Citations

ABSTRACT Background Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) are primarily used to manage type 2 diabetes mellitus (T2DM) and heart failure (HF), but their impact on reducing stroke risk in patients with atrial fibrillation (AF) remains underexplored. We aimed to investigate the impact of SGLT2‐Is for stroke risk mitigation in patients with AF. Methods Using the TriNetX database, we performed a retrospective cohort study on patients ≥ 18 years with AF and on anticoagulation. These patients were then classified into two cohorts based on their use of SGLT2‐Is. To balance the baseline demographics, comorbidities, and medication use, propensity score matching (PSM) was used. The primary outcome was ischemic and hemorrhagic strokes, and the secondary outcomes were all‐cause mortality, all‐cause hospitalizations, need for AF cardioversion or antiarrhythmic drug initiation, and cardiac arrest. Adjusted odds ratio (aORs) and hazard ratios (HRs) were estimated for both the primary and secondary outcomes. Results A total of 152,778 patients with 76,389 patients were included in each cohort (SGLT2‐Is users, and non‐users) after PSM. The mean age of both SGLT2‐Is users and non‐users was 72.8 years. For the SGLT2‐Is users, the mean follow‐up period was 317 days, whereas the mean follow‐up period for the non‐users was 306 days. For the primary outcome, we found that SGLT2‐Is users had a lower risk of ischemic stroke (aOR: 0.889; 95% CI: 0.857–0.923) and hemorrhagic stroke (aOR: 0.682; 95% CI: 0.620–0.749) compared to non‐users. Regarding the secondary outcomes, SGLT2‐Is users also had lower risk for all‐cause mortality (aOR: 0.615; 95% CI: 0.595–0.636), all‐cause hospitalizations (aOR: 0.599; 95% CI: 0.587–0.611), need of AF cardioversion (aOR: 0.846; 95% CI: 0.813–0.881), antiarrhythmic drug initiation (aOR: 0.790; 95% CI: 0.766–0.815), and cardiac arrest (aOR: 0.643; 95% CI: 0.601–0.688). Conclusions SGLT2‐I use in patients with AF is associated with lower risks of stroke and other cardiovascular and non‐cardiovascular outcomes. Future prospective research is needed to validate these findings.

Purpose Part-two of this consensus aimed to provide recommendations for the prevention of meniscus injuries, non-operative treatment of acute tears and degenerative lesions, return to sports, and patient-reported outcome measures. Methods This consensus followed the European Society of Knee Surgery, Sports Traumatology and Arthroscopy (ESSKA) formal consensus methodology. For this combined ESSKA- American Orthopedic Society for Sports Medicine (AOSSM) - American Academy of Sports Physical Therapy (AASPT) initiative, 67 experts from 14 countries, including orthopedic surgeons and physiotherapists, were involved. The 26 Steering Group members established guiding questions, screened the existing evidence, and proposed statements, and provided Grades of recommendations. The 41 Rating Group members assessed the statements according to a Likert scale (1-9). Final documents were assessed by an international peer review group for geographical adaptability. Results Low to moderate scientific level of evidence was available, so that grades of recommendations were low (three Grade A ratings, four Grade B, three Grade C and 13 Grade D), underlining the relevance of this consensus. One strong and 17 relative agreements with overall median of 8 (8-9) and a mean of 7.92 +/- 0.37 were achieved for 23 statements on 18 questions. Prevention of meniscus injuries is possible with general knee injury reduction programs and through avoidance of certain activities. Non-Operative treatment including physical therapy is the first line approach for degenerative meniscus lesions and may be an option for some acute tears. Return to sports after meniscus tear surgery should be both criterion-based and time-based. Patient reported outcomes in combination with performance-based measures are recommended to evaluate the rehabilitation process. Conclusion This international EU-US consensus established recommendations for prevention strategies, describes rehabilitation of non-operated patients and of patients after partial meniscectomy, meniscus repair and meniscus reconstruction, and establishes return to sport criteria. These updated and structured recommendations may be applied by surgeons and physiotherapists. Level of Evidence I, Formal Consensus.

