regulator genes affecting their expression and/or function. To investigate the impact of genetic variation within these genes on MM susceptibility, we selected and genotyped 10 tag Single Nucleotide Polymorphisms (SNPs) in the PXR gene and 7 tag SNPs in the CAR gene in 627 MM cases (320 males and 307 females) and 883 (459 males and 424 females) controls from different European populations. All the SNPs were in Hardy-Weinberg equilibrium (p>0.001), with the exception of the PXR SNP rs2461818 that was therefore excluded from the analysis. We found no association of any of the genotyped SNPs with MM risk. In the same way, haplotype distribution showed no differences between cases and controls. This was the first comprehensive investigation of genetic variation in xenobiotic regulators genes PXR and CAR in relation to MM risk and our data suggest that common variants in these genes have no impact in modifying MM risk. Table I. Genotype distribution of the PXR and CAR SNPs among MM cases and controls. SNP (rs) Cases (%) Controls (%) OR* 95%C.I. p-value p-trend PXR C/C 429 (69.5) 623 (70.7) 1.00 Ref 0.423 rs10511395 A/C 160 (25.9) 228 (25.9) 1.02 0.81 – 1.30 0.851 A/A 28 (4.6) 30 (3.4) 1.38 0.81 – 2.35 0.232 PXR C/C 452 (74.0) 656 (74.8) 1.00 Ref 0.451 rs1054190 C/T 137 (22.4) 200 (22.8) 1.00 0.78 – 1.28 0.993 T/T 22 (3.6) 21 (2.4) 1.56 0.84 – 2.88 0.155 PXR C/C 412 (65.9) 591 (67.2) 1.00 Ref 0.819 rs11917714 C/T 190 (30.4) 250 (28.5) 1.07 0.85 – 1.35 0.535 T/T 23 (3.7) 38 (4.3) 0.84 0.49 – 1.44 0.536 PXR C/C 223 (36.3) 296 (33.7) 1.00 Ref 0.126 rs12488820 C/T 289 (47.0) 407 (46.4) 0.93 0.74 – 1.18 0.574 T/T 103 (16.7) 175 (19.9) 0.79 0.58 – 1.06 0.119 PXR G/G 430 (69.6) 593 (67.4) 1.00 Ref 0.807 rs13071341 A/G 166 (26.9) 269 (30.6) 0.85 0.67 – 1.07 0.158 A/A 22 (3.5) 18 (2.0) 1.70 0.90 – 3.22 0.102 PXR A/A 352 (58.7) 516 (39.4) 1.00 Ref 0.981 rs3237359 A/G 209 (34.8) 291 (33.5) 1.04 0.83 – 1.30 0.720 G/G 39 (6.5) 62 (7.1) 0.90 0.59 – 1.37 0.619 PXR C/C 255 (41.2) 383 (43.6) 1.00 Ref 0.815 rs13059232 C/T 299 (48.3) 390 (44.4) 1.16 0.93 – 1.44 0.192 T/T 65 (10.5) 106 (12.0) 0.94 0.66 – 1.33 0.711 PXR A/A 300 (48.7) 437 (49.7) 1.00 Ref 0.258 rs3732357 A/G 240 (39.0) 361 (41.0) 0.94 0.75 – 1.17 0.589 G/G 76 (12.3) 82 (9.3) 1.31 0.92 – 1.85 0.130 PXR T/T 328 (53.6) 463 (52.9) 1.00 Ref 0.424 rs1357459 C/T 249 (40.7) 345 (39.4) 1.02 0.82 – 1.27 0.850 C/C 35 (5.7) 67 (7.7) 0.75 0.49 – 1.17 0.206 CAR A/A 218 (35.4) 335 (38.1) 1.00 Ref 0.571 rs3003596 A/G 296 (48.0) 393 (44.7) 1.16 0.93 – 1.46 0.191 G/G 102 (16.6) 151 (17.2) 1.04 0.77 – 1.41 0.799 CAR G/G 264 (42.7) 371 (42.0) 1.00 Ref 0.642 rs3813627 G/T 276 (44.7) 392 (44.4) 0.98 0.79 – 1.23 0.882 T/T 78 (12.6) 120 (13.6) 0.91 0.66 – 1.26 0.581 CAR A/A 441 (73.1) 635 (73.5) 1.00 Ref 0.911 rs11265571 A/T 147 (24.4) 207 (24.0) 1.01 0.79 – 1.29 0.911 T/T 15 (2.5) 22 (2.5) 0.97 0.49 – 1.89 0.921 CAR T/T 404 (64.2) 575 (65.7) 1.00 Ref 0.836 rs2307418 G/T 193 (31.1) 268 (30.6) 1.02 0.81 – 1.27 0.879 G/G 23 (3.7) 32 (3.7) 1.05 0.60 – 1.83 0.863 CAR C/C 348 (56.6) 508 (57.7) 1.00 Ref 0.527 rs2502805 C/T 220 (35.8) 313 (35.6) 1.05 0.84 – 1.30 0.693 T/T 47 (7.6) 59 (6.7) 1.16 0.77 – 1.74 0.484 CAR A/A 245 (39.8) 346 (39.4) 1.00 Ref 0.770 rs4073054 A/C 291 (47.2) 412 (46.9) 0.98 0.78 – 1.22 0.855 C/C 80 (13.0) 120 (13.7) 0.94 0.68 – 1.31 0.720 CAR C/C 360 (57.6) 524 (59.8) 1.00 Ref 0.391 rs4233368 A/C 225 (36.0) 302 (34.4) 1.09 0.88 – 1.36 0.439 A/A 40 (6.4) 51 (5.8) 1.15 0.74 – 1.78 0.538 Genotype distribution among MM cases and controls in the overall population. * OR are adjusted for age, gender and region of origin. Differences in samples numbers are due to failures in genotyping. Disclosures: No relevant conflicts of interest to declare.
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Bacher, Ulrike, Torsten Haferlach, Wolfgang Kern, Tamara Weiss, Susanne Schnittger, and Claudia Haferlach. "Correlation of Cytomorphology, Immunophenotyping, and Interphase Fluorescence in Situ Hybridization (FISH) in 381 Patients with MGUS and 310 Patients with Multiple Myeloma." Blood 114, no. 22 (November 20, 2009): 2812. http://dx.doi.org/10.1182/blood.v114.22.2812.2812.
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Abstract Abstract 2812 Poster Board II-788 From cytomorphological aspects, monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are overlapping disorders. According to the WHO classification, a threshold of 10% of plasma cells (PCs) in bone marrow (BM) aspirates separates both categories. To clarify whether this separation is justified from cytogenetic aspects, we performed comparison of interphase fluorescence in situ hybridization (FISH) patterns in 691 patients with MGUS (n=381) or MM (n=310). Also, the results of cytomorphology and immunophenotyping using multiparameter flow cytometry (MFC) were correlated. 278 females and 413 males (22.8-92.8 yrs) at first presentation of MM/MGUS were analyzed between 2005-2009 in our laboratory with a combination of cytomorphology, MFC, and FISH following magnetic activated cell sorting (MACS) of CD138+ PCs (Robosep, STEMCELL Technologies, Vancouver). According to cytomorphological WHO criteria, 381 patients were categorized as MGUS (median BM PCs, 5%), 310 as MM (median PCs, 18.5%). The number of FISH probes being applicable to samples was depending on the amount of plasma cells yielded from MACS procedure. In the MM pts, a median of 12 probes was applied (range, 0-22) which was slightly higher than in the MGUS patients (median: 11; 0-18) (p=0.00002). FISH procedure was hampered by insufficient PC numbers more frequently in MGUS (79/381, 20.7%) than in MM pts (29/310; 9.3%) (p=0.0004). In MM pts, FISH revealed a median of 2 and a maximum of 7 cytogenetic alterations per patient in contrast to a median of 0 and a maximum of 5 in MGUS (p<0.0001). In more detail, in MM the maximum number of gains of genetic material per patient was 7 (MGUS: 5), of losses 7 (MGUS: 3), and of reciprocal rearrangements 2 (MGUS: 1). Subsequently, cytogenetic alterations were compared in those 527 pts (260 MM and 267 MGUS pts; 76.3% of all pts), in whom PC numbers allowed performance of at least 5 FISH probes (t(11;14), t(4;14), t(14;16), 13q14, TP53). Abnormal FISH results were detected in 145/260 MM (55.8%) and 106/267 MGUS pts (39.7%) (p=0.0002). In MM, 31/260 (11.8%) had a t(4;14)/IGH-FGFR3 in contrast to 5/268 (1.9%) in MGUS (p<0.0001). The t(11;14)/IGH-CCND1 (MM: n=41; 15.6%; MGUS: n=50; 18.7%; n.s.) and t(14;16)/IGH-MAF were similarly frequent in both cohorts (MM: n=8; 3.1%; MGUS: n=3; 1.1%; n.s.). Monosomy13/del(13)(q14) was more frequent in MM (n=103; 39.3%) when compared to MGUS (n=59; 22.1%, p=0.0001). Deletions of TP53/17p13 were seen in 16 MM (6.1%) and in 6 MGUS pts (2.2%) (p=0.029). Notably, in 7 MGUS cases with <1% PCs in cytomorphology, FISH revealed genetic alterations in 3 cases. PCs as quantified by cytomorphology vs. MFC ranged from 0-96% vs. 0-84% (median 8.5 vs. 2.0), respectively, with a highly significant correlation between both methods (Pearson, r=0.712, p<0.0001). However, as previously reported, MFC detected lower numbers in general: the median ratio of PCs by cytomorphology:MFC amounted to 4.25 (range 0.00-178.00). In 12 MGUS cases (1.7%) as defined with cytomorphology, MFC did not detect any PCs. Conversely, in 5 MGUS cases, MFC detected PCs while cytomorphology did not. In conclusion, cytogenetic patterns showed higher genetic complexity in MM cases when compared to MGUS, and both the t(4;14) as -13/del(13)(q14) were significantly more frequent in MM when compared to MGUS. However, the cytogenetic alterations showed no specific pattern for MM or MGUS categories. Therefore, the overlaps being seen from morphological aspects do also exist on the genetic level. This suggests that a cytogenetically based categorization of these cases might correlate better with the clinical profiles than the cytomorphological separation of MM/MGUS. Finally, this study supports the performance of FISH in MGUS cases. The demonstrated detection of malignant/monoclonal PCs by MFC also in cases in which cytomorphology fails to diagnose MM/MGUS emphasizes the inclusion of MFC in a standard diagnostic procedure. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Weiss:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.
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Castanheira, Mariana, Matthew G. Johnson, Brian Yu, Jennifer A. Huntington, Patricia Carmelitano, Christopher Bruno, Elizabeth G. Rhee, and Mary Motyl. "624. Molecular Characterization of Baseline Enterobacteriaceae and Pseudomonas aeruginosa from a Phase 3 Nosocomial Pneumonia (ASPECT-NP) Clinical Trial." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S289—S290. http://dx.doi.org/10.1093/ofid/ofz360.692.
