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A portion of individuals diagnosed with primary central nervous system lymphomas (PCNSL) may experience early relapse or refractory (R/R) disease following treatment. This research explored the potential of MRI-based radiomics in forecasting R/R cases in PCNSL. Forty-six patients with pathologically confirmed PCNSL diagnosed between January 2008 and December 2020 were included in this study. Only patients who underwent pretreatment brain MRIs and complete postoperative follow-up MRIs were included. Pretreatment contrast-enhanced T1WI, T2WI, and T2 FLAIR imaging were analyzed. A total of 107 radiomic features, including 14 shape-based, 18 first-order statistical, and 75 texture features, were extracted from each sequence. Predictive models were then built using five different machine learning algorithms to predict R/R in PCNSL. Of the included 46 PCNSL patients, 20 (20/46, 43.5%) patients were found to have R/R. In the R/R group, the median scores in predictive models such as support vector machine, k-nearest neighbors, linear discriminant analysis, naïve Bayes, and decision trees were significantly higher, while the apparent diffusion coefficient values were notably lower compared to those without R/R (p < 0.05). The support vector machine model exhibited the highest performance, achieving an overall prediction accuracy of 83%, a precision rate of 80%, and an AUC of 0.78. Additionally, when analyzing tumor progression, patients with elevated support vector machine and naïve Bayes scores demonstrated a significantly reduced progression-free survival (p < 0.05). These findings suggest that preoperative MRI-based radiomics may provide critical insights for treatment strategies in PCNSL.

Drugs of abuse can persistently change the reward circuit in ways that contribute to relapse behavior, partly via mechanisms that regulate chromatin structure and function. Nuclear orphan receptor subfamily4 groupA member2 (NR4A2, also known as NURR1) is an important effector of histone deacetylase 3 (HDAC3)-dependent mechanisms in persistent memory processes and is highly expressed in the medial habenula (MHb), a region that regulates nicotine-associated behaviors. Here, expressing the Nr4a2 dominant negative (Nurr2c) in the MHb blocks reinstatement of cocaine seeking in mice. We use single-nucleus transcriptomics to characterize the molecular cascade following Nr4a2 manipulation, revealing changes in transcriptional networks related to addiction, neuroplasticity, and GABAergic and glutamatergic signaling. The network controlled by NR4A2 is characterized using a transcription factor regulatory network inference algorithm. These results identify the MHb as a pivotal regulator of relapse behavior and demonstrate the importance of NR4A2 as a key mechanism driving the MHb component of relapse.

To define the clinical, serological, and muscle histopathological characteristics, as well as treatment outcomes, of patients with anti‐Ha antibody. We performed a retrospective analysis of clinical, serological, and pathological data and long‐term treatment outcomes of anti‐Ha patients between January 2005 and July 2023 at our center. Anti‐Ha antibody was identified by immunoblot and reconfirmed by immunoprecipitation. Of the 570 patients with idiopathic inflammatory myopathies, 17 (3.0%) were found to be anti‐Ha positive, of whom 5 (29.4%) were also positive for another myositis‐specific antibody (MSA). All patients with anti‐Ha antibody as the single MSA (12/17, 70.6%) had clinical and histopathological evidence of muscle damage. Skin lesions were identified in nine of them (75%), while both interstitial lung disease and Raynaud's phenomenon were only seen in four patients. A necrotizing myopathy without a perifascicular pattern was the most common pathological manifestation (50%). Perifascicular necrosis (PFN) and myofiber major histocompatibility complex class‐II expression were observed only in one and four patients, respectively. Muscle weakness relapse was reported in five patients, and skin rashes worsening were observed in one patient. Most of the anti‐Ha patients (66.7%) finally achieved a favorable outcome at last follow‐up. Anti‐Ha antibody might not be as rare as previously thought and may coexist with other MSAs. Muscle damage is the most common manifestation in anti‐Ha patients, while extra‐muscular symptoms except for the cutaneous manifestations are unusual. The histopathological features varied with a predominance of necrotizing myopathy without PFN. These patients often finally had favorable outcomes, although relapses often occur. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Elderly people with multiple sclerosis (pwMS) present higher probability of malignancies. Immune checkpoint inhibitors (ICIs) improve cancer prognosis but pose risk of disease flares in people with pre‐existing autoimmune conditions, including MS. Data addressing the impact of ICIs on MS are scarce. This systematic review and meta‐analysis evaluates the effects of ICIs on MS disease activity.A systematic literature search in Google Scholar and PubMed, following PRISMA 2020 guidelines, identified five observational studies. Data on clinical and neuroradiological outcomes were analyzed using random‐effects models.The clinical activity meta‐analysis included 90 pwMS undergoing ICI therapy (median follow‐up = 0.62–1.85 years, 103.74 patient‐years). The pooled relapse rate was 5.45 per 100 patient‐years (95% confidence interval [CI] = 1.86–14.92). Median time to relapse was 1 month after the ICI start (range = 0.4–6 months). No relapse occurred after 58 years. The neuroradiological activity meta‐analysis was conducted on 36 pwMS (median magnetic resonance imaging [MRI] follow‐up = 0.75–1.85 years, 41.94 patient‐years). The pooled new MRI lesion rate was 24.9 per 100 patient‐years (95% CI = 10.9–47.3), with median time to new MRI lesions of 3 months (range = 1–6 months). In 80% of cases, disease‐modifying treatment (DMT) was suspended at ICI initiation.We found a low relapse rate in pwMS following ICI treatment, with no events in older pwMS. The risk of neuroradiological activity appears higher, but mainly occurs in pwMS who discontinued DMT. All events occurred within the first 6 months of ICI therapy. These conclusions are based on small observational studies, highlighting the urgent need for further research on this topic. [ABSTRACT FROM AUTHOR]

AbstractBackground and AimsMethodResultsConclusionsWhen entering substance abuse treatment centers, some individuals with substance use disorder relapse whilst others do not. Predicting who is likely to relapse or not would enable for more effective treatment by targeting those who are at increased risk. Previous research would indicate that aspects related to cognitive control including cognitive bias, inhibitory control, and working memory may all be strong indicators of relapse likelihood. Therefore, this paper explores whether aspects of cognitive control can predict relapse likelihood.Participants were patients in substance treatment centers who were abstaining. They were tested on measures of cognitive bias (REsT), inhibitory control (go/no-go), and working memory (nBack). A follow-up survey was then issued after a twelve-week period to ascertain whether participants had remained abstinent or if they had relapsed.Relative to abstainers, individuals who relapsed had shown significant impairments in working memory and inhibitory control at baseline. They had also demonstrated increased preoccupation with substance-related stimuli as indicated by the cognitive bias measure.These findings demonstrate that deficits in cognitive control contribute to the maintenance of substance use disorder and substance usage. The results indicate that inhibitory and working memory deficits may contribute to initial engagement in substance abuse, followed by an increase in cognitive bias and further deficits in inhibitory control and WM contributing to an increased likelihood of relapse. This suggests that decreased cognitive control may increase relapse likelihood. [ABSTRACT FROM AUTHOR]

