Vitamin D supplementation: Pearls for practicing clinicians.

Vitamin D supplementation is common in the United States, with about one-fifth of the adult population taking a daily supplement in one form or another. Although the detrimental effects of insufficient sun exposure in childhood was established centuries ago, the beneficial effects of vitamin D sufficiency have only recently been established, given the myriad investigations associating vitamin D deficiency with numerous chronic diseases. But it is far less clear precisely how to replete low 25-hydroxyvitamin D (25[OH]D) levels, how long treatment should be continued, if there are potential hazards in doing so, and how to assess and counsel patients regarding the use of vitamin D.

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials.

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.

Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.

Salivary miRNAs as non-invasive biomarkers of hepatocellular carcinoma: a pilot study.

Background: Improved detection of hepatocellular carcinoma (HCC) is needed, as current detection methods, such as alpha fetoprotein (AFP) and ultrasound, suffer from poor sensitivity. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate many cellular functions and impact cancer development and progression. Notably, miRNAs are detectable in saliva and have shown potential as non-invasive biomarkers for a number of cancers including breast, oral, and lung cancers.

Thyroid nodule molecular profiling: The clinical utility of Afirma Xpression Atlas for nodules with Afirma Genomic Sequencing Classifier-suspicious results.

Background: The Afirma Genomic Sequencing Classifier uses whole transcriptome RNA sequencing to identify thyroid nodules as benign or suspicious. The Afirma Xpression Atlas became available in 2018 and reports findings across 593 genes, including 905 variants and 235 fusions. When an alteration is identified, its risk of malignancy and associated neoplasm type is listed.

Misleading FT4 and FT3 Due to Immunoassay Interference From Autoantibodies.

Background: Immunoassays used to measure total and free thyroxine (T4 and FT4) and total and free triiodothyronine (T3 and FT3) can provide inaccurate results due to interference from endogenous autoantibodies.

Case Report: A 74-year-old female treated for hypothyroidism with levothyroxine replacement had elevated thyroid stimulating hormone (TSH), FT4, and FT3. Due to concern for hyperthyroidism, levothyroxine was discontinued and further workup was initiated.

Bioenergetics of Islet Preparations in a Pilot Clinical Trial of Peri-Transplant Hydroxychloroquine for Autologous Islet Transplantation.

The inflammatory response is an obstacle to success in both allogeneic and autologous islet transplantation. In autologous islet transplantation (AIT), however, the recipient is also the donor, permitting pretreatment of donor/recipient for a controlled duration prior to transplantation. We sought to exploit this feature of (AIT) by pretreating donor/recipients with chronic pancreatitis undergoing total pancreatectomy and autologous islet transplantation (TPAIT) to test the hypothesis that peri-transplant treatment with the FDA-approved anti-inflammatory hydroxychloroquine (HCQ) improves graft function.

Elevated hCG can be a benign finding in perimenopausal and postmenopausal women.

In a perimenopausal or postmenopausal woman, an elevation in human chorionic gonadotropin (hCG) can raise the concern of malignancy or even pregnancy, but it can also be a benign physiologic finding due to production in the pituitary gland in this patient population. Diagnosing the underlying cause of hCG elevation can be challenging, especially if a pituitary source is not considered. Pituitary hCG production remains largely underrecognized and can lead to unnecessary testing, harmful therapy such as chemotherapy, or delay in receiving appropriate care for other unrelated diseases.

DXA and clinical challenges of fracture risk assessment in primary care.

Dual-energy x-ray absorptiometry (DXA) can detect bone mineral density loss before it can be identified on usual skeletal radiography, making it possible to diagnose osteoporosis in postmenopausal women and older men before clinical fractures arise. However, when DXA is used outside these populations or if the clinical picture does not match the reported T-scores, mistakes can arise in interpreting results and determining the need for pharmaceutical therapy.

COVID-19: Pathophysiology and implications for cystic fibrosis, diabetes and cystic fibrosis-related diabetes.

The novel SARS-CoV-2 coronavirus (COVID-19) has become a global health crisis since its initial outbreak in Wuhan, China in December 2019. On January 30, 2020, the WHO recognized the COVID-19 outbreak as a Public Health Emergency, and on March 11, 2020, it was declared a pandemic. Although all age groups have been affected, patients with cystic fibrosis (CF) and patients with type 1 or type 2 diabeteshave been categorized as highly vulnerable to SARS-CoV-2 infection.

Ketogenic diets in the management of type 1 diabetes: Safe or safety concern?

The jury is still out on whether a low-carbohydrate, ketosis-inducing diet is an effective and safe adjunctive therapy to insulin in type 1 diabetes. The limited published literature reports an association with weight loss and improved glycemic control and may, over the long-term, lead to reduced macrovascular and microvascular harm. However, the attendant increased risk of dyslipidemia, diabetic ketoacidosis, and hypoglycemia warrant caution, close monitoring of patients who embark on the diet, and further research.

Health Care Disparities in Use of Continuous Glucose Monitoring.

Numerous studies have demonstrated that use of continuous glucose monitoring (CGM) improves glycemic control and reduces diabetes-related hospitalizations and emergency room service utilization in individuals with diabetes who are treated with intensive insulin regimens. Recent studies have revealed disparities in use of CGM within racially and ethnically diverse and lower socioeconomic populations, leading to underutilization of CGM in these populations. This article reviews the scope and impact of these disparities on utilization of CGM and explores the factors that may be contributing to this issue.

