Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 500
Filtrar
1.
Br J Haematol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32395867

RESUMO

Venous thromboembolism (VTE) is a well-known complication in adults receiving asparaginase (ASNase)-based intensification chemotherapy for acute lymphoblastic leukaemia (ALL). The optimal preventative strategy is unclear. Our objective is to determine the effects of low-molecular-weight heparin (LMWH) as primary VTE prophylaxis. A single-centred retrospective cohort study of adult patients with Philadelphia chromosome negative (Ph-) ALL who received ASNase-based intensification from 2001 to 2017, with prophylaxis given from 2011 to 2017. In all, 214 patients were included in this study with 99 in the historical control group and 125 in the prophylaxis group. The mean (range) enoxaparin dose was 0·79 (0·39-1·2) mg/kg. Of the 125 patients in the prophylaxis group 17 (13·6%) developed VTE during the intensification phase, while 27/99 patients (27·3%) in the control cohort experienced at least one thrombotic event (odds ratio [OR] 0·42, 95% confidence interval [CI] 0·21-0·83). Overall, the main sites of VTE incidences included deep vein thrombosis in the lower extremity (54·6%), pulmonary embolism (13·6%) and catheter-related thrombosis (22·7%). In addition, we found that after adjusting for age, T-phenotype ALL was associated with VTE development (OR 3·07, 95% CI 1·04-9·08). There was no documented major bleeding in the prophylaxis group. LMWH prophylaxis reduced the incidence of symptomatic VTE in adult patients with ALL receiving intensification chemotherapy with ASNase.

2.
Blood Adv ; 4(9): 1965-1973, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32384540

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

3.
Expert Opin Investig Drugs ; : 1-14, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32245330

RESUMO

Introduction: Patients with myelofibrosis (MF) have no effective treatment option after the failure of approved JAK inhibitor (JAKi) therapy. Non-JAK inhibitors (non-JAKi) that target non-canonical molecular pathways are undergoing clinical evaluations to optimize efficacy and/or to reduce hematological toxicity of JAKi.Area covered: This article reviews the efficacy data from completed and ongoing early phase clinical trials of non-JAKi agents for chronic phase MF. The article also illuminates some of the challenges of myelofibrosis drug development.Expert opinion: Most non-JAKi agents tested so far have shown modest benefit in improving the efficacy of ruxolitinib. Several novel agents such as BET inhibitor- CPI-0610, activin receptor ligand trap- luspatercept, recombinant pentraxin-PRM-151, telomerase inhibitor- imetelstat and bcl-2 inhibitor- navitoclax, have shown promising activity; however, they require vigorous evaluation in randomized controlled trials to understand the clinical benefit. Drugs that target new molecular pathways (MDM2, p-selectin, TIM-3, TGF-ß, aurora kinase) and immune-based strategies (CALR vaccine, anti-PD-1, allogeneic cord blood regulatory T cells) are in early phase trials. Further translational studies to target leukemic stem cells, improvement in trial designs by incorporating control arm and survival endpoints, and patient-focused collaborations among all stakeholders could pave a way for future success in MF drug development.

4.
J Clin Oncol ; : JCO1902515, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32298201

RESUMO

PURPOSE: The combination of lenalidomide, bortezomib, and dexamethasone (RVD) is a highly effective and convenient induction regimen for both transplantation-eligible and -ineligible patients with myeloma. Here, we present the largest cohort of patients consecutively treated with RVD induction therapy followed by risk-adapted maintenance therapy with the longest follow-up and important information on long-term outcomes. PATIENTS AND METHODS: We describe 1,000 consecutive patients with newly diagnosed myeloma treated with RVD induction therapy from January 2007 until August 2016. Demographic and clinical characteristics and outcomes data were obtained from our institutional review board-approved myeloma database. Responses and progression were evaluated per International Myeloma Working Group Uniform Response Criteria. RESULTS: The overall response rate was 97.1% after induction therapy and 98.5% after transplantation, with 89.9% of patients achieving a very good partial response (VGPR) or better and 33.3% achieving stringent complete response after transplantation at a median follow-up time of 67 months. The estimated median progression-free survival time was 65 months (95% CI, 58.7 to 71.3 months) for the entire cohort, 40.3 months (95% CI, 33.5 to 47 months) for high-risk patients, and 76.5 months (95% CI, 66.9 to 86.2 months) for standard-risk patients. The median overall survival (OS) time for the entire cohort was 126.6 months (95% CI, 113.3 to 139.8 months). The median OS for high-risk patients was 78.2 months (95% CI, 62.2 to 94.2 months), whereas it has not been reached for standard-risk patients. Five-year OS rates for high-risk and standard-risk patients were 57% and 81%, respectively, and the 10-year OS rates were 29% and 58%, respectively. CONCLUSION: RVD is an induction regimen that delivers high response rates (VGPR or better) in close to 90% of patients after transplantation, and risk-adapted maintenance can deliver unprecedented long-term outcomes. This study includes the largest cohort of patients treated with RVD reported to date with long follow-up and demonstrates the ability of 3-drug induction regimens in patients with newly diagnosed multiple myeloma to result in a substantial survival benefit.

