Phenome-wide association analysis suggests the APOL1 linked disease spectrum primarily drives kidney-specific pathways.

The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, to define the spectrum of phenotypes associated with APOL1 high-risk variants in 1,837 African American participants of Penn Medicine Biobank and 4,742 African American participants of Vanderbilt BioVU. In the Penn Medicine Biobank, outpatient creatinine measurement-based estimated glomerular filtration rate and multivariable regression models were used to evaluate the association between high-risk APOL1 status and renal outcomes.

Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.

Venous thromboembolism is a significant cause of mortality, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations.

Research Techniques Made Simple: Parabiosis to Elucidate Humoral Factors in Skin Biology.

Circulating factors in the blood and lymph support critical functions of living tissues. Parabiosis refers to the condition in which two entire living animals are conjoined and share a single circulatory system. This surgically created animal model was inspired by naturally occurring pairs of conjoined twins.

Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies.

The endogenous opioid system is thought to play an important role in the regulation of mood. Buprenorphine/samidorphan (BUP/SAM) combination is an investigational opioid system modulator for adjunctive treatment of major depressive disorder (MDD). To confirm results from early studies, we report the efficacy and safety of BUP/SAM as adjunctive treatment in patients with MDD and an inadequate response to antidepressant therapy (ADT) in FORWARD-4 and FORWARD-5: two phase 3, randomized, double-blind, placebo-controlled studies that utilized the same sequential parallel-comparison design.

Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration.

Physicians have observed that surgical wounds in the elderly heal with thinner scars than wounds in young patients. Understanding this phenomenon may reveal strategies for promoting scarless wound repair. We show that full-thickness skin wounds in aged but not young mice fully regenerate.

A tissue-engineered rostral migratory stream for directed neuronal replacement.

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mammalian brain-including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits.

Association of Interleukin 6 Receptor Variant With Cardiovascular Disease Effects of Interleukin 6 Receptor Blocking Therapy: A Phenome-Wide Association Study.

Importance: Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene-drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade.

Evaluation of the Cincinnati Veterans Affairs Medical Center Hospital-in-Home Program.

Objectives: To examine hospital readmissions, costs, mortality, and nursing home admissions of veterans who received Hospital-in-Home (HIH) services.

Design: Retrospective cohort study.

Setting: Cincinnati Veterans Affairs Medical Center (VAMC).

Preoperative Lund-Mackay computed tomography score is associated with preoperative symptom severity and predicts quality-of-life outcome trajectories after sinus surgery.

Background: Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients.

Methods: Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study.

Association of Rideshare-Based Transportation Services and Missed Primary Care Appointments: A Clinical Trial.

Importance: Transportation barriers contribute to missed primary care appointments for patients with Medicaid. Rideshare services have been proposed as alternatives to nonemergency medical transportation programs because of convenience and lower costs.

Objective: To evaluate the association between rideshare-based medical transportation and missed primary care appointments among Medicaid patients.

Impact of acute postoperative limb ischemia after cardiac and thoracic aortic surgery.

Objective: Acute limb ischemia (ALI) is the cause of significant morbidity and mortality. Although ALI after cardiac surgery is associated with high rates of morbidity and mortality, there are no robust, controlled analyses of the risk factors and outcomes of ALI in this setting. We aimed to identify risk factors for and to delineate outcomes after ALI in patients undergoing cardiac surgery.