Initial Episode Research Articles

Comprehensive approach to esophageal variceal bleeding: From prevention to treatment

Esophageal variceal bleeding is a severe complication often associated with portal hypertension, commonly due to liver cirrhosis. Prevention and treatment of this condition are critical for patient outcomes. Preventive strategies focus on reducing portal hypertension to prevent varices from developing or enlarging. Primary prophylaxis involves the use of non-selective beta-blockers, such as propranolol or nadolol, which lower portal pressure by decreasing cardiac output and thereby reducing blood flow to the varices. Endoscopic variceal ligation (EVL) may also be employed as primary prophylaxis to prevent initial bleeding episodes. Once bleeding occurs, immediate treatment is essential. Initial management includes hemodynamic stabilization followed by pharmacological therapy with vasoactive drugs such as octreotide or terlipressin to control bleeding. Endoscopic intervention is the cornerstone of treatment, with techniques such as EVL or sclerotherapy applied to directly manage the bleeding varices. In cases where bleeding is refractory to endoscopic treatment, transjugular intrahepatic portosystemic shunt may be considered to effectively reduce portal pressure. Long-term management after an acute bleeding episode involves secondary prophylaxis using beta-blockers and repeated EVL sessions to prevent rebleeding, complemented by monitoring and managing liver function to address the underlying disease. In light of new scientific evidence, including the findings of the study by Peng et al , this editorial aims to review available strategies for the prevention and treatment of esophageal varices.

Comparative efficacy of endoscopic variceal ligation versus non-selective beta-blockers in primary prevention of gastroesophageal varix type 2: an IPTW-adjusted study.

Practice guidelines recommend non-selective beta-blockers (NSBB) and endoscopic variceal ligation (EVL) for primary prevention in cirrhosis patients with esophageal varices. However, there is no clear recommendation for primary prevention strategies for gastric varices, particularly GOV-2. Our objective is to investigate the incidence of initial bleeding and liver-related complications when NSBB and EVL are used for primary prevention in GOV-2. A retrospective analysis was conducted on data from patients with GOV-2 gastric varices. Patients were divided into the NSBB group or the EVL group. Differences in the incidence of initial bleeding within 1year, as well as the occurrence of complications such as hepatic encephalopathy and ascites, were compared between the two groups before and after adjustment for Inverse Probability of Treatment Weighting (IPTW). A Cox proportional hazards model was used to identify independent risk factors for the first bleeding event. There were 60 patients in the NSBB group and 66 patients in the EVL group. Before IPTW adjustment, there were differences between the two groups in sex, portal hypertensive gastropathy, esophageal variceal diameter, red signs, FIB-4, and MELD scores. After IPTW adjustment, these differences were balanced, with standardized mean differences (SMDs) within acceptable ranges. Kaplan-Meier survival analysis showed no difference in bleeding rates between the two groups before or after IPTW adjustment. After IPTW adjustment, Cox regression analysis identified esophageal variceal diameter (HR:5.59 (2.03-15.39), p < 0.001) and MELD score (HR:1.17 (1.01-1.23), p = 0.042) were independent risk factors for bleeding. NSBB treatment did not reduce the incidence of liver-related complications within one year compared to EVL. For primary prevention of bleeding in cirrhotic patients with GOV-2, EVL does not significantly reduce initial bleeding episodes or liver-related complications compared to NSBB.

Abstract 4138497: Incidence and predictors of recurrent pericarditis in systemic lupus erythematosus

