Post-diagnostic metformin and statin use and risk of biochemical recurrence in Veterans diagnosed with prostate cancer.

OBJECTIVE: To evaluate the impact of post-diagnostic metformin or statin use and duration on risk of biochemical recurrence in a racially-diverse cohort of Veterans. METHODS: The population consisted of men diagnosed with prostate cancer in the Veterans Health Administration and treated with either radical prostatectomy or radiation (Full cohort n = 65,759, Black men n = 18,817, White men n = 46,631, Other = 311). The association between post-diagnostic (1) metformin and (2) statin use with biochemical recurrence was assessed using multivariable, time-varying Cox Proportional Hazard Models for the overall cohort and by race. In a secondary analysis, metformin and statin duration were evaluated. RESULTS: Post-diagnostic metformin use was not associated with biochemical recurrence (multivariable-adjusted hazard ratio [aHR]: 1.01; 95% confidence interval [CI]: 0.94, 1.09), with similar results observed for both Black and White men. However, duration of metformin use was associated with a reduced risk of biochemical recurrence in the cohort overall (HR: 0.94; 95% CI: 0.92, 0.95) as well as both Black and White men. By contrast, statin use was associated with a reduced risk of biochemical recurrence (HR: 0.83; 95% CI: 0.79, 0.88) in the overall cohort as well as both White and Black men. Duration of statin use was also inversely associated with biochemical recurrence in all groups. CONCLUSION: Post-diagnostic metformin and statin use have the potential to prevent biochemical recurrence in men diagnosed with prostate cancer.

The association of donor hepatitis C virus infection with 3-year kidney transplant outcomes in the era of direct-acting antiviral medications.

To determine the effect of donor hepatitis C virus (HCV) infection on kidney transplant (KT) outcomes in the era of direct-acting antiviral (DAA) medications, we examined 68,087 HCV-negative KT recipients from a deceased donor between March 2015 and May 2021. A Cox regression analysis was used to estimate adjusted hazard ratios (aHRs) of KT failure, incorporating inverse probability of treatment weighting to control for patient selection to receive an HCV-positive kidney (either nucleic acid amplification test positive [NAT+, n = 2331] or antibody positive (Ab+)/NAT- [n = 1826]) based on recipient characteristics. Compared with kidney from HCV-negative donors, those from Ab+/NAT- (aHR = 0.91; 95% confidence interval [CI], 0.75-1.10) and HCV NAT+ (aHR = 0.89; 95% CI, 0.73-1.08) donors were not associated with an increased risk of KT failure over 3 years after transplant. Moreover, HCV NAT+ kidneys were associated with a higher 1-year estimated glomerular filtration (63.0 vs 61.0 mL/min/1.73 m2, P = .007) and lower risk of delayed graft function (aOR = 0.76; 95% CI, 0.68-0.84) compared with HCV-negative kidneys. Our findings suggest that donor HCV positivity is not associated with an elevated risk of graft failure. The inclusion of donor HCV status in the Kidney Donor Risk Index may no longer be appropriate in contemporary practice.

Development and validation of the lung donor (LUNDON) acceptability score for pulmonary transplantation.

There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.

Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer.

OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.

Comparison Between Veteran and Non-Veteran Populations With Clinical Stage I Non-small Cell Lung Cancer Undergoing Surgery.

OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.

Development and Validation of the VA Lung Cancer Mortality (VALCAN-M) Score for 90-Day Mortality Following Surgical Treatment of Clinical Stage I Lung Cancer.

OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.

The association of center volume with transplant outcomes in selected high-risk groups in kidney transplantation.

