Citations

ABSTRACT Background The optimal timing for basal insulin initiation in diabetic ketoacidosis (DKA) remains unclear. British guidelines endorse early basal insulin (EBI), while the American Diabetes Association emphasises overlap duration with intravenous insulin, without mention of timing. This meta‐analysis evaluates whether EBI administration of basal insulin improves clinical outcomes in adults with DKA. Methods A systematic review and meta‐analysis were performed according to the PRISMA guidelines. Databases searched included MEDLINE, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials through December 11, 2024. Inclusion criteria included articles in the English‐language randomised controlled trials (RCTs) or observational studies evaluating EBI in adult DKA patients. Non‐human studies, conference abstracts, and case reports were excluded. The primary outcome for this study was hospital length of stay (LOS). Additional outcomes included intensive care unit (ICU) LOS, time to DKA resolution, hypoglycemia, and rebound hyperglycemia between EBI and usual care. Risk of bias was assessed using the Cochrane and Newcastle‐Ottawa tools. Grading of Recommendations Assessment, Development, and Evaluation was performed to evaluate the quality of evidence. Results From 1214 identified studies, eight (4 RCTs, 4 observational) met inclusion criteria for a total of 247 patients in the EBI group and 552 patients in the control group. No significant difference in hospital LOS was found (mean difference −11.17 h; 95% CI: −29.91 to 7.56). ICU LOS, time to DKA resolution, incidence of hypoglycemia, and rebound hyperglycemia also did not demonstrate any significant differences between groups. Significant heterogeneity existed across studies for most outcomes. All studies had a high risk of bias, and the quality of evidence was very low. Conclusion EBI did not result in significant differences in hospital LOS, ICU LOS, or time to DKA resolution; however, there were no increased adverse events with EBI. Current studies of early EBI have significant limitations. Future research should focus on developing high‐quality RCTs.

Abstract Objective This report describes the first use of the Affera Sphere-9 dual-energy catheter for slow pathway modification in atrioventricular nodal re-entrant tachycardia (AVNRT) during atrial fibrillation (AF) ablation in a patient with a dual-chamber pacemaker, illustrating a streamlined single-catheter approach. Case presentation A 74-year-old man with prior cryoablation for AF, mitral valve repair, and a recently implanted dual-chamber pacemaker was referred for repeat AF ablation due to symptomatic, recurrent AF (30% burden). Left atrial mapping with the Sphere-9 catheter revealed reconnection at the right superior pulmonary vein, right carina, and across prior roof and floor lines. Using pulsed field (4-s lesions, 8 mm spacing) and supplemental radiofrequency (RF) energy, the left atrial posterior wall was re-isolated. Cavo-tricuspid isthmus ablation was performed with RF and pulsed field applications, achieving bidirectional block. During subsequent testing, typical AVNRT was induced. To maximize efficiency, slow pathway modification was performed with the same Sphere-9 catheter, using shortened RF applications (3 s), a lower target temperature (60°C), and an 80% current limit, at an inferior-posterior site 1.3–2.5 cm from the His signal. Junctional acceleration was observed without atrioventricular block, indicating successful slow pathway modification. The procedure was completed without fluoroscopy or complications, and follow-up device interrogation showed no recurrence of AF or AVNRT. Conclusion This case demonstrates the feasibility and acute safety of using a single dual-energy lattice-tip catheter for combined AF and AVNRT ablation, potentially reducing procedure time, catheter exchanges, and cost; larger studies are needed to assess long-term outcomes.

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Measurable residual disease (MRD) has established prognostic significance in patients with myeloid disorders; however, there is limited data regarding its prognostic and predictive value and the optimal technique for measurement in the setting of post allogeneic hematopoietic cell transplantation (allo-HCT). A multi-gene next generation sequencing (NGS) panel can overcome the limitations of conventional techniques for measurement of MRD and can shed light onto the longitudinal evolution and genomic complexity of patients undergoing allo-HCT for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, patients with AML or MDS who underwent their first allo-HCT and completed NGS testing at day +100 and were in a state of morphological remission were identified from the transplant registry of Mayo Clinic in Florida. The primary aim was to evaluate the prognostic impact of somatic variants detected via NGS at day +100 post allo-HCT on long-term outcomes. In total, 105 patients who underwent allo-HCT for AML and MDS and completed NGS testing on day +100 were included in the study population. Seventeen patients were found to have detectable variants, and 88 patients were without a detectable variant. At a median follow up of 1.4 years (0.1–5.5), presence of any variant at day +100 was associated with inferior 4-year overall survival (OS) (32% vs. 69%, P < 0.001), decreased progression free survival (PFS) (34% vs. 61%, P < 0.001), and a higher incidence of relapse (64% vs. 23%, P < 0.001). In univariate models, a lower Karnofsky performance score and presence of variants post allo-HCT remained significantly associated with inferior OS, higher relapse incidence, and a decreased PFS. The presence of variants at day +100 post allo-HCT remained significant in multivariate models for relapse ( P = 0.002) but not for OS ( P = 0.06) and PFS ( P = 0.08). These results indicate that the presence of detectable somatic variants at day +100 is associated with poor long-term outcomes and are predictive of a higher incidence of relapse.

