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1
Tallarico, Michael, Jared Foster, Drew Seisler, Jacqueline Lafky, Arti Hurria, Aminah Jatoi, Harvey Jay Cohen, et al. "Toxicities and Related Outcomes of Elderly Patients (pts) (≥65 Years) with Hematologic Malignancies in the Contemporary Era (Alliance A151611)." Blood 128, no. 22 (December 2, 2016): 536. http://dx.doi.org/10.1182/blood.v128.22.536.536.
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Abstract Background: Contemporary approaches to non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) incorporate chemo-immunotherapy, biologic combinations, and immune modulating agents; toxicities in elderly pts (³65 years) receiving these therapies are not well studied. Further, clinical and biologic factors predicting these toxicities in pts receiving biologic therapy remain undefined. Methods: We reviewed data on NHL and/or CLL pts treated prospectively on 14 studies by the Alliance for Clinical Trials in Oncology from 2004-2014 (Table 1). Toxicity was assessed per the NCI CTCAE at the time of trial enrollment, and the probabilities of experiencing grade 3 and grade 4 hematologic (hem) and non-hematologic (non-hem) toxicities were modeled as a function of age (³65 years vs. < 65), time on study, treatment (biologics only vs. biologic + chemotherapy), gender, race, LDH, performance status (PS), stage, and an age-by-treatment interaction using logistic regression. Results: A total of 1199 pts (409 age ³ 65; 790 age < 65; 736=CLL and 463=NHL) were included. Among these patients, 493 received only biologic therapy (166 age ³ 65; 327 age < 65; 104 CLL; 389 NHL), and 706 received biologic + chemotherapy (243 age ³ 65; 463 age < 65; 632 CLL; 74 NHL). Among CLL pts (259 pts ³ 65), the effect of age on the probability of experiencing a grade 3 heme toxicity differed by treatment type (age-by-treatment interaction p = 0.047). Specifically, the adjusted odds ratio (OR) (age ³ 65 vs. < 65) for pts receiving only biologic therapy was 3.075 (95% CI: 1,15-8.25), and that for pts receiving biologic + chemotherapy was 1.044 (95% CI: 0.69 - 1.57). Similar results were seen in CLL pts for grade 4 heme toxicities (age-by-treatment interaction p = 0.033; biologic OR 6.937, 95% CI: 1.76-27.35; biologic + chemo OR 1.484, 95% CI: 1.04-2.13). No such interactions were found in CLL pts for grade 3 and 4 non-hem toxicities; however, older pts had significantly higher odds of experiencing a grade 3 non-hem toxicity than younger pts (adjusted OR 1.40; p = 0.047; 95% CI: 1.004-1.96). No age group differences were found in CLL pts for grade 4 non-hem toxicity. Similar analyses were performed for NHL pts (150 pts ³ 65), but no significant age group differences were found. Among CLL pts, women had significantly higher odds of experiencing a grade 3 heme toxicity than men (OR 2.01; p = 0.0007); no difference in grade 3 non-hem or any grade 4 toxicity was noted. Non-Caucasian CLL pts had higher odds of experiencing a grade 4 non-hem toxicity than Caucasians (OR 2.892; p = 0.0029), but no other toxicity differences were found. Worse PS was associated with increased toxicities (OR 1.871; p = 0.0009: grade 3 heme; OR 1.647; p = 0.0025: grade 3 non-hem; OR 1.410; p = 0.0448: grade 4 heme, and OR 1.931; p = 0.0252: grade 4 non-hem). CLL pts with advanced stage disease had higher odds of experiencing a heme toxicity (grade 3: OR 1.95; p = 0.0007, grade 4: OR 1.451; p = 0.0329), but no stage associations were found for non-hem toxicities. Among NHL pts, men had significantly higher odds of experiencing a grade 4 hematologic toxicity than women (OR 4.351; p = 0.0169), but no other toxicity differences were found. An increase in LDH was associated with significantly higher odds of experiencing grade 3 non-hem and grade 4 heme toxicities (grade 3 non-heme: OR 1.633; p = 0.021, grade 4 heme: OR 2.039, p = 0.0182), but no such effect was found for grade 3 heme or grade 4 non-hem. Worse PS was associated with higher odds of experiencing grade 3 toxicities (heme: OR 2.025; p = 0.0344, non-hem: OR 2.458; p = 0.0013), but no such differences were found for grade 4 toxicities. No significant stage or race effects were found in NHL patients. Conclusion: In pts ³65 years who have CLL or NHL, we identified several clinical and disease-related factors as potential predictors of developing grade 3 and/or 4 heme and non-hem toxicities (Table 2). A prognostic model is being constructed to predict toxicities in these under-studied pts to guide management and monitoring. Further, the impact of these toxicities on outcomes is being analyzed and will be presented at the meeting. Disclosures Hurria: Celgene: Other: Research; Optum Health Care SOlutions: Consultancy, Other: Conference panel, research; Boehringer Ingelheim Pharmaceuticals: Consultancy; Sanofi: Consultancy; Carevive: Consultancy; Novartis: Other: Research; GTx, Inc: Consultancy. Bartlett:Gilead: Consultancy. Cheson:Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nabhan:Infinity: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Seattle Genetics: Research Funding; Genentech: Consultancy, Research Funding; Astellas: Research Funding; Celgene Corporation: Consultancy, Research Funding.
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Jordan, P. M., B. I. A. Mgbeje, S. D. Thomas, and A. F. Alwan. "Nucleotide sequence for the hemD gene of Escherichia coli encoding uroporphyrinogen III synthase and initial evidence for a hem operon." Biochemical Journal 249, no. 2 (January 15, 1988): 613–16. http://dx.doi.org/10.1042/bj2490613.
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1. The hemD gene, encoding uroporphyrinogen III synthase, has been located adjacent to the hemC gene at 85 min on the Escherichia coli chromosome. 2. The entire nucleotide sequence (741 base pairs) of the hemD gene is reported. 3. E. coli strains harbouring plasmics containing the hemD gene produce greatly elevated levels of uroporphyrinogen III synthase. 4. Purified uroporphyrinogen III synthase, isolated from the hemD-containing strain ST1046, has an Mr of 29,000, in close agreement with that predicted from the nucleotide sequence. 5. The existence of a hem operon is suggested.
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Ullah, Riaz, Mansour S. Alsaid, Abdelaaty A. Shahat, Almoqbil Abdulaziz Naser, Abdullah A. Al-Mishari, Muhammad Adnan, and Akash Tariq. "Antioxidant and Hepatoprotective Effects of Methanolic Extracts of Zilla spinosa and Hammada elegans Against Carbon Tetrachlorideinduced Hepatotoxicity in Rats." Open Chemistry 16, no. 1 (March 2, 2018): 133–40. http://dx.doi.org/10.1515/chem-2018-0021.
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AbstractThe detoxification, metabolism, and excretion of various endogenous and exogenous materials occur mainly in the liver. Liver diseases are a global concern, and classified as chronic hepatitis, cirrhosis, and hepatosis. The development of safe hepatoprotective agents remains an unmet need. Therefore, we investigated the antioxidant effects of methanolic and n-hexane fractions of Zilla spinosa (ZSM and ZSH, respectively) and Hammada elegans (HEM and HEH, respectively) against carbon tetrachloride (CCl4)-induced liver toxicity in rats. Antioxidant activity was studied by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The rats were divided into 11 groups (n=6)–group, 1 (control), group 2 (CCl4 only), group 3 (CCl4+silymarin 10 mg/kg), group 4 (CCl4+HEM 250 mg/kg), group 5 (CC14+HEM 500 mg/kg), group 6 (CCl4+HEH 250 mg/kg), group, 7 (CCl4+HEH 500 mg/kg), group, 8 (CCl4+ZSM 250 mg/kg), group 9 (CCl4+ZSM 500 mg/kg), group 10 (CCl4+ZSH 250 mg/kg), and group 11 (CCl4+ZSH 500 mg/kg). Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, and total bilirubin were measured. The extent of hepatic injury was histopathologically assessed. Treatment with ZSM and ZSH at 250 and 500 mg/kg did not significantly affect biochemical results compared with the CCl4 only group. However, treatment with both HEM and HEH at 250 and 500 mg/kg provided significant (p<0.001) results compared with the CCl4 only group. These results were consistent with histological findings. HEM and HEH at 250 μg/mL significantly inhibited DPPH radical formation by 38.E6 and 35.65%, rerpectively. However antioxidant effects of ZSM and ZSH were insignificant.
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Liu, Wen-Chao, Hyeok-Min Yun, Seung-Ho Pi, and In-Ho Kim. "Supplementing lactation diets with herbal extract mixture during summer improves the performance of sows and nursing piglets." Annals of Animal Science 17, no. 3 (July 26, 2017): 835–47. http://dx.doi.org/10.1515/aoas-2016-0084.
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Abstract A total of 45 Landrace × Yorkshire multiparous sows were used to evaluate the effect of dietary herbal extract mixture (Scutellaria baicalensis and Lonicera japonica, HEM) supplementation in lactating sows under heat stress. Sows were randomly allotted to 1 of 3 dietary treatments: 1) CON, basal diet; 2) TRT 1, basal diet with 5 g/d HEM; 3) TRT 2, basal diet with 10 g/d HEM. During lactation, dietary HEM supplementation linearly increased (P<0.05) the average daily feed intake (ADFI) and linearly decreased (P<0.05) backfat loss. The digestibility of dry matter (DM) was increased after farrowing (linear, P<0.05; quadratic, P<0.05) and weaning (linear, P<0.05) by HEM supplementation. Furthermore, HEM treatment led to a lower (linear, P<0.01) serum cortisol level. In addition, administration of HEM improved (linear, P<0.05) the piglets weaning weight and overall average daily gain (ADG) during suckling period. Meanwhile, on day 7 and 14 after birth, the fecal score of piglets was decreased (linear, P<0.01) by HEM supplementation. Taken together, under high ambient temperatures, inclusion of HEM to lactation diets could improve the feed intake, digestibility of DM, piglets weaning weight and ADG, while decreasing backfat loss, serum cortisol level, as well as the diarrhea of piglets.
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Bowen, Jennifer. "Notes on the Vanuatu Megapode Megapodius layardi on Ambrym, Vanuatu." Bird Conservation International 6, no. 4 (December 1996): 401–8. http://dx.doi.org/10.1017/s0959270900001842.
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SummaryThe Vanuatu Megapode Megapodius layardi is endemic to Vanuatu (formerly New Hebrides). On the volcanic island of Ambrym it exhibited three different incubation strategies. It incubated its eggs (1) in burrows between decaying roots of trees; (2) in burrows at large communal nesting grounds in volcanically heated soils; and (3) in burrows on sun-exposed beaches. No mounds were found. In a study by the Vanuatu Protected Areas Initiative (VPAI) nesting grounds were mapped to monitor the population. Three communal nesting grounds were surveyed. Two were on promontories and one on a beach. The burrows were classified into three categories: active, probably active and old. The density of active burrows per hectare of the three sites was 82.4 for Promontory A, 43.5 for Promontory B and 10.5 for Buwoma Beach. Additional information of this poorly known species was collected from villagers in the north-west and west of the island. They have noticed a decrease in the numbers of birds and have expressed concern about the future of the species.Le Mègapode de Vanuatu, Mègapodius layardi, est uniquement originaire de Vanuatu, (dit 'Nouvelles Hebrides' autrefois). Sur l'île volcanique d'Ambrym, il fait preuve de trois stratégies d'incubation différentes. II couve ses oeufs premièrement dans des terriers situés entre les racines pourries des arbres, duexièmement dans des terriers situés dans des grands terrains communaux de nids, et troisièmement dans des terriers situés sur des plages exposées au soleil. Aucan monticule n'est évident. Lors d'une étude par l'lnitiative des Terrains Protégés de Vanuatu (Vanuatu Protected Areas Initiative, VPAI), les terrains de nids furent plannifiés afin d'étudier la population. Trois terrains communaux de nids furent enquêtés. Les terriers furent classifiés en trois catégories; actifs, probablement actifs, et anciens. La densité des terriers actifs par hectare des trois terrains étaient de 82.4 pour le Cap A, 43.5 pour le Cap B, et de 10.5 pour la plage de Buwoma. Des données additionelles pur cet espèce peu connu furent rassemblées des villageois dand le nord ouest et l'ouest de Iîle. Ils ont constaté une diminuation des nombres d'oiseaux et ils ont exprimé leurs soucis vis-à-vis le future de l'espèce.Wan pijin, nem blong hem Namalau, Megapodius layardi, i stap long Vanuatu nomo (bifo, New Hebrides i nem blong Vanuatu). Long Ambrym, wan aelan wetem volkeno, Namalau i yusum trifala defren fasin long makem nes blong hem so heg blong hem i stap gud nomo; 1) ol i putum heg blong hem nekis rus bio tri wea ol rus i rotin 2) ol i putum heg blong hem wetem plenti narafala Namalau heg long graon wea volkeno i mekem groan i hot, 3) ol i putum heg blong hem insead sanbij wea san i makem i hot. Long Ambrym ol man i no fanem ples wea Namalau putum heg blong hem insaed wanples wea i gat plenti lif mo tri antap graon. Vanuatu Protected Areas Initiative (VPAI) i mekem wan stadi long ples wea ol Namalau i putum heg mo ol i mekem wan map. VPAI i lukum long trifala ples wea Namalau i putum heg. Tufala ples i stap long graon wea i go aot long solwota mo namba tri ples i stap long wan sanbij. I gat trifala defren grup blong ples wea ol i putum heg; niufala, klosap niufala mo olfala. Namba blong nuifala ples wea Namalau i putum heg insaed long wan hectare i 82.4 long pies A, 43.5 long ples B mo 10.5 long Buwoma sanbij. I no gat plenti save blong Namalau mo VPAI toktok plenti wetem ol man blong vilej long notwes mo wes Ambrym. Ol man is e namba blong Namalau i go daon bigwan mo ol i wari long fiuja long Namalau.
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Morris, Mackenzie C., Grace M. Niziolek, Thomas C. Blakeman, Sabre Stevens-Topie, Rosalie Veile, Victor Heh, Basilia Zingarelli, Dario Rodriquez, Richard D. Branson, and Michael D. Goodman. "Intrathoracic Pressure Regulator Performance in the Setting of Hemorrhage and Acute Lung Injury." Military Medicine 185, no. 7-8 (April 30, 2020): e1083-e1090. http://dx.doi.org/10.1093/milmed/usz485.