Associations of weight loss with obesity-related comorbidities in a large integrated health system.

Aims: To determine the health outcomes associated with weight loss in individuals with obesity, and to better understand the relationship between disease burden (disease burden; ie, prior comorbidities, healthcare utilization) and weight loss in individuals with obesity by analysing electronic health records (EHRs).

Materials And Methods: We conducted a case-control study using deidentified EHR-derived information from 204 921 patients seen at the Cleveland Clinic between 2000 and 2018. Patients were aged ≥20 years with body mass index ≥30 kg/m and had ≥7 weight measurements, over ≥3 years.

Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome.

Purpose: To evaluate the performance of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome (CS).

Methods: This was a prospective, multicenter, nonrandomized, noninterventional study of a cortisol activity biomarker in adult patients (≥18 years) with documented ACTH-dependent, endogenous CS. The impact of surgery on FKBP5 mRNA expression levels in these patients and the difference in expression levels between these patients and healthy controls were evaluated.

Effectiveness of Combining Antiobesity Medication With an Employer-Based Weight Management Program for Treatment of Obesity: A Randomized Clinical Trial.

Importance: The clinical efficacy of antiobesity medications (AOMs) as adjuncts to lifestyle intervention is well characterized, but data regarding their use in conjunction with workplace wellness plans are lacking, and coverage of AOMs by US private employers is limited.

Objective: To determine the effect of combining AOMs with a comprehensive, interdisciplinary, employer-based weight management program (WMP) compared with the WMP alone on weight loss, treatment adherence, and work productivity and limitations.

Design, Setting, And Participants: This 1-year, single-center, open-label, parallel-group, real-world, randomized clinical trial was conducted at the Cleveland Clinic's Endocrinology and Metabolism Institute in Cleveland, Ohio, from January 7, 2019, to May 22, 2020.

Endocrine Toxicity and Outcomes in Patients With Metastatic Malignancies Treated With Immune Checkpoint Inhibitors.

Context: Immune checkpoint inhibitors (ICIs) have gained a revolutionary role in management of many advanced malignancies. However, immune-related endocrine events (irEEs), have been associated with their use. irEEs have nonspecific clinical presentations and variable timelines, making their early diagnosis challenging.

Effects of Wearing an N95 Respirator or Cloth Mask Among Adults at Peak Exercise: A Randomized Crossover Trial.

This randomized crossover trial examines the effects of wearing a cloth mask or N95 respirator vs no mask at peak exercise among healthy, active adults.

Strategies for overcoming therapeutic inertia in type 2 diabetes: A systematic review and meta-analysis.

Aims: To systematically investigate the effect of interventions to overcome therapeutic inertia on glycaemic control in individuals with type 2 diabetes.

Materials And Methods: We electronically searched for randomized controlled trials or quasi-experimental studies published between January 1, 2004 and December 31, 2019 evaluating the effect of interventions on glycated haemoglobin (HbA1c) control. Characteristics of included studies and HbA1c difference between intervention and control arms (main outcome) were extracted.

Patient-reported Outcomes After Metabolic Surgery Versus Medical Therapy for Diabetes: Insights From the STAMPEDE Randomized Trial.

Objective: The aim of this study was to investigate the long-term effects of medical and surgical treatments of type 2 diabetes mellitus (T2DM) on patient-reported outcomes (PROs).

Background: Robust data on PROs from randomized trials comparing medical and surgical treatments for T2DM are lacking.

Methods: The Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial showed that 5 years after randomization, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were superior to intensive medical therapy (IMT) alone in achieving glycemic control in patients with T2DM and obesity.

Lipids activate skeletal muscle mitochondrial fission and quality control networks to induce insulin resistance in humans.

Background And Aims: A diminution in skeletal muscle mitochondrial function due to ectopic lipid accumulation and excess nutrient intake is thought to contribute to insulin resistance and the development of type 2 diabetes. However, the functional integrity of mitochondria in insulin-resistant skeletal muscle remains highly controversial.

Methods: 19 healthy adults (age:28.

Association of obesity with postacute sequelae of COVID-19.

Obesity is a major risk factor for the development of severe coronavirus disease 2019 (COVID-19) infection and mortality. However, it is not known whether patients with obesity are at a greater risk of developing postacute sequelae of COVID-19 (PASC). In a median follow-up time of 8 months and counting from 30 days following a positive viral test of 2839 patients who did not require intensive care unit admission and survived the acute phase of COVID-19, 1230 (43%) patients required medical diagnostic tests, 1255 (44%) patients underwent hospital admission, and 29 (1%) patients died.

Endothelin-1 levels are decreased in pediatric Type 1 diabetes and negatively correlate with the carotid intima media thickness.

Aims: Better understanding of the timeline and risk factors for the appearance of complications in pediatric Type-1-diabetes is key for developing prevention strategies. We studied endothelial markers and their determinants in adolescents with Type-1-diabetes at different time points from diagnosis.

Methods: A cross-sectional study of 58 adolescents, mean age 15.

A Type 2 Diabetes Subtype Responsive to ACCORD Intensive Glycemia Treatment.

Objective: Current type 2 diabetes (T2D) management contraindicates intensive glycemia treatment in patients with high cardiovascular disease (CVD) risk and is partially motivated by evidence of harms in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Heterogeneity in response to intensive glycemia treatment has been observed, suggesting potential benefit for some individuals.

Research Design And Methods: ACCORD was a randomized controlled trial that investigated whether intensively treating glycemia in individuals with T2D would reduce CVD outcomes.