Background and Aims: Upadacitinib, a selective janus kinase 1 (JAK1) inhibitor, and ustekinumab, an interleukin-12/23 inhibitor, are approved for the treatment of moderate-to-severe ulcerative colitis (UC). However, real-world data in patients with anti-tumor necrosis factor (TNF)-exposure are limited. Methods: We performed a retrospective cohort study in TriNetX US Collaborative Network. Adult patients with UC and prior anti-TNF exposure were identified. Patients who received upadacitinib or ustekinumab between April 2022 and August 2024 were stratified into two cohorts. Patients with Crohn’s disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis were excluded. Propensity-score matching was performed to balance comorbidities, medications, and labs between the two cohorts. Study outcomes included rates of corticosteroid use, colectomies, change of therapy, hospital admissions or emergency department visit, and all-cause mortality. Results: A total of 724 patients in the upadacitinib cohort and 909 in the ustekinumab cohort met the inclusion criteria. After matching, 633 patients remained in each cohort, with balanced baseline characteristics. At 1-year follow-up, the rates of corticosteroid use were 40.1% in the upadacitinib group and 48.5% in the ustekinumab group (aOR= 0.71, 95% CI: 0.69-0.89), mainly driven by differences in oral corticosteroid use (aOR= 0.73, 95% CI: 0.58-0.91). All other outcomes were comparable between the two study groups. Conclusion: In patients with ulcerative colitis and prior anti-TNF exposure, upadacitinib was associated with lower oral corticosteroid use than ustekinumab over 1 year, with no significant differences in rates of colectomy, ED visits or hospitalizations. These findings suggest a potanial higher effectiveness of upadacitinib compared with ustekinumab and may help inform treatment selection in this population.

ABSTRACT Background Infection enteritis is associated with the development of irritable bowel syndrome (IBS) and functional dyspepsia. Aim This study aimed to examine the long‐term risk of IBS and functional dyspepsia, and associated health care utilisation following infection enteritis. Methods We conducted a retrospective cohort study using TriNetX U.S. Network. Adults with infection enteritis were identified and matched to controls, balancing demographics and comorbidities. Primary outcomes were the risk of incident IBS and functional dyspepsia diagnoses at 1, 5, and 10 years. Secondary outcomes were rates of IBS‐ and functional dyspepsia‐related medications, endoscopy, abdominal imaging, and hospitalizations. Pathogen‐specific and multivariate analyses were performed to assess variations in IBS risk. Results After matching, 202,244 patients were identified in each study cohort. At 1 year of follow‐up, the infection enteritis cohort had higher rates of IBS (RR = 2.35; 95% CI: 2.14–2.59), functional dyspepsia (RR = 2.02; 95% CI: 1.84–2.22), use of IBS‐related medications (RR = 1.29; 95% CI: 1.26–1.31), functional dyspepsia‐related medications (RR = 1.56; 95% CI: 1.55–1.59), abdominal imaging (RR = 2.42; 95% CI: 2.29–2.54), and Oesophagogastroduodenoscopy/colonoscopy (RR = 1.57; 95% CI: 1.50–1.65). These risks remained significantly higher in the IE cohort at 5 and 10 years. Salmonella/Shigella (RR = 6.48), and Giardia lamblia (RR = 5.05) had the highest risk of developing incident IBS. Conclusion Infection enteritis was associated with increased risk of IBS and functional dyspepsia, rates of related medication use, and greater healthcare utilisation.

