Search Results for: La nevralgia post-erpetica

Introduction
Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, readmission and failed nutritional recovery. Current management approaches fail to sufficiently promote convalescence after inpatient nutritional rehabilitation. Novel interventions during the post-discharge period could enhance convalescence to help children survive and thrive.

Methods and analysis
The Co-SAM trial is an adaptive, multicountry, phase III, individually randomised clinical trial, based on the principles that (i) interacting biological and social factors drive multimorbidity in children with SAM, and (ii) both medical and psychosocial interventions may therefore ameliorate underlying causal pathways to reduce morbidity and mortality and improve recovery. Children aged 6–59 months with complicated SAM, who have stabilised and started the transition to ready-to-use therapeutic food (RUTF), will be enrolled and randomised to one of five trial arms (standard-of-care alone; antimicrobials; reformulated RUTF; psychosocial support; or a combination of all strategies). Standard-of-care, which is provided in all trial arms, includes RUTF until nutritional recovery (defined as weight-for-height Z-score >–2, mid-upper arm circumference >12.5 cm and oedema-free since the last study visit), and other management recommended in WHO guidelines. The 12-week antimicrobial package provides daily co-formulated rifampicin and isoniazid (with pyridoxine) and 3 days of azithromycin monthly. The reformulated RUTF, which incorporates medium-chain triglycerides and hydrolysed protein to increase nutrient bioavailability and reduce metabolic stress, is provided at the same dose and duration as standard RUTF. The 12-week psychosocial package includes caregiver problem-solving therapy, educational modules, peer support groups and child play. The combined arm includes all interventions. Children start their intervention package prior to hospital discharge, with follow-up data collection in study clinics at 2, 4, 6, 8, 12 and 24 weeks. The primary composite outcome is death, hospitalisation or failed nutritional recovery within 24 weeks post-randomisation. An interim analysis will allow unpromising arms to be dropped, while the final analysis will be conducted when 1266 children have completed the study. Embedded process evaluation and laboratory substudies will explore the mechanisms of action of the interventions.

Ethics and dissemination
The trial has been approved by ethics committees in Zimbabwe, Zambia, Kenya and UK. Dissemination will be via community advisory boards in each country; Ministries of Health; and dialogue with policymakers including UNICEF.

Trial registration number
Clinicaltrials.gov: NCT05994742; Pan African Clinical Trials Registry: PACTR202311478928378.

Introduction
Post-traumatic stress disorder (PTSD) is a serious disorder that burdens individuals and society. The current standard of first-line treatment for PTSD is spaced trauma-focused treatment (S-TFT), involving weekly sessions. While effective, S-TFT may take relatively long to complete, especially in patients exposed to multiple potentially traumatic events (PTEs). Massed trauma-focused treatment (M-TFT), involving increased session frequency, potentially results in faster symptom reduction and restoration of quality of life, as well as in a reduction of societal costs. However, M-TFT is not recommended as first-line treatment. This paper describes the research protocol of a single-blind, multicentre randomised controlled trial (RCT) aimed at investigating: (1) the clinical and cost-effectiveness of M-TFT versus S-TFT in employed, multiply traumatised patients who seek first-line treatment for PTSD and (2) predictive and moderating factors related to treatment response.

Methods and analysis
186 participants are recruited from five centres and will be included if they are ≥18 years old, meet criteria for a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition PTSD diagnosis based on ≥two PTEs, seek treatment for the first time and are employed. Patients with specified comorbid disorders and insufficient Dutch language proficiency are excluded. Participants are randomised to 800 min of either M-TFT or S-TFT. M-TFT consists of two once-weekly preparatory sessions, 10 twice-daily sessions of prolonged exposure, eye movement desensitisation and reprocessing therapy for 2 weeks and two once-weekly closing sessions. S-TFT consists of weekly sessions of one of five evidence-based treatment interventions. Outcomes are assessed at baseline and at 7 weeks, 17 weeks, 6 months and 9 months after baseline. Primary outcomes are clinical effectiveness in terms of PTSD symptom severity and cost-effectiveness based on quality of life measures and societal costs. Data will be analysed with linear mixed models.

