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BACKGROUND: There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA. METHODS: This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively. RESULTS: The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m2, respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories. CONCLUSIONS: Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered.
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BACKGROUND: Alcohol cessation is the only intervention that both prevents and halts the progressions of alcohol-associated liver disease. The aim of this study was to assess the relationship between a return to alcohol use and consultation with hepatology in treatment-seeking patients with alcohol use disorder (AUD). METHODS: Two hundred forty-two patients with AUD were enrolled in an inpatient treatment program, with hepatology consultation provided for 143 (59%) patients at the request of the primary team. Patients not seen by hepatology served as controls. The primary outcome was any alcohol use after discharge assessed using AUDIT-C at 26 weeks after discharge. RESULTS: For the primary endpoint, AUDIT at week 26, 61% of the hepatology group and 28% of the controls completed the questionnaire (p=0.07). For the secondary endpoint at week 52, these numbers were 22% and 11% (p = 0.6). At week 26, 39 (45%) patients in the hepatology group versus 31 (70%) controls (p = 0.006) returned to alcohol use. Patients evaluated by hepatology had decreased rates of hazardous alcohol use compared to controls, with 36 (41%) versus 29 (66%) (p = 0.008) of the patients, respectively, reporting hazardous use. There were no significant differences in baseline characteristics between groups and no difference in rates of prescribing AUD therapy. There was no difference in outcomes at 52 weeks. CONCLUSIONS: Patients evaluated by hepatology had significantly lower rates of return to alcohol use and lower rates of hazardous drinking at 26 weeks but not at 52 weeks. These findings suggest that hepatology evaluation during inpatient treatment of AUD may lead to decreased rates of early return to alcohol use.
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Alcoolismo , Gastroenterologia , Hepatopatias Alcoólicas , Humanos , Alcoolismo/epidemiologia , Alcoolismo/terapia , Alta do Paciente , Pacientes Internados , Hepatopatias Alcoólicas/terapia , Encaminhamento e ConsultaRESUMO
Alcohol-related liver disease (ALD) is the leading indication for liver transplantation worldwide. Since Mathurin et al. described their experience in providing early liver transplantation for patients with ALD in 2011, other centers have followed suit with generally favorable survival outcomes. This patient population poses a unique clinical challenge given the expedited nature of the evaluation and the lack of any significant sobriety period prior to transplantation. The SALT (Sustained Alcohol Use Post-Liver Transplant) score is a standardized psychometric tool increasingly used to help stratify the risk of relapse and guide listing decisions for these challenging clinical situations. In 2018, our center introduced a protocol for early liver transplantation for acute alcohol-related hepatitis (AAH). In this article, we offer a retrospective review of 26 patients transplanted between May 2018 and May 2021, including at least 1-year follow-up, and compare outcomes to initial SALT scores; we further identify additional factors that may impact post-transplant success. As transplant committees continue to weigh the ethical dilemma of denying lifesaving treatment against the obligation to remain stewards of a limited resource, we aim to contribute to a more nuanced understanding of risk regarding early transplantation for ALD.
