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Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.
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Insuficiência Cardíaca , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Medição de Risco , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , TransplantadosRESUMO
Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.
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Insuficiência Hepática Crônica Agudizada/terapia , Cuidados Críticos/métodos , Encefalopatia Hepática/terapia , Síndrome Hepatopulmonar/terapia , Síndrome Hepatorrenal/terapia , Hipertensão Pulmonar/terapia , Cirrose Hepática/terapia , Insuficiência Hepática Crônica Agudizada/etiologia , Terapia Combinada , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Encefalopatia Hepática/etiologia , Síndrome Hepatopulmonar/etiologia , Síndrome Hepatorrenal/etiologia , Humanos , Hipertensão Pulmonar/etiologia , Cirrose Hepática/fisiopatologia , Transplante de FígadoRESUMO
Efficacy and Safety of intravenous albumin for non-spontaneous bacterial peritonitis infection among patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials INTRODUCTION: Bacterial infection is a common cause of acute-on-chronic liver failure (ACLF) and death among cirrhosis. The benefit of intravenous (IV) albumin among cirrhosis with non-SBP infection remains unclear as individual studies are underpowered to detect the survival benefit of IV albumin. AIM: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous albumin for non-SBP infection among cirrhosis patients. METHODS: We performed a systematic search of electronic databases (Pubmed, MEDLINE and Clinicalkey) up to 1st December 2019. Studies evaluating IV albumin for non-SBP infection were selected. Using random effect model, the pooled odds ratio (OR), 95% confidence interval (95%CI) and heterogeneity were assessed. RESULTS: A total of 3 RCTs (406 subjects) fulfilling the inclusion criteria among 218 citations were identified. There was no significant heterogeneity across included studies. In this meta-analysis, we found that the pooled risk of renal impairment (RI) (OR=0.58, 95%CI: 0.28-1.23, I2=0%), mortality at 30 days (OR=1.61, 95%CI: 0.87-3.00, I2=0%) as well as mortality at 90 days (OR=1.30, 95%CI: 0.81-2.07, I2=0%) were similar between albumin and control group. Pooled event of pulmonary edema occurred more commonly in albumin group (OR 5.17, 95%CI 1.62-16.47, I2=0%). More subjects achieved resolution of ACLF in IV albumin group as compared to control group (OR=0.11, 95%CI: 0.02-0.69, p=0.02). CONCLUSION: Albumin did not reduce the risk of RI and mortality, yet increases the risk of pulmonary edema. Albumin may promote recovery of ACLF, however, more data is required to validate this benefit.
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Albuminas/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Peritonite/tratamento farmacológico , Injúria Renal Aguda/etiologia , Insuficiência Hepática Crônica Agudizada/etiologia , Administração Intravenosa , Idoso , Albuminas/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/etiologia , Infecções Bacterianas/mortalidade , Humanos , Cirrose Hepática/complicações , Pessoa de Meia-Idade , Peritonite/etiologia , Peritonite/mortalidade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Through detailed analyses of the National Health and Nutrition Examination Survey, the Nationwide Inpatient Sample, and the United Network for Organ Sharing registry, the authors provide a view of the epidemiology of the spectrum of alcohol liver disease (ALD) in the United States. Although the prevalence of ALD among the general population has been relatively stable at 8%, over the last decade, there has been an increase in ALD with advanced fibrosis, including increased hospitalizations for liver cirrhosis and its complications, and an increase in ALD as a cause for liver transplant listing, as well as a greater proportion of liver cancer cases associated with ALD.
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Hepatopatias Alcoólicas , Transplante de Fígado , Humanos , Cirrose Hepática , Inquéritos Nutricionais , Estudos Retrospectivos , Estados UnidosRESUMO
Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] >5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End-Stage Liver Disease score of 8 (range 6-15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] -1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] -3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase-3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect.
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Hipertensão Portal/tratamento farmacológico , Ácidos Pentanoicos/uso terapêutico , Pressão na Veia Porta/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Caspase 3/sangue , Feminino , Humanos , Hipertensão Portal/sangue , Hipertensão Portal/etiologia , Queratina-18/sangue , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Ácidos Pentanoicos/farmacologiaRESUMO
Indications for liver transplant have been extended, and older and sicker patients are undergoing transplantation. Infectious, malignant, and cardiovascular diseases account for the most posttransplant deaths. Cirrhotic patients can develop heart disease through systemic diseases affecting the heart and the liver, cirrhosis-specific heart disease, or common cardiovascular. No single factor can predict posttransplant cardiovascular complications. Patients with history of cardiovascular disease, and specific abnormalities on echocardiography, electrocardiography, or serum markers of heart disease seem to be at increased risk of complications. Pretransplant cardiovascular evaluation is essential to detecting these risk factors so their effects can be mitigated through appropriate intervention.
