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Key Points Fibroblast growth factor 23 and 24,25-dihydroxyvitamin D are positively correlated and are significantly lower in Dent disease than in idiopathic calcium kidney stones patients. Dent patients with low 24,25-dihydroxyvitamin D had greater hypercalciuria and proteinuria, and, among adults, higher 1,25-dihydroxyvitamin D concentrations. Moderate phosphate supplementation mitigates hypercalciuria. Background Hypercalciuria is a prominent characteristic in Dent disease type 1 (DD1) and is associated with kidney stones and nephrocalcinosis. The objectives of this study were to assess fibroblast growth factor 23 (FGF23) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D) in DD1 patients and investigate the effects of phosphate supplementation on urinary calcium excretion. Methods Serum and 24-hour urine assessments from adult and pediatric DD1 patients ( N =10 adults; N =9 pediatrics) were compared with adult control subjects with a history of idiopathic calcium kidney stones and hypercalciuria ( N =9). Adult DD1 patients and control participants completed an oral phosphate supplementation intervention (1 g/d×14 days) with reassessment immediately after intervention. Results FGF23 was significantly lower in DD1 than in the control cohort (adults, P = 0.006) and positively correlated with 24,25(OH) 2 D across all study cohorts. The concentrations of 24,25(OH) 2 D were low with conversion ratios (25-hydroxyvitamin D: 24,25(OH) 2 D) exceeding the clinical reference limit for five of 10 adults and six of 9 pediatric DD1 patients. The DD1 cohorts were then stratified by the 24,25(OH) 2 D ratio into “normal” and “low” 24,25(OH) 2 D. Adult DD1 patients with low 24,25(OH) 2 D ( n =5) had lower FGF23, higher 1,25-dihydroxyvitamin D, greater urine calcium, and greater urine protein. Pediatric stratified data mirrored that in adults with the exception of no difference in serum 1,25-dihydroxyvitamin D. Phosphate supplementation was effective in decreasing urine calcium in both adult DD1 and control adult cohorts. Conclusions Clinical measurement of 24,25(OH) 2 D is a novel and useful analysis for evaluating the severity of calcium and protein dysregulation in DD1. In addition, moderate phosphate supplementation effectively mitigates urine calcium excretion in DD1 adult patients. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT02016235.

Background Corticosteroid injections (CSIs) are widely employed for chronic pain. These injections include peripheral nerve blocks and trigger point injections, injections of large appendicular joints, the axial facet and sacroiliac joints, and the epidural space. These injections may be performed in patients who have been recently vaccinated or plan to be vaccinated. This multisociety multispecialty position statement aims to develop evidence-based statements and recommendations (SRs) on the safe interval between CSIs and COVID-19 and influenza vaccine administration. Methods Development of the position statement was approved by the American Society of Regional Anesthesia and Pain Medicine Board of Directors and several other societies that agreed to participate. The scope of the SRs was agreed on to include the efficacy of COVID-19 and influenza vaccines, adverse events related to the CSIs, specifically the effect of CSIs on the hypothalamic–pituitary axis, incidence of COVID-19 in patients who had CSIs during the pandemic, incidence of influenza in patients who had CSIs during the influenza season, and recommend a reasonable interval between CSIs and COVID-19 and influenza vaccination 20 mg/day of prednisone s. Experts were assigned topics to perform a comprehensive literature review and draft SRs, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. A modified version of the US Preventive Services Task Force grading of evidence and strength of recommendation was followed. Results All SRs were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Boards of Directors of the participating societies also approved all SRs. If a vaccine has been recently administered or planned, then for non-urgent indications, the CSI should be offered at least 1 week before or after vaccine administration. For healthy patient(s), CSI, or vaccine administration may be performed without a 7-day interval after informed discussion with the patient and consent regarding the risk of blunted vaccine efficacy. For non-healthy patients, shared decision-making should include discussion of diminished vaccine effectiveness and the possibility of influenza or COVID-19 infection. Conclusions In this position statement, we provide recommendations on the optimal timing between CSIs and COVID-19 or influenza vaccine.

