Cardiovascular MRI with magnetic resonance angiography supports clinical indication for transcatheter pulmonary valve replacement. We aimed to: (1) assess the feasibility of generating virtual right ventricular outflow tract models directly from magnetic resonance angiography datasets and (2) compare transcatheter pulmonary valve replacement candidacy based on visualisation of anatomic and valve models in virtual reality to outcomes and dispositions suggested by industry fit analysis derived from cardiac CT. Patients with native or surgically palliated right ventricular outflow tracts considered for transcatheter pulmonary valve replacement with temporally related magnetic resonance angiography and cardiac CT were included. Magnetic resonance angiography models were generated using commercial software; virtual valves were created using industry dimensions. A blinded interventional cardiologist determined pulmonary valve replacement candidacy using virtual reality review. A total of 16 patients (N = 7 males, 44%) with a median age 15.5 years (interquartile range [IQR] 13.9, 17.8) were identified. Median time for model generation was 20.6 minutes (IQR 18.5, 22.0). 11/16 (69%) patients passed industry screening fit analysis; 14/16 (88%) ultimately underwent transcatheter pulmonary valve replacement. Four patients who passed virtual reality screening failed industry screening but underwent successful transcatheter pulmonary valve replacement. One patient passed virtual reality and industry screening but did not undergo transcatheter pulmonary valve replacement. One patient passed virtual reality screening but failed industry screening and was not offered transcatheter pulmonary valve replacement. In conclusion, generating virtual models from clinical magnetic resonance angiography datasets is feasible. Modelling may help evaluate transcatheter pulmonary valve replacement candidacy, but must be used in conjunction with other data.

Abstract Introduction Timely access to primary care is essential for Medicare beneficiaries. Amid growing workforce shortages and consolidation, little is known about whether and how organizational and market-level factors affect access. Methods We conducted a simulated-patient study of 444 primary care clinics in Chicago, Los Angeles, New York, and Portland to measure acceptance of new Medicare patients and wait times to the earliest appointment. Results Overall, 77.5% of clinics accepted new Medicare patients, ranging from 96.9% in Los Angeles to just 35.0% in Portland. Among accepting clinics, median wait times for a physician varied from 8 days in New York City to 61 days in Portland. In adjusted analyses, each additional practice site was associated with a 1.5–percentage-point lower probability of accepting new Medicare patients (p<0.001), and hospital or health system–affiliated practices had waits about 15 days longer than independent practices, with prolonged delays concentrated in Portland. Conclusions Findings highlight the importance of local organizational structure and market context in shaping access, with implications for workforce planning and access monitoring.

We describe trajectories of physical function in children newly diagnosed with juvenile idiopathic arthritis (JIA) and identify trajectories with persisting functional impairments and associated baseline characteristics. We included patients enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry between 2017 and 2024, whose parents provided Kids Disability Screen scores in at least two visits (KDS, from 0=no disability to 10=severe disability). Analyses included descriptive statistics, locally weighted scatterplot smoothing (LOWESS), Kaplan-Meier plots of time to KDS=0, latent class trajectory analysis (LCTA), and classification trees to predict trajectories with persisting impairments. We included 940 patients providing 7,351 KDS scores starting a median 6 days after diagnosis up to 7 years. Baseline KDS scores were highest for RF-positive polyarthritis (mean 4.9, SD 3.1) and lowest for psoriatic arthritis (mean 2.4, SD 2.5), and mean scores improved within the first year in all JIA categories. Median time to KDS=0 was 36 weeks (from 13w for systemic arthritis to 73w for undifferentiated arthritis). LCTA identified 5 trajectories: one with little measurable impairment (38% of patients), two with impairments resolving in 1-2 years (24%), and two with persisting mild impairments (38%). A baseline KDS≥1.5 had a sensitivity of 0.79 and specificity of 0.48 to detect persisting mild impairment trajectories. There were no trajectories with persisting moderate or severe impairments. Most children with JIA in this cohort had mild to moderate functional impairments at diagnosis that resolved in 1-2 years, but 1 in 3 followed trajectories with mild persisting impairments.