Objective: To establish comprehensive recommendations on the management of perihilar cholangiocarcinoma (pCCA) and to identify areas in need of future investigation. Summary Background Data: The lack of consensus in management of pCCA across institutions worldwide impairs optimal patient care and best-achievable oncological outcome. A holistic and critical assessment of the body of evidence and collaborative guidance are required. Methods: The Consensus4pCCA conference developed unbiased consensus using the Zurich-Danish model. An impartial and multidisciplinary jury adopted comprehensive recommendations grounded on the work of eight expert panels answering predefined clinical questions and considering the best-quality evidence through a systematic review. The development of recommendations complied with GRADE and SIGN50 methodologies. Results: Seventy-one international experts considered 570 studies. Ten jury members concluded 71 recommendations covering definition and diagnosis, preoperative assessment and optimization, surgical resection, liver transplantation, and outcome reporting for pCCA patients. The consensus underscored that making patients amenable to high-quality curative resection and reducing its associated morbidity must be of highest priority. As such, multidisciplinary expertise and centralized care at all stages of disease management are critical to ensure both safety and oncological adequacy. To overcome the evidence-gap for rare diseases like pCCA, the jury urged large-scale registries to address open questions across the disease continuum and highlighted priorities for future investigation. Conclusion: The Consensus4pCCA represents an unprecedented commitment to collectively harmonize global treatment strategies for pCCA. This collective effort bridges the gap between expert opinions and clinical evidence and holds great promise to improve patient outcomes in the future.

OBJECTIVE Reports of surgical outcomes for Cushing’s disease are mostly limited to single-center experiences by expert surgeons. Therefore, no generalizable surgical outcome metrics for endoscopic endonasal Cushing’s disease surgery are available for practitioners to guide quality-improvement efforts. This is potentially problematic, given the high morbidity and excess mortality observed in patients who do not achieve remission. This study proposes a bundle of evidence-based metrics for low-risk patients with Cushing’s disease, for whom optimal outcomes would be expected, that focus on the cost efficiency of care and surgical outcomes from multicenter collaboration of US pituitary centers. METHODS The steering committee of the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) consortium proposed the metrics based on available data from 12 US pituitary centers. A benchmarking population of low-risk patients undergoing first-time surgery was identified. Patient characteristics and outcomes were aggregated and analyzed by a data coordinating center. Metrics were reported using 2 approaches. RESULTS A total of 431 patients from 12 centers who underwent primary endoscopic transsphenoidal surgery from January 1, 2006, to December 31, 2022, were included. There were 227 patients in the low-risk cohort (age < 70 years, BMI < 50, microadenoma, and Knosp grade 0–2). For the cost-efficiency metrics, the mean (SD) length of stay was 3.8 (4.8) midnights, and the percentage of patients readmitted was 11.1%. The rate of disposition to a skilled nursing facility was 2.2%. For surgical outcomes, the rate of postoperative CSF leakage was 1.3%, and the rate of 1-year sustained surgical remission was 81.2%. The rates of permanent and temporary arginine vasopressin deficiencies were 1.8% and 11.9%, respectively. The 75th percentile performance by center was 3.0 midnights for length of stay, 6.3% for 90-day unplanned readmission, < 1% for disposition to a skilled nursing facility, < 1% for CSF leakage, and 92.2% for 1-year sustained remission. The 75th percentile was < 1% for both permanent and temporary arginine vasopressin deficiencies. CONCLUSIONS An evidence-based bundle of metrics in a Cushing’s disease patient population at low risk who underwent first-time endoscopic pituitary surgery is proposed. Surgeons can use these metrics to assess and improve the quality of their clinical pathways.

Myocardial deformation imaging has emerged as a valuable clinical tool for assessing right ventricular (RV) systolic function, providing additional diagnostic and prognostic insights compared to traditional indices of RV function. Two-dimensional speckle-tracking echocardiography is currently the standardized method of choice for measuring RV longitudinal strain (RVLS) in clinical practice. RVLS provides a more sensitive indicator of subtle myocardial dysfunction than conventional parameters for RV function assessment (i.e., tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction), with utility for the risk stratification and surveillance of conditions affecting the right heart. However, accurate interpretation of RVLS requires a comprehensive understanding of RV mechanics, pathology, and loading conditions across various cardiovascular conditions, as well as the effects of image quality and technical aspects of image acquisition and tracking in RV strain measurements. This review provides an updated overview of current practical guidelines for RV strain analysis, current clinical applications, and future directions for its potential use in clinical practice.