BACKGROUND: In context of increasing complexity and risk of deceased kidney donors and transplant recipients, the impact of center volume (CV) on the outcomes of high-risk kidney transplants(KT) has not been well determined. METHODS: We examined the association of CV and outcomes among 285 U.S. transplant centers from 2000-2016. High-risk KT were defined as recipient age ≥ 70 years, body mass index (BMI) ≥ 35 kg/m2, receiving kidneys from donors with kidney donor profile index(KDPI) ≥ 85%, acute kidney injury(AKI), hepatitisC + . Average annual CV for the specific-high-risk KT categorized in tertiles. Death-Censored-Graft-Loss(DCGL) and death at 3 months, 1, 5, and 10 years were compared between CV tertiles using Cox-regression models. RESULTS: Two hundred fifty thousand five hundred seventy-four KT were analyzed. Compared to high CV, recipients with BMI ≥ 35 kg/m2 had higher risk of DCGL in low CV(aHR = 1.11,95%CI = 1.03-1.19) at 10 years; recipients with age ≥ 70 years had higher risk of death in low CV(aHR = 1.07,95%CI = 1.01-14) at 10 years. There was no difference of DCGL or death in low CV for donors with KDPI ≥ 85%, hepatitisC + , or AKI. CONCLUSIONS: Recipients of high-risk KT with BMI ≥ 35 kg/m2 have higher risk of DCGL and recipients age ≥ 70 years have higher risk of death in low CV, compared to high CV. Future studies should identify care practices associated with CV that support optimal outcomes after KT.

Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

Simultaneous pancreas-kidney transplantation (SPK) carries about a 7%-22% risk of technical failure, but the impact of early pancreas allograft loss on subsequent kidney graft and patient survival is not well-defined. We examined national transplant registry data for type 1 diabetic patients who received SPK between 2000 and 2021. Associations of transplant type (i.e., SPK, deceased-donor kidney transplant [DDKA], living-donor kidney transplant [LDKA]) with kidney graft failure and patient survival were estimated by multivariable inverse probability of treatment-weighted accelerated failure-time models. Compared to SPK recipients with a functioning pancreas graft 3 months posttransplant (SPK,P+), LDKA had 18% (Time Ratio [TR] 0.82, 95%CI: 0.70-0.95) less graft survival time and 18% (TR 0.82, 95%CI: 0.68-0.97) less patient survival time, DDKA had 23% (TR 0.77, 95%CI: 0.68-0.87) less graft survival time and 29% (TR 0.71, 95%CI: 0.62-0.81) less patient survival time, and SPK with early pancreas graft loss had 34% (TR 0.66, 95%CI: 0.56-0.78) less graft survival time and 34% (TR 0.66, 95%CI: 0.55-0.79) less patient survival time. In conclusion, SPK,P+ recipients have better kidney allograft and patient survival compared with LDKA and DDKA. Early pancreas graft failure results in inferior kidney and patient survival time compared to kidney transplant alone.

Corrigendum: Survival After Simultaneous Pancreas-Kidney Transplantation in Type 1 Diabetes: The Critical Role of Early Pancreas Allograft Function.

[This corrects the article DOI: 10.3389/ti.2022.10618.].

Single-center experience of liver transplantation for perihilar cholangiocarcinoma.

BACKGROUND: Traditionally, curative resection was considered the cornerstone of treatment for perihilar cholangiocarcinoma. More recently, liver transplantation (LT) offered an alternative for patients with unresectable disease. The purpose of this study was to assess our experience with perihilar cholangiocarcinoma and LT. METHODS: A perihilar cholangiocarcinoma protocol was commenced in 2006 whereby diagnosed patients were enrolled onto an institutional registry for LT consideration. Data on patient progression and oncologic outcomes were assessed. RESULTS: Fifty-eight patients were initially enrolled onto the protocol and 38 proceeded to LT following neoadjuvant chemoradiation (mean age 55.6 ± 11.4 years). Mean time to LT was 3.7 ± 2 months and, among those transplanted, 14 (37%) had underlying primary sclerosing cholangitis (PSC). Thirteen (34%) patients developed malignant recurrence and there were no differences in disease recurrence between PSC (n = 3) and non-PSC (n = 10) patients (p = 0.32). Overall patient survival was 91%, 58% and 52% at 1-, 3- and 5-years corresponding with 81%, 52% and 46% graft survival, respectively. CONCLUSION: Rigorous patient selection and chemoradiation treatment algorithms can be highly effective in treating perihilar cholangiocarcinoma. For appropriately selected candidates, LT can provide a 52% 5-year survival for patients who would otherwise have no surgical treatment option.