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Doenças Cardiovasculares , Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Medição de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Saúde Global , Humanos , Incidência , Prognóstico , Fatores de RiscoRESUMO
Biliary mucoceles after deceased donor liver transplantation are a rarity, and mucoceles mimicking a gallbladder from the recipient remnant cystic duct have not been described until this case. We describe a 48-year-old male who presented with right upper quadrant pain and was found to have a recipient cystic duct mucocele 3 mo after receiving a deceased donor liver transplant. We describe the clinical presentation, laboratory and imaging findings (including the appearance of a gallbladder), multidisciplinary approach and surgical resolution of this mucocele originating from the recipient cystic duct, and a review of the literature.
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INTRODUCTION: Hepatitis C virus (HCV) infection in kidney transplant (KTX) patients reduces long-term patient and graft survival. Direct-acting antivirals (DAA) are > 90% effective in achieving sustained viral response (SVR); however, DAAs are not routinely available to patients with end-stage renal disease (ESRD). The University of Utah Transplant Program developed a protocol to allow HCV-positive potential KTX recipients to accept HCV-positive donors' kidneys. Three months after successful KTX, they were eligible for DAA therapy. METHODS: HCV-positive patients approved for KTX by the University of Utah Transplant Selection Committee were eligible to be enrolled in this study. Patients consented for the use of HCV-positive donor organs. Three to six months after successful KTX, these patients were treated for HCV with interferon-free direct-acting antiviral regimens according to viral genotype and prior treatment experience. RESULTS: Between 2014-2015, 12 HCV-positive patients were listed for KTX. Eight patients were kidney only eligible, seven patients received HCV-positive deceased donor kidneys, and one received an HCV-negative organ. Currently, six patients have completed treatment, all have achieved sustained viral response (SVR), and one patient is currently awaiting treatment. All seven patients have functioning kidney grafts. Wait time for KTX was reduced amongst all blood groups from an average of 1,350 days to only 65 days. CONCLUSIONS: HCV-positive patients with ESRD can successfully receive an HCV-positive donor's kidney. Once transplanted, these patients can receive DAA therapy and achieve SVR. Use of HCV-positive organs reduced time on the waitlist by greater than three years and expanded the donor organ pool.
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BACKGROUND AND OBJECTIVES: Biliary tract cancers (BTC) including, cholangiocarcinoma (CC) and gallbladder cancer (GBC), are rare and highly fatal malignancies. The etiology and inherited susceptibility of both malignancies are poorly understood. We quantified the risk of BTC in first-degree (FDR), second-degree (SDR), and first cousin (FC) relatives of individuals with BTC, stratified by tumor subsite. METHODS: BTC diagnosed between 1980 and 2011 were identified from the Utah Cancer Registry and linked to pedigrees from the Utah Population Database. Age- and gender-matched BTC-free controls were selected to form the comparison group for determining BTC risk in relatives using Cox regression analysis. RESULTS: Of the 1302 index patients diagnosed with BTC, 550 (42.2 %) were located in the gallbladder and 752 (57.8 %) were cholangiocarcinomas. There was no elevated risk of BTC (all subsites combined) in FDRs (HR 0.94, 95 % CI 0.29-3.0), SDRs (HR 0.25, 95 % CI 0.06-1.03), and FCs (HR 0.96, 95 % CI 0.61-1.51) of BTC cases compared to cancer-free controls. Similarly, no increased familial risk of GBC or CC was found in relatives of BTC patients stratified by tumor subsite compared to relatives of controls. CONCLUSIONS: Relatives of BTC patients are not at an increased risk of GBC or CC in a statewide population. This suggests that biliary tract cancer risk is not associated with a familial predisposition and may be mitigated more strongly by environmental modifiers.
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Adenocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Família , Neoplasias da Vesícula Biliar/genética , Linhagem , Sistema de Registros , Adenocarcinoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/epidemiologia , Ductos Biliares Extra-Hepáticos , Ductos Biliares Intra-Hepáticos , Neoplasias do Sistema Biliar/epidemiologia , Neoplasias do Sistema Biliar/genética , Colangiocarcinoma/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Utah/epidemiologia , Adulto JovemRESUMO
Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation.