Ethics and dissemination
This study protocol was approved by the Medical Ethics Review Board of the Amsterdam University Medical Center (NL86057.018.24). Participants will provide informed consent before enrolment in the trial. Results will be published in peer-reviewed journals and will be released to clinicians, patient groups and the general community.

Trial registration number
This protocol is registered at Overview of Medical Research in the Netherlands (OMON; trial register number 56960) and ClinicalTrials.gov (NCT06700590).

Stroke, Ahead of Print. BACKGROUND:Dual antiplatelet drug administration is recommended after percutaneous coronary intervention (PCI) stent placement. Although prasugrel, a newer P2Y12 inhibitor, reportedly suppresses cardiovascular events more effectively than the traditional agent clopidogrel, its preventive effects on cerebrovascular disorders remain a topic of ongoing debate. This study aimed to examine the cerebrovascular efficacy and safety of post-PCI prasugrel and clopidogrel using extensive real-world data in Japan.METHODS:Using the CLIDAS (Clinical Deep Data Accumulation System) database, 7412 post-PCI patients who received dual antiplatelet therapy between April 2013 and March 2019 were identified. The primary end point was defined as the incidence of any stroke, while secondary end points included individual ischemic and hemorrhagic cerebrovascular events. The incidence of cerebrovascular events was compared between the prasugrel (2.5–3.75 mg daily; n=2219) and clopidogrel (75 mg daily; n=5193) groups using propensity-score inverse probability of treatment weighting and Fine and Gray models to account for competing risks.RESULTS:Within 1 year after PCI, the prasugrel group had a significantly lower incidence of cerebrovascular events (subdistribution hazard ratio, 0.46 [95% CI, 0.24–0.91];P=0.027) than the clopidogrel group. The subgroup analyses did not show significant differences in the incidence of ischemic (subdistribution hazard ratio, 0.54 [95% CI, 0.25–1.14];P=0.11) and hemorrhagic cerebrovascular events (subdistribution hazard ratio, 0.30 [95% CI, 0.084–1.10];P=0.070) between the use of prasugrel and clopidogrel. One-year health care costs between patients treated with prasugrel and those treated with clopidogrel showed no significant differences.CONCLUSIONS:Our data suggest that post-PCI prasugrel use was associated with lower cerebrovascular events compared with the use of clopidogrel in combination with aspirin. Further research is necessary to substantiate the potential of prasugrel in lowering cerebrovascular risks after post-PCI while upholding a satisfactory safety profile.

Stroke, Ahead of Print. BACKGROUND:After stroke, impairment of hand sensorimotor control leads to improperly scaled and directed fingertip forces that disrupt object manipulation. The objective of this study was to determine the efficacy of finger force magnitude and direction training using 3-dimensional versus 1-dimensional biofeedback to enhance poststroke upper extremity motor recovery.METHODS:A double-blind randomized controlled trial took place in the Veterans Affairs laboratory from 2020 to 2023. Forty-five stroke survivors were randomly assigned to the experimental or control group. Both groups received 18 training sessions to generate digit force in the target magnitude and direction. The experimental group trained with visual feedback on the digit force magnitude in 3 dimensions. The control group trained with 1-dimensional visual feedback on the digit force magnitude along the target direction only. The primary outcome was the change in upper extremity function assessed using the Action Research Arm Test post-intervention.RESULTS:Baseline characteristics were comparable between the groups (mean age, 59 years, 60% male, 40% Black). The change between pretraining and posttraining Action Research Arm Test scores was significantly greater for the experimental group than for the control group (experimental mean, 3.5 [CI, 2.2–4.8] versus control mean, 0.8 [CI, −0.5 to 2.1];P=0.005). This difference was maintained at 1-month follow-up. Secondary analysis showed that individuals in the experimental group whose stroke occurred within a year prior improved more (mean, 6.1 [CI, 4.0–8.3]) than others (P

Introduction
The effects of bariatric surgery have largely been studied from a medical viewpoint, seeking to measure changes in anthropometric, physiological or quality-of-life factors after the operation. Few studies, however, have focused on the dynamics of lifestyle changes. Yet we know that changing lifestyle habits—which are often part of the established social configurations at the origin of morbid obesity—is essential for a sustainable recovery from obesity. We also know that the major bodily transformations that occur in the six to twelve months following surgery produce a high degree of biographical uncertainty and affect social interactions. From a sociological perspective, the authors propose to study the processes of disruption and re-establishment of lifestyle habits in the first 24 months following bariatric surgery.

