Efficacy of venetoclax and rituximab in the treatment of concurrent acute myeloid leukemia and untreated chronic lymphocytic leukemia: A case report and literature review.

To date, few cases of concurrent acute myeloid leukemia (AML) and untreated chronic lymphocytic leukemia (CLL) have been reported. Due to the complexity of the pathogenesis and the absence of a uniform treatment regimen, the associated prognosis remains poor. The present study reports the case of a 58-year-old male with asymptomatic leukocytosis, who was previously healthy with no malignancies. Flow cytometry analysis revealed protocytosis, monocytosis and monoclonal B lymphocytosis in a bone marrow specimen. Results of a gene rearrangement assay demonstrated positive immunoglobulin heavy-chain variable region gene status in monoclonal B lymphocytes. Thus, the patient was diagnosed with AML with maturation (AML-M2) that co-existed with untreated CLL. The normative daunorubicin (40 mg/m2 on days 1-3) and cytarabine (80 mg/m2 on days 1-7) regimen combined with venetoclax (400 mg on days 1-7) and rituximab (375 mg/m2 on day 0) was used as induction chemotherapy. The patient achieved morphological complete remission in both AML and CLL following the first course of chemotherapy. In addition, the present study retrospectively analyzed the data of 22 patients with concurrent AML and untreated CLL, and the results demonstrated that the median age at the time of AML diagnosis was 69 years (range, 52-86 years). Moreover, the male:female ratio was 6.33:1 and AML-M2 was the most frequent subtype at diagnosis. The presence of a complex karyotype was associated with the poorest prognosis, and patients who received venetoclax often exhibited an improved prognosis. In conclusion, the combination of venetoclax and rituximab improves the prognosis of patients with concurrent AML and untreated CLL.

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance.

With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic ß-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin ß-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

The prognostic value of IgA anti-citrullinated protein antibodies and rheumatoid factor in an early arthritis population with a treat-to-target approach.

The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in 'quick-attained and persistent remission' rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice.

Early progression during or after cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy indicates poor outcome with rescue protocols in dogs with multicentric lymphoma.

BACKGROUND: Dogs with lymphoma that fail cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (CHOP) before completion of their protocol are commonly thought to have poor long-term outcome, but no previous studies have evaluated the effect of early relapse on progression-free interval (PFI) or overall survival time (OST) for patients undergoing rescue chemotherapy. OBJECTIVE: Correlate rescue treatment outcomes in dogs with multicentric lymphoma with outcomes after 1st-line CHOP chemotherapy. METHODS: Data were collected from 6 previous retrospective or prospective studies in 187 dogs with multicentric lymphoma that received 1st-line CHOP chemotherapy and then received either lomustine (CCNU), L-asparaginase and prednisone (LAP), or rabacfosadine (RAB, Tanovea), with or without prednisone or L-asparaginase. RESULTS: The PFI after initiation of CHOP chemotherapy was significantly associated with response rate postprogression, PFI, and postrescue survival time (ST) for both rescue protocols. Immunophenotype (B- vs T-cell) was not significantly associated with response, PFI or OST for LAP but was significantly associated with response and PFI for RAB. CONCLUSION: Dogs that experience short PFI during or after 1st-line CHOP chemotherapy had lower response rates to rescue treatment, with shorter PFI and ST. Immunophenotype did not significantly affect outcome with LAP but was associated with PFI for RAB.

Invitation to do remission of pre-diabetes to normoglycemia.

By integrating health coaching into maritime medical clinics, we can provide tailored support to individuals at risk of developing diabetes and empower them to take control of their health.

Predictors of complete remission of hypertension in patients over 65 years of age after bariatric surgery - a multicenter study.