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Hepatite Alcoólica , Hepatopatias Alcoólicas , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Hepatite Alcoólica/etiologia , Hepatite Alcoólica/cirurgia , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/cirurgia , Consumo de Bebidas Alcoólicas , RecidivaRESUMO
BACKGROUND AND AIMS: The widespread use of peroral endoscopic myotomy (POEM) has revolutionized the management of esophageal motility disorders (EMDs). The introduction of an endoluminal functional lumen imaging probe (EndoFLIP) can serve as a complimentary diagnostic tool to assess the mechanical properties (i.e., pressure, diameter, distensibility and topography) of the esophagus. During EndoFLIP measurements, different anesthesia techniques may induce variable degrees of neuromuscular blockade, potentially affecting esophageal motility and altering the results of EndoFLIP metrics. Our study aimed to compare the impact of using total intravenous anesthesia (TIVA) versus general anesthesia with inhalational anesthetics (GAIA) on diagnostic EndoFLIP measurements. METHODS: We conducted a retrospective study of all adult patients (≥18 years) undergoing EndoFlip during the POEM procedure at our institution between February 2017 and February 2022. We obtained the differences in pressure, diameter, and distensibility index using propofol-based TIVA vs sevoflurane-based GAIA with a 30ml and 60ml balloon. The differences were divided into terciles and compared between diagnoses using univariate comparisons and logistic regression models. RESULTS: 49 patients were included (39% Type 1 achalasia, 43% Type 2 or 3 achalasia, and 18% jackhammer esophagus (JE)). Compared to spastic disorders (Type 2, 3 and JE), Type 1 had lower values of pressure differences at 60 mL in univariate (3.75 vs 15.20 p=0.001) and multivariate (aOR 0.89 95%CI 0.82-0.978) analyses. Compared to Type 1, Type 2 and 3 had higher rates of pressure differences at 60 mL in univariate (9.85 vs 3.75 p=0.04); and nearly reached significance in multivariate analysis (1.09 95%CI 1-1.20). Compared to Type 1, JE demonstrated higher values in pressure differences at 60 mL (27.7 vs 3.75 p<0.001) CONCLUSION: Esophageal pressure, as measured by EndoFLIP, was significantly reduced when patients were sedated with sevoflurane-based GAIA. The use sevoflurane-based GAIA for diagnostic EndoFLIP may potentially lead to the misclassification of spastic disorders as Type I achalasia. Therefore, propofol-based TIVA should be considered over sevoflurane-based GAIA for sedation during the diagnostic test.
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Background: Proton beam therapy (PBT) is a non-surgical treatment that spares adjacent tissues compared to photon radiation and useful for Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We present a single center experience in HCC and iCCA treated with Pencil Beam Scanning (PBS) PBT. Methods: Forty-four consecutive patients (22 patients in each group) receiving PBT were included and reviewed. PBT was delivered with hypofractionated or stereotactic body radiation therapy (SBRT) using PBS. Tumor size was approximated by clinical target volume (CTV). Outcomes were evaluated with Kaplan-Meier and liver toxicity was determined by MELD-Na and albumin-bilirubin (ALBI) grade. Results: Median follow up was 38.7 months, fourteen (35%) had multifocal disease and median CTV was 232.5cc. Four (9%) and 40 (91%) patients received SBRT and hypofractionated radiation, respectively. Two year overall survival was statistically higher for HCC (entire group: 68.9% months [95% CI: 61.3 - 76.3%]; iCCA: 49.8% [95% CI: 38.5% - 61.1%]; HCC: 89.4% [95% CI: 82.3 - 96.5%]; P <0.005). There was no statistical difference in progression-free survival or freedom from local failure. Biologically Equivalent Dose (BED) was greater than or equal to 80.5Gy in 37 (84%) patients. All iCCA patients had stable or improved ALBI grade following treatment. ALBI grade was stable in 83% of HCC patients and average MELD-Na score remained stable. Tumor size, pretreatment liver function, and total radiation dose were not associated with liver toxicity. Conclusions: PBT for unresectable HCC and iCCA is safe and effective, even for large and multifocal tumors. Liver function was preserved even in those with baseline cirrhosis in this advanced population with large tumors.
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Chronic granulomatous disease (CGD) is a rare inborn error of immunity, resulting from a defect in nicotinamide adenine dinucleotide phosphate oxidation and decreased production of phagocyte reactive oxygen species. The main clinical manifestations are recurrent infections and chronic inflammatory disorders. Current approaches to management include antimicrobial prophylaxis and control of inflammatory complications. Hematopoietic stem cell transplantation or gene therapy can provide definitive treatment. Gastrointestinal and hepatic manifestations are common in CGD and include structural changes, dysmotility, CGD-associated inflammatory bowel disease, liver abscesses, and noncirrhotic portal hypertension. The findings can be heterogeneous, and the management is complex in light of the underlying immune dysfunction. This review describes the various clinical findings and the latest studies in management of gastrointestinal and hepatic manifestations in CGD, as well as the management experience at the National Institutes of Health.
