Acute Treatment Research Articles

Metastatic melanoma: an unexpected cause of acute liver failure.

Acute liver failure secondary to metastatic melanoma is exceedingly rare with the literature limited to case reports. The disease itself presents with vague symptoms making diagnosis difficult without a high clinical suspicion. Further to this, the prognosis of acute liver failure secondary to metastatic melanoma is dismal. We present the case of a 59-year-old male with a distant history of previously excised cutaneous melanoma who presented to our institution with abdominal pain and liver enzyme derangement suggestive of acute hepatitis. Due to progressive derangement in liver function and cross-sectional imaging suggestive of an infiltrative cause, a left axillary lymph node was biopsied which demonstrated metastatic melanoma. The patient subsequently deteriorated into acute liver failure and despite acute treatment of his underlying metastatic melanoma died 17days post initial presentation. This case highlights an uncommon cause of acute liver failure as well as the poor prognosis associated with acute liver failure secondary to metastatic melanoma.

The effects of treatment, clinical and demographic factors on recovery of orientation after ECT: A care network study

BackgroundTime to reorientation after electroconvulsive therapy (ECT) has been shown to predict retrograde amnesia and is a useful measure for monitoring patients over the acute treatment course. This study investigated the effects of treatment, clinical and demographic factors on the recovery of orientation after ECT. MethodsData from 555 ECT patients across two different clinical CARE Network sites were analysed. The main outcome variable was recovery of orientation on the 10-Item Orientation Questionnaire assessed after every ECT treatment. A linear mixed-effects repeated measures model was used to predict the recovery of orientation across the ECT course based on multiple factors, including age, gender, electrode montage, ECT number and frequency, diagnosis, and baseline cognitive impairment. ResultsType of ECT demonstrated a significant effect (F(2, 2341) = 48.414, p = 0.000): individuals who received right unilateral (RUL) ultrabrief ECT or bifrontal ECT had higher orientation scores compared to those who received RUL brief pulse ECT. Older age groups and female patients had lower orientation scores. Baseline global cognitive functioning significantly influenced orientation scores (F(3, 2339) = 43.597, p = 0.000), with individuals with no or mild cognitive impairment exhibiting higher scores. LimitationsThe study involved a retrospective analysis of de-identified data, which may have introduced inherent biases with missing data. ConclusionsThis large-scale retrospective, real-world study showed that recovery of orientation after ECT was most affected by ECT type, though age, gender, and baseline level cognitive impairment also affected outcomes. These findings can inform the interpretation of post ECT orientation scores, facilitating its monitoring and optimisation of patient outcomes.

How Do People Who Undergo Ketamine Treatment for a Psychiatric Problem Subjectively Experience This Intervention? A Meta-Synthesis of Qualitative Studies.

Ketamine treatment has shown promising effects for different mental disorders. Yet, little is known on how people who receive ketamine for a psychiatric problem subjectively experience undergoing this intervention. We conducted a systematic literature search to identify relevant qualitative research on the first-person experience of undergoing ketamine treatment in a psychiatric context. 24 eligible studies were identified and analysed using a thematic meta-synthesis approach. Three main themes were identified. First, 'The Ketamine treatment experience can be understood as a three-stage journey with unique clinical features at each stage'. Second, 'The subjective experience of acute ketamine treatment is multifaceted and complex'. Third, 'Ketamine treatment can have different positive effects-but what happens if it does not work?'. In summary, the subjective experience of receiving ketamine treatment for a psychiatric problem can be understood as a journey whereby patients move towards, then undergo, and eventually depart from ketamine. Before treatment, the experiential focus lies on expectations, hopes, and feelings towards the drug. During treatment, the drug's multifaceted psychotropic effects and how they are emotionally appraised become central to experience. Once treatment is finished, the focus is on the presence or absence of clinically relevant effects. The conceptual framework we propose can guide further qualitative research on this topic and aid mental health professionals to better understand the experience of patients who undergo ketamine treatment for a psychiatric problem.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