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Abstract Introduction: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI). Methods: Swine were anesthetized and underwent a combination of sham, hemorrhage, and/or lung injury. The experimental groups included: no injury with and without ITPR (ITPR, Sham), hemorrhage with and without ITPR (ITPR/Hem, Hem), and hemorrhage and ALI with and without ITPR (ITPR/Hem/ALI, Hem/ALI). The ITPR device was initiated at a setting of −3 cmH2O and incrementally decreased by 3 cmH2O after 30 minutes on each setting, with 15 minutes allowed for recovery between settings, to a nadir of −12 cmH2O. Histopathological analysis of the lungs was scored by blinded, independent reviewers. Of note, all animals were chemically paralyzed for the experiments to suppress gasping at ITPR pressures below −6 cmH2O. Results: Adequate shock was induced in the hemorrhage model, with the MAP being decreased in the Hem and ITPR/Hem group compared with Sham and ITPR/Sham, respectively, at all time points (Hem 54.2 ± 6.5 mmHg vs. 88.0 ± 13.9 mmHg, p < 0.01, −12 cmH2O; ITPR/Hem 59.5 ± 14.4 mmHg vs. 86.7 ± 12.1 mmHg, p < 0.01, −12 cmH2O). In addition, the PaO2/FIO2 ratio was appropriately decreased in Hem/ALI compared with Sham and Hem groups (231.6 ± 152.5 vs. 502.0 ± 24.6 (Sham) p < 0.05 vs. 463.6 ± 10.2, (Hem) p < 0.01, −12 cmH2O). Heart rate was consistently higher in the ITPR/Hem/ALI group compared with the Hem/ALI group (255 ± 26 bpm vs. 150.6 ± 62.3 bpm, −12 cmH2O) and higher in the ITPR/Hem group compared with Hem. Respiratory rate (adjusted to maintain pH) was also higher in the ITPR/Hem/ALI group compared with Hem/ALI at −9 and − 12 cmH2O (32.8 ± 3.0 breaths per minute (bpm) vs. 26.8 ± 3.6 bpm, −12 cmH2O) and higher in the ITPR/Hem group compared with Hem at −6, −9, and − 12 cmH2O. Lung compliance and end expiratory lung volume (EELV) were both consistently decreased in all three ITPR groups compared with their controls. Histopathologic severity of lung injury was worse in the ITPR and ALI groups compared with their respective injured controls or Sham. Conclusion: In this swine polytrauma model, we demonstrated successful establishment of hemorrhage and combined hemorrhage/ALI models. While ITPR did not demonstrate a benefit for MAP or ICP, our data demonstrate that the ITPR device induced tachycardia with associated increase in cardiac output, as well as tachypnea with decreased lung compliance, EELV, PaO2/FIO2 ratio, and worse histopathologic lung injury. Therefore, implementation of the ITPR device in the setting of polytrauma may compromise pulmonary function without significant hemodynamic improvement.
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Ahn, Jemin, Lei Cheng, and In Ho Kim. "121 Dietary astragalus membranaceus and codonopsis pilosula extracts supplementation increases growth performance and FMD antibody titers in growing-finishing pigs." Journal of Animal Science 97, Supplement_2 (July 2019): 68–69. http://dx.doi.org/10.1093/jas/skz122.126.
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Abstract An experiment was conducted to evaluate the effects of herbal extract mixture (HEM, Astragalus membranaceus and Codonopsis pilosula) supplementation on growth performance, nutrient digestibility, and FMD antibody titers in growing-finishing pigs. A total of 120 FMD type O vaccinated growing pigs [(Yorkshire × Landrace) × Duroc] with an average initial BW of 25.19 ± 1.80 kg were randomly allotted into 3 treatments with 8 replicate of 5 pigs per pen for a 16-week feeding study. All pigs were vaccinated against FMD. Treatments consisted of CON, Corn-soybean meal based diet; TRT1, CON + 0.05% HEM; TRT2, CON + 0.1% HEM. Vaccinated pigs fed 0.1% HEM showed higher (P < 0.05) BW and ADG at week 12, 16, and overall period. The supplementation of HEM had no effect on DM, N or GE throughout the experiment (P > 0.05). Feeding 0.1% HEM showed higher FMD type O antibody titers (P < 0.05) at week 14 compared with non-supplemented group. These results indicated that 0.1% HEM supplementation conferred anti-viral effect against FMD, thereby improving ADG in the growing-finishing pigs. Herbal extract mixture could potentially be used as an anti-viral agent against FMDV.
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Hao, Lijun, Yuxi Xie, Guikai Wu, Aibin Cheng, Xiaogang Liu, Rongjuan Zheng, Hong Huo, and Junwei Zhang. "Protective Effect ofHericium erinaceuson Alcohol Induced Hepatotoxicity in Mice." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–5. http://dx.doi.org/10.1155/2015/418023.
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We investigated the effects ofHericium erinaceus(HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration. Subsequent serum alanine aminotransferase (ALT) level, aspartate aminotransaminase (AST) level, Maleic dialdehyde (MDA) level, hepatic total antioxidant status (TAOS), and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined by ELISA and immunohistochemistry, respectively. HEM administration markedly(P<0.05)decreased serum ALT, AST, and MDA levels. The hepatic histopathological observations showed that HEM had a relatively significant role in mice model, which had alcoholic liver damage. In conclusion, we observed that HEM (200 mg/kg BW) supplementation could restrain the hepatic damage caused by acute alcohol exposure.
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Michot, Jean-Marie, Nicolas Delanoy, Thibault Comont, Nora Kramkimel, Romain Dupont, Julien Lazarovici, Stéphane Champiat, et al. "Immunological Cytopenias Induced By Anti-Programmed Cell Death (ligand) 1 Antibodies." Blood 132, Supplement 1 (November 29, 2018): 2412. http://dx.doi.org/10.1182/blood-2018-99-110875.
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Abstract Background. Anti-programmed death (ligand) 1 (PD-(L)1) antibodies are novel immunotherapies for cancer. Anti-PD(L)1 can induce immune-related adverse events (irAEs), which most frequently affect the skin, endocrine glands, lung, liver and digestive tract, however all organs including the hematopoietic system can potentially be involved. Hematologic irAEs (hem-irAEs) have not yet been extensively characterized. This study based on a pharmacovigilance academic registry aims to provide a comprehensive report of hem-irAEs. Patients and methods. All grade 2 or higher hem-irAEs recorded in pharmacovigilance databases were recorded in this study over the period 2013-2018. Pharmacovilance database included REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie) and ImmunoTOX committee of Gustave Roussy, and the French nationwide CeReCAI registry (Centre de Référence des Cytopénies Auto-Immunes de l'adulte). Prevalence of hem-irAE was calculated in the prospective REISAMIC registry. The hem-irAE's severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03). Results. Thirty-five patients (21 men and 14 women) with hem-irAEs related to anti-PD(L)1s were recorded. The prevalence of grade ≥2 hem-irAEs among patients treated with anti-PD(L)1s was estimated to 0.54%. The patients' median age was 65 years (range: 30-90), tumor types were melanoma (n=15), non-small-cell lung carcinoma (n=12), lymphoma (n=4), and other types (n=4). A concomitant medical history of chronic lymphocytic leukemia was found in 3 (9%) patients. The hem-irAEs were classified as neutropenia (n=9; 26%), auto-immune hemolytic anemia (n=9; 26%), immune thrombocytopenia (IT) (n=9; 26%), pancytopenia or aplastic anemia (n=5; 14%), bicytopenia (n=2; 6%) and pure-red cell aplasia (n=1; 3%). The maximum grade of severity reported was grade 2 in 3 (9%) patients, grade 3 in 8 (23%) patients and grade 4 in 24 (69%) patients. Two patients (6%) had a poor outcome and died in the course of the hem-irAE. Treatments given for the hem-irAE were steroids in 31 (89%) patients, granulocyte colony-stimulating factor in 13 (37%) patients, intravenous immunoglobulins in 6 (17%) patients and rituximab in 2 (6%) patients. The median time to onset from anti-PD(L)1 initiation was 10.1 weeks (range 0.9 - 198.0). With a median follow-up of 19 (range 2-180) weeks, the rate of resolution of hem-irAE was 67% (78% for IT and 40% for aplastic anemia patients, p=0.524). After resolution, 6/35 (17%) patients were rechallenged and 3 of them (50%) recurred the same hem-irAE. Conclusion. The clinical spectrum of hematologic irAE is wide and dominated by neutropenia, hemolytic anemia and immune thrombocytopenia. Aplastic anemia is rarer and present as a life-threatening condition. The prevalence of grade ≥2 hematologic irAEs following anti-PD(L)1 was 0.54%. The recurrence rate after rechallenge was 50%. Further prospective investigations are warranted to better detect and manage hematologic immune-related adverse events. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Maerevoet:abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; roche: Other: travel grant; takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Ribrag:Servier: Consultancy, Honoraria; Amgen: Research Funding; BMS: Consultancy, Honoraria, Other: travel; Incyte Corporation: Consultancy; Infinity: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; MSD: Honoraria; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; argenX: Research Funding; epizyme: Consultancy, Honoraria; pharmamar: Other: travel.
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Tecle, I. Y., J. L. Hansen, A. N. Pell, and D. R. Viands. "Divergent phenotypic selection for alfalfa cell wall fractions and indirect response in digestibility." Canadian Journal of Plant Science 88, no. 5 (September 1, 2008): 891–98. http://dx.doi.org/10.4141/cjps07134.
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An alfalfa (Medicago sativa L.) breeding strategy to decrease slowly digestible or indigestible fiber and simultaneously increase digestible fiber could improve forage quality without reducing total fiber. The objectives were: (1) to estimate selection responses from divergent and opposite direction selections of (i) hemicellulose (HEM) and acid detergent fiber (ADF), (ii) acid detergent lignin (LIG) and HEM + cellulose (CEL) and (iii) CEL and HEM + LIG, and (2) to determine correlated responses in in vitro true digestibility (IVTD). Selection progress was evaluated in replicated plot trials at two locations, sampled for 2 or 3 yr. Selection for divergent HEM and ADF resulted in change only for ADF [10.9 g kg-1 dry matter (DM)]. Selection for divergent LIG and HEM + CEL, resulted in same direction change in LIG (3.3 g kg-1 DM). Selection for divergent CEL and HEM + LIG resulted in change only in CEL (5.1 g kg-1 DM). Low LIG and high HEM + CEL, and low ADF and high HEM populations had 9.7 and 8.3 g kg-1 DM higher IVTD than their counterparts, respectively. The first cycle of selection for the fiber components simultaneously in the opposite directions was not successful. However, reduced LIG or ADF concentration appears to increase alfalfa forage digestibility and decrease total fiber concentration. Key words: Alfalfa, cell wall, hemicellulose, cellulose, lignin, digestibility
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Knöferl, Markus W., Martin K. Angele, Alfred Ayala, William G. Cioffi, Kirby I. Bland, and Irshad H. Chaudry. "Insight into the mechanism by which metoclopramide improves immune functions after trauma-hemorrhage." American Journal of Physiology-Cell Physiology 279, no. 1 (July 1, 2000): C72—C80. http://dx.doi.org/10.1152/ajpcell.2000.279.1.c72.
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Although studies have shown that prolactin (Prl) and metoclopramide (Mcp) administration restores the depressed cell-mediated immune functions after hemorrhage, the underlying mechanism responsible for the immunostimulatory effects of Mcp remains unknown. We hypothesized that Mcp improves immune responses by upregulating the secretion of Prl. To test this hypothesis, male C3H/HeN mice were subjected to sham operation or laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (Hem; 35 ± 5 mmHg for 90 min) and then resuscitated. Plasma Prl levels were determined 30 min after Mcp (1 μg/g body wt sc at end of Hem) or vehicle (Veh) treatment in sham and Hem mice. The results indicate that plasma Prl levels increased significantly in Mcp-treated mice (sham-Veh 249.9 ± 5.3, Hem-Veh 229.9 ± 7.6, Hem-Mcp 596.9 ± 73.1 ng/ml, one-way ANOVA, P < 0.05 vs. Veh). To determine whether Mcp produces its salutary effects directly or indirectly via increased Prl secretion, splenocyte proliferation and splenocyte interleukin (IL)-2 and IL-3 release from untreated sham or Hem mice were determined in the presence of increasing concentrations of mouse Prl or Mcp. The addition of Mcp had no effect on splenocyte immune functions in vitro. However, the addition of Prl restored the hemorrhage-induced depressed splenocyte proliferation as well as splenocyte IL-2 and IL-3 release in vitro in a dose-dependent manner. Thus the beneficial effects of Mcp on immune functions after Hem appear to be mediated by Prl. Because Mcp increases plasma levels of the immunoenhancing hormone Prl, this agent should be considered a useful adjunct for the treatment of immunodepression in trauma victims.
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Gellerfors, P. L., J. Saltzgaber-Müller, and M. G. Douglas. "Selection by genetic complementation and characterization of the gene coding for the yeast porphobilinogen deaminase." Biochemical Journal 240, no. 3 (December 15, 1986): 673–77. http://dx.doi.org/10.1042/bj2400673.
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The porphobilinogen deaminase (PBG-D) gene of Saccharomyces cerevisiae has been isolated by genetic complementation of a mutant GL7 (alpha hem 3) strain, previously shown to be defective in this haembiosynthetic enzyme [Gollub, Liu, Dayan, Adlersberg & Sprinson (1977) J. Biol. Chem. 252, 2846-2854]. The gene was selected from a yeast wild-type genomic DNA library ligated into the shuttle vector YEp13. The complementing gene restored growth of the hem 3 (PBG-D) mutant strain on media in the absence of exogeneous haem or fatty acid and sterol supplements. The recombinant plasmid was retained in the Hem+ transformant provided that selective pressure for plasmid-dependent growth was maintained. Transformation of the mutant strain (hem 3) restored the PBG-D activity to levels up to 10-fold those of the parental strain. The mutant strain GL7 does not show any measurable enzymic activity. Analysis of the plasmid designated YEpPBG-D (containing the PBG-D gene) by hybrid-selected translation revealed that it contained the coding information for a single protein of apparent Mr 43,000. The coding region was localized on an 1.5 kb endonuclease-EcoRI fragment (E4), within the 5.5 kb genomic insert in YEpPBG-D.
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Tobin, Swanee, Joyce Fenuta, Julie Kruchowski, and Lisa K. Hicks. "High-needs hematology/oncology patients: A quality improvement project." Journal of Clinical Oncology 31, no. 31_suppl (November 1, 2013): 197. http://dx.doi.org/10.1200/jco.2013.31.31_suppl.197.
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197 Background: St. Michael’s Hospital (SMH) is an academic, inner-city hospital in Toronto, Canada. In the hematology/oncology (hem/onc) program, a small number of patients appeared to contribute disproportionately to hospital admissions and emergency department (ED) visits. We hypothesized that high needs hem/onc patients could be recognized early in their care and that ED visit and admission rates among these patients could be decreased through targeted interventions. Methods: Members of the hem/onc team were interviewed regarding characteristics, which they felt predicted higher needs and greater liklihood for hospital admission/ED visit. A list of high risk features was generated. ED visit and admission rates for a prospectively identified high needs cohort were compared to rates for the entire hem/onc clinic. An intervention targeting high needs hem/onc patients is on-going. Pre and post-intervention ED visit and admission rates will be compared. Results: Interviews with 3 nurses, 1 social worker, 1 discharge planner, and 4 physicians identified 10 factors that the hem/onc team believed were predictive of higher needs and subsequent higher ED visit and admission rates. Between December 1, 2012, and February 28, 2013, 42 high needs hem/onc out-patients were prospectively identified. The ED visit and admission rates for this cohort were retrospectively compared to those of the entire hem/onc clinic and found to be dramatically higher (Table). Begininng in June 2013, hem/onc patients identified as “high needs” were offered enrollment in a NP-based program offering telephone assessments following ED visits, hospital admissions or discharges. Assessment of the impact of this intervention is ongoing. Conclusions: It is possible to prospectively identify hem/onc patients who are at risk of higher than usual ED visit and admission rates. Identifying this population may provide an opportunity to decrease their ED visit and admission rates. An evaluation of an intervention targeting high needs hem/onc patients is ongoing. Preliminary data will be presented. [Table: see text]
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Fischer, Sean A., Francis Carolyn, and Kessler M. Craig. "Histopathological Findings on Liver Biopsies (bx) Do Not Correlate with Serum Markers of Fibrosis and Necro-Inflammation in Hemophiliacs (HEM) Co-Infected with Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV)." Blood 106, no. 11 (November 16, 2005): 3204. http://dx.doi.org/10.1182/blood.v106.11.3204.3204.
