Citations

Introduction and Hypothesis: New bleeding in cerebral cavernous malformations (CCM) heralds increased risk of future hemorrhage for several years, yet conventional imaging only detects new bleeding that occurred in the prior weeks. A biomarker of hemorrhage could help identifying high risk lesions. An increase of mean lesional quantitative susceptibility mapping (QSM) ≥6% on MRI has been adjudicated as reflecting new bleeding in CCM during longitudinal follow-up. However, mean lesional QSM from a single acquisition could not diagnose or prognosticate a bleed. We hypothesize that machine learning (ML) may identify diagnostic and prognostic features of bleeding within QSM maps at a single point in time. Material and Methods: Two hundred and sixty-five QSM maps of CCM lesions were acquired in 120 patients enrolled in National Institute of Health (NIH) multisite trial readiness project (NCT03652181). Each map was classified (Yes/No) in association with symptomatic hemorrhage (SH) and/or biomarker event with QSM increase ≥6% in the prior (diagnostic association) and subsequent (prognostic association) year. Twenty-eight features were extracted including 14 texture, 5 first-order statistical, as well as 3 size, shape, and morphological. Five-fold cross-validation was conducted on a support-vector machine (SVM) with linear stepwise kernel for both diagnostic and prognostic associations. Performance of individual features and composite classifiers was evaluated using student t-test ( p <0.05) with Bonferroni-correction and receiver operating characteristic (ROC) analysis, area under the curve (AUC). Results: Lesions with SH in the prior year had lower average values for sum variance (AUC=0.79, p<0.001), variance (AUC=0.79, p<0.001), and correlation (AUC=0.71, p=0.004) as compared to lesions without SH. The SVM classification method tasked with distinguishing lesions with mean QSM increase ≥6% in the prior year included recurrent selection of sum average, mean, sphericity and margin sharpness, yielding an AUC of 0.61 (p=0.02). In the prognostic cohort, no individual feature nor any SVM classification model was able to distinguish cases with a subsequent clinical bleed or biomarker event. Conclusion: This proof-of-concept suggests that ML may assist in deriving features on QSM maps acquired at a single timepoint, which reflect prior hemorrhagic activity in CCM. Further investigation is planned in larger cohorts and in conjunction with clinical trials of bleeding in CCM.

Summary Metabolic and bariatric surgeries (MBS), including Roux‐en‐Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), have proven effective in promoting long‐term diabetes remission among patients with type‐2 diabetes (T2D). In this multicentre retrospective cohort study, we investigated the effectiveness of RYGB and SG in achieving diabetes remission, specifically among patients with T2D and vascular complications, while accounting for similar baseline diabetes severity. Although various scores predict diabetes remission after bariatric surgery, they do not consider diabetes‐related vascular complications, which can influence outcomes even in patients with similar baseline T2D severity. We collected preoperative data on microvascular (retinopathy, nephropathy, neuropathy) and macrovascular comorbidities (coronary artery disease, cerebrovascular accidents, peripheral artery disease) to compare the efficacy of RYGB and SG. Among 961 patients analysed, those with vascular complications showed higher remission rates with RYGB (OR: 1.97) compared to SG, despite similar baseline diabetes severity. Notably, RYGB patients with microvascular complications had a significant advantage in achieving T2D remission (OR: 2.95). However, no significant differences in remission were observed in patients with macrovascular complications. These findings suggest that RYGB may be more effective than SG in specific patient populations, particularly those with microvascular complications, emphasizing the need for personalized treatment strategies.

Summary Biliopancreatic diversion with duodenal switch (BPD‐DS) and single anastomosis duodeno‐ileostomy with sleeve (SADI‐S) are associated with superior and sustained weight loss outcomes. Despite their growing popularity, long‐term safety profiles, particularly the risk of internal hernia (IH), remain underexplored. This study aimed to evaluate the incidence and characteristics of IH following BPD‐DS and SADI‐S procedures, comparing their clinical presentation, diagnostic methods, and outcomes. A retrospective chart review was performed for patients who underwent BPD‐DS or SADI‐S between 2008 and 2023 in two high‐volume tertiary referral centres for bariatric surgery in the United States. Demographic data, comorbidities, operative details, and follow‐up outcomes were collected. A subgroup analysis of IH cases was conducted to compare the incidence, location of hernias, and diagnostic modalities between procedures. Out of 1160 patients (85.1% BPD‐DS; 14.9% SADI‐S), the overall incidence of IH was 1.12%, with a higher rate in BPD‐DS (0.8%) than in SADI‐S (0.57%). Most IHs occurred within the first 24 months postoperatively. The majority of IHs in BPD‐DS patients were in the pseudo‐Petersen's space. The single IH case in the SADI‐S group occurred in the same space. Most patients presented with abdominal pain and were diagnosed by CT imaging. SADI‐S showed a lower IH rate compared to BPD‐DS, but further studies are needed to confirm these findings. The variability in clinical presentation complicates the diagnosis of IH, emphasizing the need for increased clinical vigilance.

AbstractMacitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right‐heart catheterization hemodynamic variables, N‐terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty‐seven patients were randomized to macitentan (n = 28) or placebo (n = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo‐corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58–0.94; p = .0158). No statistically significant differences were observed in secondary endpoints. In a post‐hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo (p = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903.