Abstract C077: Functional Dissection of the Highly Plastic Basal Cell State in Pancreatic Cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a treatment-refractory malignancy with a dismal prognosis. Targeting cancer cell plasticity—the capacity to adapt to cell-extrinsic pressure via non-genetic mechanisms—is a promising therapeutic strategy, yet cell states within PDAC harboring high plasticity remain poorly understood. Using genetically engineered mouse models driven by oncogenic KrasG12D and loss of p53 (“KPC” model), we profiled primary PDAC tumors using single-cell RNA sequencing and single cell ATAC sequencing. We identified a cancer cell differentiation state that co-expresses both epithelial and mesenchymal programs and has a distinct epigenetic landscape with accessible chromatin across gene sets that mark cancer cell states with divergent phenotypes, suggesting that this cell state is primed for cell state switching. Notably, this high-plasticity cell state (HPCS) signature aligns with a "basal" signature in human PDAC, which associates with poor prognosis and chemoresistance. To functionally interrogate the HPCS in PDAC progression, we developed a novel lineage-tracing and ablation system. Lineage-tracing experiments revealed that the HPCS has a robust capacity for differentiation into epithelial and mesenchymal states, indicating that the HPCS is functionally plastic and acts as a source of fixed malignant states. Strikingly, targeted elimination of the HPCS over short time periods resulted in tumor collapse, underscoring a critical role in tumor maintenance. Further, we found that the HPCS is highly dependent on KRAS activity, with acute KRAS inhibitor treatment leading to a selective depletion of the HPCS. Taken together, our data indicates that PDAC harbors a striking dependency on the HPCS and encourages therapeutic approaches aimed at eradicating this critical subset of cancer cells. Citation Format: Anupriya Singhal, Hannah C. Styers, Jonathan Rub, Zhuxuan Li, Zeynep Tarcan, Jill Hallin, Olca Basturk, Rona Yaeger, James G. Christensen, Doron Betel, Yan Yan, Elisa de Stanchina, Tuomas Tammela. Functional Dissection of the Highly Plastic Basal Cell State in Pancreatic Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C077.

The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way.

Polygala paniculata L. is a native plant from tropical America. The therapeutic potential of the hydroalcoholic extract of P. paniculata (HEPp) has been scientifically explored due to folk medicine reports on its action against several afflictions. HEPp contains several bioactive molecules with neuroprotective activities, making it a promising candidate for stroke treatment. This study used electrophysiological, biochemical, and in vivo experiments to evaluate the molecular mechanisms underlying HEPp as a neuroprotective therapy for stroke targeting Pannexin-1 (Panx1). Panx1 is a non-selective channel that opens during ischemia and contributes to neuronal death. HEPp was not toxic to cortical neurons and pre-treatment with the extract reduced neuronal death promoted by oxygen and glucose deprivation in a dose-dependent manner. Additionally, HEPp blocked Panx1 currents in a dose-dependent manner and the effect, which was shown to be partially due to rutin. Animals submitted to photothrombosis and post-treated with HEPp had reduced infarct volume, and the effective dose was lower in males (1mg/kg) than in females (10mg/kg). On the other hand, in Panx1 KD mice (50% Panx1 levels), the acute treatment reduced the infarct volume only in males. Upon chronic treatment with HEPp, a reduction in Panx1 protein levels was observed. The current study provides reliable evidence of the neuroprotective properties of HEPp in both in vitro and in vivo models of stroke. The underlying mechanism involves, at least in part, the inhibition of Panx1 channel function and possibly downregulation of protein levels, suppressing the secondary events that lead to apoptosis and inflammation.

