Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Anticoagulant Prescribing Patterns in New-Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with an increased risk of thromboembolic stroke. Recommendations regarding the optimal anticoagulant, timing of initiation, and duration of therapy remain uncertain. METHODS: Administrative databases were used to include adult patients who presented with POAF after cardiac surgery between January 1, 2015, and December 31, 2020. Key exclusion criteria included preexisting atrial fibrillation, mechanical valve replacement, or anticoagulant prescription fill within 6 months before the index admission. RESULTS: A total of 3214 of patients were included, and 878 (27.3%) were prescribed an oral anticoagulant (OAC) on discharge, with 536 (61%) prescribed warfarin and 342 (39%) prescribed a direct OAC. More than half of the patients (56.1%) stopped their OAC by 6 months. There was no difference in stroke or systemic embolism at 30 days, 3 months, or 6 months between those with and without anticoagulation prescribed. However, those on any OAC had higher rates of any bleeding at all time points. CONCLUSIONS: A minority of patients who presented with POAF after cardiac surgery were prescribed OAC, with warfarin being the most common agent. OAC initiation was associated with increased bleeding risk, warranting special consideration when assessing a patient's risk of stroke with the increased risk of bleeding, particularly in the postoperative period.

L1 Retrotransposons: A Potential Endogenous Regulator for Schizophrenia.

The long interspersed nuclear elements 1 (LINE-1/L1s) are the only active autonomous retrotransposons found in humans which can integrate anywhere in the human genome. They can expand the genome and thus bring good or bad effects to the host cells which really depends on their integration site and associated polymorphism. LINE-1 retrotransposition has been found participating in various neurological disorders such as autism spectrum disorder, Alzheimer's disease, major depression disorder, post-traumatic stress disorder and schizophrenia. Despite the recent progress, the roles and pathological mechanism of LINE-1 retrotransposition in schizophrenia and its heritable risks, particularly, contribution to "missing heritability" are yet to be determined. Therefore, this review focuses on the potentially etiological roles of L1s in the development of schizophrenia, possible therapeutic choices and unaddressed questions in order to shed lights on the future research.

Corrigendum: GABAergic System Dysfunction and Challenges in Schizophrenia Research.

[This corrects the article DOI: 10.3389/fcell.2021.663854.].

GABAergic System Dysfunction and Challenges in Schizophrenia Research.

Despite strenuous studies since the last century, the precise cause and pathology of schizophrenia are still largely unclear and arguably controversial. Although many hypotheses have been proposed to explain the etiology of schizophrenia, the definitive genes or core pathological mechanism remains absent. Among these hypotheses, however, GABAergic dysfunction stands out as a common feature consistently reported in schizophrenia, albeit a satisfactory mechanism that could be exploited for therapeutic purpose has not been developed yet. This review is focusing on the progress made to date in the field in terms of understanding the mechanisms involving dysfunctional GABAergic system and loops identified in schizophrenia research.

Reduced gray matter volume in male adolescent violent offenders.

BACKGROUND: Previous studies reported that reduced gray matter volume (GMV) was associated with violent-related behaviors. However, the previous studies were conducted on adults and no study has studied the association between GMV and violent behaviors on adolescents. The purpose of the study was to investigate GMV's effects in adolescent violent offenders based on a Chinese Han population, which can address the problem of possible confounding factors in adult studies. METHODS: We recruited 30 male adolescent violent offenders and 29 age- and sex-matched healthy controls (HCs). Differences in both whole-brain and GMV were evaluated using voxel-based morphometry (VBM). We assessed the accuracy of VBM using the receiver operating characteristic curve (ROC) and discriminant analysis. RESULTS: Compared with HCs, the male adolescent offenders showed significantly reduced GMV in five cortical and subcortical brain regions, including the olfactory cortex, amygdala, middle temporal gyrus and inferior parietal lobe in the left hemisphere, as well as the right superior temporal gyrus. Both ROC curve and discriminate analyses showed that these regions had relatively high sensitivities (58.6%-89.7%) and specificities (58.1%-74.2%) with 76.7% classification accuracy. CONCLUSIONS: Our results indicated that reduced volume in the frontal-temporal-parietal-subcortical circuit may be closely related to violent behaviors in male adolescents, which might be an important biomarker for detecting violent behaviors in male adolescents.

Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders.

Autism and autism spectrum disorders (ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells (MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD. Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review will focus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

The Role of Direct Oral Anticoagulants in Patients With Coronary Artery Disease.