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Doença Granulomatosa Crônica , Transplante de Células-Tronco Hematopoéticas , Hipertensão Portal , Humanos , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/terapia , Doença Granulomatosa Crônica/genética , Trato Gastrointestinal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , NADPH Oxidases/genéticaRESUMO
INTRODUCTION: The growing practice of living liver donation requires comprehensive understanding of the financial implications for living liver donors. While obtaining and maintaining insurance is important to financial health, little is known about the impact of liver donation on future insurability. RESEARCH QUESTIONS: The purpose of this study was to evaluate the donors' experiences with insurance following donation and identify the insurance provider-driven factors that contribute to donor insurability. DESIGN: A two center cohort of living donors with donation between January 2000 and December 2018 (N = 442) were surveyed about postdonation insurance experiences. To understand insurance provider practices towards liver donors, life (n = 11) and disability (n = 4) insurance underwriters were asked to provide policy quotes for a standardized living liver donor profile. RESULTS: Responses (N = 101) were received by August 2020 (response rate = 22.9%). Living liver donors reported owning life (58%), disability (35%), and medical (87%) insurance at rates comparable to the general population with low proportions reporting difficulty obtaining these insurance types (9%, 9%, 4%, respectively). Post-donation life insurance ownership was associated with post-donation employment (P = 0.01). Underwriter responses indicate life and disability insurability were adversely affected up to 12 months following donation. CONCLUSIONS: Living liver donors did not have difficulty maintaining insurance in the long-term but should be counseled to purchase insurance prior to surgery as short-term insurability may be affected. Perception of difficulty obtaining insurance following donation remains of significant concern among living donors. Further collaboration between the transplant community and insurance companies is warranted.
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Transplante de Fígado , Doadores Vivos , Humanos , Inquéritos e Questionários , Emprego , FígadoRESUMO
Purpose: To evaluate the performance of a deep learning (DL) model that measures the liver segmental volume ratio (LSVR) (ie, the volumes of Couinaud segments I-III/IV-VIII) and spleen volumes from CT scans to predict cirrhosis and advanced fibrosis. Materials and Methods: For this Health Insurance Portability and Accountability Act-compliant, retrospective study, two datasets were used. Dataset 1 consisted of patients with hepatitis C who underwent liver biopsy (METAVIR F0-F4, 2000-2016). Dataset 2 consisted of patients who had cirrhosis from other causes who underwent liver biopsy (Ishak 0-6, 2001-2021). Whole liver, LSVR, and spleen volumes were measured with contrast-enhanced CT by radiologists and the DL model. Areas under the receiver operating characteristic curve (AUCs) for diagnosing advanced fibrosis (≥METAVIR F2 or Ishak 3) and cirrhosis (≥METAVIR F4 or Ishak 5) were calculated. Multivariable models were built on dataset 1 and tested on datasets 1 (hold out) and 2. Results: Datasets 1 and 2 consisted of 406 patients (median age, 50 years [IQR, 44-56 years]; 297 men) and 207 patients (median age, 50 years [IQR, 41-57 years]; 147 men), respectively. In dataset 1, the prediction of cirrhosis was similar between the manual versus automated measurements for spleen volume (AUC, 0.86 [95% CI: 0.82, 0.9] vs 0.85 [95% CI: 0.81, 0.89]; significantly noninferior, P < .001) and LSVR (AUC, 0.83 [95% CI: 0.78, 0.87] vs 0.79 [95% CI: 0.74, 0.84]; P < .001). The best performing multivariable model achieved AUCs of 0.94 (95% CI: 0.89, 0.99) and 0.79 (95% CI: 0.71, 0.87) for cirrhosis and 0.8 (95% CI: 0.69, 0.91) and 0.71 (95% CI: 0.64, 0.78) for advanced fibrosis in datasets 1 and 2, respectively. Conclusion: The CT-based DL model performed similarly to radiologists. LSVR and splenic volume were predictive of advanced fibrosis and cirrhosis.Keywords: CT, Liver, Cirrhosis, Computer Applications-Detection/Diagnosis Supplemental material is available for this article. © RSNA, 2022.