Sexual dimorphism in physiological responses of turbot (Scophthalmus maximus L) under acute hypoxia and reoxygenation

Dissolved oxygen (DO) is a crucial factor throughout fish life cycle. In this study, the hematology, hepatic antioxidant levels, histomorphology of the liver and gill were determined in both female and male turbot under acute hypoxia to evaluated the underlying mechanisms and potential sexual dimorphism difference. Results showed that acute hypoxia stress treatment for 3 h significantly increased plasma cortisol, glucose, hemoglobin (HGB), cholesterol (CHO), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and hepatic malondialdehyde (MDA) contents, red blood cell count (RBC) number, hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), alanine-aminotransferase (ALT) and aspartate-aminotransferase (AST) activity in both male and female turbot. Male obtained higher plasma CHO, TG and LDL contents, GSH-Px and SOD activity than female under hypoxia. Meanwhile, hypoxia increased gill respiratory frequency, secondary lamellar length, secondary lamellar width, perimeter, lamellar surface area and gill surface area and decreased interlamellar distance. Acute hypoxia induced clubbing, hyperplasia, hypertrophy of gill filaments and hepatic vacuolization in both male and female turbot. The aforementioned parameters were recovered to normal levels after reoxygenation for 12 h. In conclusion, sex dimorphism difference of turbot hematological (RBC, HGB) and biochemical (glucose, CAT, GSH-Px, MDA) parameters were observed under hypoxia stress, while male demonstrated more hypoxia tolerance than female. These results help understand turbot hypoxia tolerance mechanisms and provide more data for management in captivity.

Differential interference with actin-binding protein function by acute Cytochalasin B.

Dynamic actin filament remodeling is crucial for a plethora of fundamental cell biological processes, ranging from cell division and migration to cell communication, intracellular trafficking or tissue development. Cytochalasin B and -D are fungal secondary metabolites frequently used for interference with such processes. Although generally assumed to block actin filament polymerization at their rapidly growing barbed ends and compete with regulators at these sites, our molecular understanding of their precise effects in dynamic actin structures is scarce. Here we combine live cell imaging and analysis of fluorescent actin-binding protein dynamics with acute treatment of lamellipodia in migrating cells with cytochalasin B. Our results show that in spite of an abrupt halt of lamellipodium protrusion, cytochalasin B affects various actin filament barbed end-binding proteins in a differential fashion. Cytochalasin B enhances instead of diminishes the accumulation of prominent barbed end-binding factors such as Ena/VASP family proteins and heterodimeric capping protein (CP) in the lamellipodium. Similar results were obtained with cytochalasin D. All these effects are highly specific, as cytochalasin-induced VASP accumulation requires the presence of CP, but not vice versa , and coincides with abrogation of both actin and VASP turnover. Cytochalasin B can also increase apparent barbed end interactions with the actin-binding β-tentacle of CP and partially mimic its Arp2/3 complex-promoting activity in the lamellipodium. In conclusion, our results reveal a new spectrum of cytochalasin activities on barbed end-binding factors, with important implications for the interpretation of their effects on dynamic actin structures.

IL-1β promotes adipogenesis by directly targeting adipocyte precursors

Postprandial IL-1β surges are predominant in the white adipose tissue (WAT), but its consequences are unknown. Here, we investigate the role of IL-1β in WAT energy storage and show that adipocyte-specific deletion of IL-1 receptor 1 (IL1R1) has no metabolic consequences, whereas ubiquitous lack of IL1R1 reduces body weight, WAT mass, and adipocyte formation in mice. Among all major WAT-resident cell types, progenitors express the highest IL1R1 levels. In vitro, IL-1β potently promotes adipogenesis in murine and human adipose-derived stem cells. This effect is exclusive to early-differentiation-stage cells, in which the adipogenic transcription factors C/EBPδ and C/EBPβ are rapidly upregulated by IL-1β and enriched near important adipogenic genes. The pro-adipogenic, but not pro-inflammatory effect of IL-1β is potentiated by acute treatment and blocked by chronic exposure. Thus, we propose that transient postprandial IL-1β surges regulate WAT remodeling by promoting adipogenesis, whereas chronically elevated IL-1β levels in obesity blunts this physiological function.

