Citations

ABSTRACT Epithelial ovarian cancer (EOC) incidence and mortality increase with age, driven in part by chronic inflammation, diminished T cell output, and heightened regulatory T cell (Treg) mediated immunosuppression. In aged EOC‐bearing mice, we observed reduced survival, accompanied by impaired CD4 + and CD8 + T cell responses and a marked expansion of FOXP3 + Tregs exhibiting elevated IL‐10 and TGFβ expression. Metabolic profiling revealed enhanced oxidative phosphorylation in Tregs from aged mice, along with a fivefold increase in intracellular succinate levels. This accumulation of succinate within the aged tumor microenvironment was found to potentiate Treg suppressive function. Notably, pharmacologic inhibition of α‐ketoglutarate dehydrogenase reversed this effect, restoring effector T cell activity. These findings highlight succinate‐driven metabolic reprogramming as a central mechanism of age‐related Treg dysfunction in EOC and suggest that targeting succinate metabolism may offer a promising strategy to rejuvenate antitumor immunity in elderly patients.

Background Medical providers often face challenges in accurately predicting the survival of critically sick patients. Optimistic forecasts can lead to the overuse of resources, while overly cautious predictions might restrict treatments. This study examines the role of specific psychological factors, analyzed realistically and holistically, in predicting survival outcomes for intensive care unit patients. Methods This single-center cohort study evaluated health care providers (e.g., physicians, residents and fellows, and advanced practice practitioners) using two 7-d clinical vignettes. Providers assessed the need for mechanical ventilation (MV), renal replacement therapy (RRT), a percutaneous endoscopic gastrostomy (PEG) tube, or palliative care. Psychological factors were measured using scales that assessed ambiguity tolerance, rationality versus emotional defensiveness, anxiety related to uncertainty, decision-making style, and risk taking. These psychological traits were analyzed using a more realistic and holistic approach, employing cluster techniques. Providers also determined whether they had enough information to evaluate the patient’s condition and compared their survival estimates to APACHE II scores. Results In general, engagement in MV and RRT was common by day 2, although physicians were significantly less likely to recommend RRT. Providers generally suggested starting a palliative care consultation by day 6, with a noticeable shift on day 4. Three distinct composite psychological groups emerged: optimistic denial individuals (ODI), optimistic providers (OP), and resilient providers (RP). While these composite psychological groups did not significantly influence engagement in mechanical therapies, they did affect palliative care decisions: RP were more likely to request palliative care, whereas ODI were much less likely to do so. In contrast, individual psychological traits had nonsignificant correlations with the decision to use therapies. Providers initially overestimated survival probabilities during the first 3 d compared with APACHE II survival estimates. However, after day 4, this trend reversed, with providers becoming significantly more pessimistic versus the predictive score and increasingly requesting palliative care involvement. Conclusions Providers’ psychological profiles, rather than their clinical experience, significantly influenced decisions about organ-support therapies and palliative care. Survival estimates showed a biphasic pattern: initially, providers overestimated survival compared with APACHE II predictions, then became more pessimistic and more likely to consult palliative care after day 4. Highlights Intensive care unit survival predictions by providers followed a biphasic pattern: optimistic early on, then increasingly pessimistic after day 4. Psychological traits such as denial and ambiguity tolerance influenced palliative care decisions more than clinical experience did. Resilient providers were more likely to initiate timely palliative care, while denial-prone providers delayed it. Clinicians and critical care teams should be aware of how their psychological makeup can affect patient care decisions and outcomes.

ABSTRACT Background Fall risk screening and prevention interventions initiated from the Emergency Department (ED) are endorsed by current national guidelines. We aimed to evaluate the effectiveness of ED‐based multi‐factorial and multi‐component interventions to prevent falls. Methods We conducted a systematic review and meta‐analysis of interventions for fall prevention initiated in the ED for older patients (age ≥ 60 years). Multi‐component and multi‐factorial interventions were included. We excluded studies without a control or comparison group. The published literature was searched from 2019 to May 2024. Risk of bias was assessed with the Newcastle Ottawa tool for observation studies and the Cochrane Risk of Bias v2 for randomized trials. A meta‐analysis was completed for the outcomes with multiple studies. Results The search resulted in 6312 abstracts with 2571 duplicates, for 3741 unique citations. A total of 18 studies were included in the systematic review; 5 were rated as high risk of bias/low quality. The articles were heterogenous in the intervention type (8 multi‐factorial and 8 multi‐component), setting (ED focused vs. outpatient), intervention components (i.e., nurses, physicians, therapists), and size (103–1435 participants). The interventions did not decrease risk of falls at 3 months (risk difference 0.05 95% CI [0.00; 0.09]), 6 months (0.07 [−0.04; 0.18]) or 12 months (−0.02 [−0.11; 0.07]). ED revisits at 1 month (−0.01 [−0.03; 0.00]), 3 months (−0.04 [−0.14; 0.06]), and 12 months (0.02 [−0.05; 0.25]) were also unchanged. Mortality and hospitalization rates were also unaffected. Improvement in functional status was noted in 4 of 5 studies reporting this outcome. Conclusions Multi‐factorial and multi‐component fall prevention interventions initiated from the ED did not decrease falls or recurrent healthcare use. These interventions may improve functional status in older adults at fall risk. Comparisons are limited by the heterogeneity in types of interventions, intervention compliance, and timing of outcomes.