Introduction: In the era of an aging society and a growing number of obese people, an increasing number of older patients are consulting bariatric surgeons. The incidence of hypertension (HT) also rises with age and body weight, making the treatment of the elderly a significant challenge. Aim: To identify predictors of HT remission after bariatric surgery in patients over 65 years of age. Material and methods: A retrospective study analyzed patients over 65 years old with HT who underwent laparoscopic bariatric procedures in Poland between 2008 and 2022. The data came from 11 bariatric centers. Patients were categorized into two groups: responders (R) and non-responders (NR). A multivariate logistic regression analysis was conducted to identify significant independent risk factors. Results: The study analyzed 244 patients, with complete HT remission observed in 55 (22.5%) patients. Almost 90% of patients showed improvement in HT. The mean follow-up time was 47.4 months. Factors contributing to HT remission included HT duration of less than 5 years, the use of single medication, and a significant correlation with %EWL. Conclusions: Bariatric surgery in patients aged over 65 has a positive effect on HT remission. The chance of HT remission increases with fewer medications, shorter HT duration, and greater weight loss after surgery.

First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis.

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997-2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10-0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and -0.13/-0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

Late adolescent outcomes of different developmental trajectories of ADHD symptoms in a large longitudinal study.

There exists substantial heterogeneity in the developmental trajectories of ADHD symptoms, with distinctions often made between persistent versus remittent, and early- versus late-onset. However, how these trajectories relate to late adolescent functioning and whether, in particular, later onset trajectories mark a milder subtype remains unclear. Building on earlier work that has examined early life predictors of ADHD symptom trajectories up to age 14, we applied latent class growth analysis to data from the UK Millennium Cohort Study (N = 10,262) to evaluate whether developmental trajectories of ADHD symptoms up to age 17 (from age 3) were similar to those identified up to age 14 and associated with differing levels of impairment in peer victimisation, mental health, substance use, and delinquency outcomes at age 17. Our optimal model included five trajectory groups, labelled unaffected (37.6%), mildly affected (34.8%), subclinical remitting (14.4%), adolescent onset (7.6%), and stable high (5.6%). Adolescent onset and stable high trajectories were similarly impaired across all outcomes, other than substance use. Subclinical remitting individuals were impaired on self-esteem and well-being compared to unaffected individuals. By the end of mid-adolescence, those with a later onset have similar impairments to those following an early onset/persistent trajectory. Residual impairment may remain for those on a remitting trajectory.

Outcomes of Patients Newly-diagnosed with Systemic Lupus Erythematosus Managed in a Tertiary Training and Referral Hospital in the Philippines.

Objective: To determine the one-year outcomes of newly-diagnosed patients with systemic lupus erythematosus (SLE) in a tertiary government hospital in Manila, Philippines. Methods: After ethics approval, we reviewed the medical records of a cohort of 44 newly-diagnosed SLE patients at 6- and 12-months post-diagnosis in 2018-2019. The outcomes of interest were: modified lupus low disease activity state as defined (mLLDAS), remission, hospitalization, 30-day readmission, organ damage, and mortality. Results: The patients were predominantly young females (mean age of 29 ± 9.9 years). There was an average interval period of six months between onset of symptoms and diagnosis (6.4 ± 10.8 months). The most common manifestations were mucocutaneous (86.4%), hematologic (63.6%), musculoskeletal (61.4%), and renal disorder (47.7%). There was at least one positive serologic test in 88.7%. Five patients (11.4%) had comorbidity, usually hypertension (9.1%). The initial lupus treatment consisted of moderate to high doses of glucocorticoids and hydroxychloroquine. Patients with life-threatening or organ-threatening disease, usually nephritis, received cyclophosphamide, azathioprine, or mycophenolate mofetil. One patient received rituximab. Fewer patients with nephritis received cyclophosphamide infusions during the first six months compared to the later six months.Most of the hospitalizations (34/36) occurred during the first six months and 22 of these were for diagnosis. Seven patients had more than one hospitalization and five (20%) had 30-day readmissions. mLLDAS was achieved by 15 (34.1%) and 30 (68.2%) patients at 6- and 12-months, respectively. Only one patient was in remission a year after diagnosis. Seven patients (15.9%) were assessed with organ damage, six (13.64%) of them at 6-months post-diagnosis. Organ damage was most commonly renal. Four (9.1%) patients died, all during their initial hospitalization. Conclusion: In our population observed over a period of one year (2018-2019), there was a very low rate of remission (1/44, 2.3%), mLLDAS in 68.2%, and organ damage in 15.9%. Most of the hospitalizations (65%) were for the diagnosis of lupus and all deaths (9.1%) occurred during this first hospital confinement. We must intensify our efforts to (1) achieve earlier diagnosis, (2) deliver optimal lupus treatment and supportive care during the first lupus hospitalization, and (3) initiate early and persistent immunosuppressive treatment for nephritis to improve outcomes for our patents with SLE.