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Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Alcoolismo/epidemiologia , Hepatite Alcoólica/cirurgia , Humanos , Hepatopatias Alcoólicas/epidemiologia , Seleção de Pacientes , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to define liver shear stiffness by magnetic resonance elastography (MRE) that distinguishes normal from abnormal liver biopsy, especially when steatosis ≥20%, among potential live liver donors. METHODS: Baseline clinical, laboratory, imaging, MRE, and liver biopsy results were recorded. Using MRE, hepatic shear stiffness in kilopascals (kPa) was measured and compared to liver biopsy. Comparison between groups was done using χ(2) or Fisher's exact test for categorical variables and Wilcoxon test for continuous variables. Receiver operating characteristic (ROC) curve was calculated to assess diagnostic accuracy. Statistical significance was set at p < 0.05. RESULTS: 38 healthy adults were included. Liver biopsy was normal in 27 and abnormal in 11. ROC curve for MRE defined optimal cutoff at 2.6 kPa (sensitivity 0.72, specificity 0.85, AUC 0.81) to distinguish these 2 groups. Hepatic steatosis ≥20% on biopsy is a contraindication for liver donation in our center. We evaluated the ability of MRE to distinguish this degree of steatosis: 8 persons had steatosis ≥20% and were excluded from donation. ROC curve for MRE defined optimal cutoff at 2.82 kPa (sensitivity 0.88, specificity 1, AUC 0.98) to identify this group. CONCLUSIONS: Liver stiffness measured by MRE, even in the absence of liver fibrosis, can be useful in differentiating normal from abnormal liver histology, and most importantly in patients under evaluation for live liver donation, can very accurately distinguish those with complicated hepatic steatosis ≥20%, our cutoff for donation. In the future, MRE might provide supplementary information to make liver biopsy unnecessary in the donor evaluation process.
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Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/patologia , Fígado/patologia , Doadores Vivos , Imageamento por Ressonância Magnética/métodos , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos TestesAssuntos
Antivirais/uso terapêutico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Administração Oral , Antivirais/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Humanos , Cirrose Hepática/etiologia , Recidiva , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Sofosbuvir , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapêuticoRESUMO
Constipation is one of the most frequent gastrointestinal disorders encountered in clinical practice in Western societies. Its prevalence increases with age and is more frequently reported in female patients. Chronic constipation has been associated with considerable impairment in quality of life, can result in large individual healthcare costs, and represents a burden to healthcare delivery systems. This review will focus on the definition, epidemiology, diagnostic approach, and non-pharmacologic as well as pharmacologic management of chronic constipation in the elderly, including an overview of new medications currently under clinical investigation.
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Constipação Intestinal , Idoso , Doença Crônica , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , HumanosRESUMO
CONTEXT: The natural history of pituitary incidentalomas (PIs) and nonfunctioning pituitary adenomas (NFPAs) remains poorly understood. OBJECTIVE: The objective of the study was to synthesize the literature on the prognostic factors involved in the progression of PIs and NFPAs in patients followed up conservatively. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL. We sought to identify further studies by reviewing the reference lists from selected studies and reviews and by querying experts. STUDY SELECTION: Eligible studies were longitudinal observational cohort studies that enrolled patients with PIs/NFPAs and followed them up without any treatment from the time of detection and reported on mortality, lesion progression, and development of pituitary hormonal deficiency, apoplexy, or visual field defects. DATA EXTRACTION: Reviewers working independently and in duplicate determined studies' eligibility and collected descriptive, methodological quality, and outcome data. Event rates per 100 person-years (PYs) and associated 95% confidence intervals (CIs) were estimated from each study and pooled using the random-effects model. DATA SYNTHESIS: The 11 included studies had noncomparative single-cohort design. Follow-up duration ranged from 3 to 15 yr. There was a greater tendency for tumor growth in macroadenomas (12.5 per 100 PYs; 95% CI 7.9, 17.2) and in solid lesions (5.7 per 100 PYs; 95% CI 2.3, 9.2) in comparison with microadenomas (3.3 per 100 PYs; 95% CI 2.1, 4.5) and cystic lesions (0.05 per 100 PYs; 95% CI 0.0, 0.2). The development of pituitary apoplexy and worsening of visual field defects were rare. The overall incidence of new endocrine dysfunction was 2.4 per 100 PYs; 95% CI 0.0, 6.4. The majority of these analyses were associated with significant heterogeneity. There was a trend that did not reach statistical significance for greater incidence of pituitary apoplexy and new endocrine dysfunction worsening in macroadenomas compared with microadenomas. The quality of the evidence (risk of bias) was very low due to heterogeneity, methodological limitations, and imprecision caused by the small number of events. CONCLUSIONS: Despite the relatively high prevalence of PIs/NFPAs, the evidence on the natural history of these entities is scarce and of low quality. PIs/NFPAs seem to have fairly rare complications that may be more common when lesions are large (>10 mm) and solid.