Introduction Burnout among healthcare professionals remains a critical public health issue linked to impaired cognition, emotional exhaustion and diminished clinical performance. Structured breathing practices have demonstrated promise in improving autonomic regulation and cerebral oxygenation, yet their feasibility, acceptability and implementation in real-world healthcare settings remain underexplored. Objectives This single-arm pilot feasibility trial aims to evaluate the feasibility, acceptability and implementation appropriateness of a structured breathing-based intervention for healthcare professionals across community-based Mayo Clinic Health System (MCHS) sites. Secondary objectives include assessing usability and engagement with the mobile breathing platform, while exploratory analyses will describe magnitude of variability and feasibility of collecting psychological and cerebral haemodynamic measures. This study will commence in November 2025 and is expected to be completed by June 2026. Methods and analysis A total of 40 clinicians (MD/DO/MBBS/PA) and nurses reporting moderate or greater burnout will be enrolled across four MCHS sites. Participants will complete a 4-month structured breathing programme delivered primarily online, supported by a mobile application for practice tracking. Assessments will occur at baseline, 2 months and 4 months, with functional near-infrared spectroscopy (fNIRS) measures of cerebral oxygenation collected at baseline and 4 months in a population subset. Primary outcomes include (1) recruitment yield, retention and adherence rates; (2) acceptability and participant satisfaction (survey and qualitative feedback); and (3) implementation appropriateness measured by the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). Secondary outcomes include digital engagement and usability through mobile analytics and the System Usability Scale. Exploratory outcomes are psychological indicators (burnout, depression, anxiety, perceived stress, sleep, fatigue, professional fulfilment and resilience) and physiological endpoints (fNIRS). Analyses will be descriptive, summarising feasibility metrics with 95% CIs. Progression criteria (recruitment≥75%, retention≥80%, adherence≥70%, AIM/IAM/FIM≥4.0) will determine readiness for a definitive hybrid effectiveness–implementation trial. Ethics and dissemination The study is approved by the Mayo Clinic Institutional Review Board (IRB # 25-009320). All participants will provide informed consent. Study procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be securely stored in REDCap and disseminated through peer-reviewed publications and scientific conference Trial registration number NCT07218458 .

Abstract Liver metastases from well-differentiated thyroid carcinomas are rare. We report 3 patients, 1 with follicular and 2 with oncocytic thyroid cancers, treated for liver metastases with yttrium-90 radioembolization. The 2 patients with oligometastatic disease received ablative radiation doses, while 1 patient with diffuse metastatic liver disease was treated palliatively with 2 sessions of reduced nonablative radiation dose due to a large hepatopulmonary shunt fraction diagnosed at work-up. The 2 cases of oligometastatic disease had a complete local response by imaging criteria, while the third case had a pronounced local partial response, without adverse events. Future guidelines should include radioembolization as a viable option for locoregional therapy of liver metastases of differentiated thyroid cancer not responsive to radioiodine in patients that do not qualify for or refuse hepatic surgery.

Abstract Context There are limited head-to-head trials comparing pharmacological treatments for acromegaly. Objective Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. Methods MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. Results Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. Conclusion This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.

Evidence-Based Practice (EBP) has increased the availability of psychological treatments, yet many people do not benefit from therapy, some report deteriorations in symptoms, and dropout rates remain high. Precision Mental Health (PMH) is proposed as an extension of EBP by combining systematic measurement with predictive analytics to support the right intervention, at the right time, for the right person. Recent advances in Artificial Intelligence (AI) make PMH increasingly feasible in routine psychotherapy; however, the implementation of these approaches in routine care is still incipient. In this context, the present article has two main aims. First, we summarize key advances in PMH, particularly measurement-based care and data-informed decision making. Second, we introduce the NOVA project (Navigating Outcomes via Analytics), a multi-phase translational program designed to implement PMH in real-world psychological services. Guided by the Implementing Precision Methods framework, NOVA integrates (i) stakeholder-informed work on clinician acceptability and intention to use, (ii) pragmatic evaluation of decision support tools in routine care, (iii) development of robust and interpretable predictive models, and (iv) training and dissemination activities aligned with responsible innovation and professional competencies for AI-supported precision care. By detailing NOVA’s implementation pathway, we aim to provide a concrete roadmap for bridging AI innovation and psychological practice, accelerating the sustainable adoption of PMH in real-world settings.

