Unfavorable Long-term Outcomes Research Articles

The Association of Heterozygous p.R4810K of RNF213 and Long-Term Unfavorable Outcomes after Encephaloduroarteriosynangiosis in Chinese Pediatric Patients with Moyamoya Disease

Background. Previous studies have established that heterozygous mutation for the p.R4810K variant can influence the severity of the clinical phenotype in patients with moyamoya disease (MMD) at disease onset. However, the relationship between the p.R4810K variant and the clinical phenotype of long-term unfavorable outcomes in Chinese pediatric patients remains unclear. Objectives. The primary aim of this study was to examine the association of heterozygous p.R4810K of RNF213 and long-term unfavorable outcomes after encephaloduroarteriosynangiosis (EDAS) in Chinese pediatric patients with MMD. Method. In this retrospective cohort study, we included 259 pediatric patients with MMD who possessed the known p.R4810K genotype. These individuals underwent EDAS along with genotyping analysis for p.R4810K via a TaqMan probe and the QuantStudio 6 Flex Real-Time PCR System. Subsequently, we evaluated their long-term outcomes. The variables we assessed were age at diagnosis, gender, p.R4810K genotypes, initial modified Rankin scale (mRS), clinical manifestations (such as hemorrhage and ischemia), posterior cerebral artery (PCA) involvement combined with angiographic stage, and their history of risk factors like hyperlipidemia and hyperhomocysteinemia. Furthermore, we scrutinized long-term unfavorable outcomes using both univariate analyses and multivariate logistic regression to identify independent predictive factors. Results. This study enrolled 259 Chinese pediatric patients with MMD, which included both newly and previously diagnosed cases, who underwent EDAS. The cohort comprised 130 male participants (50.19%) and 129 female participants (49.81%), with a median onset age of 8 years (median, IQR: 6-12 years). Among these patients, homozygous mutations were exceptionally rare, identified in only 4 individuals (1.54%), while the prevalence of heterozygous mutations was relatively higher, observed in 85 children (32.82%). The multivariate logistic regression showed that several factors were significantly associated with long-term unfavorable outcomes: older age at diagnosis (OR, 0.82 [95% CI, 0.7-0.96], P=0.014), onset with hematoma (OR, 12.76 [95% CI, 1.52-106.89], P=0.019), initial mRS (OR, 24.53 [95% CI, 6.51-92.41], P<0.001), perioperative infarction (OR, 22.16 [95% CI, 1.45-337.96], P=0.026), and infarction during follow-up (OR, 14.5 [95% CI, 2.04-103.12], P=0.008). Furthermore, the cumulative incidence of initial infarction suggested that pediatric patients with homozygous or heterozygous mutations typically present at a younger age and exhibit a higher incidence of initial infarction compared to those carrying wild-type genotypes. Conclusions. The study suggests that the p.R4810K variant is associated with the onset age of MMD in Chinese pediatric patients, potentially impacting long-term outcomes. Surprisingly low recurrent stroke rates were observed across all genotypes, including homozygous individuals for the pathogenic variant, indicating that nongenetic factors may also play a role in the course and outcomes of MMD in this population.

Study on clinical features and factors related to long-term outcomes of antibody-negative autoimmune encephalitis.

To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE. Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed. In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%). The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.

Impact of SWCNTs and CMCS on efficacy of anastomosis and optical properties in vivo during laser biological tissue soldering