5.
Leuk Lymphoma ; : 1-12, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32323602

RESUMO

Health resource utilization (HRU) and associated factors of high cost are not well understood in myeloproliferative neoplasms (MPNs). In this population-based, retrospective matched-cohort study, we used administrative health databases of Ontario, Canada to measure treatment costs and HRU for patients with MPN from 2004 to 2016 and compared them to matched controls. In 7130 patients with MPN [essential thrombocythemia (ET) = 3481; polycythemia vera (PV) = 2618; myelofibrosis (MF) = 1031], the mean annualized treatment costs were $16,646 for ET (controls, $7070); $16,360 for PV (controls, $7293); and $25,863 for MF (controls, $7386). Out of the total costs, the largest expenditure was on acute hospital care (ET: 57%, PV: 57%, MF: 66%). Older age (≥65), male gender, patients not seen by a specialist, and greater comorbidity burden were independent predictors of higher costs (p < 0.05). In addition, history of venous thrombosis in patients with ET and PV was associated with significantly higher treatment costs (p < 0.05).

6.
Gastroenterology ; 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32289375

RESUMO

BACKGROUND & AIMS: In response to tissue injury, stromal cells secrete extracellular matrix (ECM) components that remodel the tissue and lead to fibrosis. Parenchymal stellate cells are the primary contributors to fibrosis in models of hepatocellular and cholestatic injury. The liver comprises different, heterogenous compartments; stromal cells within those compartments might have unique identities and regional functions. The portal tract contains the bile duct, which is surrounded by stromal cells often called portal fibroblasts. We investigated the contributions of these cells to hepatic injury. METHODS: We performed studies with Gli1:CreERT2; Rosa26:lox-STOP-lox-tdTomato mice. Mice underwent bile duct ligation or were fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine to induce cholestatic injury or were given CCL4 to induce liver fibrosis. Liver tissues were collected and analyzed by histology and immunofluorescence, and mesenchymal cells were isolated. We performed lineage tracing experiments to determine the fates of peribiliary mesenchymal cells (PMCs) that surround the bile duct after cholestatic and hepatocellular injury. We used cell sorting, combined with RNA-sequencing, to isolate stellate cells and PMCs, and identified determinants of cell identity within each population. Liver tissues were obtained from patients with primary sclerosing cholangitis, alcoholic liver disease, nonalcoholic steatohepatitis, or without disease and analyzed by quantitative reverse transcription PCR. RESULTS: Gli1 was a marker of mesenchymal cells that surround the biliary tree, but not epithelial cells of the canals of Hering. Lineage-traced Gli1+ PMCs proliferated and acquired a myofibroblast phenotype after cholestatic injury; Gli1+ PMCs were found only surrounding the main duct of a portal tract, but not the epithelial cells of the ductular reaction, which were instead encased by stellate cells. Compared with stellate cells, Gli1+ PMCs expressed a different subset of genes, including genes that are markers of active hedgehog signaling, Osr1 (encodes a transcription factor), and ECM-related genes. Loss of hedgehog signaling reduced expression of Osr1 and PMC-specific ECM genes. Liver tissues from patients with liver disease had increased expression of genes that define PMC identity, compared with control liver tissues. CONCLUSIONS: In lineage-tracing studies of mice, we found that Gli1+ PMCs are a subset of stromal cells characterized by active hedgehog signaling that proliferate, acquire a myofibroblast phenotype, and surround the biliary tree in response to cholestatic injury.