Background: The field of metabolic and bariatric surgery (MBS) is currently an expanding surgical field with constant refinements in techniques, outcomes, indications, and objectives. MBS has been effectively applied across diverse patient demographics, including varying ages, genders, body mass indexes, and comorbidity statuses. Methods: We performed a comprehensive literature review of published retrospective cohort studies, meta-analyses, systematic reviews, and literature reviews from inception to 2024, reporting outcomes of MBS using databases such as PubMed, ScienceDirect, and Springer Link. Results: MBS is a safe and efficient therapeutic option for patients with obesity and associated medical conditions (mortality rate 0.03–0.2%; complication rates 0.4–1%). The favorable safety profile of MBS in the short-, mid-, and long-term offers the potential to treat patients with obesity and type 2 diabetes mellitus, immunosuppression, chronic anticoagulation, neoplastic disease, and end-organ failure without increased morbidity and mortality. Conclusions: In conclusion, the future of MBS lies in the ongoing innovation and adapted therapeutic strategies along with the integration of a variety of other techniques for managing obesity. Careful preoperative assessments, coupled with a multidisciplinary approach, remain essential to ensure optimal surgical outcomes and patient satisfaction after MBS.

Abstract Background This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal–external cross-validation by different regions was performed to evaluate the generalizability of the model. Results A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53–0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65–0.73) at validation, with adequate discrimination and calibration across regions. Conclusions The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) demonstrates high rates of type 2 diabetes mellitus (T2DM) remission, a phenomenon hypothesized to be mediated mainly by weight loss. Compared with procedures that do not bypass the proximal small intestines, such as sleeve gastrectomy (SG), RYGB exhibits weight loss–independent intestinal mechanisms conducive to T2DM remission. We investigated continued diabetes remission (CDR) rates despite weight recurrence (WR) after RYGB compared with an SG cohort. STUDY DESIGN: A retrospective review of patients who underwent successful primary RYGB or SG with a BMI value of 35 kg/m 2 or more and a preoperative diagnosis of T2DM was performed. Patients with less than 5 years of follow-up, absence of WR, or lack of T2DM remission at nadir weight were excluded. After selecting the optimal procedure for glycemic control, rates of CDR were then stratified into WR quartiles and compared. RESULTS: A total of 224 RYGB and 46 SG patients were analyzed. The overall rate of CDR was significantly higher in the RYGB group (75%) compared with the SG group (34.8%; p < 0.001). The odds of T2DM recurrence were 5.5 times higher after SG compared with RYGB. Rates of CDR were stratified into WR quartiles (85.5%, <25%; 81.7%, 25% to 44.9%; 63.2%, 45% to 74.9%; and 60%, >75%). Baseline insulin use, higher preoperative glycosylated hemoglobin, and longer preoperative duration of T2DM were associated with T2DM recurrence, whereas WR was not. CONCLUSIONS: T2DM remission rates after RYGB are maintained despite WR, arguing for a concurrent weight loss–independent metabolic benefit likely facilitated by bypassing the proximal small intestine.

Background: Roux-en-Y gastric bypass (RYGB) has demonstrated excellent glycemic control and type 2 diabetes mellitus (T2DM) remission for patients with obesity and T2DM. Duration of T2DM is a consistent negative predictor of remission after RYGB. However, the exact timing to offer surgical intervention during the course of the disease is not well elucidated. Material and methods: The authors performed a retrospective cohort study between 2008 and 2020 to establish the exact association between duration of T2DM and remission after RYGB. The authors divided our cohort into quartiles of preoperative disease duration to quantify the change in remission rates for each year of delay between T2DM diagnosis and RYGB. The authors also compared the average time to remission and changes in glycemic control parameters. Results: A total of 519 patients (67.2% female; age 53.4±10.7 year; BMI 46.6±8.4 kg/m 2 ) with a follow-up period of 6.6±3.8 years were included. Remission was demonstrated in 51% of patients. Longer duration of T2DM was a significant negative predictor of remission with an estimated decrease in remission rates of 7% for each year of delay [(OR=0.931 (95% CI: 0.892–0.971); P< 0.001)]. Compared to patients with <3 years of T2DM, remission decreased by 37% for patients with 3–6 years, 64% for those with 7–12 years, and 81% for patients with more than 12 years ( P <0.001). Half of the patients reached T2DM remission after 0.5 and 1.1 years, respectively, for the first and second quartiles, while patients in the other quartiles never reached 50% remission. Lastly, The authors noted an overall improvement in all glycemic control parameters for all quartiles at last follow-up. Conclusion: Patients with a recent history of T2DM who undergo early RYGB experience significantly higher and earlier T2DM remission compared to patients with a prolonged history of preoperative T2DM, suggesting potential benefit of early surgical intervention to manage patients with obesity and T2DM.

Objective Multiple scores validate long-term type-2 diabetes mellitus (T2DM) remission after metabolic and bariatric surgery (MBS). However, studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have not adequately controlled for certain parameters, which may influence procedure selection. Methods We conducted a multicenter retrospective review of patients with T2DM who underwent RYGB or SG between 2008 and 2017. Data on demographics, clinical, laboratory, and metabolic values were collected annually for up to 14 years. Each eligible RYGB patient was individually matched to an eligible SG patient based on diabetes severity, weight loss, and follow-up duration. Results Among 1149 T2DM patients, 467 were eligible for matching. We found 97 matched pairs who underwent RYGB or SG. RYGB showed significantly higher T2DM remission rates (46.4%) compared to SG (33.0%) after matching. SG patients had higher insulin usage (35.1%) than RYGB patients (20.6%). RYGB patients also experienced greater decreases in HbA1c levels and diabetes medication usage than SG patients. Conclusions RYGB demonstrates higher efficacy for T2DM remission compared to SG, regardless of baseline characteristics, T2DM severity, weight loss, and follow-up duration. Further studies are needed to understand the long-term metabolic effects of MBS and the underlying pathophysiology of T2DM remission after MBS.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH ( P =0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03652181.