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Abstract Background ASPECT-NP, a phase 3, randomized, double-blind, multicenter trial, evaluated ceftolozane/tazobactam (C/T) 3 g q8h vs. meropenem 1 g q8h for 8–14 days in adults for treatment of ventilated nosocomial pneumonia. Baseline Gram-negative (GN) isolates from patients were tested for mechanisms of resistance. Methods Lower respiratory tract (LRT) isolates were sent to a central laboratory for organism identification and susceptibility. Of 664 total Enterobacteriaceae (ENT) and Pseudomonas aeruginosa (PsA) isolates, 351 (53%) were nonsusceptible to broad-spectrum cephalosporins and/or carbapenems and underwent whole-genome sequencing, quantitative RT–PCR, and western blot analysis. ENT isolates were tested for the presence of acquired β-lactamase genes and AmpC levels (selected species). PsA isolates were tested for acquired β-lactamase genes, AmpC (PDC) levels, efflux pump expression, and OprD loss. Results Of 262 ENT isolates, 114 (44%) were susceptible to C/T (MIC ≤2 µg/mL). An extended-spectrum β-lactamase (ESBL) gene was carried by 89 (78%) of the C/T-susceptible isolates. Of 148 C/T-nonsusceptible (C/T-NS) isolates, 87 (59%) were carbapenemase negative, and the majority 135 (91%) also carried an ESBL gene. The most common ESBL was blaCTX-M15 with blaOXA-1 and blaOXA-30. Klebsiella pneumoniae often displayed higher C/T MICs compared with other species carrying the same resistance genes. Among all C/T-NS isolates, 61 (41%) were carbapenemase positive, most commonly K. pneumoniae carrying blaOXA-48, blaNDM-1, and blaNDM-5. Of 89 PsA isolates, 58 (65%) were susceptible to C/T (MIC ≤4 µg/mL), despite elevated AmpC expression, efflux pumps, or loss of OprD; only 5 isolates had an acquired β-lactamase. Of the 31 C/T-NS PsA isolates, only 12 (39%) were carbapenemase positive and carried blaVIM or blaGES; isolates carrying blaGES had lower C/T MICs (8–32 µg/mL) compared with blaVIM (MIC > 128 µg/mL). PDC alleles were similar in isolates with high and low C/T MICs. Conclusion In baseline GN LRT isolates from ASPECT-NP, the most common ESBL detected in ENT was blaCTX-M15; carbapenemases were uncommon. There was no correlation of ESBL phenotype to C/T susceptibility among ENT, nor of PDC allele to C/T susceptibility among PsA. Disclosures All authors: No reported disclosures.
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Burekovic, Azra, and Anida Divanovic. "Is It the COVID-19 and Untreated Panhypopituitarism a Deadly Combination: A Case Report?" Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A590. http://dx.doi.org/10.1210/jendso/bvab048.1203.
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Abstract Background: The possible long-term consequences of coronavirus disease (COVID-19) on the endocrine system are still not known. With the number of cases rising we have reported the first possible implications of COVID-19 on panhypopituitarism in Bosnia and Herzegovina. Clinical Case: A 59-year-old man was referred to the Endocrinology Counseling Center on 12/10/2020. For 15 years he did not take thyroid and adrenal replacement therapy. As a child, he was treated for short stature, as well as his two sisters. He had signs and symptoms of myxedema. He was urgently hospitalized to the Department of Endocrinology. His condition has worsened in the last month, more intensely in the last 10 days. He complained of general weakness, malaise, drowsiness, shortness of breath, fatigue, constipation, swelling of the lower legs. The patient was enormously adipose and moved harder with help of a walking stick. The thyroid gland appeared smaller on palpation. Laboratory investigations showed low and borderline levels of the following hormones TSH 0.590 (0.3-4.2 mU/L), FT4 1.44 (12.0-22.0 pmol/L), FT3 0.858 (3.1-6.8 pmol/L), ACTH at 8 am 2.59, ACTH at 16 pm 8.44 (7.20-63.3 pg/ml), GH 0.090 (0.0-14.0), FSH <0.7 (1.6-9.7 IU/L), LH <0.7 (0.7-7.8 IU/L), prolactin <30.8 (78-380 uIU/ml), testosterone 1.01 (above 50 years 2.5-21.6 nmol/l), cortisol at 8 am 557, cortisol at 16 pm 674, cortisol at 11 pm 674 (morning: 123-626 nmol/L, afternoon 46-389 nmol/L), DHS 1.87 (2.17-11.7 nmol/L). On 12/10/2020 he tested negative for SARS-CoV-2 infection. On 14/10/2020 his condition worsened. He was somnolent, and even though he was admitted to diuretic therapy, he had decreased urine output. His D-dimer was 3.93 (0-0.055 mcg/mL). CT findings of thoracic organs described cardiomegaly, atherosclerotic altered thoracic aorta, and changes in the pulmonary parenchyma on both sides. On 16/10/2020 the patient was transferred to the cardiology department. SARS-CoV-2 test was repeated, and it was positive. The patient exited due to pulmonary arrest on 17/10/2020. Conclusion: There are several possible mechanisms that may describe that COVID-19 infection exacerbates the symptoms of myxedema and panhypopituitarism, and consequently leads the patient to severe acute respiratory failure.
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Limsuwat, Chok, Pantaree Aswanetmanee, Mustafa Awili, Ahmed Raziuddin, and Supat Thammasitboon. "Sleep quality, sleep habits, and chronotypes of medical interns at the beginning of their training." Southwest Respiratory and Critical Care Chronicles 5, no. 20 (July 19, 2017): 4. http://dx.doi.org/10.12746/swrccc.v5i20.408.
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Introduction: Despite the implementation of resident work hour regulations, studieshave not consistently shown beneficial changes in residents’ sleep quality or duration. Wehypothesized that inter-individual sleep-related differences may exist prior to training and thepre-existing sleep health and habits may impact training.Objective: To determine interns’ baseline sleep quality, sleep hygiene, chronotypes, andtheir correlates at the beginning of their residency training program.Methods: A cross-sectional study using an anonymous “Resident Sleep Survey” includedbaseline demographic information and questionnaires, including the Epworth SleepinessScale (ESS), the Pittsburgh’s Sleep Quality Index (PSQI), the Morningness-EveningnessQuestionnaire (MEQ), and the Sleep Hygiene Index (SHI).Results: One hundred and twenty-nine subjects participated the study; 45.7 % (n=59)were male and 18.6 % (n=24) were married. Twenty percent of interns had an ESS >10. ThePSQI revealed that 28% of interns had poor sleep hygiene. The mean sleep efficiency was91.2 ±7.4% estimated from the PSQI. Non-married interns had a lower prevalence of morningchronotypes (22.3% vs. 45.8%, p=0.02). Morning chronotype interns had a lower ESS score(6.1 ±3.1 vs. 7.6 ±3.6, p=0.03) and a lower SHI (29 ±7.0 vs. 34.3 ±7.1, p=0.003).Conclusion: About a quarter of interns had poor sleep quality and excessive daytimesleepiness prior to their training. Non-morning chronotype interns appeared to have moredaytime sleepiness and poorer sleep quality. Since pre-existing sleep problems may adverselyaffect learning, we suggest that strategies to improve sleep hygiene and quality in this specificpopulation should be emphasized early in their training.
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Goldberg, Stuart L., and David P. Steensma. "Myelodysplastic Syndrome Patients Obtaining a Cytogenetic Response to Outpatient Decitabine Experience Improved Hematological Responses and Longer Survival: Additional Analyses From the ADOPT Trial." Blood 114, no. 22 (November 20, 2009): 3817. http://dx.doi.org/10.1182/blood.v114.22.3817.3817.
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Abstract Abstract 3817 Poster Board III-753 Background The multi-center ADOPT trial (J Clin Oncol 2009; 27:3942) demonstrated that decitabine (Dacogen), a cytidine analog with hypomethylating and direct cytotoxic properties, when administered to MDS patients with IPSS '0.5 on an outpatient schedule of 20 mg/m2 IV infusion 5 days per month resulted in an overall improvement rate of 51%, including 32% complete responses (CR+mCR), using the International Working Group 2006 criteria. The impact of obtaining a cytogenetic response to decitabine therapy on subsequent hematological parameters or survival is the focus of this analysis. Study Design/Methods 99 patients with de novo or secondary MDS were enrolled on the ADOPT trial. 49 patients had abnormal cytogenetics at baseline. 33 patients underwent at least one successful post-treatment karyotypic analysis and were therefore evaluable for cytogenetic response. Data analysis utilized student t-tests and comparisons of proportions. Results 17/33 evaluable patients (52%) achieved a cytogenetic response, with 11 complete responses and 6 partial responses (i.e., >50% reduction in abnormal metaphases). Responses were noted among patients in all IPSS cytogenetic risk categories: low risk cytogenetics 3/3 (100%), intermediate risk cytogenetic 5/8 (62%), and high risk cytogenetic (43%). Cytogenetic responses by abnormality included: -Y (3/3), del 5q (1/7) 1, del 20q (1/2), complex (6/14), chromosome 7 abnormalities (6/14), +8 (5/6), and others (3/7). Baseline characteristics were similar among cytogenetic responders and non-responders: mean age 72.2 vs 68.6 years (p=0.30), males 94 vs 63% (p=0.07), secondary MDS 24 vs 13% (p=0.72), high risk IPSS 35 vs 63% (p=0.21), int-2+high risk IPSS 59 vs 85% (p=0.20), blasts <10% 59 vs 31% (p=0.21), red cell transfusion dependent 41 vs 69% (p=0.21) and platelet transfusion dependent 6 vs 19% (p=0.54). The median time to cytogenetic response was 2.3 months, coinciding with the first post-treatment marrow sampling timing. Of the 17 cytogenetic responders, 13 (76%) had a clinical hematological responses (10 CR and 3 mCR) which was significantly higher (p=0.003) than the 3 of 16 evaluable patients (18%) not experiencing a cytogenetic response. Among cytogenetic responders the duration of the hematological response (451 days, 95% CI 143, NE) also was greater than the duration of hematological response among cytogenetic non-responders (219 days, 95% CI 184, NE). 71% (12/17) of cytogenetic responders were red cell transfusion independent on study by IWG criteria compared to 44% (7/16) non-cytogenetic responders (p=0.22). Significantly more cytogenetic responders achieved prolonged red cell transfusion independence lasting at least 24 weeks (10/17; 59%) compared to cytogenetic non-responders (3/16; 19%) (p=0.04). 88% (15/17) of cytogenetic responders were platelet transfusion independent during the study compared to 75% (12/16) non-cytogenetic responders (p=0.61). Higher rates of prolonged platelet transfusion independence lasting at least 24 weeks were achieved among 82% (14/17) cytogenetic responders versus only 38% (6/16) cytogenetic non-responders (p=0.03). Achieving a cytogenetic response correlated with improved survival. Cytogenetic responders had a median survival of 627 days (95% CI 420,760) versus 318 days (95% CI 265, 447) for cytogenetic non-responders. Conclusions Outpatient administration of decitabine (20mg/m2 IV 5 days per month) resulted in cytogenetic responses in 52% of patients with MDS with baseline cytogenetic abnormalities, with a median time to response of 2.3 months. Patients achieving a cytogenetic response had higher rates of hematological responses, longer durations of transfusion independence, and a doubling of projected survival. This analysis suggests that a deeper early response documented by cytogenetics with decitabine correlates with improved long term outcomes, and supports early cytogenetic testing to predict hematological response. Disclosures: Goldberg: Eisai, Inc.: Research Funding.
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Dock, Carissa C., Katie L. Freeman, J. Chris Coetzee, Rebecca Stone McGaver, and M. Russell Giveans. "Outcomes of Nitinol Compression Staples in Tarsometatarsal Fusion." Foot & Ankle Orthopaedics 5, no. 3 (July 1, 2020): 247301142094490. http://dx.doi.org/10.1177/2473011420944904.
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Background: Tarsometatarsal (TMT) arthrodesis is commonly performed in the management of midfoot arthritis, trauma, or deformity. The purpose of this study was to collect aggregate data (demographic, surgical, and perioperative outcomes) on patients who previously had a TMT fusion with BME compression staples. Methods: Sixty-six patients underwent TMT fusion with BME compression staples. Outcomes included demographics, surgical information, the Veterans Rand VR-12 Health Survey, Foot and Ankle Ability Measure (FAAM), visual analog scale (VAS), Revised-Foot Function Index (FFI-R), Ankle Osteoarthritis Scale (AOS), patient satisfaction survey scores, radiographic fusion rate, level of pain reduction, and complications. Sixty-six patients (68 feet) were analyzed (59 females) with an average age of 64 years (range, 18-83). The mean latest follow-up was 35.9 (range, 6-56.6 months). Results: The average surgical time was 38.1±14.3 minutes (range, 11-75). All outcomes improved significantly ( P < .001) from preoperative to latest follow-up except for the VR-12 Mental and Physical score. The average time to fusion determined by radiographs was 8.4 weeks (range, 6.1-46.1 weeks). Wound complications were not seen. Indications for subsequent surgeries (26.5%, 18/68 feet) in this current study included pain (n = 14), broken staples, and nonunion (n = 3). Conclusions: The fusion rate in this study, 89.7%, was similar to values reported in the literature. The patient satisfaction score of 81.9 at latest follow-up is consistent with patient satisfaction for other methods of fusion. Level of Evidence: Level IV, retrospective case series.