In order to improve the mechanical properties of skin tissue incision, enhance laser absorption efficiency, further shorten healing time and reduce skin fibrosis tendency, this study investigated the effects of CMCS or SWCNT combined with 25 % BSA and 0.4 % ICG on laser tissue welding. Nd:YAG pulsed laser was used for wound closure test on live rats with an energy density of 67.3 J/cm2 and linear scanning of skin incisions. The effects of different types and concentrations of biological dressings on wound closure were tested at different sites. The results showed that biocompatible dressings containing CMCS and SWCNTs had a significant effect in promoting wound healing after laser welding. After laser welding, the tensile strength of the control group without CMCS or SWCNTs was only between 6.5 and 9.8 N/cm2, while that with CMCS reached as high as 26.5 N/cm2. Macroscopic morphology analysis showed that components such as CMCS and SWCNTs could significantly shorten healing time from 14 days to 9–10 days. Optical performance tests demonstrated that a combination of 5 %CMCS and 4 %SWCNTs can significantly increase skin's absorption coefficient for laser photons up to7-8 Lg-1cm−1 and reduce photon diffuse reflectance. HE and Masson staining revealed that when internalized by dressing containing 0.4 %SWCNTs, nanocarbon particles promoted collagen skeleton regeneration but increased fibrosis tendency after 14 days post-laser welding, resulting in unfavorable long-term healing outcomes. However, the combination of CMSC with SWCNTs can significantly improve incision mechanical properties, laser photon absorption rate, and shorten healing time while reducing scar proliferation tendencies.

A Comprehensive Examination of Clinical Characteristics and Determinants of Long-Term Outcomes in Pediatric Cerebral Sinus Venous Thrombosis

BackgroundTo analyze the clinical and neuroimaging features, risk factors, treatment choices, and long-term clinical outcomes in children with cerebral sinus venous thrombosis (CSVT). MethodsThis is a retrospective cohort study of children diagnosed with CSVT between 2002 and 2018 at Texas Children's Hospital. ResultsA total of 183 children (male: 62.3%) with CSVT were included. The average presenting age was 7.7 years (S.D.: 5.6). The mean follow-up duration was 33.7 months (S.D.: 38.6). The most common presenting clinical feature was headache (36.6%). Head and neck infections other than meningitis (36.6%) were the most common risk factors. Prevalent neurological examination findings included motor deficit (21.3%) and altered mental status (AMS, 20.2%). Neuroimaging features included hemorrhagic infarction (19.6%), ischemic infarction (8.2%), and intracranial hemorrhage without infarction (5.5%). The most common site of thrombosis was the superior sagittal sinus (37.2%), with 78.2% of patients demonstrating involvement of multiple sinuses. Treatment of choice was low-molecular-weight heparin in 69.4% of patients. Factors associated with worse clinical outcomes included head and neck infections, malignancy (other than hematologic), cardiac disease, and recent surgery; seizure and dehydration on initial presentation; motor abnormalities and AMS on initial examination; ischemic infarct only; and involvement of vein of Trolard on neuroimaging. Thrombus condition on repeat imaging, receiving any anticoagulant/antithrombotic treatment, treatment duration, or follow-up duration was not associated with severity of long-term outcome. ConclusionsCSVT may lead to unfavorable long-term outcomes in a remarkable portion of pediatric patients. Thus, a high index of suspicion and early and appropriate management of pediatric CSVT is imperative.

Which magnetic resonance imaging feature is associated with treatment response in perianal fistulizing Crohn's disease?

Perianal fistulae are disabling complications of Crohn's Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life. Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied. Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn's disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01). The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn's disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis.

Abstract HUP3: Neighborhood Deprivation and Functional Outcomes Following Ischemic Stroke