Background: Wilms tumor (WT) is the most common malignant renal tumor in children. This study investigated the clinical features, pathological findings, and outcomes of children with malignant renal tumors in Southern Iran. Factors associated with recurrence and mortality were assessed. Methods: Electronic files of children with malignant renal tumors from 2009 to 2023 were reviewed. The 5-year overall survival (OS) and event-free survival (EFS) were reported. Results: Eighty-three patients (44 males) with a median age of 40 months (range: 3-122) were included. WT was the most common pathological variant (94%). Anaplasia was found in 17.3% of patients. Upfront chemotherapy followed by nephrectomy was performed in 54.2% of the patients. Ten patients (12%) experienced relapse, and five patients (6%) died during the 14-year follow-up. The 5-year OS and EFS were 90.75% (95% CI, 78.64–96.16%) and 81.9% (95% CI, 70.10-89.38%), respectively, and were comparable between the two treatment strategies (upfront chemotherapy vs. upfront nephrectomy). Metastasis and residual disease were associated with relapse, whereas tumor recurrence was the only predictive factor of survival. Conclusion: WT is a curable disease with excellent outcomes if diagnosed and treated promptly. The timing of nephrectomy does not affect OS and EFS. Patients with low-stage tumors and those with complete surgical excision are at a lower risk of tumor recurrence. Relapse is the primary risk factor for death. [ABSTRACT FROM AUTHOR]

This study aimed to identify laboratory factors predicting leprosy relapse (LR) after multi‐drug therapy (MDT). A case–control study included 80 patients treated with MDT at a national reference center over 12 years. The Relapse Group had 40 patients who relapsed after an average of 89.2 months post‐MDT, while the Control Group had 40 patients who remained asymptomatic for an average of 113.1 months. Significant predictors of LR included neural/perineural lymphocytic infiltrate (OR = 4.67; p = 0.0076) and foamy granulomas (OR = 15.55; p = 0.0005), increasing odds by 4.7 and 15.6 times, respectively. The Relapse Group had a mean histological bacillary index (hBI) of 3.23+ compared to 1.8 in the Control Group (p = 0.004). An hBI ≥3+ had 72% sensitivity and 65% specificity for detecting LR (AUC = 0.72; p = 0.0002). Elevated anti‐phenolic glycolipid I (anti‐PGL‐I) IgM antibody levels (ELISA index, EI ≥1) were also associated with LR (OR = 4.67; p = 0.0031). An EI ≥3.6 had 71% sensitivity and 62% specificity (AUC = 0.70; p = 0.0012). Multivariate analysis indicated that neural/perineural infiltrate, foamy granulomas, hBI ≥ 1+, and EI ≥ 1 significantly predicted LR, with up to 94.32% probability. Conclusively, these factors can identify individuals at high probability of LR after MDT. [ABSTRACT FROM AUTHOR]

The objective of this study is to report the long‐term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event‐free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre‐specified groups. Two hundred and twenty‐two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8‐year EFS was 75% (95% confidence interval: 69%–83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow‐up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post‐chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Liquid biopsy is gaining momentum for diagnosis and surveillance of cancer patients. Indeed, head and neck squamous cell carcinoma (HNSCC) is burdened with poor prognosis and high recurrence rates after treatment. It is therefore crucial to be able to detect minimal residual disease early after radical treatment or relapse, so surgery can be performed when the disease is still resectable. In this scenario, aim of this study is to create a liquid biopsy-based pipeline able to detect somatic tumor mutations in a cohort of HNSCC-affected patients undergoing follow-up after surgical intervention. Methods: Our cohort included 17 patients diagnosed with HNSCC over 4 years. The first saliva sample was collected before surgery while the rest were collected during the subsequent visits, according to the follow-up schedule. Salivary DNA (sDNA) was extracted, and a 52-gene next generation sequencing (NGS)-based panel was used for somatic variants detection. Results: 41.2% of samples collected before surgery bore a deleterious variant (n=7/17). Overall, 29.2% of samples harbored at least a pathogenic variant (n=21/72). The most frequently mutated genes were TP53 (80%), FBXW7 (8%), PDGFRA (4%) and PTEN (4%). Finally, three patients experienced a loco-regional relapse by clinical evaluations, anticipated in 67% of cases by the molecular one (n=2/3). Discussion: Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data. [ABSTRACT FROM AUTHOR]

Resurgence is a transient recovery of a previously extinguished target response following a worsening of reinforcement conditions for an alternative response. Laboratory studies with nonhuman animals typically assess resurgence in free‐operant situations where subjects can freely emit responses. The purpose of the current study was to investigate whether resurgence would be observed in a discrete‐trial procedure where only a single response could occur in each trial, using rats as subjects. The experiment consisted of three phases, and each session ended after 200 trials. All trials began with the insertion of target and alternative levers and ended once a response was emitted. In Phase 1, both target and alternative responses were reinforced with a probability of .25. In Phase 2, the target response was extinguished while still reinforcing the alternative response with a probability of .25. Finally, resurgence was tested by placing the alternative response on extinction. All rats showed robust resurgence in this highly constrained discrete‐trial situation. We also found that the latencies of resurged target responses differed from those in Phase 1. Overall, the present discrete‐trial procedure could produce reliable resurgence as with typical free‐operant procedures and has several potential benefits for studying resurgence. [ABSTRACT FROM AUTHOR]

Pregenomic hepatitis B virus RNA (HBV pgRNA) is a potential biomarker in the management of HBV infected patients. However, prior to the use in routine clinical practice potential confounders of test results need to be identified. This study investigates the stability of HBV pgRNA under various storage conditions. HBV-RNA level of 26 HBV patients were determined using the Roche cobas® 6800/8800 investigational HBV-RNA assay. Plasma and serum were stored for 6,48,169 h at 4,25 and 42 °C, respectively. Additionally, 10 serum and plasma samples underwent 4 or 11 cycles of freezing (−80 °C) and thawing (25 °C). A significant decline in mean pgRNA concentration compared to baseline was observed after storage for 48 h at 25 °C as well as after 6 h of storage at 42 °C. Accordingly, sub-analyses of predefined pgRNA baseline concentrations (≤ 10 cp/mL, > 10–100 cp/ml, > 100 cp/mL) revealed significant changes in pgRNA level after storage at 25 and 42 °C. No effect of freezing and thawing on pgRNA level was observed. A qualitative detection of HBV pgRNA is feasible in samples with > 100 cp/mL up to 48 h under storage temperatures of 4–42 °C. For most stable quantitative HBV pgRNA values storage at 4 °C should be preferred. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis (VL) is a neglected tropical disease primarily affecting Brazil, East Africa, and India, with India accounting for 18% of the global burden. While VL typically presents with systemic symptoms like fever, weight loss, and splenomegaly, it can occasionally manifest atypically, posing significant diagnostic challenges. Neurological presentations of VL are extremely rare, making them difficult to suspect and diagnose. Cases where VL predominantly presents with neurological symptoms are particularly novel, underscoring the need for heightened awareness of such atypical manifestations in endemic regions. Clinical case: A 38-year-old man with history of recurrent atypical VL presented with diffuse lower back pain, progressive tingling, numbness, weakness in the lower extremities, and double vision for one month. Clinical and radiological evaluations suggested cauda equina syndrome and cranial nerve palsy, accompanied by generalized lymphadenopathy, subcutaneous nodules, and skin papules. The differential diagnosis initially included disseminated tuberculosis, histoplasmosis, and lymphoma. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. Histopathology of lymph node and bone marrow revealed Leishmania amastigotes and subcutaneous nodule and skin biopsy revealed inflammatory cells with granulomas. Furthermore, the qPCR test on DNA from a subcutaneous nodule, lymph node, and CSF was positive for Leishmania kinetoplast DNA. The species was further confirmed as Leishmania donovani through ITS-based PCR amplification and sequencing. Finally, a diagnosis of relapse of VL with lymph node, cutaneous, and neurological involvement, including abducens nerve palsy and cauda equina syndrome, was established. He was treated with combination of liposomal amphotericin B and miltefosine, along with intrathecal hyaluronidase, resulting in significant improvement. Conclusion: Unlike previously reported cases with both systemic and neurological symptoms, our patient predominantly presented with neurological manifestations, making this a unique and novel presentation of VL. This case highlights diagnostic challenges and management of atypical VL, emphasizing neurological involvement and successful therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: The United Arab Emirates is among the countries affected by substance use disorders (SUDs), which have economic and social impacts. Relapse after successful rehabilitation is a major issue in the treatment of SUD. Several factors increase the risk of relapse in patients with SUD, such as craving and negative social experiences. Resilience could empower patients struggling with SUD. This study aims to explore levels of resilience and relapse risk in adult Emirati patients diagnosed with SUD, and also the possible correlation between the two variables. Methods: Two hundred eighty-six Emirati adult patients with SUD completed a self-administered questionnaire for demographics, resilience (Connor and Davidson Resilience Scale), and relapse risk (Stimulant Relapse Risk Scale). Descriptive statistics (frequency, percentage, mean, SD, etc.) were used to describe study participants and variables. Inferential statistics were used to analyze the relationships, associations, and correlations between resilience and relapse risk, the main variables, and the participants demographics. Result: Participants' mean total score for resilience was 72.92 out of a maximum possible score of 100 (SD = 16.99), while their mean total score for relapse risk was 59.07 out of a maximum possible score of 105 (SD = 12.23). Furthermore, examining the correlation between the resilience subscales and the relapse risk subscales revealed similar significant, negative, low-to-moderate correlations between all the subscales (r = -0.486). Discussion: Protective and risk factors to enhance resilience and reduce relapse risk in patients with SUD were discussed. [ABSTRACT FROM AUTHOR]

