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Objectives: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality.Design: Secondary analysis of three prospective, observational, multicenter studies.Setting: Cohort studies conducted in 2004, 2010, and 2016.Patients: Adult patients who received mechanical ventilation for more than 12 hours.Interventions: None.Measurements and Main Results: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma.Conclusions: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease. [ABSTRACT FROM AUTHOR]

Depression onset during and after pregnancy is prevalent and associated with significant implications for maternal, child, and family health. Although environmental risk factors important to the expression of pregnancy-related depression are well known, knowledge of the genetic underpinning is limited. Given the joint contribution of environmental and genetic factors to depression risk liability, DNA methylation presents itself as an ideal biomarker to investigate basic mechanisms and opportunities for translational research to care for pregnancy-related depression health outcomes. This article is an introduction to DNA methylation and its potential to serve as a marker of depression risk during pregnancy and the postpartum. This commentary discusses current clinical uses of DNA methylation–based testing and how it may be applied to perinatal depression clinical care and management. [ABSTRACT FROM AUTHOR]

Background--Central obesity, defined by increased waist circumference or waist:hip ratio (WHR), is associated with increased cardiovascular events, including heart failure. However, the pathophysiological link between central obesity and adverse cardiovascular outcomes remains poorly understood. We hypothesized that central obesity and larger WHR are independently associated with worse cardiac mechanics (reduced left ventricular strain and systolic [s'] and early diastolic [e'] tissue velocities). Methods and Results--We performed speckle-tracking analysis of echocardiograms from participants in the Hypertension Genetic Epidemiology Network (HyperGEN) study, a population- and family-based epidemiological study (n=2181). Multiple indices of systolic and diastolic cardiac mechanics were measured. We evaluated the association between central obesity and cardiac mechanics using multivariable-adjusted linear mixed-effects models to account for relatedness among participants. The mean age of the cohort was 51±14 years, 58% were women, and 47% were black. Mean body mass index was 30.8±7.1 kg/m², waist circumference was 102±17 cm, WHR was 0.91±0.08, and 80% had central obesity based on waist circumference and WHR criteria. After adjusting for multiple potential confounders (including age, sex, race, physical activity, body mass index, heart rate, smoking status, systolic blood pressure, fasting glucose, total cholesterol, antihypertensive medication use, glomerular filtration rate, left ventricular mass index, wall motion abnormalities, and ejection fraction), central obesity and WHR remained associated with worse global longitudinal strain, early diastolic strain rate, s' velocity, and e' velocity (P<0.05 for all comparisons). There were no significant statistical interactions between WHR and obesity status. Conclusions--In this cross-sectional study of participants with multiple comorbidities, central obesity was found to be associated with adverse cardiac mechanics. [ABSTRACT FROM AUTHOR]

Chronic elevation of sympathetic nervous system is a key factor in metabolic syndrome. Because renal denervation (RDN) is thought to modulate sympathetic activity, we performed the Denervation of the Renal Arteries in Metabolic Syndrome (DREAMS)-study to investigate the effects of RDN on insulin sensitivity and blood pressure (BP) in patients with metabolic syndrome. Twenty-nine patients fulfilling the criteria for metabolic syndrome and who used a maximum of 1 antihypertensive or 1 antidiabetic drug or 1 of both gave informed consent and were treated by RDN. Glucose tolerance tests and 24-hour ambulatory BP measurements were performed at baseline, at 6 and 12 months of follow-up. Moreover, we performed self-monitored BP measurements at home every month. To assess sympathetic activity, we performed muscle sympathetic nerve activity and heart rate variability measurements at baseline and follow-up. The majority of the included patients was men (57%), mean body mass index was 31±5 kg/m(2). Median insulin sensitivity as assessed by the Simple Index assessing Insulin Sensitivity oral glucose tolerance test did not change at 6- and 12-month follow-up (P=0.60 and P=0.77, respectively). Mean 24-hour BP decreased by 6±12/5±7 mm Hg 12 months after RDN (P=0.04/0.01). However, self-monitored BP measurements data showed no reduction over time. Measurements of sympathetic activity showed no reduction in systemic sympathetic activity. In conclusion, RDN did not lead to a significant improvement of insulin sensitivity ≤12 months after treatment. Although a significant reduction in ambulatory BP was observed in this nearly drug-naïve population, the self-monitored BP measurements data suggest that this may be explained by regression to the mean. Moreover, no effect in systemic sympathetic activity was observed. [ABSTRACT FROM AUTHOR]