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Abstract Background: Virtually all severe HEM exposed to plasma concentrates in the USA before 1985 are seropositive for HCVand HIV. HIV accelerates progression of HCV-induced chronic liver disease. HAART therapy has stabilized HIV in HEM so that end-stage liver disease is the predominant cause of death in HIV/HCV HEM. Pegylated interferon-alpha and ribavirin (IFN-R) produces significant remission in chronic HCV, and HEM with chronic HCV should benefit similarly. Liver histology is desirable to decide who should receive IFN-R since evidence of limited fibrosis with inflammation would be expected to derive the most benefit. Liver bx in HEM is fraught by significant costs of factor replacement and the small risk of significant bleeding. Thus, a surrogate marker for the information revealed by liver bx would be particularly advantageous for HEM with HCV. Diagnostic kits composed of specific and sensitive serum biochemical markers for the chronic complications of HCV are being validated as surrogates for liver bx, particularly prior to initiating IFN-R. The FibroSure assay (Labcorp, Burlington, USA) purportedly detects hepatic fibrosis and necrosis (necroinflammation) and in non-HEM cohorts appears predictive for either absent or minimal fibrosis or for advanced fibrosis/cirrhosis. The assay poorly predicts intermediate fibrosis. Patients and Methods: Histopathologic features of acute and chronic HCV and fibrosis observed from liver bx in 49 HEM were retrospectively correlated with the biochemical markers for liver fibrosis and necrosis. This was intended to determine if the FibroSure assay could substitute for liver bx in HEM. Impact of HIV/HCV co-infection on bx morphology and FibroSure results were also assessed. Trans-jugular liver bx was utilized in all HEM. Results: Of 49 HEM, 22 (44.9%) had HCV/HIV co-infection. Thirty one HEM underwent liver bx and 40 had FibroSure results. Twenty two had both liver bx and FibroSure. Only 18 had interpretable data from FibroSure. Seven of these 18 (38.9%) had morphological evidence of chronic HCV with significant fibrosis (Metavir score >2) but only 3/7 (42.8%) had FibroSure results corroborative of significant fibrosis (score of 0.48 or higher correlating with a Meatier score>2). All of these 7 HEM were co-infected. One of 18 (5.6%) HEM exhibited minimal fibrosis on liver bx but FibroSure results consistent with severe fibrosis. The 4 uninterpretable FibroSure results were from HIV/HCV HEM with opportunistic infections involving the liver but without marked fibrosis on bx. The median bx length was 1.7 cm for the entire cohort, which was adequate for representative morphological assessment. No bleeding complications occurred with transjugular liver bx. Conclusions: In this cohort of HEM, FibroSure results do not strongly correlate with the presence of severe liver fibrosis observed on bx. HIV co-infection may be responsible for this poor sensitivity since all 7 HEM with severe fibrosis on liver bx were infected with both. Trans-jugular liver bx was well tolerated and safe in HEM. In summary, our data do not support using the FibroSure assay as a sensitive or reliable surrogate marker for the extent of hepatic fibrosis in HCV/HIV co-infected HEM. Liver bx should still be considered the "gold standard" in co-infected HEM when assessing the suitability of IFN-R therapy.
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Willis, Lauren, Pan Chen, and Katie S. Lucero. "Large Impact of Continuing Medical Education on Community Hem/Oncs and Educational Gaps in Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 3489. http://dx.doi.org/10.1182/blood-2019-124836.
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Introduction: Two surveys were conducted to understand the rationale for hematologists/oncologists (hem/oncs) to seek continuing medical education (CME) as well as how the information is applied to clinical practice. Additionally, we studied the clinical decision making of hem/oncs who treat patients with multiple myeloma (MM) in order to understand the areas to focus for future CME activities. Methods: We conducted two incentivized surveys where only hem/oncs in the US who treat patients were eligible: 1) MM decision-making survey (MM survey) in November 2018 where they were asked case-based questions to assess practice patterns and they were asked to rate their level of confidence in their decisions for the cases; and 2) Information seeking behaviors and preferences survey (behavior survey) in May and June 2019 where they responded to questions about what information informs practice and how often they need new information. Physicians were paid for their participation in the surveys. Results: 93 hem/oncs participated in the behavior survey with 56% from the community setting and 44% practicing exclusively in an academic setting. Community hem/oncs visit online CME more frequently than academic hem/oncs (daily or at least once a week: 67 vs 51%, respectively). The primary factors driving hem/oncs to access online CME include the need to learn about the latest developments (45%) and looking for an answer to a specific question (25%). Community hem/oncs are 2x more likely than academic hem/oncs to access online CME in order to earn credits. All of the hem/oncs surveyed have modified or implemented a new clinical practice in the last year, with the majority of the modified or new practices related to treatment (69%). Community hem/oncs are 174% more likely than academic hem/oncs to use CME as the source of the information leading to modified/new practice (27% vs 10%). The influence of CME on clinical practices is especially striking among hem/oncs practicing in a community vs academic setting on both gaining more confidence in their current practices (71% vs 59%) and modifying treatment practices (64% vs 54%). There were 101 hem/oncs who participated in the MM survey with 51% practicing in the community setting and 55% seeing between 1 to 10 patients with MM per month, whereas 22% saw more than 20 patients with MM per month. Case 1 highlights the lack of confidence among hem/oncs in making treatment decisions for patients with relapsed/refractory MM, with the majority, between 55% to 72%, only somewhat or not confident in their clinical decision. Although various options would be acceptable and not harmful, ideally treatment decisions would be made with a sense of confidence. In case 2, a striking 48% of hem/oncs would use a bortezomib-based regimen in a patient who has severe peripheral neuropathy, despite bortezomib's known side effect of peripheral neuropathy. For those who would use carfilzomib (52%) or a non-bortezomib regimen (13%), less than half (42% and 46%, respectively) were confident in their decision. Case 3 highlights the complexity of tailoring therapy for patients with MM as any of the answers could be appropriate, but between 37% and 67% of hem/oncs were only somewhat or not confident in their choices, indicating a need for additional education. Conclusions: Large Impact of CME on Community Hem/Oncs: A majority of hem/oncs access online CME at least once a week in order to learn about the latest developments and to find answers to specific questions, with the need for CME credits being a minor driver of CME consumption. The data show that CME has a high impact on clinical practices as the majority of hem/oncs surveyed modified or implemented new clinical practices in the last year as a result of what was learned in CME activities. The impact of CME on clinical practices is particularly striking among hem/oncs who practice in community-based settings. Additional Multiple Myeloma-Focused CME is Needed:The treatment paradigm for MM is rapidly evolving and this analysis shows that in order to improve the skills of hem/oncs as well as their confidence in their clinical decision making, additional CME is needed in the areas of (1) individualizing treatment for R/R MM, (2) managing adverse events, and (3) selecting maintenance therapy for high-risk MM. Table Disclosures No relevant conflicts of interest to declare.
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Pineda, Anna. "Aspectes de la transitivitat en els inicis del català modern." Caplletra. Revista Internacional de Filologia, no. 66 (February 13, 2019): 207. http://dx.doi.org/10.7203/caplletra.66.13510.
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En aquest estudi de corpus hem volgut fer una primera aproximació a diversos aspectes de la transitivitat, entesa com a fenomen amb diversos vessants, en els textos corresponents a l’inici del català modern (segle XVII, amb un èmfasi especial en la primera meitat de segle). Hem tractat, concretament, el cas de diversos verbs que presenten un comportament vacil·lant entre l’ús transitiu i l’ús intransitiu, i ens hem acostat a aquest fenomen des del vessant del marcatge diferencial d’objecte, atès que aquest règim vacil·lant és un factor que pot crear confusió a l’hora d’analitzar l’extensió dels objectes directes introduïts per a (v. § 2). A continuació, i encara mantenint el marcatge diferencial d’objecte com a punt de referència, ens hem fixat en les diverses construccions que afavoreixen notablement l’ús d’aquest marcatge davant dels objectes directes (v. § 3). Per acabar, hem tractat de manera succinta altres aspectes interessants de la transitivitat en els textos dels inicis del català modern, com ara l’ús de verbs inergatius en patrons transitius que inclouen un objecte directe cognat o la causativització de verbs intransitius que expressen moviment (v. § 4).
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Kaul, Esha, John Paul Flores, Jessica K. Paulus, and Krishna S. Gunturu. "Hematology and Oncology: Natural Allies Or Time To Part Ways? Results Of a Medicine Resident Survey." Blood 122, no. 21 (November 15, 2013): 2920. http://dx.doi.org/10.1182/blood.v122.21.2920.2920.
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Abstract Background Over the last decade there has been a rapid increase in the body of knowledge in Hematology and Oncology with major changes in treatment strategies and available therapies. In this current climate, the majority of physicians with Hematology-Oncology training focus their practice on either Hematology or Oncology. However, currently most fellowship programs combine the two specialties. In 2012, only 16 Hematology-specific fellowship positions were available nationwide, and the number of applicants per position in the NRMP Match for Hematology and Hematology-Oncology (Hem-Onc) was 7.4 and 1.5, respectively. A report from the American Society of Clinical Oncology (ASCO) predicted an acute shortage in the Hem-Onc workforce by the year 2020. As we attempt to meet this demand by training more fellows, it is important to understand the Hem-Onc environment in which the internal medicine residents are surrounded as they choose their career pathways. We therefore conducted a survey of internal medicine residents to understand their perceptions about this field and how they make decisions about fellowship training. Methods The content and wording of the survey were developed in focus group discussions of the authors. A 5 point Likert scale was used to identify a range of responses. A pilot was performed with the Hem-Onc fellows to test the survey for clarity and relevance. The Research Electronic Database electronic capture (REDCap) software was used for survey development and distribution. Program directors were contacted via email regarding study participation. The invitation to complete a 4 page anonymous web based survey was sent to Internal Medicine residents at 4 residency programs in Massachusetts (1 university-based and 3 community-based) between January 2012 and July 2012. Counts and proportions were used to summarize survey responses. Results 77 out of the 171 current residents enrolled in the 4 residency programs completed the survey (response rate: 45%). 59 (77%) of the respondents were either committed to or had considered pursuing fellowship training. Among these residents, Hem-Onc was among the top three choices for 20 (26%) of the respondents. The top three factors that led them to consider a fellowship in Hem-Onc were intellectual stimulation, the rapidly expanding field, and a personality fit (Table 1). The top reasons cited for not considering a career in Hem-Onc were the lack of curative options, personality fit, and dealing with end of life issues (Table 2). Of the 57 residents not considering a combined Hem-Onc fellowship, 16 (26%) were willing to consider fellowships in Hematology or Oncology if tracks where offered separately [11 (69%) for Hematology alone or 5 (31%) for Oncology alone]. Even among those considering combined Hem-Onc fellowships, 3 (15%) would consider fellowships in Hematology alone and 3 (15%) would consider oncology alone. In terms of the residency training environment, the areas of Hem-Onc training where most residents felt their exposure to the field be lacking were outpatient oncology (59,77%) and benign hematology (49, 64%). (Fig.1) Discussion While Hematology and Oncology have traditionally been offered as a combined 3 year fellowship, there is substantial interest in separate Hematology and Oncology fellowships as evidenced by our survey results and NRMP data. A greater number of Hematology- or Oncology-specific fellowships could attract more residents to these subspecialties and help meet the increasing demand for Hematologists and Oncologistsin clinical practice. Also, increased exposure to outpatient, in addition to inpatient, Hem-Onc during residency would be more representative of actual practice, could dispel misconceptions about dismal outcomes in Hem-Onc, and may help attract more residents to the field. Disclosures: No relevant conflicts of interest to declare.
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Kou, Kai, Xingkai Liu, Yuelei Hu, Feixiang Luo, Dawei Sun, Guangyi Wang, Yan Li, Yuguo Chen, and Guoyue Lv. "Hem-o-lok clip found in the common bile duct 3 years after laparoscopic cholecystectomy and surgical exploration." Journal of International Medical Research 47, no. 2 (January 7, 2019): 1052–58. http://dx.doi.org/10.1177/0300060518817216.
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Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is a common and preferred choice for gallstone disease. Laparoscopic common bile duct exploration (LCBDE) and laparoscopic cholecystectomy (LC) are being increasingly used for managing choledocholithiasis and cholecystolithiasis. We report a case of a Hem-o-lok clip that was dropped into the common bile duct (CBD) after LC and surgical common bile duct exploration (CBDE). An 84-year-old man presented with right upper quadrant pain and jaundice for 2 months, and chills and hyperpyrexia for 1 day. The patient had received ERCP and surgical CBDE at a local hospital 3 years previously. The patient first received ERCP and endoscopic nasobiliary drainage (ENBD). When laboratory tests were normal, the patient then received LCBDE. During exploration, stones and a Hem-o-lok clip in the CBD were removed. The patient made good progress after LCBDE + T-tube placement and was discharged from hospital. The findings from this case suggest the following: 1) an appropriate therapy method should be considered for certain gallstone diseases, especially for choledocholithiasis and cholecystolithiasis; and 2) a Hem-o-lok clip should be carefully used during laparoscopic or robot-assisted surgery and the Hem-o-lok clip should not be in close proximity to the incision on the CBD.
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Vadhan-Raj, Saroj, Xiao Zhou, Jatin J. Shah, Robert S. Benjamin, and Gregory Gladish. "Venous Thromboembolism (VTE) in Patients with Hematologic and Non-Hematologic Malignancies: Incidence and Risk Factors for Recurrent VTE." Blood 118, no. 21 (November 18, 2011): 2303. http://dx.doi.org/10.1182/blood.v118.21.2303.2303.
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Abstract Abstract 2303 The incidence of VTE and risk for recurrence is known to be higher in patients (pt) with malignancy than in other patients. However, the exact incidence and risk factors predictive of recurrent VTE in patients with hematologic malignancies (Hem) and solid tumors (ST) are not well defined. A retrospective study was conducted to evaluate the incidence of VTE and the recurrent events during one year period at MD Anderson Cancer Center. The medical records of all patients with VTE confirmed by the radiologic studies in 2006 were reviewed. The data were collected for the incidence and type of VTE, the recurrent events during a one year follow-up from the time of primary event, and the risk factors for recurrent events, including, the pt demographics, diagnosis, prior history of VTE, transfusions, use of erythropoiesis-stimulating agents, and the laboratory parameters at the time of the index VTE event. Cox proportional hazard models were established to determine the independent predictive factors for recurrent VTE. There were 24,806 unique patients (each patient counted once) in active treatment at the Cancer Center between January 2006 and December 2006. Of the 980 pts diagnosed with VTE (480 DVT, 477 PE, and 23 DVT/PE) during this period, there were 770 ST, 208 Hem, and 2 benign conditions. The incidence of VTE was higher in Hem pts than in ST pts [208/3603 (6%) vs. 770/20212 (4%), p<0.0001]. Among Hem pts, the incidence was significantly higher in myeloma as compared to lymphoma and leukemia (9%, 6%, and 4%, respectively, p<0.0001). The proportion of VTE pts with PE was significantly higher among ST pts compared with Hem pts (55% vs 37%, p<0.0001). The incidence of recurrent VTE, as defined by any new event or progression of the index event, was 14% (140/978 pts) during one year follow-up period, and it was not different for Hem (16%) vs. ST (14%). Among Hem pts, the recurrence was higher for myeloma (19%) than lymphoma (16%) and leukemia (13%). Majority of the recurrent events (100/140, 71%) were seen during the initial 3 month period from the index event. The independent risk factors for recurrent VTE during 3 months, 6 months and 1 year were summarized in the following table:3 months6 months1 yearRisk factorsHazard ratio (95% CI)PHazard ratio (95% CI)PHazard ratio (95%CI)PPE vs. non-PE1.86 (1.20–2.88)0.0051.67 (1.12–2.42)0.0061.74 (1.20–2.51)0.003Age (<60 vs. ≥60 years)2.05 (1.34–3.15)0.0011.55 (1.08–2.23)0.0171.62 (1.14–2.32)0.008Men vs. women1.70 (1.10–2.63)0.0181.44 (0.994–2.07)0.054PE, pulmonary embolism; CI, confidence interval. Conclusions: The incidence of VTE is higher in Hem pts, especially in myeloma. Younger age (<60 years) and PE are independent risk factors predictive of recurrence during 3 month, 6 month and 1 year period. Disclosures: No relevant conflicts of interest to declare.
