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STUDY DESIGN: Delphi survey. OBJECTIVES: To obtain an expert consensus on various dilemmas in the surgical treatment of adult spinal tuberculosis (TB) patients. METHODS: Stage I included a literature review, stage II the identification of 40 Key Opinion leaders (KOLs) and a set of 46 questions, stage III included analysis of 3 rounds of the Delphi survey, and stage IV had final analysis and recommendations. For each question, the level of agreement needed to reach a consensus was set at greater than or equal to 70.0%. RESULTS: The first and second Delphi survey rounds received 62 and 58 responses, respectively, with 16 questions having more than 70% and two questions having 100% agreement in the first stage. The second stage saw a 70% agreement on six questions. Thus, a consensus was obtained on 22 questions. The recommendations that emerged were as follows: neurodeficit with corresponding radiology and neurological deficit appearing/deteriorating while on anti-tubercular chemotherapy(ATT) are absolute indications for surgery, duration of ATT before neurological deterioration need not be considered, epidural abscess does not need decompression unless concordant clinical neurological findings are present, pain not responding to medical management is not a surgical indication, active pulmonary TB, drug-resistant TB, and tubercular sacroiliitis are not considered as surgical indications, and hemoglobin and other health markers have little contribution to surgical indications. CONCLUSION: In order to resolve several conundrums in the surgical treatment of adult spinal TB, this Delphi survey is the first to achieve a national consensus from spine experts. The final recommendations cover the serological, radiographic, and clinical aspects of spinal TB.
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AIMS: Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. METHODS: Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). RESULTS: The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. CONCLUSIONS: In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.
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Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Reino Unido/epidemiologia , Tempo de InternaçãoRESUMO
A major barrier to the clinical application of psychophysical testing of central auditory processes is the time required to obtain precise estimates of different listening abilities. In this study, we validate a novel adaptive scan (AS) method of threshold estimation that is designed to adapt on a range of values around threshold rather than on a single threshold value. This method has the advantage of providing the listener with greater familiarity with the stimulus characteristics near threshold while maintaining precise measurement and increasing time-efficiency. Additionally, we explore the time-efficiency of AS through comparison with two more conventional adaptive algorithms and the method of constant stimuli in two common psychophysical tasks: the detection of a gap in noise and the detection of a tone in noise. Seventy undergraduates without hearing complaints were tested using all four methods. The AS method provided similar threshold estimates with similar precision to those from the other adaptive methods and, thus, it is a valid adaptive method of psychophysical testing. We also provide an analysis of the AS method based on precision metrics to propose a shortened version of the algorithm that maximizes the time/precision tradeoff and can achieve similar thresholds to the adaptive methods tested in the validation. This work lays the foundation for using AS across a wide variety of psychophysical assessments and experimental situations where different levels of precision and/or time-efficiency may be required.
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Algoritmos , Ruído , Humanos , Limiar Auditivo , Psicoacústica , Fatores de TempoRESUMO
BACKGROUND: IDH-mutant astrocytomas include CNS WHO grade 2 (A2), grade 3 (A3) and grade 4 (A4), of which A3 and A4 are high-grade. A3 has a heterogenous clinical outcome that cannot be explained entirely by the existing molecular biomarkers. We comprehensively studied the transcriptome profile of A3 to determine clinical significance. METHODS: TCGA mRNA-sequencing data of A3 was analyzed to derive differentially expressed genes (DEG), which were short-listed using various approaches. mRNA expression of the short-listed genes was validated using NanoString platform on a uniformly treated and molecularly characterized A3 cohort. Protein expression of one prognostically significant gene, Iroquois-class homeodomain (IRX1) was assessed by immunohistochemistry and correlated with patient survival and tumor recurrence. IRX1 expression was also studied in different grades of astrocytoma. Since DNA methyltransferase 3 alpha (DNMT3A) influences IRX1 expression, its mutations were evaluated in a subset of tumors. RESULTS: TCGA analysis identified 96 DEG in A3 tumours. 57 genes were short-listed and finally narrowed down to 14 genes. mRNA values of 12/14 genes validated in our cohort. On multiple-variable analysis, IRX1 was the most prognostically relevant gene, with respect to progression free survival of patients. Further, IRX1 immunoexpression was significantly higher in A3 and A4 when compared to A2 and glioblastoma. Higher IRX1 immunoexpression correlated with poor prognosis in patients with A3 tumours. Also, a higher IRX1 expression was associated with DNMT3A mutation. CONCLUSION: Our study identifies IRX1 as a novel biomarker overexpressed in high-grade IDH-mutant astrocytomas with prognostic significance in A3. DNMT3A mutation probably modulates IRX1 expression.
