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Abstract Context Thyroid nodules are common in clinical practice, and inappropriate selection of patients for thyroid biopsy can contribute to thyroid cancer overdiagnosis or delayed diagnosis. Objective This work aimed to evaluate the frequency of inappropriate thyroid biopsies in practice, following a framework that integrates thyroid nodule ultrasound (US) features and patient-specific clinical factors. Methods This cross-sectional study was conducted at a single academic center in the United States. Participants included adult patients who underwent their first thyroid fine-needle aspiration (FNA) biopsy between January 1, 2016, and December 31, 2023, at the University of Florida. Data collection included thyroid US characteristics, clinical factors (eg, comorbidities, patient preferences), and context for biopsy decision-making. Main outcome measures included the appropriateness of thyroid biopsy assessed using a tiered framework incorporating US features and additional clinical factors. Results A total of 899 patients were evaluated, with 441 meeting the inclusion criteria and undergoing 481 thyroid biopsies. Of these, 388 of 481 (80.7%) were classified as likely appropriate (L-APP) based on the American College of Radiology Thyroid Imaging Reporting and Data System criteria. In 34 of 481 (7%) of cases, clinical factors such as thyroid cancer risk features, comorbidities, symptoms, or patient preferences led to reclassification from likely inappropriate (L-INAP) to L-APP. In 50 of 481 (10%) of cases, limited life expectancy (eg, chemotherapy, end-stage disease) led to reclassification from L-APP to possibly or extremely inappropriate (EXT-INAP). EXT-INAP biopsies occurred in only 0.8% (4/481) of cases. Conclusion This study underscores the value of integrating US findings with clinical context to guide thyroid biopsy decisions and enhance patient-centered care.

Abstract Context Preclinical studies demonstrate that treatment with calcitriol attenuates skeletal complications in mice with X-linked hypophosphatemia (XLH). Objective This work aimed to assess serum markers of mineral metabolism, nephrocalcinosis, skeletal microarchitecture, growth, and evidence of rickets following calcitriol monotherapy in children and adults with XLH. Methods A 1-year, prospective, single-arm, open-label study was conducted comparing baseline and 12-month outcomes. Participants were recruited from outpatient endocrinology clinics in the United States. Data were collected in a research unit. Eligible participants were aged 4 years or older, not pregnant, with baseline 25-hydroxyvitamin D of 20 ng/mL or greater and normal serum calcium. Participants were treated with calcitriol, with dose based on serum and urinary calcium concentrations, for 1 year. The primary end points were change in serum phosphate and nephrocalcinosis (all participants) and rickets severity score (children). Secondary end points included changes in additional markers of mineral metabolism, skeletal microarchitecture parameters via high-resolution peripheral quantitative computed tomography (all participants), and height z-scores (children). Results Serum phosphate did not change over 12 months of optimized calcitriol treatment. Rickets improved in 2 of 4 children with open epiphyses; height z-scores were unchanged. Nephrocalcinosis scores remained stable. Adults had increased cortical thickness at the radius diaphysis (P = .012). Serum alkaline phosphatase decreased in children (P = .021) and parathyroid hormone trended lower both in children (P = .065) and adults (P = .063). Four participants developed mild hypercalcemia and 2 developed hypercalciuria that resolved with calcitriol titration. Conclusion Calcitriol monotherapy is safe and well-tolerated in XLH, with modest benefits on laboratory indices of mineral metabolism and rickets.

ABSTRACT Patient outcomes in advanced renal cell carcinoma (RCC) remain poor, with five‐year survival rates ranging from ~10% to 30%. Early projections of therapeutic outcomes could optimize precision medicine and accelerate drug development. While machine learning (ML) models integrating tumor growth inhibition (TGI) metrics have improved survival predictions over traditional models, their application in RCC remains unexplored. Herein, we used TGI metrics and baseline data to evaluate parametric (PM) and semi‐parametric (SPM) survival models alongside ML approaches for predicting progression‐free (PFS) and overall survival (OS) in 1839 RCC patients from four trials (evaluating sunitinib, axitinib, sorafenib, interferon‐alpha, and avelumab + axitinib). Data were split into training (70%) and testing (30%), and feature selection was used to determine parsimonious and robust models. Bootstrap resampling ( n = 100) was employed for models' validation, and performance was assessed using C‐index and Integrated Brier Score. In brief, training data results demonstrated that tree‐based ML models (random survival forest (RSF) and XGBoost) outperformed PM and SPM models in predicting PFS (C‐index: 0.783–0.785 vs. 0.725–0.738 for PM and SPM; p < 0.05) and OS (C‐index: 0.77–0.867 vs. 0.750–0.758 for PM and SPM; p < 0.05), with RSF achieving better prediction of PFS and OS using only 3–5 covariates, compared to 9–35 with other tested methods. Tree‐based methods were also superior in the testing data. SHapley Additive exPlanations revealed nonlinear relationships among top predictors, including TGI metrics, underscoring the ability of tree‐based methods to capture complex prognostic interactions. Further validation is required to confirm models' generalizability to additional therapies and patients with differing tumor severity.

Abstract The sections in this article are: Physiological Effects of Vitamin D and its Active Metabolites on Calcium and Phosphorus Homeostasis Sources of Vitamin D Transport of Vitamin D and its Metabolites in Plasma Metabolism of Vitamin D 3 to 25‐Hydroxyvitamin D 3 Metabolism of 25‐Hydroxyvitamin D 3 Regulation of the 25‐Hydroxyvitamin D 3 –1α‐Hydroxylase Enzyme Parathyroid Hormone Phosphorus Concentrations Calcium: Direct Effects 1,25‐Dihydroxyvitamin D 3 Calcitonin Hydrogen Ion Sex Steroids Glucocorticoids Pituitary Hormones Thyroid Hormone Pregnancy Catabolism of 1,25‐Dihydroxyvitamin D 3 Physiological Adaptations that Occur in Response to Changes in Serum Calcium and Phosphate Concentrations Hypocalcemia and Hypercalcemia Hypophosphatemia and Hyperphosphatemia Pathophysiology and Physiology of the 1,25‐Dihydroxyvitamin D 3 System Mechanisms of Action of 1,25‐Dihydroxyvitamin D 3 1,25‐Dihydroxyvitamin D 3 in the Intestine Processes in the Cell That Are Mediated by 1,25‐Dihydroxyvitamin D 3 Intestinal Brush Border Events Induced by 1,25‐Dihydroxyvitamin D 3 Events at the Contraluminal Border Effects of 1,25‐Dihydroxyvitamin D 3 on the Intestinal Cell 1,25‐Dihydroxyvitamin D 3 in the Kidney

Abstract The sections in this article are: Intrarenal Hemodynamic Control of Sodium Excretion Effects of Peritubular Starling Forces on Sodium Excretion Effects of Medullary Blood Flow on Sodium Excretion Effects of Renal Perfusion Pressure on Sodium Excretion Neural Control of Sodium Excretion Sodium Intake and Body Fluid Volumes Low‐Pressure Baroreceptors Renal Sympathetic Nerve Activity Hormonal Control of Sodium Excretion Renin–Angiotensin–Aldosterone System Renal Prostaglandin System Renal Kallikrein–Kinin System Natriuretic Hormone Atrial Natriuretic Peptide Summary