Greater Systemic Inflammation Research Articles

Food insecurity, inflammation, and immune function among older US adults: Findings from the health and Retirement study

BackgroundFood insecurity (FI) is a pressing public health concern among older adults and has been associated with adverse cardiovascular outcomes. Greater systemic inflammation may provide a pathway to explain these associations, but few studies have examined the link between FI and markers of inflammation. Thus, the objective of the present study was to evaluate the associations between FI and multiple inflammatory and immune functioning biomarkers using a nationally representative study of US adults aged > 50 years. MethodParticipants (n = 3,924) were drawn from the longitudinal Health and Retirement Study (HRS). Household FI was assessed using the six-item Short Form Food Security Survey Module from the 2013 HRS Health Care and Nutrition Study. Markers of inflammation (neutrophil–lymphocyte ratio, albumin, hs-CRP, IL6, IL10, IL-1Ra, sTNFR-1, and TGFβ-1) and immune functioning (CMV) were collected during the 2016 HRS Venous Blood Study. Multivariate logistic and linear regression models were used to evaluate associations between household FI and inflammatory and immune functioning biomarkers, adjusting for individual and household sociodemographic characteristics. ResultsThe weighted prevalence of FI was 18.8 %. Age and sex-adjusted mean showed that FI was associated with higher levels of inflammation and impaired immune functioning (Ps-value < 0.05). Older adults with FI had higher mean levels of albumin, hs-CRP, IL6, IL10, IL-1Ra, TGFß-1, and CMV seronegative and borderline (Ps-value < 0.05). Multivariate-adjusted regression model showed that FI was associated with high-risk categories of hs-CRP (OR 1.34, 95 % CI 1.06, 1.68), IL-6 (OR 1.66, 95 % CI 1.28, 2.14), IL-1Ra (OR 0.67, 95 % CI 0.48, 0.93), TGFß-1 (OR 1.87, 95 % CI 1.45, 2.42), seronegativity for CMV (OR 0.48, 95 % CI 0.35, 0.64). ConclusionIn this nationally representative sample of older adults, FI was positively associated with multiple markers of systemic inflammation and impaired immune functioning. Public health efforts that directly work to reduce FI among older adults are warranted and may result in further improvements in their health and well-being.

Associations Between Adiponectin and the Development of Diabetes in Rheumatoid Arthritis.

We evaluated associations between adiponectin and the risk of diabetes among patients with rheumatoid arthritis (RA), a systemic inflammatory disease associated with metabolic disturbance. This prospective cohort study included adults with RA from the Veterans Affairs Rheumatoid Arthritis Registry. Adiponectin and inflammatory cytokines/chemokines were measured at enrollment on stored serum samples. Adiponectin levels were categorized, and clinical variables were described across categories (<10 μg/mL; 10-40 μg/mL; >40 μg/mL). Multivariable Cox proportional hazard models evaluated associations between adiponectin and incident diabetes adjusting for age, sex, race, smoking status, body mass index (BMI), disease-modifying therapy use, calendar year, and comorbidity. Testing for modification of effect in the context of elevated cytokines/chemokines was performed. Among 2595 patients included in the analysis, those with adiponectin levels >40 μg/mL (N = 379; 15%) were older and had lower BMI. There were 125 new cases of diabetes among 1689 patients without prevalent disease at enrollment. There was an inverse association between adiponectin and incident diabetes; however, the association was positive among patients with adiponectin levels >40 μg/mL. Patients with levels >40 μg/mL were at higher risk compared to those with levels 10-40 μg/mL (HR: 1.70 [1.34, 2.16] P < .001). Those with adiponectin levels >40 μg/mL had significantly higher levels of inflammatory cytokines with evidence of a modified effect of adiponectin on diabetes risk in the setting of inflammation. The relationship between adiponectin and incident diabetes risk is U-shaped in RA. Patients with very high adiponectin levels have greater systemic inflammation and an altered relationship between adiponectin and diabetes risk.

NEURODEGENERATION BIOMARKERS HELP EXPLAIN ASSOCIATION BETWEEN INFLAMMATION AND COGNITIVE DYSFUNCTION

Abstract There is past evidence that immune aging (or immunosenescence) and high systemic inflammation are associated with cognitive dysfunction and ADRD. However, it is unknown whether these immune-related aging processes are associated with neurodegeneration, tauopathy, amyloid accumulation, and/or vascular issues in the brain. To address this gap, we utilized a set of recently assayed highly innovative markers of neurodegeneration, biomarkers of inflammation, and proportions of naïve lymphocytes (indicative of less immune aging), and cognitive dysfunction (errors on the Telephone Interview for Cognitive Status) in the Health and Retirement Study, a nationally representative sample of US adults over age 50 (N = 3985). Using structural equation modeling (SEM), we estimated latent factors representing neurodegeneration (neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphotau 181 (pTau181)), inflammation (c-reactive protein, IL10, IL1 receptor agonist, IL6, TNF receptor 1, albumin, and percentage of neutrophils), and immune aging (percentages of naïve CD8+ and CD4+ T cells). Results indicate inflammation is associated with neurodegenerative biomarkers (β = .31, p &amp;lt; .001) and with cognitive dysfunction (β = .08, p &amp;lt; .001) after controlling for age, race, gender, education, BMI, smoking, drinking, and immunosenescence. Neurodegenerative biomarkers mediated about half of the association between inflammation and cognitive dysfunction. It appears that greater systemic inflammation may be associated with brain damage and tauopathy. Interventions focused on reducing systemic inflammation may be successful in reducing neurodegeneration and cognitive dysfunction in older adults.

