Citations

ABSTRACT Legionella species are important causes of community-acquired pneumonia. The diagnostic performance and clinical implications of a fluorescence resonance energy transfer (FRET)-based real-time PCR assay targeting the Legionella 5S rRNA gene were evaluated, with emphasis on melting temperature (Tm) analysis to differentiate detected species and associated clinical outcomes. A retrospective multicenter cohort study of adults with laboratory-confirmed Legionella infection between 2019 and 2025 was conducted. PCR crossing point (Cp) and Tm data were analyzed and compared with species identified in culture from respiratory specimens. Associations between Tm and clinical outcomes were assessed using multivariable logistic regression. Among 51,489 PCR tests performed, 823 (1.6%) were positive. Among 376 Legionella infections, PCR demonstrated the highest diagnostic yield. Among patients undergoing all three diagnostic tests, the addition of PCR increased detection from 49% with urine antigen and culture combined to 100% ( P < 0.001). Of 189 PCR-positive patient specimens with available Tm data, Tm showed a bimodal distribution, being either <66°C or ≥66°C. A Tm cutoff of ≥66°C discriminated L. pneumophila / L. longbeachae from other Legionella species with excellent performance (AUC, 1.00). Overall, 29.6% of infections had a Tm <66°C, consistent with non- pneumophila/ non- longbeachae Legionella species. Infections due to L. pneumophila / L. longbeachae , which correspond to high Tm values in the study assay, were independently associated with ICU admission (adjusted odds ratio, 2.85; 95% CI, 1.33–6.11; P = 0.007), but not 90-day mortality. Real-time PCR targeting the Legionella 5S rRNA gene provides superior detection compared to culture and/or urine antigen testing and enables higher-risk species discrimination through Tm analysis. IMPORTANCE Nearly one-third of Legionella infections in this cohort were attributable to non- pneumophila species, highlighting limitations of diagnostic strategies reliant on Legionella urine antigen testing or L. pneumophila PCR. The findings suggest that species-level inference can be derived from melting-temperature data generated during routine PCR testing. Incorporating validated melting-temperature interpretation into reporting workflows may improve epidemiologic surveillance and clinical understanding of characteristics of Legionella pneumonia.

Colorectal cancer (CRC) is responsible for a high cancer burden and a high number of deaths all over the world, although effective screening can make it preventable to a significant extent. Stool-based tests, such as the fecal immunochemical test (FIT) and multitarget stool DNA (mt-sDNA) testing, are gaining considerable popularity as non-invasive procedures that can be a replacement for colonoscopies for people at an average risk for colon cancer. Despite evidence from several randomized controlled trials supporting the use of these tests for colorectal cancer screening, their external validity in a real-world setting is influenced by many factors such as adherence, timely follow-up post testing, the healthcare cost burden, accessibility and the capacity of the health system. In this article, we have performed an extensive narrative literature review of research published between 2020 and 2025 comparing FIT and the mt-sDNA test with reference to diagnostic accuracy, cost-effectiveness, adherence and outcomes of implementation. We discuss the issues of sensitivity and specificity, look at post-test requirements for colonoscopy and check if there is any discrimination in healthcare. These findings suggest that FIT and mt-sDNA tests should not be considered competing technologies but rather complementary screening methods, with their overall effectiveness contingent upon appropriate patient selection and widespread system-level implementation. It is crucial to combine strategic test selection with a robust follow-up infrastructure to ensure that the entire population benefits from the CRC prevention program.