BACKGROUND/PURPOSE: Pericarditis is the most common cardiac manifestation of systemic lupus erythematosus (SLE). In the general population, pericarditis commonly recurs (~30%), likely due to immune-mediated mechanisms. Given the broad immune dysregulation that drives the pathogenesis of SLE, we sought to identify the frequency and risk factors for the recurrence of pericarditis in this unique population. METHODS: Retrospective cohort study of SLE patients enrolled between 1988 and 2023 at a tertiary medical center. The SELENA revision of the SLE Disease Activity Index was used to define pericarditis, and all follow-up clinical encounters were examined after the first reported episode. Recurrent pericarditis was defined as that occurring at least 6 weeks after the first recorded episode of pericarditis. Statistical significance was defined as a p-value of &lt;0.05, and a pooled logistic regression was used to estimate odds ratios for risk factors. Results: Of 2931 patients in the cohort, 590 patients had a history of pericarditis. During a median follow-up of 7 years (IQR: 3 – 14), 20% (n=120) of patients experienced recurrent pericarditis (Table 1). The majority (51%) experienced only one recurrence, whereas 49% of patients had ≥2 recurrences. Several demographic, clinical, serologic, and treatment characteristics were associated with recurrence in the univariate analysis (Table 2). We performed a multivariate analysis using variables of statistical significance (P &lt;0.05) and found that independent predictors of recurrence included younger age (≥60 years vs. &lt;40, RR 0.11 (0.04, 0.32), P &lt;.001), treatment with prednisone ( ≥20 vs. 0 mg, RR 1.99 (1.17, 3.40), P = 0.012), active SLE disease (SLEDAI ≥3 vs. 0, RR 1.55 (1.21, 2.00), P &lt;.001), and time from initial episode (3-10 years vs. &lt;1, RR 0.32 (0.20, 0.52), P &lt;.001) (Figure 1). CONCLUSION: Recurrence of pericarditis in SLE is common (20%) and more likely to occur within one year of onset. Younger patients and those with higher lupus activity are at greater risk of recurrence. As in the general population, oral prednisone is independently associated with a higher chance of recurrence in SLE patients, with a dose-dependent effect. These findings set the basis for future studies to define optimal treatment for recurrent pericarditis in SLE patients and indicate that oral corticosteroids should be avoided when treating pericarditis.

Unravelling T-cell dynamics and immune responses in initial and recurrent uveitis.

This study aimed to identify novel serological targets and investigate immune responses in patients with non-infectious uveitis, focusing on differences between initial onset and recurrent episodes. Differential gene expression analysis, immunocyte typing and T-cell receptor (TCR) gene analysis were conducted on RNA-sequenced peripheral blood samples from healthy individuals (n = 6) and non-infectious uveitis patients (n = 12), divided into 6 patients each at initial onset and recurrent stages. Peripheral blood T-cell types were analysed using flow cytometry. Bioinformatics methods included tools for RNA sequencing data processing, CIBERSORT for immune cell type prediction and specialized software for TCR repertoire analysis. Findings indicated that individuals with recurrent uveitis demonstrated a stronger adaptive immune response and a more pronounced immune imbalance compared to those with initial onset. Memory T cells were predominant in recurrent episodes, suggesting their potential role as biomarkers for disease progression. Significant differences in TCR diversity and V(D)J gene usage were observed between the various uveitis groups and healthy controls. Importantly, 38 uveitis-specific TCR sequences showed substantial expansion in the uveitis patients compared to controls. An elevated expansion of these specific TCR sequences was associated with an increased risk of uveitis development. The study highlights the critical role of adaptive immune responses and specific immune cell types in the pathogenesis of recurrent uveitis. Identification of the uveitis-specific TCR repertoire set could provide deeper insights into the disease and facilitate the development of targeted therapies for uveitis patients.

Long-term Follow-up After an Initial Episode of Diverticulitis: A 13- Year Update.