Domino liver transplants: where do we stand after a quarter-century? A US national analysis.

BACKGROUND: Domino liver transplantation (DLT) utilizes a phenotypically normal explant from select recipients as a donor graft in another patient. The procedure is not widely employed and remains restricted to a small number of centers. The purpose of this study was to assess the national profile of DLT in the United States (US) and evaluate current survival outcomes. METHODS: The United Network for Organ Sharing (UNOS) database was queried for all liver transplants (LT) between 1996 and 2020. Outcomes of interest were long-term graft and patient survival. RESULTS: Of 181,976 LTs performed nationally during the study period, 185 (0.1%) were DLTs. Amyloidosis and maple syrup urine disease (MSUD) accounted for 83% of dominoed allografts. Out of 210 explants with amyloidosis, 103 (49%) were dominoed into secondary recipients. Only 50 (22%) of all MSUD explants (n = 227) were dominoed. Graft survival was 79%, 73% and 53% at 3-, 5- and 10-years, respectively, for DLT recipients. Overall patient survival was 83%, 76% and 57% at 3-, 5- and 10-years. CONCLUSION: Despite excellent long-term survival outcomes, DLT allografts comprise a very small percentage of the liver donor pool. A large proportion of potential DLTs may be unconscionably excluded despite shortages in deceased donor organs.

Kidney recipients with allograft failure, transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers.

Kidney allograft failure and return to dialysis carry a high risk of morbidity. A practice survey was developed by the AST Kidney Pancreas Community of Practice workgroup and distributed electronically to the AST members. There were 104 respondents who represented 92 kidney transplant centers. Most survey respondents were transplant nephrologists at academic centers. The most common approach to immunosuppression management was to withdraw the antimetabolite first (73%), while only 12% responded they would withdraw calcineurin inhibitor (CNI) first. More than 60% reported that the availability of a living donor is the most important factor in their decision to taper immunosuppression, followed by risk of infection, risk of sensitization, frailty, and side effects of medications. More than half of respondents reported that embolization was either not available or offered to less than 10% as an option for surgical intervention. Majority reported that ≤50% of failed allograft patients were re-listed before dialysis, and less than a quarter of transplant nephrologists performed frequent visits with their patients with failed kidney allograft after they return to dialysis. This survey demonstrates heterogeneity in the care of patients with a failing allograft and the need for more evidence to guide improvements in clinical practice related to transition of care.

Racial/Ethnic Differences in the Risk of Surgical Complications and Posthysterectomy Hospitalization among Women Undergoing Hysterectomy for Benign Conditions.