7.
J Immunother Cancer ; 8(1)2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32217756

RESUMO

BACKGROUND: Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, demonstrates predictive biomarker potential for the identification of patients with cancer most likely to respond to immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation sequencing targeted panels provide TMB estimates in a time-effective and cost-effective manner. However, differences in panel size and gene coverage, in addition to the underlying bioinformatics pipelines, are known drivers of variability in TMB estimates across laboratories. By directly comparing panel-based TMB estimates from participating laboratories, this study aims to characterize the theoretical variability of panel-based TMB estimates, and provides guidelines on TMB reporting, analytic validation requirements and reference standard alignment in order to maintain consistency of TMB estimation across platforms. METHODS: Eleven laboratories used WES data from The Cancer Genome Atlas Multi-Center Mutation calling in Multiple Cancers (MC3) samples and calculated TMB from the subset of the exome restricted to the genes covered by their targeted panel using their own bioinformatics pipeline (panel TMB). A reference TMB value was calculated from the entire exome using a uniform bioinformatics pipeline all members agreed on (WES TMB). Linear regression analyses were performed to investigate the relationship between WES and panel TMB for all 32 cancer types combined and separately. Variability in panel TMB values at various WES TMB values was also quantified using 95% prediction limits. RESULTS: Study results demonstrated that variability within and between panel TMB values increases as the WES TMB values increase. For each panel, prediction limits based on linear regression analyses that modeled panel TMB as a function of WES TMB were calculated and found to approximately capture the intended 95% of observed panel TMB values. Certain cancer types, such as uterine, bladder and colon cancers exhibited greater variability in panel TMB values, compared with lung and head and neck cancers. CONCLUSIONS: Increasing uptake of TMB as a predictive biomarker in the clinic creates an urgent need to bring stakeholders together to agree on the harmonization of key aspects of panel-based TMB estimation, such as the standardization of TMB reporting, standardization of analytical validation studies and the alignment of panel-based TMB values with a reference standard. These harmonization efforts should improve consistency and reliability of panel TMB estimates and aid in clinical decision-making.

8.
JCO Oncol Pract ; : JOP1900506, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134707

RESUMO

Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.

9.
Nat Commun ; 11(1): 1228, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144272

RESUMO

The BCL-2 antagonist venetoclax is highly effective in multiple myeloma (MM) patients exhibiting the 11;14 translocation, the mechanistic basis of which is unknown. In evaluating cellular energetics and metabolism of t(11;14) and non-t(11;14) MM, we determine that venetoclax-sensitive myeloma has reduced mitochondrial respiration. Consistent with this, low electron transport chain (ETC) Complex I and Complex II activities correlate with venetoclax sensitivity. Inhibition of Complex I, using IACS-010759, an orally bioavailable Complex I inhibitor in clinical trials, as well as succinate ubiquinone reductase (SQR) activity of Complex II, using thenoyltrifluoroacetone (TTFA) or introduction of SDHC R72C mutant, independently sensitize resistant MM to venetoclax. We demonstrate that ETC inhibition increases BCL-2 dependence and the 'primed' state via the ATF4-BIM/NOXA axis. Further, SQR activity correlates with venetoclax sensitivity in patient samples irrespective of t(11;14) status. Use of SQR activity in a functional-biomarker informed manner may better select for MM patients responsive to venetoclax therapy.

10.
PLoS One ; 15(2): e0229393, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32084236

RESUMO

OBJECTIVE: We aimed to describe the clinical and economic burden attributable to carbapenem-nonsusceptible (C-NS) respiratory infections. METHODS: This retrospective matched cohort study assessed clinical and economic outcomes of adult patients (aged ≥18 years) who were admitted to one of 78 acute care hospitals in the United States with nonduplicate C-NS and carbapenem-susceptible (C-S) isolates from a respiratory source. A subset analysis of patients with principal diagnosis codes denoting bacterial pneumonia or other diagnoses was also conducted. Isolates were classified as community- or hospital-onset based on collection time. A generalized linear mixed model method was used to estimate the attributable burden for mortality, 30-day readmission, length of stay (LOS), cost, and net gain/loss (payment minus cost) using propensity score-matched C-NS versus C-S cohorts. RESULTS: For C-NS cases, mortality (25.7%), LOS (29.4 days), and costs ($81,574) were highest in the other principal diagnosis, hospital-onset subgroup; readmissions (19.4%) and net loss (-$9522) were greatest in the bacterial pneumonia, hospital-onset subgroup. Mortality and readmissions were not significantly higher for C-NS cases in any propensity score-matched subgroup. Significant C-NS-attributable burden was found for both other principal diagnosis subgroups for LOS (hospital-onset: 3.7 days, P = 0.006; community-onset: 1.5 days, P<0.001) and cost (hospital-onset: $12,777, P<0.01; community-onset: $2681, P<0.001). CONCLUSIONS: Increased LOS and cost burden were observed in propensity score-matched patients with C-NS compared with C-S respiratory infections; the C-NS-attributable burden was significant only for patients with other principal diagnoses.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/economia , Infecções por Bactérias Gram-Negativas/mortalidade , Custos de Cuidados de Saúde/estatística & dados numéricos , Infecções Respiratórias/economia , Infecções Respiratórias/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Br J Haematol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017044

RESUMO

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded-access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109 /l) and patients without splenomegaly - populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low-platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low-platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non-haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50-100 × 109 /l. (ClinicalTrials.gov identifier NCT01493414).