Background: In children, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Given the lack of data on the best chemotherapy regimen, there is a knowledge gap in best management. Methods: This retrospective study included all pediatric patients with NLPHL diagnosed and treated at the Children's Cancer Hospital, Egypt (2007–2018). We analyzed the clinical characteristics, and treatment outcome according to disease stage (early and advanced), treatment strategy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD] or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] and explored the prognostic factors for progression-free survival. Results: The median age at diagnosis was 12 years; 40 (68%) patients had early-stage disease, and 19 (32%) had advanced-stage disease. The median follow-up was 70 months; the 5-year EFS and OS were 75% and 97%, respectively. The 5-year EFS was 78% for early-stage disease and 60% for advanced-stage disease; the 5-year OS was 100% for early-stage disease and 88% for advanced-stage disease. The patients who underwent R-CHOP had a better 3-year EFS (100%) compared with those who underwent ABVD (65%) regimen (P = 0.01). Seventeen (25%) patients relapsed: 9/40 (22%) had early-stage disease, and 8/19 (42%) had advanced-stage disease. Splenic involvement, mediastinal disease, extranodal disease, and slow early response were independent predictors of relapse risk. Conclusion: Pediatric patients with early-stage NLPHL have an excellent prognosis, with a 5-year OS of 100%. However, those with advanced stages had a high relapse rate. R-CHOP was associated with a better response and relapse-free rate than ABVD. [ABSTRACT FROM AUTHOR]

Background: Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity. The phase 3 ULTIMATE I and II studies showed significant improvements in annualized relapse rate, total number of gadolinium-enhancing (Gd+) T1 lesions, and total number of new or enlarging T2 at Week 96, as well as improvement in the proportion of participants with no evidence of disease activity (NEDA) from Weeks 24–96 with ublituximab vs. teriflunomide. Methods: In ULTIMATE I (NCT03277261; www.clinicaltrials.gov) (N = 549) and II (NCT03277248; www.clinicaltrials.gov) (N = 545), participants with relapsing multiple sclerosis received ublituximab 450 mg intravenous infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks. Pooled post hoc analyses evaluated NEDA by treatment epoch and participant subtype: age (≤ 38 or >38 years), early or later disease (<3 or ≥3 years following diagnosis), treatment history (treatment naïve or previously treated), 0 or ≥1 Gd+ T1 lesions at baseline, and Expanded Disability Status Scale score ≤ 3.5 or >3.5 at baseline. NEDA was defined as no confirmed relapses, no Gd+ T1 lesions, no new or enlarging T2 lesions, and no disability progression confirmed for ≥12 weeks. Results: NEDA rates in the ublituximab vs. teriflunomide cohorts by treatment epoch were: Weeks 0–96, 44.6% vs. 12.4% (3.6 × improvement); Weeks 24–96 (re-baselined), 82.1% vs. 22.5% (3.6 × improvement); and Weeks 48–96 (re-baselined), 88.2% vs. 30.4% (2.9 × improvement) (all p < 0.0001). The primary driver of disease activity in ublituximab-treated participants was new or enlarging T2 lesions during Weeks 0–24. 41.8% of ublituximab-treated participants who had evidence of disease activity in the first year (Weeks 0–48) experienced NEDA in the second year of treatment (Weeks 48–96) compared with 17.3% of teriflunomide-treated participants. At Weeks 24–96 (re-baselined), rates of NEDA were significantly higher with ublituximab than teriflunomide in all participant subtypes (all p < 0.0001). Conclusions: ULTIMATE I and II pooled post hoc analyses demonstrated a consistent NEDA benefit among ublituximab-treated participants across treatment epochs and key participant subpopulations. [ABSTRACT FROM AUTHOR]

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort. Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort. Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years. Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed. Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09–0.11]) compared to controls (ARR = 0.07 [95% CI 0.06–0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29–1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92–1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25–2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06–3.90]) compared to patients on BRACE therapy without COVID-19 infection. Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T-cell (CAR-T) therapy has ushered in a new era for the treatment of multiple myeloma (MM). Numerous clinical studies, especially those involving B-cell maturation antigen (BCMA)-directed CAR-T, have shown remarkable efficacy in patients with relapsed or refractory multiple myeloma (R/R MM). However, a considerable number of patients still experience disease recurrence or progression after BCMA CAR-T treatment, which is attributed to various factors, including antigen escape, CAR-T manufacturing factors, T cell exhaustion, inhibitory effects of tumor microenvironment and impact of prior treatments. The scarcity of effective treatment options following post-CAR-T disease recurrence, coupled with the lack of well-established salvage regimens, leaves patients who do relapse facing a bleak prognosis. In recent years, some academic institutions have achieved certain results in salvage treatments of patients with relapse after BCMA CAR-T treatment through secondary infusion of BCMA CAR-T, changing to non-BCMA-directed CAR-T, double-target CAR-T, bispecific antibodies or other novel therapies. This review summarizes the mechanisms of resistance or relapse after BCMA CAR-T administration and the available data on current salvage treatments, hoping to provide ideas for optimizing clinical salvage therapies. [ABSTRACT FROM AUTHOR]

