Black Patients With Cirrhosis Have Higher Mortality and Lower Transplant Rates: Results From a Metropolitan Cohort Study.

BACKGROUND AND AIMS: Estimates of racial disparity in cirrhosis have been limited by lack of large-scale, longitudinal data, which track patients from diagnosis to death and/or transplant. APPROACH AND RESULTS: We analyzed a large, metropolitan, population-based electronic health record data set from seven large health systems linked to the state death registry and the national transplant database. Multivariate competing risk analyses, adjusted for sex, age, insurance status, Elixhauser score, etiology of cirrhosis, HCC, portal hypertensive complication, and Model for End-Stage Liver Disease-Sodium (MELD-Na), examined the relationship between race, transplant, and cause of death as defined by blinded death certificate review. During the study period, 11,277 patients met inclusion criteria, of whom 2,498 (22.2%) identified as Black. Compared to White patients, Black patients had similar age, sex, MELD-Na, and proportion of alcohol-associated liver disease, but higher comorbidity burden, lower rates of private insurance, and lower rates of portal hypertensive complications. Compared to White patients, Black patients had the highest rate all-cause mortality and non-liver-related death and were less likely to be listed or transplanted (P < 0.001 for all). In multivariate competing risk analysis, Black patients had a 26% increased hazard of liver-related death (subdistribution HR, 1.26; 95% CI, [1.15-1.38]; P < 0.001). CONCLUSIONS: Black patients with cirrhosis have discordant outcomes. Further research is needed to determine how to address these real disparities in the field of hepatology.

Liver-related mortality is similar among men and women with cirrhosis.

BACKGROUND & AIMS: Sex-based differences are known to significantly contribute to outcomes in patients with chronic liver diseases; however, the role of patient sex in cirrhosis is unclear. We aimed to study the relationship between patient sex and cirrhosis. METHODS: We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database that was linked with the United Network for Organ Sharing and cause of death data from the state death registry. Adjusted Cox survival analyses and competing risk analyses were performed to obtain subdistribution hazard ratios (HRs) for liver-related cause of death. RESULTS: Female and male patients had similar age, racial distribution, insurance status, and comorbidity status by Elixhauser score. Females had higher rates of cholestatic liver disease (17.1% vs. 6.2%, p <0.001) and non-alcoholic steatohepatitis (29.8% vs. 21.2%, p <0.001) than males. They were less likely to have portal hypertensive complications and had lower peak MELD-Na scores during follow-up. Female sex was associated with a decreased hazard of all-cause mortality (adjusted HR 0.85; 95% CI 0.80-0.90). This effect was attenuated when liver-related mortality was examined (subdistribution HR 0.93; 95% CI 0.87-1.00). No significant difference was noted for women who were 'ever-listed' in competing risk analyses for either all-cause mortality (subdistribution HR 1.09; 95% CI 0.88-1.35) or liver-related death (subdistribution HR 1.12; 95% CI 0.87-1.43), despite lower rates of listing (7.5% vs. 9.8%; p <0.001) and transplant (3.5% vs. 5.2%; p <0.001). CONCLUSIONS: In this longitudinal study of patients with cirrhosis, female sex was associated with a survival advantage likely driven by lower rates of non-liver-related death. Women were not at an increased risk of liver-related death despite lower rates of listing and transplantation. LAY SUMMARY: Patient sex is an important contributor in many chronic diseases, including cirrhosis. Prior studies have suggested that female sex is associated with worse outcomes. We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database. Using multivariate competing risk analyses, we found that female sex in cirrhosis is actually associated with a lower risk of all-cause mortality and has no association with liver-related mortality. Our findings are novel because we show that women with cirrhosis have a similar risk of liver-related death as their male counterparts, despite lower rates of listing and transplantation.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Urinary incontinence imposes a significant health and economic burden to society. Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used as one the surgical treatments of stress urinary incontinence (SUI) in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable therapy with respect to continence grade (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (mean difference (MD) 0.54, 95% CI 0.16 to 0.92). Another trial, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610.12) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in RevMan) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects. Also, a Brief Economic Commentary (BEC) identified three studies suggesting that urethral bulking agent might be more cost-effective compared with retropubic mid-urethral slings, transobturator or traditional sling procedure when used as an initial treatment in women without hypermobility or as a follow-up to surgery failure provided injection is kept minimal. However, urethral bulking agent might not be cost-effective when compared with traditional sling as an initial treatment of SUI when a patient is followed up for a longer period (15 months post-surgery).