Abstract: This study examined the functional and psychological outcomes of a 2-week, group-based multicomponent treatment course that targeted patients with chronic widespread pain. Patients (192 included in the intention-to-treat population), all fulfilling the 1990 American College of Rheumatology classification criteria for fibromyalgia, were consecutively recruited from a tertiary care setting and randomized (1:1) to either the treatment course or a waiting list control group. Co-primary outcomes were the Assessment of Motor and Process Skills (AMPS) and SF-36 Mental Composite Score (MCS) evaluated at 6-month follow-up. Primary endpoints were partly achieved with a statistically significant improvement in AMPS activities of daily living motor (group mean difference: 0.20 [95% confidence interval (CI): 0.09 to 0.31] logits; P =.0003) and AMPS activities of daily living process (0.20 [95% CI: 0.12 to 0.27] logits, P <.0001) ability measures, whereas no difference in the SF-36 MCS (1.14 [95% CI: −1.52 to 3.81], P =.40) was observed. Individual patient responses varied, and the proportion of patients achieving a clinically meaningful change of at least 0.3 logits on the AMPS seemed influenced by the reporting of a pending social welfare application at the time of enrollment. We conclude that even in fibromyalgia patients presenting with a substantial disability established over many years, the 2-week multicomponent treatment course resulted in observable improvement of functional ability in a subgroup of patients at 6-month follow-up. This improvement, however, was not reflected in secondary patient reported outcomes, including scores of self-reported functional ability on standardized questionnaires. We suggest including observation-based assessments in future clinical trials focusing on functional outcomes in patients with fibromyalgia. [Copyright &y& Elsevier]

The article presents a study which investigates the Dutch experience of kidney transplantation through a pediatric donation after cardiac death (DCD). It notes that all patients who experienced pediatric DCD kidney transplantations in the transplant center in the Netherlands from January 1995 to July 2006 were examined. The results suggest that kidneys from pediatric DCD are safe for transplantation and could significantly contribute to good transplant outcomes

Background and Objectives: Post-ischemic stroke (IS) outcomes vary widely among individuals, independently of clinical factors. This variability could be related to epigenetic mechanisms that regulate biological processes involved in recovery after ischemia. While several microRNAs (miRNAs) and their target genes are implicated in the pathophysiology of IS, their role in functional outcomes remains unclear. Our aim is to identify potential miRNAs associated with the 3-month outcome in patients with IS., Methods: A discovery study was performed in patients with acute IS assessed at Hospital del Mar of Barcelona from 2009 to 2018. Main inclusion criteria were initial NIH Stroke Scale (NIHSS) score >2, hospital admission within 24 hours of IS onset, and previous functional independence. Poor 3-month outcome was defined as a modified Rankin Scale score >2. We performed miRNA next-generation sequencing on plasma samples obtained within 24 hours and performed a differential expression analysis for 2,083 miRNAs using the DESeq2 package. A replication stage was performed using real time-PCR in another multicenter cohort, with equivalent inclusion criteria and multivariate regression models. We also performed enrichment pathways analyses in both phases., Results: The discovery cohort included 215 patients with IS (mean age 74.7 ± 10.2 years, 54.9% male). Age, sex, and stroke severity (measured with the 24-hour NIHSS) were associated with the 3-month outcome ( p < 0.05). After adjusting for these potential confounders, we found 74 miRNAs significantly associated ( Q < 0.05) with the 3-month poor outcome. Pathway analysis revealed significant associations with pathways related to angiogenesis, neuronal morphogenesis, transforming growth factor β (TGF-β), endothelial development, and cognition. The replication included 191 patients (mean age 78.0 ± 6.0 years, 49.7% male). We analyzed 26 miRNAs selected from the discovery stage, and 5 miRNAs replicated their association with poor outcomes ( p < 0.05, fold change >1.7): miR-376c-3p, miR-4463, miR-199a-3p, miR-584-5p, and miR-134-5p., Discussion: We identified 5 miRNAs overexpressed in patients with poor 3-month outcomes after IS, which could be involved in biological processes such as cognition, neuronal morphogenesis, and TGF-β response, suggesting a potential role in brain recovery. These findings were not evaluated in infratentorial and lacunar strokes, which limits generalizability in these particular subtypes. Further investigation is needed to explore potential applicability of these findings.

