Citations

Background: Religious affiliation has traditionally served as a coping strategy during stressful events such as the COVID-19 pandemic. Pregnant women faced heightened stress during the pandemic due to concerns about their health as well as that of their fetus. This study examined the prevalence of self-reported religious affiliation among SARS-CoV-2-positive pregnant women and investigated differences in psychiatric diagnoses and pregnancy outcomes based on religious affiliation. Methods: The study included all asymptomatic or mildly symptomatic SARS-CoV-2-positive pregnant women who received care at the Mayo Health System from March 2020 through October 2021 and completed the routine religious affiliation questionnaire. Those selecting “none” were categorized as having no religious affiliation (RA−), whereas those selecting a specific religion were categorized as religiously affiliated (RA+). Results: Among 609 women, 49.6% were RA+ and 50.4% were RA−. RA+ women were more likely to be white, married, college-educated, and have fewer prior abortions. There were no significant differences in rates of depression, anxiety, psychotropic medication use, substance use, or pregnancy and labor complications between RA+ and RA− groups. Conclusions: Half of the women in this cohort reported no religious affiliation. Previously reported protective associations between religiosity and mental health were not observed when religious affiliation alone was examined.

Background: Localized soft tissue sarcoma (STS) is primarily treated with surgical resection with or without radiotherapy (RT), while the role of chemotherapy (CT) as a radiosensitizer remains unclear. We report our single-institution experience with combined chemoradiotherapy (CCRT) in treating localized STS. Methods: We conducted a retrospective analysis of patients with localized STS treated at Mayo Clinic with mitomycin, cisplatin, and doxorubicin (MitoAP) concurrently with RT between 1/1/85 and 12/12/19. Results: We identified 179 patients (median age 58 years; median tumor size 9.5 cm), with 83.8% of tumors located in the extremities or trunk. Among them, 77.1% received perioperative CT in addition to CCRT, with 95% of those treated in the neoadjuvant setting. Median RT dose was 50 Gray. The 5-year disease-specific survival (DSS) was 77.9% (95% confidence interval, CI: 70.8–83.4%). The addition of perioperative CT to CCRT was associated with improved DSS compared with CCRT alone (p = 0.01, Hazard Ratio, HR: 0.48, 95% CI: 0.27–0.85). Median post-CCRT tumor viability was 30% and did not differ by CT use (p = 0.39), but varied significantly by histology (p < 0.001). Conclusions: Our institutional protocol utilizing two cycles of MitoAP with RT was well tolerated. DSS in our cohort was similar to historical data using perioperative RT alone, suggesting no clear benefit from CCRT. However, the majority of patients in our cohort were classified as high risk, which may have attenuated a potential survival benefit in the absence of appropriate comparative controls. Furthermore, additional perioperative CT to CCRT was associated with improved DSS and differential histology-specific responses in tumor viability, suggesting that a more aggressive neoadjuvant and perioperative approach may be beneficial in selected patients.

Diagnosing rare genetic diseases remains a major challenge despite widespread clinical testing. Long-read RNA sequencing (RNA-seq) offers a powerful approach to capturing the effects of genetic variants on the transcriptome, yet challenges with sequencing coverage, cost, tissue selection, and scalability have limited its clinical adoption. To address this, we developed STRIPE (Sequencing Targeted RNAs Identifies Pathogenic Events), a targeted long-read RNA-seq–based strategy for rare disease diagnosis and variant interpretation. STRIPE enables deep sequencing of full-length transcripts for any customized disease-specific gene panel such that a wide range of clinically informative readouts, including transcript aberrations and sequence variants, can be detected at haplotype-level resolution. Applying STRIPE to 88 individuals spanning two major rare disease groups, we accurately reidentified known pathogenic variants and revealed their transcript consequences, including many unexpected ones. For 8 of 15 splice site region variants, we observed more complex RNA processing defects beyond single exon skipping or cryptic splice site activation. Notably, we find that donor splice site variants frequently activate cryptic intronic polyadenylation sites, leading to premature transcript termination. Leveraging unique strengths of long-read RNA-seq, STRIPE also resolved variants of uncertain significance and uncovered disease-causing variants in five previously undiagnosed individuals. Overall, STRIPE is a powerful, adaptable, and scalable strategy with broad potential to improve clinical variant interpretation and advance genetic diagnosis of rare diseases.

Abstract Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2026 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2026 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, specialty drugs, and vaccines. For nonfederal hospitals, clinics, and overall (all sectors), estimates for growth of pharmaceutical expenditures in 2026 were made based on a combination of quantitative analyses and expert opinion. Results In 2025, overall pharmaceutical expenditures in the US grew 12.7% compared to 2024, for a total of $915.2 billion. Utilization (a 9.3% increase) drove this increase, while growth due to new drugs (0.9%) and price increases (1.2%) had a modest impact. Tirzepatide was the new top drug in 2025, followed by semaglutide and apixiban. Drug expenditures were $42.9 billion (a 9.6% increase) and $190.5 billion (a 19.0% increase) in nonfederal hospitals and in clinics, respectively. In clinics, volume drove drug expense growth, contributing with a 13.6% increase, while price and new drugs each contributed with a 2.7% increase. In nonfederal hospitals, expenditure growth was driven by increases in volume (4.6%), new products (3.7%), and prices (1.5%). Several new drugs that will influence spending are expected to be approved in 2026. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2026, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate increases of 14.0%-16.0% and 4.0%-6.0%, respectively, compared to 2025. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending

Background: Stable osteochondritis dissecans (OCD) lesions are primarily treated nonoperatively. Nonoperative treatment includes several recommendations, including the use of an unloader brace. However, little is known about the clinical effectiveness of unloader bracing and its influence on OCD healing, return to sports, and patient-reported outcomes (PROs). The purpose of this investigation was to evaluate the impact of unloader bracing on patients with stable medial femoral condyle (MFC) OCD lesions treated nonoperatively. Purpose: To investigate the influence of valgus unloader bracing on the success of treating stable MFC OCD with nonoperative treatment strategies. Study Design: Cohort study; Level of evidence, 2. Methods: The authors used a prospective cohort of patients receiving nonoperative care for stable MFC knee OCD lesions. The primary variable of interest was the efficacy of bracing. The primary outcomes were transition from nonoperative care to surgical intervention, return-to-play (RTP) clearance, and PROs. Bivariate testing was used to determine if there were differences between groups. Chi-square testing was used to determine if there were differences in rates of transition to surgery by group. The timing of the transition by each group was assessed using a Wilcoxon rank-sum test, given the nonparametric nature of the data. Kaplan-Meier survival analysis was used to calculate time at risk, incidence rate, and survival times for each group. Results: A total of 185 knees (bracing group: 123 [66.5%] knees; no-bracing group: 62 [33.5%] knees) were analyzed. Overall, 142 (76.8%) knees were successfully treated nonoperatively. Transition to surgery occurred in 43 (23.2%) knees. There were no differences in transition to surgery by groups, with no differences seen by group. Of the knees that did not transition to surgical care, 65 (71.4%) in the bracing group and 38 (74.5%) in the no-bracing group received RTP clearance ( P = .693). PRO scores were similar between the 2 groups at the time of RTP clearance. Conclusion: The inclusion of an unloader brace in the nonoperative treatment for stable MFC OCD lesions did not decrease the likelihood of patients undergoing surgical intervention or improve their PRO scores at the time of RTP clearance. Registration: NCT02771496 (ClinicalTrials.gov identifier).

Objective Medium‐vessel vasculitis involving the visceral vasculature in adults is rare. Pancreatic ductal adenocarcinoma (PDAC) has been implicated in medium artery vascular thickening secondary to extravascular migratory metastasis with involvement of the celiac and superior mesenteric vessels. Methods Patients presenting to the rheumatology vasculitis subspecialty clinic were retrospectively identified using an electronic health record data exploration tool evaluating for diagnosis of pancreatic cancer, periaortitis, and vasculitis between January 2015 and December 2024. Results We retrospectively identified four patients with PDAC initially presenting with periarterial thickening of the celiac and superior celiac and superior mesenteric vessels (100% White, 50% male, median age 70.5 years). All four patients had abdominal pain with significant unintentional weight loss, with a median weight loss of 25 pounds (range 25–50 pounds). The median time to correct diagnosis was 221 days (range 162–340 days). All four patients had an elevated carbohydrate antigen 19‐9 level (range from 114 to 10,702, with a median of 341.5 U/mL). All four patients were diagnosed with endoscopic ultrasound–guided fine‐needle aspirations. The median number of biopsies required to make the diagnosis was three. Conclusion Isolated celiac and superior mesenteric periarterial thickening or “cuffing” is a vasculitis mimic that should prompt a comprehensive malignancy workup. Expedited referral to a tertiary center is essential given difficulty in tissue sampling with conventional methods and to avoid further delays in diagnosis.

Abstract A short diagnosis-to-treatment interval independently predicts inferior outcomes in follicular lymphoma. Using international discovery and validation cohorts, we demonstrate its prognostic value beyond established prognostic indices, with implications for risk stratification, clinical trial design, and interpretation.

Abstract In this systematic review, we aimed to assess the sensitivity of serum immunofixation (SIFE), urine immunofixation (UIFE), and serum free light chain (sFLC) in detecting plasma cell dyscrasia associated with light chain (AL) amyloidosis. We searched the literature using PubMed, Embase, and CENTRAL databases since inception through March 2024. We included studies reporting the diagnostic accuracy of immunofixation and/or sFLC in patients with AL amyloidosis. We used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of the evidence and QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) to assess the risk of bias. After deduplication, 29 237 records were screened, and 44 studies (n = 18 071) were included. For the meta-analysis, 28 studies reported sensitivity for SIFE (n = 3390), 24 studies for UIFE (n = 2830), 19 studies for SIFE and UIFE (n = 2819), 21 studies for sFLC ratio (n = 3678), 6 studies for SIFE and sFLC ratio (n = 372), 3 studies for UIFE and sFLC ratio (n = 242), and 10 studies for all 3 tests (n = 1430). Pooled sensitivities were as follows: SIFE, 0.68 (95% confidence interval [CI], 0.62-0.73); UIFE, 0.77 (95% CI, 0.72-0.81); SIFE and UIFE, 0.89 (95% CI, 0.84-0.93); and sFLC ratio, 0.82 (95% CI, 0.78-0.86). When SIFE, UIFE, and sFLC ratio were combined, the sensitivity reached 0.99 (95% CI, 0.96-1.00). The high sensitivity of combining SIFE, UIFE, and sFLC ratio supports their use as a reliable initial testing strategy to raise suspicion for AL amyloidosis and guide decisions regarding future diagnostic modalities.

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.