Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.

A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .034) and higher percentages of HLA-DR+ CD4+ T cells (P < .001). While not encoding replication-competent viruses, the RNA transcripts frequently encoded HIV-1 Gag-p17 and Nef proteins. These transcripts and/or resulting proteins may activate pathway(s) leading to the immunological nonresponse phenotype.

Revaccination for Hepatitis B in Previous Nonresponders Following Hepatitis C Eradication.

BACKGROUND: Patients with chronic hepatitis C virus (HCV) do not respond to hepatitis B virus (HBV) vaccination as efficiently as the general population. We assessed if revaccination after HCV treatment resulted in improved response. METHODS: Previous HBV vaccine nonresponders were prospectively recruited for revaccination after HCV eradication. Hepatitis B surface antibody (HBsAb) testing was performed 1 month after series completion. RESULTS: Follow-up HBsAb testing was performed in 31 of 34 enrolled patients with 21 (67.7%) reactive results. There were no significant differences in HBsAb reactivity based on age, sex, race, or advanced fibrosis presence. CONCLUSIONS: HBV vaccine nonresponders should be considered for revaccination following HCV cure.

Elevated Serum IL-17A in Kawasaki Disease Patients Predicts Responsiveness to Intravenous Immunoglobulin Therapy.

INTRODUCTION: This study aimed to investigate the correlation between serum interleukin (IL)-17A levels and responsiveness to intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD) patients. METHODS: A retrospective analysis on data from 192 KD patients admitted to the Anqing Municipal Hospital between January 2021 and January 2024 was conducted. Patients were categorized into IVIG-nonresponsive and IVIG-sensitive groups as per the treatment outcomes. Outcome measures included serum IL-17A levels, left coronary artery (LCA) Z scores, and relevant laboratory parameters. Logistic regression analysis was performed to identify predictive factors for IVIG responsiveness, and diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calculation of the area under the curve (AUC). RESULTS: A total of 40 IVIG-nonresponsive cases and 152 IVIG-sensitive cases were included. Prior to intervention, IVIG-nonresponsive patients had significantly higher serum IL-17A levels compared to IVIG-sensitive patients, with a statistically significant difference. After intervention, serum IL-17A levels significantly decreased in IVIG-sensitive patients while remaining elevated in IVIG-nonresponsive patients. IVIG-nonresponsive patients exhibited significantly higher levels of C-reactive protein (CRP), white blood cell count (WBC), NE, and ALT compared to IVIG-sensitive patients, whereas no significant differences in LCA Z scores between the two groups existed. Multivariable logistic regression analysis identified pre-IL-17A, CRP, WBC, and ALT as independent predictors of IVIG-nonresponsiveness in KD. When pre-IL-17A was ≥39.96 pg/mL, the specificity and sensitivity for predicting IVIG-nonresponsive KD were 63.9% and 71.9%, respectively, with an AUC of 0.637. The combined diagnosis of IL-17A, CRP, WBC, and ALT yielded an AUC of 0.780. CONCLUSION: Serum IL-17A levels were remarkably elevated in IVIG-nonresponsive KD patients both before and after intervention. A serum IL-17A level (≥39.96 pg/mL) demonstrated good predictive profile for IVIG-nonresponsive KD, and combining IL-17A with CRP, WBC, and ALT improved diagnostic performance.

HIV estimation using population-based surveys with non-response: A partial identification approach.

HIV estimation using data from the demographic and health surveys (DHS) is limited by the presence of non-response and test refusals. Conventional adjustments such as imputation require the data to be missing at random. Methods that use instrumental variables allow the possibility that prevalence is different between the respondents and non-respondents, but their performance depends critically on the validity of the instrument. Using Manski's partial identification approach, we form instrumental variable bounds for HIV prevalence from a pool of candidate instruments. Our method does not require all candidate instruments to be valid. We use a simulation study to evaluate and compare our method against its competitors. We illustrate the proposed method using DHS data from Zambia, Malawi and Kenya. Our simulations show that imputation leads to seriously biased results even under mild violations of non-random missingness. Using worst case identification bounds that do not make assumptions about the non-response mechanism is robust but not informative. By taking the union of instrumental variable bounds balances informativeness of the bounds and robustness to inclusion of some invalid instruments. Non-response and refusals are ubiquitous in population based HIV data such as those collected under the DHS. Partial identification bounds provide a robust solution to HIV prevalence estimation without strong assumptions. Union bounds are significantly more informative than the worst case bounds without sacrificing credibility.