Objectives: Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers. Core outcome sets for specific subsets of ICU patients exist, for example, respiratory failure, delirium, and COVID-19, but not for ICU patients in general. Accordingly, we aimed to develop a core outcome set for adult general ICU patients., Design: We developed a core outcome set in Denmark following the Core Outcome Measures in Effectiveness Trials Handbook. We used a modified Delphi consensus process with multiple methods design, including literature review, survey, semi-structured interviews, and discussions with initially five Danish research panels. The core outcome set was internationally validated and revised based on feedback from research panels in all countries., Setting: There were five Danish research panels and 17 panels in 13 other countries. Interviews and the three-round Delphi survey was conducted in Denmark, followed by validation of the core outcome set across 14 countries in Europe, Australasia, and India., Subjects: Adult ICU survivors, family members, clinicians, and researchers., Interventions: None., Measurements and Main Results: We identified 329 published outcomes, of which 50 were included in the 264 participant Delphi survey. In semi-structured interviews of 82, no additional outcomes were added. The first Delphi survey round was completed by 249 (94%) participants, and 202 (82%) contributed to the third and final round. The initial core outcome set comprised six outcomes. International validation involved 217 research panel members and resulted in the final core outcome set comprising survival, free of life support, free of delirium, out of hospital, health-related quality of life, and cognitive function., Conclusions: We developed and internationally validated a core outcome set with six core outcomes to be used in research, specifically clinical trials involving adult general ICU patients., Competing Interests: Drs. Kjær’s and Granholm’s institutions received funding from Sygeforsikringen and the Novo Nordisk Foundation. Dr. Kjær’s institution received funding from the Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond, Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, and Dagmar Marshalls Fond; they received support for article research from the National Institutes of Health. Dr. Drnaholm’s institution received funding from the Independent Research Fund Denmark. Dr. Laerkner received funding from National Health and Medical Research Council (NHMRC) Investigator Fellowship (GNT2017081), The George Institute for Global Health, and the Fiona Stanley Hospital Intensive Care Unit; they received support for article research from Sygeforsikringen, the Novo Nordisk Foundation, Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond, Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, and Dagmar Marshalls Fond. Dr. Sivapalan received funding from Rigshospitalet, the Ehrenreich Foundation, Sygeforsikringen, the Novo Nordisk Foundation, Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond, Savværksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, and Dagmar Marshalls Fond. Dr. Wise’s institution received funding from the National Institute of Health and Care Research National Institute for Health and Care Excellence (NICE) Rolling Call (health technology assessment programme). Dr. Hästbacka received funding from Paion. Dr. Litton received support for article research from the NHMRC Investigator Fellowship. Dr. Jha’s institution received funding from Astra Zeneca, Ousuka, and Visterra; he received funding from Visterra, Vera Therapeutics, Biocryst, Chinook, Alpine, GlaxoSmithKline (GSK), Astra Zeneca and Boehringer Ingelheim. Dr. Venkatesh received funding from the NHMRC Leadership Fellowship and Baxter. Dr. Collet’s institution received funding from Dagmar Marshall Fond. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Postoperative acute kidney injury (AKI) after major abdominal surgery leads to poor outcomes. The Hypotension Prediction Index (HPI) may aid in managing intraoperative hemodynamic instability. This study assessed if HPI-guided therapy reduces moderate-to-severe AKI incidence in moderate-to-high-risk elective abdominal surgery patients., Methods: This multicenter randomized trial was conducted from October 2022 to February 2024 across 28 hospitals evaluating HPI-guided management compared to a wide range of real-world hemodynamic approaches. 