Unveiling the Significance of MRP 1 in Achieving Complete Remission Following Induction Therapy in Acute Myeloid Leukemia.

BACKGROUND: Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes. AIMS AND OBJECTIVES: The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients. METHOD: A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored. RESULTS: Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation. CONCLUSION: Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.

Factors linked to prognosis in children with provisional tic disorder: a prospective cohort study.

The purpose of the present study was to estimate the factors linked to the prognosis of children with provisional tic disorder (PTD). We conducted a prospective cohort study enrolled children with PTD who were subsequently followed-up at three-month intervals for 1 year post-enrolment. A total of 259 PTD patients were included in the final analysis. At the end of the follow-up period, 77 (30%) of the patients had achieved clinical remission. Result of the LASSO logistic regression analysis revealed that a disease duration >3 months (OR=4.20, 95% CI 1.20-14.73), moderate/severe tic severity (OR=5.57, 95% CI 2.26-13.76), and comorbid behavioral problems (OR=2.78, 95% CI 1.15-6.69) were significant factors linked to remission in the PTD patients. The path analysis model showed that comorbid behavioral problems and recurrence partially mediated the association between tic severity and remission, with a mediating effect of 37%. Conclusions: We have identified several significant factors linked to prognosis in children with PTD, including comorbid behavioral problems and recurrence, which were found to be important mediators. These findings provide new insights for the clinical management of patients with PTD.

Impacts of Tumor Stage at Diagnosis and Adjuvant Therapy on Long-Term Survival Outcomes in Patients With Triple-Negative Breast Cancer Achieving Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.

Transferability of the NHS low-calorie diet programme: A qualitative exploration of factors influencing the programme's transfer ahead of wide-scale adoption.

INTRODUCTION: Although behavioural interventions have been found to help control type 2 diabetes (T2D), it is important to understand how the delivery context can influence implementation and outcomes. The NHS committed to testing a low-calorie diet (LCD) programme designed to support people living with excess weight and T2D to lose weight and improve diabetes outcomes. Understanding what influenced implementation during the programme pilot is important in optimising rollout. This study explored the transferability of the NHS LCD Programme prior to wider adoption. METHODS: Twenty-five interviews were undertaken with stakeholders involved in implementing the LCD programme in pilot sites (health service leads, referring health professionals and programme deliverers). Interviews with programme participants (people living with T2D) were undertaken within a larger programme of work, exploring what worked, for whom and why, which is reported separately. The conceptual Population-Intervention-Environment-Transfer Model of Transferability (PIET-T) guided study design and data collection. Constructs of the model were also used as a deductive coding frame during data analysis. Key themes were identified which informed recommendations to optimise programme transfer. RESULTS: Population: Referral strategies in some areas lacked consideration of population characteristics. Many believed that offering a choice of delivery model would promote acceptability and accessibility of the eligible population. INTERVENTION: Overall, stakeholders had confidence in the LCD programme due to the robust evidence base along with anecdotal evidence, but some felt the complex referral process hindered engagement from GP practices. ENVIRONMENT: Stakeholders described barriers to accessing the programme, including language and learning difficulties. Transferability: Multidisciplinary working and effective communication supported successful implementation. CONCLUSION: Referral strategies to reach underrepresented groups should be considered during programme transfer, along with timely data from service providers on access and programme benefits. A choice of delivery models may optimise uptake. Knowledge sharing between sites on good working practices is encouraged, including increasing engagement with key stakeholders.

Role of Electroconvulsive Therapy, Ketamine Infusion, and Deep Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression: A Case Report.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

Clinical Utility of Disease Activity Indices in Predicting Short-Term Response to Biologics in Patients with Ulcerative Colitis.