STUDY OBJECTIVE: Evaluate whether 30- and 90-day surgical complication and postoperative hospitalization rates after hysterectomy for benign conditions differ by race/ethnicity and whether the differences remain after controlling for patient, hospital, and surgical characteristics. DESIGN: Retrospective cohort study using administrative data. The exposure was race/ethnicity. The outcomes included 5 different surgical complications/categories and posthysterectomy inpatient hospitalization, all identified through 30 and 90 days after hysterectomy hospital discharge, with the exception of hemorrhage/hematoma, which was only identified through 30 days. To examine the association between race/ethnicity and each outcome, we used logistic regression with clustering of procedures within hospitals, adjusting for patient and hospital characteristics and surgical approach. SETTING: Multistate, including Florida and New York. PATIENTS: Women aged ≥18 years who underwent hysterectomy for benign conditions using State Inpatient Databases and State Ambulatory Surgery Databases. INTERVENTIONS: Hysterectomy for benign conditions. MEASUREMENTS AND MAIN RESULTS: We included 183 697 women undergoing hysterectomy for benign conditions from January 2011 to September 2014. In analysis, adjusting for surgery route and other factors, black race was associated with increased risk of 30-day digestive system complications (multivariable adjusted odds ratio [aOR], 1.98; 95% confidence interval [CI], 1.78-2.21), surgical-site infection (aOR, 1.34; 95% CI, 1.18-1.53), posthysterectomy hospitalization (aOR, 1.31; 95% CI, 1.22-1.40), and urologic complications (aOR, 1.16; 95% CI, 1.01-1.34) compared with white race. Asian/Pacific Islander race was associated with increased risk of 30-day urologic complications (aOR, 1.48; 95% CI, 1.08-2.03), intraoperative injury to abdominal/pelvic organs (aOR, 1.46; 95% CI, 1.23-1.75), and hemorrhage/hematoma (aOR, 1.33; 95% CI, 1.06-1.67) compared with white race. Hispanic ethnicity was associated with increased risk of 30-day posthysterectomy hospitalization (aOR, 1.11; 95% CI, 1.02-1.20) compared with white race. All findings were similar at 90 days. CONCLUSION: Black and Asian/Pacific Islander women had higher risk of some 30- and 90-day surgical complications after hysterectomy than white women. Black and Hispanic women had higher risk of posthysterectomy hospitalization. Intervention strategies aimed at identifying and better managing disparities in pre-existing conditions/comorbidities could reduce racial/ethnic differences in outcomes.

Three-month pancreas graft function significantly influences survival following simultaneous pancreas-kidney transplantation in type 2 diabetes patients.

Successful simultaneous pancreas-kidney transplantation (SPK) improves quality-of-life and prolongs kidney allograft and patient survival in type-1 diabetic (T1DM) patients. However, the use of SPK in type-2 diabetic (T2DM) patients remains limited. We examined a national transplant registry for 35 849 T2DM kidney disease patients who received transplant between 2000 and 2016 and survived the first 3 months with a functioning kidney, and categorized as: deceased-donor kidney transplant alone (DD-KA, 68%), living-donor kidney transplant alone (LD-KA, 30%), or SPK (2%). Among SPK recipients, 6% had pancreas allograft failure within 3 months (SPK,P-) and 94% had a functional pancreas (SPK,P+). Associations of transplant type with kidney allograft failure and death (multivariable-adjusted hazard ratio, 95%LCL aHR95%UCL ), over follow-up through December 2018, were quantified by multivariable inverse probability of treatment weighted survival analyses. SPK recipients had better kidney graft and patient survival than LD-KA or DD-KA recipients. Compared to SPK,P+, DD-KA, or LD-KA recipients had significantly higher risk of kidney allograft failure (DD-KA: aHR 1.53 2.203.17 ; LD-KA: aHR 1.29 1.872.71 ) and death (DD-KA: aHR 2.12 3.255.00 ; LD-KA: aHR 1.54 2.353.59 ). SPK,P- recipients had significantly higher risk of death (aHR 1.68 3.306.50 ). Similar to T1DM, T2DM patients with SPK have a survival benefit compared to those with kidney transplant alone, but this benefit depends upon successful early pancreas function.

Cost-effectiveness analyses demonstrate that observation is superior to sentinel lymph node biopsy for postmenopausal women with HR + breast cancer and negative axillary ultrasound.

PURPOSE: To evaluate the cost-effectiveness of axillary observation versus sentinel lymph node biopsy (SLNB) after negative axillary ultrasound (AUS). In patients with clinical T1-T2 N0 breast cancer and negative AUS, SLNB is the current standard of care for axillary staging. However, SLNB is costly, invasive, decreasing in importance for medical decision-making, and is not considered therapeutic. Observation alone is currently being evaluated in randomized clinical trials, and is thought to be non-inferior to SLNB for patients with negative AUS. METHODS: We performed cost-effectiveness analyses of observation versus SLNB after negative AUS in postmenopausal women with clinical T1-T2 N0, HR+/HER2- breast cancer. Costs at the 2016 price level were evaluated from a third-party commercial payer perspective using the MarketScan® Database. We compared cost, quality-adjusted life years (QALYs), and net monetary benefit (NMB). Multiple sensitivity analyses varying baseline probabilities, costs, utilities, and willingness-to-pay thresholds were performed. RESULTS: Observation was superior to SLNB for patients with N0 and N1 disease, and for the entire patient population (NMB in US$: $655,659 for observation versus $641,778 for SLNB for the entire patient population). In the N0 and N1 groups, observation incurred lower cost and was associated with greater QALYs. SLNB was superior for patients with > 3 positive lymph nodes, representing approximately 5% of the population. Sensitivity analyses consistently demonstrated that observation is the optimal strategy for AUS-negative patients. CONCLUSION: Considering both cost and effectiveness, observation is superior to SLNB in postmenopausal women with cT1-T2 N0, HR+/HER2- breast cancer and negative AUS.