Introduction: The association between neighborhood deprivation and risk of disease is well-documented. However, the role of neighborhood deprivation in long-term outcomes following acute brain injury remains understudied. We tested the hypothesis that neighborhood deprivation leads to unfavorable long-term functional outcomes following acute ischemic stroke (AIS). Methods: We conducted a nested study within the Yale Longitudinal Study of Acute Brain Injury, a prospective study which follows patients with acute brain injury admitted to the Yale Health System. The present study focused on AIS survivors and assessed neighborhood deprivation using the Area Deprivation Index (ADI), a metric that uses 9-digit zip codes to rank neighborhoods based on income, employment, education, and housing quality. Patients were stratified into tertiles based on their ADI, designated as low, intermediate, or high deprivation. Functional outcomes were evaluated using the modified Rankin Scale at one-year post-stroke, dichotomized into favorable (scores 0-2) and unfavorable (scores 3-6). Our analysis employed multivariable logistic regression for adjusted analyses. Results: Among 2,540 AIS patients enrolled between 2018 and 2021, 2,164 patients had zip code and outcomes data (mean age 69 years, 48% female, 7.5% Black, 7.7% Hispanic). The one-year unadjusted risk of poor outcomes was 35%, 40% and 46% for patients residing in neighborhoods with low, intermediate, and high deprivation, respectively (unadjusted p=0.001). These findings remained significant in multivariate analyses that controlled for confounding factors: compared to patients living in neighborhoods with low deprivation, those living in areas with intermediate and high deprivation had 44% (OR 1.44, 95% CI 1.11-1.86) and 107% (OR 2.07, 95% CI 1.58-2.72) greater risk of unfavorable outcomes (test-for-trend p&lt;0.001). Conclusion: Our study, focusing on survivors of AIS participating in a prospective acute brain injury study, underscores the connection between neighborhood deprivation and an elevated risk of unfavorable outcomes. We validate the utility of the ADI as a valuable analytical tool for evaluating neighborhood deprivation as a composite for several social determinants of health.

Abstract WMP53: Neighborhood Deprivation and Functional Outcomes Following Ischemic Stroke

Introduction: The association between neighborhood deprivation and risk of disease is well-documented. However, the role of neighborhood deprivation in long-term outcomes following acute brain injury remains understudied. We tested the hypothesis that neighborhood deprivation leads to unfavorable long-term functional outcomes following acute ischemic stroke (AIS). Methods: We conducted a nested study within the Yale Longitudinal Study of Acute Brain Injury, a prospective study which follows patients with acute brain injury admitted to the Yale Health System. The present study focused on AIS survivors and assessed neighborhood deprivation using the Area Deprivation Index (ADI), a metric that uses 9-digit zip codes to rank neighborhoods based on income, employment, education, and housing quality. Patients were stratified into tertiles based on their ADI, designated as low, intermediate, or high deprivation. Functional outcomes were evaluated using the modified Rankin Scale at one-year post-stroke, dichotomized into favorable (scores 0-2) and unfavorable (scores 3-6). Our analysis employed multivariable logistic regression for adjusted analyses. Results: Among 2,540 AIS patients enrolled between 2018 and 2021, 2,164 patients had zip code and outcomes data (mean age 69 years, 48% female, 7.5% Black, 7.7% Hispanic). The one-year unadjusted risk of poor outcomes was 35%, 40% and 46% for patients residing in neighborhoods with low, intermediate, and high deprivation, respectively (unadjusted p=0.001). These findings remained significant in multivariate analyses that controlled for confounding factors: compared to patients living in neighborhoods with low deprivation, those living in areas with intermediate and high deprivation had 44% (OR 1.44, 95% CI 1.11-1.86) and 107% (OR 2.07, 95% CI 1.58-2.72) greater risk of unfavorable outcomes (test-for-trend p&lt;0.001). Conclusion: Our study, focusing on survivors of AIS participating in a prospective acute brain injury study, underscores the connection between neighborhood deprivation and an elevated risk of unfavorable outcomes. We validate the utility of the ADI as a valuable analytical tool for evaluating neighborhood deprivation as a composite for several social determinants of health.