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Prince, Grace, Allison Mary Deal, Megan Jean McKee, Dimitri G. Trembath, Kevin Keith, Juanita Ramirez, Bentley Randall Midkiff, et al. "Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 2072. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.2072.
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2072 Background: Brain metastases (BM) are an increasingly common consequence of breast cancer (BC). Knowledge of the microenvironment in primary BC and its impact on prognosis is evolving. A similar understanding of the microenvironment of BC metastases is lacking, particularly for the brain, where unique immune regulation governs stroma composition. Such features of the peri-tumoral landscape, i.e. high immune infiltrate and low hemorrhage, offer prognostic value in BM from melanoma. This study reports on 4 biomarkers, gliosis (glio), immune infiltrate (immune), hemorrhage (hem) and necrosis (nec), and their prognostic significance in BCBM. Methods: A biobank of 203 patients (pts) who underwent craniotomy between 1989-2013 was created across 4 sites. Glio, immune, and hem (grouped 0 v 1-3) and nec (0-2 v 3) were scored via H&E stain (0-3). Overall survival (OS (years)) from craniotomy was estimated using the Kaplan-Meier method; log-rank tests compared OS. Cox proportional hazards regression was used to evaluate prognostic value of the 4 biomarkers. Results: Mean age at primary BC diagnosis was 48 years (range 26-77). BCBM subtype (n = 158) was 36% HER2+, 26% HR+/HER2-, 38% HR-/HER2- (TN). Across all samples, expression was 82% glio, 45% immune, 82% hem, and 13% nec. Subtype differences were seen for nec (higher in TN, p < 0.01). Across all pts, expression of glio, immune, and hem was associated with improved OS (years): 1.08 v 0.62 (p = 0.03), 1.31 v 0.93 (p = 0.03), 1.07 v 0.92 (p = 0.1), respectively. Nec was associated with inferior OS: 0.38 v 1.12 (p = 0.01). The association with improved OS was maintained for glio in TN (p = 0.02), and immune (p = 0.001) and hem (p = 0.07) in HER2+. In a multivariable model for OS, adding the 4 biomarkers to traditional clinical variables (age, race, subtype) significantly improved the model fit (p < 0.001). Conclusions: Nec is a poor prognostic finding in BCBM across all subtypes. Glio confers superior prognosis in TN, while immune and hem correlate with superior prognosis in HER2+. A deeper understanding of the rich BCBM microenvironment both refines prognostic considerations for this pt population and may lead to future investigations of targeted immunotherapies in select subtypes of BCBM.
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Eisenach, Natalie, Mason Uvodich, Sharon Wolff, and Valerie French. "Initiation of Postpartum Contraception by 90 Days at a Midwest Academic Center." Kansas Journal of Medicine 13 (August 17, 2020): 202–8. http://dx.doi.org/10.17161/kjm.v13i.14564.
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Introduction. Contraception is a critical component of addressing the health needs of women in the postpartum period. We assessed contraception initiation by 90 days postpartum at a large, academic medical center in the Midwest.
Methods. In this retrospective cohort study, 299 charts were randomly sampled and 231 were analyzed from deliveries between May 1 to July 5, 2018. Contraceptive method, maternal demographics, and obstetric characteristics at hospital discharge were collected, as well as contraceptive method at the postpartum follow-up appointment. Methods and strata of contraception were categorized as follows: 1) highly effective methods (HEM) defined as sterilization, intrauterine device, or implant, 2) moderately effective methods (MEM) defined as injectable contraception, progestin-only pills, and combined estrogen/progestin pills, patches, and rings, and 3) less effective methods (LEM) defined as condoms, natural family planning, and lactational amenorrhea. Women lost to follow-up who had initiated a HEM or injectable contraception were coded as still using the method at 90 days. We used logistic regression to identity factors associated with HEM use.
Results. Of the 231 included patients, 118 (51%) received contraception before hospital discharge and 166 (83%) by 90 days postpartum. Postpartum visits were attended by 74% (171/231) of patients. Before hospital discharge, 28% (65/231) obtained a HEM and 41% (82/200) were using a HEM by 90 days postpartum. Patients obtaining HEM or injectable contraception before hospital discharge attended a follow-up visit less often than those who did not receive HEM before discharge (RR = 0.68, 95% CI: 0.54 - 0.86, p ≤ 0.01).
Conclusion. When readily available, many women will initiate contraception in the postpartum period. Health systems should work to ensure comprehensive access to contraception for women in the postpartum period.
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Eroğlu, Gülizar, and Hüseyin Uzunboylu. "Content analysis on the orientations of place-based/outdoor environmental education." International Journal of Innovative Research in Education 4, no. 3 (October 17, 2017): 155. http://dx.doi.org/10.18844/ijire.v4i3.2555.
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“Doğadaki çocuk, soyu tehlike altında olan bir türdür ve çocukların sağlığı ile yeryüzünün sağlığı birbirine sıkı sıkıya bağlıdır.” R.Louv. Değişen yaşam tarzı ve ilerleyen teknoloji insanların hem doğayı algılamalarında hem de doğayla olan ilişkilerinde etkili olmuş, doğa ile insan arasındaki ilişki neredeyse kopma noktasına gelmiştir; bu da günümüzdeki çevre sorunlarının giderek artmasına, insanı hem psikolojik hem de fizyolojik olarak olumsuz etkileyen bir süreç yaşanmasına sebebiyet vermiştir (Tuğun, Uzunboylu & Özdamlı, 2017). Buradan yola çıkarak Birleşmiş Milletler çevre gündemini 2017 yılını doğa ile insan arasındaki bağın oluşturulması temeline dayandırmıştır. Bu çalışmanın da amacı, hem çevre sorunlarını çözebilme anlamında hem de insan ile doğa arasındaki bağı yeniden kurup daha sağlıklı, daha çevreci bireyler yetiştirmek kapsamında önemli, etkin bir çevre eğitimi yaklaşımı olan doğa eğitimini de içine alan yer/yöre temelli ve sınıfdışı çevre eğitiminin son 5 yıllık süreçteki ilerleyişini incelenmesine yönelik bir içerik analizi yapıp methodoloji, konu alanı, veri toplama, veri analizi vs. boyutlarına ilişkin yönelimleri belirlemektir. Çalışma sonucunda yer/yöre temelli ve sınıfdışı çevre eğitimi alanlarında scopus veri tabanında yapılan tarama ve eleme sonucu ulaşılan makaleler incelendiğinde en çok araştırmanın 19 ile ABD’ de yapıldığı; en çok çalışmanın ise 15 ile 2014 yılında üretildiği; 3 ile en çok Edinburgh üniversitesinde ve Environmental Education Research dergisinde yayın çıktığı görülmüştür. Anahtar kelimelerde en çok kullanılan ‘’çevre eğitimi’’ iken, ‘’sınıfdışı eğitim’’ onu takip etmektedir. Çalışmalarda genel olarak İngilizce yazım dili iken en çok sosyal bilimler alanında akabinde çevre bilimleri alanında çalışma yapıldığı; SPSS analiz programının, likert ölçek veri toplama aracının kullanıldığı tespit edilmiştir.
Anahtar Kelimeler: Çevre Eğitimi, yer/yöre temelli çevre eğitimi, sınıfdışı çevre eğitimi.
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Van Huysse, J. W., and S. L. Bealer. "Central nervous system norepinephrine release during hypotension and hyperosmolality in conscious rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 260, no. 6 (June 1, 1991): R1071—R1076. http://dx.doi.org/10.1152/ajpregu.1991.260.6.r1071.
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Extracellular norepinephrine (NE) levels in the paraventricular/anterior hypothalamic area (P/A) and in the dorsomedial medulla (DM) in conscious Sprague-Dawley rats were estimated by in vivo microdialysis before, during, and after sustained hypotension (75 mmHg mean arterial pressure) produced either by hemorrhage (Hem) or by 2-chloroadenosine infusion (2-Cl-ADO, 2.6-26.0 micrograms/min iv). P/A and DM NE were also measured before, during, and after hypertonic saline infusion (HTS; 1.5 M NaCl at 10 microliters.100 g-1.min-1 iv). P/A and DM NE increased during both Hem and 2-Cl-ADO and returned to baseline after reinfusion of hemorrhaged blood or after 2-Cl-ADO was stopped. However, Hem caused greater increases in P/A NE than 2-Cl-ADO despite equivalent decreases in blood pressure. Hem and 2-Cl-ADO produced equivalent changes in DM NE. HTS did not change P/A or DM NE despite increases in blood pressure of approximately 15 mmHg and plasma osmolality of approximately 30 mosmol/kgH2O. We conclude that 1) hypotension increases P/A and DM NE, which may mediate compensatory responses, 2) Hem is a more potent stimulus for NE release in the P/A than isovolemic hypotension induced by 2-Cl-ADO, and 3) the hypertensive response to HTS does not involve changes in P/A or DM NE.
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Vasi, İbrahim, Sevda Keleş Taşdüzen, Hava Üsküdar Teke, Eren Gündüz, Neslihan Andıç, and Olga Meltem Akay. "Hem İmatinib Hem de Nilotinib Tedavisi altında Gelişen Grade 3-4 Cilt Döküntüsü, Tirozin Kinaz İnhibitörü Başlamadan Öngörülebilir mi? Olgu sunumu." OSMANGAZİ JOURNAL OF MEDICINE 40, no. 1 (January 31, 2018): 71–74. http://dx.doi.org/10.20515/otd.347085.
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Mesut SIRRI and Cumali ÖZASLAN. "Siirt İlinde Sebze Alanlarında Görülen Yabancı Otlar." ISPEC Journal of Agricultural Sciences 4, no. 3 (September 16, 2020): 492–504. http://dx.doi.org/10.46291/ispecjasvol4iss3pp492-504.
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Sebzeler taze olarak da tüketildiğinden hem zehirli yabancı otlarla karışık olmaması hem de pestisit kalıntısı içermemesi gerekmektedir. Bu nedenle sebze alanlarında görülen yabancı otların belirlenmesi hem insan sağlığı hem de yabancı ot kontrolü yönüyle büyük önem taşımaktadır. Uygun iklim koşullarının da bir sonucu olarak Siirt ilinde sebze üretim alanları sürekli artmaktadır. Ancak yörede sebzede sorun olan yabancı otların saptanmasına yönelik olarak daha önce herhangi bir çalışma yapılmamıştır. Bu nedenle Siirt ilinde toplam 40 tarlada sürvey çalışmaları gerçekleştirilmiştir. Sürveylerde sebze ekim alanlarında sorun olan yabancı ot türleri ve bunların rastlanma sıklıkları ile yoğunluklarının belirlenmesi hedeflenmiştir. Araştırmayla çalışma alanında 20 familyaya ait 52 farklı yabancı ot türü tespit edilmiştir. Saptanan yabancı otlardan 3’ünün tam parazitik ve 11’inin dar yapraklı olduğu diğerlerinin ise geniş yapraklı oldukları saptanmıştır. Dar yapraklı yabancı otlardan en fazla rastlanan ve en fazla yoğunluk oluşturan türlerin; Sorghum halepense (%67,5), Echinocloa crus-galli (%22,50) ve Cynodon dactylon (%17,5) olduğu saptanmıştır. Bölgede en fazla görülen ve yoğunluk oluşturan geniş yapraklı yabancı otların ise; Portulaca oleracea (%92,0), Amaranthus retroflexus (%82,0), Chrozophora tinctoria (%82,0), Alhagi pseudalhagi (%77,0), Solanum nigrum (%72,0), Heliotropium europaeum (%70,0), Amaranthus albus (%67,0), Xanthium strumarium (%65,0) ve Convolvulus arvensis (%57,5) olduğu belirlenmiştir.
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Kadkhoda, Haleh, Clare Karten, Emily Van Laar, Elisa Weiss, Kevin C. Oeffinger, John Krauss, and Emily S. Tonorezos. "Shared Care For Hematologic Malignancy Survivors: Challenges Between Primary Care Physicians and Hematologist/Oncologists." Blood 122, no. 21 (November 15, 2013): 2958. http://dx.doi.org/10.1182/blood.v122.21.2958.2958.
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Abstract Background Many cancer patients are cured, or have a series of remissions interspersed with periods of re-treatment. In 2006, the Institute of Medicine's From Cancer Patient to Cancer Survivor: Lost in Transition recommended comprehensive treatment summaries and follow-up care plans for all cancer survivors. [Parry 2013] There were about 14 million cancer survivors in the US as of January 2012; this population is expected to be 18 million by 2022. [Siegel 2012] Among survivors, 64% have survived 5 years or more; 40% have survived 10 years or more; and 15% have survived 20 years or more after diagnosis. [de Moor 2013] Many survivors in this growing population experience physical, psychological, and/or financial long-term/ late effects. The complexities of managing cancer survivors suggest their care should not be conceived as a transition from the hematologist/oncologist to the primary care provider, but rather as an ongoing, flexible collaboration determined by individual survivor needs. Methods Polling surveys were conducted within the 2012 online education activity Sharing Care for Survivors of Hematologic Malignancies, developed by The Leukemia & Lymphoma Society and Medscape Oncology. Case-based education was delivered by an expert panel of hematologist/oncologists (Hem/Oncs) and primary care physicians (PCPs) to illustrate effective communication methods and critical communication points between (Hem/Oncs) and (PCPs). Results As of June 30, 116 Hem/Oncs and 171 PCPs overall responded to the polling surveys, which address current practices and barriers in shared care of cancer survivors. Responses were analyzed to identify gaps in continuity of care among specialties. A summary of responses shows the most significant barrier in effective management is the lack of survivorship care plans and treatment summaries (41% Hem/Oncs vs 51% PCPs). Only 8% and 5% of Hem/Oncs and PCPs, respectively, use survivorship care plans, although both Hem/Oncs and PCPs agreed that such plans and summaries are the most useful communication vehicle among professionals (73% Hem/Oncs vs 67% PCPs). PCPs used patient self-reported data more frequently to document cancer treatment, compared with Hem/Oncs (21% vs 7%, respectively); Hem/Oncs used caregiver reports more often than did PCPs (12% vs 3%, respectively). Similar numbers of Hem/Oncs and PCPs estimated that PCPs spend more than 4 hours of non-reimbursed time weekly researching issues related to patient care (47% Hem/Oncs vs 41% PCPs). Despite progress in electronic health records and widespread Internet access, these physicians most typically use the phone to communicate about the management of cancer survivors (64% Hem/Oncs vs 74% PCPs), followed by faxed/mailed letters, with email ranking as least used. Lack of prompt communication between Hem/Oncs and PCPs was the second highest barrier listed by respondents to effective management (22% and 27%, respectively). Conclusion Analysis of the Hem/Onc and PCP learner responses to the polling surveys point to clinical complexities and persistent challenges in the co-management of survivors of hematologic cancers. The challenges relate to communication, technological, healthcare system and healthcare coverage issues.Timely, ongoing communication of the right clinical information between Hem/Oncs and PCPs is essential for optimal management of the growing number of cancer survivors. Hem/Oncs and PCPs devote significant time each week to addressing the cancer survivors' needs; the lack of reimbursed time for PCPs may be an impediment to optimal care. Hem/Oncs and PCPs place a high value on the utility of survivorship care plans; however, they are not widely used. Phone calls are the current preferred communication mode. Until other technological solutions are more widely used to share clinical information, it is important to employ practical solutions, such as providing PCPs with information to help prioritize cancer survivors' follow-up care needs and providing patients/caregivers with brief cancer treatment summaries. Communication strategies to address potentially preventable causes of death, such as cardiac disease and second cancers, as well as acknowledgment and treatment for anxiety and depression related issues [Harrington 2010], which often accompany the uncertainty many cancer survivors live with, are critical. Disclosures: No relevant conflicts of interest to declare.