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Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Humanos , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia , Astrocitoma/genética , Astrocitoma/patologia , Glioblastoma/patologia , Prognóstico , Biomarcadores , Mutação , RNA Mensageiro/genética , Isocitrato Desidrogenase/genética , Fatores de Transcrição/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismoRESUMO
The duration of the pandemic over the last two years has witnessed the steering of multiple technological interventions by governments. These interventions - ranging from contact tracing applications to vaccine certificates - have been developed in the specific context of the pandemic, and were meant to address its unique requirements. This family of technological interventions may be termed "pandemic technology" - having diverse uses such as preventing the transmission of Covid-19, and aiding the relaxation of pandemic-induced restrictions. We propose a four-rung ethical paradigm for the deployment of such technology. We call it the STEP model and its four pillars consist of (i) sunset clauses, (ii) trust, (iii) equity, and (iv) privacy preservation.
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COVID-19 , Aplicativos Móveis , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Pandemias/prevenção & controle , Busca de Comunicante , TecnologiaRESUMO
BACKGROUND: Advances in surgical and medical technology over the years has made liver transplantation possible for older and higher risk patients. Despite rigorous preoperative cardiac testing, cardiovascular events remain a major cause of death after orthotopic liver transplantation (OLT). However, there are little data on the outcomes of OLT in patients with preexisting coronary artery disease (CAD). This study aimed to compare all-cause and cardiovascular mortality of patients with and without history of CAD undergoing OLT. METHODS: Six hundred ninety-three adult patients with cirrhosis underwent liver transplantation between July 2013 and December 2018 (female n = 243, male n = 450; median age 59). RESULTS: During the study period of 5 y (median follow-up, 24.1 mo), 92 of 693 patients (13.3%) died. All-cause mortality in the CAD group was significantly higher than in the non-CAD group (26.7% versus 9.6%; P <0.01). Cardiovascular events accounted for 52.5% of deaths (n = 21) in patients with CAD compared with 36.5% (n = 19) in non-CAD patients. At 6 mo, patients with combined nonalcoholic steatohepatitis (NASH)/CAD had significantly worse survival than those with CAD or NASH alone ( P <0.01). After 6 mo, patients with CAD alone had similar survival to those with combined NASH/CAD. CONCLUSIONS: Patients with preexisting CAD before liver transplantation are at higher risk of death from any cause, specifically cardiovascular-related death. This risk increases with coexisting NASH. The presence of NASH and CAD at the time of liver transplant should prompt the initiation of aggressive risk factor modification for patients with CAD.
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Doença da Artéria Coronariana , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/cirurgia , Cirrose Hepática/cirurgia , Fatores de Risco , Estudos RetrospectivosRESUMO
Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and extracolonic tumors. Adenocarcinoma of the pancreas and hepatocellular carcinoma are rare in FAP. In this case series, we describe a mother and daughter with FAP who developed a hepatocellular carcinoma and solid pseudopapillary neoplasm of the pancreas, respectively.
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Adenocarcinoma , Polipose Adenomatosa do Colo , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/patologia , Pâncreas/patologia , Adenocarcinoma/patologiaRESUMO
INTRODUCTION: The COVID-19 pandemic has caused oncological services worldwide to face unprecedented challenges resulting in treatment disruption for surgical patients. Hepatopancreatico-biliary (HPB) cancers are characterised by rapid disease progression. This study aims to assess delays in receiving surgery for this patient cohort during the first COVID-19 wave. METHODS: Patients undergoing surgery between April and July 2020 (COVID-19 period) were compared with a control group from the preceding year. Delay in receiving surgery was defined as more than 50 days between referral and surgery date. Statistical analysis was carried out to evaluate predictors of delay and short-term outcomes. RESULTS: During the COVID-19 and pre-COVID-19 periods, 94 and 115 patients underwent surgery, respectively. No patients contracted COVID-19 postoperatively. Some 118 patients waited more than 50 days for surgery versus 91 who received surgery within 50 days from referral. Independent predictors for surgical delay were undergoing surgery in the COVID-19 era (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.2-4.1; p=0.015), referral pathway (OR 35.1, 95% CI 4.2-296; p=0.001) and presenting pathology (OR 8.3, 95% CI 1.2-56.1; p=0.03). Short-term outcomes were comparable between groups. CONCLUSIONS: Patient referral pathway and presenting pathology may contribute to delays in undergoing HPB cancer surgery during COVID-19 outbreaks. It is hoped that a better understanding of these factors will aid in designing shifts in healthcare policy during future pandemic outbreaks.