Older adults' compliance with mobile ecological momentary assessments in behavioral nutrition and physical activity research: pooled results of four intensive longitudinal studies and recommendations for future research.

BACKGROUND: Mobile Ecological Momentary Assessment (EMA) is increasingly used to gather intensive, longitudinal data on behavioral nutrition, physical activity and sedentary behavior and their underlying determinants. However, a relevant concern is the risk of non-random non-compliance with mobile EMA protocols, especially in older adults. This study aimed to examine older adults' compliance with mobile EMA in health behavior studies according to participant characteristics, and prompt timing, and to provide recommendations for future EMA research. METHODS: Data of four intensive longitudinal observational studies employing mobile EMA to understand health behavior, involving 271 community-dwelling older adults (M = 71.8 years, SD = 6.8; 52% female) in Flanders, were pooled. EMA questionnaires were prompted by a smartphone application during specific time slots or events. Data on compliance (i.e. information whether a participant answered at least one item following the prompt), time slot (morning, afternoon or evening) and day (week or weekend day) of each prompt were extracted from the EMA applications. Participant characteristics, including demographics, body mass index, and smartphone ownership, were collected via self-report. Descriptive statistics of compliance were computed, and logistic mixed models were run to examine inter- and intrapersonal variability in compliance. RESULTS: EMA compliance averaged 77.5%, varying from 70.0 to 86.1% across studies. Compliance differed among subgroups and throughout the day. Age was associated with lower compliance (OR = 0.96, 95%CI = 0.93-0.99), while marital/cohabiting status and smartphone ownership were associated with higher compliance (OR = 1.83, 95%CI = 1.21-2.77, and OR = 4.43, 95%CI = 2.22-8.83, respectively). Compliance was lower in the evening than in the morning (OR = 0.82, 95%CI = 0.69-0.97), indicating non-random patterns that could impact study validity. CONCLUSIONS: The findings of this study shed light on the complexities surrounding compliance with mobile EMA protocols among older adults in health behavior studies. Our analysis revealed that non-compliance within our pooled dataset was not completely random. This non-randomness could introduce bias into study findings, potentially compromising the validity of research findings. To address these challenges, we recommend adopting tailored approaches that take into account individual characteristics and temporal dynamics. Additionally, the utilization of Directed Acyclic Graphs, and advanced statistical techniques can help mitigate the impact of non-compliance on study validity.

Nonresponse data in sexual well-being among breast reconstruction patients-who are we overlooking?

BACKGROUND: Missing data can affect the representativeness and accuracy of survey results, and sexual health-related surveys are especially at a higher risk of nonresponse due to their sensitive nature and stigma. The purpose of this study was to evaluate the proportion of patients who do not complete the BREAST-Q Sexual Well-being relative to other BREAST-Q modules and compare responders versus nonresponders of Sexual Well-being. We secondarily examined variables associated with Sexual Well-being at 1-year. METHODS: A retrospective analysis of patients who underwent breast reconstruction from January 2018 to December 2021 and completed any of the BREAST-Q modules postoperatively at 1-year was performed. RESULTS: The 2941 patients were included. Of the four BREAST-Q domains, Sexual Well-being had the highest rate of nonresponse (47%). Patients who were separated (vs. married, OR = 0.69), whose primary language was not English (vs. English, OR = 0.60), and had Medicaid insurance (vs. commercial, OR = 0.67) were significantly less likely to complete the Sexual Well-being. Postmenopausal patients were significantly more likely to complete the survey than premenopausal patients. Lastly, autologous reconstruction patients were 2.93 times more likely to respond than implant-based reconstruction patients (p < 0.001) while delayed (vs. immediate, OR = 0.70, p = 0.022) and unilateral (vs. bilateral, OR = 0.80, p = 0.008) reconstruction patients were less likely to respond. History of psychiatric diagnosis, aromatase inhibitors, and immediate breast reconstruction were significantly associated with lower Sexual Well-being at 1-year. CONCLUSION: Sexual Well-being is the least frequently completed BREAST-Q domain, and there are demographic and clinical differences between responders and nonresponders. We encourage providers to recognize patterns in nonresponse data for Sexual-Well-being to ensure that certain patient population's sexual health concerns are not overlooked.