Objective: In adult anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first‐line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT courses in anti‐NMDAR encephalitis. Methods: The CHASE study, a multicenter prospective observational cohort study, enrolled patients with autoimmune encephalitis from October 2011 to March 2023. Patients were grouped based on oral prednisone tapering course: ≤3 months (Group ≤3 month), 3–6 months (Group 3–6 months, including 3 months), and >6 months (Group > 6 months). Kaplan–Meier plots were used to analyze time to relapse and time to total recovery within 2 years. Results: Among 666 screened patients, 171 (median [IQR] age 27 [21.0–36.5] years, 55.0% female) met selection criteria. Responders at 3 months were prevalent in Group ≤3 months (OR 7.251 [95% CI 2.252 to 23.344] and Group 3–6 months (OR, 3.857 [95% CI 1.107 to 13.440] than in Group >6 months. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months were higher in Group >6 months than in Group ≤3 months and Group 3–6 months (β, −2.329 [95% CI −3.784 to −.875]; β, −2.871 [95% CI −4.490, −1.253]). CASE seizures subscore was higher in Group >6 months than in Group 3–6 months (β, −.452 [95% CI −.788 to −.116]). No significant difference in seizure freedom rates among the groups. Adverse events were higher in Group 3–6 months and Group >6 months than in Group ≤3 months (OR 6.045 [95% CI 2.352 to 15.538]; OR 6.782 [95% CI 1.911 to 24.073]). Significance: Longer oral prednisone courses for adult patients with anti‐NMDAR encephalitis did not show superior effects compared to shorter courses in improving modified Rankin Scale (mRS) scores and CASE scores, reducing the risk of relapse within 2 years, or achieving seizure freedom. Instead, extended prednisone courses may lead to more side effects— particularly weight gain. This outcome recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment. [ABSTRACT FROM AUTHOR]

One of the most common treatments for severe challenging behavior involves placing the challenging behavior on extinction and differentially reinforcing an alternative response (DRA). However, extinction is not always feasible and may be unsafe or impractical to implement in some circumstances. Thus, implementing a DRA without extinction intervention may be necessary for some cases. Currently, the extent to which DRA without extinction produces durable treatment outcomes, particularly as it relates to the resurgence of challenging behavior, is unclear. The present study investigated resurgence following DRA with and without extinction using a three‐phase resurgence evaluation in a translational human operant model with college students as participants. All participants demonstrated resurgence across both experimental groups. Although there were no statistically significant differences in the prevalence, magnitude, or persistence of resurgence between groups, levels of resurgence magnitude were relatively higher in the DRA‐without‐extinction group than in the DRA‐with‐extinction group. Clinical implications of these findings and directions for future human operant investigations of resurgence are discussed. [ABSTRACT FROM AUTHOR]

Summary: Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi‐institutional, single‐arm, prospective phase II trial, to investigate intensified conditioning with 'Mega‐Dose' decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo‐HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient (n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax‐based regimens. All patients underwent intravenous decitabine (400 mg/m2) along with busulfan and cyclophosphamide. Median follow‐up was 26 months (8–65) after HCT. All engrafted patients achieved MRD negativity post‐HCT, with a median 3.3‐log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III–IV toxicity peri‐engraftment. The estimated 2‐year CIR was 29.6% (18.4%–41.7%) and the est‐2‐year NRM was 15.5% (7.8%–25.5%). The est‐2‐year LFS, OS, and GRFS were 55.0% (43.5%–69.4%), 58.6% (47.0%–73.0%), and 42.9% (31.9%–57.6%), respectively. Multivariate analysis showed that pre‐HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies. [ABSTRACT FROM AUTHOR]

Summary: The immunosuppressive treatment of immune‐mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B‐cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell‐directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin‐1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse‐free survival was not reached; 12‐month ADAMTS13 relapse‐free survival was 56%. Daratumumab‐related adverse events occurred in five cases and were non‐severe infusion‐related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background and Aims: Outcome analysis of patients with Wilms' tumors (WT) is presented. Materials and Methods: A retrospective analysis of 23 children having WT managed by a single surgeon over 3 years (2021–2024) using the International Society of Paediatric Oncology Umbrella protocol was done. Results: The median age at presentation was 36 months; 32 months and 24 months for the unilateral WT (uWT) (n = 19) and bilateral WT (bWT) (n = 4), respectively. M: F ratio was 2.3: 1. WTs were localized in 19 (uWT-16; bWT-3) and metastatic in 4 (uWT-3; bWT-1) patients. Core-needle biopsy was done in 22 patients (26 renal units). Pre-therapy contrast-enhanced computed tomography volumetry (n = 20) showed a median tumor volume of 1023 ml (range: 47–2680 ml). Post-neoadjuvant chemotherapy (NACT) median tumor burden (n = 19) was 612 ml (range 59–3775 ml). Post-NACT, tumor volume decreased in 11/18 patients but increased in seven patients. NACT was avoided in one neonate. Nephroureterectomy (including one with excision of bladder cuff) and nephron-sparing surgery were done in 17 and 10 renal units including 3 with multifocal WT, respectively. Risk stratification was intermediate in 21 and High in 2. Overall staging in 19 uWT included Stage I-7, Stage II-5, Stage III-4, and Stage IV-3 (local staging-stage I in 1 and stage II in 2). Local staging in 8 renal units with bWT was Stage I in 7 and II in 1. One stage IV uWT had bilateral pulmonary metastatectomy. Adjuvant chemotherapy has been completed in 18 patients; two patients are still on adjuvant chemotherapy; flank radiation was administered in six patients. Three patients with synchronous bWT died; two due to acute kidney injury in the immediate postoperative period and one with metastatic disease who had abandoned adjuvant chemotherapy after the 1st cycle. Another patient died of a huge metachronous tumor in the contralateral kidney after a year of completion of therapy. One patient had successful multimodality treatment of local relapse with liver metastasis. 1-year overall and event-free survivals are 84% and 76%, respectively. Conclusions: Excellent short-term results for localized uWT from a center in a low-middle-income country are reported. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse. Background: Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re‐visits to emergency settings. Methods: A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta‐analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493). Results: From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52–0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01–0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14–0.75), ergot agents (RR 0.44, 95% CI 0.25–0.75), neuroleptics (RR 0.47, 95% CI 0.31–0.71), opioids (RR 0.58; 95% CI 0.35–0.94), or corticosteroids (RR 0.64, 95% CI 0.47–0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01–0.71), combination therapy (RR 0.12, 95% CI 0.02–0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44–0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses. Discussion: Corticosteroids remain the recommended first‐line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events. Plain Language Summary: After leaving the hospital, some patients will have a relapse of migraine pain and may return to the emergency department, but we do not always know why this is or how to best help these patients. While corticosteroids can reduce relapse, we systematically reviewed the direct and indirect evidence for injectable medications to reduce relapse in patients with migraine. The results of our review indicated that (1) the duration of migraine pain and having pain at discharge were associated with relapse, and (2) routinely used medicines besides corticosteroids (e.g., neuroleptics and ergot agents) may be effective in reducing relapse. [ABSTRACT FROM AUTHOR]

