Citations

Abstract DDX3X dysfunction causes an X-linked multisystem disorder with high penetrance and variable expressivity. The phenotypic spectrum spans from learning disability without somatic involvement to profound intellectual disability with severe impairments in the central nervous system and other organs. A few multicenter studies and single case reports have previously highlighted some common phenotypic patterns but were unable to delineate correlations between underlying DDX3X variants and phenotypic findings.From the second largest patient cohort published to date, we analysed clinical, psychometric and diagnostic findings of 52 female and 7 male individuals, harbouring de novo and inherited DDX3X variants. These female patients revealed previously unknown quantitative correlations between variant type and localization and specific phenotypic findings (growth features, epilepsy, brain anomalies, dysmorphisms, motor-focused neurological findings). Moreover, by analysing the in silico folding and RNA binding capability of mutant DDX3X monomers, we were able to delineate novel correlations between DDX3X monomer misfolding grade and phenotypic severity.

The author presents the case of a middle-aged woman who had a left parietal lobe infarct. Due to severe aortic regurgitation limiting her activity and aortic root aneurysm, the patient underwent aortic valve and aortic graft replacement, in addition to PFO closure. During this hospitalization, aortic root pathology was noted, leading to an ultimate diagnosis of giant cell aortitis.

Objectives: Diabetes mellitus and chronic pancreatitis are established risk factors for pancreatic ductal adenocarcinoma (PDAC). The co-occurrence of exocrine and endocrine pancreatic dysfunction may increase the risk of progression to PDAC and could play a role in early detection. We sought to explore this hypothesis by comparing PDAC risk among patients with diabetes mellitus (DM) and low fecal elastase (FE) in a real-world cohort of patients. Materials and Methods: A retrospective cohort study was conducted using the TriNetX research network including adults with continuous follow-up from 2016 to 2023. The cohort was stratified into 4 groups based on the presence or absence of DM, and normal FE (>200 µg/g) or low FE (<200 µg/g). The 4 groups included: (1) low FE and DM, (2) low FE without DM, (3) normal FE and DM, (4) normal FE without DM. Propensity score matching was performed to balance covariates including age, sex, race, comorbidities to allow for a 6-way comparison of PDAC risk between groups. Time-to-event analyses were conducted with Kaplan-Meier curves and Cox proportional hazards models to estimate hazard ratios (HR) and 95% CIs for the primary outcome of PDAC incidence. Results: Of the study cohort, 29,207 had fecal elastase levels. Low FE (<200 µg/g) was observed in 33% (n = 9585) of these patients. After 6-way comparisons, we observed a higher PDAC risk among individuals with both DM and low FE compared with other groups. The highest PDAC risk was observed in patients with both a low FE (<200 µg/g) and DM compared with those with a normal FE and without a history of DM (HR: 3.68; 95% CI, 2.07–6.53; P < 0.001). Sensitivity analysis using a stricter fecal elastase cutoff of <100 µg/g showed a similar finding, with the highest hazard ratio for PDAC among patients with both DM and very low FE levels (HR: 3.07, 95% CI, 1.37–6.91; P = 0.004). Conclusions: The coexistence of low fecal elastase and DM amplifies the risk of pancreatic ductal adenocarcinoma in our cohort of patients. These results suggest that fecal elastase values may be used to enrich the diabetic population for future PDAC risk stratification, though more studies are needed to validate these findings.

Background Despite the widespread adoption of established and emerging forensic training and education modalities, there is limited evidence supporting effective ways in which to systematically evaluate their adoption into forensic nursing practice. To address this, our team developed the Sexual Assault Nurse Examiner (SANE) Practice Integrated Competency Evaluation (SPICE) as an innovative tool to support self-reflection, goal setting, and an evaluation of role development. Aim To establish expert consensus on the content and capacity of SPICE to evaluate role development across essential forensic nurse competencies, responsibilities, and clinical practice expectations. Method We utilized a modified Delphi method to establish expert consensus. Results We engaged forensic experts in multiple rounds of review. A deductive, rapid thematic analysis synthesized qualitative discussion. Survey-based results were summarized descriptively. Discussion The expert consensus approach we describe here highlights the potential and promising utility of SPICE to evaluate, guide, and enhance SANE role performance and ongoing professional development.

Abstract Background Allowable total error (ATE) is a quality concept that defines acceptable analytical performance for a clinical laboratory assay. ATE will vary in terms of the amount of error permissible not only between assays but also based on the test setting and the assay’s clinical use. In the clinical laboratory, ATE limits are routinely applied, for example, when evaluating new analytical methodology or equipment for patient testing, troubleshooting unacceptable quality control, or in evaluating instrument comparability. Content Currently, there are no universally applicable standards for defining the maximum magnitude of allowable error. However, there are several resources available for users to consider when setting ATE limits. Examples include clinical outcomes studies, biological variation of the measurand, state-of-the-art, professional organizations, and requirements set by regulatory agencies and proficiency testing/external quality assessment scheme organizers. Each of these approaches varies in terms of the resulting magnitude of allowable error for the same assay. This review describes these resources in more detail and discusses the strengths and weaknesses of each approach. Summary ATE users should be aware of different resources and their limitations before defining acceptance criteria for an assay in their clinical laboratory.

ABSTRACT. Cervical cancer is a malignancy with a well-established viral origin linked to high-risk human papillomavirus (HPV) types. Globally, there are 348,709 estimated deaths among 662,301 cervical cancer cases. India faces a disproportionately high burden, contributing to 79,906 of these deaths and accounting for over 22% of global deaths. The nation’s high mortality rate is attributable to the low rate of cervical cancer screening and HPV vaccination uptake. There is a greater impact of cervical cancer on those of lower socioeconomic status and a cultural stigma surrounding sexually transmitted infections. We recommend a comprehensive cervical cancer prevention strategy, including screening programs, culturally sensitive education for patients and providers, government-endorsed HPV vaccination, and continuing studies on diagnostics and vaccination in the Indian context.

Abstract Context Benign thyroid nodules (BTNs) are highly prevalent, and current treatment options are primarily invasive. There is a need for effective, noninvasive alternatives. Objective To systematically evaluate the efficacy of repurposed pharmacologic agents in reducing the size of BTNs. Data Sources MEDLINE, EMBASE, Cochrane databases, and Scopus were searched from inception to December 18, 2024. Study Selection We included preclinical and clinical studies evaluating repurposed drugs for BTNs in adults. Of 1499 records screened, 20 studies met inclusion criteria: 6 randomized controlled trials (RCTs), 6 prospective cohorts, 3 retrospective observational studies, 3 case reports, 1 cross-sectional study, and 1 preclinical study. Data Extraction Data were extracted independently in duplicate using a standardized form. Data Synthesis Narrative synthesis was conducted due to heterogeneity. Metformin was the most frequently evaluated agent (7 studies), with 5 studies (including 2 RCTs) reporting statistically significant reductions in dominant nodule volume. One prospective study demonstrated a reduction in the maximum nodule diameter, which was not statistically significant, and 1 RCT showed no changes in nodule size after intervention. Statins (4 studies) and somatostatin analogues (4 studies) showed mixed results. Myo-inositol with selenium, herbal formulations, and immune checkpoint inhibitors showed promise in single studies or case reports. Conclusion Metformin shows the most consistent potential for noninvasive reduction of BTN size, particularly in patients with metabolic comorbidities. However, current evidence is limited and heterogeneous. Further large-scale studies are needed to confirm efficacy and guide clinical use.