Methods and analysis
The ChiBarAPS study relies on a mixed-method longitudinal survey, comprising three components: qualitative, quantitative, literature and data review. It aims to document three main dimensions, which must be articulated to understand the dynamics of change: (1) the work undertaken by patients on themselves in order to identify and measure the evolutionary effects of surgery, as well as to adapt to them; (2) the experience of using pre- and post-surgery information and support systems, and evaluating their effects on the agency of the people who have undergone surgery; (3) the evolution of social participation and lifestyle habits. The qualitative component concerns a cohort of 30 patients, interviewed in depth (2 hours) on these three dimensions, 6 months, 12 months and 24 months after the operation. The quantitative part uses questionnaires applied to a second group of 200 patients, following the same timeline.

Ethics and dissemination
This study complies with reference methodology MR004 of the French National Data Protection Authority and was registered by the Data Protection Officer of the University of Montpellier on the activity registry of the institution (24 April 2024). Ethics approval has been obtained from the University of Montpellier ethics research board (n°UM2024-037). Informed consent will be obtained from all participants before data collection. The project has received funding from the French National Research Agency (n°ANR-23-CE41-0020-01) from February 2024 to the end of January 2028. The first results of the research will be disseminated from 2026 onwards to researchers, health professionals and patient support organisations. The results of the study will then be published in peer-reviewed scientific journals, both national and international.

Introduction
Insomnia is a significant global health issue associated with substantial economic costs. International guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia; however, pharmacotherapy remains more common in clinical practice. Maintaining the effectiveness while reducing the time and frequency of CBT-I is essential for its implementation. We conducted a randomised controlled trial (RCT) to evaluate the effectiveness of a brief behavioural treatment for insomnia (BBTI) that focuses on sleep restriction and stimulus control (SC)—both established as effective standalone interventions. This article presents the study protocol to examine whether adding BBTI to treatment as usual improves outcomes in patients with chronic insomnia.

Methods and analysis
We will conduct a multicentre RCT. We will randomly assign patients with chronic insomnia to two groups (BBTI vs sleep hygiene) in a 1:1 ratio. The BBTI consists of three 15 min sessions over 4 weeks delivered by healthcare professionals following a detailed manual. The primary outcome is the Insomnia Severity Index at 8 weeks. Secondary outcomes include sleep latency, wake after sleep onset, total sleep time, sleep efficiency, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9 and EuroQol-5D-5L. We will conduct the assessment at weeks 0 (baseline), 4 (end of intervention), 8 (post-intervention, primary endpoint) and 12 (follow-up). We will assess each sleep variable from the sleep diary at weeks 0 and 8. The analysis will be performed on an intention-to-treat basis.

Ethics and dissemination
This study has been approved by the Ethics Committee for Clinical and Epidemiological Research of Toyama University (approval no. R2023152).

Trial registration number
UMIN000052911; pre-results.

Dr Emma Nielsen was originally acknowledged in the paper. However, on discussion and reflection, and agreement with Dr Nielsen and all co-authors, we have added Dr Nielsen as a co-author in recognition of their contributions as a full-time post-doc during the first eight months of the study to methodology, investigation and project administration.

Stroke, Ahead of Print. BACKGROUND:Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS:For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS:We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71–84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36–1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03–1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17–3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52–4.84]).CONCLUSIONS:Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03148457.

Objectives
The effect of esketamine on perioperative neurocognitive dysfunction (PND) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of perioperative esketamine administration on PND.

Design
Systematic review and meta-analysis.

Data sources
PubMed, EMBASE, Web of Science and Cochrane Library were searched from their inception to 25 April 2024.

Eligibility criteria for selecting studies
We included the randomised controlled trials (RCTs) that compared single or continuous intravenous infusion of esketamine to saline among adult surgical patients without pre-existing neurocognitive disorders.

