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Importance Prepregnancy care and counseling optimize maternal health before conception to improve outcomes for mothers and infants. In the US, 66.4% of reproductive-aged women have at least 1 modifiable risk factor for adverse pregnancy outcomes. Observations For all individuals desiring pregnancy, recommended interventions include folic acid supplementation; cessation of tobacco, alcohol, cannabis, and opioids; immunizations against hepatitis B virus, varicella, and rubella; and screening for syphilis and HIV. Folic acid use before pregnancy is associated with reduced fetal neural tube defects (relative risk [RR], 0.67; 95% CI, 0.52-0.87). Maternal tobacco smoking is associated with increased risks of stillbirth (summary RR [sRR], 1.46; 95% CI, 1.38-1.54), neonatal death (sRR, 1.22; 95% CI, 1.14-1.30), and perinatal death (sRR, 1.33; 95% CI, 1.25-1.41). Screening for and treatment of syphilis and HIV prior to and during pregnancy decrease rates of fetal and neonatal infection. Prepregnancy immunizations against hepatitis B virus, varicella, and rubella decrease neonatal infection and mortality. Individuals using tobacco, alcohol, cannabis, and opioids should receive counseling and treatment prior to pregnancy (eg, buprenorphine or methadone for opioid use disorder). For individuals with chronic disease, routine health examinations and contraceptive care in the year before conception can optimize pregnancy timing and are associated with decreased risk of severe maternal morbidity. Compared with planned pregnancies, unintended pregnancies are associated with increased risk of postpartum depression (15.7% vs 9.6%; adjusted odds ratio [aOR], 1.51; 95% CI, 1.40-1.70), preterm birth (9.4% vs 7.7%; aOR, 1.21; 95% CI, 1.12-1.31), and low infant birth weight (7.3% vs 5.2%; aOR, 1.09; 95% CI, 1.02-1.21). Weight loss prior to conception is recommended for individuals with a body mass index of 25 or greater because overweight and obesity are associated with increased risk of gestational diabetes, gestational hypertension, and cesarean delivery. Among patients with pregestational diabetes (type 1 or 2), hemoglobin A 1c of less than 6.5% is associated with a decreased risk of fetal anomaly compared with hemoglobin A 1c of 6.5% or greater. Cardiovascular complications such as hypertension and heart failure occur in 15% of pregnancies and are more common among those with preexisting cardiovascular disease. These patients should receive counseling on maternal and neonatal risk, monitoring, and medication management by specialists in cardiology and maternal fetal medicine. Conclusions and Relevance Prepregnancy counseling and care reduce maternal morbidity and neonatal morbidity and mortality. Primary care–based discussion of reproductive goals, immunizations, screening for infections and substance use, and risk-reducing interventions such as folate supplementation can optimize outcomes in individuals contemplating pregnancy.

Background: Enteral phosphate replacement offers multiple advantages over intravenous phosphate replacement, but optimal dosing and administration are unclear. Objective: This study aimed to compare 2 different dosing strategies (PRE vs POST) of enteral phosphate replacement for mild hypophosphatemia (serum phosphorus = 2.1-2.5 mg/dL) and to evaluate our dosing strategy for moderate hypophosphatemia (serum phosphorus = 1.5-2 mg/dL) in critically ill patients. Methods: This single-center quasiexperimental, institutional review board–approved study was conducted in adult patients admitted to an intensive care unit (ICU) who received enteral phosphate replacement with a follow-up serum phosphorus level obtained within 24 hours of replacement. Patients were excluded if they had diabetic ketoacidosis, acute kidney injury, or received total parenteral nutrition or targeted temperature management. The mild PRE and POST groups received 48 and 72 mmol of enteral phosphate, respectively. The moderate group received 72 mmol of enteral phosphate. Effectiveness outcomes included normalization of serum phosphorus, defined as 2.6 to 4.5 mg/dL, and median change in phosphorus concentration. Safety outcomes included the incidence of new onset diarrhea and hyperphosphatemia (serum phosphorus >4.5 mg/dL) within 24 hours after phosphate replacement. Results: Of the 138 patients included, the median age was 59 (44-70) years and 69.6% were admitted to the surgical trauma ICU. Normalization of serum phosphorus occurred in 55 (58.2%) patients in mild PRE and 44 (72.7%) patients in mild POST ( P = 0.13). Change in serum phosphorus was 0.4 (0.1-0.9) mg/dL in mild PRE vs 0.7 (0.3-1.2) mg/dL in mild POST ( P = 0.06). Normalization occurred in 39 (66.7%) patients in the moderate group with a change in serum phosphorus of 1.0 (0.6-1.6) mg/dL. Rates of new onset diarrhea and hyperphosphatemia were not significantly different between groups. Conclusion and Relevance: Enteral phosphate replacement appears safe and effective in critically ill patients with mild-to-moderate hypophosphatemia and may serve as an alternative to intravenous phosphate.

