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Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMT) have been described in immunosuppressed states, including in post-transplant patients. Here, we discuss a heart-liver transplant recipient who was found to have multifocal hepatic EBV-SMT. His immunosuppression was initially transitioned from tacrolimus to sirolimus because of the proposed benefits of the mechanistic target of rapamycin inhibitors on EBV-SMT. Unfortunately, he suffered acute rejection of his liver allograft while on sirolimus therapy, which ultimately led to consideration of retransplantation.
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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
Transforming health care remains a challenge as many continuous improvement (CI) initiatives fail or are not sustained. Although the literature suggests the importance of culture, few studies provide evidence of cultural change creating sustained CI. This improvement initiative focused on creating cultural change through goal alignment, visual management, and empowering frontline employees. Data included 113 133 encounters. Cochran-Armitage tests and X-bar charting compared wait times during the CI initiative. Odds of waiting <15 minutes increased in both phase 2 (odds ratio = 3.57, 95% confidence interval = [3.43-3.71]) and phase 3 (odds ratio = 5.39, 95% confidence interval = [5.07, 5.74]). At 3 years follow-up, 95% of wait times were <15 minutes. Productivity increased from 519 to 644 patients/full-time equivalent/month; 33/42 Press Ganey employee engagement components significantly improved. This study demonstrates the efficacy of a culture of CI approach to sustain wait time improvement in outpatient laboratory services, and should be considered for application in other areas of health care quality.
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Eficiência Organizacional , Laboratórios/normas , Cultura Organizacional , Pacientes Ambulatoriais , Qualidade da Assistência à Saúde , Gestão da Qualidade Total , Listas de Espera , Engajamento no Trabalho , Instituições de Assistência Ambulatorial , Pesquisas sobre Atenção à Saúde , HumanosRESUMO
BACKGROUND: Roux-en-Y gastric bypass (RYGB) improves the pathophysiology that contributes to obesity-related nonalcoholic steatohepatitis (NASH). Whether obesity-related fibrosis improves is unclear. We hypothesized that RYGB reverses NASH and fibrosis, and indocyanine green (ICG) clearance provides a sensitive measure for detecting asymptomatic fatty liver disease. METHODS: One hundred six obese adults scheduled for RYGB had preoperative liver function assessed using standard tests and ICG clearance and core liver biopsies obtained during RYGB. Once patients lost 60% of their preoperative weight or weight loss plateaued, liver function was reassessed. Repeat liver biopsies were obtained on patients with NASH at the time of RYGB. RESULTS: RYGB improved steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. Serum albumin, AST, and ALT decreased the most in patients with NASH and NASH plus fibrosis. Twenty seven (26%) patients had normal baseline liver histology and 45 (43%) had NASH or NASH plus fibrosis. Nine of 13 patients with substantial fatty liver had normalized histology after weight loss, while severity of disease in the rest had stabilized or was reduced. Mean ICG clearance in patients with normal/mild fatty liver disease and those with histological fatty livers did not differ significantly. CONCLUSIONS: RYGB surgery reverses NASH and liver fibrosis. Underlying mechanisms that facilitate improvement remain unclear.
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The most frequent chromosomal structural loss in hepatocellular carcinoma (HCC) is of the short arm of chromosome 8 (8p). Genes on the remaining homologous chromosome, however, are not recurrently mutated, and the identity of key 8p tumor-suppressor genes (TSG) is unknown. In this work, analysis of minimal commonly deleted 8p segments to identify candidate TSG implicated GATA4, a master transcription factor driver of hepatocyte epithelial lineage fate. In a murine model, liver-conditional deletion of 1 Gata4 allele to model the haploinsufficiency seen in HCC produced enlarged livers with a gene expression profile of persistent precursor proliferation and failed hepatocyte epithelial differentiation. HCC mimicked this gene expression profile, even in cases that were morphologically classified as well differentiated. HCC with intact chromosome 8p also featured GATA4 loss of function via GATA4 germline mutations that abrogated GATA4 interactions with a coactivator, MED12, or by inactivating mutations directly in GATA4 coactivators, including ARID1A. GATA4 reintroduction into GATA4-haploinsufficient HCC cells or ARID1A reintroduction into ARID1A-mutant/GATA4-intact HCC cells activated hundreds of hepatocyte genes and quenched the proliferative precursor program. Thus, disruption of GATA4-mediated transactivation in HCC suppresses hepatocyte epithelial differentiation to sustain replicative precursor phenotype.
