Baseline Clinical Characteristics Research Articles

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Genomic Characteristics and Its Therapeutic Implications in Breast Cancer Patients with Detectable Molecular Residual Disease.

Molecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown. In this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery. Baseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration-approved mutational biomarkers and targeted therapy. Our study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.

Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS)-Thalamotomy for Essential Tremor: Lesion Location and Clinical Outcomes.

Factors predicting clinical outcomes after MR-guided focused ultrasound (MRgFUS)-thalamotomy in patients with essential tremor (ET) are not well known. To examine the clinical outcomes and their relationship with patients' baseline demographic and clinical features and lesion characteristics at 6-month follow-up in ET patients. A total of 127 patients were prospectively evaluated at 1 (n = 122), 3 (n = 102), and 6 months (n = 78) after MRgFUS-thalamotomy. Magnetic resonance imaging (MRI) was obtained at 6 months (n = 60). Primary outcomes included: (1) change in the Clinical Rating Scale of Tremor (CRST)-A+B score in the treated hand and (2) frequency and severity of adverse events (AEs) at 6 months. Secondary outcomes included changes in all subitems of the CRST scale in the treated hand, CRST-C, axial tremor (face, head, voice, tongue), AEs, and correlation of primary outcomes at 6 months with lesion characteristics. Statistical analysis included linear mixed, standard, and logistic regression models. Scores for CRST-A+B, CRST-A, CRST-B in the treated hand, CRST-C, and axial tremor were improved at each evaluation (P < 0.001). Five patients had severe AEs at 1 month that became mild throughout the follow-up. Mild AEs occurred in 71%, 45%, and 34% of patients at 1, 3, and 6 months, respectively. Lesion volume was associated with the reduction in the CRST-A (P = 0.003) and its overlapping with the ventralis intermedius nucleus (Vim) nucleus with the reduction in CRST-A+B (P = 0.02) and CRST-B (P = 0.008) at 6 months. MRgFUS-thalamotomy improves hand and axial tremor in ET patients. Transient and mild AEs are frequent. Lesion volume and location are associated with tremor reduction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review

PurposeImmunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations.MethodsLiterature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies.ResultsA total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review.ConclusionIt is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

Disease etiology impact on outcomes of hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a real-world, multicenter study

Introduction The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post-hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab is equally effective in viral and non-viral patients. Methods We retrospectively analyzed 885 HCC patients treated with first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% non-viral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multi-variate models to explore potential differences on overall survival (OS), time to progression (TTP), disease control rates based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to second-line treatments and outcomes were also reported and compared between etiologies. Results Overall, no statistically significant differences were found in OS (mOS: viral 15.9 months; non-viral 16.3 months), TTP (mTTP: viral 8.3 months; non-viral 7.2 months), and disease control rates (DCR: viral 78.1%; non-viral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and non-viral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e. NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. Conclusion Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post-hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and non-viral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.