The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5), Sildenafil, in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats.

The use of phosphodiesterase inhibitors in the treatment of Parkinson's disease is currently widely discussed. The study aimed to investigate the impact of acute and chronic treatment with the phosphodiesterase 5 inhibitor, sildenafil, at low and moderate doses of 2 mg/kg and 6 mg/kg, and L-DOPA (12.5 mg/kg), alone or in combination, on asymmetric behavior and dopamine (DA) and serotonin metabolism in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Acute administration of sildenafil at both tested doses jointly with L-DOPA significantly increased the number of contralateral rotations during a 2 h measurement compared to L-DOPA alone. The effect of a lower dose of sildenafil combined with L-DOPA was much greater in the second hour of measurement. However, the acute combined administration of a higher dose of sildenafil with L-DOPA resulted in an immediate and much stronger increase in the number of contralateral rotations compared to L-DOPA alone, already visible in the first hour of measurement. Interestingly, the chronic combined administration of 2 mg/kg of sildenafil and L-DOPA significantly reduced the number of contralateral rotations, especially during the first hour of measurement, compared to the long-term treatment with L-DOPA alone. Such an effect was not observed after the long-term combined treatment of a higher dose of sildenafil and L-DOPA compared to L-DOPA alone. The concentration of DA in the ipsilateral striatum and substantia nigra after the last combined chronic dose of sildenafil (2 or 6 mg/kg) and L-DOPA (12.5 mg/kg) was significantly higher than after L-DOPA alone. In spite of much stronger increases in the DA concentration in the ipsilateral striatum and substantia nigra, the number of contralateral rotations was reduced in the group of rats treated with the combination of 2 mg/kg sildenafil and L-DOPA compared to the group receiving L-DOPA alone. Moreover, the combined treatment with a low dose of sildenafil and L-DOPA had an opposite effect on DA catabolism, as assessed by DOPAC/DA and HVA/DA indexes, and these indexes were reduced in the ipsilateral striatum but increased in the contralateral striatum and substantia nigra compared to the treatment with L-DOPA alone. The results of the present study show that the addition of a low dose of a PDE5 inhibitor to the standard L-DOPA therapy differently modulates rotational behavior, the tissue DA concentration and its catabolism in the striatum and substantia nigra.

Predictors of attrition during acute pharmacotherapy of psychotic depression in a clinical trial

Little is known about factors that contribute to attrition in clinical trials of the pharmacotherapy of psychotic depression. The purpose of this study was to identify factors associated with attrition during acute pharmacotherapy in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II) clinical trial. Sociodemographic and clinical variables were assessed at baseline in 269 men and women, aged 18–85 years, who were treated with up to 12 weeks of open-label sertraline plus olanzapine. Univariate analyses examined the association of baseline variables with overall non-completion, as well as reasons for non-completion. Logistic regression was used to model the relationship of the significant univariate predictors with non-completion and its reasons. Seventy-four (27.5 %) participants did not complete the acute treatment phase of STOP-PD II. Male gender, younger age, inpatient status, higher Clinical Global Impression (CGI) severity of illness, and higher severity of psychomotor disturbance were associated with non-completion in univariate analyses. In regression models, higher CGI severity of illness score was the only significant independent predictor of non-completion, explained by withdrawal of consent. Our findings have implications for the retention of persons with psychotic depression in clinical trials.