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

Background Tricuspid regurgitation (TR) is a common valvular disorder that can affect patients’ quality of life and survival. The impact of TR etiology on overall survival and the associated risk factors in each subgroup are not well studied. Methods Multisite, retrospective study evaluating survival based on TR etiology using Kaplan–Meier and Cox regression models. Stepwise approach was used to define TR etiology (≥moderate): primary (PTR; presence of a primary valvular pathology), lead associated (LTR; lead interfering with closure), and secondary TR (STR) in the setting of left‐sided valvular disease, left ventricular disease, other causes of pulmonary hypertension, right ventricular disease, and atrial secondary TR. Results A total of 12 899 patients were included (3% PTR, 90% STR, 7% LTR). The mean age was 68±14, 73±13, and 71±13 years, respectively (44%–55% female patients). Adjusting for age, sex, and TR severity, patients with PTR had better overall survival (PTR: reference; STR hazard ratio [HR], 1.4 [1.2–1.6], LTR HR, 1.5 [1.1–1.7]). On multivariable Cox regression, the Tricuspid Regurgitation Impact on Outcomes score was associated with mortality across all groups ( P <0.05 for all). In addition, other risk factors associated with worse outcomes included pulmonary hypertension and ≥moderate right ventricular enlargement in PTR; left‐sided valvular disease, pulmonary hypertension, and ≥moderate right ventricular dysfunction in STR; and left ventricular disease and ≥moderate right ventricular dysfunction in LTR. Conclusions Patients with PTR have better survival than STR and LTR. Tricuspid Regurgitation Impact on Outcomes score was associated with mortality across etiologies, whereas other risk factors are etiology specific. Improved risk profiling may enhance patient selection, treatment decisions, and outcomes.

BACKGROUND: Cerebral microbleeds (CMBs) are associated with dementia, but the impact of specific microbleed patterns (with distinct pathophysiologies) is unclear. Lobar CMBs commonly result from cerebral amyloid angiopathy (sometimes with cortical superficial siderosis [cSS]), while subcortical microbleeds indicate a hypertensive cause. This study investigates the association of CMB presence, patterns, and frequency with dementia risk. METHODS: Participants from the ARIC-NCS (Atherosclerosis Risk in Communities-Neurocognitive Study), a community-based longitudinal cohort, with a 3T research magnetic resonance imaging scan at visit 5 (2011–2013) and without prior intracerebral hemorrhage or dementia were included. CMB and cSS presence and location were evaluated using a T2* gradient-recalled echo sequence. Each individual’s pattern of CMBs was classified as no CMBs, subcortical only, mixed (subcortical and lobar±cSS), lobar±cSS only, or cSS. Dementia adjudication was determined by blinded review of cognitive testing, informant interviews, and hospital discharge codes or death certificates (from follow-up visits and ongoing surveillance). Cox proportional hazards models assessed associations between CMBs and incident dementia through 2020, adjusted for demographics, vascular risk factors, and white matter hyperintensities. RESULTS: Among 1583 participants (mean age, 76 years; 24.7% cumulative dementia incidence over a median of 23.6 follow-up years), 361 had CMBs. Compared with individuals without CMBs, those with mixed (hazard ratio, 1.99 [95% CI, 1.40–2.83]) or lobar±cSS (hazard ratio, 1.96 [95% CI, 1.30–2.97]) CMB patterns had increased dementia risk, whereas individuals with a subcortical-only pattern did not (hazard ratio, 1.04 [95% CI, 0.78–1.39]). cSS presence (n=21; versus absence) showed an increased risk of dementia (hazard ratio, 2.57 [95% CI, 1.36–4.89]). Greater numbers of microbleeds across all CMB subtypes exhibited an increased risk of dementia. CONCLUSIONS: Lobar and mixed CMB patterns and increasing numbers of CMBs are associated with incident dementia. Certain CMB patterns have differential associations with dementia, but severe enough disease burden, regardless of CMB distribution, is associated with increased dementia risk.