For patients with recurrent diverticulitis, the trigger to proceed to elective sigmoid colectomy is unclear. Current clinical practice guidelines suggest this is an individualized decision between surgeon and patient. To assess long-term risk of diverticulitis recurrence and determine predictors of recurrent disease. Retrospective case series. Tertiary care center. Consecutive patients with CT-proven diverticulitis who presented as inpatient or outpatient between 2002-2008. Incidence of diverticulitis recurrence determined via chart review and questionnaire. Risk of recurrent diverticulitis or surgery for diverticulitis. A total of 753 patients with first-time diverticulitis were identified. Patients were 61.5 years old (SD 15.3). Median follow-up was 13.2 years (IQR 3.8-18.3). There were 486 (64.5%) patients alive at time of follow-up. During initial presentation, 29 (3.9%) required IR drainage and 37 (4.9%) required emergency surgery. Forty-three (5.7%) underwent elective surgery after initial presentation, and 77 (10.2%) underwent surgery after more than 1 episode. Of those without surgery for first episode, 353 (52.4%) experienced recurrent disease with median time to recurrence of 2.9 years (IQR 0.83-8.5 years). On multivariate analysis, female sex (HR 1.28, p = 0.04), sigmoid disease (HR 1.35, p = 0.03), smoldering disease (HR 3.17, p < 0.01), length of involved segment >5 cm (HR 1.28, p = 0.04), and maximum fat stranding diameter >1.8 cm (HR 1.29, p = 0.03) were associated with disease recurrence. Kaplan Meier estimates of freedom from recurrence were 73.1% (69.6-76.3%) at 1 year, 47.9% (44.0-51.6%) at 5 years, and 34.6% (31.0-38.2%) at 10 years following initial presentation. Retrospective design. After a single episode of diverticulitis, incidence of recurrence is more than 50% on long-term follow-up. Variables such as female sex, sigmoid disease, smoldering disease, length of involved segment greater than 5 cm, and maximum fat stranding diameter greater than 1.8 cm were associated with an increased risk of recurrence. These findings should be considered when counseling patients on decision to proceed with elective colectomy. See Video Abstract.

First bipolar episode following booster dose of COVID-19 vaccination

Introduction and importance: The interactions between the susceptibility of the host and some of the COVID-19 vaccine components happened. Viral infections, including COVID-19, are related to the pathogenesis of bipolar disorder (BD). These findings could trigger an initial bipolar episode. Case presentation: A 48-year-old Syrian married female, presented to the out-clinic of Modern Medical Centre Hospital, in July 2022 for episodes of sub-maniac/mania episodes, which began within 15 days after the booster dose of COVID-19 vaccination, preceded by depressive mood. Both family and personal past psychiatric and/or trauma history were negatives. Initiation of carbamazepine 600 mg/day showed significant improvement within 3 days; 3 months later, carbamazepine dose was decreased to 200 mg/day, as there were no clinical symptoms. Clinical discussion: mRNA vaccines of COVID-19 increase the levels of type I interferon (INF), an inflammatory cytokine that creates a signal leading to the expression of interleukins, INF, and tumor necrosis factor-alpha. The pathology of BD is also unclear. Genetic predisposition, immunological effects, and the classification of BD, itself, as an autoimmune disease play a role. Although rapid improvement following treatment, prolonged and maintenance treatment by essentially mood stabilizer should be considered in bipolar episodes initiated by COVID-19 vaccination. Rare data are available about maniac episodes after COVID-19 infection, but to our knowledge, we reported the first case of bipolar onset after the booster vaccination of COVID-19. Conclusion: Bipolar disease can present following a booster dose of COVID-19 vaccination in previously healthy people.

Risk factors for and timing of presumptive recurrent TB.

<sec><title>INTRODUCTION</title>Understanding factors associated with increased risk for tuberculosis (TB) recurrence is essential in lowering the TB burden. We aimed to quantify the burden, risk factors, and timing of TB presumptive recurrence.</sec><sec><title>METHODS</title>We analyzed test results from 2013 to 2017 in the South African National Health Laboratory Service's database. We defined a person's TB episode to start with their first positive TB test. In the absence of treatment outcome data, we assumed the episode concluded 6 months later for rifampicin-susceptible TB (RS-TB) and 18 months later for rifampicin-resistant TB (RR-TB), provided that at least one negative smear or culture test was recorded within this period. We defined a presumptive recurrent TB episode to start with a positive TB test after the completion of a prior episode. We calculated recurrence measures stratified by various demographics and RR-TB status.</sec><sec><title>RESULTS</title>Of 574,316 people with RS-TB, 4.7% experienced at least one presumptive recurrent TB episode. Higher local TB notification rates, HIV coinfection, and males experienced higher recurrence rates. Most (89.4%) of the first RS-TB recurrences occurred within a year of the initial episode.</sec><sec><title>CONCLUSION</title>Our findings of when and among whom recurrent TB is more likely to occur can be used to assist early interventions and inform impact on patient care.</sec>.