Data extraction and synthesis
Two reviewers independently extracted pertinent information from the included studies. Risk of bias was assessed using Cochrane’s risk of bias criteria. Risk ratios (RRs) and their corresponding 95% CIs were synthesised using a random-effects model. The overall evidence quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework.

Results
10 RCTs were included in our meta-analysis, involving 854 surgical patients. Perioperative esketamine was associated with a reduced risk of postoperative delirium (POD) (relative risk (RR): 0.46, 95% CI: 0.30 to 0.71, p

Introduction
Despite the established status of trauma-focused psychotherapy (TFP) as a first-line treatment for post-traumatic stress disorder (PTSD), a substantial proportion of individuals do not achieve clinically significant improvement or discontinue treatment. Exploring augmentation strategies to enhance treatment outcomes is essential to reduce the overall burden PTSD puts on individuals and society. This protocol outlines a systematic review and meta-analysis of randomised controlled trials (RCTs) evaluating the efficacy of non-pharmacological augmentation strategies in addition to TFP for PTSD treatment.

Methods and Analysis
We comprehensively searched PubMed, Embase, CENTRAL, PTSDpubs, PsycArticles, PsycINFO, PSYNDEX and CINAHL for RCTs without restrictions on publication dates or languages in October 2024. Study screening is currently ongoing. Additionally, we will perform forward and backward searches of the included studies and relevant reviews. Two reviewers will independently screen and select studies, extract data and assess the risk of bias. We will conduct a narrative review to qualitatively synthesise data and a meta-analysis to quantitatively compare the treatment efficacy of augmented TFP with TFP alone or TFP plus placebo. Primary outcomes will be both symptom severity and response rates. The secondary outcome will be dropout rates. We will explore sources of between-study heterogeneity and potential moderators through subgroup and meta-regression analyses. We will assess the overall quality of the included studies with the Grading of Recommendations Assessment, Development, and Evaluation system.

Ethics and dissemination
Ethical approval is not required. We intend to publish results in a peer-reviewed journal and provide materials and data through the Open Science Framework.

PROSPERO registration number
CRD42024549435.

Introduction
Intensive care units (ICUs) manage patients with or likely to have one or more life-threatening acute organ failures that might require the use of invasive supportive therapies. The use of physical restraint is frequent, with rates up to 50%, and usually initiated to maintain patient safety especially if the patient is agitated. Physical restraints have been associated with delirium, post-traumatic stress disorder and physical injuries while restricting patients’ individual freedom. Moreover, the incidence of invasive therapeutic devices’ self-removal by patients might not be decreased by physical restraint use. No recommendation is available concerning ICU patients and physical restraint management, despite being a daily practice. The main objective is to evaluate whether a strategy aimed at decreasing physical restraint use in ICU patients with that of a strategy based on routine and subjective caregivers’ decision is safe and efficient.

Methods and analysis
ARBORea is a multicentre randomised, stepped-wedge trial testing an innovative, dedicated web-based, multiprofessionally developed, experts validated, nursing management strategy in comparison with standard care. The primary outcome is physical restraint use rate (effectiveness) measured at least every 8 hours and incidents’ rate (tolerance) defined as the rate of incidents attributable to non-compliance, corresponding to the deterioration or self-removal of critical devices, a fall or self-aggressive or heteroaggressive behaviours. Planned enrolment is 4000 ICU adult participants at 20 French academic and non-academic centres. Safety and long-term outcomes will be evaluated.

Ethics and dissemination
Trial results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines. Findings will be published in peer-reviewed journals and presented at local, national and international meetings and conferences to publicise and explain the research to clinicians, commissioners and service users. The trial is funded by the French Ministry of Health and has been approved by the French local ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse, France with registration number: 2020-A02904-35).

Trial registration number
(ClinicalTrials.gov) NCT04957238 on 12 July 2021 before first inclusion in study.

Objectives
To update our previous systematic review to synthesise latest data on the prevalence of long-term pain in patients who underwent total hip replacement (THR) or total knee replacement (TKR). We aim to describe the prevalence estimates and trends in this review.

Design
Systematic review and meta-analysis.

Data sources
Update searches were conducted in MEDLINE and Embase databases from 1 January 2011 to 17 February 2024. Citation tracking was used to identify additional studies.