13.
Dig Dis Sci ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026280

RESUMO

BACKGROUND: Percutaneous catheter drainage (PCD) performed pro-actively for collections in acute pancreatitis (AP) is associated with better outcomes. However, there are only a few studies describing this protocol. AIM: We aimed to evaluate an aggressive PCD protocol. METHODS: Consecutive patients with AP who underwent PCD with an aggressive protocol between January 2018 and January 2019 were included. This protocol involved catheter upsizing at a pre-specified interval (every 4-6 days) as well as drainage of all the new collections. The indications and technical details of PCD and clinical outcomes were compared with patients who underwent standard PCD. RESULTS: Out of the 185 patients with AP evaluated during the study period, 110 (59.4%) underwent PCD, all with the aggressive protocol. The historical cohort of standard PCD comprised of 113 patients. There was no significant difference in the indication of PCD and interval from pain onset to PCD between the two groups. The mean number of catheters was significantly higher in the aggressive PCD group (1.86 ± 0.962 vs. 1.44 ± 0.667, p = 0.002). Additional catheters were inserted in 54.2% of patients in aggressive group vs. 36.2% in the standard group (p = 0.006). Length of hospital stay and intensive care unit (ICU) stay were significantly longer in the standard PCD group (34.3 ± 20.14 vs. 27.45 ± 14.2 days, p < 0.001 and 10.46 ± 12.29 vs. 4.12 ± 8.5, p = 0.009, respectively). There was no significant difference in mortality and surgery between the two groups. CONCLUSION: Aggressive PCD protocol results in reduced length of hospital stay and ICU stay and can reduce hospitalization costs.

14.
Nat Commun ; 11(1): 253, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937774

RESUMO

Colonization of new habitats is expected to require genetic adaptations to overcome environmental challenges. Here, we use full genome re-sequencing and extensive common garden experiments to investigate demographic and selective processes associated with colonization of Japan by Lotus japonicus over the past ~20,000 years. Based on patterns of genomic variation, we infer the details of the colonization process where L. japonicus gradually spread from subtropical conditions to much colder climates in northern Japan. We identify genomic regions with extreme genetic differentiation between northern and southern subpopulations and perform population structure-corrected association mapping of phenotypic traits measured in a common garden. Comparing the results of these analyses, we find that signatures of extreme subpopulation differentiation overlap strongly with phenotype association signals for overwintering and flowering time traits. Our results provide evidence that these traits were direct targets of selection during colonization and point to associated candidate genes.


Assuntos
Aclimatação/genética , Lotus/genética , Evolução Biológica , Genes de Plantas/genética , Variação Genética , Genoma de Planta/genética , Estudo de Associação Genômica Ampla , Genótipo , Geografia , Japão , Lotus/crescimento & desenvolvimento , Lotus/fisiologia , Fenótipo , Seleção Genética
15.
Haematologica ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896684

RESUMO

Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and the fusion proteins RUNX1-RUNX1T1 and CBFB-MYH11. International guidelines recommend monitoring for measurable residual disease every 3 months for 2 years after treatment. However, it is unknown if serial molecular monitoring can predict and prevent morphologic relapse. We conducted a retrospective single-center study of 114 patients in complete remission who underwent molecular monitoring with RT-qPCR of RUNX1-RUNX1T1 or CBFB-MYH11 transcripts every 3 months. Morphologic relapse was defined as re-emergence of >5% blasts and molecular relapse as ≥1 log increase in transcript level between 2 samples. Over a median follow-up time of 3.7 years (range 0.2-14.3), remission persisted in 71 (62.3%) patients but 43 (37.7%) developed molecular or morphologic relapse. Patients who achieved <3 log reduction in RUNX1-RUNX1T1 or CBFB-MYH11 transcripts at end of chemotherapy had a significantly higher risk of relapse compared to patients who achieved ≥3 log reduction (61.1% vs. 33.7%, p=0.004). The majority of relapses (74.4%, n=32) were not predicted by molecular monitoring and occurred rapidly with <100 days from molecular to morphologic relapse. Molecular monitoring enabled the detection of impending relapse and permitted pre-emptive intervention prior to morphologic relapse in only 11 (25.6%) patients. The current practice of molecular monitoring every 3 months provided insufficient lead-time to identify molecular relapses and prevent morphologic relapse in the majority of patients with core-binding factor acute myeloid leukemia treated at our institution. Further research is necessary to determine the optimal monitoring strategies for these patients.