Factors Underlying Racial Disparity in Utilization of Hepatitis C-Viremic Kidneys in the United States.

Utilization of hepatitis C (HCV) viremic kidneys is increasing in the United States. We examined racial disparity in this utilization using UNOS/OPTN data (2014-2020) and mixed effects models adjusting for donor/recipient/center factors. Included in the study were 58,786 adults receiving a deceased donor kidney transplant from 191 centers. Two thousand six hundred thirteen (4%) received kidneys from HCV-viremic donors. Of these, 1598 (61%) were HCV seronegative and 1015 (49%) were HCV seropositive. Among seronegative recipients, before adjusting for waiting time and education, Blacks (OR 0.69, 95%CI (0.60, 0.80)), Hispanics (OR 0.63, 95%CI (0.51, 0.79)), and Asians (OR 0.69, 95%CI (0.53, 0.90)) were less likely than Whites to receive HCV-viremic kidneys. In final models, effect of race was attenuated. Notably, shorter waiting time (OR 0.65, 95%CI (0.63, 0.67)) and increasing educational level (grade school less likely compared to high school OR 0.67, 95% CI (0.49, 0.92) and college more likely than high school (OR 1.16 95% CI (1.02, 1.31)) were associated with receipt of HCV-viremic kidneys. Among HCV-seropositive recipients, recipient race was not independently associated with receipt of HCV-viremic kidneys; however, centers with larger populations of Black waitlisted patients were more likely to utilize HCV-viremic kidneys (OR 1.71, 95%CI (1.20, 2.45)) compared to other centers. Our results suggest recipient race does not independently determine who receives HCV-viremic kidneys; however, other underlying factors including waiting time, education (among seronegative), and center racial mix (among seropositive) contribute to the current differential distribution of HCV-viremic kidneys among races.

Urethral injection therapy for urinary incontinence in women.