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Carcinoma Hepatocelular/metabolismo , Fator de Transcrição GATA4/metabolismo , Hepatócitos/metabolismo , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Hepatocelular/genética , Diferenciação Celular , Linhagem Celular Tumoral , Linhagem da Célula , Proliferação de Células , Células Epiteliais/citologia , Feminino , Fator de Transcrição GATA4/genética , Deleção de Genes , Mutação em Linhagem Germinativa , Haploinsuficiência , Células Hep G2 , Hepatócitos/citologia , Humanos , Inflamação , Cariotipagem , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Knockout , Mutação , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: Hepatitis C virus (HCV) recurrence after liver transplantation decreases survival rates. Improved understanding of the multiple factors influencing HCV recurrence could aid decision-making for donor-recipient pairing and maximize transplant outcomes. The aim of this study was to create a model based on pretransplant variables to stratify patients at risk of HCV-related allograft failure. METHODS: This retrospective study enrolled 154 liver transplant recipients with HCV at Cleveland Clinic. RESULTS: Among the study population, 54 recipients (35.1%) experienced HCV recurrence, histologically defined as moderate to severe hepatitis and/or bridging fibrosis to cirrhosis. The multivariate analysis found donor age (≥60 years, P < 0.002), donor body mass index (≥30 kg/m2 , P < 0.05), African American recipient (P < 0.01) and genotype 1 (P < 0.02) as risk factors for HCV-related allograft failure. When these four factors were scored as a combined index (no factor [n = 15], one factor [n = 76], two factors [n = 43] and three or more factors [n = 20]), the HCV recurrence-free survival showed good stratification according to the scores: 93.3% with no factor, 79.3% with one factor, 52.0% with two factors and 24.4% with three or more factors at 3 years after transplant (P < 0.0001). Moreover, this risk index also identified the patient group at high risk of HCV recurrence after acute rejection. CONCLUSION: While the introduction of direct-acting antiviral agents has been changing the paradigm of HCV treatment, the natural history of recipients with HCV as shown in this study would help estimate the risk of HCV-related allograft failure in those who do not tolerate such new treatment.
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BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced and aggressive form of non-alcoholic fatty liver disease (NAFLD), which remains difficult to diagnose without a liver biopsy. Hyperferritinemia has increasingly been associated with the presence of NASH. Hence, we sought to explore the relationship between ferritin and NASH and to develop a composite model based on ferritin to predict the presence of NASH. METHODS: A total of 405 patients with biopsy-proven NAFLD were enrolled in the study. Comparison was explored to assess differences between patients with and without NASH, upon which a scoring model was established using variables found to be independent predictors of NASH. RESULTS: Among all patients with NAFLD, 291 (72%) had biopsy-proven NASH, and 114 (28%) had non-NASH. Mean age was 48 ± 12 years, and 56% were female. Ferritin was significantly higher in NASH compared with non-NASH patients (184 vs 126, respectively; P < 0.001) but lacked diagnostic accuracy for predicting NASH alone (area under the curve [AUC 0.62]). The addition of other significant variables such as aspartate aminotransferase, body mass index, platelet count, diabetes, and hypertension to ferritin improved the prediction of NASH with an AUC 0.81 (95% confidence interval: 0.76-0.86). Internal validation of the model using imputed data sets demonstrated that AUC did not change materially. CONCLUSIONS: While higher ferritin was significantly associated with NASH, ferritin alone lacked diagnostic accuracy to predict NASH. However, incorporating several easily obtainable variables with ferritin allowed the construction of a novel scoring system that can be easily applied in the clinical setting to guide management of NAFLD.
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Técnicas de Apoio para a Decisão , Ferritinas/sangue , Indicadores Básicos de Saúde , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Área Sob a Curva , Biomarcadores/sangue , Biópsia , Estudos Transversais , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. METHODS: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. RESULTS: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. CONCLUSION: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.
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BACKGROUND AND AIM: While histological differences have been reported between pediatric and adult nonalcoholic fatty liver disease (NAFLD), potential age-related changes in serum transaminases and liver histology remain largely unexplored. Our study sought to investigate the clinical and histological characteristics of NAFLD across age. METHODS: This was a prospective cross-sectional study of 502 biopsy-proven NAFLD patients. Clinical data were evaluated and compared among different age groups; group A (ages 18-44), B (ages 45-64), and C (≥ ages 65). RESULTS: 34.9, 56.0, and 9.1 % of the cohort were distributed among group A, B, and C, respectively. While the prevalence of nonalcoholic steatohepatitis (NASH) was comparable across age groups, the prevalence of advanced fibrosis increased with age (p = 0.000). Although the mean ALT progressively decreased with age; 87, 64, 56 U/L in group A, B, and C, respectively (p = 0.000), there was no difference in mean AST (p = 0.939) across age. The AST:ALT ratio (AAR) progressively increased from 0.7, 0.9, and 1.1 in group A, B, and C, respectively (p = 0.000). In group C, an AAR ≥ 1 was found in 74 and 40 % of patients with and without advanced fibrosis. CONCLUSION: With advancing age, ALT levels progressively declined while AST levels remained stable, leading to a higher AAR. Although higher AAR is often used as a surrogate measure of advanced fibrosis, advancing age can also contribute to increased AAR. In fact, an AAR ≥ 1 was found in significant number of elderly patients without advanced fibrosis. Consequently, an increased AAR may be a function of decreasing ALT with age in addition to progressive fibrosis.