Calibration and XGBoost reweighting to reduce coverage and non-response biases in overlapping panel surveys: application to the Healthcare and Social Survey.

BACKGROUND: Surveys have been used worldwide to provide information on the COVID-19 pandemic impact so as to prepare and deliver an effective Public Health response. Overlapping panel surveys allow longitudinal estimates and more accurate cross-sectional estimates to be obtained thanks to the larger sample size. However, the problem of non-response is particularly aggravated in the case of panel surveys due to population fatigue with repeated surveys. OBJECTIVE: To develop a new reweighting method for overlapping panel surveys affected by non-response. METHODS: We chose the Healthcare and Social Survey which has an overlapping panel survey design with measurements throughout 2020 and 2021, and random samplings stratified by province and degree of urbanization. Each measurement comprises two samples: a longitudinal sample taken from previous measurements and a new sample taken at each measurement. RESULTS: Our reweighting methodological approach is the result of a two-step process: the original sampling design weights are corrected by modelling non-response with respect to the longitudinal sample obtained in a previous measurement using machine learning techniques, followed by calibration using the auxiliary information available at the population level. It is applied to the estimation of totals, proportions, ratios, and differences between measurements, and to gender gaps in the variable of self-perceived general health. CONCLUSION: The proposed method produces suitable estimators for both cross-sectional and longitudinal samples. For addressing future health crises such as COVID-19, it is therefore necessary to reduce potential coverage and non-response biases in surveys by means of utilizing reweighting techniques as proposed in this study.

Health estimate differences between six independent web surveys: different web surveys, different results?

Most general population web surveys are based on online panels maintained by commercial survey agencies. Many of these panels are based on non-probability samples. However, survey agencies differ in their panel selection and management strategies. Little is known if these different strategies cause differences in survey estimates. This paper presents the results of a systematic study designed to analyze the differences in web survey results between agencies. Six different survey agencies were commissioned with the same web survey using an identical standardized questionnaire covering factual health items. Five surveys were fielded at the same time. A calibration approach was used to control the effect of demographics on the outcome. Overall, the results show differences between probability and non-probability surveys in health estimates, which were reduced but not eliminated by weighting. Furthermore, the differences between non-probability surveys before and after weighting are larger than expected between random samples from the same population.

Persistent Depression and Suicidal Ideation in People Living with HIV in Tanzania: A Longitudinal Cohort Study.

Suicidal ideation and depression are common in people living with HIV (PLWH) in sub-Saharan Africa, but longitudinal data on their persistence in the modern antiretroviral therapy era are lacking. We examined the prevalence of persistent suicidal ideation and depression symptoms using the PHQ-9 in a well-characterized cohort of PLWH and HIV-uninfected community controls. Multivariable logistic regression models were used to determine the relationship between HIV and persistent depression and suicidal ideation. Persistent suicidal ideation was more common in PLWH but there was no difference in persistent depression by HIV status. Approximately one out of five participants with depression at baseline had persistent depression after 12-24 months and only about one out of four participants reporting suicidal ideation at baseline had persistent suicidal ideation after 12-24 months. HIV was associated with suicidal ideation at baseline. Persistent suicidal ideation was significantly associated with HIV immune non-response (p = 0.022). These findings highlight the need for integration of mental health services into HIV care in sub-Saharan Africa with a focus on suicide prevention.