Young Adult Cancer Patients (AYA): Preferences for Outpatient Psychosocial Care and Gender-Specific Differences - Results from the AYA-LE study

To investigate the importance of individual topics in outpatient care services and the preferences for their design from the perspective of young adults with cancer (AYA="adolescents and young adults") in Germany. A total of 514 AYAs aged 18-39 years were surveyed twice over a 12-month period (t1=immediately after acute treatment, t2=12 months post-treatment) regarding the importance and satisfaction with topics such as anxiety, the impact of the illness on partnerships/family and social environment, future perspectives, personal coping strategies, sexuality, and desire for children/fertility, as well as the types of care services. The subjective importance and satisfaction with the care topics and services were analyzed using variance and moderator analyses. The most important topics for care services were future career prospects (M=3.22, SD=1.56), social impact (M=3.19, SD=1.54), and personal coping strategies (M=3.52, SD=1.46). The greatest dissatisfaction was noted in the areas of sexuality (M=2.01, SD=1.59) and desire for children/fertility (M=2.08, SD=1.72). At time t2, relaxation techniques (M=3.46, SD=1.36) and psychological counseling (M=3.43, SD=1.46) were the most desired care services. Female AYAs rated psychological counseling (F[1.199)=9.21, p=0.003), social counseling (F[1.221]=6.60, p=0.011), creative therapy options (F[1.219]=21.74, p<0.001), support groups (F[1.215]=4.29, p=0.040), patient education (F[1.210]=6.96, p=0.009), and relaxation techniques (F[1.194]=23.68, p<0.001) significantly more important than male AYAs. The study highlighted several areas of dissatisfaction with the current outpatient care services for AYAs. The results demonstrate the need to incorporate cross-sex and gender-specific care preferences of AYAs to improve outpatient psychosocial care. A specific set of AYA-care services should be designed and implemented to address the aforementioned psychosocial topics, which include sexuality and the desire for children/fertility. It is also crucial for outpatient practice to raise awareness among the involved professional groups. Further research is required to gain a deeper understanding of sex differences.

Qualitative Evaluation of a Quality Improvement Collaborative Implementation to Improve Acute Ischemic Stroke Treatment in Nova Scotia, Canada.

The Atlantic Canada Together Enhancing Acute Stroke Treatment (ACTEAST) project is a modified quality improvement collaborative (mQIC) designed to improve ischemic stroke treatment rates and efficiency in Atlantic Canada. This study evaluated the implementation of the mQIC in Nova Scotia using qualitative methods. The mQIC spanned 6 months, including two learning sessions, webinars, and a per-site virtual visit. The learning sessions featured presentations about the project and the improvement efforts at some sites. Each session included an action planning period where the participants planned for the implementation efforts over the following 2 to 4 months, called "action periods". Eleven hospitals and Emergency Health Services (EHS) of Nova Scotia participated. The Consolidated Framework for Implementation Research (CFIR) was utilized to develop a semi-structured interview guide to uncover barriers and facilitators to mQIC's implementation. Interviews were conducted with 14 healthcare professionals from 10 entities, generating 458 references coded into 28 CFIR constructs. The interviews started on 17 June 2021, 2 months after the intervention period, and ended on 7 October 2021. Notably, 84% of these references were positively framed as facilitators., highlighting the various aspects of the mQIC and its context that supported successful implementation. These facilitators encompassed factors such as networks and communications, strong leadership engagement, and a collaborative culture. Significant barriers included resource availability, relative priorities, communication challenges, and engaging key stakeholders. Some barriers were prominent during specific phases. The study provides insights into quality improvement initiatives in stroke care, reflecting the generally positive opinions of the interviewees regarding the mQIC. While the quantitative analysis is still ongoing, this study highlights the importance of addressing context-specific barriers and leveraging the identified facilitators for successful implementation.

Deep Learning-Based ASPECTS Algorithm Enhances Reader Performance and Reduces Interpretation Time.

