Ankle- and Toe-Brachial Index for Peripheral Artery Disease Identification: Unlocking Clinical Data Through Novel Methods.

Background: Despite its high prevalence and clinical impact, research on peripheral artery disease (PAD) remains limited due to poor accuracy of billing codes. Ankle-brachial index (ABI) and toe-brachial index can be used to identify PAD patients with high accuracy within electronic health records.

Methods: We developed a novel natural language processing (NLP) algorithm for extracting ABI and toe-brachial index values and laterality (right or left) from ABI reports.

The current state of knowledge of the immune ecosystem in alopecia areata.

Alopecia areata (AA) is an autoimmune disease that affects approximately 2% of the general population. Patients with AA most commonly present with one or more patches of hair loss on the scalp in defined circular areas. A fraction of patients progress to more severe forms of the disease, in some cases with involvement of all body surfaces.

Lipid Droplets' Role in the Regulation of β-Cell Function and β-Cell Demise in Type 2 Diabetes.

During development of type 2 diabetes (T2D), excessive nutritional load is thought to expose pancreatic islets to toxic effects of lipids and reduce β-cell function and mass. However, lipids also play a positive role in cellular metabolism and function. Thus, proper trafficking of lipids is critical for β cells to maximize the beneficial effects of these molecules while preventing their toxic effects.

Risk-Adjusted, 30-Day Home Time After Transcatheter Aortic Valve Replacement as a Hospital-Level Performance Metric.

Background: Patient-centric measures of hospital performance for transcatheter aortic valve replacement (TAVR) are needed.

Objectives: This study evaluated 30-day, risk-adjusted home time as a hospital performance metric for patients who underwent TAVR.

Methods: This study identified 160,792 Medicare beneficiaries who underwent elective TAVR from 2015 to 2019.

Implementation of large-scale laboratory-based detection of COVID-19 in the Veterans Health Administration, March 2020 - February 2021.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presented numerous operational challenges to healthcare delivery networks responsible for implementing large scale detection of Coronavirus Disease 2019 (COVID-19), the infection caused by SARS-CoV-2. We describe testing performance, review data quality metrics, and summarize experiences during the scale up of laboratory-based detection of COVID-19 in the Veterans Health Administration, the largest healthcare system in the United States. During March 2020 to February 2021, we observed rapid increase in testing volume, decreases in test turnaround time, improvements in testing of hospitalized persons, changes in test positivity, and varying utilization of different tests.

T-Cell Expression of Angiotensin-Converting Enzyme 2 and Binding of Severe Acute Respiratory Coronavirus 2.

The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not completely understood. SARS-CoV-2 infection frequently causes significant immune function consequences including reduced T cell numbers and enhanced T cell exhaustion that contribute to disease severity. The extent to which T cell effects are directly mediated through infection or indirectly result from infection of respiratory-associated cells is unclear.

Deciphering regulatory protein activity in human pancreatic islets via reverse engineering of single-cell sequencing data.

The loss of functional β cell mass contributes to development and progression of type 2 diabetes (T2D). However, the molecular mechanisms differentiating islet dysfunction in T2D from nondiabetic states remain elusive. In this issue of the JCI, Son et al.

Influential Factors in the Recovery Process of Burn Survivors in a Predominately Rural State: A Qualitative Study.

Navigating the recovery journey following a burn injury can be challenging. Survivor stories can help define recovery constructs that can be incorporated into support programs. We undertook this study to determine themes of recovery in a predominately rural state.

A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity.

Viral vector-mediated gene therapies have the potential to treat many human diseases; however, host immune responses against the vector and/or the transgene pose a safety risk to the patients and can negatively impact product efficacy. Thus, novel strategies to reduce vector immunogenicity are critical for the advancement of these therapies. T cell activation (TCA) is required for the development of immune responses during gene therapy.

Community-Level Economic Distress, Race, and Risk of Adverse Outcomes After Heart Failure Hospitalization Among Medicare Beneficiaries.

Background: Socioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure. However, the contribution of community-level economic distress to adverse outcomes in heart failure may differ across races and ethnicities.

Methods: Patients of self-reported Black, White, and Hispanic race and ethnicity hospitalized with heart failure between 2014 and 2019 were identified from the Medicare MedPAR Part A 100% Files.

Diagnosis Documentation of Critically Ill Children at Admission to a PICU.

Objectives: Multidisciplinary PICU teams must effectively share information while caring for critically ill children. Clinical documentation helps clinicians develop a shared understanding of the patient's diagnosis, which informs decision-making. However, diagnosis-related documentation in the PICU is understudied, thus limiting insights into how pediatric intensivists convey their diagnostic reasoning.

iPSC-Derived Trabecular Meshwork Cells Stimulate Endogenous TM Cell Division Through Gap Junction in a Mouse Model of Glaucoma.