Gestational diabetes (GDM) results in adverse outcomes for the pregnant individual and neonate. Lifestyle modifications are first-line interventions used to achieve pregnancy-specific glucose targets. We investigated how temporal eating patterns influence glucose concentrations in individuals with GDM. We hypothesise that eating the first meal early in the morning may lower overall 24 h interstitial glucose, which could be an intervention to improve 24 h glucose metrics among people with GDM. This is a secondary analysis of pregnant people with GDM randomised to self-capillary blood glucose (SCBG) with or without additional real-time continuous glucose monitoring (CGM) for management of GDM. Participants measured SCBG and were included in the analysis if postprandial SCBG were available to infer meal timing (n=71). The cohort was split by the median time of first meal into early (first meal before 09:56 hours) and late eating (first meal after 09:56 hours) groups. The 24 h CGM glucose profiles were compared between groups by cosinor and linear analyses, adjusted for maternal and gestational age, medication usage, and primary study group assignment. Over 24 h, glucose increased during the day and decreased during the night. This rhythm was shifted earlier for the early eating group (time-of-day: 24 h component: -0.32 mmol l-1 min-1, t102,232=-188.9, p<0.001; 12 h component: -0.11 mmol l-1 min-1, t102,232=-65.2, p<0.001; and group × time-of-day: 24 h component: 0.09 mmol l-1 min-1, t102,232=37.9, p<0.001; 12 h component: 0.04 mmol l-1 min-1, t102,232=15.3, p<0.001). During the daytime, there was a significant time-of-day (7.0×10-4 mmol l-1 min-1, t72,418=150.8, p<0.001) and group × time-of-day effect (7.0×10-5 mmol l-1 min-1, t72,418=10.0, p<0.001), but no group effect (0.01 mmol/l, t65=0.06, p=0.950). Overnight, glucose decreased in both groups by approximately 0.67±0.39 mmol/l. The late eating group, however, had significantly higher nocturnal glucose compared with the early eating group (group: 0.26 mmol/l, t65=2.3, p=0.023, time-of-day: -0.09 mmol l-1 min-1, t29,818=-119.0, p<0.001; and group × time-of-day effect: -0.01 mmol l-1 min-1, t29,818=-11.8, p<001). These results suggest that meal timing, with an emphasis on earlier eating patterns, is a potential lifestyle intervention that can improve nocturnal interstitial glucose.

ABSTRACT Endocrine dysfunction is one of the most common immune-related adverse events (irAEs) reported in immune checkpoint inhibitors (ICIs) clinical trials. The aim of this research was to thoroughly assess the clinical features of endocrine irAEs, investigate the risk and predictive variables, and provide guidance for clinical therapy. This study performed a retrospective review of clinical data from 269 patients with malignant malignancies who underwent initial immune checkpoint inhibitor treatment at the First Bethune Hospital of Jilin University between May 2021 and October 2022.The incidence of endocrine irAEs was 31.6% (85/269), while the autoimmune polyendocrinopathy syndrome (APS) was observed in 1.1% (3/269). The median time for the first adverse reaction was 46 (33.5, 100.5) d. The occurrence of ICIs-related thyroid injury events was significant, with the incidence at 27.5% (74/269), whereas the frequency of grade 2 and higher adverse reactions was 33.8% (25/74). Female gender (OR = 2.723, 95 % CI: 1.447–5.125) and a history of chemotherapy (OR = 2.716, 95 % CI: 1.079–6.836) were distinct risk factors for thyroid injury associated with ICIs. In the 106/269 who had baseline antibody testing, the presence of anti-thyroglobulin antibodies (TGAb) (AUC = 0.717) and thyroid peroxidase antibody (TPOAb) (AUC = 0.690) could aid in predicting this injury, with TGAb demonstrating greater reliability. The prevalence of ICIs-related diabetes was 3.7% (10/269), with a higher occurrence in male patients compared to female patients, and the rate of grade 3 and above adverse reactions was 10% (3/10). The occurrence of ICIs-related pituitary inflammation was 1.1% (3/269), primarily involving pituitary hormones such as thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH). The incidence of ICIs-related adrenocortical hypofunction was 0.4% (1/269), with a grade 3 adverse event. The antibody testing was performed in a nonrandom subset and thus the predictive AUC results might be affected by bias.