ASPECTS is a long-standing and well documented selection criteria for acute ischemic stroke treatment, however, the interpretation of ASPECTS is a challenging and time-consuming task for physicians with significant interobserver variabilities. We conducted a multi-reader, multi-case study in which readers assessed ASPECTS without and with the support of a deep learning (DL)-based algorithm in order to analyze the impact of the software on clinicians' performance and interpretation time. A total of 200 NCCT scans from 5 clinical sites (27 scanner models, 4 different vendors) were retrospectively collected. Reference standard was established through the consensus of three expert neuroradiologists who had access to baseline CTA and CTP data. Subsequently, eight additional clinicians (four typical ASPECTS reader and four senior neuroradiologists) analyzed the NCCT scans without and with the assistance of CINA-ASPECTS (Avicenna.AI, La Ciotat, France), a DLbased FDA-cleared and CE-marked algorithm designed to automatically compute ASPECTS. Differences were evaluated in both performance and interpretation time between the assisted and unassisted assessments. With software aid, readers demonstrated increased region-based accuracy from 72.4% to 76.5% (p<0.05), and increased ROC AUC from 0.749 to 0.788 (p<0.05). Notably, all readers exhibited an improved ROC AUC when utilizing the software. Moreover, use of the algorithm improved the score-based inter-observer reliability and correlation coefficient of ASPECTS evaluation by 0.222 and 0.087 (p<0.0001), respectively. Additionally, the readers' mean time spent analyzing a case was significantly reduced by 6% (p<0.05) when aided by the algorithm. With the assistance of the algorithm, readers' analyses were not only more accurate but also faster. Additionally, the overall ASPECTS evaluation exhibited greater consistency, less variabilities and higher precision compared to the reference standard. This novel tool has the potential to enhance patient selection for appropriate treatment by enabling physicians to deliver accurate and timely diagnosis of acute ischemic stroke. ASPECTS = Alberta Stroke Program Early Computed Tomography Score; DL = Deep Learning; EIC = Early Ischemic Changes; ICC = Intraclass Correlation Coefficient; IS = Ischemic Stroke; ROC AUC = Receiver Operating Characteristics Area Under the Curve.

Diagnostic and Therapeutic Challenge Caused by Candida albicans and Aspergillus spp. Infections in a Pediatric Patient as a Complication of Acute Lymphoblastic Leukemia Treatment: A Case Report and Literature Review.

Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient's condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy's condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia.

Acute and preventive treatment of menstrual migraine: a meta-analysis

Background and objectivesAbout a quarter of migraine cases among women have menstrual migraine (MM), which is usually more severe, longer lasting, and less responsive to treatment than typical migraine. Randomized controlled trials (RCTs) have evaluated the efficacy of several medication in the acute and preventive treatment of MM; this meta-analysis compared the effectiveness of these treatments.MethodsWe conducted systematic searches in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase databases. The primary outcomes of acute treatment trials were pain relief at 2 and 24 h after treatment compared with placebo or another treatment. The three endpoints we checked for studying MM prevention were: no recurrence of headaches each month, a 50% reduction in monthly migraine days from baseline, and a decrease in the mean number of headache days per month.ResultsOut of 342 studies, 26 RCTs met the criteria. Triptans, combined with or without other analgesics, were superior to placebo in providing pain relief in the acute treatment and prevention of MM. Among the treatments, sumatriptan and lasmiditan demonstrated superior pain relief at 2 h (OR: 4.62) and 24 h (OR: 4.81). Frovatriptan exhibited effectiveness in preventing headache recurrence, whereas galcanezumab and erenumab displayed significant preventive benefits in reducing headache days per month.ConclusionSumatriptan and lasmiditan are effective first-line treatments for acute MM. For prevention, frovatriptan may be the more effective of triptans. Compared with triptans, CGRP monoclonal antibodies, here including erenumab and galcanezumab, are more effective in reducing headache days, and therefore, in preventing MM.

The Dual-layer CGuard Stent Is Safe and Effective in Emergent Carotid Artery Stenting and in Tandem Occlusions: aMulti-centric Study.