BACKGROUND: Periurethral or transurethral injection of bulking agents is a minimally invasive surgical procedure used for the treatment of stress urinary incontinence in adult women. OBJECTIVES: To assess the effects of periurethral or transurethral injection therapy on the cure or improvement of urinary incontinence in women. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 November 2010) and the reference lists of relevant articles. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials of treatment for urinary incontinence in which at least one management arm involved periurethral or transurethral injection therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality of each study using explicit criteria. Data extraction was undertaken independently and clarification concerning possible unreported data sought directly from the investigators. MAIN RESULTS: Excluding duplicate reports, we identified 14 trials (excluding one that was subsequently withdrawn from publication and not included in this analysis) including 2004 women that met the inclusion criteria. The limited data available were not suitable for meta-analysis because they all came from separate trials. Trials were small and generally of moderate quality.One trial of 45 women that compared injection therapy with conservative treatment showed early benefit for the injectable with respect to continence grade (risk ratio (RR) 0.7, 95% confidence interval (CI) 0.52 to 0.94) and quality of life (RR 0.54, 95% CI 0.16 to 0.92). Another, comparing Injection of autologous fat with placebo, terminated early because of safety concerns. Two trials that compared injection with surgical management found significantly better objective cure in the surgical group (RR 4.77, 95% CI 1.96 to 11.64; and RR 1.69, 95% CI 1.02 to 2.79), although the latter trial data did not reach statistical significance if an intention-to-treat analysis was used.Eight trials compared different agents and all results had wide confidence intervals. Silicone particles, calcium hydroxylapatite, ethylene vinyl alcohol, carbon spheres and dextranomer hyaluronic acid combination gave improvements which were not shown to be more or less efficacious than collagen. Dextranomer hyaluronic acid compound treated patients appeared to have significantly higher rates of injection site complications (16% with the hyaluronic acid compound versus none with collagen; RR 37.78, 95% CI 2.34 to 610) and this product has now been withdrawn from the market.A comparison of periurethral and transurethral methods of injection found similar outcomes but a higher (though not statistically significant) rate of early complications in the periurethral group. One trial of 30 women showed a weak (but not clinically significant) advantage for patient satisfaction (data not suitable for analysis in Revman) after mid-urethral injection in comparison to bladder neck injection but with no demonstrable difference in continence levels. AUTHORS' CONCLUSIONS: The available evidence base remains insufficient to guide practice. In addition, the finding that placebo saline injection was followed by a similar symptomatic improvement to bulking agent injection raises questions about the mechanism of any beneficial effects. One small trial comparing silicone particles with pelvic floor muscle training was suggestive of benefit at three months but it is not known if this was sustained, and the treatment was associated with high levels of postoperative retention and dysuria. Greater symptomatic improvement was observed with surgical treatments, though the advantages need to be set against likely higher risks. No clear-cut conclusions could be drawn from trials comparing alternative agents, although dextranomer hyaluronic acid was associated with more local side effects and is no longer commercially available for this indication. There is insufficient evidence to show superiority of mid-urethral or bladder neck injection. The single trial of autologous fat provides a reminder that periurethral injections can occasionally cause serious side effects.

Resolution of Disseminated Angiosarcoma in a Kidney Transplant Recipient After Treatment With Sirolimus: A Case Report.

Angiosarcoma is a rare, almost universally fatal malignant neoplasm in kidney transplant recipients. No evidence-based guidelines are available for disseminated disease. Here, we report a case of a 66-year-old woman who developed disseminated angiosarcoma 4 months after living nonrelated kidney transplant. She underwent only 2 rounds of chemotherapy because of intolerable adverse effects. Her mycophenolic acid and tacrolimus were withdrawn and sirolimus use was started. In addition to its immunosuppressant effects, sirolimus has been shown to have antineoplastic properties. Remarkably, at almost 2 years post-transplant, the patient has had complete resolution of all gross metastatic disease with only immunosuppressant medication changes. This case highlights the interesting possibility that sirolimus is an effective adjunct treatment for disseminated angiosarcoma in kidney transplant recipients.

Observational Study of the Clinical Characteristics and Short-Term Outcomes of Kidney Transplant Recipients Diagnosed With COVID-19 Infection (SARS-CoV-2) Requiring Hospitalization in New Orleans.

Background: Kidney transplant recipients are at increased risk of severe disease and death caused by coronavirus disease 2019 (COVID-19) infection. The role of immunosuppressive medications in the clinical presentation, disease course, and outcomes is not well understood. Methods: We analyzed kidney transplant recipients diagnosed with COVID-19 and requiring hospitalization during the initial infection surge at 2 large transplant centers in New Orleans, Louisiana, between February 1, 2020 and April 30, 2020. Patient presentation, clinical course, kidney transplant function, and postdischarge details are included in this analysis. Results: Twenty-three kidney transplant recipients hospitalized with COVID-19 were included in the study. The majority of patients were Black (95.7%). Diabetes, hypertension, and obesity were present in more than 50% of the patients. The most common presenting symptom was fever, present in 52.2% of patients. All patients were managed with reduction in immunosuppression. Patients received azithromycin (60.9%), hydroxychloroquine (47.8%), remdesivir (8.7%), and intravenous methylprednisolone pulse (8.7%). The average length of stay was 4.5 days (range, 2-18 days). In this study population, 73.9% of the patients sustained acute kidney injury, with an average peak serum creatinine of 3.81 mg/dL. Twenty-six percent of the patients required renal replacement therapy. Seventy-seven percent of patients developed proteinuria (at least 1+ proteinuria on urinalysis). Of the patients in this population who required mechanical ventilation (39.1%), 77.8% died. Overall, 30.4% of patients died of COVID-19-related complications during admission. Of the 16 patients discharged, the average serum creatinine at discharge was 2.09 mg/dL compared with an average preadmission serum creatinine of 1.8 mg/dL. Conclusion: During the initial COVID-19 infection surge in New Orleans, we noted that kidney transplant recipients had initial symptoms similar to the general population. However, we recorded a higher incidence of acute kidney injury and death compared to nontransplant patients. Patients who required mechanical ventilation had a high mortality rate. Black patients are overrepresented in our study.