BACKGROUND Biologic therapies, including anti-tumor necrosis factor agents, have significantly improved the management of inflammatory bowel disease (IBD). However, their high cost can limit patient access. Biosimilars are a more affordable option than originator biologics and offer potential for improved accessibility, though real-world evidence comparing their effectiveness remains limited. AIM To describe real-world, comparative outcomes of IBD patients taking biologics and biosimilars, focusing on remission and healthcare use. METHODS We used data from a multicenter registry-based cohort, which includes participants from six Canadian IBD clinical centers. Adults with ulcerative colitis or Crohn’s disease who initiated biosimilar, or originator formulations of infliximab or adalimumab were included. The primary outcome was clinical remission; secondary outcomes included hospitalizations and emergency department (ED) visits. Kaplan-Meier survival analyses and multivariable Cox regression models were used to assess time to these outcomes, adjusting for disease activity, treatment history, and demographic characteristics. RESULTS A total of 258 individuals were analyzed (192 biosimilar initiators and 66 originator users). The median time to remission was similar between biosimilars (12.2 months) and originators (12.8 months). We did not detect difference in the likelihood of achieving remission when comparing biosimilar and originator treatments (adjusted hazard ratio: 1.49; 95% confidence interval: 0.96-2.32). Hospitalization and ED visit rates were also comparable. Corticosteroid use and prior hospitalizations were associated with increased hospitalization risk. CONCLUSION This study suggests biosimilars and originators have similar remission, ED visits, and hospitalization in IBD. This reinforces confidence in their equivalence, improving access while supporting healthcare system sustainability.

Robotic sealing devices, such as SynchroSeal and Vessel Sealer Extend, have shown that parenchymal transection is possible without using laparoscopic instruments Finotti (Hepatobiliary Surg Nutr. 12:56-68, 2023), Palucci (J Robot Surg 19(1):36, 2024), Birgin (Lancet Reg Health Eur 43, 2024). However, there is still a need for detailed procedural guidance to ensure that these techniques can be applied effectively and consistently. We describe the Sealer and Moisture-Based Approach (SAMBA) hepatectomy technique a standardized purely robotic approach for hepatic parenchymal transection that combines robotic vessel-sealing tools with targeted saline irrigation. Between February 2021 and October 2024, a total of 72 consecutive robotic hepatectomies were performed using the SAMBA hepatectomy technique at Ulm University Hospital. The Da Vinci Xi-system was used for all hepatectomies. Parenchymal transection was performed with the SynchroSeal in 55 and the Vessel Sealer Extend in 17 cases. Of these, 27 resections were nonanatomical, and 45 resections were anatomical hepatectomies with a median operative time of 174 minutes (interquartile range [IQR] 134-236), and blood loss of 200 mL (IQR 100-400). No cases of posthepatectomy hemorrhage or mortality were observed within 90 days after surgery. SAMBA hepatectomy technique is an effective method for robotic liver parenchymal transection. Incorporating moisture during sealing improves tissue handling, minimizes carbonization, and enhances visualization. Prospective studies are warranted to compare the SAMBA technique with other techniques of parenchymal transection.

Individuals with normal coronary arteries may develop coronary artery disease (CAD). Coronary computed tomography (CT) angiography (CCTA) offers a non-invasive method to assess the development of CAD. In a post-hoc observational study of the Scottish Computed Tomography of the HEART (SCOT-HEART) trial, we identified patients with normal coronary arteries on initial CCTA who subsequently underwent clinically indicated CT. Images were visually assessed for the presence, severity, and type of CAD. Normal coronary arteries on baseline CCTA were present in 524 patients (mean age 53 ± 10 years, 38% male). After a median of 9.3 (Interquartile range, IQR: 9.3-10.8) years, 31 (6%) underwent repeat CCTA and 162 (31%) underwent chest CT. There were no differences in baseline clinical characteristics amongst those who did or did not have repeat CCTA, but those with subsequent chest CT were older and had higher cardiovascular risk scores. CAD was identified on 48% (n = 15) of CCTA and 25% (n = 41) of chest CT. Median time to CT scan on which CAD was identified was 8.1 (IQR: 6.9-9.7) years. There was no difference in all-cause mortality or combined CAD death or non-fatal myocardial infarction in patients who had CAD identified on subsequent CT. However, they were more likely to undergo invasive coronary angiography (adjusted hazard ratio [aHR] 4.94, 95% confidence interval [CI]: 1.95, 12.51; p < 0.001) and revascularization (aHR 19.99, 95% CI: 1.69, 237.1; p = 0.018), adjusted for age and sex. One third of patients with previously normal CCTA will develop CAD on clinically indicated CT imaging over a 10-year period. Question In patients with normal coronary arteries on coronary computed tomography angiography (CCTA), the risk of developing CAD in the future is uncertain. Findings Among 524 patients with normal coronaries, CAD was identified on 48% of CCTA and 25% of chest CT during 10 years of follow-up. Clinical relevance A substantial proportion of patients with initially normal coronary arteries on CCTA later develop CAD, highlighting the need for clinicians to be alert for the development of new CAD in patients with initially normal coronary arteries.

