Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors.

Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1-15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.

Longitudinal analysis of the relationship between PTSD symptom clusters, cigarette use, and physical health-related quality of life.

PURPOSE: Posttraumatic stress disorder (PTSD) symptoms, particularly numbing and hyperarousal symptoms, are related to poor physical health-related quality of life (HRQoL). Tobacco dependence is also associated with poor HRQoL, and individuals with PTSD may smoke at higher rates than the general population. Our study aimed to examine the impact of quitting smoking and changes in PTSD symptoms over time on changes in physical HRQoL. METHODS: The study used archival data from enrollees (N = 943) in a smoking cessation clinical trial for veterans with PTSD (VA Cooperative study #519). RESULTS: Two of the physical HRQoL domains were sensitive to changes in PTSD symptoms over time: General Health and Vitality. CONCLUSIONS: Our findings suggest that particular physical HRQoL domains may be subject to improvement if PTSD symptoms decrease over time.

[The health conditions of prison inmates in Tuscany]. / Lo stato di salute della popolazione detenuta all'interno delle strutture penitenziarie della Regione Toscana.

OBJECTIVE: Investigation of health conditions of prison inmates in Tuscany (Italy) compared with non-institutionalized population and literature data. DESIGN: Cross-sectional descriptive study of a sample recruited for a prospective cohort study. SETTING E PARTICIPANTS: Prison inmates detained in Tuscany on June 15th 2009. Istat data concerning the survey "Aspects of daily life" 2006-2009 has been used for comparison. MAIN OUTCOME MEASURES: The measures used for the analysis are prevalence data by age classes and odds ratios obtained through a logistic regression model. Outcome variables are: broad disease groups, in particular infectious and parasitic diseases and psychic disorders. RESULTS: Prison inmates from Northern Africa and Eastern Europe are 40% of the population studied. A high consumption of tobacco is observed, with 70.6% of regular smokers among prisoners vs 33.2% among free citizens. Digestive system diseases are the most frequent diseases (25.1%), followed by infectious and parasitic diseases (15.7%). Among digestive disease,more than half are teeth and oral cavity pathologies that affect 13.7% of prisoners.Other frequently reported disease groups were diseases of the bone-muscular and connective systems (11.0%), of the circulatory system (10.8%), endocrine and metabolic systems (9.2%), traumatisms and poisonings (6.8%), respiratory system diseases (5.9%), and nervous system diseases (4.9%). The prevalence of ischemic heart diseases, diabetes, obesity and esophagitis, gastritis and gastro-duodenal ulcers is significantly higher among prisoners than in the general population. The most frequent infectious and parasitic diseases are Hepatitis C Virus (HCV) infection with a prevalence of 9.0%, Hepatitis B Virus (HBV) infection (2.2%), and Human Immunodeficiency Virus (HIV) infection (1.4%). Hepatitis C, HIV and hepatitis A have a higher prevalence among inmates of Italian nationality, while syphilis is more common among prisoners from Eastern Europe (1.2%). The prevalence of psychic disorders among prison inmates is 33.3% (vs 11.6% in the general population), while it decreases to 29.3% if we exclude the population detained in the Psychiatric Prison. CONCLUSIONS: According to previous national and international studies, the cohort is more affected than the general population by physical and psychic disorders, partly associated to the prison inmate's country of origin.

Impact of childhood maltreatment on physical health-related quality of life in U.S. active duty military personnel and combat veterans.

Previous studies have found an association between childhood maltreatment (CM) and health-related quality of life (HRQoL), and to a lesser extent have considered whether psychiatric symptoms may explain the relationship. This study aimed to further our understanding of the link between CM and HRQoL by testing whether posttraumatic stress disorder (PTSD) or depressive symptoms mediate the relationship between childhood maltreatment and physical HRQoL. Mediation models were examined in a sample of male Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) active duty and combat veterans (n=249). PTSD and depressive symptoms mediated the relationship between CM and overall physical HRQoL, as well as participation in daily activities due to physical health, bodily pain, and social functioning. Mediation of the relationship between childhood maltreatment and physical and social functioning by depression and PTSD symptoms may lend support to neurobiological hypotheses that childhood maltreatment sensitizes the nervous system and after repeated trauma may lead to the development of psychiatric symptoms, which have a major impact on morbidity and mortality.

The cumulative effect of different childhood trauma types on self-reported symptoms of adult male depression and PTSD, substance abuse and health-related quality of life in a large active-duty military cohort.

History of childhood trauma (CT) is highly prevalent and may lead to long-term consequences on physical and mental health. This study investigated the independent association of CT with symptoms of adult depression and posttraumatic stress disorder (PTSD), mental and physical health-related quality of life (HRQoL), as well as current tobacco consumption and alcohol abuse in a large homogenous cohort of 1254 never-deployed, young male Marines enrolled in the Marine Resiliency Study. Independent effects of CT history, number and type of CT on outcomes were analyzed using hierarchical multivariate logistic regression models. Our results suggested dose-dependent negative effect of an increasing number of trauma types of CT on depression, PTSD and HRQoL. Experience of single CT type demonstrated overall weak effects, while history of multiple CT types distinctively increased the likelihood of adult PTSD symptomology (OR: 3.1, 95% CI: 1.5-6.2), poor mental (OR: 2.3, 95% CI: 1.7-3.1) and physical HRQoL (OR: 1.4, 95% CI: 1.1-1.9). Risk for depression symptoms was similar for both single and multiple CT (OR: 2.2, 95% CI: 1.3-3.8 and OR: 2.1, 95% CI: 1.2-3.5 respectively). CT history had no effects on current tobacco use and alcohol abuse. Our study thus provides evidence for substantial additive effect of different CT types on adult mental and physical health with increasing levels of exposure.

PTSD and depression as predictors of physical health-related quality of life in tobacco-dependent veterans.

OBJECTIVE: Smoking, depression and PTSD are related to poor physical health outcomes and health-related quality of life (HRQoL). Previous studies examining the effects of quitting smoking on HRQoL have been mixed. This study aimed to examine the effects of PTSD, depressive symptoms and smoking cessation on HRQoL in a sample receiving treatment for PTSD. METHOD: This study utilized archival interview and self-report data from a clinical trial (VA Cooperative Study 519) that recruited tobacco dependent veterans with chronic PTSD (N=943). RESULTS: Analyses were conducted using hierarchical linear modeling and indicated that PTSD and depressive symptoms differentially affected the various physical health status domains. Additionally, quitting smoking was associated with better self-perceived health status and social functioning. CONCLUSION: Our findings further explain the interrelationships of PTSD, depression, and smoking in the prediction of physical HRQoL and advocate the importance of integrated care.