Citations

Abstract Background Some centres advocate preoperative radiotherapy in patients with pancreatic cancer and arterial involvement despite a lack of Level 1 evidence on survival benefit. Although it has been suggested that preoperative radiotherapy may increase the risk of postpancreatectomy haemorrhage (PPH) and morbidity, evidence is again lacking. This study investigated the association between preoperative radiotherapy and both PPH and major morbidity following arterial divestment/resection during pancreatic adenocarcinoma resection after chemotherapy. Methods Consecutive patients diagnosed with pancreatic adenocarcinoma and > 180° arterial involvement who were treated with preoperative chemotherapy with or without radiotherapy followed by pancreatic resection with arterial divestment/resection were included in the study. Logistic regression analyses including propensity score-based overlap weighting were performed to investigate associations between radiotherapy and in-hospital PPH grade B/C and major morbidity, expressed as adjusted risk differences (aRDs). Results Overall, 246 patients undergoing pancreatic resection with arterial resection (169, 69%) or divestment (77, 31%) were included. Radiotherapy was not associated with PPH (aRD 6%; 95% confidence interval (c.i.) −3 to 14), regardless of arterial divestment (aRD 3%; 95% c.i. −5 to 11) or arterial resection (aRD 12%; 95% c.i. 1 to 23; Pinteraction = 0.189). Radiotherapy was associated with a 14% (95% c.i. 2 to 25) higher risk of major morbidity, especially after arterial resection (aRD 27%; 95% c.i. 11 to 43) compared with arterial divestment (aRD −12%; 95% c.i. −35 to 11; Pinteraction = 0.006) and after external beam radiotherapy (aRD 21%; 95% c.i. 8 to 32) compared with stereotactic body radiotherapy (aRD −12%; 95% c.i. −27 to 6; Pinteraction = 0.0001). Ninety-day mortality was increased, albeit not significantly, after preoperative radiotherapy (10 (8%) versus 3 (3%) deaths with versus without preoperative radiotherapy, respectively; P = 0.067). Conclusions Radiotherapy before resection of pancreatic cancer with > 180° arterial involvement was associated with an increased risk of postoperative major morbidity when arterial resection, but not arterial divestment, was performed. This risk should be taken into account when considering preoperative radiotherapy in patients who may require arterial resection.

Abstract Background The increased use of superior mesenteric artery (SMA) divestment has been a driver behind the increased resection rate for locally advanced pancreatic cancer following preoperative therapy. This has also resulted in an increase in the rate of postoperative neurogenic diarrhoea, but knowledge about postoperative neurogenic diarrhoea is lacking. The aims of this study were to determine the incidence, risk factors, management, and outcomes of neurogenic diarrhoea after SMA divestment/resection for pancreatic adenocarcinoma. Methods This multicentre retrospective study included consecutive patients undergoing pancreatic adenocarcinoma resection, including SMA divestment/resection, after preoperative chemotherapy with or without radiotherapy between 2016 and 2022. Primary endpoints were the incidence of postoperative neurogenic diarrhoea, associated factors, treatment strategies, and outcomes. Secondary endpoints were the rate of adjuvant chemotherapy and the impact of neurogenic diarrhoea on overall survival (OS). Results Overall, 291 patients who underwent pancreatic resection with concomitant SMA divestment (240, 82%) or resection (51, 18%) were included in the study. Postoperative neurogenic diarrhoea was diagnosed in 193 patients. The adjusted risk of developing neurogenic diarrhoea was 59% (95% confidence interval (c.i.) 46 to 73) after ≤ 180° SMA divestment, 80% (95% c.i. 67 to 93) after > 180° SMA divestment, and 77% (95% c.i. 66 to 88) after SMA resection. Postoperative neurogenic diarrhoea was treated with non-opioid drugs (29, 15%), non-opium opioids (140, 73%), opium tincture (69, 36%), and/or octreotide (49, 25%), and normalized in 51% of patients. After adjusting for confounders, neurogenic diarrhoea was not significantly associated with OS (hazard ratio 0.83; 95% c.i. 0.55 to 1.25). Conclusion Neurogenic diarrhoea occurred in two-thirds of patients following resection of pancreatic adenocarcinoma with concomitant SMA divestment/resection, particularly after > 180° SMA divestment or SMA resection. Although challenging to manage, neurogenic diarrhoea is not associated with impaired OS. Evidence-based treatment strategies are needed for adequate management.

ABSTRACT Background Visceral myopathy (VSCM) is an ultra‐rare life‐threatening condition characterized by severe impairment of gastrointestinal (GI), genitourinary, and uterine smooth muscle. This disorder represents a significant clinical challenge due to variable presentation and the lack of standardized diagnostic and therapeutic protocols. Methods To discuss advances in the field, scientists and clinicians with a special interest in VSCM met in Arenzano, Genova, Italy in October 2024 for the second International Forum on Visceral Myopathy 2024 (IFVM2024) ( https://ifvm2024.ge.ibf.cnr.it/ ). Key Results As in the previous edition of the event ( https://poic‐e‐dintorni.org/efvm‐2022/ ), attendees included clinicians and researchers from around the world who study this disease, representatives from support organizations, patients affected by VSCM and their families, and companies that co‐funded the event. The present manuscript aims to summarize knowledge shared during the IFVM2024 conference, thus providing an updated state‐of‐the‐art summary of VSCM biology and disease management. Conclusions Here, we pay particular attention to the epidemiology of the disease, histopathology, genetics, novel treatments, advances in molecular and cell biology, experimental models, and the lived experiences and impact of this disorder on families.