The prognosis of patients with high-risk acute myeloid leukemia (AML) is dismal even after allogeneic stem cell transplantation (allo-HSCT), with relapse remaining the leading cause of treatment failure. Here, we investigated whether ruxolitinib and decitabine plus modified busulfan-cyclophosphamide (mBu/Cy) conditioning could reduce relapse in high-risk AML after allo-HSCT. This prospective, single-arm, phase II trial enrolled 37 patients who received allo-HSCT between September 2020 and March 2022 at the First Medical Center of Chinese People's Liberation Army (PLA) General Hospital. Eligible patients (10–62 years) had relapsed/refractory, positive measurable residual disease (MRD) prior to conditioning or adverse genetic abnormalities. Ruxolitinib (35 mg twice daily, days − 15 to − 10) and decitabine (20 mg/m2/day, days − 15 to − 10) were administered followed by mBu/Cy conditioning. All patients achieved engraftment. The cumulative incidences (CIs) of acute graft-versus-host disease (GVHD) grades II–IV and III–IV were 35.0% and 10.5%, respectively. The 1-year cumulative incidence of chronic GVHD was 8.1%. The 1-year CI of relapse was 29.7% among all patients, 0% in patients who achieved the first complete remission (CR1) prior to conditioning, and 0% in those with MRD-negative prior to conditioning. The 1-year non-relapse mortality was 5.4%. The 1-year probabilities of overall survival, disease-free survival, and GVHD-free relapse-free survival were 70.3%, 62.2%, and 54.1%, respectively. In conclusion, the novel conditioning showed primary efficacy in terms of a reduction in relapse in high-risk patients with AML after allo-HSCT, especially in those who achieved CR1 and MRD-negative prior to conditioning. Also, the new conditioning regimen may help reduce the incidence of chronic GVHD. ClinicalTrials.govidentifier: NCT04582604. [ABSTRACT FROM AUTHOR]

Focusing on how to deal with relapses when trying to desist from crime, this article utilises findings from a qualitative and prospective interview study to illustrate what it means to desist. Ten women's desistance journeys have been studied longitudinally since 2015. Over these years, the women have encountered setbacks and relapses, yet somehow persevered on their path towards a different 'normal' life, free from crime, condemnation and marginalisation. Their struggle highlights the need for persistence to sustain desistance from crime. Persistence and desistance are generally conceptualised as each other's counterparts within life-course criminology, yet putting persistence at the heart of desistance journeys can deepen our understanding of the process involved. [ABSTRACT FROM AUTHOR]

Mesolimbic dopamine (DA) transmission is believed to play a critical role in mediating reward responses to drugs of abuse, including alcohol (EtOH). The neurobiological mechanisms underlying EtOH-seeking behavior and dependence are not fully understood, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Here, we developed novel RGS6fl/fl; DAT-iCreER mice to determine the role of RGS6 in DA neurons on EtOH consumption, reward, and relapse behaviors. We found that RGS6 is expressed in DA neurons in both human and mouse ventral tegmental area (VTA), and that RGS6 loss in mice upregulates DA transporter (DAT) expression in VTA DA neuron synaptic terminals. Remarkably, loss of RGS6 in DA neurons significantly reduced EtOH consumption, preference, and reward in a manner indistinguishable from that seen in RGS6−/− mice. Strikingly, RGS6 loss from DA neurons before or after EtOH behavioral reward is established significantly reduced (~ 50%) re-instatement of reward following extinguishment, demonstrating distinct roles of RGS6 in promoting reward and relapse susceptibility to EtOH. These studies identify DA neurons as the locus of RGS6 action in promoting EtOH consumption, preference, reward, and relapse. RGS6 is unique among R7 RGS proteins in promoting rather than suppressing behavioral responses to drugs of abuse and to modulate EtOH behavioral reward. This is a result of RGS6's pre-synaptic actions that we hypothesize promote VTA DA transmission by suppressing GPCR-Gαi/o-DAT signaling in VTA DA neurons. These studies identify RGS6 as a potential therapeutic target for behavioral reward and relapse to EtOH. [ABSTRACT FROM AUTHOR]

Background: Hyperkeratotic hand and foot dermatitis significantly affects quality of life. Some patients respond suboptimally to topical corticosteroids and have multiple recurrences. Objective: Our aim was to compare the efficacy and safety profile of apremilast and topical corticosteroid versus corticosteroid alone in hyperkeratotic hand and foot dermatitis. Methods: This randomized controlled study involved 77 patients treated for 3 months. Group A (39 patients) received mometasone furoate 0.1% cream with oral apremilast 30 mg twice daily, and Group B (38 patients) received mometasone alone. They were assessed monthly using the Hand Eczema Clinical Severity Index (HECSI) and Visual Analogue Scale (VAS) scores for pruritus. Investigator Global Assessment (IGA) and Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were conducted at the end of 3 months. Results: The HECSI, VAS score, and QOLHEQ showed a significant decrease in both groups from baseline to the third month. Intergroup comparisons of HECSI failed to reach the significance level. When compared, patients receiving apremilast had significantly better improvement in the third month according to the Patient Global Assessment (PGA) and Investigator Global Assessment (IGA). They also had a smaller number of flares. Conclusion: Adding apremilast to topical corticosteroid leads to better patient and physician‐perceived improvement and reduces the number of flares in hyperkeratotic hand eczema. [ABSTRACT FROM AUTHOR]

Objective: To identify the risk factors for relapse of idiopathic inflammatory myopathies (IIMs). Methods: Patients who were newly diagnosed with IIMs and underwent muscle biopsy between 2000 and 2017 at Asan Medical Center were retrospectively reviewed. The relapse of IIMs was defined as the recurrence of muscle or cutaneous manifestations with a ≥50% increase in glucocorticoid dosage after reaching the low-dose glucocorticoid phase with clinically significant improvement. The factors associated with the relapse of IIMs were investigated by Cox proportional hazards analysis. Results: Of 105 patients with IIMs, relapse was observed in 65 patients (62%). The titer of antinuclear antibody (ANA) was higher in the relapse group than in the non-relapse group (P = 0.033). Multivariable analysis showed that the relapse of IIMs was significantly associated with histopathologic features consistent with IIMs (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.01–2.83, P = 0.045) and the use of immunosuppressants before relapse (HR, 0.50; 95% CI, 0.29–0.86, P = 0.013). Doubling of ANA titer was also associated with relapse, albeit without statistical significance (HR, 1.13; 95% CI, 1.00–1.27, P = 0.052). Conclusion: In patients with IIMs, the use of immunosuppressants had a significant negative association with relapse. Administering immunosuppressants from the early period during the initial glucocorticoid tapering phase may be useful in reducing the risk of relapse in patients with IIMs. Key Points • Since idiopathic inflammatory myopathies (IIMs) have a low prevalence, it is poorly understood which factors are associated with the relapse of IIMs. • In this study, about two-thirds of 105 patients with IIMs experienced a relapse of IIMs. • The risk of relapse in patients with IIMs was negatively associated with the use of immunosuppressants during glucocorticoid tapering and low-dose glucocorticoid phase. • Even in less severe cases, the use of immunosuppressants might be a good option for the management of IIMs. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is recognized as a chronic relapsing disorder. Alcohol Relapse Risk Scale (ARRS), a multidimensionally self-rating scale, was developed initially by the Japanese to assess the risk of alcohol reuse. The study aimed to validate the reliability and factor structure of the Chinese version of the ARRS (C-ARRS) for patients with AUD. A total of 218 patients diagnosed with AUD according to DSM-5 were recruited for self-administering C-ARRS. We assessed the internal consistency of C-ARRS using Cronbach's α coefficients and examined the factor structure through confirmatory factor analysis (CFA). Additionally, we investigated the concurrent validity by correlating C-ARRS with the Visual Analog Scale of Alcohol Craving (VAS), Penn Alcohol Craving Score (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores. CFA demonstrated inadequate data fit for the original 32-item C-ARRS, prompting the development of a revised 27-item version consisting of 6 subscales with satisfactory model fit estimates. The 27-item C-ARRS exhibited favorable internal consistency, with Cronbach's α ranging from 0.611 to 0.798, along with adequate factor loadings. The 27-item C-ARRS scores displayed significant correlations with the scores of VAS, PACS, BDI and BAI (p <.001). Our results indicated favorable reliability and factor structure of the 27-item C-ARRS. The significant correlation between the 27-item C-ARRS and clinical measures (such as depression, anxiety, and craving) demonstrates satisfactory concurrent validity. These observations collectively support the feasibility of using 27-item C-ARRS to assess the risk of alcohol relapse in patients with AUD. • AUD is a prevalent psychiatric disorder characterized by a high rate of relapse. • No tools are available in Chinese to assess the relapse risk in patients with AUD. • We validated the 32-item Chinese version of Alcohol Relapse Risk Scale (CARRS). • The modified 27-item C-ARRS version exhibits satisfactory reliability and validity. • C-ARRS could provide information on relapse risk and facilitate early treatment. [ABSTRACT FROM AUTHOR]