The presence of oligoclonal bands predicts conversion to multiple sclerosis in isolated myelitis

Acute transverse myelitis (ATM) is a disease characterized by inflammation of the spinal cord and may have various causes. In the context of this work, the distinction between isolated ATM and initial manifestation of autoimmune-mediated diseases of the central nervous system such as multiple sclerosis (MS) is crucial. Hence, the aim of this work was to identify predictive factors associated with the conversion to definite MS in a collective of individuals after their initial episode of isolated ATM (no initial identified cause). In this retrospective data analysis from the Vienna MS Database, all patients from Jan. 1, 1999, to Dec. 31, 2019, with a diagnosis of isolated ATM (according to the criteria of the Transverse Myelitis Consortium Working Group) who underwent lumbar puncture were extracted. Electronic medical records were reviewed on the availability of clinical data including therapy and follow-up, laboratory results including cerebrospinal fluid (CSF) analysis, evoked potentials (EP) as well as magnetic resonance imaging data. Among 42 patients with the diagnosis of isolated ATM, 12 (29%) were subsequently diagnosed with MS over a median follow-up period of 7.7 years. Univariately, MS converters were younger (32 years [25–39] vs. 42 years [31–50], p = 0.032), had a lower CSF/serum albumin ratio (29 [24–35] vs 37 [27–52], p = 0.037), lower CSF total protein (4.5 [2.8–4.8] vs. 5.5 [3.4–8.5], p = 0.023) and a higher proportion of CSF-specific oligoclonal bands (OCB; 83% vs. 30%, p = 0.002). In the multivariate regression analysis, the presence of CSF-specific OCB emerged as the sole predictive factor of subsequent MS diagnosis (OR: 14.42, 95% CI 1.39 to 149.48, p = 0.03). In a collective of 42 patients with isolated ATM and an MS conversion rate of nearly 30%, the only but highly predictive factor were CSF-specific OCB. This emphasizes the significance of conducting timely CSF analysis in such patients and underscores the need for tailored monitoring and follow-up strategies in this specific group.

Risk Factors of Relapse in Nephrotic Syndrome

Background: Nephrotic syndrome (NS) is a kidney disease with high incidence, typically in young children. NS is a disease of relapse, and it is a major problem to manage the cases with relapse. So, it is very important to find out such children who are prone to develop relapse. Hence, this study was carried out to find out the risk factors of relapse in children with NS. Objective: To determine the risk factors of relapse in patients with nephrotic syndrome. Methods: This case-control study was conducted at the Department of Paediatric Nephrology and Department of Paediatrics, Dhaka Medical College Hospital, for 12- months following ethical approval. A total of 100 NS children (age: 2-12 years) were enrolled in this study, among them 50 were cases (NS with relapse) and 50 were controls (initial attack of NS with no relapse within one year of disease onset). After obtaining written informed consent from parents/legal guardian, a detailed history, thorough clinical examination and necessary investigations were carried out in each patient during initial episode of NS. Data analysis was done by SPSS 26.0. Results: Mean age of the cases and controls was6.11±3.01years and 6.96±3.14years, respectively (p=0.169), with an overall boys-girl ration of 1.3:1. Maximum cases (56.0%) had infrequent relapse. Lower age of onset was prevalent among case group than control (31.96±15.15 months vs 46.48±27.76 months; p=0.002). Infection was significantly more prevalent among cases than controls (68.0% vs 38.0%; OR=3.46; p=0.003), UTI (38.0% vs 10.0%; OR; 5.52; p=0.001). Cases had significantly higher history of atopy (52.0% vs 30.0%; OR=2.53; p=0.025). Higher serum cholesterol (441.62±61.46 mg/dL vs 389.12±72.18 mg/dL; &lt;0.001) and lower serum albumin (15.74±2.20 gm/L vs 17.30±2.99 gm/L; p=0.004) were seen in cases than control. Conclusion: Lower age of onset, history of atopy, infection, higher serum cholesterol and lower serum albumin level during initial attack were associated .......

