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1.
Ann Intern Med ; 172(6): 369-380, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066146

RESUMO

Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred. Objective: To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo. Design: Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333). Setting: North America. Participants: Adults with known cardiovascular disease and diabetes or metabolic syndrome. Intervention: Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week. Measurements: Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication. Results: After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93]). Limitation: The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period. Conclusion: Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased. Primary Funding Source: National Institutes of Health.


Assuntos
Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos
2.
J Card Surg ; 36(2): 735-738, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33305839

RESUMO

Individuals with single-ventricle congenital heart disease who are palliated to a Fontan circulation are at risk for heart failure and liver disease, with recurrent ascites being a potentially debilitating cause of late morbidity. Although ascites associated with heart failure or liver failure is usually characterized by a high serum-ascites albumin gradient (SAAG), we have observed multiple instances of ascites in Fontan patients with low SAAG, suggesting an inflammatory process. We present three cases in which recalcitrant ascites severely and adversely impacted the quality of life and describe our initial experience with intraperitoneal corticosteroids in this setting.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Corticosteroides , Ascite/tratamento farmacológico , Ascite/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Humanos , Qualidade de Vida
3.
J Clin Gastroenterol ; 53(10): e424-e430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30148764

RESUMO

BACKGROUND: Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up. GOALS: Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up. MATERIALS AND METHODS: We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases). RESULTS: The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60). CONCLUSIONS: Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.


Assuntos
Hepatite B Crônica/epidemiologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Cuidado Pré-Natal , Adulto , Fatores Etários , Bases de Dados Factuais , Etnicidade , Feminino , Hepatite B Crônica/etnologia , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/transmissão , Humanos , Gravidez , Complicações Infecciosas na Gravidez/etnologia , Complicações Infecciosas na Gravidez/prevenção & controle , Prevalência , Estados Unidos/epidemiologia
4.
Anticancer Drugs ; 29(9): 919-923, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30096127

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening drug-induced hypersensitivity reaction, characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with hypereosinophilia, and elevated liver function tests, which in severe cases may lead to fulminant hepatic failure and death. Although DRESS syndrome has been associated with over 50 different drugs including imatinib, it has never been reported in association with imatinib treatment in solid tumors. We recently treated a patient with metastatic dermatofibrosarcoma protuberans, a rare cutaneous mesenchymal tumor characterized by constitutive activation of the PDGFß receptor and high sensitivity to imatinib therapy, who had a DRESS reaction to imatinib. Given an initial dramatic clinical and radiological response to treatment and lack of effective alternative targeted therapies, following imatinib discontinuation and resolution of DRESS, we cautiously reintroduced imatinib therapy using a desensitization protocol under the care of the allergy and immunologic clinic. Imatinib was carefully titrated from an initial dose of 50 mg to a target dose of 400 mg daily, while tapering down the prednisone dose. The patient was able to tolerate the treatment without recurrent episodes of DRESS or interruptions, and gained additional 6 months of clinical benefit from imatinib treatment. Although suspected causative drugs should not be reintroduced in DRESS whenever possible, in this case of metastatic disease and lack of effective alternative treatments, a carefully designed drug rechallenge helped minimize the risk of overt clinical reaction and resulted in an overall clinical benefit.


Assuntos
Dermatofibrossarcoma/tratamento farmacológico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Mesilato de Imatinib/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Dermatofibrossarcoma/patologia , Dessensibilização Imunológica/métodos , Relação Dose-Resposta a Droga , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Prednisona/administração & dosagem , Neoplasias Cutâneas/patologia
5.
Matern Child Health J ; 22(9): 1345-1351, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29512054

RESUMO

Objectives Hepatitis B (HBV) remains a significant public health burden, despite effective therapy. Routine HBV screening is recommended during pregnancy to reduce the risk of vertical transmission, but the rates of follow-up care peri-partum are low. The aim of this study was to evaluate physician practices and knowledge regarding HBV in women diagnosed perinatally. Methods A survey was distributed to obstetricians and midwives within the Partners HealthCare system at Brigham and Women's Hospital and Massachusetts General Hospital. Results Of 118 survey respondents (response rate 56%), 97% reported that they always tested for hepatitis B, and 77% referred new diagnoses of HBV during pregnancy to a HBV specialist for further care. Only 10% of respondents reported that there was formal referral mechanism in place to facilitate follow-up care for mothers diagnosed with hepatitis B infection. 91% of survey respondents selected hepatitis B surface antigen as the correct screening test, and 76% selected hepatitis B immune globulin with vaccination for the newborn as the correct prophylaxis regimen. Only 40 and 51% of respondents accurately identified serologies that were consistent with acute and chronic infection, respectively. Conclusions for Practice Routine screening for HBV in this population presents an important opportunity to identify cases and to reduce the public health burden of this disease. Providers were somewhat knowledgeable about HBV, but the lack of formal referral mechanism may explain why HBV follow-up is suboptimal in this healthcare system. Supplemental provider education and formal linkage to care programs may increase rates of follow-up HBV care.


Assuntos
Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Período Periparto , Médicos/estatística & dados numéricos , Padrões de Prática Médica , Adulto , Feminino , Hepatite B/diagnóstico , Hepatite B/terapia , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Massachusetts , Aceitação pelo Paciente de Cuidados de Saúde , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Encaminhamento e Consulta , Inquéritos e Questionários
6.
Clin Transplant ; 30(5): 502-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26854749

RESUMO

AIMS: To examine the relationship between and impact of spontaneous bacteria peritonitis (SBP) and renal failure requiring dialysis in waitlisted liver transplant (LT) candidates. BACKGROUND: Renal failure is a common and severe complication in cirrhotic patients with SBP. Approximately one-third of patients with SBP develop renal failure despite treatment of infection. However, the incidence of renal failure requiring dialysis in LT waitlisted patients who have developed SBP is unknown. The high mortality observed in this group has also raised debate about resource utilization in the care of these patients. METHODS: Data from the United Network for Organ Sharing Standard Transplant and Research files were collected retrospectively between 1994 and 2012. The primary endpoint measured was first time initiation of dialysis while on the LT wait list. Secondary endpoints included waitlist time and mortality on wait list. RESULTS: A total of 42,085 patients were included. SBP at time of listing was diagnosed in 2,352 patients (5.6%) and first time initiation of dialysis while on the wait list occurred in 2,367 patients (6.2%). Unadjusted OR for requiring dialysis for patients listed with SBP was 1.66 (p < 0.001). When controlled for age, gender, BMI, diabetes mellitus, baseline creatinine, MELD score, serum albumin at listing, the adjusted OR for dialysis was 1.24 (p = 0.007) in waitlisted patients with SBP. Patients with SBP at time of listing had a mean waitlist time 142.1 d vs. 198.7 d in non-SBP patients (p < 0.001). CONCLUSIONS: Spontaneous bacteria peritonitis patients have a significantly increased likelihood to require dialysis and mean shorter waitlist time. Furthermore, the combined occurrence of SBP and dialysis is a strong risk factor for all-cause mortality while on the LT wait list.


Assuntos
Infecções Bacterianas/microbiologia , Cirrose Hepática/complicações , Transplante de Fígado , Peritonite/microbiologia , Diálise Renal , Insuficiência Renal/terapia , Listas de Espera , Infecções Bacterianas/patologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Peritonite/patologia , Prognóstico , Insuficiência Renal/etiologia , Estudos Retrospectivos , Fatores de Risco
7.
J Clin Gastroenterol ; 50(6): e60-4, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27092430

RESUMO

GOALS: To determine postpartum hepatitis B virus (HBV) laboratory testing rates and identify factors associated with a lack of follow-up testing in Massachusetts. BACKGROUND: Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. STUDY: We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. RESULTS: We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P=0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P<0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). CONCLUSIONS: Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered.


Assuntos
Assistência ao Convalescente/estatística & dados numéricos , Hepatite B Crônica/diagnóstico , Período Pós-Parto , Adulto , Fatores Etários , Estudos de Coortes , Bases de Dados Factuais , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Modelos Logísticos , Massachusetts , Análise Multivariada , Guias de Prática Clínica como Assunto , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Adulto Jovem
8.
Am J Obstet Gynecol ; 212(3): 365.e1-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25281364

RESUMO

OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.


Assuntos
Hepatite B Crônica/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cuidado Pós-Natal/estatística & dados numéricos , Complicações Infecciosas na Gravidez/terapia , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Feminino , Seguimentos , Gastroenterologia , Hepatite B Crônica/diagnóstico , Humanos , Modelos Logísticos , Massachusetts , Análise Multivariada , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Atenção Primária à Saúde/estatística & dados numéricos , Encaminhamento e Consulta , Estudos Retrospectivos
9.
Dig Dis Sci ; 60(12): 3735-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26173503

RESUMO

BACKGROUND: Several lines of evidence suggest that abnormal iron homeostasis may itself play an important role in the development of celiac disease. AIM: We sought to determine whether abnormalities in iron status could be detected prior to the diagnosis of celiac disease, and to understand the relationship between altered iron indices and the natural history of celiac disease. METHODS: We conducted a case-control study at two major tertiary referral hospitals. Cases were comprised of patients with celiac disease in whom iron status was assessed prior to the diagnosis. Each case was matched to five controls without known gastrointestinal disease according to age and sex. Information on potential covariates and laboratory values within 1, 1-3, and 3-5 years prior to diagnosis was collected. We used conditional logistic regression to evaluate the effect of iron indices on risk of celiac disease. RESULTS: We identified 157 celiac cases and 695 matched controls. Compared to participants with normal TIBC, the age-adjusted risk of celiac disease was significantly elevated among patients with elevated TIBC. For each 10 µg/dL increase in TIBC, the risk of celiac disease increased by 4.6, 3.8, and 7.9% within 1, 1-3, and 3-5 years prior to diagnosis, respectively. Patients with elevated pre-diagnosis TIBC were more likely to have abnormal liver enzymes and osteoporosis. CONCLUSIONS: Elevated TIBC is associated with an increased risk of celiac disease. Further investigation into the potential role of altered iron homeostasis may uncover important environmental factors that contribute to the development of celiac disease.


Assuntos
Doença Celíaca/patologia , Ferro/metabolismo , Estudos de Casos e Controles , Doença Celíaca/sangue , Doença Celíaca/metabolismo , Feminino , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
11.
Nat Cell Biol ; 9(12): 1370-80, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17994011

RESUMO

SNX-BAR proteins are a sub-family of sorting nexins implicated in endosomal sorting. Here, we establish that through its phox homology (PX) and Bin-Amphiphysin-Rvs (BAR) domains, sorting nexin-4 (SNX4) is associated with tubular and vesicular elements of a compartment that overlaps with peripheral early endosomes and the juxtanuclear endocytic recycling compartment (ERC). Suppression of SNX4 perturbs transport between these compartments and causes lysosomal degradation of the transferrin receptor (TfnR). Through an interaction with KIBRA, a protein previously shown to bind dynein light chain 1, we establish that SNX4 associates with the minus end-directed microtubule motor dynein. Although suppression of KIBRA and dynein perturbs early endosome-to-ERC transport, TfnR sorting is maintained. We propose that by driving membrane tubulation, SNX4 coordinates iterative, geometric-based sorting of the TfnR with the long-range transport of carriers from early endosomes to the ERC. Finally, these data suggest that by associating with molecular motors, SNX-BAR proteins may coordinate sorting with carrier transport between donor and recipient membranes.


Assuntos
Dineínas/fisiologia , Endocitose , Receptores da Transferrina/metabolismo , Proteínas de Transporte Vesicular/fisiologia , Compartimento Celular , Membrana Celular/metabolismo , Endossomos/metabolismo , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Microtúbulos/metabolismo , Fosfoproteínas , Ligação Proteica , Transporte Proteico , Proteínas/metabolismo , Nexinas de Classificação
12.
Gastroenterology ; 143(5): 1237-1243, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22885329

RESUMO

BACKGROUND & AIMS: Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF. METHODS: Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices. RESULTS: Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF. CONCLUSIONS: The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD.


Assuntos
Queratina-18/sangue , Falência Hepática Aguda/sangue , Fragmentos de Peptídeos/sangue , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Bilirrubina/sangue , Distribuição de Qui-Quadrado , Coma/etiologia , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Coeficiente Internacional Normatizado , Falência Hepática Aguda/complicações , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Estatísticas não Paramétricas , Análise de Sobrevida , Adulto Jovem
13.
Surg Pathol Clin ; 16(3): 443-456, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37536881

RESUMO

This article focuses on how hepatologists view the role of liver biopsy in diagnosis, assessment, and management of chronic and acute liver disease, and its variable use among different etiologies of liver disease and in the evaluation of liver fibrosis.


Assuntos
Gastroenterologistas , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Biópsia
14.
J Imaging ; 8(10)2022 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-36286371

RESUMO

BACKGROUND: Radiomics extracts quantitative image features to identify biomarkers for characterizing disease. Our aim was to characterize the ability of radiomic features extracted from magnetic resonance (MR) imaging of the liver and spleen to detect cirrhosis by comparing features from patients with cirrhosis to those without cirrhosis. METHODS: This retrospective study compared MR-derived radiomic features between patients with cirrhosis undergoing hepatocellular carcinoma screening and patients without cirrhosis undergoing intraductal papillary mucinous neoplasm surveillance between 2015 and 2018 using the same imaging protocol. Secondary analyses stratified the cirrhosis cohort by liver disease severity using clinical compensation/decompensation and Model for End-Stage Liver Disease (MELD). RESULTS: Of 167 patients, 90 had cirrhosis with 68.9% compensated and median MELD 8. Combined liver and spleen radiomic features generated an AUC 0.94 for detecting cirrhosis, with shape and texture components contributing more than size. Discrimination of cirrhosis remained high after stratification by liver disease severity. CONCLUSIONS: MR-based liver and spleen radiomic features had high accuracy in identifying cirrhosis, after stratification by clinical compensation/decompensation and MELD. Shape and texture features performed better than size features. These findings will inform radiomic-based applications for cirrhosis diagnosis and severity.

15.
Liver Transpl ; 17(3): 251-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21384507

RESUMO

Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5-year period (2004-2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation. Depression was defined as past or active depression or an adjustment disorder. The associations between pretransplant depression and various outcomes (time to death, graft failure, first acute cellular rejection episode, first infection, and first rehospitalization) were assessed. In the entire sample, more patients with depression required posttransplant psychiatric care (37% versus 18%); the adjusted hazard ratio was 2.28 (1.27-4.11). The rates of other outcomes, including hospital readmission, acute cellular rejection, graft failure, mortality, and infection, were similar for patients with depression and patients without depression. Among those with depression, patients on antidepressants at the time of transplantation had acute cellular rejection less frequently than those not taking antidepressants (13% versus 40%); the adjusted hazard ratio was 0.14 (0.03-0.62). The rates of other outcomes were similar between these 2 groups. These data indicate that depression affects posttransplant psychiatric morbidity but not other medical outcomes of liver transplantation. Pharmacological treatment of depression may significantly reduce the incidence of acute cellular rejection in patients undergoing liver transplantation. However, future prospective studies of mental health and liver transplantation are required to definitively assess the effects of antidepressant medications on medical outcomes.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Hepatopatias/cirurgia , Transplante de Fígado/psicologia , Adulto , Boston/epidemiologia , Distribuição de Qui-Quadrado , Doenças Transmissíveis/etiologia , Comorbidade , Depressão/diagnóstico , Depressão/mortalidade , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Hepatopatias/mortalidade , Hepatopatias/psicologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Projetos Piloto , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
16.
Int J Comput Assist Radiol Surg ; 16(3): 457-466, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33646521

RESUMO

PURPOSE: We aimed to develop a predictive model of disease severity for cirrhosis using MRI-derived radiomic features of the liver and spleen and compared it to the existing disease severity metrics of MELD score and clinical decompensation. The MELD score is compiled solely by blood parameters, and so far, it was not investigated if extracted image-based features have the potential to reflect severity to potentially complement the calculated score. METHODS: This was a retrospective study of eligible patients with cirrhosis ([Formula: see text]) who underwent a contrast-enhanced MR screening protocol for hepatocellular carcinoma (HCC) screening at a tertiary academic center from 2015 to 2018. Radiomic feature analyses were used to train four prediction models for assessing the patient's condition at time of scan: MELD score, MELD score [Formula: see text] 9 (median score of the cohort), MELD score [Formula: see text] 15 (the inflection between the risk and benefit of transplant), and clinical decompensation. Liver and spleen segmentations were used for feature extraction, followed by cross-validated random forest classification. RESULTS: Radiomic features of the liver and spleen were most predictive of clinical decompensation (AUC 0.84), which the MELD score could predict with an AUC of 0.78. Using liver or spleen features alone had slightly lower discrimination ability (AUC of 0.82 for liver and AUC of 0.78 for spleen features only), although this was not statistically significant on our cohort. When radiomic prediction models were trained to predict continuous MELD scores, there was poor correlation. When stratifying risk by splitting our cohort at the median MELD 9 or at MELD 15, our models achieved AUCs of 0.78 or 0.66, respectively. CONCLUSIONS: We demonstrated that MRI-based radiomic features of the liver and spleen have the potential to predict the severity of liver cirrhosis, using decompensation or MELD status as imperfect surrogate measures for disease severity.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Doença Hepática Terminal/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Baço/diagnóstico por imagem , Adulto , Idoso , Algoritmos , Área Sob a Curva , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Artigo em Inglês | MEDLINE | ID: mdl-32909466

RESUMO

The HeadUp collar (previously known as the Sheffield Support Snood) provides support for neck weakness caused by amyotrophic lateral sclerosis (ALS) and has shown to be superior to alternative options in a small cohort of patients from one single center. Here we report the assessment of the HeadUp collar in a larger cohort of patients, exploring the use in other neurological conditions and expanding to other centers across the UK and Ireland. An interventional cross-sectional study design was implemented to investigate the usability and acceptability of the HeadUp collar. A total of 139 patients were recruited for the study, 117 patients had a diagnosis of ALS and 22 patients presented with neck weakness due to other neurological conditions. Participants were assessed at baseline, fitted a HeadUp collar and followed-up one month later. The performance of the HeadUp collar was rated favorably compared to previously worn collars in terms of the ability to eat, drink and swallow. Findings suggest that the collar also permitted a more acceptable range of head movements whilst maintaining a good level of support. We conclude that the HeadUp collar is a suitable option for patients with neck weakness due to ALS and other neurological conditions.


Assuntos
Esclerose Lateral Amiotrófica , Braquetes , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/terapia , Estudos Transversais , Humanos , Irlanda , Pescoço
18.
Surgery ; 167(6): 991-998, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32113580

RESUMO

BACKGROUND: Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. METHODS: Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. RESULTS: The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6-8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation. CONCLUSION: This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.


Assuntos
Transplante de Face , Pele/patologia , Transplantados , Aloenxertos , Antígenos CD4/metabolismo , Carcinoma Hepatocelular/virologia , Seguimentos , Taxa de Filtração Glomerular , Hepatite C Crônica/complicações , Humanos , Imunossupressores/uso terapêutico , Interleucina-17/metabolismo , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
World J Pediatr Congenit Heart Surg ; 10(3): 357-359, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30354929

RESUMO

Recurrent ascites is a common manifestation of failing Fontan circulation. We present the hemodynamic response to large-volume paracentesis in a patient with Fontan circulation and Fontan-associated liver disease, documenting an immediate and substantial decline in systemic venous pressure and increase in cardiac output. These preliminary observations may have implications for the management of ascites in adults with Fontan circulation.


Assuntos
Ascite/cirurgia , Técnica de Fontan/métodos , Cardiopatias Congênitas/cirurgia , Hemodinâmica/fisiologia , Paracentese/métodos , Adulto , Ascite/etiologia , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/fisiopatologia , Humanos
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