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Adenoma/terapia , Achados Incidentais , Neoplasias Hipofisárias/terapia , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/epidemiologia , Algoritmos , Progressão da Doença , Seguimentos , Humanos , Incidência , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologiaRESUMO
BACKGROUND: Surgery is commonly used in the management of pituitary nonfunctioning adenomas (NFPA). The goal of this systematic review and meta-analysis is to evaluate the effect of surgery on mortality, surgical complications, pituitary function and vision. METHODS: We searched MEDLINE, EMBASE and Cochrane CENTRAL, queried experts and reviewed the reference list of included publications. Eligible studies were comparative and noncomparative longitudinal studies that enroled patients with NFPA who underwent surgery (alone or in combination with other therapies). Reviewers, working independently and in duplicate, determined study eligibility with adequate reproducibility and extracted descriptive, quality and outcome data. Risks, relative risks (RR) and 95% confidence intervals (CIs) were estimated from each study and pooled using random-effects meta-analysis. RESULTS: Most included studies were uncontrolled case series in which patients received a combination of surgery and radiotherapy. The overall quality of the evidence was very low. Median follow-up was 4·29 years. When surgery was not combined with radiotherapy, there was an increased risk of tumour recurrence (RR 1·97; 95% CI, 1·15-3·35). Complications were more likely with the transcranial than with the transsphenoidal approach (mortality RR 4·89; 95% CI, 3·15-6·47; new anterior pituitary deficits RR 4·90; 95% CI, 2·94-7·82; and persistent diabetes insipidus RR 2·50; 95% CI, 1·05-5·35). Overall, transsphenoidal surgery had fairly low perioperative mortality (≤ 1%) and low complication rate (≤ 5% for all patient-important outcomes), but only less than a third of the patients had improvement in pituitary function. CONCLUSIONS: Observational evidence supports the association between a combined approach of transsphenoidal surgery with radiotherapy and improvements in visual field defects and reduction in tumour recurrence.
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Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/radioterapia , Resultado do Tratamento , Adulto JovemRESUMO
CONTEXT: Treatment for patients with congenital adrenal hyperplasia (CAH) may affect the final height of these patients. OBJECTIVE: Our objective was to determine the distribution of achieved height in patients with classic CAH diagnosed at infancy or early childhood and treated with glucocorticoids. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, ISI Web of Science, and Scopus through September 2008; the reference sections of included studies; and expert files. STUDY SELECTION: Eligible studies included patients diagnosed with CAH before age 5 and followed to final height. DATA EXTRACTION: Reviewers working in duplicate independently extracted data on study characteristics and outcomes and determined each study's risk of bias. DATA SYNTHESIS: The sd score (SDS) for final height and corrected height (defined as final height SDS - midparental height SDS) were estimated from each study and pooled using random-effects metaanalysis. The I(2) statistic was used to assess inconsistency in results across studies. RESULTS: We found 35 eligible studies, most of which were retrospective single-cohort studies. The final height SDS achieved by CAH patients was -1.38 (-1.56 to -1.20; I(2) = 90.2%), and the corrected height SDS was -1.03 (-1.20 to -0.86; I(2) = 63.1%). This was not significantly associated with age at diagnosis, gender, type and dose of steroid, and age of onset of puberty. Mineralocorticoid users had a better height outcome in comparison with the nonusers (P = 0.02). CONCLUSION: Evidence derived from observational studies suggests that the final height of CAH patients treated with glucocorticoids is lower than the population norm and is lower than expected given parental height.
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Hiperplasia Suprarrenal Congênita/fisiopatologia , Estatura , Hiperplasia Suprarrenal Congênita/complicações , Adulto , Algoritmos , Estatura/fisiologia , Glucocorticoides/uso terapêutico , Transtornos do Crescimento/complicações , Transtornos do Crescimento/terapia , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Mineralocorticoides/uso terapêutico , Resultado do TratamentoRESUMO
By interrupting the adenoma-carcinoma sequence, endo-scopic polypectomy can prevent the development of colorectal cancer (CRC). Endoscopic polypectomy has, therefore, become an accepted screening and surveillance modality for CRC and has been widely adopted by clinicians, policymakers, and professional organizations as an effective screening tool. Most gastroenterologists are adequately trained to endoscopically excise the majority of polyps found in a routine colonoscopy. However, some polyps, due to their size, location, or configuration, are considered more technically challenging or are associated with an increased risk of complications (such as bleeding or perforation) and, hence, are not routinely resected. These so-called complex polypectomies are the focus of this paper.