P386 Persistence of bowel urgency despite clinical remission after induction therapy is associated with unfavorable long-term outcomes in patients with ulcerative colitis: results from the multicenter UC-RGENCY study

Abstract Background STRIDE 2 recommendations define clinical remission as no rectal bleeding and normalization of stool frequency in patients with ulcerative colitis (UC), without including bowel urgency (BU) despite its negative impact on quality of life. In this large multicenter cohort, we aimed to assess whether the persistence of BU after induction therapy is independently associated with poor long-term outcomes in patients with UC. Methods From a multicenter retrospective study, we included consecutive UC adult patients previously exposed to at least one anti-TNF agent, with partial Mayo score (pMS) &amp;gt; 2, who started biologics or small molecules between Jan2019 and June2022. BU was defined as a binary criterion based on the SCCAI definition. The primary endpoint was the time to drug discontinuation due to active UC. Secondary endpoints were time to relapse, time to colectomy as well as steroid-free clinical remission (pMS ≤ 2) (CFREM), endoscopic remission (CFREM + Mayo endoscopic score (MES) ≤ 1), and mucosal healing (CFREM + MES ≤ 1 + histological remission i.e. Nancy index ≤ 1) at last follow-up. Results Among 473 patients with UC, 270 were assessed for BU after induction therapy (week 16) (mean age 43.0±17.0 years-old, median UC duration 6 [3-11] years, female gender=54.0%, pancolitis=45.9%). The median follow-up was 14 [8-22] months. The rate of CFREM after induction therapy was 54.4% (147/270) while 21.5% (58/270) had remaining bowel urgencies after induction therapy. Among the 147 patients achieving remission after induction therapy, 12 had persistent BU (8.2%), while 62.6% (77/123) of patients with no CFREM after induction therapy did not have any BU. The agreements between BU and rectal bleeding (75.2%, κ-coefficient = 0.33±0.06) or normalization of stools frequency (67.9%,κ-coefficient = 0.35±0.05) were mild. Among the patients with persistent BU after induction therapy, only 3.7% had no endoscopic activity (MES = 0). In multivariable analyses including CFREM at week 16, persistence of BU after induction therapy was independently associated with the time to drug discontinuation (HR=2.0[1.1-3.5], p=0.016) and colectomy (HR=4.4[2.3-8.4], p&amp;lt;0.001), and absence of mucosal healing (OR = 5.0[1.1-24.8], p=0.046) at last follow-up. A trend was also observed regarding the association between remaining BU after induction therapy and no CFREM (OR=6.1[0.8-48.0], p=0.085) or absence of endoscopic remission (OR=2.4[0.9-6.1], p=0.077) at last follow-up. Conclusion Persistence of BU despite clinical remission is associated with higher risk of drug discontinuation due to active UC, colectomy and lower likelihood of mucosal healing. Bowel urgency should be implemented into international guidelines to define clinical remission in patients with UC.

Coronary Slow-Flow Phenomenon in Takotsubo Syndrome: The Prevalence, Clinical Determinants, and Long-Term Prognostic Impact.

Patients with takotsubo syndrome (TTS) may present coronary slow flow (CSF) in angiography performed in the acute myocardial infarction (MI). However, the detailed clinical relevance and its long-term impact remain poorly understood. Among 7771 MI patients hospitalized between 2012 and 2019, TTS was identified in 82 (1.1%) subjects. The epicardial blood flow was assessed with thrombolysis in myocardial infarction (TIMI) scale and corrected TIMI frame count (TFC), whereas myocardial perfusion with TIMI myocardial perfusion grade (TMPG). CSF was defined as TIMI-2 or corrected TFC > 27 frames in at least one epicardial vessel. CSF was identified in 33 (40.2%) TTS patients. In the CSF-TTS versus normal-flow-TTS group, lower values of left ventricular ejection fraction on admission (33.5 (25-40) vs. 40 (35-45)%, p = 0.019), more frequent midventricular TTS (27.3 vs. 8.2%, p = 0.020) and the coexistence of both physical and emotional triggers (9.1 vs. 0%, p = 0.032) were noted. Within a median observation of 55 months, higher all-cause mortality was found in CSF-TTS compared with normal-flow TTS (30.3 vs. 10.2%, p = 0.024). CSF was identified as an independent predictor of long-term mortality (hazard ratio 10.09, 95% confidence interval 2.12-48.00, p = 0.004). CSF identified in two-fifths of TTS patients was associated with unfavorable long-term outcomes.