Purpose: Decreased trabecular meshwork (TM) cellularity has been implicated as a major reason for TM dysfunction and aqueous humor (AH) outflow abnormalities in primary open angle glaucoma. We previously found that transplantation of induced pluripotent stem cell (iPSC)-derived TM cells can restore TM function and stimulate endogenous TM cell division. The goal of the present study is to investigate whether signaling via gap junctions is involved in this process.

Evaluation of Undiagnosed HIV Estimates Computed from the CD4 Depletion Model in a Rural, Medium-low HIV Prevalence State.

The CD4 depletion model estimates diagnosis delays by approximating infection date from CD4 T-cell count at diagnosis, and back-calculation can compute the proportion of undiagnosed PLWHA. The model assumes the immigration of PLWHA to the U.S.

Skeletal muscle regeneration in post-myofascial flap reconstruction specimens mimicking sarcoma: A potential diagnostic pitfall.

Skeletal muscle regeneration (SMR) encompasses a sequence of events that unfolds after injury to muscle fibers. Nearby satellite cells become activated and function as precursor muscle cells by proliferating and differentiating into myoblasts, which eventually fuse to form myotubes and ultimately mature muscle fibers. Compared to other forms of mesenchymal repair, SMR has higher morphologic heterogeneity with the potential to show histopathologic similarities to sarcomas and other malignancies.

Mitochondrial Efflux of Citrate and Isocitrate Is Fully Dispensable for Glucose-Stimulated Insulin Secretion and Pancreatic Islet β-Cell Function.

The defining feature of pancreatic islet β-cell function is the precise coordination of changes in blood glucose levels with insulin secretion to regulate systemic glucose homeostasis. While ATP has long been heralded as a critical metabolic coupling factor to trigger insulin release, glucose-derived metabolites have been suggested to further amplify fuel-stimulated insulin secretion. The mitochondrial export of citrate and isocitrate through the citrate-isocitrate carrier (CIC) has been suggested to initiate a key pathway that amplifies glucose-stimulated insulin secretion, though the physiological significance of β-cell CIC-to-glucose homeostasis has not been established.

Xeno- and Feeder-Free Differentiation of Human iPSCs to Trabecular Meshwork-Like Cells by Recombinant Cytokines.

Purpose: Stem cell-based therapy has the potential to become one approach to regenerate the damaged trabecular meshwork (TM) in glaucoma. Co-culture of induced pluripotent stem cells (iPSCs) with human TM cells has been a successful approach to generate autologous TM resembling cells. However, the differentiated cells generated using this approach are still problematic for clinical usage.

Veteran-Reported Receipt of Prepregnancy Care: Data from the Examining Contraceptive Use and Unmet Need (ECUUN) Study.

Objectives: To identify the prevalence of women Veterans reporting receipt of counseling about health optimization prior to pregnancy, topics most frequently discussed, and factors associated with receipt of this care.

Methods: We analyzed data from a nationally representative, cross-sectional telephone survey of women Veterans (n = 2302) ages 18-45 who used VA for primary care in the previous year. Our sample included women who were (1) currently pregnant or trying to become pregnant, (2) not currently trying but planning for pregnancy in the future, or (3) unsure of pregnancy intention.

Risk-Standardized Home Time as a Novel Hospital Performance Metric for Pneumonia Hospitalization Among Medicare Beneficiaries: a Retrospective Cohort Study.

Background: The Centers for Medicare & Medicaid Services (CMS) use hospital readmissions as a performance metric to incentivize hospital care for acute conditions including pneumonia. However, there are limitations to using readmission alone as a hospital performance metric.

Objective: To characterize 30-day risk-standardized home time (RSHT), a novel patient-centered post-discharge performance metric for acute pneumonia hospitalizations in Medicare patients, and compare hospital rankings based on this metric with mortality and readmissions.

Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.

Perilipin 2 (PLIN2) is a lipid droplet (LD) protein in β cells that increases under nutritional stress. Downregulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was downregulated in mouse β cells, INS1 cells, and human islet cells.

A Functionally Distinct CXCR3/IFN-γ/IL-10 Subset Defines Disease-Suppressive Myelin-Specific CD8 T Cells.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS. We have previously demonstrated that CNS-specific CD8 T cells possess a disease-suppressive function in MS and variations of its animal model, experimental autoimmune encephalomyelitis (EAE), including the highly clinically relevant relapsing-remitting EAE disease course. Regulatory CD8 T cell subsets have been identified in EAE and other autoimmune diseases, but studies vary in defining phenotypic properties of these cells.

Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats.

Previous work by ourselves and others showed that mitoquinone (mitoQ) reduced oxidative damage and prevented hepatic fat accumulation in mice made obese with high-fat (HF) feeding. Here we extended these studies to examine the effect of mitoQ on parameters affecting liver function in rats treated with HF to induce obesity and in rats treated with HF plus streptozotocin (STZ) to model a severe form of type 2 diabetes. In prior reported work, we found that mitoQ significantly improved glycemia based on glucose tolerance data in HF rats but not in the diabetic rats.