Health Literacy Gaps in Online Resources for Cirrhotic Patients.

BACKGROUND: The average readability level in the USA is a sixth grade level and for patients with chronic disease it is lower. Cirrhosis is a prevalent chronic disease that requires complex knowledge and instructions to manage. No research has been done about the understandability of online educational content for cirrhotic patients. Patients can find online materials curated by both general health platforms and high-volume liver transplant centers, and thus these materials were analyzed. METHODS: After determining exclusion criteria, the websites of the top 20 general health platform results and the websites of the top 20 high-volume hepatology centers were analyzed. Readability was assessed using the Patient Education Materials Assessment Tool (Audiovisual Materials) (PEMAT-A/V), Flesch-Kincaid Grade Level tests, word counts, sentence counts, words per sentence, and time for an average sixth grader to read. RESULTS: The mean grade level readabilities were 12.3 and 11.3 for the general resources and the transplant center resources, respectively. The online resources ranged from 9 to 389 sentences requiring an average of 9.8 min to read. The mean PEMAT-A/V scores were 70.05% for the general resources and 72.45% for the transplant center resources. There was a statistically significant difference in the Flesch-Kincaid grade level, sentence number, words per sentence, word count, and time for an average sixth grader to read the general resources and transplant center resources (P < 0.05). CONCLUSIONS: The online resources both from health platforms and hepatology centers available to patients with cirrhosis are too long and complex and underscore the need for simpler and shorter resources.

A Comprehensive Review of Outcome Predictors in Low MELD Patients.

Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.

Patients With Persistently Low MELD-Na Scores Continue to Be at Risk of Liver-related Death.

BACKGROUND: The vast majority of patients with cirrhosis have low Model for End-Stage Liver Disease-Sodium (MELD-Na) scores; however, the ability for the MELD-Na score to predict patient outcomes at low scores is unclear. METHODS: Adult patients in a multicenter, Chicago-wide database of medical records with International Classification of Disease, Ninth Edition codes of cirrhosis and without a history of hepatocellular carcinoma were included. Records were linked with the state death registry, and death certificates were manually reviewed. Deaths were classified as "liver-related," "non-liver-related," and "non-descript" as adjudicated by a panel comprised of a transplant surgeon, a hepatologist, and an internist. A sensitivity analysis was performed where patients with hepatocellular carcinoma were included. RESULTS: Among 7922 identified patients, 3999 patients had MELD-Na scores that were never higher than 15. In total, 2137 (27%) patients died during the study period with higher mortality rates for the patients in the high MELD-Na group (19.4 (41.6%) versus 4.1 (12.6%) per 100 person-y, P < 0.001). The high MELD-Na group died of a liver-related cause in 1142 out of 1632 (70%) as compared to 240 out of 505 (47.5%) deaths in the low MELD-Na group. There was no difference in the distribution of subcategory of liver-related death between low and high MELD-Na groups. Among subclassification of liver-related deaths, the most common cause of death was "Infectious" in both groups. CONCLUSIONS: Despite persistently low MELD-Na scores, patients with cirrhosis still experience high rates of liver-related mortality.