917 patients (≥65 years or >18 years with ASA status >II) undergoing moderate-to-high-risk elective abdominal surgery were included in the intention-to-treat analysis. HPI-guided management triggered interventions when the HPI exceeded 80, using fluids and/or vasopressors/inotropes based on hemodynamic data. The primary outcome was the incidence of moderate-to-severe AKI within the first 7 days after surgery. Secondary outcomes included overall complications, the need for renal replacement therapy, duration of hospital stay, and 30-day mortality., Results: Median age was 71 years (IQR, 65-77) in the HPI group and 70 years (IQR, 63-76) in standard care group. ASA status III/IV was 58.3% (268/459) in the HPI group and 57.9% (263/458) in standard care group. The incidence of moderate-to-severe AKI was 6.1% (28/459) in the HPI group and 7.0% (32/458) in the standard care group (RR 0.89, 95% 0.54-1.49; P=0.66). Overall complications occurred in 31.9% (146/459) of the HPI group and 29.7% (136/458) of the standard care group (RR 1.08, 95% CI 0.85-1.37; P = 0.52). The incidence of renal replacement therapy did not differ between groups. Median length of hospital stay was 6 days (IQR, 4-10) in both groups. The 30-day mortality was 1.1% (5/459) in the HPI group versus 0.9% (4/458) in standard care group (RR 1.35, 95% CI 0.36-5.10; P = 0.66)., Conclusions: HPI-guided hemodynamic therapy did not reduce the incidence of postoperative AKI or overall complications compared to standard care., Clinicaltrialsgov Identifier: NCT05569265., Competing Interests: Conflicts of Interest: Dr Ripollés-Melchor reports personal fees from Edwards Lifesciences, Bazter and Fresenius Kabi outside the submitted work. Dra. Colomina reports personal fees from Octapharma AG (Lachen, Switzerland), Fresenius Kabi España and CSL Vifor España, S.L. outside the submitted work. Dr .Lorente reports personal fees from Edwards Lifesciences, bioMérieux. Fresenius Kabi, Grifols, Vifor Pharma and Baxter outside the submitted work. Dr. Carrasco-Sánchez reports personal fees from Edwards Lifesciences outside the submitted work. Dr. Navarro-Pérez reports personal fees from Edwards Lifesciences outside the submitted work. Dr. Navarro-Pérez reports personal fees from Edwards Lifesciences outside the submitted work. Dr. Pedregosa-Sanz reports personal fees from Edwards Lifesciences outside the submitted work. Dr. Monge-García reports personal fees from Edwards Lifesciences outside the submitted work. The other authors declare no competing interests., (Copyright © 2025 American Society of Anesthesiologists. All Rights Reserved.)

Abstract: Chronic pain is a serious and prevalent condition that can affect many facets of life. However, uncertainty remains regarding the strength of the association between chronic pain and death and whether the association is causal. We investigate the pain-mortality relationship using data from 19,971 participants aged 51+ years in the 1998 wave of the U.S. Health and Retirement Study. Propensity score matching and inverse probability weighting are combined with Cox proportional hazards models to investigate whether exposure to chronic pain (moderate or severe) has a causal effect on mortality over a 20-year follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) are reported. Before adjusting for confounding, we find a strong association between chronic pain and mortality (HR: 1.32, 95% CI: 1.26-1.38). After adjusting for confounding by sociodemographic and health variables using a range of propensity score methods, the estimated increase in mortality hazard caused by pain is more modest (5%-9%) and the results are often also compatible with no causal effect (95% CIs for HRs narrowly contain 1.0). This attenuation highlights the role of confounders of the pain-mortality relationship as potentially modifiable upstream risk factors for mortality. Posing the depressive symptoms variable as a mediator rather than a confounder of the pain-mortality relationship resulted in stronger evidence of a modest causal effect of pain on mortality (eg, HR: 1.08, 95% CI: 1.01-1.15). Future work is required to model exposure-confounder feedback loops and investigate the potentially cumulative causal effect of chronic pain at multiple time points on mortality., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Adequate nurse staffing is crucial for quality healthcare, necessitating accurate predictions of patient arrival rates. These forecasts can be determined using supervised machine learning methods. Optimization of machine learning methods is largely about minimizing the prediction error. Existing models primarily utilize data such as historical patient visits, seasonal trends, holidays, and calendars. However, it