Risk of Potentially Preventable Hospitalizations After SARS-CoV-2 Infection

Research demonstrates that SARS-CoV-2 infection is associated with increased risk of all-cause hospitalization. However, no prior studies have assessed the association between SARS-CoV-2 and potentially preventable hospitalizations-that is, hospitalizations for conditions that can usually be effectively managed in ambulatory care settings. To examine whether SARS-CoV-2 is associated with potentially preventable hospitalization in a nationwide cohort of US veterans. This cohort study used an emulated target randomized trial design with monthly sequential trials to compare risk of a potentially preventable hospitalization among veterans with SARS-CoV-2 and matched comparators without SARS-CoV-2. A total of 189 136 US veterans enrolled in the Veterans Health Administration (VHA) who were diagnosed with SARS-CoV-2 between March 1, 2020, and April 30, 2021, and 943 084 matched comparators were included in the analysis. Data were analyzed from May 10, 2023, to January 26, 2024. SARS-CoV-2 infection. The primary outcome was a first potentially preventable hospitalization in VHA facilities, VHA-purchased community care, or Medicare fee-for-service care. Extended Cox models were used to examine adjusted hazard ratios (AHRs) of potentially preventable hospitalization among veterans with SARS-CoV-2 and comparators during follow-up periods of 0 to 30, 0 to 90, 0 to 180, and 0 to 365 days. The start of follow-up was defined as the date of each veteran's first positive SARS-CoV-2 diagnosis, with the same index date applied to their matched comparators. The 1 132 220 participants were predominantly men (89.06%), with a mean (SD) age of 60.3 (16.4) years. Most veterans were of Black (23.44%) or White (69.37%) race. Veterans with SARS-CoV-2 and comparators were well-balanced (standardized mean differences, all <0.100) on observable baseline clinical and sociodemographic characteristics. Overall, 3.10% of veterans (3.81% of those with SARS-CoV-2 and 2.96% of comparators) had a potentially preventable hospitalization during 1-year follow-up. Risk of a potentially preventable hospitalization was greater among veterans with SARS-CoV-2 than comparators in 4 follow-up periods: 0- to 30-day AHR of 3.26 (95% CI, 3.06-3.46); 0- to 90-day AHR of 2.12 (95% CI, 2.03-2.21); 0- to 180-day AHR of 1.69 (95% CI, 1.63-1.75); and 0- to 365-day AHR of 1.44 (95% CI, 1.40-1.48). In this cohort study, an increased risk of preventable hospitalization in veterans with SARS-CoV-2, which persisted for at least 1 year after initial infection, highlights the need for research on ways in which SARS-CoV-2 shapes postinfection care needs and engagement with the health system. Solutions are needed to mitigate preventable hospitalization after SARS-CoV-2.

Botulinum toxin A injection for post-stroke upper limb spasticity and rehabilitation practices from centers across Asian countries

PurposeDescribe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings.MethodsSubgroup analysis of a prospective, observational study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described.ResultsOverall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (p &amp;lt; 0.001). The majority (96.1%) of Asian patients were rated as having improved.ConclusionIn the Asian treatment setting, BoNT-A demonstrated a clinically significant effect on goal attainment for the real-life management of upper limb spasticity following stroke.

Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Outcomes With Hybrid Catheter-Directed Therapy Compared With Aspiration Thrombectomy for Patients With Intermediate-High Risk Pulmonary Embolism.

Intermediate-high-risk pulmonary embolism (IHR PE) is a challenging form of embolism obstruction that causes right ventricular(RV) dysfunction. The optimal management of IHR PE has not been established. This single-center prospective, observational study aimed to evaluate the efficacy and safety of complex catheter-directedtherapy (CDT)-catheter-directed mechanical aspiration thrombectomy (CDMT) supplemented with catheter-directed thrombolysis (hybrid CDT)in comparison to CDMT alone for IHR PE. A propensity score based on the pulmonary embolism severity index class and Miller obstruction index (MOI) was calculated, and 21 hybrid CDT cases (mean age 54.8 (14.7) years, 9/21 women) were matched with 21 CDMT cases (mean age 58.8 (14.9) years, 13/21 women). The baseline demographics, clinical,and treatment characteristics were analyzed. No significant differences were detected regarding baseline demographics and PE severity parameters. Hybrid CDT demonstrated a higher reduction in mean pulmonary artery pressure (mPAP) (hybrid CDT: median mPAP reduction 8mmHg (IQR: 6-10mmHg) vs CDMT: median mPAP reduction 6mmHg (IQR: 4-7mmHg); P = 0.019), MOI score (hybrid CDT: median change - 5 points (IQR: 5-6 points) vs CDMT median change - 3 points (IQR: 3-5 points); P = 0.019), and median RV: left ventricular ratio (hybrid CDT: median change 0.4 (IQR: 0.3-0.45) vs CDMT median change 0.26 (IQR: 0.2-0.4); P = 0.007). No major bleeding was observed. Both the hybrid CDT and CDMT alone treatments are safe and effective in managing IHR PE. Hybrid CDT is a promising technique for the management of IHR PE with insufficient thrombus load reduction by CDMT. NCT0447356-registration date 16 July 2020.