From evidence to practice: real-world insights into outpatient management of acute uncomplicated diverticulitis.

Diverticulitis is experiencing a significant increase in prevalence and its widespread in-hospital management results in a high burden on healthcare systems worldwide. This study compared inpatient and outpatient approach of acute non-complicated diverticulitis using a non-selected population in a real-world setting. This observational retrospective study included all consecutive patients from two Portuguese institutions diagnosed between January 2017 and December 2021 with non-complicated diverticulitis according to the modified Hinchey Classification. The primary endpoints were to identify criteria for inpatient treatment and compare the outcomes on the basis of the treatment regimen. The secondary endpoints were to determine the predictive factors for clinical outcomes, focusing on treatment failure, pain recurrence, and the need for elective surgery following the initial episode. A total of 688 patients were included in this study, 437 treated as outpatients and 251 hospitalized. Inpatient management was significantly associated with higher preadmission American society of anesthesiologists (ASA) score (p = 0.004), fever (p = 0.030), leukocytosis (p < 0.001), and elevated C-reactive protein (CRP) (p < 0.001). No significant association was found between failure of conservative treatment and patient's age, ASA score, baseline CRP, presence of systemic inflammatory response syndrome (SIRS), and inpatient or outpatient treatment regimen. Pain recurrence was significantly associated with higher CRP levels (p = 0.049), inpatient treatment regime (p = 0.009) and post index episode mesalazine prescription (p = 0.006). Moreover, the need for elective surgery was significantly associated with the presence of previous episodes (p = 0.004) and pain recurrence (p < 0.001). The majority of patients with uncomplicated diverticulitis of the left colon experience successful conservative approach and can be safely managed in an ambulatory setting. Neither treatment failure, recurrence of pain, or need for posterior elective surgery are associated with outpatient treatment regimen.

AN UPDATED VIEW ON THE INFLUENCE OF INITIAL OPIOID PRESCRIPTION CHARACTERISTICS ON LONG-TERM OPIOID USE AMONG OPIOID NAÏVE PATIENTS

OBJECTIVESThis retrospective cohort study provides an updated view on the association between the likelihood of long-term opioid use (LTOU) and characteristics of the initial opioid prescription (dose, opioid type) and initial opioid prescription episode (days’ supplied) among opioid-naïve patients utilizing IQVIA PharMetrics®Plus for Academics database representative of commercially insured patients in the US. METHODSKaplan-Meier estimates were used to determine opioid continuation likelihood at 365 days stratified by the characteristics of the initial opioid prescription and initial opioid prescription episode. Cox-proportional hazard models were estimated to determine the strength of association between initial opioid prescription characteristics and opioid continuation. RESULTSA total of 578,403 cancer-free, SUD-free, opioid-naïve subjects aged ≥14 years that filled ≥1 opioid prescriptions between April 13, 2016 and April 18, 2020 were identified and categorized based on time to opioid discontinuation. After accounting for censoring, 5.05% of persons continued opioid use for ≥365 days. Compared to a 1-2 days’ supply (DS), the likelihood of opioid discontinuation was consistently lower with higher DS [HRs (CIs): 3–4 days' supply = 0.66 (0.65-0.66); 5–7 DS = 0.41 (0.41-0.41); 8–10 DS = 0.33 (0.33-0.34); 11–14 DS = 0.30 (0.29-0.31); 15–21 DS = 0.26 (0.26-0.27); ≥22 DS = 0.17 (0.17-0.18)]. These associations between increased DS and decreased likelihood of discontinuing opioid remained consistent across different pain etiologies. CONCLUSIONSIn this era of more conservative opioid prescribing, increases in DS remains the strongest factor associated with a higher likelihood of LTOU.