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Pontefract, Benjamin, and Karl Madaras-Kelly. "1470. Linezolid for Treatment of Urinary Tract Infections Caused by Vancomycin-resistant Enterococci." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S537. http://dx.doi.org/10.1093/ofid/ofz360.1334.
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Abstract Background Urinary tract infections (UTI) caused by vancomycin-resistant enterococcus (VRE) are difficult to manage due to lack of effective oral treatment options. Linezolid is an antibiotic with activity against VRE that is available orally, but only 30% of each dose is excreted in the urine. Data on the efficacy of linezolid in the treatment of UTI is limited. The purpose of this analysis was to assess the comparative efficacy of linezolid to other VRE-active antibiotics in the treatment of UTI. Methods A national retrospective cohort of inpatient veterans with a positive urine culture for VRE during years 2013 through 2018 was developed. Patient demographics, vital signs, urinary symptoms, antibiotics prescribed, and 14-day post-treatment outcomes were collected. Patients without UTI symptoms, urine cultures with < 105 CFU/mL (<103 CFU/mL for catheterized patients), or patients not treated with VRE-active antibiotics were excluded. Odds ratios were used to compare linezolid and non-linezolid antibiotics for 14-day VRE bacteriuria, UTI retreatment, and death endpoints. Results Of 3,846 urine cultures identified with VRE, 624 (16%) patients were eligible for evaluation of UTI symptoms. Of these, 92/624 (15%) met study criteria. The primary reason for exclusion was asymptomatic bacteriuria [339/532 (64%)]. Linezolid was prescribed in 54/92 (59%) of cases. Comparators included penicillin’s [12/92 (13%)], nitrofurantoin [11/92 (12%)], daptomycin [7/92 (8%)], tetracycline’s [6/92 (7%)], and others [2/92 (2%)]. Between linezolid and comparator groups, mean (+S.D.) patient age [70 (12) vs. 68 (13) years, P = 0.45] and Charlson Comorbidity Index [8.9 (3.1) vs. 8.3 (3.5), P = 0.39] were similar. Negative outcomes were uncommon: 7% VRE bacteriuria, 8% UTI re-treatment, 4% death. No difference in [(OR) +95% CI] between linezolid and comparators was observed: positive VRE bacteriuria [0.3 (0.1, 1.9), P = 0.20], UTI retreatment [1.8 (0.3, 10.0), P = 0.49], death [1.4 (0.1, 16.1), P = 0.79]. Conclusion Most patients with a VRE positive urine culture who received antibiotics did not meet diagnostic criteria for UTI, and negative outcomes were uncommon. Linezolid and comparator regimens with VRE activity were effective for treating mild VRE UTI. Disclosures All authors: No reported disclosures.
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Dent, Susan Faye, Freya L. Crawley, Nadine A. Graham, and Michelle M. Campbell. "Vascular toxicities of endocrine therapy in early-stage breast cancer: Encouraging observations in a nontrial setting." Journal of Clinical Oncology 30, no. 27_suppl (September 20, 2012): 68. http://dx.doi.org/10.1200/jco.2012.30.27_suppl.68.
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68 Background: Endocrine therapy (ET) is the standard of care for postmenopausal (PM) women with early stage breast cancer (EBC). Studies suggest higher risk of vascular toxicities (VT) on aromatase inhibitor (AI) therapy. We report incidence/discontinuation rates of VTs in a cardiac clinic. Methods: PM women with hormone receptor positive EBC treated with ET (tamoxifen (T) ± AI) at Ottawa Hospital Cancer Center 01/99-2/06. Data included: demographics, vascular co-morbidities (VCM), ET, duration, VTs. Results: 626 pts, median age 59 years (r: 30-92), median follow-up 98 months (m), stage: I (196 pts), II (341 pts) III (89 pts) EBC. Majority (52.5%) pts had VCM at ET initiation; hypertension (HTN) (36%), hyperlipidemia (HYLP) (17%), coronary disease (12%), thrombosis (9%), angina (6%) TIA (6%). Treatment discontinued due to VT 3x more with T vs. AI. Most common VTs: edema, arrhythmias (ARR), cardiovascular (CVS) event, and HYLP. With Letrozole and T, previous VCM significantly increased risk of developing VT (chi-square: P=0.022 and 0.009). Time to develop VT shortest for T and exemestane. Previous VCM did not affect this interval. Longer exposure to T correlated with higher VT rate (t-test: p=0.046) not seen with AIs. Exposure to multiple AIs associated with higher VT rate (t-test: p=0.009). Conclusions: This cohort study reports similar VT rates with AI therapy as reported in the literature. T was associated with higher discontinuation rates (10.5%) due to VTs compared to AIs (2.8-3.3%). Longer duration of AI therapy was not associated with increased risk of VTs. These encouraging results reflect the real-life experience of women exposed to ET. [Table: see text]
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Chamorey, E., C. Lebrun, D. Fontaine, F. Vandenbos, J. Michiels, P. Paquis, and M. Frenay. "General epidemiology and survival rate of malignant and non-malignant brain and central nervous system tumors in Nice area (France)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 17078. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.17078.
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17078 Background: The aim of this cohort study was to produce descriptive epidemiological data from the Group of Neuro- Oncology of Nice (GNON) database. Data were collected from the Comprehensive Cancer Center and the University Hospital of Nice (France). Methods: All cases that have been discussed during multidisciplinary meetings of neuro-oncology were entered. Data were compared with the Central Brain Tumor Registry of the United States (CBTRUS) report taken as reference tool. Follow-up information was obtained from the patient medical chart and from the national death registry. Results: 1,395 patients (718 males, 677 females) were registered in the data base. There were 938 tumors of neuroepithelial tissue (percentage of all reported cases in our study: 67.9%, median age in our study; 58 yrs, percentage in CBTRUS report: 43.6%, median age in CBTRUS report: 53 yrs), 55 tumors of cranial and spinal nerves (4.0%, 53 yrs; 8%, 52 yrs), 270 tumors of meninges (19.5%, 59 yrs; 31.4%, 63 yrs), 54 lymphoma and hemopoietic neoplasm (3.9%, 68 yrs; 3.1%, 60 yrs), 16 germ cell tumors, cysts and heterotopias (1.2%, 17yrs; 0.6%, 16yrs), 12 craniopharyngioma (0.9%, 50 yrs; 0.7%, 48 yrs), 9 chordoma/chondrosarcoma (0.6%, 65 yrs; 0.2%, 48 yrs), 27 unclassified tumors (2.0%, 46 yrs; 6.1%, 68 yrs). The table shows the survival rates at one, three and five years respectively for some selected brain and central nervous system tumors (results from the CBTRUS report in parentheses). Conclusions: A comparison between results from the CBTRUS and GNON data base showed some similarities and didn't point out any major unexplainable discrepancy. [Table: see text] No significant financial relationships to disclose.
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Munro, Allan, Lee Herrington, and Michael Carolan. "Reliability of 2-Dimensional Video Assessment of Frontal-Plane Dynamic Knee Valgus During Common Athletic Screening Tasks." Journal of Sport Rehabilitation 21, no. 1 (February 2012): 7–11. http://dx.doi.org/10.1123/jsr.21.1.7.
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Context:Two-dimensional (2D) video analysis of frontal-plane dynamic knee valgus during common athletic screening tasks has been purported to identify individuals who may be at high risk of suffering knee injuries such as anterior cruciate ligament tear or patellofemoral pain syndrome. Although the validity of 2D video analysis has been studied, the associated reliability and measurement error have not.Objective:To assess the reliability and associated measurement error of a 2D video analysis of lower limb dynamic valgus.Design:Reliability study.Participants:20 recreationally active university students (10 women age 21.5 ± 2.3 y, height 170.1 ± 6.1 cm, weight 66.2 ± 10.2 kg, and 10 men age 22.6 ± 3.1 y, height 177.9 ± 6.0 cm, weight 75.8 ± 7.9 kg).Main Outcome Measurement:Within-day and between-days reliability and measurement-error values of 2D frontal-plane projection angle (FPPA) during common screening tasks.Interventions:Participants performed single-leg squat and drop jump and single-leg landings from a standard 28-cm step with standard 2D digital video camera assessment.Results:Women demonstrated significantly higher FPPA in all tests except the left single-leg squat. Within-day ICCs showed good reliability and ranged from .59 to .88, and between-days ICCs were good to excellent, ranging from .72 to .91. Standard error of measurement and smallest detectable difference values ranged from 2.72° to 3.01° and 7.54° to 8.93°, respectively.Conclusions:2D FPPA has previously been shown to be valid and has now also been shown to be a reliable measure of lower extremity dynamic knee valgus. Using the measurement error values presented along with previously published normative data, clinicians can now make informed judgments about individual performance and changes in performance resulting from interventions.
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Eruslanova, K. A., L. V. Matchekhina, E. N. Dudinskaya, Yu V. Kotovskaya, D. A. Gudkov, V. M. Govorun, and O. N. Tkacheva. "Lipid and glucose metabolism in centenarians: risk factors of cardiovascular diseases and frailty." Russian Journal of Geriatric Medicine, no. 4 (January 3, 2021): 294–304. http://dx.doi.org/10.37586/2686-8636-4-2020-294-304.
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Aim: to assess the most important metabolic factors in centenarians and their impact on prognosis Materials and methods. It was a longitudinal study, including 64 centenarians (95 years and older), who live in Moscow. Complex geriatric assessment (FRAIL, IADL-C, MNA, GDS-15 and МOCA scores) and blood tests (HbA1c, cholesterol, LDL, HDL and TG) were performed. In 3 years we contacted patients’ relatives or social workers to find out about patients’ status. Results. Mean age of the patients was 98,3±1,9 years. We found out that 34,4% of the patients were frail. Cognitive impairments of different severity were presented in 84,4% of the patients. The median lipids values were as follows: cholesterol — 4,8 [4,2 ;5,8], TG — 0.97 [0,8; 1.2], HDL — 1.3 [4.2; 5,8), LDL — 3,1 [2,6; 3,7], HbA1c — 5,8 [5,6; 6,1]. In 59% of the patients HbA1c was below 6%; 33% had concentrations between 6% and 6,4%, and only in 8% we found HbA1c higher than 6,5%. No correlation was also found between HbA1c values and lipids profile. Comparing survivors and non-survivors groups we did not find any significant differences in total cholesterol, LDL, HDL and HbA1c (p<0,005). While comparing functional status with metabolic profile we discovered positive correlation (r= 0.834) between total cholesterol and index of instrumental activity, and between LDL and IADL as well as MNA score (r=0.732 and 0.634 respectively). Conclusions. In centenarians usual prognostic factors such as HbA1c and lipids do not have any impact on prognosis but they influence functional status and QoL. Further investigations of metabolic status in super old persons are needed to personalize their lifestyle and treatment goals.
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Lees, P. D., D. T. Lynch, H. K. Richards, A. H. J. Lovick, S. Perry, and J. D. Pickard. "Blood Flow in Portal Systems with Special Reference to the Rat Pituitary Gland." Journal of Cerebral Blood Flow & Metabolism 12, no. 1 (January 1992): 128–38. http://dx.doi.org/10.1038/jcbfm.1992.16.