16.
Transplantation ; 104(2): 308-316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31283669

RESUMO

BACKGROUND: The principle in right lobe living donor liver transplantation is to use "near-perfect" grafts to maximize recipient benefit with minimal donor risk. Whether and what degree of graft macrovesicular steatosis is safe for both recipient and donor is debatable. METHODS: We compared donor and recipient outcomes in 623 primary right lobe living donor liver transplantations, using grafts with (Group A; 10%-20% steatosis, n = 92) and without (Group B; <10%, n = 531) significant macrovesicular steatosis, on pre- or intraoperative biopsy. RESULTS: Group A donors had higher body mass index, transaminases, fasting blood sugar, triglyceride, low density lipoprotein level, and lower high density lipoprotein, and liver attenuation index on CT scan, and similar future liver remnant. Mean postoperative day (POD) 7, aspartate aminotransferase (61.13 + 24.77 vs 73.17 + 53.71 IU/L; P = 0.04), and prothrombin time-international normalized ratio (1.16 + 0.36 vs 1.28 + 0.24; P = 0.0001) were lower in Group A donors. POD3 of 7 total bilirubin and alanine aminotransferase; POD3 aspartate aminotransferase and prothrombin time-international normalized ratio; postoperative morbidity (Dindo-Clavien >3b), hospital stay were similar in both groups. Recipients in both groups had similar age, model for end-stage liver disease score. Right lobe graft weight (764.8 + 145.46 vs 703.24 + 125.53 grams; P < 0.0001) and GRWR (1.09 + 0.29 vs 1.00 + 0.21; P = 0.0004) were higher in Group A. All biochemical parameters at POD 3 of 7, as well as hospital stay, 30-day mortality were similar in recipients of both groups, even after matching both groups for age, model for end-stage liver disease, and GRWR. CONCLUSIONS: Use of well-selected right lobe grafts (adequate future liver remnant in donor, GRWR in recipient), with up to 20% macrovesicular steatosis, does not compromise graft function and outcomes and is safe for the donor.

17.
Dysphagia ; 35(1): 73-83, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30929058

RESUMO

BACKGROUND AND AIMS: This retrospective study was aimed at assessing the efficacy of endoscopic dilation for esophageal anastomotic strictures, and to compare response between caustic anastomotic strictures (CAS) and non-caustic anastomotic strictures (NCAS). MATERIALS AND METHODS: Patients with anastomotic strictures (enrolled during January 1996-December 2015) were analyzed. Short- and long-term outcomes of dilation, in terms of clinical success, refractory, and recurrent strictures were compared between NCAS and CAS. Patients with refractory and recurrent strictures were managed with adjunctive therapy including intralesional steroids. Factors predicting refractoriness at start of dilation and reasons for more than ten lifetime dilations were also evaluated. RESULTS: Of the 142 patients, 124 (mean age-44.02; males-74) underwent dilation. Clinical success was achieved in 113 (91.3%) patients requiring a median [Interquartile range (IQR)] of 4 (2-10) sessions. The number of dilations to achieve clinical success, refractory strictures, and recurrent strictures, and the use of adjunctive therapy were significantly higher for CAS than for NCAS. Intralesional steroid use decreased periodic dilation index (PDI) significantly in CAS. Caustic etiology and starting dilation diameter of < 10 mm were found to be predictors of refractoriness, with the former alone being an independent predictor of more than ten lifetime dilations. No patient had free perforation; however, five required revision surgery. CONCLUSION: Patients with CAS fared worse than those with NCAS in terms of number of dilations, refractoriness, recurrence of strictures, and need of adjunctive therapy. Endoscopic dilation can successfully ameliorate dysphagia due to anastomotic strictures in a majority of patients.