This Latin American research supported the use of teduglutide following the early identification of advantageous anatomy (partial colon in continuity) and reduced reliance on parenteral nutrition at baseline. The therapy was maintained for 24 weeks, with the evaluation commencing after 12 weeks of treatment, leading to total parenteral nutrition independence in 26.6% of patients. The reported adverse effects related to the treatment were minimal and aligned with those found in existing literature. Limitations of the study included limited patient recruitment, a lack of discussion regarding the actual treatment duration, no data on routine endoscopies/colonoscopies performed to detect tumor or polyp recurrence during treatment, and the cost implications of such treatment. In a recent article, the median time for adverse events to occur was 393 days (56 weeks). At the same time, the current study lasted 24 weeks, suggesting that theoretically, numerous adverse events may have gone unnoticed.

To evaluate the initial clinical experience with the Saroa surgical system for pulmonary anatomical resection and to assess its perioperative safety. This retrospective observational study included 45 consecutive patients who underwent pulmonary anatomical resection using the Saroa surgical system. Pulmonary anatomical resections included lobectomy (n = 26) and segmentectomy (n = 19). Robot-related lung and vascular injuries were defined as the safety-specific endpoints. The median age was 69 years, and 24 patients (53.3%) were male. The cohort comprised 36 patients with primary lung cancer, seven with metastatic lung tumors, and two with benign lung tumors. The median total operative time was 199min, and the median console time was 145min, accounting for approximately 70-75% of the total operative time. The median estimated intraoperative blood loss was 40 mL. Postoperative complications occurred in 15.6% of patients and were limited to postoperative air leaks. No perioperative mortalities were observed. In this initial clinical experience, Saroa-assisted pulmonary anatomical resection was performed safely without robot-related lung or vascular injuries. This suggests that the incorporation of haptic feedback does not compromise surgical safety during early clinical use.

Objectives Cladribine, a synthetic analog of deoxyadenosine, exhibits potent activity against hematological malignancies. While cladribine-containing regimens combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been proposed as a potential strategy to improve outcomes in relapsed or refractory (R/R) acute myeloid leukemia (AML), additional clinical evidence is needed, particularly in pediatric populations. This single-center retrospective study aimed to describe the efficacy and safety of a cladribine-based conditioning regimen for allo-HSCT in children with R/R AML. Materials and methods Clinical data of 16 children with R/R AML who underwent allo-HSCT following a cladribine-based conditioning regimen at our hospital from October 2020 to June 2024 were analyzed retrospectively. Key outcomes included hematopoietic reconstruction, regimen-related toxicity (RRT), cumulative incidence of graft-versus-host disease (GVHD), infection profiles, overall survival (OS), disease-free survival (DFS), relapse rate, and non-relapse mortality (NRM). Flow-cytometry minimal residual disease (MRD) results before HSCT were collected and analyzed as an additional key baseline index. Results All 16 patients attained hematopoietic reconstruction, with pre-transplant flow-cytometry MRD negative in 13 cases (81.25%) and positive (MRD ≥0.01%) in three cases (18.75%). The median time of neutrophil and platelet engraftment was 12 (10–16) days and 15 (10–25) days, respectively. The incidence of I/II grade RRT was 31.3% (oral cavity: three cases, liver: two cases), with no III/IV grade RRT observed. The cumulative incidence of acute GVHD (aGVHD) was 50.0% (grade I/II skin: five cases, grade IIIl: three cases). Among 15 evaluable patients, the cumulative incidence of chronic GVHD (cGVHD) was 26.7% (local skin: three cases, ocular keratoconjunctivitis sicca: one case). Post-transplant infections occurred in 31.3% of patients, predominantly viral pathogens: one case of BK virus-associated hemorrhagic cystitis, one case of BK virus combined with bacterial infection, and three cases of cytomegalovirus (CMV) DNAemia. The median follow-up time was 28.03 (11.67–55.34) months (follow-up cutoff: 30 June 2024). Using the Kaplan–Meier method, the 1-year OS rate was 87.5% (95% CI: 65.2%−96.4%), and the 1-year DFS rate was 87.4% (95% CI: 64.9%−96.3%). The relapse rate and NRM were both 6.3% (95% CI: 0.8%−29.1%); the NRM case was confirmed as bronchiolitis obliterans syndrome (BOS) induced by pulmonary cGVHD. Conclusion In this small single-center retrospective series, the cladribine-based conditioning regimen was associated with favorable hematopoietic reconstruction, mild RRT, and promising survival outcomes in children with R/R AML, even in partial patients with pre-transplant MRD positivity. However, due to the limited sample size, single-arm design, and lack of a control group, conclusions regarding superiority (e.g., improved OS or reduced relapse) cannot be drawn. Larger prospective multi-center studies are required to validate these preliminary findings.