Background: Conflicts of interest pose a risk to the integrity of clinical research. As part of the Sunshine Act, the Open Payments Program was established to provide transparency in financial relationships between commercial entities and physicians. Previous research indicates disparities between industry payments self-reported by plastic surgeon authors and those disclosed by commercial entities. This study sought to revisit the accuracy of conflict-of-interest disclosures, comparing current trends with previously published data, and introduce a novel automated search tool designed to facilitate future reviews of self-disclosures. Methods: Articles from the Aesthetic Surgery Journal and Plastic and Reconstructive Surgery published between 2017 and 2022 were reviewed. Self-reported disclosures for plastic surgeon authors were aggregated and compared against the Open Payments database using Python. Results: A total of 8040 articles were reviewed. After filtering and applying inclusion criteria, 961 unique authors and 4226 authorships were identified. A total of 5802 discrepancies were found, with 78.6% of eligible authors having at least 1 discrepancy. Four percent of the included publications were estimated to contain undisclosed relationships that qualified as conflicts of interest. The median total payments for authors with discrepancies were greater than for authors without discrepancies ($9600 vs. $2500; P <0.001). A discrepancy in self-reporting was more likely to be identified among senior authors ( P <0.001). Conclusions: Plastic surgeon authors continue to underreport their financial relationships. Automated screening may help identify disclosure discrepancies and support more complete author self-reporting.

Introduction Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are progressive neurodegenerative disorders characterized by alpha-synuclein pathology. As current therapies largely target symptoms, there is a clear need for disease-modifying treatments. Emerging evidence links these disorders to glucose metabolism dysregulation, suggesting antidiabetic agents may hold therapeutic potential. Methods This was a prospective, randomized, double-blind pilot study involving 12 subjects with PD or DLB to evaluate the tolerability and preliminary effects of a dipeptidyl peptidase 4 (DPP4) inhibitor (sitagliptin 100 mg) vs. sodium glucose like transporter 2 (SGLT2) inhibitor (dapagliflozin 10 mg) over a 4-week period, compared to a placebo. We assessed changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, cognitive function, and autonomic biomarkers. Both sitagliptin and dapagliflozin were well-tolerated, with no adverse events. While no significant changes were observed in cognitive scores, a significant difference was found in the change from baseline for MDS-UPDRS part 1 ( P = 0.008), part 2 ( P = 0.020), and total scores ( P = 0.047) when comparing the three groups. Discussion The dapagliflozin group showed more favorable trends in MDS-UPDRS scores. Limitations include small study size and duration as well as all participants had PD except one subject in the DPP4 inhibitor group with DLB. This pilot study suggests that these inhibitors are safe in PD and DLB patients. The preliminary findings, particularly the trends in the dapagliflozin group, provide a basis for larger-scale, long-term studies to confirm these potential symptomatic benefits and explore disease-modifying effects. Clinical trial registration https://clinicaltrials.gov/study/NCT06263673 , identifier: NCT06263673.

Background: Perianal Crohn’s disease (PCD) is a severe and disabling phenotype of Crohn’s disease that often requires multidisciplinary medical and surgical management. Although ustekinumab (UST) and vedolizumab (VDZ) are widely used after antitumor necrosis factor (anti-TNF) failure, direct comparative data specifically in PCD remain limited. Methods: We conducted a multicenter, retrospective cohort study using the TriNetX US Collaborative Network to compare the effectiveness of UST versus VDZ in adults (18 y or older) with PCD between January 2017 and May 2023. Outcomes were perianal-specific clinical events, including definitive fistula surgery, incision and drainage, diversion procedures, and antibiotic use (metronidazole or ciprofloxacin), assessed at 1 and 2 years after biological initiation. Propensity score matching (PSM) (1:1) was performed to balance baseline variables. Time-to-event analyses were conducted in the matched population using Kaplan–Meier methods, and hazard ratios (HRs) were estimated using Cox proportional hazards models within the matched cohorts. Results: A total of 2936 patients were identified before PSM: 1997 patients in the UST group and 939 patients in the VDZ group. After PSM, 936 patients were included in each cohort. In the matched cohorts, UST was associated with significantly lower risk of definitive perianal fistula surgery (HR: 0.66, 95% CI: 0.50-0.89; P <0.01), and composite surgical events (HR: 0.70, 95% CI: 0.54-0.87; P <0.01) compared with VDZ at 1 year. Rates of antibiotic use, incision and drainage of perianal abscess, and diversion procedures were numerically lower but not statistically significant. At 2 years, these findings persisted, with significantly lower cumulative incidence of definitive perianal fistula surgery (HR: 0.78, 95% CI: 0.61-0.90; P =0.03), composite surgical events (HR: 0.81, 95% CI: 0.69-0.90; P <0.01), and antibiotic use (HR: 0.86, 95% CI: 0.75-0.93; P =0.04) in the UST cohort compared with VDZ. Rates of incision and drainage and diversion procedures remained similar between groups. Conclusion: In this large real-world cohort, UST was associated with lower risks of perianal surgical interventions at one and two years and reduced antibiotic utilization at two years compared with VDZ in patients with PCD. These findings highlight meaningful differences in real-world effectiveness between therapies and support the need for prospective studies to further evaluate comparative effectiveness in this population.