Despite contemporary management, patients with coronary artery disease (CAD) remain at high risk for thrombotic events. Several randomized controlled trials have evaluated the use of direct oral anticoagulants (DOACs) in patients with CAD, including in the setting of acute coronary syndrome (ACS) and stable CAD, and in patients with concomitant atrial fibrillation. Trials of apixaban and dabigatran in patients with ACS demonstrate no benefit with an increased risk of bleeding. Conversely, rivaroxaban at a reduced dose of 2.5 mg twice daily reduced thrombotic events and all-cause mortality when added to dual antiplatelet therapy in patients with ACS. Similarly, the addition of low-dose rivaroxaban to acetylsalicylic acid reduced the risk of thrombotic events in patients with stable CAD. However, the addition of a DOAC to antiplatelet therapy increased the risk of major bleeding. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dual-pathway or low-dose triple therapy regimens including dabigatran or rivaroxaban reduced bleeding risk compared to traditional warfarin-based triple therapy, although it remains unclear whether these regimens preserve antithrombotic efficacy. DOAC-based antithrombotic regimens prove useful in patients with CAD in various settings; however, careful selection of patients and regimens per trial protocols are critical to achieving net benefit.

Gender differences among homicide offenders with schizophrenia in Hunan Province, China.

This study aimed to understand the demographic, clinical and criminological characteristics of Chinese homicide offenders with schizophrenia from a gender-based perspective. Information on all homicide offenders with schizophrenia who received forensic psychiatric assessment between 2010 and 2016 in Hunan Province, China, was systematically retrieved (n = 669). Gender differences in the above characteristics were analyzed, and independent correlates of homicide were explored. The male to female ratio of homicide offenders was about 4:1. Proportionally more males were single, unemployed and younger when committing their first crime than was apparent in females. Male perpetrators were more often influenced by delusions. Females were more likely to target their close family members. For males, living in rural areas and having a family history of mental disorder were positively associated with homicide, while having a criminal history and being unemployed were negatively associated. For females, younger age was positively, while being unmarried and unemployment were negatively associated with homicide. Our results indicate significant gender differences among Chinese homicide offenders with schizophrenia in demographic, clinical and criminological characteristics and in independent correlates of homicide. Further research in this field, especially aims at determining risk factors for crime in this population, should take the gender differences into account.

Disrupted small-world brain network topology in pure conduct disorder.

OBJECTIVES: Conduct disorder (CD) is characterized by the violation of the rights of others or basic social rules and a repetitive, persistent pattern of antisocial and aggressive behaviors. A large number of functional and structural neuroimaging studies have identified widely abnormalities in specific brain regions in CD, but the alterations in the topological organization of functional networks among them remain largely unknown. METHODS: Resting-state functional magnetic resonance imaging was applied to investigate the intrinsic functional connectivity in 18 pure CD patients and eighteen typically developing healthy controls. We first constructed the functional networks and then examined the CD-related alteration in topology properties using graph theoretical analysis. RESULTS: Both the CD group and healthy controls exhibited small-world topology. However, the CD group showed decreased global and local efficiency. Changes in the nodal characteristics in CD group were found predominantly in the default-mode network, visual, and striatum regions. In addition, altered fronto-limbic-striatum network topology was found to have a relationship with clinical scores. CONCLUSIONS: Our findings indicate the altered nodal topology of brain functional connectivity networks in CD. SIGNIFICANCE: The results provide unequivocal evidence of a topological disruption in the brain networks that suggest some possible pathophysiological mechanisms underlying CD.

Association between schizophrenia and violence among Chinese female offenders.

Little is known about the association between schizophrenia and violence in women in China. This study aimed to examine the association between schizophrenia and violence in Chinese female offenders. Fifty-two schizophrenia patients were identified from the female offenders who received forensic psychiatric assessments in 2011 in Hunan province, China. Using a propensity score matching method, 104 matched controls without psychiatric disorders were selected from female criminals in Hunan province. Violent offences and homicides were verified and recorded. The percentages of violent offences and homicides were significantly higher in female offenders with schizophrenia than in controls (78.8% vs. 30.8%, P < 0.001; 44.2% vs. 18.3%, P = 0.001, respectively). Multivariate logistic regression analyses revealed that diagnosis of schizophrenia, younger age at first offence, living in rural area and a lower education level were independently and positively associated with violent offences, while having a diagnosis of schizophrenia and lower education level were associated with homicides. There appears to be an independent and positive association between schizophrenia and violent offence in Chinese female offenders. Effective preventive approaches on violence in female schizophrenia patients are warranted.

Short- and long-range functional connectivity density alterations in adolescents with pure conduct disorder at resting-state.

Conduct disorder (CD) is a developmental disorder defined by a repetitive and persistent display of antisocial and aggressive behaviors that violates the rights of others or basic social rules. Recently, resting-state functional magnetic resonance imaging (rsfMRI) has been widely adopted to investigate the altered intrinsic neural activities and the disrupted endogenous brain connectivity of CD. In this study, functional connectivity density (FCD) mapping, a newly developed ultrafast voxel-wise method based on rsfMRI, was applied for the first time to examine the changes in the brain functional connectivity in CD at the voxel level. We assessed the differences in FCD between eighteen male adolescents with CD and eighteen typically-developing (TD) individuals. Then, the identified brain regions in which CD patients and healthy controls exhibited significant difference in FCD were extracted to calculate the correlations between measures of FCD values and clinical data. We discovered that compared to healthy controls, CD patients showed increased short-range FCD in the default-mode network including the bilateral posterior cingulate cortex (PCC) and the bilateral precuneus (PCUN). More importantly, increased short-range FCD values in the bilateral PCC, the bilateral PCUN, and increased long-range FCD values in the left MCC showed significant correlations with the impulsivity. Overall, these results suggested that the FCD abnormalities in CD patients occurred in brain regions known to be involved in cognition, emotion and visual perception.