S262 Increasing Gastroenterology Follow-Up and Colonoscopy Completion for Patients With Initial and Complicated Episodes of Diverticulitis: A Quality Improvement Project

S262 Increasing Gastroenterology Follow-Up and Colonoscopy Completion for Patients With Initial and Complicated Episodes of Diverticulitis: A Quality Improvement Project

Personal relationships during and after an initial psychotic episode. First-person experiences

Background Psychosis is often associated with loneliness, the absence of a confidant and a perceived lack of social support. In addition, the social isolation and solitude experienced can aggravate internalised stigma, depressive symptoms and/or suicidal tendencies, and worsen the course of the disorder. Aim This study explores the experiences and perceptions of persons with psychosis concerning how their interpersonal relationships have evolved from the earliest symptoms of the disorder to its subsequent clinical stabilisation. Method A qualitative content analysis was performed of the findings from five focus groups and six in-depth interviews (36 participants). Results In the prodrome and initial symptoms stage, five themes were coded: social withdrawal, loss of friends, loss of personal skills, communication difficulties and breakdown of life project. During the recovery phase, four themes were coded: family support, partner support, loneliness and the desire for more close relationships. Finally, during the clinical stabilisation phase, three themes were coded: the recovery of interpersonal relationships, including with peers; reconstruction of the life project and increased interpersonal sensitivity. Conclusions These findings highlight the impact that psychosis can have on social life and show that recovery is also related to the development of maeningful interpersonal relationships.

Identification and preclinical evaluation of MMV676558 as a promising therapeutic candidate against Clostridioides difficile

Clostridioides difficile, a gram-positive, toxin-producing, spore-forming anaerobe, is a major cause of antibiotic-associated diarrhoea. The bacterium's intrinsic drug resistance limits current treatment options to fidaxomicin and vancomycin for initial episodes, with anti-toxin B monoclonal antibody or faecal microbiota transplantation recommended for complicated or recurrent cases. This underscores the urgent need for novel therapeutics. In this study, we screened the MMV Pathogen Box at a 10 µM concentration against C. difficile R20291. Primary hits were evaluated for minimum inhibitory concentrations (MIC), killing kinetics, and biofilm inhibition. Bacterial cytological profiling (BCP) and transmission electron microscopy (TEM) were employed to study the mode of action. MMV676558 was further tested in a mouse model to assess survival, histopathology, and gut microbiota effects. We identified nineteen hits that inhibited over 50 % of C. difficile growth. MIC assays revealed three hits with MICs below 16 µg/mL: MMV676558, MMV688755, and MMV690027. These hits were effective against various C. difficile ribotypes. Killing kinetics were comparable or superior to vancomycin and fidaxomicin, and biofilm assays showed inhibitory effects. BCP and TEM analyses suggested membrane function disruption as the mode of action. Furthermore, MMV676558 demonstrated a protective effect in mice, with favourable histopathology and gut microbiota profiles. Given the urgent threat posed by C. difficile antibiotic resistance, discovering new treatments is a top priority. Our study identified three promising hits from the MMV Pathogen Box, with MMV676558 showing significant in vivo potential for further evaluation.

Atrial Fibrillation and Underlying Structural and Electrophysiological Heterogeneity.

As atrial fibrillation (AF) progresses from initial paroxysmal episodes to the persistent phase, maintaining sinus rhythm for an extended period through pharmacotherapy and catheter ablation becomes difficult. A major cause of the deteriorated treatment outcome is the atrial structural and electrophysiological heterogeneity, which AF itself can exacerbate. This heterogeneity exists or manifests in various dimensions, including anatomically segmental structural features, the distribution of histological fibrosis and the autonomic nervous system, sarcolemmal ion channels, and electrophysiological properties. All these types of heterogeneity are closely related to the development of AF. Recognizing the heterogeneity provides a valuable approach to comprehending the underlying mechanisms in the complex excitatory patterns of AF and the determining factors that govern the seemingly chaotic propagation. Furthermore, substrate modification based on heterogeneity is a potential therapeutic strategy. This review aims to consolidate the current knowledge on structural and electrophysiological atrial heterogeneity and its relation to the pathogenesis of AF, drawing insights from clinical studies, animal and cell experiments, molecular basis, and computer-based approaches, to advance our understanding of the pathophysiology and management of AF.

Clinical characteristics and predictive factors of recurrent idiopathic transverse myelitis.