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Hepatitis delta virus (HDV) infection is associated with accelerated progression of liver disease to cirrhosis. Shear wave elastography (SWE) is a non-invasive evaluation method of liver fibrosis. Its performance in accurately characterizing HDV fibrosis compared to other noninvasive markers remains unknown. We assessed the performance of SWE in patients with chronic HDV, Hepatitis B (HBV) and Hepatitis C (HCV) infection. Cirrhosis was determined by histology or clinical data. Area under receiver operator characteristics (AUROC) was used to assess diagnostic performance in identifying cirrhosis by SWE in comparison with Fibroscan® (VCTE) and serologic tests of fibrosis. 158 patients with chronic hepatitis (HDV:44%, HBV: 46% and HCV: 29%) were evaluated. Cirrhosis was diagnosed in 28 (17.7%) patients. Mean noninvasive fibrosis measurements for the HBV/HCV and HDV groups, respectively, were as follows: APRI: 0.73 ± 1.08 and 1.3 ± 1.38; FIB-4: 1.90 ± 2.24 and 2.33 ± 2.24; VCTE: 8.9 ± 6.7 kPa vs 10.4 ± 5.3 kPa; SWE: 1.5 ± 0.2 m/s and 1.6 ± 0.2 m/s. The performance of SWE in detecting HDV-induced cirrhosis (AUROC 0.84, 95% CI 0.71-0.97) was slightly lower than in HBV/HCV induced disease (AUROC 0.88, 95% CI 0.81-0.96). For HDV patients, the performance of SWE was comparable to VCTE and slightly better than APRI and FIB-4 especially in APRI and FIB-4 indeterminate zones. The overall less accurate performance of noninvasive markers in HDV in comparison with HBV and HCV may be a result of significant hepatic inflammation in HDV.
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Técnicas de Imagem por Elasticidade , Hepatite C , Hepatite D Crônica , Humanos , Técnicas de Imagem por Elasticidade/métodos , Hepatite D Crônica/diagnóstico , Vírus Delta da Hepatite , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Biomarcadores , Hepatite C/patologia , Fígado/diagnóstico por imagem , Fígado/patologiaRESUMO
OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.
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Doenças Hereditárias Autoinflamatórias , NF-kappa B , Proteínas Quinases/genética , Amiloidose , Animais , Estudos de Coortes , Mutação com Ganho de Função , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Inflamação/genética , Camundongos , Mutação , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Quinases/metabolismo , Qualidade de Vida , Proteína Amiloide A Sérica , Síndrome , Inibidores do Fator de Necrose TumoralRESUMO
Hepatic chronic graft-versus-host disease (cGVHD) causes morbidity and current diagnostic criteria are nonspecific. An accurate diagnosis is imperative because overdiagnosis can lead to unnecessary treatment with immunosuppressive agents and raising the risk of opportunistic infections. We aim to characterize different patterns of liver injury and cytokine profiles associated with hepatic dysfunction in cGVHD, to evaluate the accuracy of the NIH Consensus Criteria (NCC) for hepatic cGVHD and to explore predictors for hepatic cGHVD. Patients were evaluated in this prospective cross-sectional study of patients with cGVHD recruited under a natural history protocol. Laboratory tests and cytokines were measured. The cGVHD were diagnosed and scored based on NCC. Clinically indicated liver biopsy specimens or autopsies were reviewed by an expert hepatopathologist (D.E.K.). Comparisons were made between groups, and univariable and multivariable logistic regression were calculated. Of the 302 patients enrolled, 151 fulfilled hepatic cGVHD based on NCC; however, 69% had at least 1 abnormal liver test result. Abnormal alanine aminotransferase (ALT) and aspartate aminotransferase were associated with lower platelets, higher