Prevalence of borderline personality disorder and its risk factors in female prison inmates in China.

High prevalence of borderline personality disorder (BPD) has been found in Western prisons but no such data exists in China. The objective of this study was to determine the lifetime prevalence of BPD in Chinese female prison inmates and its associated risk factors. This cross-sectional study was conducted in Hunan Provincial Female Prison. Data on consenting inmates' socio-demographic and clinical characteristics were collected and the diagnosis of lifetime BPD was established using the Structural Clinical Interview for DSM-IV. The prevalence of BPD was 10.6% in the cohort of 2709 participating inmates. Multiple logistic regression analysis revealed that younger age, unmarried marital status, higher education level, fewer major medical conditions, more frequent personal and family members' drug use, more frequent comorbid psychiatric disorders and family history of psychiatric disorders were positively and independently associated with BPD. BPD is common in Chinese female prison inmates. Considering its adverse social consequences and impact on physical and mental well-being, serious attempts should be made to diagnose BPD early and improve access to treatment in women prisons.

Physical restraint for psychiatric patients and its associations with clinical characteristics and the National Mental Health Law in China.

Physical restraint (PR) for patients is an ongoing controversial topic in psychiatry. This study examined the percentage of PR and its associations with clinical characteristics and the implementation of the National Mental Health Law (NMHL) in China. The study consecutively assessed a sample of 1364 psychiatric inpatients. Socio-demographic and clinical data including use of PR were collected from the medical records using a form designed for this study and confirmed via interview. Psychopathology and insight were measured using standardized instruments. The percentage of PR was 27.2% in the whole sample with 30.7% and 22.4% occurring respectively before and after the NMHL implementation (p=0.001). In multiple logistic regression analysis PR was positively associated with unemployment, lower income, aggression in the past month, being admitted before the NMHL implementation and poorer insight. The percentage of PR in Chinese psychiatric patients is associated with various clinical factors and appeared to decrease after the implementation of the NMHL. Focused and individualized care for patients who are unemployed, have low income, recent aggression and poor insight would be necessary at early stages of admission.

Prevalence of aggression in hospitalized patients with schizophrenia in China: A meta-analysis.

INTRODUCTION: Aggression is a major concern in psychiatric inpatient care. Variations in study designs, settings, populations and data collection methods render comparisons of the prevalence of aggressive behavior in high-risk settings difficult. We proposed to estimate the pooled prevalence of aggression among inpatients with schizophrenia in China. METHODS: Reports on aggressive behaviour involving physical contact or risks of interpersonal violence, in schizophrenia in Chinese general psychiatric wards were retrieved by using computer-assisted searches and manual searches of the reference lists of the relevant literature. Statistical analyses were conducted using the Comprehensive Meta-Analysis V2 software. Potential sources of heterogeneity were analyzed with Cochrane's Q analysis. RESULTS: The search yielded 19 eligible studies involving a total of 3,941 schizophrenia patients. The prevalence of aggressive behavior in psychiatric wards ranged between 15.3% and 53.2%. The pooled prevalence of aggression was 35.4% (95% CI: 29.7%, 41.4%). The most commonly reported significant risk factors for aggression were positive psychotic symptoms: hostility or suspiciousness, 78.9% (15 studies); delusions, 63.2% (12 studies); disorganized behavior, 26.3% (5 studies); and auditory hallucinations, 10.5% (2 studies); together with: past history of aggression, 42.1% (8 studies); and involuntary admission, 10.5% (2 studies). CONCLUSIONS: Aggressive behaviour is common in Chinese inpatients with schizophrenia. The prevalence figures indicate the need to identify reliable clinical and illness predictors for aggression in inpatient psychiatric wards and to test investigations aimed at reducing aggressive episodes and their adverse outcomes.

Rare presentation of a right retroperitoneal accessory spleen: A case report.

An accessory spleen is a congenital malformation, which is defined as ectopic splenic parenchyma. Here, an extremely rare case of a right retroperitoneal accessory spleen, mimicking a retroperitoneal neoplasm, is reported. A 40-year-old woman was referred following the incidental detection of a retroperitoneal neoplasm. Computed tomography and magnetic resonance imaging scans confirmed the presence of a retroperitoneal neoplasm at the hepatorenal recess. Retroperitoneoscopic excision was conducted, with excellent results. Pathological examination of the resected specimen revealed splenic tissue. In conjunction with a review of the literature and a discussion of the salient radiological features, the present case highlights the requirement for accurate preoperative diagnosis of an accessory spleen in the right retroperitoneal space, in order to avoid unnecessary surgical intervention.