18.
Eur J Pain ; 24(3): 639-648, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31782864

RESUMO

BACKGROUND: Opioids and non steroidal anti inflammatory drugs (NSAIDs) are commonly used for pain relief in acute pancreatitis (AP). Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis, few reports of diclofenac associated AP are also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety. MATERIALS AND METHODS: Forty-six eligible participants were randomized to either diclofenac or tramadol. Primary objectives of our study were improvement in pain intensity on visual analogue scale (VAS pain score after 1 hr of drug administration) and number of patients requiring supplementary analgesia. The secondary objectives were total number of times of supplementary analgesia requirement, time to significant decrease (33%) in VAS pain score from baseline, number of painful days (VAS pain score >5), VAS pain score on 7th day, side effects, all cause death and complications of pancreatitis between the two groups. RESULTS: Although 46 patients were randomized, the final analysis included 41 participants. Five patients were withdrawn from the study (intubation = 3, altered sensorium = 2). No significant difference was seen in terms of VAS score after 1 hr of drug administration, number of patients requiring supplementary analgesic and number of painful days. However, time taken to significant reduction of pain was lower in the diclofenac group (p = .028). Both the agents were comparable in terms of safety. Although complications were less in the diclofenac group, the difference was not statistically significant. CONCLUSION: Both diclofenac and tramadol are equally effective in controlling pain in AP with similar safety profile. SIGNIFICANCE: There are no studies that have compared the safety and efficacy of two commonly used analgesics for pain relief in patients with AP. We found that both diclofenac and tramadol are equally effective in decreasing the pain associated with AP. There is also no significant difference in the incidence of side effects between both the groups. Hence both diclofenac and tramadol can be used safely and effectively for pain control in AP. TRIAL REGISTRATION: The trial was registered with clinical trials registry India (Number- CTRI/2018/05/014309).

19.
Theor Appl Genet ; 133(3): 689-705, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31811315

RESUMO

KEY MESSAGE: A novel recessive bacterial blight resistance locus designated as a xa-45(t) was identified from Oryza glaberrima accession IRGC 102600B, transferred to O. sativa and mapped to the long arm of chromosome 8 using ddRAD sequencing approach. The identified QTL spans 80 kb region on Nipponbare reference genome IRGSP-1.0 and contains 9 candidate genes. An STS marker developed from the locus LOC_Os08g42410 was found co-segregating with the trait and will be useful for marker-assisted transfer of this recessive resistance gene in breeding programs. Bacterial blight, caused by Xanthomonas oryzae pv. oryzae, is one of the major constraints of rice productivity in Southeast Asia. In spite of having 44 bacterial blight resistance genes from cultivated rice and wild species, the durability of resistance is always at stake due to the continually evolving nature of the pathogen and lack of suitable chemical control. Here, we report high-resolution genetic mapping of a novel bacterial blight resistance gene tentatively designated as a xa-45(t) from an introgression line derived from Oryza glaberrima accession IRGC 102600B. This introgression line was crossed with the susceptible rice indica cultivar cv. Pusa 44 to generate F2 and F2:3 populations for inheritance and mapping studies. The inheritance studies revealed the presence of single recessive locus controlling resistance to the Xanthomonas pathotype seven. A high-density linkage map was constructed using double-digest restriction-associated DNA sequencing of 96 F2 populations along with the parents. The QTL mapping identified a major locus on the long arm of rice chromosome 8 with a LOD score of 33.22 between the SNP markers C8.26737175 and C8.26818765. The peak marker, C8.26810477, explains 49.8% of the total phenotypic variance and was positioned at 202.90 cM on the linkage map. This major locus spans 80 kb region on Nipponbare reference genome IRGSP-1.0 and contains 9 candidate genes. A co-segregating STS marker was developed from the LOC_Os08g42410 for efficient transfer of this novel gene to elite cultivars.

20.
Semin Perinatol ; 44(1): 151167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31519366

RESUMO

Congenital diaphragmatic hernia (CDH) is a neonatal pathology in which intrathoracic herniation of abdominal viscera via diaphragmatic defect results in aberrant pulmonary and cardiovascular development. Despite decades of study and many advances in the diagnosis and treatment of CDH, morbidity and mortality remain high, largely due to pulmonary hypertension (PH), along with pulmonary hypoplasia and cardiac dysfunction. In patients with CDH, hypoplastic pulmonary vasculature and alterations in multiple molecular pathways lead to pathophysiologic pulmonary vasculopathy and, for severe CDH, sustained, elevated pulmonary arterial pressures. This review addresses the multiple anatomic and physiologic changes that underlie CDH-associated PH (CDH-PH), along with the multimodal treatment strategies that exist currently and future therapies currently under investigation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA