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Patients with chronic liver disease would benefit from pragmatic trial designs. A pragmatic trial seeks to inform clinical decision-making by providing evidence for the adoption of an intervention into real-world clinical practice. A trial's pragmatism is based on the efficiency by which it identifies, recruits, and follows patients, the degree to which the interventions and design mirror the usual clinical care, and the importance of the outcomes to the patients. We review the promise, trade-offs, and purpose of pragmatic trials in hepatology.
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Gastroenterologia , Ensaios Clínicos Pragmáticos como Assunto , HumanosRESUMO
BACKGROUND AND AIMS: While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH. APPROACH AND RESULTS: A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum's deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p =0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001). CONCLUSIONS: Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.
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OBJECTIVE: This study was undertaken to evaluate the role of regional social vulnerability in geographic disparity for patients listed for liver transplantation with non-hepatocellular carcinoma (HCC) model for end-stage liver disease (MELD) exceptions. SUMMARY AND BACKGROUND: Prior work has demonstrated regional variability in the appropriateness of MELD exceptions for diagnoses other than HCC. METHODS: Adults listed at a single center for first-time liver-only transplantation without HCC after June 18, 2013 in the Scientific Registry of Transplant Recipients database as of March 2021 were examined. Candidates were mapped to hospital referral regions (HRRs). Adjusted likelihood of mortality and liver transplantation were modeled. Advantaged HRRs were defined as those where exception patients were more likely to be transplanted, yet no more likely to die in adjusted analysis. The Centers for Disease Control's Social Vulnerability Index (SVI) was used as the measure for community health. Higher SVIs indicate poorer community health. RESULTS: There were 49,494 candidates in the cohort, of whom 4337 (8.8%) had MELD exceptions. Among continental US HRRs, 27.3% (n = 78) were identified as advantaged. The mean SVI of advantaged HRRs was 0.42 versus 0.53 in nonadvantaged HRRs ( P = 0.002), indicating better community health in these areas. Only 25.3% of advantaged HRRs were in spatial clusters of high SVI versus 40.7% of nonadvantaged HRRs, whereas 44.6% of advantaged HRRs were in spatial clusters of low SVI versus 38.0% of nonadvantaged HRRs ( P = 0.037). CONCLUSIONS: An advantage for non-HCC MELD exception patients is associated with lower social vulnerability on a population level. These findings suggest assigning similar waitlist priority to all non-HCC exception candidates without considering geographic differences in social determinants of health may actually exacerbate rather than ameliorate disparity.
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Carcinoma Hepatocelular , Doença Hepática Terminal , Neoplasias Hepáticas , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Estados Unidos/epidemiologia , Doença Hepática Terminal/cirurgia , Vulnerabilidade Social , Índice de Gravidade de Doença , Listas de EsperaRESUMO
Helicobacter pylori (HP) is a causative agent in gastric cancer (GC).1 In the United States, HP is more prevalent in racial and ethnic minorities, including African Americans, Asian Americans, Latinos, and immigrants, the same groups that are more likely to develop and die from GC.2 Although screening for HP is not presently performed in the United States, there are plausible benefits to doing so, because HP is considered a group 1 carcinogen by the World Health Organization, and its link to GC parallels that of human papilloma virus and cervical cancer.1 HP eradication as a means of preventing GC also fulfils the Wilson and Jungner criteria for a successful screening program, and literature has consistently demonstrated that HP eradication reduces GC risk and death from GC.3 In fact, in countries with a high burden of GC, HP eradication is considered primary prevention for GC. As such, targeted HP testing in the United States may reduce GC burden in high-risk groups.4 We evaluate the results of community-based HP testing in an at-risk, underserved population.
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INTRODUCTION: There is considerable debate over the indication of liver transplantation (LT) for critically ill patients with cirrhosis, in part due to their potentially poor post-LT prognosis. We analyzed the epidemiology and outcome of LT for critically ill patients with cirrhosis over 4 time periods of 4 years. METHODS: We included adult patients who underwent liver transplant alone between 2005 and 2020 using the United Network for Organ Sharing registry database. We defined critically ill patients with cirrhosis as being in the intensive care unit with 1 or more of the following characteristics at the time of LT: (i) grade III/IV hepatic encephalopathy, (ii) mechanical ventilation, (iii) dialysis, and (iv) vasopressors. RESULTS: A total of 85,594 LT recipients were included, 5,827 (6.8%) of whom were classified as being critically ill with cirrhosis at the time of LT. The number and percentage of critically ill LT recipients with cirrhosis increased over the study period: 819 (4.3%) in 2005-2008 vs 2,067 (7.9%) in 2017-2020, P < 0.001. There was a 17% absolute increase in 1-year survival after LT: 72.5% in 2005-2008 vs 89.5% in 2017-2020, P < 0.001. The 1-year post-LT survival gap between critically ill and noncritically ill patients with cirrhosis narrowed over the study period: 16.7 percentage points in 2005-2008 vs 4.6 percentage points in 2017-2020. The year of LT was independently associated with lower 1-year post-LT mortality (hazard ratio 0.92, 95% confidence interval 0.91-0.93, P < 0.001). DISCUSSION: The absolute number and relative percentage of LT recipients who were critically ill increased over time, as did 1-year post-LT survival. Meanwhile, the gap in survival between this group of patients and noncritically ill patients with cirrhosis decreased but persisted. Cautious access to selected LT candidates who are critically ill may be warranted, provided the gap in survival with noncritically ill patients remains as small as possible.
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There is a subset of patients with lower MELD scores who are at substantial risk of waitlist mortality. In order to transplant such patients, transplant centers must utilize "nonstandard" donors (eg, living donors, donation after circulatory death), which are traditionally offered to those patients who are not at the top of the waitlist. We used Organ Procurement and Transplantation data to evaluate center-level and region-level variability in the utilization of nonstandard donors and its impact on MELD at transplant among adult liver-alone non-status 1 patients transplanted from April 1, 2020, to September 30, 2022. The center-level variability in the utilization of nonstandard donors was 4-fold greater than the center-level variability in waitlisting practices (waitlistings with a MELD score of <20). While there was a moderate correlation between center-level waitlisting and transplantation of patients with a MELD score of <20 ( p = 0.58), there was a strong correlation between center-level utilization of nonstandard donors and center-level transplantation of patients with a MELD score of <20 ( p = 0.75). This strong correlation between center-level utilization of "nonstandard" donors and center-level transplantation of patients with a MELD score of <20 was limited to regions 2, 4, 5, 9, and 11. Transplant centers that utilize more nonstandard donors are more likely to successfully transplant patients at lower MELD scores. Public reporting of these data could benefit patients, caregivers, and referring providers, and be used to help maximize organ utilization.
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Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Doença Hepática Terminal/cirurgia , Doadores Vivos , Índice de Gravidade de Doença , Listas de EsperaRESUMO
End-stage renal disease (ESRD) after liver transplantation (LT) is associated with high morbidity and mortality. The consequences of hospitalizations for post-LT acute kidney injury (AKI) are poorly understood. Using linked Medicare claims and transplant registry data, we analyzed adult liver alone recipients not receiving pre-transplant dialysis between 1/1/2007-12/31/2016. Covariate-adjusted Cox proportional hazards models stratified by center evaluated factors associated with AKI readmission during the first post-LT year, and whether AKI readmission was associated with de novo early (<1 y) or late (≥1 y) ESRD post-LT. The cohort included 10,559 patients and was 64.5% male, 72.5% White, 8.1% Black and 14.0% Hispanic with median age 62 years. Overall, 2,875 (27.2%) patients had ≥1 AKI hospitalization during the first year. eGFR at LT was associated with AKI readmission (aHR 1.16 per 10 mL/min/1.73m2 decrease; p<0.001). The aHR for early ESRD in patients with ≥1 AKI readmission <90 days post-LT was 1.90 (p<0.001). The aHRs for late ESRD with 1 and ≥2 prior AKI readmissions were 1.57 and 2.80 respectively (p<0.001). AKI readmissions in the first post-LT year impact over one-quarter of recipients. These increase the risk of subsequent ESRD, but may represent an opportunity to intervene and mitigate further renal dysfunction.
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The Liver Simulated Allocation Model (LSAM) is used to evaluate proposed organ allocation policies. Although LSAM has been shown to predict the directionality of changes in transplants and nonused organs, the magnitude is often overestimated. One reason is that policymakers and researchers using LSAM assume static levels of organ donation and center behavior because of challenges with predicting future behavior. We sought to assess the ability of LSAM to account for changes in organ donation and organ acceptance behavior using LSAM 2019. We ran 1-year simulations with the default model and then ran simulations changing donor arrival rates (ie, organ donation) and center acceptance behavior. Changing the donor arrival rate was associated with a progressive simulated increase in transplants, with corresponding simulated decreases in waitlist deaths. Changing parameters related to organ acceptance was associated with important changes in transplants, nonused organs, and waitlist deaths in the expected direction in data simulations, although to a much lesser degree than changing the donor arrival rate. Increasing the donor arrival rate was associated with a marked decrease in the travel distance of donor livers in simulations. In conclusion, we demonstrate that LSAM can account for changes in organ donation and organ acceptance in a manner aligned with historical precedent that can inform future policy analyses. As Scientific Registry of Transplant Recipients develops new simulation programs, the importance of considering changes in donation and center practice is critical to accurately estimate the impact of new allocation policies.
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BACKGROUND AND AIMS: Data on the epidemiology of autoimmune hepatitis (AIH) in the United States are limited. This study investigated the sociodemographic and geographic factors associated with AIH incidence and prevalence with and without cirrhosis. APPROACH AND RESULTS: In a retrospective cohort of adults in the Optum Clinformatics Data Mart (2009-2018), we identified AIH cases using a validated claims-based algorithm. Incidence and prevalence were compared between sociodemographic subgroups. Logistic regression evaluated the association of US Census Division with AIH incidence and the factors associated with incident AIH with cirrhosis. From 2009 to 2018, the age- and sex-standardized prevalence of AIH in the Optum cohort was 26.6 per 100,000 persons with an incidence of 4.0 per 100,000 person-years. AIH incidence increased earlier among Hispanics (age 50-59 years) and later among Asians (≥80 years). Adjusted AIH incidence was higher in the Mountain Division (odds ratio [OR] 1.17) and lower in the Pacific (OR 0.68), Middle Atlantic (OR 0.81), and West North Central Divisions (OR 0.86 vs. East North Central; p < 0.001). Male sex (OR 1.31, p = 0.003), Black race (OR 1.32, p = 0.022), and Hispanic ethnicity (OR 1.37 vs. non-Hispanic White, p = 0.009) were associated with incident AIH with cirrhosis. Incident AIH with cirrhosis was greater in the West South Central Division (OR 1.30 vs. South Atlantic; p = 0.008). CONCLUSIONS: AIH epidemiology differs according to sociodemographic and geographic factors in the United States. Studies are needed to determine the genetic, epigenetic, and environmental factors underlying the heterogeneity in AIH risk and outcomes.
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Hepatite Autoimune , Cirrose Hepática , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Etnicidade , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Hispânico ou Latino , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Estudos Retrospectivos , Estados Unidos/epidemiologia , Brancos , Negro ou Afro-Americano , Feminino , Idoso de 80 Anos ou mais , AsiáticoRESUMO
BACKGROUND: In May 2019, liver transplant (LT) allocation policy changed to limit MELD exception points for hepatocellular carcinoma (HCC) to median MELD at transplant minus three (MMaT-3). We evaluated this policy's impact on waitlist outcomes for HCC candidates, by race and ethnicity, hypothesizing that the introduction of the MMaT-3 reduced inequities in waitlist outcomes. METHODS: Retrospective cohort study of the Scientific Registry for Transplant Recipients, including all adult LT candidates (N = 10 751) who received HCC exception points from May 17, 2017 to May 18, 2019 (pre-policy; N = 6627) to May 19, 2019 to March 1, 2021 (post-policy; N = 4124). We compared incidence of LT and waitlist removal for death or becoming too sick pre- and post-policy for non-Hispanic White, non-Hispanic Black, Hispanic/Latinx, and Asian patients using competing risk regression adjusted for candidate characteristics. RESULTS: One-year cumulative incidence of LT decreased significantly pre-/post-policy among White (77.4% vs. 64.5%; p < .01) and Black (76.2% vs. 63.1%; p < .01) candidates only, while a 1-year incidence of death/non-LT waitlist removal decreased significantly only among Hispanics (13.4% vs. 7.5%; p < .01). After covariate adjustment, the effect of the policy change was a significantly decreased incidence of LT for White (SHR: .63 compared to pre-policy; p < .001), Black (SHR: .62; p < .001), and Asian (SHR: .68; p = .002), but no change for Hispanic patients. Only Hispanic patients had a significant decrease in death/waitlist removal after the policy change (SHR: .69; p = .04). Compared to White patients in the pre-policy era, Hispanic (SHR: .88, p < .007) and Asian candidates (SHR: .72; p < .001) had lower unadjusted incidence of LT. This disparity was mitigated in the post-policy era where Hispanic patients had higher likelihood of LT than Whites (SHR: 1.22; p = .002). For the outcome of death/non-LT waitlist removal, the only significant difference was a 42% lower incidence of waitlist removal for Asian compared to White patients in the post-policy era (SHR: .58; p = .03). CONCLUSION: Among LT recipients with HCC, racial/ethnic subpopulations were differentially affected by the MMAT-3 policy, resulting in a post-policy reduction of some of the previous disparities.
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Carcinoma Hepatocelular , Etnicidade , Neoplasias Hepáticas , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Listas de Espera , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Masculino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Etnicidade/estatística & dados numéricos , Seguimentos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Prognóstico , Taxa de Sobrevida , Disparidades em Assistência à Saúde/estatística & dados numéricos , Adulto , Sistema de Registros/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , IdosoRESUMO
BACKGROUND: Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. METHODS: We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1 year post transplant) and late (>1 year) OIs, with a particular focus on immunosuppression. RESULTS: There were 11 320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p > .05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p = .003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1 year post LT were independently associated with increased late OI (p < .001 overall). CONCLUSION: This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.
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Hospitalização , Transplante de Fígado , Medicare , Infecções Oportunistas , Humanos , Estados Unidos/epidemiologia , Masculino , Medicare/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Idoso , Infecções Oportunistas/epidemiologia , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Infecções por Citomegalovirus/epidemiologiaRESUMO
DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.
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Hepatite C Crônica , Hepatite C , Insuficiência Renal Crônica , Humanos , Hepacivirus , Antivirais/uso terapêutico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Hepatite C/tratamento farmacológico , RimRESUMO
Despite data demonstrating increased utilization of kidneys from hepatitis C virus (HCV)-infected donors, it is unknown whether this is due to an increase in the donor pool or improved organ utilization and whether data from early pilot trials were temporally associated with changes in organ utilization. We used data from the Organ Procurement and Transplantation Network on all kidney donors and recipients of kidney transplants from January 1, 2015, to March 31, 2022 to evaluate temporal changes using joinpoint regression. Our primary analyses compared donors on the basis of their HCV viremic status (HCV-infected vs HCV-negative). Kidney utilization changes were assessed by evaluating the kidney discard rate and kidneys transplanted per donor. A total of 81 833 kidney donors were included in the analysis. There was a statistically significant decrease in the discard rates of HCV-infected kidney donors from 40% to just over 20% over a 1-year period, with a concurrent increase in kidneys transplanted per donor. This increased utilization occurred in tandem with the publication of pilot trials involving HCV-infected kidney donors in HCV-negative recipients rather than an increase in the donor pool. Ongoing clinical trials may strengthen existing data, which could result in this practice becoming the accepted standard of care.
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Hepatite C , Transplante de Rim , Humanos , Estados Unidos/epidemiologia , Hepacivirus , Rim , Doadores de Tecidos , Antivirais/uso terapêuticoRESUMO
Over the last 50 years, there have been shifts in the incidence of gastric and esophageal cancers in the United States, including a decline in noncardia gastric adenocarcinoma (NCGC), and increases in cardia gastric adenocarcinoma (CGC) and esophageal adenocarcinoma (EAC).1,2 Hypotheses for the changing incidences include eradication of Helicobacter pylori, the main causative agent of NCGC, and rising rates of reflux, obesity, and diet, which are risk factors associated with EAC and CGC.1,3.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gastrointestinais , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Estados Unidos/epidemiologia , Incidência , Neoplasias Gastrointestinais/patologia , Neoplasias Gástricas/patologia , Cárdia/patologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/patologia , Fatores de Risco , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologiaRESUMO
BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.
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Neoplasias do Colo , Neoplasias Gastrointestinais , Detecção Precoce de Câncer , Humanos , Modelos Lineares , População Rural , Estados Unidos/epidemiologiaRESUMO
Our previous Multicenter Trial to Transplant HCV-infected Kidneys (MYTHIC) observed that 100% of hepatitis C virus (HCV)-uninfected patients who received a kidney from an HCV-infected deceased donor were cured of HCV with an 8-week regimen of glecaprevir and pibrentasvir (G/P) initiated 2-5 days after transplantation. Following acute and chronic infection with HCV, immune system perturbations have been reported to persist even after viral clearance. The aim of this study was to determine whether HCV viremic kidney recipients in the MYTHIC study experience sustained changes in the soluble inflammatory milieu associated with HCV infection. Among nine patients with HCV viremia at day 3 post-kidney transplant (post-KT D3), IP-10, IL-10, MIP-1ß, and IL-8 were significantly elevated from baseline. However, over the subsequent visits, there was a rapid, dramatic reduction back to baseline levels. Among seven patients who were not HCV viremic at post-KT D3, the cytokine levels did not significantly change. HCV-uninfected patients who received a kidney from an HCV-viremic deceased donor and were treated with early G/P experienced only transient alterations in the soluble inflammatory milieu. These data provide reassuring evidence that there appear to be no persistent cytokine disturbances with transient HCV viremia accompanying HCV donor positive/recipient negative kidney transplant.
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Hepatite C Crônica , Hepatite C , Humanos , Hepacivirus , Viremia , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Rim , Doadores de Tecidos , CitocinasRESUMO
Continued fossil fuel emissions will increase CO2 concentrations in the atmosphere and could require removal of 10 Gt of CO2 per year or more to reach IPCC global climate goals. Large-scale construction of direct air capture (DAC) hubs to scrub CO2 from the atmosphere paired with geological storage is a prominent approach to potentially meet this target. We consider one location for theoretical scale-up of a DAC hub: the Kerguelen plateau in the Southern Indian Ocean which has high-potential renewable energy resources (wind) and large volumes of basalt rock for mineral storage. With consistent wind, previous studies indicate a hub in this location could collect approximately 75 Mt of CO2 annually, with conservative storage resources for 150-300 Mt of CO2 each year. Even with its immense wind and storage potentials, 14 Kerguelen-scale hubs would be needed to capture and store 1 Gt of CO2 per year. This brings into focus the important social, economic, and environmental trade-offs that must be considered in finding an acceptable balance between climate solutions, renewable energy requirements, and nature. Engaging public groups on these trade-off considerations will be crucial for gigaton scale-up of CO2 removal in just and responsible ways.
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Dióxido de Carbono , Vento , Dióxido de Carbono/análise , Carbono , Atmosfera , MineraisRESUMO
Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.
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Hepatite C , Insuficiência Renal Crônica , Humanos , Hepacivirus , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Hepatite C/tratamento farmacológico , Taxa de Filtração Glomerular , RimRESUMO
Although early studies suggest the Acuity Circles (AC) allocation policy has increased access to deceased donor liver transplants (DDLTs) for patients with the highest MELD scores, changes in center- and region-level practices among patients with the highest MELD scores in response to AC are not well-characterized. OPTN/UNOS data were analyzed to compare center-level changes in the number of DDLTs based on allocation-MELD (aMELD) categories used for AC sharing performed in the 18-month periods before and after AC enactment on February 4, 2020. There was large center-level variation in the number and proportion of aMELD ≥ 37 DDLTs performed from pre-AC to AC period; 13 centers accounted for 196 of the 198 total net increase in aMELD ≥ 37 DDLTs performed after AC, 5 of these being from UNOS region 5. Similar center-level variation was seen for MELD 33-36 and MELD 29-32 DDLTs, with 17 centers and 14 centers, respectively, accounting for the entire net increase in DDLTs in the aMELD categories. In conclusion, AC increased access to livers for transplantation for high MELD patients nationally, but imbalances remain in transplant practice patterns at the center and regional levels. Longer-term study is necessary to assess effectiveness of AC in improving equitability of liver transplantations.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Transplantes , Humanos , Listas de Espera , Doadores Vivos , PolíticasRESUMO
To meet new Centers for Medicare and Medicaid Services (CMS) metrics, organ procurement organizations (OPOs) will benefit from understanding performance across decedent and hospital types. We sought to determine the utility of existing data-reporting structures for this purpose by reviewing Scientific Registry of Transplant Recipient (SRTR) OPO-Specific Reports (OSRs) from 2013 to 2019. OSRs contain both the Standardized donation rate ratio (SDRR) metric and OPO-reported numbers of "eligible deaths" and donors by hospital. Donor hospitals were characterized using information from Homeland Infrastructure Foundation-Level Data, Dartmouth Atlas Hospital Service Area data, and the US Census Bureau. Hospital data reported by OPOs showed 51% higher eligible death donors and 140% higher noneligible death donors per 100 inpatient beds in CMS ranked top versus bottom-quartile OPOs. Top-quartile OPOs by the CMS metric recovered 78% more donors than those in the bottom quartile, but were indistinguishable by SDRR rankings. These differences persisted across hospital sizes, trauma case mix, and area demographics. OPOs with divergent performance were indistinguishable over time by SDRR, but showed changes to hospital-level recovery patterns in SRTR data. Contemporaneous recognition of underperformance across hospitals may provide important and actionable data for regulators and OPOs for focused quality improvement projects.