Introduction Video visits in primary care have decreased significantly since their surge early in the COVID-19 pandemic. Methods Clinicians including physicians, nurse practitioners, and physician assistants in the Mayo Clinic Department of Family Medicine were invited to dedicate one to two half-days per month exclusively to video visits. Schedules for these half-day sessions remained restricted to video appointments until the day prior. If at least 80% of slots were not filled by then, remaining openings were converted to in-person visits. If the half-day sessions were at least 80% full with video visits, clinicians had the option of performing these sessions remotely. Results Of 155 eligible clinicians, 34 (22%) participated voluntarily in this scheduling intervention. For the participating clinicians, the average video visit rate increased from 6.3% per month preintervention to 11.5% postintervention ( p < 0.001). On a departmental level, the trend line for the percent of outpatient visits via video visit was decreasing by −0.1% per month preintervention. The postintervention slope of the trend line was 0.3% per month ( p < 0.001). The majority (65%) of the time the half-day video visit schedules filled at least 80% and did not require conversion to allow in-person visits allowing clinicians to work remotely if they chose. Conclusion Allowing family medicine clinicians to perform 1–2 half-day schedules dedicated to only video visits increases the percentage of video visit performed per month both for individual clinicians and on a departmental level.

ABSTRACT The HLA‐C*14:84 allele is characterised by a single nucleotide substitution in codon 181 in exon 3.

Objective This study aims to identify factors associated with patient global assessment (PtGA) and physician global assessment (PhGA) and discordance between them in systemic sclerosis (SSc). Methods Data from adults with early SSc (<5 years) from the Collaborative National Quality and Efficacy Registry were included. PtGA and PhGA (0–10 scale), clinical evaluations, and patient‐reported outcomes (PROs) were collected every six months. Multivariable mixed‐effects linear regression identified factors associated with PtGA and PhGA using (1) clinical variables and (2) clinical variables plus PROs. Relative weight analysis (RWA) determined the relative importance of each variable. Discordance (≥2 points between PtGA and PhGA) was assessed using multinomial mixed‐effects logistic regression. Results Among 956 patients (83% women, 33% limited disease), mean PtGA and PhGA at enrollment were 4.2 (SD 2.6) and 3.4 (SD 2.0), respectively ( P < 0.001). RWA of clinical variables identified modified Rodnan skin score (mRSS) and New York Heart Association (NYHA) functional class as most influential for both global assessments. After including PROs, PtGA was most influenced by measures of pain, skin symptoms, and physical function. Discordance occurred in 53% of patients (35% PtGA worse, 18% PhGA worse). Worse PtGA was associated with higher overall pain and discomfort. Worse PhGA was associated with higher mRSS, worse NYHA class, higher pain interference, and lower diffusing capacity of the lung. Conclusion Discordance between PtGA and PhGA occurs commonly, highlighting the need for comprehensive symptom management and measurement of disease burden in this complex disease. In SSc, differences in PtGA and PhGA reflect dissimilar weighting of data elements.

Apply It! • This electrocardiogram (ECG) primer will provide basic knowledge and standardized strategies needed to prepare and complete a resting ECG, as well as adjust electrode placement for exercise testing. • A simple, evidence-based, systematic approach to resting and exercise ECG interpretation is included. • Exercise professionals may directly apply these concepts to diverse settings, including clinics, hospitals, cardiac rehabilitation, stress testing, research, and academia.