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Neoplasias do Sistema Biliar , Procedimentos Cirúrgicos do Sistema Biliar , COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Tempo para o TratamentoRESUMO
BACKGROUND: Patients undergoing simultaneous liver-kidney transplantation (SLK) have impaired native kidney function. The relative contribution of allograft versus native function after SLK is unknown. We sought to characterize the return of native kidney function following SLK. METHODS: Following SLK, patients underwent technetium-99 m-mercaptoacetyltriglycine renal scintigraphy following serum creatinine nadir. Kidney contributions to estimated glomerular filtration rate (eGFR) were determined. Patients with native kidney function at serum creatinine nadir contributing eGFR ≥30 versus <30 mL/min/1.73 m 2 were compared, and multiple linear regression analysis for native eGFR improvement was performed. RESULTS: Thirty-one patients were included in this analysis. Average native kidney contribution to overall kidney function following SLK was 51.1% corresponding to native kidney eGFR of 44.5 mL/min/1.73 m 2 and native kidney function eGFR improvement of 30.3 mL/min/1.73 m 2 ( P < 0.001). Twenty-six of 31 patients had native kidney contribution of eGFR ≥30 mL/min/1.73 m 2 . Hepatorenal syndrome as the sole primary etiology of kidney dysfunction was 100% specific for native kidney eGFR >30 mL/min/1.73 m 2 and predicted native eGFR improvement ( P = 0.03). CONCLUSIONS: Substantial improvement in native kidney function follows SLK, and hepatorenal syndrome as the sole primary etiology of kidney dysfunction is predictive of improvement. Whether such patients are suitable for liver transplant followed by surveillance with option for subsequent kidney transplants requires investigation.
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Síndrome Hepatorrenal , Transplante de Rim , Insuficiência Renal , Humanos , Transplante de Rim/efeitos adversos , Recuperação de Função Fisiológica , Creatinina , Rim/diagnóstico por imagem , Rim/cirurgia , Taxa de Filtração Glomerular , Cintilografia , Estudos RetrospectivosRESUMO
Primary sclerosing cholangitis (PSC) is a progressive liver disease for which there is no effective therapy. Hepatocytes and cholangiocytes from a PSC patient were cocultured with mesenchymal stem cells (MSCs) to assess in vitro change. A single patient with progressive PSC was treated with 150 million MSCs via direct injection into the common bile duct. Coculture of MSCs with cholangiocytes and hepatocytes showed in vitro improvement. Local delivery of MSCs into a single patient with progressive PSC was safe. Radiographic and endoscopic evaluation showed stable distribution of multifocal structuring in the early postoperative period. MSCs may be effective for the treatment of PSC.
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Colangite Esclerosante , Células-Tronco Mesenquimais , Humanos , Colangite Esclerosante/terapia , Células EpiteliaisRESUMO
Postcapillary pulmonary hypertension (PH) can be seen in cirrhosis. Research and treatment goals exist for patients with portopulmonary hypertension but not for postcapillary PH. The aim of this study was to investigate outcomes after liver transplant (LT) for patients with postcapillary PH. Methods: This was a retrospective cohort study of 1173 patients who underwent LT at our center between 2010 and 2020. Using a propensity score matched analysis followed by multivariable Cox modeling on matched patients, we compared post-LT survival between patients with and without postcapillary PH. We also compared several post-LT outcomes between patient with different types of PH. Results: Sixty-eight patients had PH, and 50 had postcapillary PH. The median age was 59 y and the sample was 54% male. There was no significant difference in mortality between patients with postcapillary PH and patients without PH (hazard ratio, 1.72; 95% confidence interval, 0.90-3.31; P = 0.10). There was no significant difference in survival between patients with any type of PH and those without PH. There was no significance difference in post-LT survival, acute kidney injury, or pulmonary edema between patients with different types of PH. Patients with postcapillary PH who survived had a higher cardiac output than those who died (11 L/min in patients who lived, as compared with 8 L/min in patients who died; P = 0.03). Conclusions: Postcapillary PH does not appear to convey a negative impact on post-LT survival. A higher cardiac output may be protective against mortality in patients with postcapillary PH.