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CONTEXT: The risks of testosterone therapy in men remain poorly understood. OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies. STUDY SELECTION: Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data. DATA SYNTHESIS: The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes. CONCLUSIONS: The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.
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Testosterona/efeitos adversos , Adulto , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Interpretação Estatística de Dados , Humanos , Masculino , Mortalidade , Policitemia/induzido quimicamente , Policitemia/epidemiologia , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa/normas , Fatores de Risco , Testosterona/uso terapêutico , Resultado do Tratamento , Doenças Urológicas/induzido quimicamente , Doenças Urológicas/epidemiologiaRESUMO
CONTEXT: Prenatal treatment with dexamethasone to prevent virilization in pregnancies at risk for classical congenital adrenal hyperplasia (CAH) remains controversial. OBJECTIVE: To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception through August 2009. Review of reference lists and contact with CAH experts further identified candidate studies. STUDY SELECTION: Reviewers working independently and in duplicate determined trial eligibility. Eligible studies reported the effects on either foetal or maternal outcomes of dexamethasone administered during pregnancy compared to a control group that did not receive any treatment. DATA EXTRACTION: Reviewers working independently and in duplicate determined the methodological quality of studies and collected data on patient characteristics, interventions, and outcomes. DATA SYNTHESIS: We identified only four eligible observational studies (325 pregnancies treated with dexamethasone). The methodological quality of the included studies was overall low. Meta-analysis demonstrates a reduction in foetus virilization measured by Prader score in female foetuses treated with dexamethasone initiated early during pregnancy (weighted mean difference, -2.33, 95% CI, -3.38, -1.27). No deleterious effects of dexamethasone on stillbirths, spontaneous abortions, foetal malformations, neuropsychological or developmental outcomes were found although these data are quite sparse. There was increased oedema and striae in the mothers treated with dexamethasone. There were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone. CONCLUSIONS: The observational nature of the available evidence and the overall small sample size of the whole body of the literature significantly weaken inferences about the benefits and harms of dexamethasone in this setting. Dexamethasone seems to be associated with reduction in foetus virilization without significant maternal or foetal adverse effects. However, this review underscores the current uncertainty and further investigation is clearly needed. The decision about initiating treatment should be based on patients' values and preferences and requires fully informed and consenting parents.
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Dexametasona/efeitos adversos , Feto/efeitos dos fármacos , Virilismo/prevenção & controle , Hiperplasia Suprarrenal Congênita/induzido quimicamente , Feminino , Humanos , Gravidez , RiscoRESUMO
Our aim was to assess long-term survival in patients transplanted for HCV-related end-stage liver disease (ESLD) and evaluate potentially modifiable predictors of survival. We performed a retrospective analysis of adult liver transplants (LT) at our institution for HCV-related ESLD since the program's inception. Pertinent demographic, clinical, and biochemical information was retrieved from electronic medical records and histological data from 990 per-protocol liver biopsies were collected. Three hundred eighty LT were performed at our institution during the study period, 206 patients were transplanted for HCV-related ESLD; 6 died within 30 days of transplantation and were not included. The remaining 200 recipients (DDLT 168 LDLT 32) constituted the evaluable population. The demographics were as follows: 150 males, median age 53 years; median donor age 39 years; hepatocellular carcinoma (HCC) in 26%. Overall 1-, 5-, and 7-year survival: 95%, 81%, and 79%; median survival 43 months, mortality 15%. Significant HCV recurrence (HAI >or=6 and/or fibrosis >or=2) was present in 49%, "early recurrence" (within 1 year of LT) in 30.5% and biopsy-proven acute rejection was present in 27%. Factors with a significant negative impact on patient survival included: fibrosis stage >or=2 at 12-month biopsy, advanced donor age, history of HCC and early acute rejection. Survival was similar regardless of the donor type (DDLT vs. LDLT). Early and aggressive HCV recurrence has a very heavy toll on patient survival. Prompt recognition and treatment of "rapid fibrosers" may impart benefit. As has been described before, avoidance of rejection and selection of young donors for HCV-positive recipients will also improve survival in this population. On the basis of our findings, LDLT is a good option for HCV-positive recipients.