Clonal haematopoiesis of indeterminate potential (CH), somatic genetic mutations conferring stem cells selective advantage, are associated with increased inflammatory cytokine production, cardiovascular disease (CVD), and malignancy. We investigated whether CH was related to risk of rheumatoid arthritis (RA), an inflammatory autoimmune disease. Within the UK Biobank, we studied 186,577 unrelated individuals with baseline data collection, genome-wide genotyping, whole exome sequencing (WES) read for CHIP, and linked general practice (GP) data for identification of incident RA in follow-up. We excluded those with prevalent RA or taking RA medications at baseline. We tested for associations between variant allele fraction (VAF) >2% and >10% for the 8 most common CHIP mutations in the general population, and incident RA, identified by billing code algorithms. Cox regression models estimated hazard ratios (HR, 95% confidence interval) for incident RA. 594 participants developed incident RA over median follow-up 7.1 years (IQR 6.4-8.0); median time to RA was 3.9 years (IQR 2.0-5.6). Incident RA cases were slightly older at enrolment, more likely to be female, have smoked, have higher body mass index (BMI), and have prevalent CVD, and hypercholesterolaemia at baseline. However, there was no difference in the presence of CHIP mutations at baseline; 6.3% vs. 6.4% of those who did and did not develop incident RA in follow-up had any CHIP mutation at >2% VAF. Common CHIP mutations, including TET2, TP53, and SF3B1 mutations, were not associated with risk of incident RA when restricted to those with most complete general outpatient and hospital record follow-up in the UK Biobank.

Rhynocoris fuscipes (Hemiptera: Reduviidae)is an important predatory insect that targets Spodoptera litura (Lepidoptera: Noctuidae) in tobacco fields. Here, laboratory tests were conducted to identify the optimal temperature, duration, and developmental stage for the low-temperature storage of R. fuscipes. This study examined the effects of storage temperatures (7°C°C, 9°C, 11°C, 13°C, 15°C) and durations (5d, 10d, 15d, 20d, 25d, 30d) on the hatching rate, lifespansr and survival rates of fifth-instar nymphs and adult females, egg production, adult female median lethal time, and the predation capacity of adult female R. fuscipes on S. litura. The results showed that under various low-temperature conditions, storing adult R. fuscipes was more effective than storing nymphs or eggs, and the optimal storage temperature ranged from 13 to 15°C. At 15°C, the average lifespan of adult female R. fuscipes was 25.47days, with a median lethal time of 36.53days. The eclosion rate for R. fuscipes eggs stored at 15°C for 12days exceeded 78%. Storage temperature and duration significantly influenced the predation capacity of adult female R. fuscipes on S. litura. These findings provide a theoretical basis for the large-scale storage and transportation of R. fuscipes.