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BACKGROUND: We aim to assess the diagnostic accuracy of procalcitonin (PCT) and interleukin-6 (IL-6) as diagnostic biomarkers for postoperative infection/sepsis following major abdominal surgery. Postoperative infection is an important cause for morbidity and mortality in major surgery. Early diagnosis and antimicrobial treatment improves outcomes, and high-performing biomarkers could guide clinical decision making. METHODS: A systematic database search was conducted for studies reporting diagnostic performance of biomarkers (including PCT and IL-6) for infection/sepsis following major abdominal surgery. Studies were assessed for reporting of diagnostic accuracy, relevance and quality. Data were extracted for meta-analysis. RESULTS: Ten studies with 1,611 participants reported the diagnostic accuracy of PCT, with pooled sensitivity, specificity and summary receiver operator curve of 72% (95% CI 66-78), 62% (95% CI 59-64) and 0.766, respectively. Four studies with 175 participants reported the diagnostic accuracy of IL-6, with pooled sensitivity, specificity and summary receiver operator curve of 84% (95% CI 72-92), 76% (95% CI 68-84) and 0.878, respectively There was variability in the timing of sampling and cut-off values and significant heterogeneity and inconsistency between studies (I2 diagnostic odds ratio (DOR)= 43.2% for PCT, I2 DOR=0% for IL-6). CONCLUSIONS: PCT performs only moderately well as a diagnostic test for postoperative infection/sepsis in major abdominal surgery, demonstrating limited sensitivity and specificity. Heterogeneity between studies is a limitation of the meta-analysis. There is an ongoing need for a rapid, accurate biomarker for postoperative infection or sepsis.
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Procedimentos Cirúrgicos do Sistema Digestório , Sepse , Biomarcadores , Humanos , Interleucina-6 , Complicações Pós-Operatórias/diagnóstico , Pró-Calcitonina/análise , Sepse/diagnósticoRESUMO
Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.
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Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: This paper examines the incidence, clinical presentation, and pathophysiology of portal vein thrombosis (PVT) in cirrhosis. Additionally, we have reviewed the literature regarding the current status of medical and interventional radiology management of PVT and have proposed a novel algorithm for the management given different clinical scenarios. Lastly two representative cases displaying endovascular treatment options are provided. Background: Portal vein thrombus in the setting of cirrhosis is an increasingly recognized clinical issue with debate on its pathophysiology, natural course, and optimal treatment. Approximately one-third of patients are asymptomatic, and detection of the thrombus is an incidental finding on imaging performed for other reasons. In 30% to 50% of patients, PVT resolves spontaneously. However, there is increased post-transplant mortality in patients with completely occlusive PVT, therefore effective early revascularization strategies are needed for patients with complete PVT who are expected to undergo liver transplant. Additionally, no consensus has been reached regarding PVT treatment in terms of timing and type of interventions as well as type and duration of anticoagulation. Methods: Computerized literature search as well as discussion with experts in the field. Conclusions: Management of PVT is complex, as many variables affect which treatments can be used. Anticoagulation appears to be the optimal first-line treatment in patients with acute PVT but without bleeding varices or mesenteric ischemia. Minimally invasive treatments include various methods of mechanical thrombectomy, chemical thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS) placement with or without variceal embolization. Definitive recommendations are difficult due to lack of high quality data and continued research is needed to evaluate the efficacy of different anticoagulants as well as the timing and use of various minimally invasive therapies in specific circumstances.
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Cardiovascular events have a major impact on overall outcomes after liver transplantation. Today's transplant patients are older than those in the past and therefore are more likely to have coexisting cardiac comorbidities. In addition, pathophysiologic effects of advanced liver disease on the circulatory system pose challenges in perioperative management. This review discusses important preoperative, intraoperative, and postoperative cardiac considerations in patients undergoing liver transplant.
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Hepatopatias , Transplante de Fígado , Coração , Humanos , Complicações Pós-Operatórias , Período Pós-OperatórioRESUMO
Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.
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Hepatite C Crônica , Hepatite C , Transplante de Fígado , Antivirais/uso terapêutico , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Cynometra travancorica, endemic to Western Ghats of India is pharmacologically similar to Saraca asoca and occasionally used as substitute in a well-known Ayurvedic uterine tonic Asokarishta. S. asoca possess various biological properties, but there are no reports on C. travancorica. The present study evaluated the pharmacological properties of C. travancorica and its efficacy in attenuating the sodium fluoride (NaF) induced oxidative stress in mice. METHODS: Antioxidant potential of methanolic extract of C. travancorica (CTE) stem bark was evaluated using DPPH, superoxide radical scavenging and total antioxidant assays. The effect of CTE on mitigating NaF deteriorated redox status in the liver tissue of mice was evaluated. Functional groups in CTE were analyzed by FTIR analysis. RESULTS: CTE effectively scavenged the free radicals in in vitro condition. CTE could augment catalase (46.6%), superoxide dismutase (53.8%) activities and GSH level (48.1%) against NaF induced decline in the liver tissue of mice. The peroxidation of lipids was found to be decreased by 44.9% and tissue damage abated as inferred by histopathology. FTIR analysis revealed the presence of biologically active functional groups in CTE. CONCLUSIONS: The study revealed the ameliorative effect of C. travancorica against NaF induced deleterious effect in experimental animals by its potent antioxidant potential.