Idiopathic transverse myelitis (iTM) is defined as an inflammatory myelopathy of undetermined etiology, even after a comprehensive workup to identify other possible causes. Generally, the characteristics of recurrent iTM are not clearly defined. This study aimed to identify the clinical characteristics and predictive factors of recurrence in patients with iTM. We retrospectively recruited patients with transverse myelitis (TM) who visited Chungnam National University Hospital between January 2011 and December 2021. We included patients who were followed up for at least 2 years and excluded those diagnosed with multiple sclerosis or neuromyelitis optica spectrum disorder (NMOSD) during the initial episode or follow-up period. Patients with iTM were categorized into two groups: monophasic idiopathic TM (mTM) and recurrent idiopathic TM (rTM). We compared the clinical characteristics and spinal magnetic resonance imaging findings between the two groups. In total, 167 patients were reviewed, of whom 112 were excluded. Finally, we included 55 patients with iTM. In 55 patients, 11 (20.0%) and 44 (80%) were classified into the rTM and mTM groups, respectively. Male predominance was observed in the iTM, rTM, and mTM groups. The percentage of patients with low vitamin D levels was significantly higher in the rTM group (100.0%) compared with the mTM group (70%) (p = 0.049). In addition, longitudinally extensive transverse myelitis (LETM) was observed more frequently in the rTM group, in 8 of 11 (72.7%) patients, compared with 15 of 44 (34.1%) patients in the mTM group, with the difference being statistically significant (p = 0.020). In multivariate regression analysis, female sex, younger age at onset, low serum vitamin D level (<30 ng/mL), and LETM were risk factors for recurrence. LETM was a significant predictor of relapse in iTM (p = 0.043, odds ratio = 13.408). In this study, the clinical features of mTM and rTM are nearly indistinguishable. In conclusion, >20% of the patients with iTM experience recurrence, and LETM is the most significant risk factor for recurrence. In cases of recurrence, there is a favorable response to immunotherapy, and the prognosis is generally good. Although LETM may be the initial symptom of NMOSD, it may be manifestation of iTM, and in cases of idiopathic LETM, it is important to be mindful of the elevated risk of recurrence. Based on these results, idiopathic rTM has good clinical prognosis and response to immunosuppressive treatment.

The impact of diabetes mellitus on tuberculosis recurrence in Eastern China: a retrospective cohort study

BackgroundThe comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a significant global public health issue. This study aims to explore the recurrence risk and related factors of active pulmonary TB, specifically focusing on the impact of DM.MethodsA retrospective cohort study was conducted in Lianyungang City, Jiangsu Province, Eastern China by recruiting 12,509 individuals with newly diagnosed pulmonary TB between 2011 and 2019. The Cox proportional hazards models were performed to identify risk factors of recurrence and assess the association between DM and recurrence. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association.ResultsAfter a median follow-up period of 5.46 years, we observed 439 recurrent cases (incident recurrence rate: 6.62 per 1000 person-years). Males (HR: 1.30, 95% CI: 1.03–1.64), patients aged ≥ 60 years (HR: 1.39, 95% CI: 1.15–1.70), DM (HR: 2.40, 95% CI: 1.68–3.45), and etiologic positivity in the initial episode (HR: 2.42, 95% CI: 2.00-2.92) had a significantly increased risk of recurrence.ConclusionsRecurrence of pulmonary TB patients who have completed treatment, especially those who also suffer from DM, should be a concern. Enhanced follow-up and targeted surveillance of these high-risk groups are needed.

Correlating plasma protein profiles with symptomatology and treatment response in acute phase and early remission of major depressive disorder.

This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode. In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID). Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms. This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools. The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.