The impact of CARE Frailty Index on overall survival in older adults with hepatocellular carcinoma.

462 Background: Pre-treatment frailty is associated with unfavorable short and long-term outcomes among patients with hepatocellular cancer (HCC) post liver resection.However, there is a knowledge gap in identifying the subset of older adults with HCC at high risk for inferior survival outcomes. Methods: We evaluated the association between patient-reported geriatric assessment (GA)-based frailty index and overall survival (OS) among older adults (≥60y) diagnosed with HCC enrolled in a single institutional prospective registry (Cancer and Aging Resilience Assessment (CARE) registry). All patients underwent a patient-reported GA at enrollment that encompassed multiple health domains related to aging. To determine frailty, we utilized a 44-item CARE Frailty Index (CARE-FI) based on the principles of deficit accumulation (Giri S et al JAGS 2021). We categorized frailty into robust, pre-frail and frail. The primary outcome was OS from the time of GA. Comparison of survival between groups was made using log-rank statistic. A multivariable Cox regression model measured the independent association between frailty and OS adjusted for age, etiology, Child-Pugh score and cancer stage. Results: A total of 116 older adults with HCC were identified with a median follow-up 2.1 year, median age was 67y (63-72) with 82% males, 27% blacks, 64% with Child-Pugh-A and 78% with stage III/IV disease. Overall, 50.1% (n=58) were frail, 33.6% (n=39) pre-frail and 16.3% (n=19) robust. No significant clinico-demographic differences across the 3 frailty groups were observed. In univariable analysis, there was a marginally significant difference between the three frailty groups (p value 0.06). However, in multivariable analysis, being frail vs robust was associated with an increased risk of mortality (HR 2.6 [95% CI 1.03 – 6.56]; p=0.04) after adjustment for aforementioned confounders. Conclusions: Frailty status assessed by patient-reported GA using CARE-FI is associated with an increased risk of mortality in older adults with HCC. Frailty assessment should be encouraged and considered in prospective clinical trials to estimate the impact of treatment on the most vulnerable adults. [Table: see text]

Association of non-contrast CT markers with long-term functional outcome in deep intracerebral hemorrhage.

Hematoma expansion (HE) is the most important therapeutic target during acute care of patients with intracerebral hemorrhage (ICH). Imaging biomarkers such as non-contrast CT (NCCT) markers have been associated with increasing risk for HE. The aim of the present study was to evaluate the influence of NCCT markers with functional long-term outcome and with HE in patients with deep (basal ganglia and thalamus) ICH who represent an important subgroup of patients at the highest risk for functional deterioration with HE due to the eloquence of the affected brain region. From our prospective institutional database, all patients maximally treated with deep ICH were included and retrospectively analyzed. NCCT markers were recorded at diagnostic imaging, ICH volume characteristics were volumetrically evaluated, and all patients received follow-up imaging within 0-48 h. We explored associations of NCCT makers with unfavorable functional outcome, defined as modified Rankin scale 4-6, after 12 months and with HE. Bias and confounding were addressed by multivariable regression modeling. In 322 patients with deep ICH, NCCT markers were distributed as follows: irregular shape: 69.6%, heterogenous density: 55.9%, hypodensities: 52.5%, island sign: 19.3%, black hole sign: 11.5%, and blend sign: 4.7%. Upon multivariable regression analyses, independent associations were documented with the functional outcome for irregular shape (aOR: 2.73, 95%CI: 1.42-5.22, p = 0.002), heterogenous density (aOR: 2.62, 95%CI: 1.40-4.90, p = 0.003) and island sign (aOR: 2.54, 95%CI: 1.05-6.14, p = 0.038), and with HE for heterogenous density (aOR: 5.01, 95%CI: 1.93-13.05, p = 0.001) and hypodensities (aOR: 3.75, 95%CI: 1.63-8.62, p = 0.002). NCCT markers are frequent in deep ICH patients and provide important clinical implications. Specifically, markers defined by diverging intra-hematomal densities provided associations with a 5-times higher risk for HE and a 2.5-times higher likelihood for unfavorable functional long-term outcome. Hence, these markers allow the identification of patients with deep ICH at high risk for clinical deterioration due to HE.