total bilirubin (TB), total cholesterol, serum amyloid A, and IL 15. Abnormal ALP and gamma-glutamyl transpeptidase were associated with higher cholesterol, and IL7. Lower platelet count was associated with higher ALT, TB, and triglycerides and lower albumin. Of the 27 with liver tissue, 16 had histologic features of GVHD, only eight met clinical criteria for hepatic GVHD. Sensitivity and specificity of NCC in identifying hepatic GVHD were 50% and 27% (Kappa = -0.23). Only 6 had only hepatic GVHD, whereas 10 had hepatic GVHD with either iron overload, nodular regenerative hyperplasia, or steatosis. Multivariable logistic regression showed that ALP and total cholesterol were associated with hepatic GVHD and total cholesterol >220 mg/dL increased the sensitivity for histologic hepatic GVHD. In conclusion, abnormal liver enzymes in cGVHD are nonspecific and have poor correlation with histologic evidence for hepatic GVHD, highlighting the importance of histology. Cytokines provide insight into the pathogenesis of hepatic cGVHD. Decreased platelet count was associated with factors associated with liver disease including portal vein diameter, which may suggest progression of liver disease. This highlights the need of incorporating these factors in natural history study and using liver biopsy to understand the development of liver dysfunction in hematopoietic stem cell transplantation and to develop better instruments to decreased hepatic cGVHD related morbidity and mortality. The study was registered with a ClinicalTrials.gov identifier NCT00092235.
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Doença Enxerto-Hospedeiro , Hepatopatias , Humanos , Doença Enxerto-Hospedeiro/diagnóstico , Consenso , Estudos Transversais , Estudos Prospectivos , Doença Crônica , Hepatopatias/diagnóstico , Citocinas/uso terapêutico , Colesterol/uso terapêuticoRESUMO
Hepatic graft-versus-host disease (HGVHD) contributes significantly to morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Clinical findings and liver biomarkers are neither sensitive nor specific. The relationship between clinical and histologic diagnoses of HGVHD was assessed premortem and at autopsy. Medical records from patients who underwent HSCT at the National Institutes of Health (NIH) Clinical Center between 2000 and 2012 and expired with autopsy were reviewed, and laboratory tests within 45 days of death were divided into 15-day periods. Clinical diagnosis of HGVHD was based on Keystone Criteria or NIH Consensus Criteria, histologic diagnosis based on bile duct injury without significant inflammation, and exclusion of other potential etiologies. We included 37 patients, 17 of whom had a cholestatic pattern of liver injury and two had a mixed pattern. Fifteen were clinically diagnosed with HGVHD, two showed HGVHD on autopsy, and 13 had histologic evidence of other processes but no HGVHD. Biopsy or clinical diagnosis of GVHD of other organs during life did not correlate with HGVHD on autopsy. The diagnostic accuracy of the current criteria was poor (κ = -0.20). A logistic regression model accounting for dynamic changes included peak bilirubin 15 days before death, and an increase from period -30 (days 30 to 16 before death) to period -15 (15 days before death) showed an area under the receiver operating characteristic curve of 0.77. Infection was the immediate cause of death in 68% of patients. In conclusion, liver biomarkers at baseline and GVHD elsewhere are poor predictors of HGVHD on autopsy, and current clinical diagnostic criteria have unsatisfactory performance. Peak bilirubin and cholestatic injury predicted HGVHD on autopsy. A predictive model was developed accounting for changes over time. Further validation is needed.
