Background: The objectives of this study were to delineate whether delirium in older adults is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, T helper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and T regulatory profiles. Methods: We recruited 65 older adult patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. Results: We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. Conclusions: Post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

Introduction: To assess the burden of depression, anxiety and suicidality; and to determine the impact of integrated mental health and HIV services on treatment outcomes among Thai adolescents and young adults living with HIV (AYHIV).Methods: A multicentre prospective cohort study was conducted among AYHIV (15 to 25 years), and age‐ and sex‐matched HIV‐uninfected adolescents and young adults (HUAY). The Patient Health Questionnaire 9‐item (PHQ‐9) and Generalized Anxiety Disorder 7‐item scales (GAD‐7) were used as screening tools for depressive and anxiety symptoms respectively. History of lifetime and recent suicidal ideations/attempts were ascertained. Elevated mental health screening scores were defined as having either significant depressive symptoms (PHQ‐9 ≥9), significant anxiety symptoms (GAD‐7 ≥10) or suicidality (lifetime; and recent [within two weeks]). Participants meeting these criteria were referred to psychiatrists for confirmatory diagnosis and mental health services. Follow‐up assessment with PHQ‐9 and GAD‐7 was performed one year after psychiatric referral.Results: From February to April 2018, 150 AYHIV and 150 HUAY were enrolled, median age was 19.0 (IQR:16.8 to 21.8) years and 56% lived in urban areas. Among AYHIV, 73% had HIV RNA <50 copies/mL, and median CD4 count was 580 (IQR:376 to 744) cells/mm³. At enrolment, 31 AYHIV (21%; 95%CI:14% to 28%) had elevated mental health screening scores; 17 (11%) significant depressive symptoms, 11 (7%) significant anxiety symptoms and 21 (14%) suicidality. Seven AYHIV (5%) had all three co‐existing conditions. These prevalences were not substantially different from HUAY. Urban living increased risk, whereas older age decreased risk of elevated mental health screening scores (p < 0.05). All AYHIV with elevated mental health screening scores were referred to study psychiatrists, and 19 (13%; 95%CI: 8% to 19%) had psychiatrist‐confirmed mental health disorders (MHDs), including adjustment disorder (n = 5), major depression (n = 4), anxiety disorders (n = 2), post‐traumatic stress disorder (n = 1) and mixed MHDs (n = 4). One year after psychiatric referral, 42% of AYHIV who received mental health services demonstrated an absence of significant mental health symptoms from the reassessments, and 26% had an improved score.Conclusions: With the significant burden of MHDs among AYHIV, an integration of mental health services, including mental health screenings, and psychiatric consultation and referral, is critically needed and should be scaled up in HIV healthcare facilities.

Objectives Activation of the immune-inflammatory response system (IRS) and a deficiency in the compensatory immunoregulatory system (CIRS), neuronal injuries, and alterations in the glutamate receptor (GlutaR), aquaporin-4 (AQP4), and heat shock protein 60 (HSP60) are involved in delirium. Increased serum levels of neurofilament protein (NFP), glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) are biomarker of neuronal injury and post-surgery cognitive impairments. Polyreactive antibodies (PAbs) contribute to the development of immune-mediated disease. This investigation delineates whether elevated IgA and IgG reactivity against those self-antigens is associated with enhanced IRS responses and delirium severity. Methods We measured peak Delirium Rating Scale (DRS) scores on days 2 and 3 following surgery in 59 hip fracture older adults, and IgA/IgG antibody levels against MBP, NFP, GFAP and myelin oligodendrocyte glycoprotein (MOG), GlutaR, N-Methyl-D-Aspartate receptor (NMDAR), APQ4 and HSP60. Results The IgA antibody levels against those self-antigens, especially GFAP, MBP and HSP60, strongly predict peak DRS scores on days 2 and 3 post-surgery. IgA reactivity against NMDAR and baseline DRS scores explained 40.6% of the variance in peak DRS scores, whilst IgA against NMDAR, IgG against MBP and age explained 29.1% of the variance in the IRS/CIRS ratio. There was no correlation between DRS scores and IgG directed against these self-antigens. Conclusions Increased IgA levels against neuronal self-antigens, AQP4, and HSP60 are risk factors for delirium. PAb-associated breakdown of immune tolerance, IRS activation and injuries in the neuronal cytoskeleton, oligodendrocytes, astrocytes, glial cells, and myelin sheath are involved in the pathophysiology of delirium.

The objectives of this study were to delineate whether delirium is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, Thelper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and Tregulatory profiles. We recruited 65 elderly patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. The pain scores during delirium were significantly and positively associated with CXCL8 and CCL3 and negatively with IL-4 and sIL-1RA. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. In conclusion, post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.