Background: The Mayo Score [MS], endoscopic Mayo Score [eMS] and the Ulcerative Colitis Index of Severity [UCEIS] are employed in the assessment of ulcerative colitis [UC] severity. This study compared the aforementioned indices in terms of predictory value for response to remission induction treatment with anti-TNF and anti-integrin biologics. Methods: A total of 38 patients were retrospectively evaluated in the study, 23 male and 15 female, aged 18-74 years old who had undergone a total of 53 biological therapy courses with either infliximab [IFX] or vedolizumab [VDZ] at the Department of Gastroenterology of the Medical University of Lódz. The clinical and endoscopic activity of UC was assessed at the outset of biological therapy and the 14th week remission induction assessment juncture. Results: The study analyzed 19 IFX and 34 VDZ treatment courses. The response rate of patients receiving IFX reached 73.67% and the response rate was 58.82% for VDZ. The mean MS, eMS and UCEIS improved among all patient groups: 8.316 ± 1.974 to 4.158 ± 2.218 (p < 0.05), 2.632 ± 0.597 to 1.790 ± 0.713 (p < 0.05) and 4.790 ± 1.745 to 3.000 ± 1.453 (p < 0.05) for IFX, 7.088 ± 2.234 to 3.618 ± 2.412 (p < 0.05), 2.706 ± 0.524 to 1.677 ± 1.065 (p < 0.05) and 4.235 ± 1.350 to 2.735 ± 1.880 (p < 0.05) for VDZ. Conclusions: The outcome assessment in induction treatment of UC includes clinical data and endoscopic evaluation. Severity of inflammatory lesion activity according to the eMS and UCEIS indices correlates with the overall disease presentation as evaluated with MS. The UCEIS provides an overall better predictor for biological induction treatment when compared with the eMS in both patient groups, particularly in those receiving VDZ. It provides a promising alternative to the eMS and can be employed for both initial disease severity assessment as well as for treatment response monitoring.

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention.

BACKGROUND: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. OBJECTIVE: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. MAIN FINDINGS: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a "proof of concept" for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.

The long shadow of early-change patterns: a 3-year follow-up after the use of a web-based intervention for mild to moderate depressive symptoms.

Web-based interventions can be effective in treating depressive symptoms. Patients with risk not responding to treatment have been identified by early change patterns. This study aims to examine whether early changes are superior to baseline parameters in predicting long-term outcome. In a randomized clinical trial with 409 individuals experiencing mild to moderate depressive symptoms using the web-based intervention deprexis, three latent classes were identified (early response after registration, early response after screening and early deterioration) based on early change in the first four weeks of the intervention. Baseline variables and these classes were included in a Stepwise Cox Proportional Hazard Multiple Regression to identify predictors associated with the onset of remission over 36-months. Early change class was a significant predictor of remission over 36 months. Compared to early deterioration after screening, both early response after registration and after screening were associated with a higher likelihood of remission. In sensitivity and secondary analyses, only change class consistently emerged as a predictor of long-term outcome. Early improvement in depression symptoms predicted long-term outcome and those showing early improvement had a higher likelihood of long-term remission. These findings suggest that early changes might be a robust predictor for long-term outcome beyond baseline parameters.

Global, interhemispheric and intrahemispheric functional connection patterns in male adults with alcohol use disorder.

A growing body of evidence indicates the existence of abnormal local and long-range functional connection patterns in patients with alcohol use disorder (AUD). However, it has yet to be established whether AUD is associated with abnormal interhemispheric and intrahemispheric functional connection patterns. In the present study, we analysed resting-state functional magnetic resonance imaging data from 55 individuals with AUD and 32 healthy nonalcohol users. For each subject, whole-brain functional connectivity density (FCD) was decomposed into ipsilateral and contralateral parts. Correlation analysis was performed between abnormal FCD and a range of clinical measurements in the AUD group. Compared with healthy controls, the AUD group exhibited a reduced global FCD in the anterior and middle cingulate gyri, prefrontal cortex and thalamus, along with an enhanced global FCD in the temporal, parietal and occipital cortices. Abnormal interhemispheric and intrahemispheric FCD patterns were also detected in the AUD group. Furthermore, abnormal global, contralateral and ipsilateral FCD data were correlated with the mean amount of pure alcohol and the severity of alcohol addiction in the AUD group. Collectively, our findings indicate that global, interhemispheric and intrahemispheric FCD may represent a robust method to detect abnormal functional connection patterns in AUD; this may help us to identify the neural substrates and therapeutic targets of AUD.