Background Cervical intraepithelial neoplasia (CIN) recurrence after loop electrosurgical excision procedure (LEEP) remains a clinically consequential barrier to cervical cancer prevention, and risk stratification tools tailored to real-world practice are limited in China. This study developed and internally validated a clinical prediction nomogram for histologically confirmed CIN2+ recurrence after LEEP. Methods A retrospective single-center cohort was assembled of women treated with LEEP for CIN2+ between January 2018 and October 2024. Candidate predictors included demographic and reproductive factors, smoking, HPV vaccination, prior cervical treatment, transformation zone type, LEEP pathology (including adenocarcinoma in situ [AIS] and margin status), pre-/post-treatment high-risk HPV measures, and neutrophil-to-lymphocyte ratio (NLR). Time-to-recurrence was analyzed using Cox regression with hierarchical domain modeling. A nomogram was constructed from the final multivariable model and evaluated for discrimination and calibration. Results Among 2,230 women (median follow-up 31.8 months, IQR 19.6–43.5), 334 developed CIN2+ recurrence (15.0%), with a median time to recurrence of 15.6 months (IQR 8.2–24.3). Persistent HPV infection occurred in 50.6% of women with recurrence versus 23.1% without recurrence ( p &amp;lt; 0.001). Persistent HPV infection (same genotype pre-/post-LEEP) was the strongest independent predictor (adjusted hazard ratio [aHR] 2.51, 95% CI 1.99–3.16). Additional independent predictors included unvaccinated status (aHR 1.54, 95% CI 1.08–2.20), multiple positive margins (aHR 1.52, 95% CI 1.08–2.14), AIS versus CIN2 (aHR 1.48, 95% CI 1.03–2.12), prior cervical treatment (aHR 1.38, 95% CI 1.04–1.84), single positive margin (aHR 1.38, 95% CI 1.02–1.87), and higher NLR (per one-unit increase: aHR 1.21, 95% CI 1.02–1.44). Model discrimination increased across hierarchical models from 0.516 (model 1) and 0.562 (model 3) to 0.619 in the final model. Risk stratification separated low-, intermediate-, and high-risk groups with observed 24-month recurrence rates of 6.2%, 14.8%, and 31.5%, respectively ( p for trend &amp;lt;0.001). Conclusion In a contemporary Chinese single-center cohort, genotype-defined persistent HPV infection and margin burden were dominant determinants of CIN2+ recurrence after LEEP, with vaccination status and NLR providing additional stratification. The resulting nomogram offers a pragmatic framework for risk-adapted surveillance, pending external multicenter validation.

Intra-articular drug delivery systems (DDS) are emerging as promising therapies for osteoarthritis (OA), yet their efficacy in spontaneous clinical cases remains largely untested. This uncontrolled, descriptive pilot study was designed to provide a proof of concept for the feasibility, safety, and preliminary clinical effects of intra-articular administration in sport horses with naturally occurring OA. The study involved a peptide-functionalized nanogel composed of chitosan and hyaluronic acid, delivering endothelin type A (BQ-123) and bradykinin B1 (R-954) receptor antagonists, which have previously demonstrated anti-inflammatory and chondroprotective properties in preclinical models. Eight client-owned sport horses with moderate OA of the metacarpophalangeal (MCPJ) or distal interphalangeal joint (DIPJ) received a single intra-articular injection of 2.4mL nanogel and were followed for 12months. No major adverse events were observed. Two horses developed mild, transient joint swelling that resolved within three days. Seven of eight horses showed improvement in lameness scores by week 12, although complete resolution on hard ground circles was observed in only two horses. All horses were sound on soft ground and returned to competition, with a median time of 128days post-treatment. Six horses remained in active competition at one year without additional intervention. Four horses (50%) met the predefined primary outcome of return to the same level and frequency of competition as before lameness onset. Horses treated for DIPJ OA and those showing radiographic joint space narrowing were overrepresented among treatment failures. Intra-articular administration of a peptide-functionalized nanogel was feasible and well tolerated in sport horses with naturally occurring OA and was associated with partial but prolonged clinical improvement. Although only half of the horses achieved full return to pre-lameness performance, most showed sustained clinical benefit without additional treatment over one year. These findings support further investigation of this drug delivery system in larger, randomized controlled trials to better define its therapeutic efficacy and optimal indications.