Differences in Health-Related Quality of Life among Patients with Heart Failure.

Heart failure (HF) is characterized by a progressive clinical course marked by frequent exacerbations and repeated hospitalizations, leading to considerably high morbidity and mortality rates. Patients with HF present with a constellation of bothersome symptoms, which range from physical to psychological and mental manifestations. With the transition to more advanced HF stages, symptoms become increasingly more debilitating, interfere with activities of daily living and disrupt multiple domains of life, including physical functioning, psychological status, emotional state, cognitive function, intimate relationships, lifestyle status, usual role activities, social contact and support. By inflicting profuse limitations in numerous aspects of life, HF exerts a profoundly negative impact on health-related quality of life (HRQOL). It is therefore not surprising that patients with HF display lower levels of HRQOL compared not only to the general healthy population but also to patients suffering from other chronic diseases. On top of this, poor HRQOL in patients with HF becomes an even greater concern considering that it has been associated with unfavorable long-term outcomes and poor prognosis. Nevertheless, HRQOL may differ significantly among patients with HF. Indeed, it has consistently been reported that women with HF display poorer HRQOL compared to men, while younger patients with HF tend to exhibit lower levels of HRQOL than their older counterparts. Moreover, patients presenting with higher New York Heart Association (NYHA) functional class (III-IV) have significantly more impaired HRQOL than those in a better NYHA class (I-II). Furthermore, most studies report worse levels of HRQOL in patients suffering from HF with preserved ejection fraction (HFpEF) compared to patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF). Last, but not least, differences in HRQOL have been noted depending on geographic location, with lower HRQOL levels having been recorded in Africa and Eastern Europe and higher in Western Europe in a recent large global study. Based on the observed disparities that have been invariably reported in the literature, this review article aims to provide insight into the underlying differences in HRQOL among patients with HF. Through an overview of currently existing evidence, fundamental differences in HRQOL among patients with HF are analyzed based on sex, age, NYHA functional class, ejection fraction and geographic location or ethnicity.

Blood Pressure Trajectories and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke.

Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes. We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios. There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50]). Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes.

Interleukin-6 and uric acid among type 2 diabetes mellitus patients with coronary artery disease.

The type 2 diabetes mellitus is considering as metabolic disorder, the unfavourable long-term outcomes and closely associated with chronic inflammation. The present study investigated to explore the association of interleukin-6 and uric acid in patients with type 2 diabetes mellitus and coronary artery disease. Newly diagnosed CAD patients with T2DM (100) and T2DM and CAD patients after 5 years (100) underwent detailed anthropometric, demographic, biochemical and experimental characterization. The serum levels of interleukin 6 were measured by enzyme linked immuno-sorbent assay. The T2DM and CAD patients after 5 years had significant higher circulating levels of interleukin 6 and significant decreased levels of uric acid. The newly diagnosed CAD patients with T2DM had significant higher circulating levels of interleukin 6. Significant positive correlation was found between fat mass and IL-6, and negative correlation with uric acid and IL-6, (P<0.05). The both the groups of T2DM with CAD patients shown significantly elevated levels of interleukin 6, based on this findings interleukin 6 might be used as early predictable and prognostic marker for CAD in patients with T2DM.

Aging Modulates the Ability of Quiescent Radial Glia-Like Stem Cells in the Hippocampal Dentate Gyrus to be Recruited into Division by Pro-neurogenic Stimuli.