Investigating sources of non-response bias in a population-based seroprevalence study of vaccine-preventable diseases in the Netherlands.

BACKGROUND: PIENTER 3 (P3), conducted in 2016/17, is the most recent of three nationwide serological surveys in the Netherlands. The surveys aim to monitor the effects of the National Immunisation Programme (NIP) by assessing population seroprevalence of included vaccine preventable diseases (VPDs). The response rate to the main sample was 15.7% (n = 4,983), following a decreasing trend in response compared to the previous two PIENTER studies (P1, 55.0%; 1995/1996 [n = 8,356] and P2, 33.0%; 2006/2007 [n = 5,834]). Non-responders to the main P3 survey were followed-up to complete a "non-response" questionnaire, an abridged 9-question version of the main survey covering demographics, health, and vaccination status. We assess P3 representativeness and potential sources of non-response bias, and trends in decreasing participation rates across all PIENTER studies. METHODS: P3 invitees were classified into survey response types: Full Participants (FP), Questionnaire Only (QO), Non-Response Questionnaire (NRQ) and Absolute Non-Responders (ANR). FP demographic and health indicator data were compared with Dutch national statistics, and then the response types were compared to each other. Random forest algorithms were used to predict response type. Finally, FPs from all three PIENTERs were compared to investigate the profile of survey participants through time. RESULTS: P3 FPs were in general healthier, younger and higher educated than the Dutch population. Random forest was not able to differentiate between FPs and ANRs, but when predicting FPs from NRQs we found evidence of healthy-responder bias. Participants of the three PIENTERs were found to be similar and are therefore comparable through time, but in line with national trends we found P3 participants were less inclined to vaccinate than previous cohorts. DISCUSSION: The PIENTER biobank is a powerful tool to monitor population-level protection against VPDs across 30 years in The Netherlands. However, future PIENTER studies should continue to focus on improving recruitment from under-represented groups, potentially by considering alternative and mixed survey modes to improve both overall and subgroup-specific response. Whilst non-responder bias is unlikely to affect seroprevalence estimates of high-coverage vaccines, the primary aim of the PIENTER biobank, other studies with varied vaccination/disease exposures should consider the influence of bias carefully.

Testing the role of associative learning in evidence-based treatments for anorexia nervosa.

Treatments for anorexia nervosa (AN) remain ineffective for many patients. Processes that can account for differential treatment outcomes remain mostly unknown. We propose that the field test the role of associative learning in current psychological treatments. We hold that this line of research could yield actionable information for understanding non-response and improving long-term outcomes. To make this argument, we define associative learning and outline its proposed role in understanding psychiatric disorders and their treatment. We then briefly review data exploring associative learning in AN. We argue that associative learning processes are implicitly implicated in existing treatments; by this rationale, baseline differences in learning may interfere with treatment response. Finally, we outline future research to test our hypotheses. Altogether, future research aimed at better understanding how associative learning may contribute to AN symptom persistence has the potential to inform novel directions in intervention research. PUBLIC SIGNIFICANCE: There is a pressing need to improve outcomes in treatments for anorexia nervosa (AN). We propose that individual differences in associative learning-the ability to form and update associations between cues, contexts, behaviors, and outcomes-may account for differential response to existing treatments. Undertaking this research could provide an understanding of how current treatments work and inform new approaches for those who may be at risk of poor outcomes.

Predictors of nonresponse to treatment and low adherence to internet-based cognitive behavioral therapy in depressed/anxious women facing the couple's fertility problems: a secondary analysis of a randomized control trial.