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Regional pituitary blood flow has been studied in adult female Fischer 344 rats by [14C]iodoantipyrine autoradiography. A general mathematical solution has been derived to allow the calculation of blood flow in the second compartment of a portal system and the proportion of blood “shunted” through the first compartment without exposure to tissue uptake from a knowledge of (a) the volume ratios of the two compartments, (b) the tissue tracer uptakes of the two compartments, and (c) the arterial tracer concentration with respect to time of a freely diffusible tracer. Significant diffusion limitation and/or arteriovenous shunting has been demonstrated in the neurohypophysis, suggesting that the majority of incoming blood is “shunted” unchanged to the adenohypophysis. The mean value of the shunt is 89% (range of 84–93%) for the median eminence and lies between 72% (range of 52–82%) and 73% (range of 59–81%) for the posterior pituitary. Neurohypophysial flow rates of 1.20 (range of 0.99–1.55) ml g−1 min−1 for the median eminence and 1.68 (range of 0.83–3.53) ml g−1 min−1 for the posterior pituitary were measured. These values represent “tissue-available” (nonshunted) flow; estimated mean total (shunted plus nonshunted) neurohypophysial flow rates were 11.7 (range of 9.5–17.5) ml g−1 min−1 for the median eminence and 6.1 (range of 3.1–8.9) ml g−1 min−1 (minimum) for the posterior pituitary. Adenohypophysial blood flow is heterogeneous. In the long portal territory, the flow rate was 1.18 (range of 0.95–1.75) ml g−1 min−1 but short portal territory flow calculation is complicated by an unquantifiable nonportal venous drainage; using the natural limits of zero and 100% gives a minimum adenohypophysial flow rate of 1.42 (range of 0.76–2.07) ml g−1 min−1 and a maximum value of 1.97 (range of 1.03–2.82) ml g−1 min−1.
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Berg, Gina M., Ransom J. Wyse, Jennifer L. Morse, John Chipko, Jeneva M. Garland, Andrea Slivinski, Mark Lieser, et al. "Decreased adult trauma admission volumes and changing injury patterns during the COVID-19 pandemic at 85 trauma centers in a multistate healthcare system." Trauma Surgery & Acute Care Open 6, no. 1 (February 2021): e000642. http://dx.doi.org/10.1136/tsaco-2020-000642.
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BackgroundReports indicate social distancing guidelines and other effects of the COVID-19 pandemic impacted trauma patient volumes and injury patterns. This report is the first analysis of a large trauma network describing the extent of these impacts. The objective of this study was to describe the effects of the COVID-19 pandemic on patient volumes, demographics, injury characteristics, and outcomes.MethodsFor this descriptive, multicenter study from a large, multistate hospital network, data were collected from the system-wide centralized trauma registry and retrospectively reviewed to retrieve patient information including volume, demographics, and outcomes. For comparison, patient data from January through May of 2020 and January through May of 2019 were extracted.ResultsA total of 12 395 trauma patients (56% men, 79% white, mean age 59 years) from 85 trauma centers were included. The first 5 months of 2020 revealed a substantial decrease in volume, which began in February and continued into June. Further analysis revealed an absolute decrease of 32.5% in patient volume in April 2020 compared with April 2019 (4997 from 7398; p<0.0001). Motor vehicle collisions decreased 49.7% (628 from 1249). There was a statistically significant increase in injury severity score (9.0 vs. 8.3; p<0.001). As a proportion of the total trauma population, blunt injuries decreased 3.1% (87.3 from 90.5) and penetrating injuries increased 2.7% (10.0 from 7.3; p<0.001). A significant increase was found in the proportion of patients who did not survive to discharge (3.6% vs. 2.8%; p=0.010; absolute decrease: 181 from 207).DiscussionEarly phases of the COVID-19 pandemic were associated with a 32.5% decrease in trauma patient volumes and altered injury patterns at 85 trauma centers in a multistate system. This preliminary observational study describes the initial impact of the COVID-19 pandemic and warrants further investigation.Level of evidenceLevel II (therapeutic/care management).
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Lakshman, Arjun, Jithma P. Abeykoon, Shaji Kumar, S. Vincent Rajkumar, Taxiarchis Kourelis, Francis Buadi, David Dingli, et al. "Daratumumab-based combination therapies (DCT) in heavily-pretreated patients (pts) with relapsed and/or refractory multiple myeloma (RRMM)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 8038. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.8038.
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8038 Background: Daratumumab-based Combination Therapies (DCT) with bortezomib (V)/ lenalidomide (R)/ pomalidomide (P) and dexamethasone (d) showed exceptional activity in RRMM in trials. Experience outside of trials since the approval of Daratumumab (D) in 2015 is limited. Methods: RRMM pts seen at Mayo Clinic, MN from 12/2015 -12/2016 were reviewed. Pts who received ≥ 1cycle of DCT were included. Time-to-event analyses were done from date of starting DCT. Common terminology criteria for adverse events v4.0 were used to grade toxicities. Results: Of 130 pts, 59% were males and median age at DCT initiation was 67 (43-93) years, ECOG performance score was ≥2 in 29%. Pts were classified as mSMART high (22%), intermediate (22%) or standard (56%) risk. Median time from diagnosis to initiation of DCT was 51.3 (5-156) months (m), and median number of prior therapies was 4 (1-14). 14% of pts were refractory to prior D monotherapy. Fifty-three (41%), 34 (26%) and 25 (19%) received DPd, DRd and DVd respectively. Eighteen (14%) pts received ‘other’ DCT. Median time to first response (≥ PR) was 3.1 m (95% CI 2.1-4.6). Overall response rate was 46%, [CR-2%, VGPR-18%, PR-26%]. Minimal response was seen in 17%, with clinical benefit rate of 62%. Median estimated follow up from initiation of DCT was 5.5 m (CI 4.2-6.1). The median duration of response was 6.1 m [CI 5.1- not reached (NR)]. Median progression free survival (PFS) was 5.5 m (CI 4.1-7.8) and median time to next therapy (TTNT) was 5.9 m (CI 4.6-9.4). Median PFS for DPd, DRd, DVd and other DCTs were 4.6 (CI 2.7-NR), 7.8 (CI 5-NR), 3.9 (CI 2.1-NR) and 3.9 (CI 2.8-8.2) m, respectively (p = 0.3). Median PFS for quadruple refractory (n = 28) MM was 2.8 m (CI 2.2-5.3) vs 5.9 m (CI 4.9-NR) for the rest (p < 0.01). Median overall survival (OS) from DCT was NR (CI 11.4-NR). Grade 3 or higher hematological toxicities were seen in 42% of pts. Other toxicities included infections (37%), fatigue (31%), infusion reactions (16%) and diarrhea (10%). Conclusions: DCT are effective in RRMM, but the PFS remains short particularly in quadruple refractory pts, reflecting the challenges encountered in managing heavily-pretreated, and often less fit patients, in routine practice.
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Brewster, Lizzy Maritza, and Jim Fernand. "Creatine kinase during non-ST-segment elevation acute coronary syndromes is associated with major bleeding." Open Heart 7, no. 2 (December 2020): e001281. http://dx.doi.org/10.1136/openhrt-2020-001281.
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BackgroundIt was recently reported that highly elevated plasma activity of the ADP-scavenging enzyme creatine kinase (CK), to >10 times the upper reference limit (URL), is independently associated with fatal or non-fatal bleeding during treatment for ST-segment elevation myocardial infarction (OR 2.6 (95% CI, 1.8 to 2.7)/log CK increase). Evidence indicates that CK attenuates ADP-dependent platelet aggregation. This study investigates whether moderately elevated CK in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is associated with major bleeding.MethodsThe Thrombolysis In Myocardial Ischemia (TIMI) 3B trial compared recombinant tissue-type plasminogen activator (rt-PA) (35–80 mg) with placebo and early catheterisation with conservative management in patients with NSTE-ACS. Main outcomes of the current study are the independent association of peak plasma CK (CKmax) with adjudicated fatal or non-fatal major bleeding (primary) and with combined major bleeding, stroke and hospital death (secondary), with covariables including age, sex, body mass index, systolic blood pressure, creatinine and assignment to add-on rt-PA versus placebo. Discrimination was assessed with C-statistics.ResultsThe study included 1473 patients (66% men, 80% white, mean age 59 years, SE 0.3). CKmax ranged between 15 and 19 045 IU/L (mean (SE), 450 (24) IU/L; two times URL). Major bleeding occurred in 2.0% (mean age 65 (1.3) years; mean CKmax 1015 (319) IU/L; six times URL), and the combined outcome in 4.3% of the patients, adjusted OR per log CK increase, respectively, 3.1 (1.6 to 5.9) for major bleeding and 3.9 (2.5 to 6.1) for the combined outcome; C-index 0.8 for both outcomes. The association between CK and bleeding was independent of the use of thrombolytic therapy.DiscussionThe presented data add to the existing evidence that proportionate to its plasma activity, the ADP-binding enzyme CK is strongly and independently associated with non-fatal and fatal major bleeding during treatment for NSTE-ACS. CK might increase the accuracy of prediction models for major bleeding in patients with NSTE-ACS.Trial registration numberNCT00000472.
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Colorio, Cecilia Claudia, Dolores P. Puente, Andrea Rossi, Maria Tabares, Gonzalo Pombo, and Ricardo Forastiero. "Oral Anticoagulation in Atrial Fibrillation. Comparison Between Patients Younger and Older Than 75 Years." Blood 112, no. 11 (November 16, 2008): 4060. http://dx.doi.org/10.1182/blood.v112.11.4060.4060.
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Abstract Atrial fibrillation (AF) is the most common cardiac rhythm disorder. The prevalence is nearly 10 % in patients (pts) older than 75 years (yrs). Some authors are reluctant to give oral anticoagulant therapy for older pts based on their higher incidence of bleeding Objective : to compare characteristics, incidence of thrombosis and bleeding in 2 groups of pts with AF, under OA for at least 3 months. Methods: we retrospectively analyzed 184 pts below 75 yrs (Group A) and 133 pts with 75 yrs and older (Group B), between Jan 2002 and Aug 2007. Results: the mean follow-up was 514 pts/year for the A group and 382 pts/year for group B. The features of each group are listed in the table below: Group A Group B p Age (mean- range) 64,9 (33/74) 79,8 (75/91) Gender (M/F) 116/68 (1,7/1) 55/78 (0,7/1) Rheumatic AF 89/184 61/114 Non valvular AF 80/184 53/114 Previous thrombosis 21/184 (11.4%) 29/133 (21.8%) 0,01 Diabetes mellitus 28/184 (15.2%) 10/133 (7.5%) 0,05 Arterial Hypertension 78/184 (42.3 %) 53/133 (39.8%) Hyperthyroidism 29/184 (15.7%) 18/133 (13.5%) Left Mega Atrium 43/174 (24.7%) 32/110 (29%) Coronary Artery Disease 38/184 (20.6%) 31/133 (23.3%) Cardiomegaly 53/170 (31.1%) 41/122 (33.6%) Ejection Fraction ≤30% 26/175 (14,8%) 20/112 (17.8%) Creatinin ≥ 2 mg/dl 8/184 (4.3%) 8/133 (6.1%) Thromboses 4/184 (2.1%) 3/133 (2.2%) Bleeding minor 59/184 (32%} 49/133 (36.8%) major 5/184 (2.7%) 2/133 (1.5%) fatal 0 2/2 (100%) Controls with INR 2-3 61 % 60,5 % Conclusion: There was no difference in the incidence of major and minor bleeding/thrombotic complications between the groups. Group B disclosed a higher number of thromboses previous to OA therapy, and fewer pts with diabetes. In our experience, OA seemed to be equally safe and effective when we compared both populations. There was no difference in the incidence of major and minor bleeding/thrombotic complications between the groups.
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Abdelmonem, M., M. Elshamsy, H. Wasim, M. Shedid, and A. Boraik. "Epidemiology Of Helicobacter Pylori In Delta Egypt." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S130. http://dx.doi.org/10.1093/ajcp/aqaa161.284.
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Abstract Introduction/Objective Introduction: Helicobacter pylori (H. pylori) infection is one the most prevalent bacterial infection in the world, affecting more than 50% of the world’s population. H. pylori are gram negative bacteria usually found in the stomach, penetrate the lining of the stomach, small intestine, or esophagus. After many years, they can cause sores, called ulcers, in the lining of your stomach or the upper part of your small intestine. For some people, an infection can lead to Gastric cancer which is the second most common cancer worldwide Objectives: The aim of this study is to predict the prevalence of Helicobacter pylori infection in gastrointestinal tract patients in Egypt. Methods Subjects and methods: A total of 1120 patients were enrolled in this study from The Delta region in Egypt. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect H. pylori stool Antigen. Among the 1120 patient; 301 patients (26.9%) were males, 510 patients (45.6%) were females and 309 patients (27.5%) were children with age range from 1 years to 76 years. The mean of the age was 8,35,34 for children, males and females respectively. Results The overall prevalence of H. pylori infection was 52%. Among the 1120 patients, 576 patients (48%) were negative while 624 patients (52%) of the patients were Positive. It was observed that 169 patients (51.6%) of males were positive,275 patients (52.9%) of females were positive and 135 patients (41%) of children were positive. Furthermore, 133 patients (48.4%) of males were negative, 227 patients (47.2%) of females were negative and 181 patients 59% of children are negative. Conclusion This study revealed that the incidence and prevalence rates of H. Pylori in Egypt are relatively high. The high H. pylori prevalence is related to poor standard of living, low socio-economic conditions, poor sanitation and fecal contamination of food or water. It is crucial to launch educational awareness program for H. pylori in Egypt.