SUMMARY Tuberculosis induces diverse lesions, such as necrotic pneumonia, contributing to disease progression and transmission. Despite advances in understanding the role of ATP-gated P2RX7 ion channels in developing severe forms of tuberculosis, the regulation of this important signaling pathway remains unclear. Herein, we show that the ectonucleotidase CD39 plays an essential regulatory role in TB progression by preventing lung tissue damage, bacterial dissemination, and excessive inflammatory responses. Mechanistically, through its enzymatic activity on the cellular surface, CD39 protects infected macrophages from undergoing necrotic death mediated by P2RX7 activation. We proposed that by protecting macrophages from P2RX7-mediated cell death and bacterial dissemination, CD39 prevents the development of necrotic lesions. Altogether, these findings uncover a significant role for CD39 as an essential component of the molecular regulation underlying the development of severe tuberculosis. GRAPHICAL ABSTRACT Brief In tuberculosis, necrotic granuloma-like structures release extracellular ATP (eATP), which triggers P2RX7-mediated immune cell death. CD39 degrades eATP, preventing P2RX7 activation and promoting macrophage survival, thereby limiting inflammation, tissue damage, and bacterial dissemination.

Klippel–Trenaunay (KT) syndrome and Cardiac Sarcoidosis (CS) are two distinct medical conditions that rarely coexist, each presenting unique challenges in diagnosis and management. Here, we present a rare case of a 30-year-old male with a history of KT syndrome complicated by recurrent deep vein thrombosis, who presented with symptoms of acute heart failure including shortness of breath, fatigue, dizziness, palpitations, and chest pain and was subsequently diagnosed with isolated CS. We discuss the importance of thorough clinical evaluation and multimodal diagnostic approaches in this complex scenario with overlapping symptoms and diagnostic dilemmas.

e23011 Background: Eligibility criteria for clinical trials are crucial for maintaining safety and study integrity. However, they often exclude patients due to medical conditions that are not relevant, leading to gaps in understanding the real-world effectiveness of treatments. Addressing potentially modifiable exclusions (PMEs) could enhance accessibility and participation in trials without compromising safety, particularly given the low rates of enrollment. Methods: We retrospectively analyzed ‘screen-failed’ patients (those who were excluded after providing consent because they did not meet the eligibility criteria or other protocol requirements) with biliary tract (BTC) or pancreatic cancer (PDAC) between August 2019 and November 2024. Screening logs and electronic health records provided clinical data. PMEs were identified and validated by two independent medical oncologists. Results: Of 585 screen-failed patients from 18 trials, 76 were excluded due to incomplete data. Among the 509 patients analyzed (367-PDAC, 142-BTC), the leading causes of screen failure were declined participation (99, 19%), comorbidities (59, 12%), suboptimal organ function (56, 11%), absence of biomarker (49, 10%), and insufficient biospecimens (36, 7%). Among patients declining participation, reasons included preference for standard care (23%), travel (22%), competing trials (5%), adverse event concerns (4%), financial issues (3%), and unknown reasons (43%). Of the 509 patients deemed ineligible for study entry at screening, we identified 69 patients (13.6%) with PMEs, primarily related to borderline laboratory abnormalities: liver function (16, 23%), kidney function (14, 20%), platelet count (8, 12%), hemoglobin (5, 7%), and white blood cell count (4, 6%). Other PMEs included previous or concurrent malignancies (6, 9%) and viral hepatitis (3, 4%). PMEs were evenly distributed across trials. Notably, all screen-failed patients proceeded to receive standard therapy. Conclusions: This analysis underscores the potential for rigid eligibility criteria to exclude stable patients who might benefit from investigational treatments. Easing specific criteria, particularly those related to laboratory abnormalities, could broaden trial accessibility. Furthermore, examining the reasons for declined participation and addressing PMEs could help develop strategies to enhance trial enrollment.