is unclear what other features reduce the prediction error. Our systematic literature review identifies studies that use supervised machine learning to predict patient arrival numbers using nontemporal features, which are features not based on time or dates. We scrutinized 26 284 studies, eventually focusing on 27 relevant ones. These studies highlight three main feature groups: weather data, internet search and usage data, and data on (social) interaction of groups. Internet data and social interaction data appear particularly promising, with some studies reporting reduced errors by up to 33%. Although weather data are frequently used, its utility is less clear. Other potential data sources, including smartphone and social media data, remain largely unexplored. One reason for this might be potential data privacy challenges. In summary, although patient arrival prediction has become more important in recent years, there are still many questions and opportunities for future research on the features used in this area., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Clinical trials of treatments for stroke have generally utilized 2-arm, randomized designs to evaluate a single intervention against a control. Running separate clinical trials, with each addressing a single therapeutic question, is resource intensive and slows evidence generation, especially in a field with rapidly expanding treatment options and evolving practices. Platform trials-randomized clinical trials designed to evaluate multiple interventions that may enter and exit the ongoing platform based on a master protocol-accelerate the investigation of multiple therapeutic options within a single infrastructure. This in turn has the potential to accelerate access to new interventions for patients with stroke that can save lives and improve outcomes. In the context of acute ischemic stroke, 2 new platform trials have been established, the STEP trial (StrokeNet Thrombectomy Endovascular Platform) and ACT-GLOBAL (A Multi-Factorial, Multi-Arm, Multi-Stage, Randomised, Global Adaptive Platform Trial for Stroke), to address multiple therapeutic questions simultaneously using a multifactorial design including Bayesian modeling and other adaptive features. These trials are designed to maximize the information obtained from each participant, to align clinical research more closely with the complexities of clinical care, and to accelerate the identification of effective therapies. This article explores conceptual, practical, and statistical considerations in the design and implementation of adaptive platform trials and highlights their potential to accelerate the identification of new therapies, management, and rehabilitation in stroke., Competing Interests: Drs Lorenzi and Crawford report employment by Berry Consultants LLC. Dr Anderson reports grants from the National Health and Medical Research Council, compensation from AstraZeneca Australia for consultant services, and grants from Medical Research Foundation of the United Kingdom to other. Dr Menon reports compensation from Boehringer Ingelheim for consultant services, employment by the University of Calgary, and stock options in Neurostasis. E. Mistry reports grants from the National Institute of Neurological Disorders and Stroke; compensation from the American Heart Association for consultant services; compensation from AbbVie for consultant services; grants from the Patient-Centered Outcomes Research Institute; compensation from Silver Creek Pharmaceuticals, Inc, for other services; compensation from Translational Sciences for other services; grants from the Society of Vascular and Interventional Neurology; compensation from RAPID AI for consultant services; grants from the National Institutes of Health; and employment by the University of Cincinnati. Drs Khatri, Elm, and Beall report grants from the National Institutes of Health. Dr Saville reports an ownership stake in Adaptix Trials. Dr Berry reports part ownership of Consultants LLC. Dr Lewis reports employment by the Journal of the American Medical Association and employment by Berry Consultants LLC. Berry Consultants LLC is a consulting company specializing in the design, conduct, oversight, and analysis of adaptive and platform clinical trials. Employees of Berry Consultants are involved in the design of STEP (StrokeNet Thrombectomy Endovascular Platform) and ACT-GLOBAL (A Multi-Factorial, Multi-Arm, Multi-Stage, Randomised, Global Adaptive Platform Trial for Stroke), which are referenced in this review. The other author reports no conflicts.