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Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Biópsia , Estudos Transversais , Feminino , Humanos , Cirrose Hepática/epidemiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de RiscoRESUMO
Intensive care unit (ICU) resources are scarce, yet demand is increasing at a rapid rate. Optimizing throughput efficiency while balancing patient safety and quality of care is of utmost importance during times of high ICU utilization. Continuous improvement methodology was used to develop a multidisciplinary workflow to improve throughput in the ICU while maintaining a high quality of care and minimizing adverse outcomes. The research team was able to decrease ICU occupancy and therefore ICU length of stay by implementing this process without increasing mortality or readmissions to the ICU. By improving throughput efficiency, more patients were able to be provided with care in the ICU.
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Ocupação de Leitos , Unidades de Terapia Intensiva , Fluxo de Trabalho , Idoso , Ocupação de Leitos/estatística & dados numéricos , Eficiência Organizacional , Feminino , Humanos , Comunicação Interdisciplinar , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Centros de Atenção TerciáriaRESUMO
BACKGROUND & AIMS: Therapeutic options are limited for patients with non-alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation of necroinflammation and fibrosis by inhibition of the renin-angiotensin system (RAS). We explored whether the risk of fibrosis was associated with the use of commonly used medications in NAFLD patients with hypertension. Specifically, we sought to determine the association between RAS blocking agents and severity of hepatic fibrosis in NAFLD patients with hypertension. METHODS: Cross-sectional study where clinical information including demographics, anthropometry, medical history, concomitant medication use, biochemical and histological features were ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients with and without RAS blocker use. Other risk factors for fibrosis were evaluated from the electronic medical records and patient follow-up. RESULTS: Baseline characteristics of hypertensive patients treated with and without RAS blockers were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01-1.06, P = 0.012) and presence of diabetes (OR: 2.55; 95%CI: 1.28-5.09, P = 0.008) had an independent positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21-0.65, P = 0.001) and statins (OR: 0.52; 95%CI: 0.29-0.93, P = 0.029) had a negative association with advanced fibrosis. CONCLUSION: Hypertensive patients with NAFLD on baseline RAS blockers had less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD.
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Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Estudos de Coortes , Estudos Transversais , Feminino , Fibrose , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common and severe in patients with diabetes mellitus. Although, there are no effective treatments for NASH in diabetic patients, preliminary reports suggest that polyunsaturated fatty acids (PUFA) may be beneficial in these patients. AIM: A prospective, randomized, double-blind placebo-controlled study (NCT 00323414) was performed in NASH patients with diabetes. Clinicaltrials.gov (NCT 00323414). SUBJECTS AND METHODS: A total of 37 patients (50.6 ± 9.8 y) with well-controlled diabetes (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic acid (2160 mg) and docosahexaenoic acid (1440 mg) daily or an isocaloric, identical placebo containing corn oil for 48 weeks under CONSORT guidelines. Clinical, demographics, biochemical laboratory tests, body composition using DEXA, and liver biopsy were performed at randomization and at the end of treatment. Liver biopsy was scored by the NASH CRN criteria. An intention-to-treat analysis was performed. RESULTS: At inclusion, sex, age, body weight, biochemical tests, glucose control, and liver histology were similar in the 2 treatment groups. There was no change in liver enzymes, body weight, or body composition during the study in either group. At the end of the treatment, hepatic steatosis and the activity score improved (P<0.05) and lobular inflammation worsened (P<0.001) with placebo but was unchanged with PUFA. At the end of the treatment, insulin resistance (serum glucose and HOMA) worsened with PUFA but not placebo. CONCLUSIONS: PUFA provided no benefit over placebo in NASH patients with diabetes. The effects of PUFA on histology and insulin resistance were inferior to placebo. These data provide no support for PUFA supplements in NASH.
