APOE ε4 and late-life cognition: mediation by structural brain imaging markers

European Journal of Epidemiology - The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer’s disease....     

Minority Race and Ethnicity is Associated With Higher Complication Rates After Revision Surgery for Failed Total Hip and Knee Joint Arthroplasty

BackgroundRacial and ethnic disparities in access to hip and knee total joint arthroplasty (TJA) and postoperative outcomes have wide-reaching implications for patients and the health care system. The aim of this study is to evaluate the effect of ethnicity on clinical outcomes and complications following revision hip and knee TJA.MethodsA single-institution, retrospective analysis of a consecutive series of 4424 revision hip and knee TJA patients was evaluated. Student’s t-test and chi-squared analysis were used to identify significant differences in patient demographics and clinical outcomes between Caucasians and various ethnic minorities, including African Americans, Hispanics, and Asians.ResultsWhen compared with white patients, African American patients demonstrated a significantly higher BMI (P = .04), ASA score (P = .04), length of hospital stay (P = .06), and postoperative infection rates (P = .04). Hispanics demonstrated a significantly higher BMI (P = .04), when compared with white patients, alongside a significantly higher risk for postoperative infection (P < .01). African American demonstrated a significantly higher ASA score (P = .02; P = .03), when compared with Hispanics and Asians, alongside a significantly increased length of stay (P = .01) and higher risk for postoperative infection (P = .02).ConclusionThe study findings demonstrate an underutilization of revision TJA by ethnic minority groups, suggesting that disparities in access to orthopedic surgery increase from primary to revision surgery despite higher failure rates of minority ethnic groups reported after primary TJA surgery. In addition, inferior postoperative outcomes were associated with African Americans and Hispanics, when compared to white patients, with African Americans demonstrating the highest risk of postoperative complications.     

Restarting LDLT During COVID-19: Early Results After Restructuring

IntroductionLiving-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic.Materials and MethodsThe changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months).ResultsNineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected.ConclusionThis study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.     

Predictive Value of DXA Appendicular Lean Mass for Incident Fractures,Falls, and Mortality,Independent of Prior Falls,FRAX, and BMD: Findings from the Women's Health Initiative (WHI)

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX^®) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height²) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height² (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height² was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83–0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98–1.14). There were no associations between ALM/height² and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height², depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height² and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Biliary disease and cholecystectomy after initiation of elexacaftor/ivacaftor/tezacaftor in adults with cystic fibrosis

Individuals with cystic fibrosis (CF) have an increased risk for gallbladder abnormalities and biliary tract disease, but the reported incidence of these manifestations of CF varies widely in the literature. With the approval of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), increasing numbers of CF patients have been initiated on highly effective cystic fibrosis transmembrane regulator (CFTR) modulator therapy. While elevations in hepatic panel are known potential side effects of CFTR modulators, there have been no published cases of biliary disease or acute cholecystitis attributed to these medications. In this case series, we describe seven patients at two adult CF centers with biliary colic shortly after initiation with ELX/TEZ/IVA, six of whom required cholecystectomy.     

Demographic changes and their financial implications

The impressive rise in the number of elderly persons (65 years and over) will continue in the next two to three decades. Urinary incontinence is a common problem in the elderly, adversely affecting medical, social, and "quality of life" aspects. The cost of urinary incontinence is substantial and is expected to escalate enormously (e.g., by 160% from 1980 to 2040). An aggressive approach toward the diagnosis and management of urinary incontinence can result in an impressive reduction in health care costs and improvement in the quality of life.     

Intravitreal drug administration with depot devices

The administration of medications by depot devices is a rapidly developing technology in ocular therapeutics. Sustained delivery of ophthalmic medications is a novel approach to treating chronic ocular conditions where systemic therapy may be accompanied by unwanted side effects and where repeated intravitreal drug administration carries significant risks. Eye diseases particularly suitable to this form of treatment include proliferative vitreoretinopathy and chronic intraocular infections such as cytomegalovirus retinitis. Liposomes, which have been extensively investigated over the last two decades, have not found any acceptable clinical application. Nonerodible polymers such as the ethylvinyl acetate/polyvinyl alcohol cup are in advanced phase III trials. The current status of microsphere development in the treatment of posterior segment disease is examined in the review and studies investigating the potential uses of the osmotic minipump are mentioned.     

Splenic abscess following blunt abdominal trauma

A rare case of splenic abscess occurring after blunt abdominal trauma in a previously healthy boy is reported. The diagnosis was made by ultrasonography. The patient recovered after splenectomy and drainage of subphrenic and intraperitoneal pus.