Estimating the impact of increasing cervical cancer screening in the National Breast and Cervical Cancer Early Detection Program among low-income women in the USA.

PURPOSE: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides free cervical cancer screening to low-income women. This study estimated the health benefits gained in terms of life years (LYs) saved and quality-adjusted life years (QALYs) gained if cervical cancer screening by the NBCCEDP increased to reach more eligible women. METHODS: Data from Surveillance, Epidemiology, and End Results, NBCCEDP, and Medical Expenditure Panel Surveys were used. LYs saved and QALYs gained/100,000 women were estimated using modeling methods. They were used to predict additional health benefits gained if screening by the NBCCEDP increased from 6.5% up to 10-25% of the eligible women. RESULTS: Overall, per 100,000 women screened by the NBCCEDP, 1,731 LYs were saved and 1,608 QALYs were gained. For white women, 1,926 LYs were saved and 1,780 QALYs were gained/100,000 women screened by the NBCCEDP. For black women, 1,506 LYs were saved and 1,300 QALYs were gained/100,000 women screened. If the proportion of eligible women screened by the NBCCEDP increased to 10-25%, the estimated health benefits would range from 6,626-34,896 LYs saved and 6,153-32,407 QALYs gained. CONCLUSIONS: The reported estimates emphasize the value of cervical cancer screening program by extending LE in low-income women. Further, it demonstrates that screening a higher percentage of eligible women in the NBCCEDP may yield more health benefits.

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data.

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.

Obesity-related multimorbidity and risk of cardiovascular disease in the middle-aged population in the United States.

To investigate the prevalence of obesity-related multimorbidity (co-occurrence of ≥2 obesity-related chronic diseases, ORCDs) and the risk of cardiovascular disease in the presence of multimorbidity in middle-aged adults in the United States. National Health and Nutrition Examination Survey data from 2007 to 2016 were used. Target ORCDs included hypertension (H), diabetes (D), coronary heart disease (C), and stroke (S). Age-standardized prevalence for obesity-related multimorbidity in its combination and permutation was calculated. Risk for cardiovascular disease (C or S) was estimated conditional on demographics, degree of obesity, and presence and duration of pre-existing ORCDs. Analyses were conducted at Washington University in 2019. The analytic sample included 14,243 individuals age 40-79 years, representing a population size of 110,003,550. Age-standardized prevalence for obesity-related multimorbidity was 12.3%. Hypertension was most commonly the first diagnosed ORCD for populations with 2-4 ORCDs, followed by diabetes for populations with 2-3 ORCDs. Compared with no pre-existing hypertension/diabetes/stroke, pre-existing hypertension in combination with diabetes/stroke significantly increased risk of coronary heart disease [H + S (multivariable-adjusted hazard ratio, aHR 27.6, 95% CI 10.9-70.2), D + H + S (aHR 20.3, 95% CI 7.9-52.2)]. Compared with no hypertension/diabetes/coronary heart disease, pre-existing hypertension in combination with diabetes/coronary heart disease significantly increased risk of stroke [C + D + H (aHR 32.6, 95% CI 12.2-87.1), C + H (aHR 25.4, 95% CI 12.1-53.6), D + H (aHR 5.3, 95% CI 2.6-10.8)]. Obesity-related multimorbidity is prevalent and highly associated with cardiovascular disease development. To reduce the detrimental health impact of multimorbidity, intervention strategies should target preventing increasing multimorbidity and detecting/managing diabetes and hypertension prior to the onset of cardiovascular disease.