BACKGROUND: The study aimed to examine the predictors of treatment nonresponse and low adherence to Internet-based cognitive behavioral therapy and face-to-face therapy for treating depression and anxiety in women facing the couple's fertility problems. METHODS: This is a secondary analysis based on a previous randomized controlled trial including 152 depressed/anxious women facing the couple's fertility problems. The study defines low adherence as receiving less than 4 sessions (out of 8 sessions). Nonresponse to treatment refers to a < 50% reduction in the anxiety and depression total scores. RESULTS: A high level of anxiety/depression score before psychotherapy increases the risk of nonresponse to both Internet-based and face-to-face psychotherapies by 1.4 to 2 times in women facing the couple's fertility problems after the treatment and in the 6-month follow-up. However, 4 factors, including diagnosis of mixed anxiety and depression, low education level, long marriage duration, and infertility caused by mixed female/male factors, reduced the risk of nonresponse to psychotherapies. CONCLUSION: Women facing the couple's fertility problems with high depression and anxiety scores are at risk of poor prognosis in response to psychotherapy. Psychologists and healthcare providers of infertility centers should pay more attention to the timely identification and referral of depressed/anxious patients to psychologists.

Prevalence estimates for COVID-19-related health behaviors based on the cheating detection triangular model.

BACKGROUND: Survey studies in medical and health sciences predominantly apply a conventional direct questioning (DQ) format to gather private and highly personal information. If the topic under investigation is sensitive or even stigmatizing, such as COVID-19-related health behaviors and adherence to non-pharmaceutical interventions in general, DQ surveys can lead to nonresponse and untruthful answers due to the influence of social desirability bias (SDB). These effects seriously threaten the validity of the results obtained, potentially leading to distorted prevalence estimates for behaviors for which the prevalence in the population is unknown. While this issue cannot be completely avoided, indirect questioning techniques (IQTs) offer a means to mitigate the harmful influence of SDB by guaranteeing the confidentiality of individual responses. The present study aims at assessing the validity of a recently proposed IQT, the Cheating Detection Triangular Model (CDTRM), in estimating the prevalence of COVID-19-related health behaviors while accounting for cheaters who disregard the instructions. METHODS: In an online survey of 1,714 participants in Taiwan, we obtained CDTRM prevalence estimates via an Expectation-Maximization algorithm for three COVID-19-related health behaviors with different levels of sensitivity. The CDTRM estimates were compared to DQ estimates and to available official statistics provided by the Taiwan Centers for Disease Control. Additionally, the CDTRM allowed us to estimate the share of cheaters who disregarded the instructions and adjust the prevalence estimates for the COVID-19-related health behaviors accordingly. RESULTS: For a behavior with low sensitivity, CDTRM and DQ estimates were expectedly comparable and in line with official statistics. However, for behaviors with medium and high sensitivity, CDTRM estimates were higher and thus presumably more valid than DQ estimates. Analogously, the estimated cheating rate increased with higher sensitivity of the behavior under study. CONCLUSIONS: Our findings strongly support the assumption that the CDTRM successfully controlled for the validity-threatening influence of SDB in a survey on three COVID-19-related health behaviors. Consequently, the CDTRM appears to be a promising technique to increase estimation validity compared to conventional DQ for health-related behaviors, and sensitive attributes in general, for which a strong influence of SDB is to be expected.

Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.

Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies.

OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease.

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4ß7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

[Treatment resistance in anxiety disorders-Definition and treatment options]. / Therapieresistenz bei Angsterkrankungen ­ Definition und Behandlungsoptionen.