A delicate balance between quiescence and division of the radial glia-like stem cells (RGLs) ensures continuation of adult hippocampal neurogenesis (AHN) over the lifespan. Transient or persistent perturbations of this balance due to a brain pathology, drug administration, or therapy can lead to unfavorable long-term outcomes such as premature depletion of the RGLs, decreased AHN, and cognitive deficit. Memantine, a drug used for alleviating the symptoms of Alzheimer's disease, and electroconvulsive seizure (ECS), a procedure used for treating drug-resistant major depression or bipolar disorder, are known strong AHN inducers; they were earlier demonstrated to increase numbers of dividing RGLs. Here, we demonstrated that 1-month stimulation of quiescent RGLs by either memantine or ECS leads to premature exhaustion of their pool and altered AHN at later stages of life and that aging of the brain modulates the ability of the quiescent RGLs to be recruited into the cell cycle by these AHN inducers. Our findings support the aging-related divergence of functional features of quiescent RGLs and have a number of implications for the practical assessment of drugs and treatments with respect to their action on quiescent RGLs at different stages of life in animal preclinical studies.

Abstract 17921: Diastolic Dysfunction Might Predict Outcomes in Acute Coronary Syndrome Patients Undergoing Primary Percutaneous Coronary Intervention

Introduction: Acute coronary syndrome (ACS) leads to diastolic dysfunction which might cause unfavorable long-term clinical outcomes. We aim to evaluate the association between diastolic parameters in patients with an ACS and event rates including 30-day mortality and 6-month readmission rates. Methodology: We studied 1579 patients with ACS who underwent primary percutaneous coronary intervention (PCI) from January 1, 2010 through December 31, 2020. Clinical, laboratory, transthoracic echocardiographic (TTE) and coronary angiographic parameters were retrospectively reviewed. Diastolic parameters (E/A ratio, TR velocity, LVEF and LAVI) in patients with left anterior descending artery (LAD) PCI (n=879) were compared with those who underwent PCI to non-LAD artery (n=700). Percentage of 6-month all-cause readmission, cardiogenic shock as well as mortality rates were calculated in both cohorts. Results: The mean age of 1579 ACS patients was 65 + 12 years, BMI 29 + 5 kg/m 2 , peak high sensitivity troponin 624 ng/L, E/A ratio 1.065, TR velocity 3.2 m/s, LAVI 34.26 mL/m 2 and LVEF 50.1%. The percentage of hospital readmission within 6 months was higher in patients with diastolic dysfunction and LAD PCI compared to those with non-LAD PCI (19% versus 16%, p - value=0.004). Although patients with diastolic dysfunction and LAD PCI had higher percentage of cardiogenic shock compared to non-LAD PCI group (6.0% versus 3.7%, p -value&lt;0.001), 1-year mortality did not differ between the 2 groups ( p -value=0.84). Conclusion: Diastolic dysfunction is associated with worse clinical outcomes in patients undergoing LAD PCI which warrants a larger prospective clinical study.

A Genetic Risk Variant for Multiple Sclerosis Severity is Associated with Brain Atrophy.

The minor allele of the genetic variant rs10191329 in the DYSF-ZNF638 locus is associated with unfavorable long-term clinical outcomes in multiple sclerosis patients. We investigated if rs10191329 is associated with brain atrophy measured by magnetic resonance imaging in a discovery cohort of 748 and a replication cohort of 360 people with relapsing multiple sclerosis. We observed an association with 28% more brain atrophy per rs10191329*A allele. Our results encourage stratification for rs10191329 in clinical trials. Unraveling the underlying mechanisms may enhance our understanding of pathophysiology and identify treatment targets. ANN NEUROL 2023;94:1080-1085.

"Light" on Phototherapy-Complications and Strategies for Shortening Its Duration, A Review of the Literature.