The Hispanic Paradox in Patients With Liver Cirrhosis: Current Evidence From a Large Regional Retrospective Cohort Study.

BACKGROUND: Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW). METHODS: We used multivariable Cox regression to assess whether this "Hispanic paradox" applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database. RESULTS: Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease. CONCLUSIONS: Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.

Real-World Study of Once-Daily, Extended-Release Tacrolimus Versus Twice-Daily, Immediate-Release Tacrolimus in Kidney Transplantation: Clinical Outcomes and Healthcare Resource Utilization.

INTRODUCTION: Real-world data with extended-release tacrolimus (ER-T) are lacking in the USA. This study examined clinical outcomes and healthcare resource utilization in kidney transplant patients receiving ER-T in clinical practice. METHODS: This was a retrospective, single-center analysis (February-June 2016) using data from Northwestern University's Enterprise Data Warehouse. Adult patients receiving a kidney transplant in the preceding 4 years, treated de novo or converted to ER-T from immediate-release tacrolimus (IR-T) within 10 days post-transplantation, and maintained on ER-T (at least 3 months) were included. Patients were matched for demographic and clinical characteristics with IR-T-treated control patients. Endpoints included clinical outcomes and healthcare resource utilization up to 1 year post-transplantation. RESULTS: A total of 19 ER-T-treated patients were matched with 55 IR-T-treated patients. No ER-T-treated patients experienced biopsy-confirmed acute rejection (BCAR) or graft failure versus 3 (5.5%) and 3 (5.5%) IR-T-treated patients, respectively. Mean estimated glomerular filtration rate (eGFR), the number of all-cause outpatient visits, readmissions, and all-cause hospitalization days were comparable between groups. Tacrolimus trough levels, days to target level (6-10 ng/mL), and number of required dose adjustments were also similar. CONCLUSION: Real-world clinical outcomes and healthcare resource utilization were similar with ER-T and IR-T. Larger studies will need to investigate the trend toward fewer BCAR events, and increased graft survival with ER-T. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

How close are we to knowing whether orthotopic bladder replacement surgery is the new gold standard?--evidence from a systematic review update.

OBJECTIVES: To compare the clinical effectiveness and risk profile of the different types of surgeries using transposed intestinal segments in a systematic review update. Urinary diversion is designed to improve or replace the function of the diseased urinary bladder. METHODS: Studies reporting on surgery involving intestinal segments transposed into the urinary tract were identified between January 1990 and January 2007 using MEDLINE, PubMed, EMBASE, CINAHL, and the Cochrane Library. All articles published in English language reporting on at least 10 patients and follow-up of at least 1 year were included. This is a substantive update of our previously published systematic review that reported on the evidence between January and to January 2003 (Nabi G, Yong SM, Ong E, et al. J Urol. 2005;174:21-28). RESULTS: Between January 1990 and January 2007, a total of 5651 abstracts were reviewed. Of them, 557 studies met the inclusion criteria reporting on 46,921 participants (an additional 14,126 participants reported on between January 2003 and January 2007). Operative complications were lowest in ileal conduit diversion, whereas postoperative morbidity and mortality were lower for orthotopic bladder replacement surgery. Of the 35 quality-of-life studies, only 2 studies (Dutta SC, Chang SC, Coffey CS, et al. J Urol. 2002;168:164-167; Hobisch A, Tosun K, Kinzl J, et al. World J Urol. 2000;18:338-344) reported a better quality of life with orthotopic bladder replacement. CONCLUSIONS: This systematic review update fails to reveal a clear winner, with each intervention type having advantages and disadvantages. With > 46,000 patients included in transposed intestinal segment research over the past 16 years, it is surely a criticism of our speciality that we are no closer to answering the question of what is the best way to improve or replace the function of the diseased bladder.