Treatment resistance in anxiety disorders represents a clinical challenge, contributes to the chronicity of the diseases as well as sequential comorbidities, and is associated with a significant individual and socioeconomic burden. This narrative review presents the operational definition of treatment resistance in anxiety disorders according to international consensus criteria (< 50% reduction in the Hamilton Anxiety Scale, HAM­A, score or < 50% reduction in the Beck Anxiety Inventory, BAI, score or a clinical global impression-improvement, CGI­I, score > 2). At least two unsuccessful guideline-based treatment attempts with pharmacological monotherapy or at least one unsuccessful treatment attempt with adequately delivered cognitive behavioral therapy are required. Pharmacotherapeutically, after excluding pseudo-resistance, switching the medication within one class or to another class and augmentation strategies with other antidepressants (mirtazapine, agomelatine), antipsychotics (quetiapine) or anticonvulsants (valproate) are recommended. Psychotherapeutically, third-wave therapies, psychodynamic therapy, systemic therapy and physical exercise can be considered for therapy resistance. In cases of no response to psychotherapy or pharmacotherapy, the respective other form of therapy or a combination of both should be offered. Compounds targeting the glutamatergic and endocannabinoid systems as well as neuropeptides are being tested as potential innovative pharmaceuticals for treatment-resistant anxiety disorders. There is an urgent need for further research to identify predictive markers and mechanisms as well as to develop innovative pharmacological and psychotherapeutic interventions for treatment-resistant anxiety disorders.

Altered gut microbiota is associated with different immunologic responses to antiretroviral therapy in HIV-infected men who have sex with men.

The association between gut microbiota and immunologic nonresponse among people living with HIV (PLHIV) on antiretroviral therapy (ART) is not well documented. This study aimed to characterize gut microbiota among HIV-infected men who have sex with men (MSM) with different immunologic responses. We recruited HIV-infected MSM and HIV-uninfected MSM (healthy controls, HC) in Guangzhou, June-October 2021. HIV-infected MSM were grouped into good immunological responders (GIR) (CD4 + T cell count ≥ 350 cells/µL) and poor immunological responders (PIR) (<350 cells/µL). Blood and stool samples were collected. Microbial translocation in serum was performed using enzyme-linked immunosorbent assay (ELISA). Bacterial 16S ribosomal DNA sequencing was performed on stool samples, and microbial metabolites were obtained through gas chromatography-mass spectrometry. 56 GIR, 41 PIR, and 51 HC were included. Microbial translocation marker soluble cluster of differentiation 14 (sCD14) in both GIR and PIR groups was significantly higher than that in HC. Compared with PIR or HC groups, the genera of Coprococcus, Blautia, Clostridium, and SMB53 were decreased, whereas Megamonas and Megasphaera were more abundant in GIR group. Compared with GIR or PIR groups, Bifidobacterium, Collinsella, Faecalibacterium, Oscillospira, and Roseburia were more abundant, whereas Escherichia was decreased in HC group. The levels of benzenoids, imidazoles, phenylpropanoic acids, phenylpropanoids, and pyridines showed strongly significant correlations between differential genera. This study presented a comprehensive landscape of gut microbiota in PLHIV with different treatment outcomes. Megamonas, Coprococcus and Blautia were the major genera correlated with different immunologic responses in PLHIV.

Primary non-response to antiviral therapy affects the prognosis of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIM: Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. METHODS: A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan-Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. RESULTS: This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase < 50 IU/L and cirrhosis groups, primary nonresponse was related to poor overall survival and progression-free survival. Based on multivariate risk analysis, primary non-response (hazard ratio (HR) = 1.883, 95% CI 1.289-2.751, P = 0.001), tumor multiplicity (HR = 1.488, 95% CI 1.036-2.136, P = 0.031), portal vein tumor thrombus (HR = 2.732, 95% CI 1.859-4.015, P < 0.001), hemoglobin < 120 g/L (HR = 2.211, 95% CI 1.548-3.158, P < 0.001) and tumor size ≥ 5 cm (HR = 2.202, 95% CI 1.533-3.163, P < 0.001) were independent risk factors for 1-year OS. According to the scoring chart, patients were divided into three risk groups (high-, medium-, and low-risk groups) with mortality rates of 61.7%, 30.5%, and 14.1%, respectively. CONCLUSIONS: The level of viral decline at 3 months post-antiviral treatment may predict the OS of patients with HBV-related HCC, and primary non-response may shorten the median survival time of patients with high HBV-DNA levels.

Modulation of resting-state functional connectivity in default mode network is associated with the long-term treatment outcome in major depressive disorder.

BACKGROUND: Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. METHODS: Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. RESULTS: Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. CONCLUSION: Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.