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Fabaceae , Fluoreto de Sódio , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Peroxidação de Lipídeos , Camundongos , Estresse Oxidativo , Fluoreto de Sódio/farmacologia , Superóxido Dismutase/metabolismoRESUMO
Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial.
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Anemia , Telangiectasia Hemorrágica Hereditária , Anemia/tratamento farmacológico , Anemia/etiologia , Epistaxe/tratamento farmacológico , Epistaxe/etiologia , Humanos , Indazóis , Pirimidinas , Estudos Retrospectivos , Sulfonamidas , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/tratamento farmacológicoRESUMO
BACKGROUND Dobutamine stress echocardiography (DSE) is commonly used for cardiovascular assessment before orthotopic liver transplantation (OLT). The coronary artery calcium score (CACS) is a useful screening tool for coronary artery disease (CAD). We aimed to compare the sensitivity and specificity of DSE and CACS for CAD in OLT candidates. MATERIAL AND METHODS A total of 265 of the 1589 patients who underwent OLT at our center between 2008 and 2019 had preoperative coronary angiography (CAG). Of these, 173 had DSE and 133 had a CT scan suitable for CACS calculation within 1 year of OLT. Patients with a nondiagnostic DSE were excluded (n=100). Two reviewers evaluated CACS on CT scans. The sensitivity/specificity of DSE and CACS for detection of angiographically significant CAD were calculated for patients with both tests (n=36). A separate analysis compared the sensitivity/specificity of a diagnostic DSE (n=73) and CACS (n=133) against CAG for all patients with either test. RESULTS Sensitivity and specificity were 57.1% and 89.7%, respectively, for DSE, compared with 71.4% and 62.1% for CACS at ≥100 Agatston score. For the analysis of all patients with either test, the sensitivity/specificity of DSE for detection of CAD and CACS were 30.8% and 85.0% and 80.0% and 62.8%, respectively. On ROC analysis, CACS was a satisfactory predictor of obstructive CAD (AUC, 0.76±0.06, 95% CI, 0.66-0.87; P<0.001). CONCLUSIONS CACS may be an important tool for cardiovascular assessment in patients undergoing OLT. DSE was nondiagnostic in a large percentage of OLT candidates, limiting its use in this population.
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Doença da Artéria Coronariana , Transplante de Fígado , Cálcio , Doença da Artéria Coronariana/diagnóstico por imagem , Dobutamina , Ecocardiografia sob Estresse , Humanos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: As the population of the United States ages, there has been an increasing number of elderly patients with cirrhosis listed for transplant. Previous studies have shown variable results in terms of the relative survival benefit for elderly liver transplant (LT) recipients. There may be factors that are associated with a poor post-transplant outcome which may help determine which elderly patients should and should not be listed for LT. AIM: To identify factors associated with futility of transplant in elderly patients. METHODS: This was a retrospective study of all patients above the age of 45 who underwent liver transplantation at our tertiary care center between January 2010 and March 2020 (n = 1019). "Elderly" was defined as all patients aged 65 years and older. Futile outcome was defined as death within 90 d of transplant. Logistic regression analysis was performed to determine what variables, if any were associated with futile outcome in elderly patients. Secondary outcomes such as one year mortality and discharge to facility (such as skilled nursing facility or long-term acute care hospital) were analyzed in the entire sample, compared across three age groups (45-54, 55-64, and 65 + years). RESULTS: There was a total of 260 elderly patients who received LT in the designated time period. A total of 20 patients met the definition of "futile" outcome. The mean Model of End-Stage Liver Disease scores in the futile and non-futile group were not significantly different (21.78 in the futile group vs 19.66 in the "non-futile" group). Of the variables tested, only congestive heart failure was found to have a statistically significant association with futile outcome in LT recipients over the age of 65 (P = 0.001). Of these patients, all had diastolic heart failure with normal ejection fraction and at least grade I diastolic dysfunction as measured on echocardiogram. Patients aged 65 years and older were more likely to have the outcomes of death within 1 year of LT [hazard ratio: 1.937, confidence interval (CI): 1.24-3.02, P = 0.003] and discharge to facility (odds ratio: 1.94, CI: 1.4-2.8, P < 0.001) compared to patients in younger age groups. CONCLUSION: Diastolic heart failure in the elderly may be a predictor of futility post liver transplant in elderly patients. Elderly LT recipients may have worse outcomes as compared to younger patients.