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Arxiu, Revista. "Introducció." Arxiu d'Etnografia de Catalunya, no. 4-5 (February 12, 2016): 13. http://dx.doi.org/10.17345/aec4-5.13-16.
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A les ratlles anteriors hem parlat d'una de les fites d'aquesta tasca bibliogràfica: l'obtenció i compilació de dades subministrades directament pels mateixos autors. Tanmateix, aquesta font d’informació primària va ésser complementada, des del començament, amb el buidat sistemàtic d'altres fonts de caràcter més general, que per comoditat expositiva hem dividit en una sèrie d'apartats: 1) Bibliografies generals; 2) Bibliografies sectorials; 3) Actes de Congressos, (distingint les actes de congressos estatals dels regionals o monogràfics); 4) Publicacions generades per seminaris, cicles de conferències i edició de readings, i 5) Revistes especialitzades.
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Pocoski, Jennifer, Brittny Rule, Augustina Ogbonnaya, Lois Lamerato, Michael Eaddy, Orsolya Lunacsek, and Thomas J. Humphries. "Cardiovascular Comorbidities in a United States Patient Population with Hemophilia a: A Comprehensive Chart Review." Blood 128, no. 22 (December 2, 2016): 4966. http://dx.doi.org/10.1182/blood.v128.22.4966.4966.
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Abstract Introduction: Two previous retrospective claims database analyses (Pocoski J, et al. Haemophilia. 2014;20(4):472-478 and Humphries TJ, et al. Am J Hematol. 2016;91(5):E298-299) reported increased prevalence and earlier onset of cardiovascular (CV) comorbidities in patients with vs without hemophilia A (HEM A). Because of many known limitations of claims databases, a comprehensive chart review at a large integrated delivery network was conducted to assess differential CV comorbidities. Aim: This study was designed to confirm the previous findings on CV risk factors and associated diseases in 2 large claims databases of male patients with HEM A in the United States. Methods: This was a retrospective chart review study conducted at the Henry Ford Health System in patients diagnosed with HEM A (n=74) and matched Control patients (3:1) without a diagnosis of HEM A (Control, n=222). Baseline demographics, bleeding events, treatment parameters, co-existing diseases, hemophilia-associated events, and the prevalence of 12 CV risk factors and associated diseases were compared between the HEM A and Control cohorts. P values generated from a chi-square test for categorical variables and a t test for continuous variables were reported. To address the small sample size, statistical differences between the cohorts were also assessed using absolute standardized difference (SDiff), where a value ≥0.10 was considered statistically meaningful. Results: The Control cohort was well matched to the HEM A group by age, race, healthcare payer, and study year. As expected, the prevalence of hepatitis B and C, hepatocellular carcinoma, and HIV/AIDS was much higher in the HEM A cohort. Gastrointestinal, intracranial, muscle, and joint bleeds occurred only in HEM A patients. Bleeds of various types were recorded in 35 HEM A patients vs 1 in the Control group. HEM A was severe in 52.7% of patients, moderate and mild in 10.8% each, and unknown in 25.7%. The prevalence of hypertension, diabetes, obesity, hyperlipidemia, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease was numerically higher in the Control cohort, but differences were statistically significant (P≤0.05) for diabetes and hyperlipidemia only. Statistical significance using SDiff was not reached for venous and arterial thrombosis and atrial fibrillation. Conclusions:The results of this retrospective chart review did not confirm diffuse statistically significant differences in CV comorbidities and their earlier onset in HEM A vs Controls. Reasons for the lack of confirmation are not clear but may include differences in methodology and patient populations among the studies. The Control group in this current study may have a greater medical burden than in the published studies. Our current results suggest numerically higher comorbidities in Controls for most variables. The conclusions of this study are limited by the small sample size of the hemophilia cohort and a potential selection bias associated with identification of the Control cohort. Disclosures Pocoski: Bayer: Employment. Rule:Bayer: Employment. Ogbonnaya:Takeda: Research Funding. Lamerato:Amgen, Inc.: Research Funding. Lunacsek:Bayer: Research Funding. Humphries:Bayer: Employment.
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Roukema, Riemer. "‘Mijn volk, wat heb ik u gedaan?’ Micha 6:3-4a in de Improperia voor Goede Vrijdag en bij de kerkvaders." NTT Journal for Theology and the Study of Religion 64, no. 3 (August 18, 2010): 200–217. http://dx.doi.org/10.5117/ntt2010.64.200.rouk.
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In de tekst van de Septuaginta staat in Micha 6:3-4a: ‘Mijn volk, wat heb ik u gedaan? Of waarmee heb ik u bedroefd, of waarmee heb ik u lastig gevallen? Antwoord mij! Want ik heb u uitgeleid uit het land Egypte.’ In de Byzantijnse, Mazarabische en Romeinse liturgieën van Goede Vrijdag worden deze of vergelijkbare woorden Christus in de mond gelegd als zijn verwijten (of Improperia) aan degenen die hem kruisigden, hoewel hij hen toch bevrijd had van de slavernij in Egypte. Dit artikel zoekt een antwoord op twee vragen: 1. uit welke tijd dateert de oudste tekst waaruit het gebruik van de tekst in de liturgie van Goede Vrijdag blijkt, en 2. hoe zijn deze woorden geïnterpreteerd in het vroege en middeleeuwse christendom? De tekst uit Micha komt voor in de zevende-eeuwse liturgie voor Goede Vrijdag uit Jeruzalem, maar werd in die setting waarschijnlijk ook al eerder gebruikt. Al in de late vierde eeuw citeerden kerkvaders de tekst als een uitspraak van de pre-existente Christus, maar er zijn nog geen liturgische teksten uit die tijd gevonden waarin hij voorkomt. Een excurs belicht een toenmalige joodse interpretatie van Micha 6:3-5.
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Pelosi, Elvira, Mauro Valtieri, Simona Coppola, Rosanna Botta, Marco Gabbianelli, Valentina Lulli, Giovanna Marziali, et al. "Identification of the hemangioblast in postnatal life." Blood 100, no. 9 (November 1, 2002): 3203–8. http://dx.doi.org/10.1182/blood-2002-05-1511.
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Abstract Postnatal CD34+ cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34+KDR+ cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoietic and endothelial cell growth, CD34+KDR+ cells generate large hemato-endothelial (Hem-End) colonies (5% of seeded cells), whereas CD34+KDR− cells do not. Limiting-dilution analysis indicates that Hem-End colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or Hem-End colonies, depending on the specific culture conditions. Identification of endothelial cells was based on the expression of VE-cadherin and endothelial markers and with lack of CD45 and hematopoietic molecules, as evaluated by immunofluorescence, immunocytochemistry, and reverse transcription–polymerase chain reaction. Furthermore, endothelial cells were functionally identified using low-density lipoprotein (LDL) uptake and tube-formation assays. In the second series, to evaluate the self-renewal capacity of hemangioblasts, single CD34+KDR+ cells were grown in 3-month extended long-term culture (ELTC) through 3 serial culture rounds—that is, blast cells generated in unicellular ELTC were reseeded for a subsequent round of unicellular ELTC. After 9 months, 10% blasts from tertiary ELTC functioned as hemangioblasts and generated macroscopic Hem-End colonies in clonogenic culture. These studies identified postnatal hemangioblasts in a CD34+KDR+ cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity. Although exceedingly rare, hemangioblasts may represent the lifetime source/reservoir for primitive hematopoietic and endothelial progenitors.
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Cai, Xiao Lan, and Xiao Fei Wang. "Research the Al Material Reinforced by CNT(Carbon Nanotubes)." Materials Science Forum 694 (July 2011): 337–40. http://dx.doi.org/10.4028/www.scientific.net/msf.694.337.
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This paper using high energy ball milling(HEM), researched the technology of preparation of Al compound material reinforced by CNT. Researched the different milling time, rotary speed, amount of CNT and sinter technology on properties of hardness and density. Preparation the Al-CNT at milling time about 30 to 100 min, rotational speed is about 300-600/rpm.the wt% of CNT is 0-5%, Analyzed the XRD patterns、SEM and STM micrograph, the results showed the Al material could be reinforced by CNT using HEM. the hardness of Al-CNT is 75 HB and the density is 2.65 g/cm3 when milling 90 min and CNT 3%.
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Bataller Torralba, Alex, Marina Diaz-Beyá, Ana Garrido, Susana Vives, Mar Tormo, Montserrat Arnan Sangerman, Olga Salamero, et al. "Favorable Outcome in Patients with Acute Myeloblastic Leukemia (AML) with NPM1 Mutation Who Present an Inadequate Clearance or Relapse of Minimal/Measurable Residual Disease (MRD): Results of a Preemptive Intervention Policy (CETLAM-2012 Protocol)." Blood 132, Supplement 1 (November 29, 2018): 1385. http://dx.doi.org/10.1182/blood-2018-99-110895.
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Abstract Introduction Patients diagnosed with AML with NPM1mutation (NPM1mut AML) included in the European LeukemiaNet favorable genetic risk category (ELNfav, i.e., without FLT3-ITD or with a low allelic burden FLT3-ITD comutation [FLT3-ITD/FLT3wt <0.5; FLT3-ITDLOW]) do not benefit from an allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1). However, a significant proportion of these patients fail to frontline chemotherapy and require salvage therapy. Persistence or detection of MRD after post-CR treatment is associated with a high relapse risk and worse prognosis. With this background, the cooperative group CETLAM proposed an early therapeutic intervention in CETLAM-2012 protocol for patients with ELNfavNPM1mut AML patients not achieving a sustained MRD clearance after consolidation therapy, defined as molecular failure (MF). Herein we analyzed the outcome and predictive risk factors of MF. Methods All patients diagnosed with ELNfav NPM1mut AML treated according to CETLAM-12 protocol who achieved CR after 1 or 2 courses of induction chemotherapy were included in the study. Intended post-CR therapy consisted of 3 courses of high-dose cytarabine chemotherapy (HDAC). MRD was assessed in bone marrow samples after each chemotherapy course and thereafter, at regular 3-month interval during 3 years, in reference labs from CETLAM group following standard NPM1-mutation specific RQ-PCR. MF was defined as failure to achieve a molecular response (molCR) after consolidation therapy (i.e., NPM1mut/ABL·100 ratio > 0.05) or MRD reappearance after molCR. All MFs were confirmed in a second sample collected at least 4 weeks apart from previous sample. For patients who present a MF, alloSCT was recommended, without a predefined indication of debulking previous salvage chemotherapy. Results Out of 145 patients with ELNfav NPM1mut AML (75 M/70 F; median age, 56, 18-74), 132 (91%) achieved CR after 1 (n=124) or 2 courses (n=8). After a median follow-up of 25 months, 2-year overall survival (OS), event-free survival (EFS), leukemia-free survival (LFS) of the entire cohort were 79.9% (±3.6), 71.8% (±4) and 79.4% (±3.8), respectively. Among patients with available complete MRD information (n=89), 33 patients developed an hematological and/or molecular failure (Mol/Hem failure), resulting into a Mol/Hem failure-free survival at 2 years of 62% (±5.6%); median time from CR to Mol/Hem failures was 8.2 months (2-43). Fourteen patients presented with an overt hematological relapse (hREL), preceded by a detectable MF in 8. Overall, 14 received salvage therapy in morphological CR, MRD(+) status (MF), and 14 For hREL. Among MF, 5 patients received HDAC-type salvage treatment (followed by alloSCT in 3) and 9 proceeded directly to alloSCT. In 5 additional MF patients with MRD persistence after consolidation, subsequent MRD monitoring showed decreasing MRD levels until complete clearance (n=4) or intermitent detection (n=1) and have not received further therapy. After salvage therapy, 12/14 (86%) patients with MF achieved molCR, and 10/14 (71%) treated for hREL achieved CR2 (MRD negative in 7, 50%), followed by alloSCT in 9. OS after Mol/Hem failure was 64.8% (± 8.4) at 2 years, 88.8 (±7.5%) in patients treated for MRD(+)-status (MF) and 32.1% (±13.6%) in patients treated with overt hREL (p<0.001; figure 1). Potential predictive factors of Mol/Hem failure were investigated. Interestingly, a ratio of NPM1mut/ABL*100 ≥1 after induction allowed distinction of two patient subpopulation with strikingly different Mol/Hem failure risk: Mol/Hem failure-free survival at 2 years of 84±6% vs. 33±10% in patients with a lower (<1) and higher (³1) tumor burden (p<0.001; figure 2). Remarkably, concurrence of FLT3-ITDLOWdid not correlate with outcome or Mol/Hem failure risk. Conclusion Despite a significant proportion of Mol/Hem failures, NPM1mut AML patients allocated in the ELN favorable risk group presented a favorable overall outcome. NPM1mut-based MRD surveillance is able to anticipate most hematological relapses, and a MRD-driven early intervention policy, at time of MF, allowed a successful rescue of a significant proportion of patients. Moreover, an early measure of residual tumor burden, after induction therapy, might identify those patients with a high risk of molecular or hematological subsequent failure, allowing the potential implementation of preemptive intensification strategies. Disclosures No relevant conflicts of interest to declare.
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Balsat, Marie, Vincent Alcazer, Gabriel Etienne, Gaelle Fossard, Francoise Huguet, Marc G. Berger, Emilie Cayssials, et al. "First-Line Second Generation Tyrosine Kinase Inhibitors in Newly Diagnosed Accelerated Phase Chronic Myeloid Leukemia Patients." Blood 132, Supplement 1 (November 29, 2018): 48. http://dx.doi.org/10.1182/blood-2018-99-113058.
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Abstract Introduction Up to 10% of patients (pts) with chronic myeloid leukemia (CML) are already in accelerated phase (AP) at diagnosis and despite treatment advances in the field of tyrosine kinase inhibitors (TKIs), management of these pts is challenging. This study aims to examine the benefit of second generation BCR-ABL tyrosine kinase inhibitors (TKI2) as first-line treatment for newly diagnosed AP-CML. Methods Pts meeting criteria for AP-CML at diagnosis and treated with first-line TKI2 (i. e. Nilotinib or Dasatinib) were included in this retrospective multicenter observational national study. AP-CML were defined according to the ELN (Baccarani, Blood 2013) as hematological acceleration (HEM-AP, any of the following features: blasts in PB or marrow 15-29%, or blasts+promyelocytes in PB or marrow >30% with blasts <30%, basophils in PB ≥20%, or persistent thrombocytopenia <100×109/L (unrelated to therapy) and/or chromosomal abnormalities in addition to the Ph at diagnosis (ACA-AP). Pts initiated nilotinib at 6-800 mg BID or dasatinib at 100-140 mg QD with further dose adaptations according to toxicities or response. Overall survival (OS), progression-free survival (PFS) and failure-free survival [FFS= progression to blast crisis, death, loss of any previous response (CHR, CCyR, or MMR) discontinuation of TKI2 for toxicity], were analysed since TKI2 initiation in intention-to-treat. Results Sixty-six pts were analysed: 45 males (68%) and 21 females (32%) with a median age at diagnosis of 49 (15-78.5) years. The median follow-up of the cohort was 43.5 (1.7-117) months. We segregated the pts in HEM-AP (n=33) and ACA-AP (n=33) for further analyses. Nine pts with HEM-AP harboured ACA and were analysed in the HEM-AP group. Fusion transcripts were of the Major BCR in 57 pts, 6 pts had atypical BCR-ABL transcripts (2 e19a2, and 1 e1a2 in the HEM-AP group and 2 e19a2 and 1 Ma3 in the ACA-AP group), and 3 transcripts unknown. Not surprisingly, spleen enlargement was significantly greater in the HEM-AP group [10 (5-14.75) vs. 3 (0-10)cm, p=0.014]. PB basophils [median 10 (6-16) vs. 3 (2-5)%, p <0.001], PB blasts [median: 12.05 (7.5-15) vs. 1.5 (0-4)%, p<.001], as well as PB blasts+promyelocytes [median 14 (11-20) vs. 4 (1-7)%, p<.001]. Hemoglobin levels were significantly lower in the HEM-AP group [median 93 (6-113.5) vs 120 (100-134) g/L, p<0.001]. Neither WBC counts, platelets counts, nor BCR-ABL/ABL load differed significantly between the 2 groups. In the ACA-AP group, 10 (30%) pts harbored major route ACA and 23 (70%) pts harbored minor route ACA of whom 3 pts with i(17q) and 1 with 7q abnormalities. In the ACA-AP group, Sokal score was low in 42%, intermediate in 32% and high in 26% of pts (2 pts unknown). Dasatinib was initiated in 19/33 pts (57.5%) in the HEM-AP group and in 8/33 pts (24%) in the ACA-AP group. Treatment responses did not significantly differ between ACA-AP and HEM-AP group, regardless of the TKI2 administered, with 33/33 (100%) vs 31/33 (94%) pts achieving a CHR, 2/33 (6%) pts vs 0/33 (0%) pts achieving a MCyR, 5/33 (15%) pts vs 5/33 (15%) pts achieving CCyR, 9/33 (27%) pts vs 4/33 (12%) pts achieving a MMR respectively. However, 11/33 (33%) HEM-AP vs 22/33 (66%) ACA-AP pts achieved a deep molecular response (p=0.013, Fisher test). Median times to CHR and MMR were not significantly different between ACA-AP group and HEM-AP group with 1.05 vs 1.25 months (p=0.088) for CHR and 6 vs 7 months (p=0.156) for MMR, respectively. Overall, the estimated 7-yr FFS rate was 56.92% (95%CI: 40-81), 7-yr PFS was 83.42% (95% CI: 69.6-100%) and 7-yr OS was 87.14% (95%CI: 73.5-100%) (Figure 1.) with no significant differences between ACA-AP vs HEM-AP pts [7-yr FFS: 57.7 vs. 62%, p=0.739; 7-yr PFS: 84.7% vs. 84%, p=0.185; 7-yr OS: 88.9% vs 86.6%, p=0.132] respectively. There was also no difference in FFS, PFS and OS according to the type of TKI2. The only factors influencing negatively OS were the % of BM blasts (HR=1.17, 95%CI: 1.1-1.28, p<0.001) and the % of BM blasts+promyelocytes (HR=1.14, 95%CI: 1.06-1.22, p<0.001). We identified too few significant factors in univariate analysis to perform a multivariate analysis. Conclusion The initiation of a TKI2 in newly diagnosed AP-CML pts induces excellent response and survival rates, probably superior to that of Imatinib first-line, and counterbalances the negative impact of this advanced disease, particularly in HEM AP subgroup. Disclosures Etienne: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Patents & Royalties, Speakers Bureau. Berger:Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mahon:Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Speakers Bureau; BMS: Speakers Bureau. Rea:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Pfizer: Honoraria. Nicolini:BMS: Consultancy, Speakers Bureau; Incyte Biosciences: Consultancy, Speakers Bureau; Sun Pharma Ltd: Consultancy.
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Tortella, Bartholomew J., Amit Chhabra, José Alvir, Emily R. Rubinstein, Lisa J. Young, and Patrick F. Fogarty. "Analysis of US Claims Real World Data of Hemophilia a & B Patients: Units Dispensed & Expenditures Associated with Utilization of and Switching from Standard to Extended Half-Life Factor Products." Blood 132, Supplement 1 (November 29, 2018): 3508. http://dx.doi.org/10.1182/blood-2018-99-119133.
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Abstract Background: Both standard half-life (SHL) and extended half-life (EHL) factor replacement products are used to treat patients with hemophilia A (hem-A) and B (hem-B). A comparison of international unit (IU) utilization and expenditures ($USD) was made between patients on SHL and EHL factor replacement products to compare utilization and to determine the impact of switching from an SHL to an EHL product. Methods: De-identified claims data from both the Truven Health MarketScan® Research (Truven) and Optum® Clinformatics® (Optum) US claims databases included male patients with hem-A (Truven from Aug 2014-Apr 2018 and Optum from Aug 2014-Dec 2017) and hem-B (Truven from Jun 2014-Apr 2018 and Optum from Jul 2014-Dec 2017) who had data for at least 3 months of product dispensation. The SHL and EHL groups were compared. A separate "switch" analysis using the Truven database examined expenditures and IUs before and after switching from nonacog-α (SHL) to FIX-Fc (EHL). Descriptive statistics were used and medians reported for expenditures and IUs to accommodate for the skewness of data distribution. Results: Hem-A: The analysis included 896 SHL and 202 EHL patients, including those who switched from an SHL to an EHL product. Quarterly expenditures and IUs dispensed were analyzed. Both the Optum and Truven databases (see Table) demonstrated higher IU dispensation (Optum: 35%, Truven: 50% higher) and expenditures (Optum: 87%, Truven: 117%) associated with EHL products versus SHL products. In the switch analysis, 35 patients switched from nonacog-α to FIX-Fc; median IUs rose from 61,228 to 75,914 [24%] and median expenditures rose from $78,945 to $155,203 [97%]. Hem-B: The analysis included 50 FIX-Fc, 13 FIX-Alb, and 132 nonacog-α patients. Both databases (see Table) demonstrated higher median expenditures for the EHL products compared with nonacog-α (Optum: 179% for FIX-Fc, 189% for FIX-Alb; Truven: 234% for FIX-Fc, 245% for FIX-Alb). The IU results varied in Optum: FIX-Fc was 23% higher than nonacog-α, but FIX-Alb was 9 % lower than nonacog-α. Similarly, in Truven, the IU results varied: IUs were mixed for the SHL product compared with the EHL products: 62% higher for FIX-Fc than nonacog-α, and approximately the same for FIX-Alb and nonacog-α. In the switch analysis, 16 patients switched from nonacog-α to FIX-Fc; median IUs rose from 62,857 (nonacog-α) to 69,816 (FIX-Fc) [11%], while expenditures rose from $75,064 (nonacog-a) to $210,482 (FIX-Fc) [180%]. Conclusions: This analysis in more than 1000 patients, unadjusted for severity of disease or treatment scheme, demonstrated in hem-A that higher IU utilization and expenditures were associated with EHL use compared with SHL use, and in hem-B, that higher expenditures were seen with EHL products, while IU dispensation in some cases decreased, remained the same, or increased. In patients switching from the SHL to an EHL product, higher IU dispensation and expenditures were seen. These real-world data may challenge assumptions regarding typical factor usage and expenditures associated with EHL products in patients with hem-A and hem-B. Additional analyses with adjustment for treatment scheme and disease severity are needed. Table. Table. Disclosures Tortella: Pfizer Inc.: Employment. Chhabra:Pfizer Inc.: Employment. Alvir:Pfizer Inc.: Employment. Rubinstein:Pfizer Inc.: Employment. Young:Pfizer Ltd.: Employment. Fogarty:Pfizer Inc.: Employment.
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Federici, Augusto B., Mariagrazia Rumi, Elena Santagostino, Antonio Russo, Massimo Colombo, and Pier M. Mannucci. "The Impact of the First Exposure to Different Blood Products on the Prevalence and Natural History of Hepatitis C Virus Infection in Von Willebrand Disease (VWD): Results from a Large Cohort Study Comparing VWD and Hemophilia Patients." Blood 104, no. 11 (November 16, 2004): 4108. http://dx.doi.org/10.1182/blood.v104.11.4108.4108.
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Abstract Background: Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with inherited bleeding disorders who received clotting factors concentrates before the introduction of viral inactivation procedures in the mid 1980s. Severity of hepatitis C has been largely associated to male gender, long duration of infection, high prevalence of genotype 1, high levels of viremia and multiple inocula with HCV. Compared to hemophiliacs (HEM), patients with von Willebrand disease (VWD) have been less extensively exposed to large-pool concentrates because they usually have a less severe bleeding diathesis and bleedings could be often controlled in the past by desmopressin (DDAVP) or cryoprecipitates prepared by national blood banks. Aims and Study design: To assess the prevalence and natural history of HCV infection in VWD, 358 patients (VWD types 1=41%; 2=53%;3=6%) regularly followed up at the Angelo Bianchi Bonomi Hemophilia Thrombosis Center of Milan have been surveyed since 1998 in this six-year cohort study. Blood borne viral markers have been controlled yearly in all transfused patients and liver function tests have been monitored in all HCV infected cases at least every six months. To explore the impact of different blood products on HCV infection, the 358 VWD were also compared with 397 HEM (mild =27%, moderate = 9%, severe = 64%) similarly followed up at the same Center, taking into account the type of blood components or FVIII concentrates to which individual patients of both populations were first exposed. Methods: The comparison between VWD and HEM data were performed by univariate analysis (t-test). Multivariate unconditional logistic regression was used to analyze the association between HCV genotypes and VWD/HEM status: maximum likelihood estimates of odds ratios and 95% confidence intervals were also calculated. Results: Data obtained in VWD/HEM are as follows: A) Blood transfusions: 1) transfused patients= 39/95%; 2) First exposures to: whole blood or plasma=58/9%; cryoprecipitate=22/4%; large-pool FVIII concentrates=20/87%. B) Blood borne infections: 1) anti-HIV=1.4/23%; 2) anti-HCV=43/96%; 3) HCV-RNA negative=19/20%; 4) HCV genotype distribution: 1a=17/38%; 1b=32/30%; 2=26/16%; 3=21/14%; 4=4/2%. Even though genotype distribution was clearly different in VWD, only the risk to be infected by HCV type 1a was significantly reduced (OR=0.36; 95% CI 0.15–0.84). However, no difference was found in the exposure to large-pool concentrates between VWD and HEM with HCV type 1a infection (57 versus 67%, p-value=0.3). C) Natural history of HCV infection: 1) Male gender=41/99%; 2) Median age at infection=24/7 years with ranges = 10-69/5-68; 3) Serum ALT activity persistently or intermittently high= 67/79% (p-value=0.06) in cases with positive HCV-RNA; 4) Cirrhosis and HCC= 4/9% (p-value=0.4) of patients, respectively. Conclusions: VWD Italian patients showed a sporadic risk of infection with HIV and a lower prevalence of HCV. HCV genotypes distribution seems to reflect the source of blood products and can influence the natural history of HCV in VWD, as shown by the relatively lower incidence of liver abnormalities.
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Zaborovskii, Nikita, Dmitrii Ptashnikov, Dmitrii Mikaylov, Sergei Masevnin, and Oleg Smekalenkov. "RENAL CELL CARCINOMA METASTASIS OF THE SPINE: BLEEDING CONTROL METHODS." Coluna/Columna 17, no. 3 (July 2018): 233–36. http://dx.doi.org/10.1590/s1808-185120181703193262.
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ABSTRACT Objective: This report compares various methods of bleeding control, and their influence on outcome and survival after decompression procedures for spinal metastasis of renal cell carcinoma (MRCC). Methods: A retrospective study. All patients underwent palliative decompression procedures. We compared 3 groups of patients stratified by methods of bleeding control. The first group (EMB) included 22 patients who underwent preoperative embolization of a tumor. The second group (HEM) consisted of 20 patients, treated surgically using intraoperative local hemostatic agents. In the third group (COMBI) 15 patients were treated with a combination of methods. Results: The average intraoperative blood loss for the EMB group was slightly less than the average for the HEM and COMBI groups, but without significant differences. The postoperative drainage loss in the HEM and COMBI groups was significantly less than in EMB group. The complication rate (infections, hematomas, neurological deficit) was practically equal in all groups. No statistically significant differences in local tumor recurrence and overall survival were found between groups. Conclusions: The overall results did not show that usage of different bleeding control methods can affect early or long-term outcomes. Level of Evidence III; retrospective study.
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BİLGİNOĞLU, Elif, and Uğur YOZGAT. "ULTRA-KISA İŞE ANGAJE OLMA ÖLÇEĞİ TÜRKÇE FORMUNUN GEÇERLİLİK VE GÜVENİLİRLİK ÇALIŞMASI." Business & Management Studies: An International Journal 7, no. 5 (December 25, 2019): 2863–72. http://dx.doi.org/10.15295/bmij.v7i5.1354.
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İşe angaje olma, son yıllarda önemli bir konu haline gelmiş ve bu yüzden de hem iş bağlamında hem de akademik çalışmalarda üzerinde durulmuş bir kavram olmuştur. Günümüz iş dünyasında çalışanları işe angaje etmek en büyük rekabetçi ayırt edici unsurlardan biri haline gelmiştir ve bir örgütün başarısında hayati önem taşıyor olarak görülmektedir. Ancak yapılan araştırmalar çalışanların işlerine angaje olmadıklarını ve onları işlerine tamamen angaje hale getirmenin yöneticilerin karşı karşıya kaldıkları en büyük zorluklardan biri olduğunu ortaya koymaktadır. Utrecht İşe Angaje Olma Ölçeği’nin Türkçe formunun geçerlilik ve güvenilirlik çalışması farklı araştırmacılarca test edilmiş olmakla birlikte, ölçeğin 3 soruluk ultra-kısa versiyonunun Türkçe geçerlilik ve güvenilirlik çalışmasını yapan bir çalışmaya rastlanmamıştır. Bu çalışma belirtilen boşlukların doldurulabilmesi amacıyla Ultra-Kısa İşe Angaje Olma Ölçeği’nin Türkçe formunun geçerlilik ve güvenilirlik çalışmasını içermektedir.
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Willis, Lauren, Tristin Abair, Pan Chen, and Jason Westin. "Innovative, Consequence-Based Educational Intervention Improves Hematologists/Oncologists Skills Using CAR T-Cell Therapies for R/R Diffuse Large B-Cell Lymphoma." Blood 136, Supplement 1 (November 5, 2020): 11–12. http://dx.doi.org/10.1182/blood-2020-136205.
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Background: Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) and these novel therapies have unique administration considerations and toxicity profiles. Underlying clinical practice gaps and educational needs were identified and a study was conducted to determine if an online educational intervention specifically designed to address the identified practice gaps could improve knowledge and competence of hematologists/oncologists (hem/oncs) with respect to evidence-based use of CAR T-cell therapies in patients with R/R DLBCL and management of CAR T-cell toxicities. Methods: A cohort of hem/oncs participated in an innovative educational intervention that used a problem-based learning model and short-branching technology. Clinical decision questions were included at 3 critical points in each of the 2 case vignettes, with tailored feedback and clinical consequences provided based on the specific decision made. Learners who did not make the correct decision on the first attempt were given a second opportunity to change the decision that was made. Each case also included knowledge assessment questions pre- and post-intervention and self-efficacy assessment (Figure 1). The educational activity was launched on December 16, 2019 and data collected through April 8, 2020 were analyzed and reported. McNemar's tests were used to assess changes in percent correct responses to individual questions between the 1st and 2nd attempt to determine the effectiveness of the clinical feedback provided following an incorrect answer on the 1st attempt. P value <.05 indicates statistical significance. Results: A total of 860 learners participated in the activity, including 106 hem/oncs, during the data collection period and 38 hem/oncs who answered one or more of the assessment questions were included in the analysis. Case 1: After education, 68% of hem/oncs demonstrated knowledge that CAR T-cell therapies are given as a single infusion (relative 36% increase, P <.05). Between 38% and 71% of hem/oncs made the clinical decisions correctly on the first attempt. After consequence-based feedback (CBF), between 55% to 88% of hem/oncs who failed the first attempt made the right decisions during the 2nd attempt. After CBF, hem/onc improvements in specific clinical decisions were as follows: 80% improved competence determining when a patient with R/R DLBCL needed to switch to a new therapy (P < .01); 85% improved competence selecting CAR T-cell therapy as an appropriate next therapy for the patient (P < .001); 55% improved competence counseling the patient about the need to start the CAR T-cell therapy as soon as possible, due to the risk for disease progression or death (P < .001). Case 2: After education, 63% of hem/oncs demonstrated knowledge of patient eligibility criteria for CAR T-cell therapy (relative 13% increase, P = .480) and 73% demonstrated knowledge that hypogammaglobulinemia is a possible delayed toxicity of CAR T-cell therapy (relative 46% increase, P < .05). Between 30% and 77% of hem/oncs made the right clinical decisions on the first attempt. After CBF, between 43% to 76% of hem/oncs who failed the first attempt made the right decisions during the 2nd attempt. After CBF, hem/onc improvements in specific clinical decisions were as follows: 64% improved competence diagnosing delayed cytopenia after CAR T-cell therapy (P < .01); 76% improved competence treating delayed cytopenia after CAR T-cell therapy (P < .001); 43% improved competence treating hypogammaglobulinemia after CAR T-cell therapy (P = .083). Conclusion: This innovative, case-based CME-certified activity using branching logic with tailored CBF improved clinical decision making with regards to use of CAR T-cell therapies for R/R DLBCL. The results indicate that such unique educational methodologies and platforms, which are available on-demand, can be effective tools for advancing clinical decision making, which would then translate into improved clinical decision making and better patient outcomes. Acknowledgements: This CME activity was supported by an independent educational grant from Celgene Corporation and Kite, A Gilead Company. Reference: https://www.medscape.org/viewarticle/922133 Disclosures Westin: Curis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Amgen: Consultancy; Kite: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; 47: Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding.
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Rabenstein, L., T. Krumpen, S. Hendricks, C. Koeberle, C. Haas, and J. A. Hoelemann. "A combined approach of remote sensing and airborne electromagnetics to determine the volume of polynya sea ice in the Laptev Sea." Cryosphere 7, no. 3 (June 19, 2013): 947–59. http://dx.doi.org/10.5194/tc-7-947-2013.
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Abstract. A combined interpretation of synthetic aperture radar (SAR) satellite images and helicopter electromagnetic (HEM) sea-ice thickness data has provided an estimate of sea-ice volume formed in Laptev Sea polynyas during the winter of 2007/08. The evolution of the surveyed sea-ice areas, which were formed between late December 2007 and middle April 2008, was tracked using a series of SAR images with a sampling interval of 2–3 days. Approximately 160 km of HEM data recorded in April 2008 provided sea-ice thicknesses along profiles that transected sea ice varying in age from 1 to 116 days. For the volume estimates, thickness information along the HEM profiles was extrapolated to zones of the same age. The error of areal mean thickness information was estimated to be between 0.2 m for younger ice and up to 1.55 m for older ice, with the primary error source being the spatially limited HEM coverage. Our results have demonstrated that the modal thicknesses and mean thicknesses of level ice correlated with the sea-ice age, but that varying dynamic and thermodynamic sea-ice growth conditions resulted in a rather heterogeneous sea-ice thickness distribution on scales of tens of kilometers. Taking all uncertainties into account, total sea-ice area and volume produced within the entire surveyed area were 52 650 km2 and 93.6 ± 26.6 km3. The surveyed polynya contributed 2.0 ± 0.5% of the sea-ice produced throughout the Arctic during the 2007/08 winter. The SAR-HEM volume estimate compares well with the 112 km3 ice production calculated with a~high-resolution ocean sea-ice model. Measured modal and mean-level ice thicknesses correlate with calculated freezing-degree-day thicknesses with a factor of 0.87–0.89, which was too low to justify the assumption of homogeneous thermodynamic growth conditions in the area, or indicates a strong dynamic thickening of level ice by rafting of even thicker ice.
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Rabenstein, L., T. Krumpen, S. Hendricks, C. Koeberle, C. Haas, and J. A. Hoelemann. "A combined approach of remote sensing and airborne electromagnetics to determine the volume of polynya sea ice in the Laptev Sea." Cryosphere Discussions 7, no. 1 (February 1, 2013): 441–73. http://dx.doi.org/10.5194/tcd-7-441-2013.
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Abstract. A combined interpretation of synthetic aperture radar (SAR) satellite images and helicopter electromagnetic (HEM) sea-ice thickness data has provided an estimate of sea-ice volume formed in Laptev Sea polynyas during the winter of 2007/08. The evolution of the surveyed sea-ice areas, which were formed between late December 2007 and middle April 2008, was tracked using a series of SAR images with a sampling interval of 2–3 days. Approximately 160 km of HEM data recorded in April 2008 provided sea-ice thicknesses along profiles that transected sea-ice varying in age from 1–116 days. For the volume estimates, thickness information along the HEM profiles was extrapolated to zones of the same age. The error of areal mean thickness information was estimated to be between 0.2 m for younger ice and up to 1.55 m for older ice, with the primary error source being the spatially limited HEM coverage. Our results have demonstrated that the modal thicknesses and mean thicknesses of level ice correlated with the sea-ice age, but that varying dynamic and thermodynamic sea-ice growth conditions resulted in a rather heterogeneous sea-ice thickness distribution on scales of tens of kilometers. Taking all uncertainties into account, total sea-ice area and volume produced within the entire surveyed area were 52 650 km2 and 93.6 ± 26.6 km3. The surveyed polynya contributed 2.0 ± 0.5% of the sea-ice produced throughout the Arctic during the 2007/08 winter. The SAR-HEM volume estimate compares well with the 112 km3 ice production calculated with a high resolution ocean sea-ice model. Measured modal and mean-level ice thicknesses correlate with calculated freezing-degree-day thicknesses with a factor of 0.87–0.89, which was too low to justify the assumption of homogeneous thermodynamic growth conditions in the area, or indicates a strong dynamic thickening of level ice by rafting of even thicker ice.
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Sharathkumar, Anjali, Mehul Patel, Ronald Thomas, Yaddanapudi Ravindranath, and Jeffrey W. Taub. "Outcome of Children with Hyperdiploid Acute Lymphoblastic Leukemia- an Apparent Predisposition for Extramedullary Relapse and High Salvage Rate. A Single Institution Experience." Blood 104, no. 11 (November 16, 2004): 1956. http://dx.doi.org/10.1182/blood.v104.11.1956.1956.
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Abstract Background: In pediatric B-precursor acute lymphoblastic leukemia (ALL), hyperdiploidy (51 to 65 chromosomes and/or DNA index > 1.16) comprises approximately 25% of cases and is associated with a favorable prognosis. Aim: To evaluate the clinical and relapse characteristics of children with hyperdiploid (HY) ALL treated at Children’s Hospital of Michigan from 1991 to 2002. Methodology: Children were treated per several successive Pediatric Oncology Group ALL studies. Data was obtained by retrospective chart review. Study end-points were "relapse" or "death" whichever came first. Univariate and multivariate analysis was performed to study the association of various clinical and biological factors on outcome. Survival curves were drawn using Log-rank test. Results: 139 children diagnosed with ALL were included in the study: 31 (22%) HY-ALL; 108 (88%) non-HY-ALL (Table). In HY-ALL, 11(35%) relapsed: 3 (27%) isolated hematopoietic (HEM); 8 (73%) extra-medullary (EM) [TESTES: 4; TESTIS+HEM: 1; CNS+HEM: 3]. Two (18%) relapsed while on treatment. Non-HY-ALL relapses occurred in 25 (23%): HEM 16 (64%); EM 9 (46%) [TESTIS: 1; TESTIS+HEM: 1; CNS: 6; CNS+HEM: 1]. Thus, HY-ALL children were predisposed to EM involvement at relapse compared to non-HY-ALL (p<0.02; OR 3.82; 95%CI 1.37 to 10.7). Twenty percent (4/20) of boys with HY-ALL experienced testicular relapse as opposed to 3% (2/58) in non-HY-ALL (p 0.06; OR 7.0; 95% CI 1.35 to 35.65). For the HY-ALL group, age >10 years and Caucasian race were associated with poor EFS (p<0.03). Within the HY-ALL group, there was no significant difference in cumulative methotrexate and 6-mercaptopurine doses between patients who relapsed and patients who remained in remission. Respective 10 year event-free survival for the HY-ALL and non-HY-ALL cohort was 52.9± 10.6% and 70.6±4.8% (p 0.12) and overall survival (OS) for HY-ALL and non-HY-ALL groups was 92±5.6 and 74±4.7, (p 0.14). Relapse related mortality was 18% (2/11) for HY-ALL and 80% (20/25) for non-HY-ALL (p 0.002; OR 0.06; 95% CI 0.01 to 0.32). Conclusion: Relapses in HY-ALL predominantly involved EM sites. Despite relapses, HY-ALL cases remained sensitive to salvage therapy with a high OS. This suggests that the basis of relapse may differ between HY-ALL and non-HY-ALL cases and the relationship of drug resistance with relapse. Older children (>10 yr) with HY-ALL may require more intensive treatment and monitoring of sanctuary sites to prevent treatment failures. Figure Figure Patient Characterisitcs at Diagnosis Patient characterisitcs Hyperdiploid ALL (n=31) Non-Hyperdiploid ALL (n=108) CAUC: Caucasian; AA: African American; O: Other Median age (yrs) 3.9 (1.3–16.0) 5.8 (3.0–17.0) Race: CAUC/AA/O 21(69%)/ 6(19%)/ 4(12%) 66(61%)/ 28(26%)/ 14(12%) Age>10 yr 5 (16%) 13 (12%) Male:Female 20 (65%):11(35%) 58 (54%):50(46%) Median follow up (yrs) 5.9 ± 4.0 5.3 ±3.4 Events 11 (35%) 30 (28%)
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TANYAŞ, Hilal, and Mine MISIRLISOY. "Kaynak Belleği: Derleme Çalışması." Ankara Üniversitesi Dil ve Tarih-Coğrafya Fakültesi Dergisi 58, no. 2 (December 28, 2018): 1436. http://dx.doi.org/10.33171/dtcfjournal.2018.58.2.13.
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Bellek kayıtları bir anıyı kimden, nasıl, nerede ve ne zaman edindiğimiz gibi çok çeşitli bilgi içerir. Kaynak izleme, edindiğimiz bu bellek kayıtlarının kökenlerine atfedildiği bir bilişsel süreçtir. Bu izleme mekanizması sayesinde, spesifik bir anı belleğimizde var olan diğer anılardan ayırt edilebilir. Bireylerin hangi durumlarda kaynak belleği hatalarına daha yatkın, hangi durumlarda ise daha dayanıklı olduğunu incelemek, bilginin kökeninin izlendiği bu mekanizmayı anlamamıza yardımcı olacaktır. Kaynak izleme teorisine göre bellek yanılmaları bu izleme mekanizmasındaki bir hata sonucu oluşur (Johnson, Hashtroudi ve Lindsay 3; Lindsay 325). Dolayısıyla, kaynak belleği çalışmaları hem teorik hem pratik açıdan çok büyük önem taşımaktadır. Derlemenin giriş bölümünde kaynak belleği alanyazını detaylı incelenmiş ve kaynak izleme sürecini etkileyen faktörlerden bahsedilmiştir. Derlemenin ikinci bölümünde bilginin kendisi ve kaynağı arasındaki ilişki, üçüncü bölümünde ise kaynak belleği çalışmalarında kullanılan yöntemler ele alınmıştır.
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Sengpiel, Klaus-Peter, and Bernhard Siemon. "Examples of 1-D inversion of multifrequency HEM data from 3-D resistivity distributions." Exploration Geophysics 29, no. 1-2 (March 1998): 133–41. http://dx.doi.org/10.1071/eg998133.
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Birgen, Nur, Mustafa Okudan, Mesut Okyay, and Mehmet Akif İnanıcı. "İş Kazasına Bağlı Olgularda Maluliyet Oranı Hesaplanması Adli Tıp Açısından Değerlendirilmesi." Bulletin of Legal Medicine 4, no. 3 (December 1, 1999): 101–8. http://dx.doi.org/10.17986/blm.199943374.
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Yıllar boyunca maluliyet oranının hesaplanması ve adli tıp açısından değerlendirilmesi konusunda birçok sorunla karşılaşılmıştır. Bu sorunlar vücuttaki arızaların eksik ya da yanlış saptanmasından kaynaklanmaktadır, Adli tıp uzmanlarının hem davacı hem de davalı için adil olacak şekilde maluliyet oranı hesaplamaları gerekmektedir. Bu çalışmanın amacı, maluliyet hesabı gereken iş kazasına bağlı olguların epidemiyolojik dökümlerini yapmak ve maluliyet oranı hesaplanmasının en doğru şeklini göstermektir. Çalışmamız, 1994-1998 yılları arasında iş kazası sonucu maluliyet oranının belirlenmesi amacıyla Adli Tıp Kurumu 3. İhtisas Kuıulu’na gönderilen tüm olguları içermektedir. Toplam 139 olgunun 135'i (%97) erkek, 4'ii (%3) kadındır. Olgular 29-33 yaşları arasında (%25)yoğunlaşmaktadır. Lez- yonlar en çok pelvis ve alt ekstremitededir (%3D. Fonksiyon kayıplarına göre yapılan sınıflamada ise, bacak kısalığı gibi ortopedik kayıplar ilk sırayı almaktadır (%45). Maluliyet oranı %10-25 arasında değişen kişiler %32’lik oranla ilk sırayı almaktadır. Diğer çalışmalarla karşılaştırıldığında, yaş, cinsiyet, lezyon bölgeleri ve maluliyet oranları yönünden çalışmamızla benzerlikler saptanmıştır. Maluliyet oranı hesaplanmasında dikkat edilecek özellikler vurgulanarak raporların eksiksiz yazılabilmesi için önerilerde bulunulmuştur.Anahtar Kelimeler: Maluliyet, Maluliyet oranı, İş kazaları.
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McIntyre, Kaitlin, Cory Patrick, Rakesh Singal, and Damien Mikael Hansra. "Evaluation of hematologist/oncologist attributes by physicians and patients: A survey study." Journal of Clinical Oncology 34, no. 26_suppl (October 9, 2016): 124. http://dx.doi.org/10.1200/jco.2016.34.26_suppl.124.
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124 Background: We aim to compare what attributes are important to hematology/oncology (hem/onc) physicians (MD) and patients (pts). Methods: IRB approval obtained. Pts and MDs at an academic tertiary care medical center were enrolled to complete a survey. Demographics include: age, gender, race, and ethnicity. Clinical info collected: cancer subtype and treating MD. Survey consisted of 5 questions assessing opinions on physician attributes. Patients were asked: “It is important that my doctor” is friendly, is empathetic, is knowledgeable, well dressed, and engaged in research. MDs were asked: “It is important to be” friendly, empathetic, knowledgeable, well dressed, and engaged in research. Answers recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) & converted into 2 categories (1,2,3 = neutral/disagree vs. 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance between MD & pts responses. Results: 1008 pts and 55 MDs enrolled from June 2013 to October 2015. Pt mean age 55, range 18-88 with 45% male & 55% female. 62% of pts were Hispanic vs. 38% not Hispanic. 16% white, 14% black/African American, 2% Asian/Pacific Islander, & 6% other. 21% of pts had hematologic disorders (92% malignant 8% benign) vs. 79% of pts had solid malignancies. Significant difference was seen for research where 93% of pts agree that having a doctor who is engaged in research is important vs. 63% of MDs, p < 0.0001. A majority of pts and MDs agree that friendliness (92% vs. 91% resp., p = 0.6032), empathy (91% vs. 93% resp., p = 1.000), fund of knowledge (95% vs. 94% resp., p = 0.7442), being well dressed (79% vs. 69% resp., p = 0.0901), is important but no significant differences seen. Conclusions: Hem/onc pts and MD agree that friendliness, empathy, fund of knowledge, being well dressed are important attributes in a hem/onc MD. A significantly increased percentage of patients find it important that their hem/onc MD is engaged in research. It is expected that increased hem/onc MD research will not only contribute to society but also it could improve patient satisfaction.
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García-Gutiérrez, Valentín, Begoña Maestro, Alejandra Martinez-Trillo, Jose Luis Lopez Lorenzo, Maria Luisa Martin Mateos, Alberto Alvarez, Ana Iglesias Pérez, et al. "Bosutinib Apears to be Safe, with Low Cross Intolerance, in Patients Treated in 4th Line. Results of the Spanish Compassionate Use Program." Blood 124, no. 21 (December 6, 2014): 5523. http://dx.doi.org/10.1182/blood.v124.21.5523.5523.
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Abstract Second-generation TKIs have demonstrated efficacy and an acceptable tolerability in patients (pts) with chronic myeloid leukemia (CML); however, new data from so called “off target” side effects have been published. For example, serious concerns have been raised about cardiovascular (CV) events with ponatinib, and, in lesser degree with nilotinib (NI), impeding or difficulting the treatment in patients with previous CV risk factors. Besides, patients with previous history of pleural effusion or pulmonary hypertension should avoid dasatinib (DA) if possible. Bosutinib could be a good candidate for situations which preclude the use of other TKI’s. We have previously presented efficacy data of 29 patients treated with bosutinib in forth line. The aim of this study is to report safety data of heavily CML patients treated with bosutinib in 4th line. We have studied 30 pts previously treated with imatinib (IM), dasatinib and nilotinib and 5 pts previously treated with IM-DA or NI since 2012 under the Spanish Compassionate Use Program. Patient’s baseline characteristics and previous treatments are shown in table 1. We have classified patients in 2 groups regarding to investigator-driven cause of discontinuation: intolerant (INT) or resistant (RES). At the data cutoff on June 16, 2014, the median follow up was 11.47 months (range, 2.03-45.97 months). Median duration of BOS treatment across all cohorts was 9.23 months (range, 0.63-23.40 months). We observed no significant differences in terms of Index prognostic factors (Sokal, Hasford or Eutos), sex, median duration of TKIs treatment or comorbidities. However, patients with resistance where significantly older observed: 56 years vs. 67 years (p<0.05). Toxicity spectrum pre-BOS: Main reason for treatment discontinuation for each TKI was: treatment failure in the case of IM (14/35) and intolerance for both DA 16/34 and NI 13/31. Hematological (HEM) toxicities grade 3-4 with all TKIs were more common in RES pts, being dasatinib the one that showed the highest rate of grade 3-4 HEM toxicities. Non-HEM toxicities to all TKIs were significantly more frequent in INT than in RES pts (p<0.05). Most common grade 3-4 non-HEM toxicities were rash for IM (3/35), pleural effusion for DA (7/34) and vascular events for NI (3/31 Peripheral arterial disease (PAOD), 3/31 Ischemic heart disease (IHD)). Toxicity spectrum with BOS treatment: treatment interruptions were more frequent in INT than in RES pts 52% vs 25%, as well as dose reductions 78% vs 66% respectively. Grade 3-4 HEM toxicities were more common in RES than INT pts (41.6% vs 4.3% respectively). Non-HEM toxicities were also more frequent in RES pts than INT: diarrhea (50% vs 43%), rash (16% vs 8%), ALT or AST increase (25% vs 13%) abdominal pain (16% vs 4%), grade 3-4 non HEM toxicities were more frequent in RES than INT pts (41% vs 17%) (Diarrhea 16.7% vs 4.3%, AST/ALT increase: 16.7% vs 0%). None (0/12) vs 4/23 (17%) pts discontinued treatment due to toxicity in the RES vs. INT group respectively. Cross intolerance was extremely rare, of the 7 pts who had rash with IM, only 1 suffered rash with BOS. None pts had pleural effusion with BOS out of 15 who previously suffered with DA neither vascular events out of the 10 pts that previously suffered with NI. EFS by 20 months was 75% vs 50% for INT and RES patients. We have shown how in previously heavily pretreated CML patients, most of them in 4th line bosutinib has an excellent safety profile with no patients interrupting treatment due to side effects in previously intolerant patients. Importantly, rates of cross intolerance (namely CV, pleural and skin ) have also been very low. We conclude that Bosutinib is an excellent alternative also in patients who are left without a suitable treatment option. Table IM+NI-I +DA-R IMA+NI-R +DA-R IM+NI-I +DA-I IM+NI-R +DA-I IM+NI/DA TOTAL Pts, N(%) 2 (5.7) 7 (20) 15 (43) 6 (17) 5 (14) 35 (100) Age of diagnosis, med yr 61.0 46.7 54.7 53.8 58.7 54.2 Age of BOS initiation, med yr 74.7 61.5 64.6 64.8 65.5 63.8 Sokal index at diagnosis, N (High/intermidiate/low) 1/0/1 1/2/4 0/5/7 1/2/2 0/2/2 3/11/16 Time from first TKI to BOS, med yr 11.7 10.0 9.9 7.4 10.7 10.0 Duration of IM treatment, med, mo 63.3 33.1 26.6 21.4 78.2 27.2 Duration of DA treatment, med, mo 48.7 16.0 41.9 19.2 18.7 23.6 Duration of NI treatment, med ,mo 29.1 14.2 9.0 21.0 24.2 11.6 I:iIntolerance, R: resistant, med: median, yr: year, mo: months Disclosures García-Gutiérrez: Novartis: Consultancy; BMS: Consultancy; Pfizer: Consultancy; Ariad: Consultancy. Steegmann:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Ariad: Consultancy.
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Conran, Nicola, Juliete A. F. Silva, Erica M. F. Gotardo, Hanan Chweih, Lediana I. Miguel, Flávia Costa Leonardo, Wilson A. Ferreira, Bo E. Hedlund, Howard L. Elford, and Fernando F. Costa. "The Ribonucleotide Reductase Inhibitor, Didox, Reduces the In Vivo Vascular Inflammation and Oxidative Stress Induced By Acute Hemolysis." Blood 132, Supplement 1 (November 29, 2018): 1034. http://dx.doi.org/10.1182/blood-2018-99-119224.
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Abstract Introduction: Several diseases and disorders, including hereditary and acquired hemolytic anemia, blood transfusion reactions, preeclampsia and some infections, incur intravascular hemolysis to varying degrees. The destruction of red blood cells and the release of hemoglobin (Hb) and heme into the circulation results in vascular inflammation, characterized by the recruitment of leukocytes to the vascular endothelium, reduced nitric oxide bioavailability and oxidative stress, all of which may contribute to complications seen in hemolytic diseases, such as pulmonary hypertension, cutaneous leg ulcers and priapism. Didox (3,4-dihydroxybenzohydroxamic acid), a ribonucleotide reductase inhibitor, has been shown to have anti-inflammatory and anti-oxidative effects. This molecule has potential as a cancer therapy and has demonstrated beneficial effects in numerous pathologies, diminishing vaso-occlusive processes in mice with sickle cell disease, and suppressing mast cell activation and degranulation, amongst other effects. Aims: The aim of this study was to evaluate the effects of didox on the vascular inflammatory effects of in vivo acute hemolysis. Methods: C57BL/6 mice received i.v. didox (10 mg/animal) or the same volume of saline vehicle immediately before receiving the hemolytic stimulus. In some mice, didox (10 mg) was given intraperitonally (i.p.) 30 min before hemolysis. Acute hemolysis (HEM) was induced by injecting mice (i.v.) with 100 µl sterile water; for non-hemolysis controls (CON), the same quantity of saline was administered i.v.. At 15 min post-hemolysis, blood was obtained by cardiac puncture for biochemical and flow cytometry analyses; other animals were submitted to cremaster muscle exposure followed by intravital microscopy. Results: Intravascular H2O administration successfully induced hemolysis within 15 min, as demonstrated by elevated plasma cell-free Hb and heme levels (plasma Hb: 0.20±0.05 and 0.66±0.16 mg/ml, P<0.01; total plasma heme: 26.3±4.9 and 87.1±18.4 µM, for CON and HEM, respectively, N=≥6, P<0.001). Interestingly, pre-administration of mice with didox slightly, but significantly, decreased plasma Hb and Heme (plasma Hb: 0.43±0.07 and 0.54±0.07 mg/ml, P<0.05; total plasma heme: 62.7.3±9.5 and 71.5±6.7 µM for i.v. and i.p. didox, respectively, N=6, P<0.05). Concomitantly, acute hemolysis significantly augmented leukocyte (WBC) recruitment and extravasation in the cremaster microcirculation (WBC adhesion: 3.07±0.28 and 13.41±1.02 WBC µm-1, P<0.001; WBC extravasation: 0.72±0.16 and 2.93±0.45 WBC (100x50 µm-2) for CON and HEM, respectively, N=≥5, P<0.001). Didox significantly abrogated this effect of hemolysis, decreasing WBC adhesion to 6.12±0.62 and 2.10±0.30 WBC µm-1 and WBC extravasation to 1.32±0.24 and 1.14±0.21 WBC (100x50 µm-2) (for i.v. and i.p. didox, respectively, N≥5, P<0.001). Flow cytometry demonstrated that hemolysis elevated both the generation of reactive oxygen species (ROS) in the granulocytes of mice and their expression of the Mac-1 integrin subunit, CD11b (ROS: 590±58 and 1140±187 MFI, P<0.01; CD11b: 3028±387 and 4534±416 MFI, for CON and HEM, respect. N=3-6, P<0.01). Importantly, the inhibition of vascular inflammation by didox was associated with a significant decrease in both ROS generation and CD11b expression by granulocytes (ROS: 591±53 and 699±120 MFI, P<0.01; CD11b 2399±126 and 2379±207 MFI, for i.v. and i.p. didox, respectively. N=3-6, P<0.01). Conclusion: Didox, when administrated both intravascularly and intraperitoneally in mice, can inhibit the significant elevations in leukocyte integrin expression and cellular recruitment in the microcirculation that are induced by acute hemolysis. This improvement in vascular inflammation is accompanied by the prevention of oxidative stress in the leukocytes. While didox was found to slightly reduce hemolysis in response to osmotic shock, an interesting observation in itself, it is probable that the beneficial effects of this molecule on vascular inflammation are mediated largely by its effect on oxidative stress parameters. As such, this molecule may provide a novel therapeutic approach to reduce the oxidative stress and vascular inflammation caused by hemolytic events. This includes potential clinical use to treat sickle cell disease and other disorders in which hemolysis is a contributing factor to the pathophysiology. Disclosures Elford: Molecules for Health, Inc.: Equity Ownership, Patents & Royalties: Didox.
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Korkmaz, Saniye, Serpil Erermiş, Müge Tamar, Cahide Aydın, and Ayşe Kayahan. "Küçük Yaştaki Ensest Olgularında Tanı ve Adli Süreçte Yaşanan Sorunlar Nedeniyle Üç Olgu Sunumu." Bulletin of Legal Medicine 6, no. 2 (August 1, 2001): 81–86. http://dx.doi.org/10.17986/blm.200162456.
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Ensest çocuğun bir başka aile üyesi tarafından cinsel istismara maruz bırakılması olarak tanımlanmaktadır. Ensestin ortaya çıkma sıklığı yaygınlığından çok daha azdır. Ensest yalnızca çocukta değil tüm ailede önemli dinamik ve toplumsal değişiklikler oluşturmaktadır. Çocuk Psikiyatri kliniklerine yapılan başvurular çoğu kez yasal yollardandır. Küçük yaştaki çocukların hem zihinsel, duygusal özellikleri hem de ailenin baskı ve etkisi rapor düzenleme sürecini etkileyebilmektedir. Bu yazıda kliniğimize ensest şüphesiyle başvuran üç olgunun tanı ve adli rapor düzenlenmesinde yaşanan güçlükleri tartışmak ve bu alanda oluşturulabilecek standart normları gündeme getirmek amaçlanmıştır. Olgu A 5,5 yaşında öz baba - kız ensesti şüphesi, olgu B, 5,5 yaşında öz baba-oğul ensesti, olgu C 4,5 yaşında üvey baba-kız ensesti şüphesidir. Bu yazıda 3 olgunun sosyodemografik, aile özellikleri, şimdiki psikiyatrik durumları, psikometrik inceleme sonuçları ile birlikte ele alınarak tanı ve yasal süreçte yaşanan güçlükler tartışılmıştır. Böylesi çalışmaların multidisipliner ekiplerce yapılması gerektiğini düşünüyoruz.Anahtar sözcükler: Çocuk, ensest, yasal süreç.
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Mistry, Pramod K., Sara Sadan, Ruhua Yang, John Yee, and Mei Yang. "Consequences of Diagnostic Delays in Type 1 Gaucher Disease: A Unique Opportunity among Hematologists/Oncologists for Early Diagnosis and Intervention." Blood 108, no. 11 (November 16, 2006): 3308. http://dx.doi.org/10.1182/blood.v108.11.3308.3308.
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Abstract Gaucher disease (GD) is a progressive lysosomal storage disease that can lead to life-threatening complications. Anecdotal experiences of patients and physicians suggest that symptoms and signs of the disease may go undiagnosed for many years, resulting in severe yet preventable complications. We conducted surveys of patients and Hematology/Oncology specialists to assess the frequency of diagnostic delays. Furthermore, we reviewed a series of patients in whom prolonged misdiagnosis resulted in serious complications of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 3–4 years. Up to 86% of patients reported having visited a Hematologist/Oncologist (Hem/Onc) concerning their condition and two thirds reported current management of their symptoms by a Hem/Onc. The frequency of intial symptoms at presentation to Hem/Oncs is depicted in Table 1. In a global survey of 406 Hem/Oncs, only 20% of respondents considered GD in the differential diagnosis when presented with all six classic symptoms: anemia, thrombocytopenia, hepatomegaly, splenomegaly, bone pain, bone crisis. In contrast, the diagnoses considered more frequently for this constellation of symptoms were leukemia (65%), lymphoma (36%), and multiple myeloma (22%). When asked to list additional signs and symptoms of GD other than the six classic symptoms, 47% could not list any additional manifestations; the common signs and symptoms of easy bruising and bleeding, fatigue, and pathological fractures were identified by 9%, 5%, and 4% of respondents, respectively. Fifty-three percent of surveyed Hem/Oncs considered their specialty the best equipped to manage Gaucher patients and their self-assessed knowledge of GD on a scale of 1 (not at all knowledgeable) to 10 (extremely knowledgeable) was 4.1±2.4, with responses showing normal distribution around the mean. In a review of 14 patients with GD in whom up to 10 years elapsed from the appearance of symptoms to final diagnosis of GD, reversible or preventable complications occured including avascular necrosis, bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure and liver pathology. In this series, patients with GBA genotype N370S/N370S, which is typically associated with a mild GD phenotype, were most vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur frequently in GD that may result in severe complications. Physician education is needed to increase early detection of patients with GD and improve its management, and Hem/Oncs have a unique opportunity for timely diagnosis and optimal management of this treatable disorder. Table 1. Symptoms of Patients Presenting to Hematologists/Oncologists Signs and Symptoms Percentage of Patients (n = 92) *Including thrombocytopenia, anemia, epistaxis, chronic infection, leg pain, enlarged liver and/or spleen Easy bruising or bleeding 51.1% Enlarged abdomen 46.7% Fatigue 31.5% Pain in bone and joints/bone fractures 26.1% Delayed growth 17.4% Other* 29.3%
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Chiara, Francesca, Aurora Badaloni, Laura Croci, Mason L. Yeh, Anna Cariboni, Anna Hoerder-Suabedissen, G. Giacomo Consalez, et al. "Early B-cell factors 2 and 3 (EBF2/3) regulate early migration of Cajal–Retzius cells from the cortical hem." Developmental Biology 365, no. 1 (May 2012): 277–89. http://dx.doi.org/10.1016/j.ydbio.2012.02.034.
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