Objective: To characterize the extent of private equity (PE) investment affecting surgical care., Background: Over the last decade, investor-backed, for-profit PE groups have invested in health care at an unprecedented rate, but the breadth of these investments affecting surgical practice remains largely unknown., Methods: Four nationally representative databases were used to identify all merger/acquisitions involving surgical practices between 2015 and 2019, determine PE investment in those transactions, and link the acquisitions with a physician data set., Results: A total of 1542 unique transactions were identified, of which 539 were financed by PE. Fifty-eight transactions were then classified into their respective categories within surgical care: digestive disease, orthopedics, urology, vascular surgery, and plastic/cosmetic surgery. These transactions accounted for 199 practice sites and 1405 physicians, averaging 24.2 physicians per transaction. Acquisition activity peaked in 2017, with a total of 63 practices involved. Digestive disease, urology, and orthopedic surgery accounted for the most activity. General surgeons were involved in a small share of the digestive disease practice acquisitions. Three "surgery-adjacent" categories were also identified: anesthesiology, ambulatory surgery centers, and surgical staffing firms. Among these, anesthesia was the largest category in terms of practices (194) and physicians (2660) involved in transactions across the study period. Medical Service Organizations were a key mechanism through which PE firms invested in surgical care., Conclusions: PE has engaged in substantial investment within surgical specialties, creating increased practice consolidation. These investments affect all levels of medical care and have notable implications for patients, practitioners, and policymakers., Competing Interests: D.B. is a past board member and equity owner of BioStar Ventures, LLC and Assembly Ventures, LLC (venture capital firms). J.B.D. is a co-founder and equity owner of ArborMetrix Inc. K.R.C. receives consulting fees from GI Windows Inc., a surgical device company unrelated to the submitted work. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Background: Acute infections and sepsis are a leading cause of death. These patients are primarily encountered at the emergency department (ED), where early assessment for sepsis is necessary to improve outcome. In sepsis, the inflammatory response causes several characteristic pathophysiological changes, including a dysregulated and generalized activation of the endothelium. This study aimed to analyze endothelial markers released to the blood as diagnostic biomarkers for acute infection and sepsis in the ED, as smaller studies have previously shown promising results in other settings. Methods : Serum samples from n = 312 adult patients with suspected acute infections at presentation to the ED were utilized. Patients' courses of disease and outcomes were assessed by clinical adjudication. E-selectin, P-selectin, ICAM-1, and VCAM-1 were measured by ELISAs. The accuracy of each marker for predicting bacterial infection, sepsis, and in-hospital mortality was evaluated. Results : For sepsis, E-selectin and ICAM-1 both showed an area under the receiver operating characteristic (AUROC) of 0.62, lower than procalcitonin with 0.77 (both P < 0.01) and lactate with 0.73 ( P = 0.030 and 0.046, respectively), but similar to CRP with 0.60 ( P = 0.758 and 0.876, respectively). For 28-day in-hospital mortality among patients with infection, ICAM-1 performed best with an AUROC of 0.75. Conclusions : Despite promising results in small studies and specific cohorts, particularly in intensive care units, this large-scale evaluation of four endothelial biomarkers highlights their limited diagnostic utility in a broader inclusion setup design at the earliest possible time point of evaluation., (Copyright © 2024 by the Shock Society.)

The latest research on socioeconomic status (SES) and stroke continues to demonstrate that individuals with low SES are at a higher risk of stroke, receive lower-quality care, and experience poorer outcomes. Despite growing evidence on the impact of SES on stroke, gaps remain in understanding the underlying mechanisms and the influence of SES in different contexts, particularly in low- and middle-income countries. This narrative review builds upon our previous reviews from 2006 to 2015, focusing on studies published since 2015 to update on the influence of SES on stroke. Reports from nationwide or population-based observational studies in the past decade have confirmed that these inequalities persist globally and have provided new evidence on their mechanisms. In high-income countries, inadequate control of cardiovascular risk factors (hypertension, diabetes, obesity, and dyslipidemia) among lower socioeconomic groups has been found to explain much of the inequality in stroke risk. Exposure to particulate air pollution (both environmental and indoor from solid fuel cooking) synergizes with cardiovascular risk factors, especially hypertension, as major causes in low- and middle-income countries. Lower SES is persistently associated with disparities in care and increased poststroke disability and mortality. Lower SES also exacerbates other causes of health inequality among women, ethnic minorities, and migrants. Addressing stroke inequalities requires an interdisciplinary approach. Targeting cardiovascular risk factors, providing equitable quality of acute and rehabilitative stroke care, enacting legislative measures, and implementing societal changes remain leading global priorities.