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Colestase , Doença Enxerto-Hospedeiro , Bilirrubina , Biomarcadores , Colestase/diagnóstico , Estado Terminal , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Fígado/patologiaAssuntos
Hemangioendotelioma Epitelioide , Hepatite C , Neoplasias Hepáticas , Transplante de Fígado , Hemangioendotelioma Epitelioide/patologia , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversosRESUMO
OBJECTIVE: The model for end-stage liver disease (MELD) score can be used to predict survival of patients undergoing transjugular intrahepatic portosystemic shunt procedures (TIPS). The effect of hyponatremia on survival resulted in the development of the MELD-Na score. The aim of this study is to compare the prognostic value of MELD and MELD-Na scores in predicting post-TIPS outcomes. METHODS: A retrospective chart review was performed on consecutive patients with cirrhosis who underwent TIPS placement from 2012 to 2017. Indications for TIPS were either refractory ascites or variceal bleeding. Primary outcomes analyzed were death or liver transplantation. Follow-up data were censored at 1 year. RESULTS: Eighty-three patients underwent TIPS. There was no difference in MELD or MELD-Na score between indication groups. However, the delta MELD (MELD-Na subtracted by MELD score) was higher in those with refractory ascites. There was no difference in outcomes of death or liver transplantation between the MELD and MELD-Na at 1 year. (area under the curve 0.79 vs 0.72, respectively, P = 0.119). In patients with a MELD-Na greater than 18, higher delta MELD was protective (hazard ratio 0.74, P < 0.05). CONCLUSIONS: There was no prognostic difference using either score despite a higher delta MELD in those with refractory ascites. The decision to pursue TIPS should utilize the original MELD score, as the MELD-Na score alone may exclude patients with refractory ascites who may benefit from TIPS.
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Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Derivação Portossistêmica Transjugular Intra-Hepática , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Systems composed of soft matter (e.g., liquids, polymers, foams, gels, colloids, and most biological materials) are ubiquitous in science and engineering, but molecular simulations of such systems pose particular computational challenges, requiring time and/or ensemble-averaged data to be collected over long simulation trajectories for property evaluation. Performing a molecular simulation of a soft matter system involves multiple steps, which have traditionally been performed by researchers in a "bespoke" fashion, resulting in many published soft matter simulations not being reproducible based on the information provided in the publications. To address the issue of reproducibility and to provide tools for computational screening, we have been developing the open-source Molecular Simulation and Design Framework (MoSDeF) software suite. In this paper, we propose a set of principles to create Transparent, Reproducible, Usable by others, and Extensible (TRUE) molecular simulations. MoSDeF facilitates the publication and dissemination of TRUE simulations by automating many of the critical steps in molecular simulation, thus enhancing their reproducibility. We provide several examples of TRUE molecular simulations: All of the steps involved in creating, running and extracting properties from the simulations are distributed on open-source platforms (within MoSDeF and on GitHub), thus meeting the definition of TRUE simulations.
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Using molecular dynamics simulations, it is demonstrated that a partial coating of single-stranded DNA (ssDNA) reduces the penetration depth of a graphene nanoflake (GNF) into a phospholipid bilayer by attenuating the hydrophobic force that drives the penetration. As the GNF penetrates the bilayer, the ssDNA remains adsorbed to the GNF outside of the bilayer where it shields the graphene from the surrounding water. The penetration depth is found to be controlled by the amount of ssDNA coating the GNF, with a sparser coating resulting in a deeper penetration since the ssDNA shields less of the GNF surface. As the coating density is increased, the likelihood of the GNF entering the bilayer is reduced where it instead tends to lie flat on the bilayer surface with the sugar phosphate backbone of ssDNA interacting with the hydrophilic lipid head groups. While no bilayer disruption is observed for a partially inserted ssDNA-coated GNF, a larger, bare, partially inserted GNF is found to preferentially extract phospholipids from the bilayer, offering further evidence of lipid extraction as a main cytotoxicity mechanism of GNFs. Therefore, a coating of ssDNA may reduce the cytotoxicity of GNFs by shielding the unfavorable graphene-water interaction, thus preventing graphene penetration and lipid extraction.
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DNA de Cadeia Simples/química , Grafite/química , Bicamadas Lipídicas/química , Nanocompostos/química , Fosfolipídeos/química , Simulação de Dinâmica MolecularRESUMO
Systemic amyloidosis is a rare condition that can manifest with cardiomyopathy, hepatic dysfunction, and renal disease. Diagnosis is often missed and/or delayed due to chronic multi-system involvement and indeterminate signs and symptoms. Treatment generally involves systemic therapy and autologous stem-cell transplantation.