In order to evaluate the early radiographic characteristics of the lateral talocalcaneal (L-TC) angle in patients with idiopathic clubfoot (ICF) and to investigate its prognostic significance for relapse after initial treatment with the Ponseti method. We retrospectively included 151 patients (96 males and 55 females; 227 feet) with ICF treated at our Institution between January 2005 and December 2014. The age at initial treatment was less than 6 months, and radiographs were obtained within 3 months of the Achilles tenotomy (mean age: 2.3 months; range: 0.77-6.8). All patients were followed up for at least 7 years (range, 7-18). The participants' feet were classified into 3 groups: relapsed (Group A), not relapsed (Group B), and normal foot groups which consisted of healthy feet in patients with unilateral ICF (Group C). All angle measurements were expressed in degrees. Forty-seven ICF feet in 33 patients relapsed, while 180 feet in 118 patients did not, and the age at relapse was 5.92 ± 1.91 years. Seventy-five normal feet were included in Group C. The average L-TC angle in Group A and B patients was 33.57° ± 12.05° and 39.37° ± 12.55°, respectively, while Group C was 49.61° ± 9.11°. A significant difference was found among the 3 groups of patients (F = 31.48, p <.001). The L-TC angle cut-off value below which a recurrence could be predicted was 36.1° (sensitivity, 74.47%). The L-TC angle of ICF patients treated using the Ponseti method were reduced compared to normal feet. An L-TC angle of <36.1° has relative value in predicting ICF relapse. [ABSTRACT FROM AUTHOR]

Background/Aim: Pediatric patients with primary refractory or relapsed B-cell non-Hodgkin lymphoma (BNHL) have highly unfavorable prognosis. In this study, we retrospectively analyzed outcomes in pediatric B-NHL patients treated in a single center in Poland from 1995 to 2022, with emphasis on therapy results in patients with progression or relapse. Patients and Methods: The primary objectives were a 5-year probability of overall survival (pOS) and a 5-year probability of event-free survival (pEFS). The secondary objectives involved the assessment of prognostic factors. Results: A total of 76 children were eligible for the analysis. The 5-year pOS was 76.7%, and the 5-year pEFS was 72.9%. At diagnosis, elevated lactate dehydrogenase activity, the presence of B symptoms, bone marrow, skeletal or mediastinal involvement, and stage IV disease were associated with inferior outcomes. Nine children experienced progression and four relapse. The 5- year pOS for patients with progression was 38.1%. Two patients treated with hematopoietic stem cell transplantation (HSCT) as part of salvage therapy survived. However, only one out of seven patients who were treated without HSCT survived. The 5-year pOS was 0.0% in patients with relapsed disease. Conclusion: The most significant factor related to outcomes in pediatric B-NHL is therapy response, with a high mortality rate in children with refractory disease and relapse. There is no consensus on the salvage therapy approach; however, HSCT appears to be the optimal choice. [ABSTRACT FROM AUTHOR]

The Japan Children's Cancer Group Relapsed Acute Lymphoblastic Leukemia (ALL) Committee conducted a prospective observational study (ALL-R14) to explore promising reinduction therapy regimens for relapsed ALL to investigate in future trials. In Japan, clofarabine- and bortezomib-based regimens were of interest since they were newly introduced for ALL in the study period (2015–2018). Seventy-five pediatric patients were enrolled in total. The 2-year event-free/overall survival rates in patients with first (n = 59) or second (n = 11) relapse were 40.1% (95% confidence interval [CI]: 25.5–52.3%)/66.3% (95% CI 52.3–77.0%) and 34.1% (95% CI 9.1–61.6%)/62.3% (95% CI 27.7–84.0%), respectively. Clofarabine- or bortezomib-based regimens were used only in patients with high-risk disease. The first reinduction therapy used in the 41 patients with early or multiple relapsed B-cell precursor ALL was clofarabine in 7 patients and bortezomib in 9 patients. The odds ratio for reinduction failure risk with a clofarabine- or bortezomib-based regimen compared with other regimens was 9.0 (95% CI 0.9–86.4, P = 0.057) or 1.9 (95% CI 0.4–8.7, P = 0.42), respectively. Thus, clofarabine- or bortezomib-based regimens had no obvious advantage as reinduction therapy for relapsed ALL in children. [ABSTRACT FROM AUTHOR]

Background: Second and third surgeries were demonstrated as safe and efficient in recurrent diffuse low-grade glioma (LGG). Here, the feasibility of more than 3 resections is investigated. Methods: Patients who underwent 4 or 5 operations for recurrent initially WHO grade 2 IDH-mutated gliomas were consecutively selected. Results: Twenty-three operations were performed in five patients (all males, mean age 27.2 ± 4 years). Three patients underwent 5 surgeries and two patients underwent 4 surgeries. Twelve procedures (52%) were achieved with awake mapping, including all 4th and 5th operations but one. Repeat electrical mapping detected changes of the cortical maps between at least two awake surgeries in 4 patients. No patients experienced permanent neurological impairment (KPS score ≥ 80 in all cases). The patients returned to work after 22 surgeries among 23 (95.6%). There were 3 oligodendrogliomas and 2 astrocytomas (4 gliomas became malignant at fourth or fifth operation). Although the preoperative tumor volume significantly increased before the fourth (p = 0.026) and fifth operation (p = 0.003) compared with the first operation, there was no significant difference between the residual tumor volume after the fourth or fifth resection versus the first one. The mean delay was 10.6 ± 3.9 years before chemotherapy and 15.4 ± 3.4 years before radiotherapy (one patient never received adjuvant treatment after 21.5 years). The mean follow-up duration was 18.3 ± 3.1 years since the first surgery (2.3 ± 1.8 years since the last surgery). Three patients were still alive at last follow-up. Conclusions: This is the first series showing that to reoperate beyond three times is feasible with a low functional risk and a long survival in multiple LGG recurrences, with the use of awake mapping in 87.5% of 4th and 5th surgeries. [ABSTRACT FROM AUTHOR]

Introduction: This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. Methods: The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. Results: As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Discussion: Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. [ABSTRACT FROM AUTHOR]