Eligibility criteria
We included prospective cohort studies reporting long-term pain after THR or TKR at 3, 6, 12 and 24 months postoperative.

Data extraction and synthesis
Two reviewers independently identified studies as eligible. One reviewer conducted data extraction, checked by a second reviewer. The risk of bias assessment was performed using Hoy’s checklist. Bayesian, random-effects meta-analysis was used to synthesise the results.

Results
For TKR, 68 studies with 89 time points, including 598 498 patients, were included. Multivariate meta-analysis showed a general decrease in pain proportions over time: 21.9% (95% CrI 15.6% to 29.4%) at 3 months, 14.1% (10.9% to 17.9%) at 6 months, 12.6% (9.9% to 15.9%) at 12 months and 14.6% (9.5% to 22.4%) at 24 months. Considerable heterogeneity, unrelated to examined moderators, was indicated by substantial prediction intervals in the univariate models. Substantial loss to follow-up and risk of bias led to low confidence in the results. For THR, only 11 studies were included, so it was not possible to describe the trend. Univariate meta-analysis estimated 13.8% (8.5% to 20.1%) and 13.7% (4.8% to 31.0%) of patients experiencing long-term pain 6 and 12 months after THR, respectively, though concerns in risk of bias results reduced confidence in these findings.

Conclusions
Our review suggests that approximately 22% of patients report pain 3 months post-TKR, with 12%–15% experiencing long-term pain up to 2 years. At least 14% report pain 6–12 months after THR. Given the prevalence of chronic postsurgical pain, implementing existing and developing new preventive and management strategies is crucial for optimal patient outcomes.

PROSPERO registration number
CRD42023475498.

Introduction
Breast cancer is the most common form of cancer in women. A considerable number of women with breast cancer who have been treated with chemotherapy subsequently develop neurological symptoms such as concentration and memory difficulties (also known as ‘chemobrain’). Currently, there are no validated therapeutic approaches available to treat these symptoms. Cognitive training holds the potential to counteract cognitive impairment. Combining cognitive training with concurrent transcranial direct current stimulation (tDCS) could enhance and maintain the effects of this training, potentially providing a new approach to treat post-chemotherapy subjective cognitive impairment (PCSCI). With this study, we aim to investigate the effects of multi-session tDCS over the left dorsolateral prefrontal cortex in combination with cognitive training on cognition and quality of life in women with PCSCI.

Methods and analysis
The Neuromod-PCSCI trial is a monocentric, randomised, double-blind, placebo-controlled study. Fifty-two women with PCSCI after breast cancer therapy will receive a 3-week tDCS-assisted cognitive training with anodal tDCS over the left dorsolateral prefrontal cortex (target intervention), compared with cognitive training plus sham tDCS (control intervention). Cognitive training will consist of a letter updating task. Primary outcome will be the performance in an untrained task (n-back task) after training. In addition, feasibility, safety and tolerability, as well as quality of life and performance in additional untrained tasks will be investigated. A follow-up visit will be performed 1 month after intervention to assess possible long-term effects. In an exploratory approach, structural and functional MRI will be acquired before the intervention and at post-intervention to identify possible neural predictors for successful intervention.

Ethics and dissemination
Ethical approval was granted by the ethics committee of the University Medicine Greifswald (BB236/20). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences.

Trial registration number
ClinicalTrials.gov; NCT04817566, registered on 26 March 2021.

Introduction
Stroke is a leading cause of death and disability worldwide. Stroke survivors and their caregivers often face profound social isolation and various participation restrictions, resulting in frustration and adverse health outcomes. Dyad-focused interventions, which address both survivor and caregiver needs, are essential during the transition process. However, few interventions equally prioritise the outcomes of both survivors and caregivers. This study aims to evaluate the efficacy of a newly developed dyad-focused strategy training intervention in enhancing participation among stroke survivors and their caregivers.