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Diabetes Mellitus/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Administração Oral , Adulto , Biomarcadores/sangue , Biópsia , Cápsulas , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Ácido Eicosapentaenoico/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Resistência à Insulina , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Ohio , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and can progress to liver cirrhosis during childhood. Patients with more advanced fibrosis on biopsy tend to have more liver complications. Noninvasive hepatic fibrosis scores have been developed for adult patients with NAFLD; however, these scores have not been validated in children. The aim of our study was to evaluate some of these scores in assessing the presence of fibrosis in children with biopsy-proven NAFLD. METHODS: Our study consisted of 92 biopsy-proven NAFLD children from five major US centers. Fibrosis was determined by an experienced pathologist (F0-4). Clinically significant fibrosis was defined as fibrosis stage ≥ 2, and advanced fibrosis was defined as F3-4. The following fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 index. ROC was performed to assess the performance of different scores for prediction of presence of any, significant, or advanced fibrosis. A p value < 0.05 was considered statistically significant. RESULTS: Mean age was 13.3 ± 3 years, and 33 % were females. Eleven (12 %) subjects had no fibrosis, 35 (38 %) had fibrosis score of 1, 26 (28 %) had fibrosis score of 2, and 20 (22 %) had a score of 3. APRI had a fair diagnostic accuracy for the presence of any fibrosis (AUC of 0.80) and poor diagnostic accuracy for significant or advanced fibrosis. AST/ALT, NFS, and FIB-4 index all either had poor diagnostic accuracy or failed to diagnose the presence of any, significant, or advanced fibrosis. CONCLUSION: Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing significant fibrosis in children with NAFLD. Our results highlight the urgent need to develop a reliable pediatric fibrosis score.
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Cirrose Hepática/diagnóstico , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adolescente , Fatores Etários , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Criança , Ensaios Enzimáticos Clínicos , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Contagem de Plaquetas , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Estados UnidosRESUMO
OBJECTIVES: Duplicate laboratory tests that are unwarranted increase unnecessary phlebotomy, which contributes to iatrogenic anemia, decreased patient satisfaction, and increased health care costs. MATERIALS AND METHODS: We employed a clinical decision support tool (CDST) to block unnecessary duplicate test orders during the computerized physician order entry (CPOE) process. We assessed laboratory cost savings after 2 years and searched for untoward patient events associated with this intervention. RESULTS: This CDST blocked 11,790 unnecessary duplicate test orders in these 2 years, which resulted in a cost savings of $183,586. There were no untoward effects reported associated with this intervention. CONCLUSIONS: The movement to CPOE affords real-time interaction between the laboratory and the physician through CDSTs that signal duplicate orders. These interactions save health care dollars and should also increase patient satisfaction and well-being.
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Sistemas de Apoio a Decisões Clínicas/economia , Atenção à Saúde/economia , Sistemas de Registro de Ordens Médicas/economia , Sistemas Computadorizados de Registros Médicos/economia , Serviços de Laboratório Clínico/economia , Serviços de Laboratório Clínico/estatística & dados numéricos , Redução de Custos , Humanos , Satisfação do PacienteRESUMO
Complement 4d (C4d) is a marker of complement activation that has been used to evaluate humoral rejection in renal and heart allografts. Studies suggested a role for C4d detection in liver allografts in diagnosing acute cellular and humoral rejection but none correlated this with the pre-transplant liver disease. Our study analyzed the association of C4d deposition in liver allografts with the pre-transplant liver disease. C4d deposition was evaluated by indirect immunofluorescence and correlated with lymphocytotoxic crossmatch results, post-transplant clinicopathological diagnosis and type of pre-transplant liver disease. Allograft biopsies were classified by the native liver disease. After excluding 20 patients with rare liver diseases; C4d deposition was evaluated in 506 biopsies from 310 patients including 25 with PSC, 198 with viral hepatitis and 87 with other diseases. C4d immunereactivity distribution was not different among biopsies from patients with different lymphocytotoxic crossmatch results. Sinusoidal C4d deposition was noted in 11.9% of biopsies and 15.2% of patients (in one or more biopsies). 26% (9/35) of biopsies from patients with PSC had sinusoidal C4d deposition; more frequently than from patients with viral hepatitis 12% (43/348) (p=0.04) and other liver diseases 7% (8/123) (p=0.005). In conclusion, C4d deposition in liver allografts is independent of the crossmatch results. It occurs with a variety of pathologic abnormalities and underlying liver diseases; but is more frequent in patients with PSC. This suggests that mechanisms other than allo-immunity activate complement. The mechanisms and clinical significance of C4d deposition in liver allografts in patients with PSC remain to be determined.