Sociodemographic and patient reported outcomes by racial and ethnicity status among participants in a randomized controlled trial for methamphetamine use disorder

BackgroundThere has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. ObjectivesThis secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. MethodsThe ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. ResultsOf the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. ConclusionsAlthough we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

365 Enlight-LN Registry: Baseline Demographics and Clinical Characteristics of an Initial Cohort of Patients Treated with Voclosporin for Lupus Nephritis in the United States

365 Enlight-LN Registry: Baseline Demographics and Clinical Characteristics of an Initial Cohort of Patients Treated with Voclosporin for Lupus Nephritis in the United States

Therapeutic benefit of probiotic in alcohol dependence syndrome: Evidence from a tertiary care centre of India

Probiotic adjuvant has promising effects in treating alcohol induced hepatitis, depression, and anxiety. This study aimed to assess the effectiveness of adjuvant probiotic use in improving the liver functions, anxiety, and depression among patients with alcohol dependence syndrome (ADS) in a tertiary care hospital in Andhra Pradesh, India. In this prospective observational design, ADS patients with or without probiotics were followed-up at one and three months after initiation of treatment. They were assessed for liver function test (LFT), anxiety by HAM-A and depression by HAM-D scale. A total of 120 patients complied with the treatment, 60 in each group, mean age being 35.0 years (SD 9.5 years). The baseline socio-demographic and clinical characteristics were similar in both the groups. Significant reduction was noted in the probiotic group for total bilirubin (Mean difference (MD) 0.18; 95% CI: 0.04, 0.31), AST (MD 5.0; 95% CI: 0.5, 9.5), and ALT (MD 8.6; 95% CI: 1.4, 15.7) at one month after treatment. Both the groups showed a considerable change in anxiety and depression scores (HAM-A and HAM-D) till three months. At three months of treatment initiation, proportional improvement of severity grade to mild form in anxiety was more in the probiotic group (35%) than the non-probiotic group (13.3%) (p<0.05). Hence, probiotic supplementation can significantly reduce the hepatic enzymes and depression severity in patients with alcohol dependence syndrome but demands additional robust evidence on the causal inference.

A machine learning approach to predicting vascular calcification risk of type 2 diabetes: A retrospective study.

Recently, patients with type 2 diabetes mellitus (T2DM) have experienced a higher incidence and severer degree of vascular calcification (VC), which leads to an increase in the incidence and mortality of vascular complications in patients with T2DM. To construct and validate prediction models for the risk of VC in patients with T2DM. Twenty-three baseline demographic and clinical characteristics were extracted from the electronic medical record system. Tenclinical features were screened with least absolute shrinkage and selection operator method and were used to develop prediction models based on eight machine learning (ML) algorithms (k-nearest neighbor [k-NN], light gradient boosting machine, logistic regression [LR], multilayer perception [(MLP], Naive Bayes [NB], random forest [RF], support vector machine [SVM], XGBoost[XGB]). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, and precision. A total of 1407 and 352 patients were retrospectively collected in the training and test sets, respectively. Among the eight models, the AUC value in the NB model was higher than the other models (NB: 0.753, LGB: 0.719, LR: 0.749, MLP: 0.715, RF: 0.722, SVM: 0.689, XGB:0.707, p < .05 for all). The k-NN model achieved the highest sensitivity of 0.75 (95% confidence interval [CI]: 0.633-0.857), the MLP model achieved the highest accuracy of 0.81 (95%CI: 0.767-0.852) and specificity of 0.875 (95%CI: 0.836-0.912). This study developed a predictive model of VC based on MLand clinical features in type 2 diabetic patients. The NB model is a tool with potential to facilitate clinicians in identifying VC in high-risk patients.

373 Modified 5-Item Frailty Index: A Useful Tool for Assessing the Impact of Frailty on Postoperative Morbidity and Mortality Following Surgical Fixation of Thoracolumbar Fractures