Purpose To evaluate the clinical, radiographic, and functional outcomes of arthroscopic treatment of scaphoid nonunion in adolescents, using cancellous bone grafting combined with headless compression screw fixation. Methods This retrospective study included adolescent patients treated between 2015 and 2022 with arthroscopically assisted bone grafting and headless compression screw fixation for scaphoid nonunion. Inclusion criteria were nonunion ≥6 months after injury and minimum 12‐month follow‐up; exclusion criteria included degenerative wrist changes. Collected variables included demographic data, injury‐to‐surgery interval, radiographic parameters (including scapholunate angle), time to union, pain scores (visual analog scale), functional outcomes (QuickDASH), and range of motion. Statistical analysis showed significant improvements in visual analog scale and QuickDASH scores ( P < .05). Results Fifteen patients (14 males; mean age 16 years, range 13‐19) met inclusion criteria. The mean follow‐up was 29.2 months. All patients achieved bone union, with an average healing time of 5.7 weeks. Pain (visual analog scale) improved from 2.6 to 0.8, and QuickDASH scores improved from 26.5 to 7.9. The scapholunate angle improved from 60.6° to 46.6°, with stable range of motion postoperatively. No major complications or reoperations occurred. Minimal clinically important difference analysis confirmed meaningful clinical improvement in 93% of patients for pain and 87% for QuickDASH. Conclusions Arthroscopic treatment of scaphoid nonunion in adolescents shows high union rates, improved function, and low morbidity. Level of Evidence Level IV, therapeutic retrospective case series.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity affecting 30–40% of patients treated with neurotoxic chemotherapy. Sensory symptoms arise from injury to dorsal root ganglion (DRG) neurons and their axons; yet, the underlying mechanisms remain incompletely understood. While human induced pluripotent stem cell (iPSC)-derived sensory neuron (iSN) monolayers have provided mechanistic insight, they lack the three-dimensional architecture and cellular heterogeneity of native DRG tissue. Here, we generated human iPSC-derived DRG organoids (iDRGOs) containing mixed neuronal and peripheral glial populations and established a quantitative neurite outgrowth assay to model chemotherapy-induced neurotoxicity in a 3D context. iDRGOs from three healthy donors were exposed to bortezomib, vincristine, or paclitaxel. All three drugs caused dose-dependent neurite outgrowth impairment without significant short-term changes in organoid size, consistent with early axonal injury. Vincristine reduced MAP2 levels when normalized to total protein, whereas bortezomib and paclitaxel showed divergent microtubule-associated responses compared to monolayer cultures. The developmental stage significantly influenced the baseline neurite outgrowth, highlighting the need for age standardization. These results establish iDRGOs as a physiologically relevant human platform that complements monolayer models for mechanistic studies and therapeutic screening in CIPN.

Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) exhibit great therapeutic potential in ischemia-associated conditions and diseases such as myocardial infarction, ischemic stroke, and wound healing. Enhancing the therapeutic efficacy of MSC-EVs could advance their clinical application. Diverse cargos (proteins, mRNA, microRNA, etc.) in MSC-EVs contribute to the therapeutic effects in various diseases. Vascular endothelial growth factor (VEGF) is one of the primary driving molecules in promoting angiogenesis and protecting endothelial cells lining blood vessels from apoptosis. In this study, we explored the feasibility of engineering parent MSCs with VEGF mRNA to potentiate therapeutic effects of their derived EVs. We first detected elevated levels of VEGF mRNA and protein in transfected MSCs and demonstrated the bioactivity of secreted VEGF by an angiogenesis assay. Furthermore, EVs derived from VEGF mRNA-engineered MSCs (VEGF-MSC-EVs) contained high levels of VEGF mRNA and protein and showed superior ability to protect human umbilical vein endothelial cells (HUVECs) from apoptosis compared to EVs derived from control MSCs (control MSC-EVs). To our knowledge, this is the first report demonstrating that VEGF-MSC-EVs boost therapeutic efficacy by promoting endothelial cell survival. Our findings offer a novel approach for cell-free therapy in ischemia-associated conditions and diseases.

Abstract Background Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized among people with human immunodeficiency virus (PWH), which is likely related to metabolic alterations and fat redistribution. Anthropometric measures such as body mass index (BMI) and waist circumference (WC) are commonly used for assessing metabolic risk. However, their predictive accuracy for MASLD in this population remains uncertain. Method This multicenter cross-sectional study enrolled adults with HIV who underwent transient elastography with controlled attenuation parameter (CAP) measurement. Anthropometric and metabolic indices, including BMI, WC, hip circumference, waist-to-hip ratio (WHR), and visceral adiposity index (VAI), were collected from the study participants. Receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic performance of these indices for detecting hepatic steatosis, defined as CAP value of ≥248 dB/m. Analyses were stratified by sex assigned at birth. Results Altogether, 256 participants were included. WC demonstrated the numerically highest discrimination for CAP-defined steatosis (area under the ROC curve 0.769), followed by BMI and hip circumference, whereas WHR and VAI showed weaker performance. In sex-stratified analyses, WC remained the numerically highest-performing measure among males, whereas BMI, WC, hip circumference, and VAI showed similar discrimination among females. Conclusions Simple anthropometric measures, particularly WC, show fair ability to discriminate CAP-defined hepatic steatosis in PWH and may facilitate targeted fatty liver screening in routine HIV care.