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Quiroga, Josué, Omar Flor, Santiago Solórzano, and José Calahorrano. "Design of a Videolaryngoscope with sensor and pressure alert." Athenea 2, no. 3 (March 7, 2021): 21–27. http://dx.doi.org/10.47460/athenea.v2i3.13.
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This work presents the design and construction of a laryngoscope model with camera vision that has a vibrating device to alert the medical specialist when the force exerted causes possible damage to the patient's airway during the intubation process. Design and fabrication considerations are described using Cast Material Position (FFD). The design is validated with the use of a high-fidelity simulator, the performance is compared with commercial models and the criteria of specialists are taken into account to improve all the necessary aspects. The model presented a great functional advantage, providing greater patient safety, reducing the risk of exposure of the internal tissue to high forces in the intubation process, facilitating clinical processes for health personnel.
Keywords: Video laryngoscope, intubation, 3d printer, PLA.
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Knyazyuk, O., V. Horbatyuk, and I. Melnyk. "Planting dates and row spacing influence on biometric indicators and productivity of Clary sage plants (Salvia solaria L.)." Agrobìologìâ, no. 2(142) (December 22, 2018): 53–59. http://dx.doi.org/10.33245/2310-9270-2018-142-2-53-59.
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Potential crop productivity can be achieved under meeting the requirements on biological needs of crops on their nutrition area twith essential number of nutrients, optimum temperature, lighting and moisture supply. Growing medicinal and essential oil crops leads to uneven seedling in unstable temperature conditions of the spring period. Therefore, it is important to determine the favorable time for sowing, as well as the optimal placement of plants in the area aimed at the seed germination energy growth as well as good and even sprouts. Sowing time and methods influenced Clary sage seeds germination. The highest seed germination rate was observed with a sowing period of April 15 and a wide-row sowing method of 45 cm – 92,3 %. These techniques contributed to better survival of Clary sage plants at the end of the growing season (fruit formation phase) as well, the figure was 95,1 %. The highest growth rate of Clary sage (6.1–14.1) cm was observed in the period of complete formation of leaves rosette. By the budding phase, its growth was slow – 2–3 cm in ten days, and from budding to flowering the crops growth rates significantly increased to 8–10 cm. After the flowering phase, the growth of Clary sage decreased, which ensured a uniform redistribution of nutrients from the vegetative to generative part. The greatest crops height was noted for the winter period of sowing and row spacing of 15 cm (31.8 cm). A change in the ratio of accumulation of crops green mass parts (stems, leaves, inflorescences) was observed in the process of Clary sage growth and development. So, in the budding phase, the share of leaves was 1.9–2.9 % of the total plant weight and in the fruit formation phase it made 3.6–5.9 %. The same trend was observed in the change of the total stems weight. An increase in the row spacing (up to 45) influenced the growth of Clary sage biomass. In the fruit formation phase, the total plant weight increased by 0.4–3.1 g in comparison with that under 15 cm row spacing Late sowing dates for Clary sage (April 15) contributed to the formation of a larger number of stems, leaves and inflorescences on the plant. The total number and productive inflorescences was larger under 15 cm width method of sowing, which is more than those compared with the wide-row sowing of 45 cm. Solid sowing method (15 cm)provides a larger number of Clary sage stalks, but only in subwinter sowing. Indicators of individual productivity of Clary sage such as stems, leaves and inflorescences number determine the optimal application of growing technology methods to realize the potential of this crop. The most favorable conditions for Clary sage high productivity formation are created for a sowing period of April 15. Maximum values of crop production were obtained with a row spacing of 30 cm. The enhancement of plant density (with a row spacing of 15 cm) results in Clary sage productive inflorescences number increase. Consequently, the maximum values for Clary sage plants (average data for the experimental sites) were noted with a sowing period of April 15 with 45 cm row spacing (plant weight – 17.6 g, leaves weight – 5.7 g, inflorescences weight – 5.3 g). Key words: Clary sage, sowing time, row spacing, phenological phases, green weight, leaves, inflorescences.
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Gugliotta, Gabriele, Fausto Castagnetti, Massimo Breccia, Alessandra Iurlo, Mariella D'Adda, Fabio Stagno, Luciano Levato, et al. "Outcome of 472 Chronic Myeloid Leukemia Patients Treated with Frontline Nilotinib: A Gimema CML WP Analysis." Blood 132, Supplement 1 (November 29, 2018): 458. http://dx.doi.org/10.1182/blood-2018-99-119182.
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Abstract BACKGROUND: In chronic phase (CP) chronic myeloid leukemia (CML) nilotinib showed better efficacy compared to imatinib. The higher rates of deep molecular response with nilotinib may translate in more patients (pts) eligible for treatment discontinuation. On the other hand, cardiovascular toxicity may limit nilotinib use in selected groups of pts (e.g. elderly pts). AIM: To investigate the efficacy and safety, overall and according to age, of first-line treatment with nilotinib in CML pts. METHODS: We analyzed response rates, events and outcome of 472 pts ≥ 18 y of age with CP CML, enrolled in clinical trials of the GIMEMA CML WP with nilotinib frontline. Pts were treated with: nilotinib 300 mg BID (n=276); nilotinib 400 mg BID (n=73); rotation of nilotinib 400 mg BID / imatinib 400 mg OD (3-month periods for each drug)(n=123). The median follow-up was 36 (3-82) months. Pts were further analyzed considering 3 age groups: 18-39 y (98 pts); 40-59 y (217 pts); and ≥ 60 y (157 pts). Definitions: Major molecular response (MR3): BCR-ABL≤0.1% (IS), with > 10.000 ABL copies; MR4: BCR-ABL≤0.01% (IS), with > 10.000 ABL copies. Events: permanent discontinuation of nilotinib for any reason, including adverse events, progression to accelerated/blast phase (AP/BP), or deaths. Arterial thrombotic events (ATEs): peripheral arterial obstructive disease, acute coronary syndrome, chronic ischemic heart disease, significant carotid stenosis and ischemic stroke, or other significant ischemic events. RESULTS: Overall, the cumulative incidences of MR3 by 12, 24, and 36 months were 75, 88, and 93%, respectively. The cumulative incidences of MR4 by 12, 24, and 36 months were 38, 63, and 76%, respectively. Events leading to permanent nilotinib discontinuation occurred in 132 (27.9%) pts. ATEs occurred in 33 (7% of pts) ATEs, corresponding to 19.7 ATEs/1000 pt-y. Fifteen (3.1%) pts progressed to AP/BP. Overall, 23 (4.9%) pts died, 11 of them after progression to AP/BP. The estimated 5-year OS was 93%. The sub-analysis according to age showed that: MR3 and MR4 rates were similar across the 3 age groups (cumulative incidences of MR4 by 24 months were 55, 62, and 70% in pts 18-39 y, 40-59 y, and ≥ 60 y, respectively; p=0.25). Progressions to AP/BP were: 6.1% in pts 18-39 y, 2.8% in pts 40-59 y, and 1.9% in pts ≥ 60 y. ATEs were: 0 in pts 18-39y, 4.1% (11.7/1000 pt-years) in pts 40-59 y, and 15.3% (41.3/1000 pt-years) in pts ≥ 60 y (no difference in ATEs was found between pts 60-69 y and those ≥ 70 y). The 5-y OS was 91, 97, and 89% in pts 18-39 y, 40-59 y, and ≥ 60 y, respectively (p=0.065). Death was always leukemia-related in pts 18-39 y (100%), while it was mainly leukemia-unrelated (75%) in pts ≥ 60 y. SUMMARY/CONCLUSION: Nilotinib as first-line treatment of newly diagnosed CP CML pts showed high rates of deep molecular responses, few progressions to AP/BP, and a high OS. Deep molecular response were similar in all age groups; as expected, ATEs were more frequent in pts > 60 y. These data suggest that: in pts > 60 y, the high efficacy of nilotinib should be weighed against its potential toxicity; in pts < 60 years, nilotinib may be a very good choice, with high efficacy and low toxicity. Disclosures Gugliotta: Novartis: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Bristol-Myers Squibb: Honoraria. Castagnetti:Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Breccia:Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Incyte: Honoraria. Levato:Novartis: Other: Advisory board. Abruzzese:Pfizer: Consultancy; Ariad: Consultancy; Novartis: Research Funding; BMS: Consultancy. Soverini:Bristol Myers Squibb: Consultancy; Incyte Biosciences: Consultancy; Novartis: Consultancy. Foà:NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; AMGEN: Other: ADVISORY BOARD. Cavo:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Pane:Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau; AMGEN: Speakers Bureau.
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Mohamed, Abduraheem, Clement Leung, Louise Hitchman, Tom Wallace, George Smith, Daniel Carradice, and Ian Chetter. "A prospective observational cohort study of concomitant versus sequential phlebectomy for tributary varicosities following axial mechanochemical ablation." Phlebology: The Journal of Venous Disease 34, no. 9 (March 13, 2019): 627–35. http://dx.doi.org/10.1177/0268355519835625.
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Introduction Endovenous mechanochemical ablation (MOCA) is an increasingly popular non-thermal non-tumescent technique used to treat axial reflux in patients with superficial venous incompetence. However, the optimal management of varicose tributaries following this technique is unknown and may impact on patient outcomes. This study compares MOCA with concomitant phlebectomy (MOCAP) versus ablation with sequential phlebectomy if required (MOCAS). Methods Patients with symptomatic Comprehensive Classification System for Chronic Venous Disorders (CEAP C2–C6) unilateral axial reflux were studied. Patient choice determined whether concomitant treatment of varicosities was carried out. The primary outcome was the Aberdeen Varicose Veins Questionnaire (AVVQ) at one year. Secondary outcomes included: Venous Clinical Severity Scores (VCSS), EuroQol 5-Domain quality of life scores, complications, procedure duration, procedural and post-operative pain scores and need for secondary procedures. Outcomes were assessed at baseline and then one week, six weeks, six months and one year post intervention. Results Fifty patients underwent MOCAP and 33 patients MOCAS. The two groups were comparable at baseline. MOCAP was associated with lower (better) AVVQ scores at six weeks (3.4 (0.5–6.0) vs. 6.1 (1.8–12.1); P = 0.009) and at six months (1.6 (0.0–4.5) vs. 3.34 (1.8–8.4); P = 0.009) but by one year the difference was no longer statistically significant (1.81 (0.0–4.5) vs. 3.81 (0.2–5.3); P = 0.099). MOCAP was associated with longer procedural duration (45 min (36–56) vs. 30 min (25–37); P < 0.001) and higher maximal periprocedural pain (31 (21–59) vs. 18 (7–25); P = 0.001). VCSS at all time points were lower in favour of MOCAP (0 (0–1) vs. 1 (0–3); P < 0.001). MOCAP was associated with fewer episodes of clinically significant thrombophlebitis (6 of 50 (12%) vs. 10 of 33 (30%); P = 0.039) and lower numbers of secondary procedures (2 (4%) vs. 6 (18%); P = 0.032). Conclusion Concomitant treatment of tributary varicosities following MOCA improves quality of life and clinical severity, while reducing rates of re-intervention and post-operative thrombophlebitis compared to sequential treatment. The penalty is a modest increase in procedural duration and discomfort. Further evidence from longer-term follow-up is needed.