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Ativação do Complemento , Complemento C4b/análise , Hepatopatias/imunologia , Hepatopatias/cirurgia , Transplante de Fígado , Fígado/imunologia , Fígado/cirurgia , Fragmentos de Peptídeos/análise , Aloenxertos , Biomarcadores/análise , Biópsia , Citometria de Fluxo , Imunofluorescência , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Ohio , Valor Preditivo dos TestesRESUMO
BACKGROUND AND AIM: Oxidative stress is a core abnormality responsible for disease progression in nonalcoholic fatty liver disease (NAFLD). By employing a highly sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) approach we recently were able to define the circulating profile of bioactive lipid peroxidation products characteristic of patients with nonalcoholic steatohepatitis (NASH) and developed the OxNASH score for NASH diagnosis. The aims of this study were to assess the utility of OxNASH as a predictor of NASH and study the association between OxNASH and specific histologic features of NAFLD. METHODS: Our cohort consisted of 122 patients undergoing liver biopsy for clinical suspicion of NAFLD. The NAFLD activity score (NAS) was calculated for each patient. Levels of fatty acid oxidation products were quantified using stable isotope dilution LC/MS/MS, and OxNASH was calculated. RESULTS: The mean age of our patients was 49.3 (±11.6) years, and the mean body mass index was 31.5 (±4.8) kg/m(2). The majority of patients were Caucasian (82 %) and 48 % were female. OxNASH correlated with NAS and with the individual histologic features of NAFLD, namely, steatosis, inflammation, and ballooning (P < 0.05), with the strongest association being with inflammation [rho (ρ) 0.40, 95 % confidence interval 0.23, 0.57, P < 0.001]. There was also a correlation between the stage of fibrosis and OxNASH (P = 0.001). These associations remained statistically significant after adjustment for multiple confounders. CONCLUSIONS: Based on our results, in adult patients with NAFLD, OxNASH correlates with histologic features of NASH and appears to be a promising noninvasive marker.
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Fígado Gorduroso/diagnóstico , Peroxidação de Lipídeos , Fígado/patologia , Estresse Oxidativo , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Cromatografia Líquida , Estudos Transversais , Fígado Gorduroso/sangue , Fígado Gorduroso/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Prognóstico , Curva ROC , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers.
Assuntos
Hepatectomia , Imageamento Tridimensional , Transplante de Fígado/métodos , Fígado/cirurgia , Doadores Vivos , Imageamento por Ressonância Magnética , Modelos Anatômicos , Impressão , Tomografia Computadorizada por Raios X , Adulto , Pontos de Referência Anatômicos , Feminino , Hepatectomia/efeitos adversos , Humanos , Fígado/anormalidades , Fígado/diagnóstico por imagem , Fígado/patologia , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Cuidados Pré-Operatórios , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador , Resultado do TratamentoRESUMO
BACKGROUND: Autoimmune pancreatitis (AIP) is a recently characterized disease with specific clinical, radiographic, and histological features. These diagnostic features have been codified in the recently revised HISORt criteria. The aim of this study was to determine how the recognition and management of AIP has evolved at our center since the publication of the HISORt criteria in 2006. METHODS: We conducted a historical cohort study consisting of patients with AIP based on the revised HISORt criteria seen at our tertiary care center since 1990. Cases were identified from pathology, laboratory, and pancreas clinic databases. The medical records were reviewed to ascertain demographic and clinical characteristics, radiologic and laboratory results, and patient outcomes. When available, prior images and pathology slides were retrospectively reviewed. The clinical outcomes of the patients were assessed following surgical or medical treatment, and compared based on the calendar year of presentation (before or after 2006). RESULTS: Forty-seven cases were identified based on the revised HISORt criteria. Of these, 22 were evaluated before and 25 after January 1, 2006. In the early cohort, the diagnosis was frequently missed, including 15 patients that underwent surgical resections. None from the early cohort had a serum IgG4 drawn or mention of possible AIP in the imaging reports. When histology was obtained, the surgical pathologist did not perform IgG4 or Movat stain to allow a histological diagnosis of AIP. Several patients developed diabetes (n=3), calcific pancreatitis with exocrine insufficiency (n=3), proximal biliary strictures (n=7), and pancreatic cancer (n=1) during follow-up. In contrast, patients in the late cohort were less likely to undergo a surgical resection that the early cohort (36% vs. 68%, p=0.042). They were more likely to have a serum IgG4 drawn (80% vs. 0%) and to undergo a corticosteroid trial (44% vs. 0%, p=0.0003). 10/11 patients (92%) who underwent corticosteroid trials had resolution of their symptoms and improvement in structural abnormalities on imaging. CONCLUSION: A growing multidisciplinary awareness of AIP has led to improved diagnostic evaluation, prompter diagnosis, fewer surgical resections, and more frequent corticosteroid trials.