Background and Importance: Elderly patients often have atypical clinical presentations. Lactate measurement on arrival at the Emergency Department (ED) could be useful to identify elderly patients with a bad prognosis., Objective: The study aimed to investigate the relationship between serum lactate determined at ED arrival and the probability of inhospital mortality and intensive care (ICU) admission in elderly patients., Design: Retrospective multipurpose registry. Secondary analysis of the EDEN cohort (Elderly Department and Elder Needs)., Settings and Participants: All patients ≥65 years attending 52 Spanish EDs during 2 week and in whom serum lactate was determined at ED arrival., Outcome Measures and Analysis: The relationship between serum lactate values and the risk of inhospital all-cause death and transfer from the ED to the ICU was assessed by unadjusted and adjusted logistic regression assuming linearity and restricted cubic spline models assuming nonlinearity., Results: The cohort included 25 557 patients. The 3024 patients in whom lactate was measured were analyzed. The median age was 81 years (74-87), 1506 (27.2%) were women, 591 (19.5%) had serious comorbidities, 475 (15.7%) severe dependency, and 648 (21.4%) dementia. Death occurred during hospitalization in 217 patients (7.2%) and 53 patients (1.75%) were admitted to the ICU. Serum lactate values were nonlinear related to inhospital mortality and ICU admission. Serum lactate >3.1 mmol/L [odds ratio (OR): 1.60, 95% confidence interval (CI): 1.02-2.50] for inhospital mortality and 3.2 mmol/L (OR: 2.83, 95% CI: 1.03-6.79) for ICU admission were associated with significantly increased ORs in the adjusted models., Conclusion: Serum lactate measured at ED arrival has a significant and exponential relationship with inhospital mortality and ICU admission in elderly patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aimed to estimate the risk of malignancy associated with ixekizumab in randomized controlled trials (RCTs) and long-term extension studies (LTEs) in patients with rheumatological indications., Methods: A systematic review of the literature up to June 2024 was performed to analyze the risk of malignancy associated with ixekizumab use in patients with psoriatic arthritis and axial spondyloarthritis. The primary endpoint was overall malignancy risk in RCTs and LTEs. Meta-analyses of RCTs were performed when at least 3 studies had comparable outcome measures using Peto odds ratios. For LTEs, meta-analyses were performed using random-effects computing incidence rates (IRs) per 100 patient-years., Results: Twelve articles, 4 LTEs and 8 pooled analyses, were included. Meta-analyses of RCTs for malignancy risk at week 24 showed a Peto odds ratio of 0.45 (0.11-1.86), with an I2 of 43.0%. When stratified according to the comparator, heterogeneity decreased. Malignancy risk comparing ixekizumab with placebo was 1.43 (0.18-11.53), with an I2 of 39.6%. Malignancy risk comparing ixekizumab with adalimumab was 0.11 (0.01-0.77), with an I2 of 0%. At week 52, the IR of all malignancies with ixekizumab was 0.31 (0.07-0.72), with an I2 of 18.9%. At 156 weeks, the IR of all malignancies with ixekizumab was 0.58 (0.29-0.96), with an I2 of 0%., Conclusion: Ixekizumab appears to confer a low malignancy risk in patients treated for rheumatological indications. Patients with psoriatic arthritis and axial spondyloarthritis appeared to be at similar risk, except for those with nonmelanoma skin cancer., Competing Interests: The authors declare no conflict of interest. All authors have completed and submitted the International Committee of Medical Journal Editors Form for the Disclosure of Potential Conflicts of Interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes., Methods: Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers. Electrophysiological study, imaging, and outcomes data after ablation were assessed in relation to genotype., Results: Seventy-one patients were included (49.6 Q1-Q3 [40-60] years, 76% men). They were divided into 4 groups according to the affected protein: desmosomal ( DSP , PKP2 , DSG2 , and DSC2 ), nuclear membrane ( LMNA and TMEM43 ), cytoskeleton ( FLNC and DES ), and sarcoplasmic reticulum ( PLN ). Desmosomal genes, TMEM43 , and PLN were associated with biventricular disease, while variants in LMNA and cytoskeleton genes had predominant left ventricle involvement ( P =0.001). The location of the clinical-SMVT substrate was significantly different based on genotype ( P =0.005). DSP and cytoskeleton genes presented SMVTs with right bundle branch block morphology, which origin was identified in the inferolateral segments of the left ventricle. The other desmosomal genes ( PKP2 and DSG2 ), along with TMEM43 , showed SMVTs with left bundle branch block morphology and predominantly right ventricular substrate. In contrast, LMNA substrate was mainly observed in the interventricular septum. During a median of 26 Q1-Q3 (10.6-65) months, 27% of patients experienced recurrences of clinical SMVT with differences between genotypes (log-rank 0.016). Nuclear membrane genes demonstrated the highest recurrence rate compared with desmosomal genes (hazard ratio, 4.56 [95% CI, 1.5-13.8])., Conclusions: The anatomic substrate of SMVTs shows a strong correlation with the underlying genotype, electrocardiographic morphology, and recurrence rate. Particularly, patients with nuclear membrane gene variants have a significantly higher recurrence rate compared with those with desmosomal gene variants., Competing Interests: None.