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Jehn, Christian, L. Böning, Hendrik Kröning, Kurt Possinger, Antonio Pezzutto, and Diana Lueftner. "Influence of comorbidity and ECOG on efficacy and safety in irinotecan-refractory elderly patients (>65 years) with metastatic colorectal cancer (mCRC) treated with cetuximab plus irinotecan." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e14140-e14140. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14140.
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e14140 Background: In clinical practice elderly patients (pts) with comorbidities may not be treated appropriately based on perceptions about their life expectancy and ability to tolerate potential side effects of chemotherapy. We investigated the influence of comorbidity, ECOG status and age on the efficacy and safety profile of cetuximab and irinotecan in irinotecan pretreated mCRC patients aged < 65 and > 65 years. Methods: 497 irinotecan-pretreated pts with mCRC were entered in the database of this noninterventional study. Comorbid conditions were recorded and scored according to the Charlson Comorbidity Index (CCI). Descriptive statistics, χ²-or Fishers exact test and multivariate analysis were applied. Results: A total of 247 and 250 pts aged < 65 (median:59) and > 65 (median:70) years, respectively, were documented. 79% of the pts showed a reduced ECOG status of 1–2, with no difference the age groups (p=0.65). Grade III/IV toxicities occurred in 18 % of pts without any difference between age groups although older pts had more comorbidities, with a higher CCI (p=0.002). The duration of any grade of skin reaction was in pts age < 65 significant longer (42 d), than in patients aged > 65 (31 d); (p=0.04). However, there was a trend towards higher grade (≥2) skin toxicity in pts aged > 65. A total of 71% of the pts developed skin rash, which was strongly related to response (P=0.006). Age, line of therapy, ECOG, gender, CCI had no influence on response in multiple regression analysis. The objective response rates were similar for both groups: 38.1% for age < 65 vs. 36.4% for age > 65 (p=0.57). Progression-free survival (PFS) did not differ between pts 18–65 years old (6.0 months) in comparison with pts >65 years (6.1 months) (p=0.99; log-rank test). In a multivariate analysis only ECOG status had a negative impact on PFS (HR: 0,499; 95% Cl, 0.34–0.72; p=0.002), but not CCI, age or gender. Conclusions: Only ECOG had a negative influence on PFS. There were no significant differences in response rate and safety profile for patients aged < 65 and > 65 years when treated with cetuximab and irinotecan. Comorbidities had no influence on efficacy or toxicity.
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Sharma, Shubham, Connor Wells, Joey C. Del Paggio, Wilma M. Hopman, Bishal Gyawali, C. S. Pramesh, Richard Sullivan, and Christopher M. Booth. "Methodology, results, and publication of oncology clinical trials: Insights from all the world’s randomized controlled trials (RCTs) 2014-2017." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 2019. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.2019.
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2019 Background: Clinical cancer research is now a global effort. Most published overviews of oncology trials are restricted to a specific disease site or cohort of high-profile journals. Here we describe authorship, trial characteristics, design, and results of all oncology RCTs published globally during 2014-2017. Methods: A structured literature search was designed using PUBMED to identify all RCTs evaluating anti-cancer therapies published during 2014-2017. Data were captured regarding authorship, participants, study characteristics, design, and results. Among superiority RCTs that met the primary endpoint (i.e. statistically “positive”), we calculated the ESMO-MCBS to identify trials with substantial clinical benefit (MCBS scores 4/5 or A/B). Outcomes were compared with Chi Square or Fisher’s Exact tests. Results: The study cohort included 694 RCTs. The most common cancers evaluated were breast (17%, 121/694), lung (15%, 104/694) and colorectal (8%, 58/694). Treatment intent was curative, adjuvant/neoadjuvant, and palliative in 10% (68/694), 25% (176/694), and 65% (448/694) of trials respectively. Median sample size was 443 (IQR 246-718). Seventy percent (488/694) of RCTs were supported by industry; 87% (601/694) of experimental arms tested systemic therapy. Ninety-two percent (636/694) of RCTs were led by investigators in 28 high-income countries; the most common countries leading these trials were US (27%, 174/636), France (10%, 64/636), Germany (10%, 62/636), Japan (9%, 59/636), and UK (9%, 57/636). The most common primary endpoints were PFS (32%, 220/694), OS (31%, 215/694), and DFS (11%, 79/694); Forty-six percent of all trials (318/694) met their primary endpoint. Among superiority trials with “positive” results, 33% met ESMO-MCBS threshold for substantial clinical benefit. The median impact factor (IF) of journals which published the overall study cohort of trials was 21 (IQR 7-27); trials meeting their primary endpoint were published in higher profile journals (median IF 25 vs 18, p < 0.001). Conclusions: At the global level, oncology clinical trials are dominated by high-income countries and study diseases which do not necessarily reflect the global burden of cancer. The vast majority of trials are funded by industry and only one third of “positive” trials meet ESMO-MCBS threshold for substantial clinical benefit.
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Spahn, Martin, Marianna Kruithof-de Julio, Silvan Boxler, Marc-Alain Furrer, George N. Thalmann, and Urs E. Studer. "PSA-recurrence after radical prostatectomy for intermediate/high risk prostate cancer: A helpful parameter or just a patient stress amplifier." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e16535-e16535. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e16535.
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e16535 Background: Development of biochemical recurrence with a rising PSA level after radical prostatectomy causes significant anxiety for patients and treating oncologist. Management of these patients is controversial. Here, we characterize the natural course and pattern of disease progression and survival in men with biochemical recurrence (BCR) after radical prostatectomy (RP) for intermediate and high-risk prostate cancer (PCa) untreated until clinical failure (CF). Methods: Retrospective analysis of consecutive men with BCR after RP for intermediate/high risk PCa. All patients underwent RP+extended pelvic lymph node dissection. A PSA level > 0.2 ng/ml on two consecutive measures was considered BCR. None received neoadjuvant or adjuvant therapy prior to documented clinical failure by body imaging, which was performed at the time point of BCR or symptoms and at least once per year. Results: Of the 622 men with BCR included into the analysis, 267 (43%) had high risk PCa. Median follow-up after RP was 9.4 yrs. (IQR 4.8-15.1) and median time from RP to BCR was 1.4 yrs. (IQR 0.4-3.6). Of the patients 324 (52%) never experienced CF (Æfollow-up from BCR 5.8yr, IQR2.1-11.9); 88 (14%) had local recurrence only; 59 (9%) had lymph node metastasis +/-local recurrence and 151(24%) distant metastasis. The median times from BCR to CF were: 9.5 yrs. (IQR 5.6-13.5) for local failure; 4.9 yrs. (IQR 3.1-8.8) for lymph node failure and 5.6 yrs. (IQR 3-10.5) for distant failure. The 10-yrs cancer specific (CSS) and overall survival (OS) of the entire group from time point of BCR was 78% and 66%, respectively. 5- and 7-yrs conditional CSS from time of CF was strongly depended on recurrence pattern and ranged from 90% and 79% (local only) to 70% and 47% (lymph node+/-local) and 47% and 36% (distant mets), respectively. PSA-doubling time < 12 months and > 2 positive nodes were independent predictors of outcome in multivariate analysis. Conclusions: These data may be useful in informing men with intermediate/high risk PCa regarding the natural course of PSA recurrence and counseling the timing of additional therapies.
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Tonorezos, Emily S., Dana Barnea, Amber Khan, Joanne F. Chou, Chaya S. Moskowitz, Rana Kaplan, and Kevin C. Oeffinger. "Chest CT findings among adult survivors of childhood and young adult cancer with a history of chest radiation." Journal of Clinical Oncology 35, no. 5_suppl (February 10, 2017): 103. http://dx.doi.org/10.1200/jco.2017.35.5_suppl.103.
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103 Background: While survivors of childhood and young adult cancer with a history of radiation therapy (RT) to the chest are known to be at increased risk for lung cancer, whether a CT-based lung cancer screening program is appropriate for this population is unknown. We sought to describe CT findings in a clinic-based population of childhood and young adult cancer survivors. Methods: We performed a detailed review of all diagnostic chest CT scans performed among patients seen in the Adult Long-Term Follow-Up Program at Memorial Sloan Kettering between August 2005 and May 2016. Included survivors were at least 5 years from diagnosis and had a history of RT to the mediastinum, mantle, axilla, lung, thoracic spine, or total body irradiation fields. Results were reviewed by at least two authors (ET, DB, or AK) and discrepancies were resolved by consultation with a pulmonologist (RK). Results: We identified 620 survivors with a history of chest field RT who were at least 5 years from diagnosis. The population was 48% male, with a median age at diagnosis of 17.2 years. Approximately half were survivors of Hodgkin Lymphoma (N=306; 49.5%) and almost one-third had undergone hematopoietic cell transplant (N=188; 31%); other diagnoses included non-Hodgkin Lymphoma and sarcoma. The most frequently cited RT field was mantle (N=219; 36%), followed by total body irradiation (N=142; 24%) and whole lung (N=110;18%). Among 351 survivors with at least one chest CT, 206 (59%) had at least one pulmonary nodule, 174 (50%) had fibrosis, and 132 (38%) had a ground glass opacity. Among those with a pulmonary nodule, the large majority (91% of those with a nodule) were followed expectantly or underwent repeat imaging; these patients were spared biopsy or resection. Among 18 patients who underwent biopsy, wedge resection, fine needle aspiration, or bronchoscopy, 4 were diagnosed with lung adenocarcinoma, 3 with metastatic sarcoma, and one with marginal zone lymphoma (MALT). Conclusions: Benign pulmonary nodules among adults with a history of RT for childhood or young adult cancer are common. Any strategy for lung cancer screening in this population will need to account for a high likelihood of benign findings on chest CT.
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Othieno-Abinya, Nicholas Anthony, Gladwell Wanjiru Kamere Kiarie, Alice Musibi, Amina Habib Kidee, Tom Nyaboga, Ruth Wanjohi, and Richard Baraza. "Breast cancer as seen at the Nairobi Hospital." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e12514-e12514. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e12514.
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e12514 Background: Breast cancer is the most common cancer and the second leading cause of death among women globally. The Nairobi Hospital has a comprehensive cancer centre, with various practitioners treating cancer patients individually. To document breast cancer diagnosis, treatment and outcome at the Nairobi Hospital. Methods: A retrospective cohort study involving records of breast cancer patients between Jan 2014 and Dec 2019 inclusive. Details included, demographic details, comorbidities, pathology, stage, treatment and outcome. The study was approved by the hospital’s Ethics and Research Committee. Results: 591 patients; 580 (98.1%) women and 11(1.9%) men. Age group 41-60 years had 330 patients(57.2%). Mean parity was 3. Fifteen (2.5%) were smokers, 73 (12.4%) took alcohol, 159 (12.4%) used hormonal contraceptives, 4(0.7%) had been exposed to iatrogenic radiation. Family history of cancer was present in 112 (19%), 25 (4.2%) had personal history of cancer, breast cancer in 8 (1.4%). Diagnosis was by core needle biopsy in 301 (50.9%), excision biopsy in 238 (40.3%), and fine needle aspiration cytology in 52 (8.8%). Pathology was invasive ductal carcinoma in 502(84.9%), invasive lobular in 12(2%). Oestrogen receptors were expressed in 329 (55.7%), progesterone receptors in 264 (44.7%), and Her2 in 129(21.8%). Triple negative were 86( 18%). T1 tumors were 84 (14.2%), T2 were 197 (33.3%), T3 were 126 (15.9%,) and T4 in 94 (15.9%), 126 (21.3%) had distant metastases. Neoadjuvant combination of doxorubicin and cyclophosphamide (AC) was in 109(18.4%) of patients, a taxane following AC (AC-T) in 79 (13.4), and 5-FU with doxorubicin and cyclophosphamide (CAF) in 105 (17.8%). Adjuvant AC was administered to 59 (10%), AC-T to 65 (11%), and CAF to 105 (17.8%), adjuvant tamoxifen to 160 (27.1%). Overall 93 patients (15.7%) received trastuzumab. Adjuvant radiotherapy was completed in 367 (62.1%). At a median follow-up of 36 months, patients 33 (5.6%) were recorded dead. The younger patients had worse survival. Conclusions: Ductal carcinoma constituted 85% of cases and metastatic disease was in 21.3 %. Triple negative cancer were 18%. Younger patients had higher risk of early death.
