Citations

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.

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: Eight Global Ophthalmology (GO) fellowship programs are available in the United States, and more than 30 U.S. GO fellows are now alumni. There are no standardized learning objectives for these programs, and fellows’ experiences vary widely between institutions. Purpose: To survey GO fellowship program directors in the United States to elucidate differences in learning objectives, duration of time abroad, funding sources, and other differences between GO fellowships. Methods: All program directors at all institutions with current GO fellowship programs in the United States were sent a 25-question questionnaire via email from October through December 2022. The questionnaire included distinct domains regarding the GO fellowship experience, care delivery, didactics, and best practices. Most questionnaire items were quantitative; 3 were qualitative. Responses to the quantitative and qualitative questions items were summarized descriptively. Results: All 10 program directors from the 8 GO fellowship programs that were current at the time of the survey participated. GO fellowship positions at most (88%) institutions were funded, in part, by the billing of care services provided by the fellows, with 50% of programs receiving supplemental funding from donations and 25% from nongovernmental organizations. Non-GO duties at the program home institutions constituted 29.5% of the time spent during the fellowships, on average. Policy advocacy occupies 2.3% of fellowship time, on average. Specific didactic topics covered in the GO programs and director perspectives on the pragmatic best practices for GO outreach varied considerably; however, inclusion of at least some public health topics and ethics appeared to be consistent among all of the programs. Conclusions: These findings provide insights into the landscape of GO fellowship programs in the United States, highlighting variations in funding, formal educational opportunities, and the allocation of time fellows spent working at the program home institution. Establishing standardized core competencies for fellows is recommended.

Importance Total thyroidectomy is the established surgical standard for hereditary and sporadic medullary thyroid cancer (sMTC). However, for unilateral sporadic tumors, its benefit over lobectomy remains uncertain. Objective To compare oncologic outcomes between total thyroidectomy and lobectomy in patients with sMTC. Data Sources and Study Selection MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception to December 2025 to identify comparative studies on patients with sMTC who underwent total thyroidectomy or lobectomy. Data Extraction and Synthesis Reviewers working independently and in duplicate screened titles, abstracts, and full-text articles for eligibility using standardized instructions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) and Meta-Analysis of Observational Studies in Epidemiology ( MOOSE ) guidelines were used for reporting. Main Outcomes and Measures Primary outcomes were mortality, overall survival, structural recurrence, biochemical cure, and distant metastasis development. The secondary outcome was postoperative complications. Effect measures were calculated as odds ratios (ORs) or relative risks (RRs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results Nine retrospective studies met inclusion criteria and comprised 1371 patients (295 of 397 patients [74.3%] with documented sex were female, and median age ranged from 45.0 to 58.2 years). A total of 531 patients (38.7%) underwent lobectomy and 840 (61.3%) underwent total thyroidectomy. Of 341 tumors, 280 (82.1%) lacked extrathyroidal extension, 284 of 401 tumors (70.8%) measured smaller than 2 cm (70.8%), and 197 of 343 tumors (57.4%) were node negative; central neck dissection was performed in 445 of 492 patients (90.4%). Multifocal disease was uncommon and reported in 30 of 330 patients (9.1%). Mortality did not differ at 5 years (RR, 0.30; 95% CI, 0.07-1.35) or beyond (RR, 1.00; 95% CI, 0.40-2.47). Overall survival at 5 years was similar (RR, 1.02; 95% CI, 0.94-1.11). Total thyroidectomy was not associated with lower structural recurrence rates at 5 years (OR, 0.45; 95% CI, 0.14-1.49), but it was associated beyond 5 years (OR, 7.26; 95% CI, 1.07-49.21). No differences were observed for biochemical cure at 5 years (OR, 0.86; 95% CI, 0.47-1.56) or beyond 5 years (OR, 0.87; 95% CI, 0.26-2.89). Distant metastasis development did not differ at 5 years (OR, 1.64; 95% CI, 0.09-31.52). Sensitivity analyses revealed no differences across any outcomes. Postoperative complications were more common in total thyroidectomy. Risk of bias was high in 4 studies, moderate in 4, and low in 1. Conclusions and Relevance Findings in this systematic review and meta-analysis, based on data from retrospective studies, suggest that thyroid lobectomy may be associated with oncologic outcomes comparable to total thyroidectomy in selected patients with sMTC.