Neonatal hyperbilirubinemia is an extremely common metabolic complication of the neonatal period which may be associated with bilirubin encephalopathy and even death. Adverse neurological consequences are preventable if a timely diagnosis and treatment are provided. Phototherapy is usually the preferred option to decrease hyperbilirubinemia. Although considered to be safe, evidence in recent years has shown that this treatment may not be free of side effects and short- and long-term unfavorable outcomes. These are usually mild or rare, but should be decreased or avoided if possible. Many useful complementary measures and treatments have been described that could shorten the duration of exposure to phototherapy. However, there is no current unequivocal recommendation to use any of the methods presented in this review. Our review aims to depict the wide range of possible complementary treatments to phototherapy, and to provide the scientific and clinical evidence available regarding their usefulness. It is essential that, while utilizing the full potential of phototherapy to treat hyperbilirubinemia, caregivers are aware of its side effects and possible inherent dangers, and seek ways to minimize the exposure to phototherapy to what is really needed for the newborn. Further studies are needed to clarify the preferred complementary treatments that could reduce the duration of exposure to phototherapy without impairing its effectiveness.

Acute Phase Protein Orosomucoid (Alpha-1-Acid Glycoprotein) Predicts Delayed Cerebral Ischemia and 3-Month Unfavorable Outcome after Aneurysmal Subarachnoid Hemorrhage.

The pathophysiology and consequences of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) remain incompletely understood. This study aims to investigate the role of orosomucoid (ORM) in aSAH, its potential as a marker for assessing the extent of EBI-induced damage, and its correlation with delayed cerebral ischemia (DCI) and functional recovery over a 3-month period. We collected serum specimens 72 h post-aSAH to measure ORM levels. The study included 151 aSAH patients and 105 healthy subjects. The serum ORM levels within the patient cohort significantly exceeded those in the control group (p < 0.001). The ORM value showed significant correlation with the admission WFNS (p < 0.0001) and mFS scores (p < 0.05). Substantially elevated serum ORM levels at 72 h post-aSAH were detected among patients experiencing DCI, as well as those with poor functional outcomes after 3 months (p = 0.009 and p < 0.001). Binary logistic regression analyses revealed that serum ORM at 72 h post-SAH was independently associated with DCI and 3-month functional outcome after adjusting for confounders. The early stage events of aSAH influence the level of ORM. ORM serves as a marker for assessing the extent of damage during EBI and is linked to the occurrence of DCI as well as unfavorable long-term functional outcomes.

Prognostic Value of Mitral Regurgitation in Patients with Primary Hypertrophic Cardiomyopathy.

Background and Objectives: Mitral valve pathology and mitral regurgitation (MR) are very common in patients with hypertrophic cardiomyopathy (HCM), and the evaluation of mitral valve anatomy and degree of MR is important in patients with HCM. The aim of our study was to examine the potential influence of moderate or moderately severe MR on the prognosis, clinical presentation, and structural characteristics of HCM patients. Materials and Methods: A prospective study examined 176 patients diagnosed with primary asymmetric HCM. According to the severity of the MR, the patients were divided into two groups: Group 1 (n = 116) with no/trace or mild MR and Group 2 (n = 60) with moderate or moderately severe MR. All patients had clinical and echocardiographic examinations, as well as a 24 h Holter ECG. Results: Group 2 had significantly more often the presence of the obstructive type of HCM (p < 0.001), syncope (p = 0.030), NYHA II class (p < 0.001), and atrial fibrillation (p = 0.023). Also, Group 2 had an enlarged left atrial dimension (p < 0.001), left atrial volume index (p < 0.001), and indirectly measured systolic pressure in the right ventricle (p < 0.001). Patients with a higher grade of MR had a significantly higher E/e' (p < 0.001) and, as a result, higher values of Nt pro BNP values (p < 0.001) compared to Group 1. Kaplan-Meier analysis demonstrated that the event-free survival rate during a median follow-up of 88 (IQR 40-112) months was significantly higher in Group 1 compared to Group 2 (84% vs. 45% at 8 years; log-rank 20.4, p < 0.001). After adjustment for relevant confounders, the presence of moderate or moderately severe MR remained as an independent predictor of adverse outcomes (HR 2.788; 95% CI 1.221-6.364, p = 0.015). Conclusions: The presence of moderate or moderately severe MR was associated with unfavorable long-term outcomes in HCM patients.