With the advent of new effective treatments for obesity, the field is rapidly changing creating an urgent need for evidence to guide best patient management. To help prioritise and plan for future trials, a meeting of experts was convened with the aim of reviewing the current literature to identify and prioritise current knowledge gaps; identify relevant research questions, and discuss appropriate trial methodologies that could be utilised to address the identified gaps in a timely and pragmatic manner. Participants included research-active academic surgeons and physicians, and industry representatives from various pharmaceutical and device companies. This report summarizes the key outcomes from this meeting. Treatment options for obesity are rapidly evolving. To provide best personalised care for patients, more evidence is required to understand how to best utilise currently available treatments as well as combine treatments. Trials focused on improving the treatment of obesity may need to be pragmatic and more agile than the traditional RCT to enable real time impact on patient care.
Abstract Janus kinase inhibitors (JAKi) are standard of care for patients with myelofibrosis (MF) but can be associated with treatment-limiting cytopenias and do not modify underlying disease. Novel treatments targeting other clinically relevant pathways are needed. Inhibitors of bromodomain (BD) and extraterminal domain (BET) proteins are a promising class of drugs that have demonstrated the ability to modulate key pathways involved in inflammation, fibrosis, and apoptosis. ABBV-744 is a novel small molecule that targets the BDII of BET proteins and has previously been shown to be well tolerated when administered daily at doses of 120 and 180 mg to patients with acute myeloid leukemia. We report the outcomes of a multicenter, open-label phase 1b study of ABBV-744 in patients with MF who received ≥1 previous lines of therapy, including a JAKi. The primary objective was safety, including dose-limiting toxicities (DLTs). Secondary end points included a reduction in spleen volume of ≥35% (SVR35), ≥50% reduction in total symptom score (TSS50), objective response rate, and pharmacokinetics. All 21 patients experienced at least 1 treatment-emergent adverse event, and 11 patients experienced a DLT. The most common events leading to DLTs were thrombocytopenia (33%) and anemia (24%). SVR35 was attained in 24% of patients at week 12 and 33% at week 24. TSS50 was reported for 29% of patients at 12 weeks and 19% at week 24. These outcomes are noteworthy in this heavily pretreated population considering the advanced disease state and limited treatment options for this patient population. This trial was registered at www.clinicaltrials.gov as NCT04454658.
Temporary mechanical circulatory support (t-MCS) is increasingly used in fulminant myocarditis (FM), yet long-term outcomes and risk factors remain poorly defined. From the FULLMOON international cohort (419 adults with suspected FM across 36 centers in 15 countries), 295 patients treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO) and/or Impella were analyzed. The primary endpoint was mortality at 1 year, heart transplantation (HTx), or left-ventricular assist device (LVAD). Multivariate Cox regression identified predictors of adverse outcomes. A propensity score-weighted analysis assessed outcomes based on timing of endomyocardial biopsy (EMB): early (≤ 2 days), delayed (> 2 days), or none. The median age was 39 years (IQR 28–60), and 55
A BSTRACT Background and Purpose: Neurological deterioration (ND) occurs in 5%–40% of patients with acute ischaemic stroke (AIS) during the 1 st week and is associated with worse outcomes and increased mortality. We aimed to develop and internally validate a simple bedside score for predicting ND in AIS patients not receiving reperfusion therapy. Methods: We conducted a retrospective cohort study including adults hospitalised with AIS between May 2021 and December 2023. ND within 7 days was recorded. A multivariable logistic regression model was developed using stepwise selection based on the Akaike Information Criterion. Internal validation was performed with 1000 bootstrap resamples. Calibration was assessed using the Hosmer–Lemeshow test and calibration plots. The optimal cut-off was determined using the Youden index. Results: A total of 444 patients were included, and 90 (20.3%) developed ND. Five independent predictors were identified: admission hyperglycaemia, leucocytosis, National Institutes of Health Stroke Scale severity, symptomatic intracranial stenosis and symptomatic extracranial stenosis. The derived GLaSSES score showed good discrimination and calibration. The Hosmer–Lemeshow test showed no significant lack of fit ( P = 0.1008). A cut-off of 17.5 points yielded a sensitivity of 75.6%, specificity of 90.1%, positive predictive value of 66.0% and negative predictive value of 93.5%. Mortality was higher among patients with ND (47.8%). Conclusions: The GLaSSES score is a simple bedside tool for predicting ND after AIS. External validation is required before clinical implementation.
Abstract Introduction The Barthel Index (BI) is widely used to assess functional independence after critical illness. Although it demonstrates strong reliability and prognostic value, some studies suggest that it may be highly specific but poorly sensitive in detecting subtle or multidimensional impairments in health-related quality of life (HRQoL). Patients may regain autonomy in basic activities of daily living (ADL) yet continue to experience fatigue, pain, or psychological limitations not captured by the BI. We tested the hypothesis that ICU survivors would show a discordance between functional recovery (BI) and perceived health evaluated through the SF-36 and EQ-5D-3L questionnaires. Method A cross-sectional study was conducted including 52 survivors of respiratory critical illness who required mechanical ventilation. Assessments were performed 6-12 months after ICU discharge using the Barthel Index (0-100), the SF-36 (domains: Physical Functioning [PF], Role Physical [RP], Bodily Pain [BP], General Health [GH], Vitality [VT]), and the EQ-5D-3L (utility index [UTIL5D, 0-1] and visual analogue scale [VAS, 0-100]). Clinical discordance was defined as BI ≥ 90 combined with (a) PF < 50 or GH < 50 (SF-36), (b) UTIL5D <0.80, or (c) VAS <50. t-tests and Pearson correlations were used to compare BI with each PROM domain. Results Mean (±SD) scores were: BI 91.3±14.1; PF 76.4±25.3; RP 46.6±47.2; BP 60.3±24.4; GH 47.3±24.8; VT 44.1±20.7; UTIL5D 0.695±0.213; VAS 0.734±0.186; Age 52.7±15.6; APACHE II 14.8±4.4; SOFA 7.3±2.9; ICU stay 12.6±7.8 days; and Mechanical Ventilation 9.4±5.6 days. Correlations between BI and SF-36 domains were: PF r = 0.80 (p < 0.001), RP r = 0.56, BP r = 0.57, GH r = 0.42, and VT r = 0.43. Clinical discordance was observed in 3.8% (PF < 50), 32.7% (GH < 50), 59.6% (UTIL5D<0.80), and 75.0% (VAS<50) of patients. Discordance was more frequent among younger survivors (<65 years: 41.7% vs ≥ 65 years: 12.5% for GH < 50). Conclusion Despite recovering functional independence (BI ≥ 90), a substantial proportion of ICU survivors report poor perceived health and quality of life. These findings suggest that the BI is specific but not sensitive in detecting post-ICU HRQoL impairments. Integrating PROMs such as SF-36 and EQ-5D-3L (including VAS) may improve detection of residual physical, emotional, and social limitations, guiding patient-centered rehabilitation strategies. This abstract is funded by: None