INTRODUCTION: The modified 5-item frailty index (mFI-5) is a comorbidity-based risk stratification tool that has been shown to predict adverse events following various neurological surgeries. METHODS: The 2011-2021 American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to identify patients undergoing fusion surgeries for thoracolumbar spine fractures. The mFI-5 score was calculated based on the presence of the 5 comorbidities: congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, partially dependent or totally dependent functional health status, and hypertension. Multivariate analysis was used to assess the independent impact of increasing mFI-5 score on postoperative 30-day morbidity and mortality while controlling for baseline clinical characteristics. RESULTS: A total of 66,904 patients were included in our analysis (54.2% female, mean age 62.27 ± 12.93 years). On univariate analysis, higher mFI-5 score was significantly associated with increased risks of superficial surgical site infection(SSI), deep SSI, wound dehiscence, unplanned reoperation, pneumonia, unplanned intubation, postoperative ventilator use, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, myocardial infarction, cardiac arrest, pulmonary embolism, deep vein thrombosis, bleeding requiring transfusion, sepsis, septic shock, and longer hospital length of stay (LOS). On multivariate logistic regression, increasing mFI-5 score versus mFI-5 = 0 was associated with higher odds of overall complications (mFI-5 =2: odds ratio [OR] 1.44 CI: 1.35–1.52, p &lt; 0.001; mFI-5 = 1: OR 1.18 CI: 1.12–1.24, p &lt; 0.001) and 30-day mortality (mFI-5 =2: OR 2.32 CI: 1.60–3.37, p &lt; 0.001). CONCLUSIONS: This study demonstrates that frailty, when measured using the mFI-5, independently predicts postoperative complications, hospital LOS, and 30-day mortality after surgical repair of thoracolumbar fractures. These findings are important for risk stratification in patients undergoing thoracolumbar fusion surgery and for standardization in reporting outcomes after those procedures.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report

BackgroundRECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. ObjectiveTo describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. MethodsMedical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). ResultsUnipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least 1 INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. ConclusionsRECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing 1 or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. Trial registrationClinicalTrials.gov Identifier NCT03887715.

The association between C-reactive protein to albumin ratio and infarct location in patients with ST-segment elevation myocardial infarction

Purpose: Inflammation has a crucial role in the pathogenesis of ST segment elevation myocardial infarction (STEMI). Recently, the C-reactive protein to albumin ratio (CAR) has emerged as a novel parameter of systemic inflammation. Although studies have demonstrated the that anterior STEMI location is associated with a higher infarct size and worse prognosis, no study has investigated the CAR in relation to infarct location. We herein aimed to evaluate whether there is a difference regarding the CAR between patients with anterior and non-anterior STEMI location.&#x0D; Materials and Methods: The study population comprised 273 consecutive STEMI patients who were divided into 2 groups based on the STEMI location, as the anterior STEMI group (n=114) and non-anterior STEMI group (n=159). Baseline characteristics were recorded, and the CAR was calculated for all patients. &#x0D; Results: Both groups were similar in terms of the baseline clinical characteristics. However, syntax score (p

Electrical Activity Changes and Neurovascular Unit Markers in the Brains of Patients after Cardiac Surgery: Effects of Multi-Task Cognitive Training

Background: There is growing interest in finding methods to enhance cognitive function and comprehend the neurophysiological mechanisms that underlie these improvements. It is assumed that non-pharmacological interventions have better results in cognitive recovery. The aim of this study was to assess the effect of multi-task cognitive training (MTT) on electroencephalographic (EEG) changes and markers of the neurovascular unit in patients undergoing coronary artery bypass grafting (CABG). Methods: This prospective cohort study involved 62 CABG patients aged 45–75 years, 30 of whom underwent a 5–7-day MTT course. The groups of patients were comparable with respect to baseline clinical and anamnestic characteristics. An EEG study was performed before surgery and 11–12 days after CABG. Markers of the neurovascular unit (S100β, NSE, and BDNF) were examined at three time points: before surgery, within the first 24 h after surgery, and 11–12 days after CABG. Results: Patients without training demonstrated higher relative theta power changes compared to the MTT patients. The course of MTT was associated with low plasma S100β concentration but high BDNF levels at the end of the training course. Conclusions: The theta activity changes and the markers of the neurovascular unit (S100β, BDNF) indicated that the severity of brain damage in cardiac surgery patients after a short course of MTT was slightly reduced. Electrical brain activity indicators and vascular markers can be informative for monitoring the process of cognitive rehabilitation in cardiac surgery patients.

Baseline clinical and neuroradiological predictors of outcome in patients with large ischemic core undergoing mechanical thrombectomy: A retrospective multicenter study.

Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT. The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm. A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206-0.770) or M4 (OR = 0.496, 95% CI = 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact. Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT. The data that support the findings of this study are available upon reasonable request.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.