Leptomeningeal disease (LMD) is a devastating complication of metastatic melanoma, affecting up to 15% of patients with central nervous system involvement. Despite advances in systemic therapy, LMD carries poor prognosis. Patients with LMD are often excluded from clinical trials. Contemporary real-world data on prognostic factors and treatment outcomes in melanoma LMD are limited. We conducted a retrospective cohort study of patients diagnosed with leptomeningeal metastasis from melanoma between 1 January 2018 and 31 December 2025, across Mayo Clinic sites. LMD diagnosis was made by magnetic resonance imaging showing leptomeningeal enhancement and confirmation from cerebrospinal fluid cytology and clinical presentation. Demographic, clinical, treatment, and outcome data were collected. Overall survival (OS) from LMD diagnosis was the primary endpoint. Forty-four patients were identified (median age: 60.0 years, range: 30.5–82.7). Before diagnosis of LMD, systemic therapy for metastatic disease was given to 91% of patients. BRAF mutations were present in 65.9%. After LMD diagnosis, 88.6% were treated for LMD. Median OS was 2.96 months (95% confidence interval: 1.39–4.53). Poor Eastern Cooperative Oncology Group performance status was independently associated with worse OS (hazard ratio: 2.10, P = 0.036). Any treatment for LMD (hazard ratio: 0.16, P = 0.005) was associated with improved OS. Melanoma-related LMD remains rapidly fatal. Studies of novel treatments are needed to improve outcomes for patients with this diagnosis.

Discoidin Domain Receptor 2 (DDR2) is a collagen-activated tyrosine kinase required for bone and tooth development as well as regeneration of calvarial and long bones. Although DDR2 is expressed in alveolar bone, its functions in this site have not been previously examined. The present study used global and conditional knockout approaches and lineage tracing to examine the functions of DDR2 in alveolar bone formation during tooth socket healing. First molars were extracted from the maxillae of wild-type and globally Ddr2 -deficient ( Ddr2 LacZ/LacZ ) mice, and socket healing was measured after 1, 2, or 4 wk. At all times, Ddr2 inactivation significantly reduced socket healing. These changes were associated with decreased cell proliferation 3 d after extraction without any detectable changes in apoptosis. In addition, collagen fibril orientation, measured using Picrosirius Red staining under polarized light, was disrupted in tooth sockets from Ddr2 -deficient mice. For lineage tracing, 4-wk-old Ddr2 mer-cre-mer ; R26R tdTomato and Gli1 CreERT2 ; R26R tdTomato mice were induced with tamoxifen, first molars were extracted, and socket healing was examined after 1, 3, or 7 d. In both cases, tdTomato+ cells migrated into sockets, where they sequentially co-localized with preosteoblast and osteoblast markers. Thus, both DDR2 + and GLI1 + cells contribute to socket healing. The considerable overlap observed between DDR2 + and GLI1+ cells suggested that DDR2 functioned in GLI1 + cells, which are known to have skeletal progenitor properties. Consistent with localization data, conditional knockout ( Gli1 CreERT2 ; Ddr2 fl/fl ) mice exhibited reductions in socket healing 1 wk postextraction, although the inhibition of socket repair was less than that seen in global Ddr2 knockouts. In summary, this work demonstrates a role for DDR2 in alveolar bone repair, a finding that may have therapeutic implications for the treatment of alveolar bone loss associated with periodontal disease and other disorders.

Abstract Background Abdominal arterial calcification is a well-established predictor of cardiovascular events and mortality in kidney failure. Autosomal dominant polycystic kidney disease (ADPKD), a common genetic cause of kidney failure, presents with a distinct vascular profile. However, the burden of abdominal arterial calcification in ADPKD remains inadequately characterized. Clarifying these differences may improve cardiovascular risk stratification and transplant timing. Methods We conducted a retrospective cohort study of 4088 adult patients listed for kidney transplant at three Mayo Clinic sites (2005–2024). Patients were categorized by kidney failure cause: ADPKD vs. non-ADPKD. Abdominal arterial calcification was quantified on non-contrast computed tomography (CT) scans using a modified Agatston scoring method. Propensity score matching (1:1) adjusted for age, sex, race, lipid levels, left ventricular ejection fraction, dialysis exposure, coronary artery disease, neurovascular disease, and smoking history, was performed. Abdominal arterial calcification scores were compared between matched groups, and subgroup analyses evaluated abdominal arterial calcification severity across dialysis durations in ADPKD patients. Results After matching, 309 patients with ADPKD were compared with 309 non-ADPKD chronic kidney disease (CKD) controls. Abdominal arterial calcification scores were significantly lower in the ADPKD group (median: 425.3; IQR: 0.0–2033.5) than in the non-ADPKD group (median: 1256.8; IQR: 96.5–5033.8). Among ADPKD patients, abdominal arterial calcification scores increased with dialysis duration (P &lt; .001). Conclusion ADPKD patients exhibit lower abdominal arterial calcification scores than their non-ADPKD counterparts after adjusting for clinical variables. Abdominal arterial calcification progression with dialysis highlights the importance of early transplant evaluation. This study introduces a novel adaptation of coronary calcium scoring software for quantifying abdominal calcification, offering a standardized approach to vascular risk assessment in kidney transplant candidates.