Abstract Travelling waves are a prominent feature of hippocampal activity, but the mechanisms determining their propagation and influence on the cerebral cortex remain unclear. Using a biophysically-grounded model of neural activity evolving across hippocampal and cortical surfaces, we show that spatial gradients in external in-put or neural excitability are a sufficient mechanism for the emergence of travelling waves along the long axis of the hippocampus. These waves emerge only above a critical gradient threshold, propagate with biologically-plausible velocities and exhibit frequency-dependent reversals in direction across slow and fast theta regimes. When coupled to the cerebral cortex, anterior-to-posterior hippocampal waves selectively reorganise globally synchronous cortical activity into metastable travelling waves, whereas posterior-to-anterior hippocampal waves do not, revealing a directional asymmetry in hippocampal–cortical communication. Conversely, cortical waves aligned with large-scale functional gradients induce structured hippocampal waves, revealing complementary direction specific effects across the two systems. These analyses identify structured excitability gradients as a principle governing wave propagation in the hippocampus and suggest how wave-to-wave interactions may coordinate complex cortical and hippocampal interactions during mnemonic and perceptual processes.

Over the past 2 decades, the landscape of serious illness has changed dramatically, with patients living longer and undergoing prolonged treatment. This has increased the need for specialty palliative care (PC) in both inpatient and outpatient settings. Specialty PC teams are interprofessional, composed of diverse healthcare professionals who collaborate seamlessly to provide whole-person care. The palliative care registered nurse plays a pivotal role on the PC team by enhancing communication, holistic compassionate care, and expert care coordination. This article explores the multifaceted specialty palliative care registered nurse role, providing examples of how this role can be used to expand the reach of PC. Specific examples include the expansion of the registered nurse role on an interprofessional PC team to deliver integrative nursing interventions and opportunities for ongoing professional development to meet the complex needs of patients and families impacted by serious illness.

Background: Epstein–Barr virus (EBV) is a key environmental risk factor for multiple sclerosis (MS), and tonsils and adenoids serve as a primary viral reservoir. This study investigates the potential role of adenotonsillectomy in pediatric-onset multiple sclerosis (POMS) risk and relapse rate. Objectives: POMS participants and controls were recruited from 16 pediatric MS clinics between 1 November 2011 and 1 July 2017. Clinical and demographic information, including history of adenotonsillectomy, EBV serostatus, and HLA-DRB1*15:01:01 status, were collected. Multivariable logistic regression assessed the association between adenotonsillectomy and MS risk. In addition, negative binomial regression offset by follow-up time was used to assess the relationship between adenotonsillectomy and relapse rate in POMS participants with available follow-up data. Results: The case-control analysis included 359 POMS participants and 560 pediatric controls. Individuals with a history of adenotonsillectomy had a 63% increased odds of MS (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.01–2.64, p = 0.046). Among the 239 POMS participants with available follow-up data, adenotonsillectomy was associated with a twofold increase in annualized relapse rate (adjusted incidence rate ratio (IRR) = 2.00, 95% CI = 1.15–3.48, p = 0.013). Conclusions: Prior adenotonsillectomy was associated with increased risk of MS and greater relapse rate in pediatric patients, suggesting a potential interplay between EBV, immune regulation, and MS pathogenesis.