Abstract Objectives Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases. Methods Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset. Results Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression. Conclusions Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.

INTRODUCTION: The adjunctive use of p53 immunohistochemistry has been proposed as a potential tool to improve risk stratification in Barrett's esophagus (BE) with conflicting results. We performed a systematic review and meta-analysis to evaluate the performance of p53 in predicting progression to advanced neoplasia (high-grade dysplasia [HGD] and esophageal adenocarcinoma [EAC]) among patients with BE. METHODS: We searched multiple databases for studies that evaluated the use of aberrant p53 in esophageal biopsies among patients with BE and reported progression rates to HGD/EAC. The outcomes were p53 test characteristics and incidence and risk ratio (RR) for progression to HGD/EAC in patients with and without aberrant p53 using random effects models. RESULTS: Among the 27 included studies, the proportion of patients with aberrant p53 expression at baseline was 20% (95% CI: 14%, 27%). The rate of progression with and without aberrant p53 was 8 per 100 person-years (95% CI: 6, 11) and 0.3 per 100 person-years (95% CI: 0.1, 0.6), respectively. Compared with patients without aberrant p53 expression, those with aberrant p53 had a higher risk for progression to HGD/EAC in cohort studies (RR = 10.2 [95% CI: 6.9, 15.0]) and case control studies (RR = 3.3 [95% CI: 2.5, 4.4]). The sensitivity for progression for non-dysplastic Barrett's esophagus and low-grade dysplasia/indefinite for dysplasia was 42% and 77% and specificity was 96% and 76%, respectively. DISCUSSION: While aberrant p53 expression has been associated with an increased risk of progression to advanced neoplasia in patients with BE undergoing surveillance, the diagnostic characteristics are suboptimal precluding uniform clinical adoption. Prospective studies with standardized grading protocols are needed to determine whether p53-guided surveillance strategies can meaningfully improve patient outcomes.

Abstract Background Penile inversion vaginoplasty (PIV) is a commonly performed gender-affirming procedure that requires postoperative dilation to maintain vaginal canal patency. Aim To characterize patient-reported dilation experiences and evaluate temporal trends in postoperative outcomes. Methods Consecutive patients undergoing primary PIV at a single center were prospectively surveyed at 1, 3, 6, 9, and 12 months postoperatively. Surveys were author-developed based on clinical experience and clinical review. Surveys assessed dilation frequency, session duration, depth achieved, and challenges encountered. Univariate analyzes were used to evaluate changes over time. Outcomes The primary outcome was the proportion of patients reporting any dilation-related challenge over time. Secondary outcomes included adherence metrics (frequency, days/week, session duration), depth achieved, and specific challenges. Results Seventeen of 27 patients completed all survey time points (63% response rate). On average, participants dilated 6.6 ± 1.4 days/week and 2.4 ± 0.9 times/day; sessions lasted 38.3 ± 16 minutes. Mean depth achieved was 4.05 ± 1.32 (13 cm standardized dilator set), with no significant decline over time. All patients reported at least one difficulty, most commonly tightness (71%), bleeding (71%), pain (65%), discharge (47%), and logistical barriers (24%). The prevalence of reported challenges declined significantly after six months (P < .05). Clinical Implications Early dilation-related difficulties are nearly universal and should be anticipated with proactive counseling and structured postoperative support, though symptoms improve over time. Strengths and Limitations This is the first prospective, longitudinal study of dilation following PIV, using an author-developed survey instrument to capture patient-reported outcomes. Limitations include modest sample size, potential response bias, and lack of assessment of challenge severity. Conclusion Reported dilation adherence following PIV is high, but most patients experience early challenges that diminish over time, highlighting the need for anticipatory counseling and individualized, symptom-responsive dilation protocols.

Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by persistent restriction or avoidance of food intake leading to clinically significant nutritional, medical, and/or psychosocial consequences, without associated body-image disturbance. Although historically described in pediatric populations, ARFID is increasingly recognized in adults, particularly among patients with gastrointestinal (GI) disorders. Emerging data demonstrate a strong bidirectional relationship between ARFID and GI disease—especially disorders of gut–brain interaction—where fear of GI symptoms commonly drives restrictive eating, and chronic undernutrition may worsen GI motility, visceral sensitivity, and symptom severity, reinforcing a self-perpetuating cycle. Despite growing recognition of ARFID in adult gastroenterology patients, evidence guiding nutritional management and the use of nutrition support therapies in this population remains limited. This narrative review synthesizes the current literature on the epidemiology, clinical features, and nutritional consequences of ARFID in adults with GI disease, with a focus on screening and diagnostic considerations relevant to GI clinicians and principles of multidisciplinary management. Particular attention is given to the role of nutrition support therapies, including oral nutritional supplementation, enteral nutrition, and parenteral nutrition. While oral strategies are foundational to nutritional rehabilitation, available evidence supporting enteral or parenteral nutrition in adults with ARFID is sparse and largely extrapolated from pediatric or retrospective studies. Expert guidelines caution against routine or prolonged use of invasive nutrition support due to risks of reinforcing food avoidance, medical complications, and poor long-term outcomes, recommending their use only in carefully selected, medically necessary, and time-limited circumstances. Overall, ARFID represents an underrecognized but clinically significant contributor to malnutrition and symptom burden in adult patients with GI disorders, underscoring the need for routine screening, individualized multidisciplinary care, and high-quality prospective research to inform evidence-based treatment guidelines.

Abstract Aims Calcium release channel deficiency syndrome (CRCDS) results from loss-of-function (LOF) variants in the RYR2-encoded type 2 ryanodine receptor (RyR2), predisposing patients to sudden cardiac arrest/death (SCA/SCD) without abnormalities on a stress electrocardiogram (ECG). Undetected CRCDS may underlie idiopathic ventricular fibrillation (IVF) and sudden unexplained death in the young (SUDY). We aimed to determine the prevalence of potential CRCDS-causative RYR2 variants in IVF and SUDY. Methods and results We reviewed clinical evaluation and RYR2 genetic analysis of 169 IVF patients and 279 SUDY victims. Only ultra-rare (<0.005% in gnomAD) nonsynonymous RYR2 variants were considered potentially pathogenic. Among IVF patients, 6/169 (3%) overall—and 6/67 (9%) with exertion-related SCA—harboured an RYR2 variant and represent potential CRCDS cases. All exhibited normal resting and stress ECGs. Genetic analysis revealed six distinct RYR2 variants, two previously characterized as LOF. In SUDY, 31/279 victims (11%) had a RYR2 variant (30 unique variants), predominantly observed in exertion-related SCD 20/83 (24%) vs. rest-related 11/196 (6%). Of the 14 SUDY victims with functionally characterized RYR2 variants, five (2% of total cohort) had a LOF variant; among the 56 exertion-related SUDY cases, four (7%) had a LOF variant. Conclusion CRCDS may account for 3% of IVF overall and 9% of exertion-related SCA in IVF. Ultra-rare RYR2 variants may underlie up to 11% of SUDY, with 65% of RYR2-positive cases occurring during exertion. LOF-RYR2 variants may contribute to ≥7% of exercise-associated SUDY. Accurate identification of the underlying ryanodinopathy is essential for clinical management of affected patients.