Background Impaired glymphatic function is linked to cerebral atrophy and contributes to clinical disability in patients with relapsing-remitting multiple sclerosis (RRMS). Deep gray matter volume (DGMV) loss is associated with disability; however, its mediating effect in MS-related disability and glymphatic function changes remains underexplored. Methods One hundred and thirty-one RRMS patients and 50 healthy controls (HC) underwent MRI scans. The DTI-ALPS index was used to evaluate glymphatic function. Z-scores of cortical and deep gray matter volumes (CGMV and DGMV) and WM-FA in RRMS patients were determined based on the mean and standard deviation of HC. RRMS patients were divided into two subgroups: the “MS-DGM-preserved” subgroup (z-scores of both CGMV, DGMV, and WM-FA &amp;gt; -2) and the “MS-DGM-atrophied” subgroup (z-scores of DGMV &amp;lt; -2) according to combinations of z-scores compared to HC. The mediating effect of DGMV in the relationship between the DTI-ALPS index and the clinical disability was further explored. Patients were followed up and had longitudinal outcomes. Results Among all participants, 79 cases (60.3%) were classified as the MS-DGM-preserved subgroup, and 52 cases (39.7%) as the MS-DGM-atrophied subgroup. The MS-DGM-atrophied subgroup exhibited lower DTI-ALPS index (d=1.42, p-FDR&amp;lt; 0.001), higher T2-hyperintense white matter lesion volume (d=0.98, p-FDR&amp;lt; 0.001) and EDSS scores (d=0.49, p-FDR&amp;lt; 0.001), and longer disease duration (d=0.33, p-FDR=0.005) compared to the MS-DGM-preserved subgroup. Additionally, in the MS-DGM-atrophied subgroup, the DTI-ALPS index was significantly positively correlated with DGMV (r=0.59, p-FDR&amp;lt;0.001), and negatively correlated with EDSS scores and disease duration (r=-0.59, r=-0.56, p-FDR&amp;lt;0.001). Mediation analysis revealed that DGMV partially mediated the relationship between the DTI-ALPS index and clinical disability (EDSS and disease duration). In the longitudinal cohort, 18 MS patients were followed for a median time of 14 months (12.75, 14.00 months; range: 8–18 months). Compared to baseline, the DTI-ALPS index significantly decreased during follow-up (d=0.92, p-FDR=0.009). Conclusion The RRMS subgroups based on the gradient classification of DGMV using structural MRI effectively distinguishes differences in glymphatic function and clinical disability. When DGM atrophy reaches a certain threshold, it partially mediates the relationship between glymphatic function and clinical disability.

Diagnostic criteria for multiple sclerosis (MS) have undergone numerous revisions, the latest announced in 2024. This study compared the 2024 McDonald criteria with earlier iterations regarding sensitivity, time to MS diagnosis, and disability. Patients with clinically or radiologically isolated syndrome (CIS, RIS) between 2013 and 2022, aged 18-50, visited within 6 months, and with brain MRI were included. The primary outcome was MS diagnosis according to 2024 versus 2017 criteria. Secondary outcomes included time to diagnosis and disability by Multiple Sclerosis Severity Score. Outcomes were stratified into pre-2017 and 2017-2022 cohorts, with 2010 criteria applied to the pre-2017 group. Finally, 2024 criteria were prospectively tested. Among 163 patients (mean age 31.4; 72% female), for the 2024 criteria, diagnosis sensitivity was 81.4% versus 74.9% for 2017 criteria; in the pre-2017 cohort, 49.4% for 2010 criteria. Median time to diagnosis was shorter with 2024 criteria (2.0 [IQR 1.1-4.2] months) compared to 2017 and 2010 criteria (2.1 [1.2-4.7] and 3.8 [1.5-11.2], respectively). Patients fulfilling 2024 and 2017 criteria at baseline showed lower MSSS during follow-up than those meeting 2010 criteria. Prospectively, 11/13 (85%) fulfilled 2024 criteria at baseline. The 2024 McDonald criteria increased sensitivity, shortened time to diagnosis, and identified patients with milder disease course.

Objective Patients with eosinophilic oesophagitis (EoE) may experience diagnostic delays. This study quantifies the time to EoE diagnosis and examines associated factors. Method A retrospective cohort study was conducted between 2006 and 2022 using Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients were followed from first proton pump inhibitor (PPI) prescription or presentation in primary or secondary care with EoE-related symptoms (food bolus obstruction (FBO) or dysphagia) to diagnosis. A Robust Poisson regression model examined factors influencing diagnostic delay. Results Of 2300 EoE patients (67.7% male; median age 38 (IQR 30–49)), the median time to diagnosis was 3.6 (IQR 0.5–8.8) years. Before diagnosis, 80.7% patients had a record of PPI prescription in primary care, with a median delay of 4.9 (IQR 1.5–9.7) years. Factors associated with more than 3 years to diagnosis included female (adjusted risk ratio (aRR) 1.14, 95% CI 1.06 to 1.22); PPI prescription in primary care (2.27, 1.87 to 2.75); urgent endoscopy for dysphagia (0.77, 0.62 to 0.95), urgent endoscopy for FBO (0.86, 0.72 to 1.03) and dysphagia presentation in primary care (0.69, 0.62 to 0.77). Following diagnosis, 77% of patients received a PPI prescription, and 21% without asthma or chronic obstructive pulmonary disease were prescribed a steroid inhaler, presumably for EoE. Conclusions The median time to EoE diagnosis was 3.6 years. Longer time to EoE diagnosis was associated with being female and PPI prescriptions in primary care. In contrast, presentations involving FBO and dysphagia, whether in primary or secondary care settings, were associated with a shorter time to EoE diagnosis.