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Prasad, Vinod K., Premjit Gill, Richard Vinesett, Suhag H. Parikh, Paul Szabolcs, Timothy A. Driscoll, Kristin M. Page, et al. "Single Donor 4/6 Matched Banked Unrelated Cord Blood Is An Effective Graft Source for Children Undergoing Myeloablative Transplantation for Malignant and Nonmalignant Disorders: Single Center Analysis of 318 Patients." Blood 112, no. 11 (November 16, 2008): 1975. http://dx.doi.org/10.1182/blood.v112.11.1975.1975.
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Abstract Background: Despite millions of donors in unrelated registries, many patients, in particular those belonging to ethnic minorities can not find a suitable donor in a timely fashion. In contrast, with an inventory of 250,000 banked cord blood unit, almost every patient will find a 4/6 cord blood unit matched by low resolution HLA-A and –B and high resolution –DRB1 typing. The current study evaluates the outcomes of umbilical cord blood transplants (UCBT) performed using a 4/6 matched donor treated at a single center. Methods: Between August 1993 and November 2007 a total of 318 consecutive pediatric patients (under 21 years old) underwent UCBT from a single 4/6 unit after myeloablative conditioning regimen. The patients were a median of 6.1 (range 0.05–20.33) years and weighed a median of 21.2 (range 3.27–118.4) kg at transplant. Overall, 36.5% (n=116) were girls and 39.2% (n=123) were CMV seropositive. A significant proportion (34.6%) of patient identified as belonging to ethnic and racial minorities. Sixty-five percent (n=205) of the patients had malignant diseases including acute lymphoblastic leukemia (n=87), acute myeloid leukemia (n=58), infant leukemia (n=14), and others (n=46). The nonmalignant patients (n=113) included inherited metabolic disorders (n=75), primary immunodeficiency diseases (n=16), bone marrow failure syndromes (n=11), and others (n=11). The cellular composition of the donor cord blood unit showed a median pre-cryopreservation total nucleated cell (TNC) dose of 6.2×107/kg (range 0.9–38.2), infused TNC of 4.8×107/kg (range 0.5–27.4), infused CD34 of 1.8×105/kg (range 0.02–104.8), and infused CFU of 3.6×104/kg (range 0.0–49.9). Kaplan-Meier estimates of survival were calculated using log-rank test. Descriptive statistics were used for other analyses. Results: The median time to engraftment (ANC>500/mm3 and platelets>50K/uL) were 25 and 83 days. By day 42, 87.4% had achieved ANC>500/mm3 and by day 180, 74.7% had achieved platelets>50K/uL. Acute grades III/IV GvHD developed in 15.5% while the incidence of extensive chronic GvHD at 2 years was 15.2% in evaluable patients. A total of 9.7% of patients had either primary graft failure (n=19) or autologous recovery (n=12). The probabilities of overall survival (OS) are presented in the table. N 1-yr OS 3-yr OS 5-yr OS Diagnosis Group Malignant 205 52% 44% 43% Nonmalignant 113 59% 51% 46% Patient CMV status Positive 123 45% 38% 38% Negative 190 62% 52% 49% TNC cryopreserved x107/Kg <2.5 29 31% 24% 24% 2.5 – 4.99 92 51% 43% 43% 5.0 – 7.5 79 56% 50% 48% > 7.5 118 63% 53% 48% Conclusions: A 4/6 single donor unit is an effective graft source for patients younger than 21 yrs and should be seriously considered if the cryopreserved cell dose is more than 2.5×107TNC/kg. The use of 4/6 matched units will make transplant accessible to many more patients in particular those of ethnic and racial minorities who are unable to find a suitable adult unrelated donor.
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Haferlach, Claudia, Vera Grossmann, Alexander Kohlmann, Susanne Schnittger, Wolfgang Kern, and Torsten Haferlach. "The Type of Genetic Abnormalities Causing Loss of 5q Varies Between MDS and AML and Is Associated with Worse Prognosis in MDS." Blood 120, no. 21 (November 16, 2012): 697. http://dx.doi.org/10.1182/blood.v120.21.697.697.
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Abstract Abstract 697 Background: Deletions of the long arm of chromosome 5 are frequent abnormalities in MDS and AML. Their size varies considerably. Two commonly deleted regions (CDR) have been described on 5q: a distal CDR deleted in the 5q- syndrome and a proximal region lost in higher-risk MDS and AML. However, the majority of MDS and AML patients with del(5q) show large deletions encompassing both CDRs. Recently, Jerez et al. (JCO 2012) reported on commonly retained regions (CRRs) using SNP arrays and observed that deletions involving the centromeric and telomeric extremes of 5q are associated with a more aggressive clinical course. From a cytogenetic view loss of 5q either occurs due to interstitial deletions, unbalanced translocations or monosomy 5. While in interstitial deletions the telomeric region of 5q is retained, this region is lost in cases with unbalanced 5q translocations and monosomy 5. Aim: Analyze whether the type of 5q loss (interstitial deletion vs unbalanced translocation/ monosomy) is associated with other biological markers and prognosis in AML and MDS. Patients and Methods: In total, 1,200 patients (pts) with loss of 5q were studied including 627 AML pts (de novo: 454, s-AML: 101, t-AML: 72) and 573 MDS pts (de novo: 511, t-MDS: 62) with a median age of 71.7 yrs (range: 30–90) and 73.2 yrs (range: 34–93). Interphase FISH had been performed in all pts with a probe for EGR1 (5q31) and all showed a heterozygous EGR1 deletion. Further, all cases had been studied by chromosome banding analysis and in addition by 24-color FISH whenever necessary to resolve complex karyotypes. Data on TP53 mutation status was available in 263 pts (AML: 152, MDS: 111). Results: Type of 5q loss: AML and MDS cases were separated into 2 groups according to type of 5q loss: 1) interstitial 5q deletion (idel5q): AML: 341/627 (54.4%), MDS: 385/573 (67.2%), and 2) 5q loss due to an unbalanced translocation (ut5q): AML: 286/627 (45.6%), MDS: 188/573 (32.8%). Cases with complete loss of chromosome 5 (AML: 12, MDS: 1) were assigned to the second group. 530/627 (84.5%) AML pts and 303/573 (52.9%) MDS pts with 5q loss showed a complex karyotype (defined as 4 or more abnormalities). Further, in 345 AML (55.0%) and 233 MDS (40.7%) cases clonal evolution was evident as subclones with additional aberrations were detected. Impact of 5q loss in MDS: In MDS clonal evolution and complex karyotypes were more frequent in pts with ut5q as compared to idel5q (109/188 (58.0%) vs 124/385 (32.2%), p<0.0001; 179/188 (95.2%) vs 124/385 (32.2%), p<0.0001). In MDS TP53mut was more frequent in ut5q than in idel5q (8/10 (80%) vs 25/101 (24.8%), p=0.001), in pts with clonal evolution (9/14 (64.3%) vs 24/97 (24.7%), p=0.005) and in pts with complex karyotype (13/15 (86.7%) vs 20/96 (20.8%) p<0.0001). Further, median OS was shorter in pts with ut5q as compared to pts with idel5q (15.3 months (mo) vs not reached, p<0.0001). Impact of 5q loss in AML: Similar to MDS, in AML complex karyotypes were more frequent in pts with ut5q as compared to pts with idel5q (274/286 (95.8%) vs 256/341 (75.1%) p<0.0001). However, in contrast to MDS no association between ut5q and clonal evolution was observed in AML. Moreover, also in contrast to MDS no association between TP53mut and type of 5q loss was observed in AML (TP53mut 59/67 (88.1%) in ut5q pts and 66/85 (77.6%) in idel5q pts). In AML, median OS was comparable in pts with ut5q and pts with idel5q (5.9 mo vs 5.8 mo). However, complex karyotype and the presence of TP53mut were associated with shorter OS in AML (5.5 mo vs 14.0 mo, p=0.32 and 4.8 mo vs 25.1 mo, p<0.0001). In multivariable Cox regression analysis of AML pts including the parameters significant in univariable analyses (complex karyotype, TP53mut, age and WBC count) only TP53mut (HR: 3.28, p=0.011) and WBC count (HR: 1.15 per 10 G/L, p=0.044) were independently associated with shorter OS. Conclusions: 1. Loss of 5q due to unbalanced translocations encompassing the telomeric 5q region is more frequent in AML (45.6%) than in MDS (32.8%) and in both entities associated with a complex karyotype. MDS patients with unbalanced 5q translocations show a shorter survival as compared to patients with interstitial 5q deletions. This data suggests that in MDS unbalanced 5q translocations reflect chromosomal instability which most probably is associated with progression to AML and adverse prognosis. 2. In AML with loss of 5q the presence of TP53 mutations is the strongest adverse prognostic factor. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Grossmann:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.
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Zygourakis, Corinna C., Janelle Lee, Julio Barba, Errol Lobo, and Michael T. Lawton. "Performing concurrent operations in academic vascular neurosurgery does not affect patient outcomes." Journal of Neurosurgery 127, no. 5 (November 2017): 1089–95. http://dx.doi.org/10.3171/2016.6.jns16822.
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OBJECTIVEConcurrent surgeries, also known as “running two rooms” or simultaneous/overlapping operations, have recently come under intense scrutiny. The goal of this study was to evaluate the operative time and outcomes of concurrent versus nonconcurrent vascular neurosurgical procedures.METHODSThe authors retrospectively reviewed 1219 procedures performed by 1 vascular neurosurgeon from 2012 to 2015 at the University of California, San Francisco. Data were collected on patient age, sex, severity of illness, risk of mortality, American Society of Anesthesiologists (ASA) status, procedure type, admission type, insurance, transfer source, procedure time, presence of resident or fellow in operating room (OR), number of co-surgeons, estimated blood loss (EBL), concurrent vs nonconcurrent case, severe sepsis, acute respiratory failure, postoperative stroke causing neurological deficit, unplanned return to OR, 30-day mortality, and 30-day unplanned readmission. For aneurysm clipping cases, data were also obtained on intraoperative aneurysm rupture and postoperative residual aneurysm. Chi-square and t-tests were performed to compare concurrent versus nonconcurrent cases, and then mixed-effects models were created to adjust for different procedure types, patient demographics, and clinical indicators between the 2 groups.RESULTSThere was a significant difference in procedure type for concurrent (n = 828) versus nonconcurrent (n = 391) cases. Concurrent cases were more likely to be routine/elective admissions (53% vs 35%, p < 0.001) and physician referrals (59% vs 38%, p < 0.001). This difference in patient/case type was also reflected in the lower severity of illness, risk of death, and ASA class in the concurrent versus nonconcurrent cases (p < 0.01). Concurrent cases had significantly longer procedural times (243 vs 213 minutes) and more unplanned 30-day readmissions (5.7% vs 3.1%), but shorter mean length of hospital stay (11.2 vs 13.7 days), higher rates of discharge to home (66% vs 51%), lower 30-day mortality rates (3.1% vs 6.1%), lower rates of acute respiratory failure (4.3% vs 8.2%), and decreased 30-day unplanned returns to the OR (3.3% vs 6.9%; all p < 0.05). Rates of severe sepsis, postoperative stroke, intraoperative aneurysm rupture, and postoperative aneurysm residual were equivalent between the concurrent and nonconcurrent groups (all p values nonsignificant). Mixed-effects models showed that after controlling for procedure type, patient demographics, and clinical indicators, there was no significant difference in acute respiratory failure, severe sepsis, 30-day readmission, postoperative stroke, EBL, length of stay, discharge status, or intraoperative aneurysm rupture between concurrent and nonconcurrent cases. Unplanned return to the OR and 30-day mortality were significantly lower in concurrent cases (odds ratio 0.55, 95% confidence interval 0.31–0.98, p = 0.0431, and odds ratio 0.81, p < 0.001, respectively), but concurrent cases had significantly longer procedure durations (odds ratio 21.73; p < 0.001).CONCLUSIONSOverall, there was a significant difference in the types of concurrent versus nonconcurrent cases, with more routine/elective cases for less sick patients scheduled in an overlapping fashion. After adjusting for patient demographics, procedure type, and clinical indicators, concurrent cases had longer procedure times, but equivalent patient outcomes, as compared with nonconcurrent vascular neurosurgical procedures.