Racial/Ethnic Disparities/Differences in Hysterectomy Route in Women Likely Eligible for Minimally Invasive Surgery.

STUDY OBJECTIVE: Evaluate racial/ethnic variation in hysterectomy surgical route in women likely eligible for minimally invasive hysterectomy. DESIGN: Cross-sectional study. SETTING: Multistate including Colorado, Florida, Maryland, New Jersey, and New York. PATIENTS: Women aged ≥18 years without diagnoses of leiomyomas, obesity, or previous abdominopelvic surgery who underwent hysterectomy for benign conditions from the State Inpatient and Ambulatory Surgery Databases, 2010-2014. INTERVENTIONS: None. Primary exposure is race/ethnicity. MEASUREMENTS AND MAIN RESULTS: Racial/ethnic variation in annual hysterectomy rates and surgical route. To calculate hysterectomy rates per 100 000 women/year, denominators were adjusted for the proportion of women with previous hysterectomy. A marginal structural log binomial regression model was used to estimate adjusted standardized prevalence ratios (aPRs) for vaginal or laparoscopic vs abdominal hysterectomy, controlling for clustering within hospitals. In addition, hospitals were stratified into quintiles to examine surgical route in hospitals that serve a higher vs lower proportion of African American patients. A total of 133 082 adult women underwent hysterectomy for benign conditions from 2010 to 2014. Annual laparoscopic rates increased more slowly for African Americans (1.6-fold) than for whites (1.8-fold) and Hispanics (1.9-fold). African American and Hispanic women were less likely to undergo vaginal (aPR = 0.93; 95% confidence interval [CI], 0.90-0.96 and aPR = 0.95; 95% CI 0.93-0.97, respectively) and laparoscopic hysterectomy (aPR = 0.90; 95% CI, 0.87-0.94 and aPR = 0.95; 95% CI, 0.92-0.98, respectively) than white women; Asian/Pacific Islander women were less likely to undergo vaginal hysterectomy (aPR = 0.88; 95% CI, 0.81-0.96). Hospitals serving a higher proportion of African American persons performed more abdominal and fewer vaginal procedures across all groups, and more racial/ethnic minority women sought care at those hospitals than white women. CONCLUSION: African American, Hispanic, and Asian/Pacific Islander women eligible for minimally invasive hysterectomy were more likely than white women to receive abdominal hysterectomy. The proportion of all women undergoing abdominal hysterectomy was highest at hospitals serving higher proportions of African American persons. This difference in treatment type can lead to disparities in outcomes, in part owing to their association with complications.

An economic assessment of contemporary kidney transplant practice.

Kidney transplantation is the optimal therapy for end-stage renal disease, prolonging survival and reducing spending. Prior economic analyses of kidney transplantation, using Markov models, have generally assumed compatible, low-risk donors. The economic implications of transplantation with high Kidney Donor Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA incompatible living donors have not been assessed. The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10-year period, with data from the United States Renal Data System, University HealthSystem Consortium, and literature review. Graft failure rates and expenditures were adjusted for donor characteristics. All transplantation options were associated with improved survival compared with dialysis (transplantation: 5.20-6.34 quality-adjusted life-years [QALYs] vs dialysis: 4.03 QALYs). Living donor and low-KDPI deceased donor transplantations were cost-saving compared with dialysis, while transplantations using high-KDPI deceased donor, ABO-incompatible or HLA-incompatible living donors were cost-effective (<$100 000 per QALY). Predicted costs per QALY range from $39 939 for HLA-compatible living donor transplantation to $80 486 for HLA-incompatible donors compared with $72 476 for dialysis. In conclusion, kidney transplantation is cost-effective across all donor types despite higher costs for marginal organs and innovative living donor practices.