Abstract Background Pregnancy-related acute kidney injury (PrAKI) is an uncommon but serious complication associated with adverse maternal and neonatal outcomes, with limited data in high-resource settings. Methods We conducted a retrospective cohort study of 29 586 deliveries at Mayo Clinic hospitals between 2017 and 2022. PrAKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Maternal characteristics, nephrotoxin exposure, clinical interventions, and neonatal outcomes were compared between patients with and without PrAKI. Results PrAKI occurred in 341 patients (1.15%). Compared with controls, PrAKI was associated with higher rates of chronic hypertension (28.7% vs 5.2%), cesarean delivery (68.5% vs 35.1%), intensive care unit (ICU) admission (59.1% vs 6.2%), and nephrotoxin exposure (58.7% vs 31.6%) (all P < .0001). Dialysis was required in 7.1% of patients with PrAKI, with 1.17% remaining dependent at discharge and 0.88% at 30 and 90 days; no control patients required dialysis. Neonates of mothers with PrAKI had higher rates of prematurity and neonatal ICU (NICU) admission (48.7% vs 9.8%; P < .0001). Maternal mortality was rare. Conclusions PrAKI is a marker of severe maternal illness and is associated with adverse maternal and neonatal outcomes. Although most patients recover kidney function, a subset develop persistent dysfunction. Early identification, cautious use of nephrotoxic medications, and structured postpartum follow-up are essential.

Despite advances in imaging, instrumentation, surgical techniques, and postoperative care, outcomes for certain peripheral nerve procedures remain consistently disappointing. In this article, we describe five surgical scenarios--adult pan-brachial plexus injuries, peroneal nerve injury after knee dislocation, sciatic nerve injury after total hip arthroplasty, radiation-induced brachial plexopathy, and lower trunk injury after cardiac surgery--that, in our experience and review of the literature, frequently lead to limited and consistently poor functional recovery after nerve surgery. These challenging cases reflect not only technical and anatomical complexity but the profound biological limitations of nerve regeneration in specific contexts. By critically analyzing these five procedures, we aim to promote more realistic patient counseling, support timely and individualized decision-making, and foster a more nuanced understanding of when and what type of surgical intervention may or may not be beneficial.

Abstract Carpal fractures are uncommon, representing a small proportion of hand fractures. This study aimed to determine the incidence, injury mechanisms, treatment patterns, and complication rates of carpal fractures in Olmsted County, Minnesota, United States. A retrospective review was performed using the Rochester Epidemiology Project registry to identify carpal fractures between 2013 and 2023. Fractures were confirmed by radiographs, computed tomography, or radiology reports. Demographic data, injury mechanism, fracture laterality, and fracture characteristics were recorded. A total of 699 carpal fractures were identified. Most patients were men (57%) with a mean age of 43 years. The most common fracture was the scaphoid (44%), followed by the triquetrum (31%), hamate (9%), and trapezium (3%). The overall incidence was 53.6 per 100,000 person-years. Concomitant wrist fractures occurred in 22%, and multiple ipsilateral carpal fractures in 4.6%. Patients with triquetrum fractures had the highest mean age (54 years) and low surgical rates (2%), whereas hamate and trapezoid fractures occurred at younger ages (39 and 38 years) and had the highest surgical rates (28 and 33%, respectively). The most common injury mechanism was a fall onto an outstretched hand (n = 438). Overall, 14% (n = 98) of patients underwent surgery, of whom 77% were men. The highest nonunion rate was seen in hamate fractures (10.9%), followed by scaphoid waist and proximal pole fractures (10.5%). Nonscaphoid carpal fractures occur more frequently than previously reported and demonstrate variable age distribution, treatment rates, and nonunion risks. Understanding these patterns can improve diagnosis, guide treatment planning, and inform patient expectations. IV.

Abstract Background Even for experienced operators, endovascular treatment of unruptured intracranial aneurysms involves intraoperative uncertainty that may lead to adjustments in strategy, prolong the procedure, and potentially cause inefficiency and device waste. This study aimed to evaluate whether pre-procedural testing (PPT) of endovascular treatment using patient-specific models was associated with increased operator confidence and perceived clinical utility, including improvements in procedural efficiency and reduced resource waste. Methods We enrolled a cohort of patients who underwent PPT before endovascular treatment for complex unruptured intracranial aneurysms and compared their outcomes with a control group treated without PPT. The primary outcome was the Training Fidelity Score, a composite of three operator-reported Likert items defined a priori. Secondary outcomes included perceived clinical utility, intraoperative strategy changes, procedural time, radiation exposure, device waste and safety. Results A total of 85 patients met the inclusion criteria (PPT=40; control=45). The Training Fidelity Score was high across the PPT group (median, 4.33/5). Perceived clinical utility was high and further increased significantly after the procedure. A significant reduction was observed in intraoperative strategy changes, with no changes recorded in the PPT group, compared to 6/45 in the control group (RR 0.09; p=0.027). Reductions in treatment time, radiation exposure and device waste were also noted. Conclusion PPT using patient-specific models was associated with increased operator confidence, fewer intraoperative strategy changes, improved procedural efficiency, and reduced device waste without compromising safety. These findings support its use in pre-interventional preparation, but require prospective multicenter validation.