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Offin, Michael, Chongrui Xu, Harsh Jain, Alex Makhnin, Sara A. Hayes, Andrew J. Plodkowski, Darragh Halpenny, et al. "Efficacy of ramucirumab and docetaxel given either before or after immune checkpoint inhibitors in patients with lung cancers." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 9078. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.9078.
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9078 Background: Ramucirumab and docetaxel (RamDoce) is a treatment for lung cancer patients after platinum-based therapy regardless of histology, the presence of oncogenic drivers, or prior immune checkpoint inhibition (ICI). Past data has shown a possible differential response to chemotherapy based on ICI exposure. We determined the activity of RamDoce given to patients before or after ICI. Methods: We evaluated patients with stage IV lung cancers who received RamDoce at MSK from 1/2015 - 6/2018. We grouped them based on timing of RamDoce: Before (including never receiving ICI) or After ICI. Ram was given at 8-10mg/kg with Doce 60-75mg/m2 every 2-3 weeks. Demographics, oncogene status and histologic comparisons were done with Mann-Whitney and Fisher’s exact tests. Time to treatment discontinuation (TTD) and overall survival (OS), were compared by long-rank test. Results: 194 patients received RamDoce: 78 Before and 116 After ICI. Median line of therapy for RamDoce in both cohorts was 3. Demographics in the Before and After ICI respectively included: 45 vs 53 female (p = 0.56), 50 vs 96 ever-smokers (p = 0.004), 59 vs 64 years old (p = 0.003), 73 vs 103 adenocarcinoma (p = 0.30). 83% (64/77) of patients with available tissue were PD-L1 negative. TMB was similar between cohorts (7.8 vs 6.1 mut/Mb, p = 0.68). Before ICI had a greater proportion of oncogenes present (64% vs 47%, p = 0.02). Combining Cohorts, TTD for EGFR-mutant (n = 41) and KRAS-mutant (n = 45) lung cancers was 4.0 and 3.9 months respectively vs 2.3 months for EGFR/KRAS-WT (p = 0.051). There was no difference in TTD for adenocarcinoma (n = 176) vs squamous cancers (n = 15, 2.6 vs. 3.1 months respectively; HR 0.8, 95% CI 0.4-1.7, p = 0.51). We saw no difference in TTD between Before (1.5 months) and After ICI (3.0 months, HR 0.88, 95% CI 0.7-1.2, p = 0.39). There was no difference in OS: Before ICI (1.6 years) and After ICI (2.0 years; HR 1.1, 95% CI 0.8-1.5, p = 0.49). Conclusions: There was no difference in TTD or OS for RamDoce when given before or after ICI. There was a trend toward prolonged benefit from RamDoce in EGFR/KRAS-mutant lung cancers. Data on the efficacy of RamDoce in oncogene-driven groups can help guide care and serve as a benchmark for new drug evaluations.
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Jin, Jie, Jianxiang Wang, Feifei Chen, Depei Wu, Jiong Hu, Jianfeng Zhou, Jianda Hu, et al. "Homoharringtonine-Based Induction Regimens for Patients with De Novo Acute Myeloid Leukemia: A Multicenter Randomized Controlled Phase 3 Trial." Blood 120, no. 21 (November 16, 2012): 45. http://dx.doi.org/10.1182/blood.v120.21.45.45.
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Abstract Abstract 45 Background Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukemia (AML), which have shown to improve the rate of complete remission (CR) and long-term survival. We aimed to further evaluate its efficacy and safety in treatment of de novo AML. Methods This phase 3 study was done in 17 institutions in China. Patients between the age of 14 and 59 with untreated AML were randomly assigned to receive HAA (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7, aclarubicin 20 mg/day, days 1–7), HAD (homoharringtonine 2 mg/m2/day, days 1–7; cytarabine 100 mg/m2/day, days 1–7; daunorubicin 40 mg/m2/day, days 1–3) or DA (daunorubicin 40–45 mg/m2/day, days 1–3; cytarabine 100 mg/m2/day, days 1–7) regimen as induction therapy. Patients who achieved partial remission or had a decrease of blast ¡Ý60% could receive a same second induction course. All patients who had a complete remission were offered the same consolidation chemotherapy according to the cytogenetic-risk. The primary endpoints were CR and event-free survival (EFS). The trial is registered in Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. Results 620 patients were randomly assigned to receive HAA (n=207), HAD (n=206) and DA (n=207) regimens. HAA or HAD regimen, as compared with DA regimen, resulted in a higher rate of CR in the first course of induction therapy (67.5% vs. 54.0%, P=0.005; 64.9% vs. 54.0%, P=0.026, respectively). The overall CR rate remained significantly higher in the HAA arm as compared with DA arm (75.0% vs. 61.9%, P=0.005). HAA or HAD regimen has similar rates of adverse events as compared with DA regimen, but was associated with significantly increased risk of induction death (5.8% vs. 1.0%, P=0.007; 6.6% vs. 1.0%, P=0.003, respectively). The EFS was greatly improved in the HAA arm (3-year EFS 35.4±3.5% vs.23.1±3.1%, P=0.002), while not significantly in the HAD arm (3-year EFS 32.7±3.5% vs.23.1±3.1%, P=0.078) as compared with the DA arm. Overall survival (OS) and relapse-free survival (RFS) did not differ significantly in the HAA or HAD arm as compared with DA arm, but an OS and RFS advantage of the HAA arm over the DA arm was observed in patients with favorable or intermediate cytogenetic profile (OS: P=0.014; RFS: P=0.022, respectively). Patients in the HAD arm with NPM1 but not FLT3ITD mutations, as compared with the patients in the DA arm, had an improved EFS (P=0.038). In intermediate cytogenetic profile, patients with mutant CEBPA had prolonged RFS in the HAA arm as compared with the DA arm (P=0.045). Conclusions Homoharringtonine-based induction regimens are associated with a higher rate of CR and improved survival as compared with DA regimen in AML. The toxicity is mild with the exception of a higher rate of induction death. Disclosures: No relevant conflicts of interest to declare.
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Richards, J., A. Testori, E. Whitman, G. B. Mann, J. Lutzky, L. Camacho, G. Parmiani, A. Hoos, R. Gupta, and P. Srivastava. "Autologous tumor-derived HSPPC-96 vs. physician’s choice (PC) in a randomized phase III trial in stage IV melanoma." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 8002. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.8002.
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8002 Background: Vitespen (Oncophage; formerly HSPPC-96) is an autologous, tumor-derived, heat shock protein (gp96)-peptide complex vaccine that has shown signals of clinical activity in patients (pts) with metastatic melanoma, and colon and renal cancers. Methods: This phase 3 trial compares vitespen v. PC in AJCC stage IV melanoma. Pts had ECOG PS 0/1 and ≥7 g tumor tissue for vaccine production. Randomization was 2:1 favoring vitespen, and stratified by ECOG PS and AJCC substage (M1a, -b, -c). Vitespen was administered s.c. weekly for 4 weeks, then biweekly until vaccine depletion or disease progression (DP). PC treatment was any regimen including IL-2 and/or dacarbazine/temozolomide and/or tumor resection. Pts were evaluated every 3 months for 1st year, every 6 months for 2nd year, then annually until DP. Primary endpoint was overall survival (OS). OS data, based on ITT, were analyzed using 1-sided log-rank tests. Results: From Jan 2002-Sept 2004, 322 pts at 76 centers (US, Europe, Russia/Ukraine, Australia) were enrolled. 215 pts were randomized to vitespen, 107 pts to PC. Mean age was 55 y; 59% were male; ECOG was 0 in 71% of pts; 19% of pts were M1a, 24% M1b, 57% M1c. 62% of pts in vaccine arm received vitespen; median number of vaccines was 6 (range, 0–74). As of Sept 2005, 18 pts were in tumor evaluation phase, 53 in survival follow-up, 251 off-study (death, withdrew consent, lost to follow-up). Median follow-up time for vaccine and PC arms was 250 and 289 d, respectively. Estimated median survival for vaccine and PC arms was 281 and 322 d, respectively (P = .078). M1a pts in the vaccine arm survived longer than those in the PC arm (626 v. 383 d, P = .177). Survival was comparable in both arms for M1b pts (297 v. 320 d, P = .478), and longer in the PC arm for M1c pts (299 v. 226 d, P = .015). Impact of number of doses was examined using landmark analyses to correct potential biases. Pts who received ≥10 doses of vaccine survived longer than those who received PC (377 v. 478 d, P = .072). Conclusions: Vitespen confers qualitative survival benefit over PC for M1a melanoma pts. If 10 doses of vaccine can be administered, vitespen also appears to confer survival benefit over PC for M1b pts. A phase 3 trial evaluating vitespen in M1a and M1b pts is planned. [Table: see text]
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Loureiro, B., A. M. Brad, and P. J. Hansen. "133 ROLE OF CASPASE-9 AND STAGE OF DEVELOPMENT IN INDUCTION OF APOPTOSIS BY HEAT SHOCK AND TUMOR NECROSIS FACTOR-α IN BOVINE PRE-IMPLANTATION EMBRYOS." Reproduction, Fertility and Development 18, no. 2 (2006): 175. http://dx.doi.org/10.1071/rdv18n2ab133.
Full textAbstract:
Heat shock and tumor necrosis factor-α (TNF-α) can increase apoptosis in bovine embryos in a developmental-dependent manner. It was hypothesized that addition of the caspase-9 inhibitor, z-LEHD-fmk, would block induction of apoptosis caused by heat shock of 41°C and TNF-α. Furthermore, it was hypothesized that the magnitude of induced apoptosis would increase with stage of development. Embryos were collected on day 4, 5, and 6 after in vitro insemination and were cultured for 24 h in the presence of either 100 μm z-LEHD-fmk reconstituted in 0.5% (v/v) dimethyl sulfoxide or vehicle dimethyl sulfoxide at either (1) 38.5°C for 24 h (control), (2) 41°C for 15 h followed by 38.5°C for 9 h, or (3) 38.5°C for 24 h with 10 ng/mL murine TNF-α. Embryos were then fixed, and the proportion of blastomeres undergoing apoptosis was determined using TUNEL labeling. Heat shock did not increase the percentage of blastomeres that were TUNEL-positive (% apoptosis) at day 4 (n = 100 embryos total). In contrast, heat shock increased % apoptosis at day 5 and day 6 (P < 0.04) and this effect was blocked by z-LEHD-fmk (temperature × inhibitor, P < 0.04). At day 5, % apoptosis in the absence and presence of z-LEHD-fmk was 3.8 ± 1.9% and 3.7 ± 1.7% at 38.5°C vs. 8.9 ± 1.5% and 4.1 ± 1.7% at 41°C (n = 75 embryos total). At day 6, % apoptosis in the absence and presence of z-LEHD-fmk was 3.6 ± 1.1% and 3.7 ± 1.2% at 38.5°C vs. 11.1 ± 1.1% and 6.1 ± 1.2% at 41°C (n = 168 embryos total). Mean cell number at the end of culture ranged from 21 to 26 cells at day 4, 43 to 73 cells at day 5, and 101 to 114 cells at day 6. Treatment with TNF-α also increased apoptosis at all days (P < 0.01), and z-LEHD-fmk blocked this effect (TNF × inhibitor, P = 0.05; n = 361 embryos total). Across days, % apoptosis was 3.6 ± 1.4% (control), 3.3 ± 1.3% (inhibitor), 11.1 ± 1.3% (TNF-α), and 6.0 ± 1.4% (TNF-α + inhibitor). Mean cell number at the end of culture ranged from 21 to 27 cells at day 4, 59 to 74 cells at day 5, and 105 to 115 cells at day 6. In conclusion, activation of caspase-9 dependent pathways is involved in the induction of apoptosis by heat shock and TNF-α. Moreover, the magnitude of induced apoptosis increases as embryos advance in development. This work was supported by USDA Grant No. 2004–34135–14715 and BARD Grant No. US–3551–04.