Dual-layer stents have fallen into disrepute after several studies reported high rates of in-stent occlusions in acute stroke treatments. The CGuard stent is anew-generation hybrid dual-layer stent that has been designed to provide less thrombogenicity and to prevent peri- and postinterventional emboli. The aim of the study is to evaluate the safety and efficacy of the CGuard stent for the acute treatment of occlusion or high-grade stenosis of the extracranial internal carotid artery (ICA) in patients with acute ischemic stroke (AIS) with and without concomitant intracranial large vessel occlusion (LVO). All patients who underwent emergent carotid artery stenting (CAS) with the CGuard stent were identified and analyzed from the stroke registries from four tertiary German stroke centers. Clinical, procedural, and imaging data were evaluated. Stent patency within 72 h, intracranial hemorrhage, and modified Rankin score (mRS) at discharge were the safety and efficacy end points. Overall, ninety-six patients were included (mean age70.2 ± 11.8, 66males (68.8%), median NIHSS score at admission 11 (7-17), IVlysis: n = 44 (45.8%)). Stent placement was successful in all patients. Eighty-three (86.4%) patients had tandem occlusions. In-stent occlusion occurred in 5patients (5.2%) and 3patients developed early in-stent stenosis (3.1%). Median mRS at discharge was 2 (1-4). In this multicenter study, the use of the dual-layer CGuard stent for emergent CAS, particularly in tandem occlusions, was safe and resulted in low rates of in-stent occlusions.

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

Early Intervention after Rape to prevent post-traumatic stress symptoms (the EIR-study): an internal pilot study of a randomized controlled trial

BackgroundRape is one of the trauma incidents with the highest risk of subsequent post-traumatic stress disorder. Early interventions, such as prolonged exposure therapy (PE), have shown promise in preventing PTSD following a sexual assault. The primary objective of this internal pilot trial was to examine the feasibility of the EIR study protocol, which used modified prolonged exposure therapy (mPE) as a preventive intervention after rape.MethodsThis parallel two-arm clinical pilot study involved three sexual assault centers (SACs) in Trondheim, Oslo, and Vestfold, with data collected between June 2022 and March 2023. Women seeking assistance at one of these three SACs within 72 h after rape or attempted rape received acute medical treatment and forensic examinations. Women who wanted further psychosocial treatment were, if eligible and consenting, recruited to complete baseline assessments and a clinical interview before being randomized to one of two study arms. The intervention group prescribed up to five sessions of modified PE (mPE) in addition to treatment as usual (TAU), starting within the first 14 days after the rape incident, followed by weekly sessions. The other group received TAU.The present pilot evaluation is based on 22 participants, i.e., nine mPE + TAU and 13 TAU alone. Primary outcomes were predefined progression criteria regarding recruitment, retention, intervention implementation, a harm reporting system, and applying biological measurements and actigraphy.ResultsDuring the 6-month recruitment period, 235 women visited the three SACs. After eligibility screening and consent, 22 (9.4%) women were randomized. Three months later, 14 (63.6%) participants completed the final assessments. Intervention implementation was successful using trained SAC personnel to deliver mPE. The harm reporting system was used according to the study’s plan, and adverse and serious adverse events were detected during the trial. The biological measurements and actigraphy had substantial missing data but were still considered usable for statistical analyses.ConclusionIt may be feasible to conduct a full-scale RCT of early intervention after rape by comparing mPE + TAU to TAU alone. Minor design refinements were made to the protocol to enhance the main study outcome.Trial registrationClinicalTrials.gov Identifier: NCT05489133. Registered on 15 July 2022, retrospectively.

Trends in sex differences of functional outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies-including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR)-detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. Among 11,840 patients receiving IVT, 2489 of 5503 (45.4%) women achieved favorable functional outcome compared to 3787 of 6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjusted odds ratio (adjOR) = 0.87, 95% confidence interval (CI) = 0.79-0.96, p = 0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) = 1.04, 95% CI = 1.02-1.06, p < 0.001) but not in women (adjOR (per year) = 1.01, 95% CI = 0.99-1.03, p = 0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction, and longer door-to-needle times were significantly associated with outcome only in women. Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future. Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (D.M.), access inquiries have to be addressed to the registry's academic review board.