Background: This study considers how the COVID-19 pandemic impacted individuals recovering from a substance use disorder (SUD). Method: Fifty individuals recovering from SUD in Vermont, a rural New England state (U.S.), were recruited for an interview from 12-step recovery meetings (Alcoholics Anonymous, Narcotics Anonymous) as well as via word-of-mouth. Interviews were transcribed and coded, and qualitative analyses were performed. Results: Many of the participants who were in recovery prior to the pandemic starting remained substance-free and in recovery throughout the pandemic period. Some individuals used substances during the pandemic period, although not typically in the context of a relapse caused by negative emotions (eg, distress over a loved one contracting COVID-19). The majority of those individuals indicated that the risk of catching COVID-19 did not alter their substance use. Conclusions: Many individuals already in SUD recovery before COVID-19 remained in recovery despite the challenges of pandemic era. The role of peer support in recovering individuals managing negative emotions caused by COVID-19 is considered. [ABSTRACT FROM AUTHOR]

ABSTRACT International guidelines suggest cessation of nucleos(t)ide analogues (NA) independent of HBsAg loss in HBeAg‐negative patients after 2–3 years of viral suppression. Detectable HBV‐RNA levels at the time of NA cessation were linked to a better prediction of relapse after NA withdrawal in small cohorts of HBeAg‐negative patients. This study proves the impact of HBV‐RNA levels in the prediction of relapse in a large cohort of HBeAg‐negative patients, mainly infected with genotype B or C. Serum levels of HBV‐RNA, HBsAg, anti‐HBc and HBcrAg were determined before NA withdrawal in 154 HBeAg‐negative patients, participating either in a therapeutic vaccination trial (NCT02249988) or in an observational register trial (NCT03643172). Importantly, vaccination showed no impact on relapse. Endpoints of the study were virological relapse (HBV‐DNA > 2000 IU/mL) or biochemical relapse (attendant ALT levels ≥ 2 × ULN) 24 weeks after NA cessation. Virological relapse occurred in 54.5% of patients (N = 84/154), including eight patients (10%) developing an ALT flare. Baseline HBV‐RNA level did not differ significantly between relapsers and off‐treatment responders (p = 0.92). No significant difference occurred in proportions of detectable HBV‐RNA levels between off‐treatment responders (N = 27/70; 38.6%) and relapsers (N = 31/84; 36.9%) (p = 0.99). Combining predefined HBsAg cut‐offs (100 IU/mL, p = 0.0013), anti‐HBc cut‐offs (325 IU/mL, p = 0.0117) or HBcrAg cut‐offs (2 log U/mL, p = 0.66) with undetectable HBV‐RNA (HBsAg, p = 0.0057; anti‐HBc, p = 0.085; HBcrAg, p = 0.60) did not improve relapse prediction. The value of HBV‐RNA levels at timepoint of NA cessation for the prediction of relapse is limited in HBeAg‐negative patients.Trial Registration: ABX 203‐002: NCT02249988; Terminator 2: NCT03643172 [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the differential positional changes of the proximal and distal segments during mandibular setback surgery relapse. Thirty patients with mandibular prognathism who underwent bilateral sagittal split ramus osteotomy were included. Skull models from pretreatment, postsurgery, and post-treatment cone-beam computed tomography were superimposed to evaluate condylar displacement and rotational changes, and to determine the center of rotation (CRot) in the proximal and distal segments. During postsurgical relapse, the proximal segment rotated 2.4 ± 2.1° counterclockwise, with the CRot located near the mandibular condyle. The distal segment rotated 2.0 ± 2.3° counterclockwise, resulting in forward and upward movement of the chin. The displaced condyle partially returned to its original position during postsurgical orthodontic treatment. A vertical bony step (VBS) between the proximal and distal segments commonly occurs during mandibular setback surgery. As the VBS increases, the CRot of the distal segment shifts posterosuperiorly, following a predictable pattern outlined by regression equations. These findings suggest that relapse after mandibular setback surgery consistently occurs in an anterosuperior direction, with translatory movement becoming more prominent as the VBS increases. Including these regression equations in presurgical planning can enhance the precision of relapse simulations and help clinicians more accurately anticipate postsurgical relapse. [ABSTRACT FROM AUTHOR]

Because of the stigma surrounding patients with substance use disorder (SUD) and difficulties with follow-up, data on outcomes is limited. We explore real-world data from a prospectively collected database to determine characteristics that contribute to the completion of acute treatment. Our cohort consisted of data from 1039 patients treated at a single facility. Success was defined as successful discharge from the program. Failure was defined as relapse or signing out against medical advice during treatment. We examined 43 distinct features collected at time of treatment using multivariate analysis. In the total cohort and both sexes, longer length of stay (p ≤ 0.01) was linked to treatment failure. When we examined the cohort by sex, variables associated with success and failure differed between groups. Among females, goal-directed thinking (p ≤ 0.05) correlated with treatment success. Taking unnecessary risks (p < 0.05), having a detailed suicide plan (p ≤ 0.001), and constricted thinking (p ≤ 0.01) predicted treatment failure. In males, prior arrest for driving under the influence (p ≤ 0.05), and presence of phobias, paranoias, and delusions (p ≤ 0.05) were associated with treatment failure. Identifying patients prone to acute therapy failure may guide more personalized treatment, thereby increasing success rates. When considering SUD treatments for patients, we must stratify based on patient characteristics. [ABSTRACT FROM AUTHOR]

For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41–0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02–1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28–6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85–1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis. [ABSTRACT FROM AUTHOR]

Background: Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). Methods: Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. Results: Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15–17.7]; p = 0.03). Conclusion: The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing. [ABSTRACT FROM AUTHOR]

Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi‐experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19–73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow‐up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24‐h post‐cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes. [ABSTRACT FROM AUTHOR]

While outcomes for newly diagnosed children with acute lymphoblastic leukemia (ALL) have improved over the last few decades, 10–15% will relapse. Outcomes for those children with relapse remains a challenge, with 5-year overall survival of approximately 35–60%. Large cooperative group trials have identified factors associated with favorable (low risk, LR) outcome at relapse, including later relapse, B-cell phenotype, isolated extramedullary relapse and a good response to initial re-induction therapy. Contemporary therapeutic regimens are aimed at improving outcomes, while decreasing toxicity. A main focus of current research involves how immunotherapy can be best incorporated with cytotoxic chemotherapy to improve survival in relapsed ALL. Here we review therapeutic strategies for LR relapse, including review of recently completed and ongoing trials. [ABSTRACT FROM AUTHOR]

Objectives: While autoimmune pancreatitis (AIP) responds well to steroid therapy, the high relapse rate in type 1 AIP remains a critical problem. The present study examined predictors of relapse of type 1 AIP following steroid therapy. Materials and methods: Nine factors potentially predictive of relapse were analyzed in 81 AIP patients receiving steroid therapy with follow-up ≥ 12 months. The rate of serum IgG4 decrease following steroid therapy was calculated by dividing the difference between serum IgG4 values before and at two months after the start of steroid by the IgG4 value before steroid. Results: A relapse occurred in 11 patients (13.5%) during a median of 38 months. Multivariate analysis revealed that the presence of IgG4-related retroperitoneal fibrosis (HR: 5.59; 95% CI: 1.42–22.0; p = 0.014) and the low rate of serum IgG4 decrease after steroid therapy (HR: 0.048; 95% CI: 0.005–0.46; p = 0.008) were significant, independent predictors of AIP relapse. The cut-off value based on receiver operating characteristic curve data for the rate of serum IgG4 decrease before and at two months after steroid therapy distinguishing patients with and without a relapse was 0.65. Using this cut-off value, the area under the curve, sensitivity, and specificity were found to be 0.63, 0.73, and 0.60, respectively. Conclusion: The low rate of serum IgG4 decrease after the start of steroid therapy and the presence of IgG4-related retroperitoneal fibrosis were predictive of type 1 AIP relapse. Cautious, gradual tapering of steroid dosage and longer maintenance therapy are recommended for patients with these factors. [ABSTRACT FROM AUTHOR]