Onset and tempo of ignimbrite flare-up volcanism in the eastern and central Mogollon-Datil volcanic field, southern New Mexico, USA

The Cenozoic ignimbrite flare-up (40–18 Ma) generated multiple volcanic fields in the southwestern United States and northern Mexico resulting from asthenospheric mantle upwelling after removal of the Farallon slab. The correlation of tuffs to one another and to source calderas within these volcanic fields is essential for determining spatiotemporal patterns in volcanism and magma geochemistry, which have been used to deduce migration of the Farallon slab at depth and associated mantle melting. However, the correlation of Eocene–Oligocene tuffs in the southwestern U.S. is difficult because of post-emplacement erosion and faulting. This study focuses on spatiotemporal patterns of the initial episode of ignimbrite flare-up activity (ca. 36.5–33.8 Ma) in the Mogollon-Datil volcanic field in south-central New Mexico, USA. We show that alkali feldspar major and trace element geochemistry is an effective tool for correlating tuffs when combined with high-precision, single-crystal 40Ar/39Ar geochronology and bulk-rock geochemistry. Using these data, we correlate several tuff units and differentiate other tuffs that have the same eruption age but very different geochemistry, and we conclude that there was a broadly northwestward migration in volcanism over time. The new tuff correlations are used to investigate spatiotemporal variations in magma geochemistry, erupted volumes, and recurrence intervals during the initial episode of Mogollon-Datil volcanic field volcanism. Early-erupted tuffs restricted to the eastern Mogollon-Datil volcanic field share similarities with western U.S. topaz rhyolites, which suggests that the silicic magmas were generated by partial melting of mafic lower crustal rocks. We also find differences in the compositions, crystallinities, and mineral assemblages between the early- and late-erupted tuffs. The early-erupted tuffs tend to have single-feldspar mineralogies, lower feldspar Or contents, large negative Eu anomalies, and low-whole–rock Ba concentrations. Conversely, late-erupted tuffs have two feldspar plus quartz assemblages, lesser Eu anomalies, higher whole-rock Ba concentrations, and feldspars have higher Or contents. Thus, we suggest that for some of the early eruptions, after magmas underwent crystal fractionation in the crust, the silicic melt largely separated from the crystalline mush prior to eruption, whereas late-erupted tuff magmas underwent crystal fractionation at near the eutectic minimum and were remobilized and erupted with a larger proportion of their crystalline mush. Using our new ages, correlations, and previously published data, we find that the initial phase of Mogollon-Datil volcanic field volcanism produced at least 15 eruptions between 36.5 Ma and 33.8 Ma, with a minimum total erupted volume of ~1350 km3 and an average recurrence interval of 170 k.y. However, eruptions were generally smaller in volume (most &amp;lt;15 km3) than in other coeval fields, and most eruptions (n = 11) occurred in the first 1.2 m.y. (ca. 36.5–35.3 Ma) of activity. Altogether, our work sheds new light on variations in the composition, timing, and migration of volcanism during the initial phase of Mogollon-Datil volcanic field activity and highlights the utility of feldspar geochemistry in both “fingerprinting” tuffs and elucidating magma evolution.

Evaluation of the Psychometric Properties of the 18-Items Dysfunctional Attitudes Scale (Form B) in a Portuguese Sample of People Aged 60 and Over.

The aim of the study is to assess the psychometric properties of the Portuguese version of the 18-items Dysfunctional Attitudes Scale (Form B) in a Portuguese sample of people aged 60 and over. Background: The 18-item Dysfunctional Attitudes Scale (Form B) is an instrument for assessing dysfunctional attitudes and can be useful as a predictor of depression for both initial episodes and relapses Methods: This was a one-stage cross-sectional survey of Portuguese-speaking people aged 60 years and over, able to read and write, functionally autonomous, and living in the community in their usual residences. The instrument was evaluated for its psychometric properties. Convergent validity with the Beck Depression Inventory-II was assessed. Results: The Portuguese version of the 18-item Dysfunctional Attitudes Scale (Form B) was structured into three factors, which explained a total of 58.95% of the total variance of the instrument. The exploratory factor analysis resulted in a modified model in which three factors were obtained with an eigenvalue greater than one (Kaiser's criterion). Three factors were obtained instead of two as in the original study. It showed an internal consistency (Cronbach's alpha = 0.770) and an interclass correlation coefficient ranging from 0.166 to 0.449, and the overall convergent validity with the Beck Depression Inventory-II was considered good; Conclusions: The Portuguese version of the Dysfunctional Attitudes Scale (DAS-18B) of people aged 60 and over demonstrated good psychometric properties.