Abstract Background Approximately 12 000 adolescents and young adults (ages 15-39, AYAs) are diagnosed with a primary central nervous system (CNS) tumor each year. DNA methylation profiling has transformed CNS tumor classification by refining diagnostic accuracy and identifying biologically distinct subtypes, but its application has not been systematically evaluated in the AYA population. In this study, we examined the spectrum of CNS tumor types across age groups, with a focus on the AYA population. Methods We assembled a large dataset of CNS tumor samples with age annotations and methylation profiles matching with high confidence to a CNS tumor type using the NCI/Bethesda classifier. Prevalence of tumor type, methylation class and DNA copy number aberrations were compared across age strata (pediatric, AYA, and adult). Results The cohort of 21 712 CNS tumors included 5351 tumors from AYAs (25%), which showed a mixed pattern, with tumors typical of childhood (eg, medulloblastoma) as well as those common in older adults (eg, glioblastoma). Several tumor types were specifically enriched in the AYA, including IDH-mutant astrocytoma, pleomorphic xanthoastrocytoma, posterior fossa group B ependymoma, and diffuse hemispheric glioma, H3 G34-mutant, among others. Distinct methylation subclasses of multiple tumor types were observed in the AYA, and patterns of genomic aberrations showed age-specific distributions. Conclusion Large-scale methylation profiling revealed unique classification patterns of CNS tumors in AYAs, with specific tumor types, subclasses, and genomic alterations enriched in this population. These data may serve as a valuable reference resource for better understanding the spectrum of CNS tumors affecting AYA patients.

ABSTRACT We report on the 2025 International ICU Diary Conference that provided a comprehensive update on current knowledge, innovations and global practices related to ICU diaries. Held in a 6‐week online format, the event featured 23 speakers and was attended by mean 69.7 (SD 20.5) participants per session. Topics included development of ICU diaries, use in special settings, digital diaries, survivors' and families' experiences, Post‐Intensive‐Care Syndrome and follow‐up and implementation projects. Highlights were innovative solutions for digital diaries and the report of persons with lived and living experiences with diaries, changing the focus on humanising critical care. Relevance for Practice ICU diaries support patient‐ and family‐centred care and should be implemented more widely across healthcare systems. Their successful adoption requires contextual adaptation and policy support, with future development likely to be shaped by the increasing use of digital ICU diaries.

OBJECTIVE: A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN: Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING: Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS: A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS: A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS: A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

The results underscore a multifaceted interaction among cardiopulmonary hemodynamics, right heart pressures, ventilatory response, and autonomic regulation. In particular, altered RV-PA coupling correlated with heightened sympathetic drive, indicating that cardiopulmonary efficiency and hemodynamics may influence central autonomic outputs. This suggests that mechanical stress or overload in the right heart could modulate sympathovagal balance, thereby contributing to altered autonomic responses during exercise in patients with cardiopulmonary disorders.

Abstract Despite growing interest in AI for pancreatic cyst management, no prior study has systematically investigated how lesion characteristics influence model behavior or provided a comprehensive explainability analysis in IPMN malignancy risk stratification. We present the first multi-center study integrating explainable AI with uncertainty quantification to evaluate how cyst type, size, and location affect deep learning performance in IPMN malignancy prediction. Our retrospective study analyzed 170 IPMNs from seven centers using a radiomics-deep learning fusion model. Cases were stratified by dysplasia grade, IPMN type, size, and location; with model interpretability assessed using SHAP, LIME, Grad-CAM, and uncertainty quantification. Overall accuracy was 67.1%, with model uncertainty lower for correct versus incorrect predictions (0.72 vs 0.78, p < 0.001). On subgroup analysis: Low-Risk lesion accuracy exceeded High-Risk (81.3% vs. 42.9%, p < 0.001), BD accuracy was inversely correlated with cyst size while MD remained stable, and body and whole-pancreas cysts stratified more accurately than tail cysts (77.8%, 76.6% vs. 47.8%). AI models face significant, previously uncharacterized performance drops when evaluating complex high-risk IPMNs. Our study shows that integrating uncertainty quantification can successfully flag unreliable predictions, enabling a selective-prediction framework where clinicians can confidently rely on AI for low-risk, low-uncertainty lesions while deferring high-uncertainty cases to expert review.

Background Medication nonadherence has been associated with poor outcomes in transplant recipients yet identifying these behaviors pre-transplant remains challenging. The simplified medication adherence questionnaire (SMAQ) is a brief, reliable instrument to assess medication adherence. The aim of this study was to perform SMAQ testing on thoracic organ candidates and examine correlations between these scores and individual patient factors predicting medication nonadherence. Methods Consenting waitlisted lung, heart, and heart-lung transplant candidates from six thoracic transplant centers were mailed a survey that included demographic information and the Simplified Medication Adherence Questionnaire (SMAQ). Univariate logistic regression analysis was performed to assess association between pre-transplant medication adherence and demographic characteristics, psychosocial factors, and mortality. Results Among 298 participants, 60.7% were medication nonadherent. Nonadherence was associated with some college education (OR: 1.73; CI: 1.06, 2.81), lower positive affect (OR: 0.95; CI: 0.92, 0.99), and higher uncertainty (OR: 1.02; CI: 1.01, 1.04). Higher positivity ratio predicted adherence. Conclusion Identifiable patient-specific characteristics associated with medication nonadherence can be screened for during thoracic transplant evaluation. Interventions aimed at improving these factors during the pre-transplant period may improve clinical post-transplant outcomes, however, larger studies are needed to validate these findings.

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.