Healthcare across Europe was affected by COVID-19 pandemic lockdowns. How different national healthcare systems coped with this impact remains unclear. Healthcare in Switzerland differs significantly from that in Scotland, for example, in terms of centralization. The aim of this study was to assess the impact of the COVID-19 pandemic on the diagnosis and surgical treatment of colorectal cancer (CRC) in contrasting healthcare systems. This retrospective cohort study was conducted in south-east Scotland and in the extended north-west of Switzerland from January 1st, 2019 to February 28th, 2023. All patients diagnosed with CRC were included. The primary outcomes were the time from CRC diagnosis to treatment and the UICC stage at diagnosis, assessed prior to, during, and following the period of lockdown. The lockdown in Scotland lasted from March 2020 to October 2020 and in Switzerland from March 2020 to April 2020. A total of 6745 patients were included (4127 from Scotland and 2618 from Switzerland). Median time from diagnosis to treatment remained unaltered during the lockdown period in both countries. However, after the lockdown, the median time from diagnosis to treatment increased from 59 to 76days in Scotland. The median number of patients who were diagnosed per annual quarter declined from 177 (IQR: 171-190) to 152 (IQR: 150-154), and the median number of who received treatment from declined from 256 (IQR: 253-259) to 203 (IQR: 186-218) during lockdown in Scotland. In multivariable logistic regression, the odds of being diagnosed with UICC stage IV increased by 42% for patients diagnosed during lockdown (95%-CI: 12%-81%). In Switzerland, the time from diagnosis to treatment increased slightly after the pandemic. However, the other effects described above were not observed in Switzerland. This descriptive study demonstrated that the impact of the pandemic on colorectal cancer care was less pronounced in Switzerland, but considerable in Scotland. Because separate subgroup analyses were conducted, direct comparisons cannot be made between Scotland and Switzerland. This trial is registered on clinicaltrials.gov as part of the EvaCol study (NCT04550156).

Pediatric acromioclavicular (AC) joint injuries are rarely reported, and data on return-to-sport rates (RTS) in this population are limited. This study aims to characterize management strategies and return-to-sport outcomes following AC joint injuries in pediatric athletes, addressing a gap in the current literature. Patients under 18 years of age who sustained an AC joint injury between March 1, 2014, and March 1, 2024, were identified using databases from a large tertiary referral hospital and a large children's hospital. Extracted data included patient demographics, injury patterns, management approaches, and RTS status. A total of 108 patients (110 shoulders) were included (74% male; mean age, 12.77±2.13​​​​​y; range 8 to 17 years). Low-grade injuries accounted for 95% of cases, and all injuries were managed nonoperatively. Sling immobilization was used in 40%, physical therapy (PT) in 29%, rest in 17%, and a combination of sling and PT in 15%. The most common mechanisms were football (29, 26%), motor vehicle collisions (11, 10%), and soccer (10, 9%). At least 48% (52) of patients had documented return-to-sport dates, with the median RTS time being 21 days (IQR 14 to 49.45​​​​​d). Concomitant injury was associated with a longer RTS time (HR 0.33, 95% CI 0.16-0.69, P=0.003). In this cohort of pediatric athletes, AC joint injuries were predominantly low-grade and managed nonoperatively. Of the patients with documented follow-up and RTS, the median RTS time was 3 weeks. These findings reinforce the favorable prognosis of nonoperative treatment for low-grade injuries in this population. Given the rarity of pediatric AC joint injuries and the limited published data, reporting these outcomes is essential to guide evidence-based management in pediatric sports medicine. IV: retrospective cohort study.