Background: The contribution of interspecies interactions between coinfecting pathogens to chronic refractory infection by affecting pathogenicity is well established. However, little is known about the impact of intraspecific interactions on infection relapse, despite the cross-talk of different strains within one species is more common in clinical infection. We reported a case of chronic refractory pulmonary infection relapse, caused by two methicillin-sensitive S. aureus (MSSA) strains (SA01 and SA02) and revealed a novel strategy for relapse via intraspecific cooperation. Methods: The hemolytic ability, growth curve, biofilm formation, virulence genes and response of G. mellonella larvae to S. aureus infection were analysed to confirm this hypothesis. Results: SA02 hemolytic activity was inhibited by SA01, along with the expression of hemolysin genes and the virulence factor Hla. Additionally, SA01 significantly enhanced the biofilm formation of SA02. AIP-RNAIII may be a possible pathway for this interaction. Compared with mono-infection, a worse outcome (decreased larval survival and increased microbial burden) of the two MSSA strains coinfected with G. mellonella confirmed that intraspecific interactions indeed enhanced bacterial survival in vivo. Conclusion: The intraspecific interaction of S. aureus could lead to chronic refractory infection via pathogenicity changes. [ABSTRACT FROM AUTHOR]

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47–3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97–9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV. Key Points • RTX might be superior to traditional treatments as an induction therapy for severely relapsed AAV. • RTX has the potential to sustain long-term remission with fewer occurrences of infections in the treatment of severely relapsed AAV. [ABSTRACT FROM AUTHOR]

Rationale: When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse. Objective: We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration. Methods: During 15–20 intermittent-access sessions, rats self-administered i.v. cocaine or sucrose pellets paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues. Results: Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS- periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Presenting the DS- alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+. Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+ , CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value. Conclusions: After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non‐psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder.Individuals aged 15–65 with bipolar disorder were identified from Finnish national health registers in 1996–2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time‐varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non‐psychiatric hospitalization (treatment safety). Stratified Cox regression in within‐individual design was used.The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow‐up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57–0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56–0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non‐psychiatric hospitalization. Lithium was associated with a decreased risk of non‐psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84–0.93) and standard doses (aHR 0.81, 95% CI 0.74–0.88).Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non‐psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose. [ABSTRACT FROM AUTHOR]

While alcohol addiction is a significant social problem in Romania, there has been no research into mutual-help groups, such as Alcoholics Anonymous (AA) in the context of the COVID-19 pandemic. The purpose of this study was to investigate the influence of affiliation to AA, perceived stress, and length of sobriety on the recurrence of alcohol craving and obsession, and relapse during the COVID-19 pandemic, as well as to determine whether there are any differences between the level of AA affiliation and AA attendance before and after the pandemic began. A convenience sample of individuals suffering from alcohol addiction from Romania who attend AA meetings (n = 107, 69 men and 38 women) completed an online questionnaire in October 2020 to analyze the intricate relationship between affiliation to AA, perceived stress, and length of sobriety, and recurrence of alcohol craving and obsession and relapse, as well as to compare between the level of affiliation to AA and AA attendance before and after the COVID-19 pandemic began. Multiple logistic regression analysis was performed to investigate whether affiliation to AA, perceived stress, and length of sobriety had influenced the recurrence of craving and alcohol obsession and relapse during the COVID-19 pandemic. A paired samples t-test was performed to evaluate whether there were any differences between the level of AA affiliation and AA attendance before and after the COVID-19 pandemic began. Results indicated that affiliation to AA 12 months before the COVID-19 pandemic started (AAA), perceived stress in the last 9 months since the COVID-19 pandemic started (PSS) and length of sobriety are predictors of both relapse (together the three predictors accounted for 89.7% of the variance in relapse) and recurrence of alcohol craving and obsession during the COVID-19 pandemic (together the three predictors accounted for 81.3% of the variance in recurrence of alcohol craving and obsession). Surprisingly, the length of sobriety was found to be a significant predictor over and above AAA in the past 12 months before the COVID-19 pandemic started in both regression models. In addition, the level of AA affiliation and AA attendance after the COVID-19 pandemic started decreased compared to the level of AA affiliation and AA attendance before the COVID-19 pandemic began, with a very small effect size, respectively with a small effect size. The findings suggest that those working in the area of substance abuse should pay more attention to the influence of affiliation to AA and perceived stress in attaining and maintaining sobriety, as well as to the length of sobriety in maintaining abstinence, as these appear to play an important role in avoiding both recurrence of craving and alcohol obsession, and relapse during times of distress. [ABSTRACT FROM AUTHOR]

Numerous countries are significantly impacted by substance use disorder (SDU) crimes without effective solutions, including Malaysia. The current study aims to systematically review relevant literature on community education and factors contributing to SDU relapse, especially among former youth prisoners in Malaysia. A literature search was conducted through three databases, namely Scopus, Web of Science (WoS), and Google Scholar. The initial search provided over 700 articles ranging from 2013 to 2023. Nevertheless, the screening and eliminating processes resulted in only 10 articles. The screening process coincided with the study objectives to thoroughly comprehend the major factors contributing to SDU relapse among former youth prisoners and explore the effectiveness of community education in preventing SDU relapse. The findings answered the research questions and suggested several future research directions to improve the study. [ABSTRACT FROM AUTHOR]

Background and objectives: Neuromyelitis optica spectrum disorder (NMOSD) is a group of demyelinating diseases of the nervous system with high relapse rate and high disability rate without treatment, and we aimed to explore the influencing factors related to the recurrence of NMOSD and provide basis for clinical treatment in this study. Methods: Referring to the diagnostic criteria for NMOSD issued in 2015, 259 patients were enrolled. Clinical information, cerebrospinal fluid (CSF) and serum analysis results, brain and spinal cord magnetic resonance imaging (MRI) findings, treatment details, and prognosis were all recorded. Results: 176 (68.00%) participants were found to be AQP4 Ab-positive in serum or CSF, and the relapse rate was 36.67% (95/259). These 259 individuals were separated into two groups: non-release (n = 164) and relapse (n = 95). In terms of EDSS scores at onset, EDSS score after treatment, lesion location, serum creatinine (Cr) and treatment strategy, there were statistical differences between the two groups. Multivariable logistic regression analyses revealed five predictors for recurrence of NMOSD patients within two years: EDSS scores at onset, transverse myelitis, brain/brainstem, Cr, and Rituximab/immunosuppressants. Conclusion: It is essential to explore the risk factors related to recurrence and prevent them to reduce the risk of disability and improve the prognosis, and the recurrence rate of NMOSD may be affected by several factors. [ABSTRACT FROM AUTHOR]