Methods and analysis
This study employs a single-blind, parallel-group randomised controlled trial with allocation concealment and assessor blinding. We aim to enrol 138 stroke survivor-caregiver dyads, randomly assigned in a 1:1 ratio to either the experimental intervention group or the control group. Both groups will receive their usual rehabilitation plus 45–60 min sessions of the intervention twice weekly for a total of 12 sessions. Outcome measures, including the Participation Measure-3 Domains, 4 Dimensions, General Self-Efficacy Scale and Activity Measure for Post-Acute Care, will be collected at baseline, post-intervention and at 3-month, 6-month and 12-month follow-ups. Data will be analysed using multiple linear regression and mixed-effects regression models. Qualitative indepth interviews with participants, caregivers and therapists will be conducted post intervention, transcribed and thematically analysed.

Ethics and dissemination
Ethics approval was obtained from the Ethics Committee of Taipei Medical University (approval number: N202203083), National Taiwan University Hospital (approval number: 202207096RINA) and Taipei Tzu Chi Hospital (approval number: 11 M-107). Findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals.

Trial registration number
NCT05571150; Preresults.

Circulation, Ahead of Print. BACKGROUND:Myocardial ischemia/reperfusion (I/R) injury is a substantial challenge to the management of ischemic heart disease, the leading cause of mortality worldwide. Arachidonic acid (AA) is a prominent polyunsaturated fatty acid in the human body and plays an important role in various physiological and pathological conditions. AA metabolic enzymes determine AA levels; however, currently there is no comprehensive analysis of AA enzymes in cardiac I/R injury.METHODS:The profiling of AA metabolic enzymes was analyzed with the RNA sequencing transcriptome data from the mouse heart tissues with I/R injury. Cultured neonatal and adult rat ventricular myocytes, human embryonic stem cell–derived cardiomyocytes, and in vivo mouse I/R models were used to confirm the role of L-PGDS (lipocalin-type prostaglandin D2 synthase)/15d-PGJ2 in I/R injury. A biotin-tagged 15d-PGJ2 analog combined with liquid chromatography–tandem mass spectrometry was used to identify the downstream signaling of L-PGDS/15d-PGJ2.RESULTS:Based on the transcriptome data and experimental validations, L-PGDS, together with its downstream metabolite 15d-PGJ2, was downregulated in cardiac tissue with I/R injury. Functionally, L-PGDS overexpression mitigates myocardial I/R injury, whereas knockdown exacerbates the damage. Supplementation of 15d-PGJ2 alleviated I/R injury. Mechanistically, 15d-PGJ2 covalently bound to the Ca2+/CaMKII (calmodulin protein kinase II) and induced lipoxidation of its cysteine 495 (CaMKII-δ9) to dampen the formation of CaMKII oligomers and alleviate its overactivation, consequently ameliorating cardiomyocyte death and cardiac injury.CONCLUSIONS:Our study uncovered L-PGDS/15d-PGJ2/CaMKII signaling as a new mechanism underlying I/R-induced cardiomyocyte death. This provides new mechanistic insights and therapeutic targets for myocardial I/R injury and subsequent heart failure. We also showed that lipoxidation is a new post-translational modification type for CaMKII, deepening our understanding of the regulation of its activity.

Stroke, Ahead of Print. Background:Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (.088” inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial.Methods:SUMMIT MAX was a prospective, randomized, controlled, open label clinical trial of patients with ICA and MCA M1 occlusions, comparing the super large bore HiPoint Reperfusion system (Route 92 Medical) to the Vecta Aspiration system (Stryker Neurovascular) (NCT05018650). We hypothesized that the effectiveness and safety of the HiPoint reperfusion system was non-inferior (12.5% non-inferiority margin) to the Vecta Aspiration system. The primary effectiveness endpoint was successful reperfusion, defined as mTICI ≥ 2b as adjudicated by an independent core lab, using only the assigned study device, with any use of a non-study device prior to or following use of study device defined as failure. The primary safety endpoint was symptomatic intracranial hemorrhage (sICH) within 24h (-8/+24) post-procedure.Results:There were 250 patients enrolled of whom 166 met criteria for the modified intent-to-treat population: 89 in HiPoint and 77 in Vecta. The median age was 69; 54.2% were female. Successful reperfusion with any adjunctive therapy counted as a failure was 77.5% (69/89) in the HiPoint group versus 50.6% (39/77) in the Vecta group (p