Systemic inflammation and biological aging in the Health and Retirement Study

Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (N = 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.

Pre-pregnancy obesity is associated with greater systemic inflammation and increased risk of antenatal depression

BackgroundPre-pregnancy obesity is an emerging risk factor for perinatal depression. However, the underlying mechanisms remain unclear. We investigated the association between pre-pregnancy body mass index (BMI) and perinatal depressive symptoms in a large population-based pre-birth cohort, the Barwon Infant Study. We also assessed whether the levels of circulating inflammatory markers during pregnancy mediated this relationship. MethodsDepressive symptoms were assessed in 883 women using the Edinburgh Postnatal Depression Scale (EPDS) and psychological stress using the Perceived Stress Scale (PSS) at 28 weeks gestation and 4 weeks postpartum. Glycoprotein acetyls (GlycA), high-sensitivity C-reactive protein (hsCRP) and cytokines were assessed at 28 weeks gestation. We performed regression analyses, adjusted for potential confounders, and investigated mediation using nested counterfactual models. ResultsThe estimated effect of pre-pregnancy obesity (BMI ≥ 30 kg/m2) on antenatal EPDS scores was 1.05 points per kg/m2 increase in BMI (95% CI: 0.20, 1.90; p = 0.02). GlycA, hsCRP, interleukin (IL) −1ra and IL-6 were higher in women with obesity, compared to healthy weight women, while eotaxin and IL-4 were lower. Higher GlycA was associated with higher EPDS and PSS scores and partially mediated the association between pre-pregnancy obesity and EPDS/PSS scores in unadjusted models, but this association attenuated upon adjustment for socioeconomic adversity. IL-6 and eotaxin were negatively associated with EPDS/PSS scores, however there was no evidence for mediation. ConclusionsPre-pregnancy obesity increases the risk of antenatal depressive symptoms and is also associated with systemic inflammation during pregnancy. While discrete inflammatory markers are associated with antenatal depressive symptoms and perceived stress, their role in mediating the effects of pre-pregnancy obesity on antenatal depression requires further investigation.

Characterizing the mental health of South African women living with comorbid HIV and breast cancer.

e12549 Background: In South Africa’s public hospitals, 20% of new breast cancer (BC) diagnoses are in women living with HIV (WLWH). These women experience 49% higher mortality than BC patients without HIV. Mental health disorders are prevalent in both WLWH and women with BC. Symptoms of depression, anxiety, and acute stress are linked to increased circulating serum inflammatory markers, which may provide a pathophysiologic explanation for poorer outcomes. We aimed to explore whether South African BC patients living with HIV report more mental health symptoms than women with HIV alone, BC alone, or neither and to determine if comorbid HIV and BC is associated with greater systemic inflammation. Methods: We conducted a cross-sectional study of black South African women ≥18 years old. We enrolled four arms: newly diagnosed BC patients with HIV, newly diagnosed BC patients without HIV, WLWH without BC, and women with benign breast diagnoses. Participants were recruited from the breast clinic or HIV clinic at Chris Hani Baragwanath Academic Hospital. Consenting women completed the Center for Epidemiologic Studies Depression Scale (CES-D), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Perceived Stress Scale (PSS). Blood samples were tested for serum concentrations of inflammatory markers (c-reactive protein (CRP) and S100A8/A9), pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), and anti-inflammatory cytokines (IL-4, IL-5, and IL-10) via ELISA assays performed at the University of Miami. Results: The first three arms enrolled 25 women each and the benign arm enrolled 22 women. Participant scores on the CES-D, GAD-7, and PSS were higher than expected in all groups and seemed to be worse in participants with HIV alone. Scores consistent with clinical depression, moderate to severe anxiety, and moderate to severe stress were reported by 68-88%, 28-76%, and 72-94% of participants, respectively. We found trends towards higher concentrations of CRP, TNF-α, IL-6, and IL-8 in participants with co-morbid BC and HIV versus benign breast disease but no pattern of increased inflammatory marker concentrations in participants with dual diagnoses versus either diagnosis alone. Conclusions: Our pilot study did not find evidence of increased mental health symptom burden or systemic inflammation in South African women with comorbid breast cancer and HIV, versus either diagnosis alone. Increased mental health symptoms in women with HIV alone may reflect reduced access to supportive service available at the HIV clinic compared to the breast clinic. [Table: see text]

Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation.

Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions-Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.

First-Generation College Students, Emotional Support, and Systemic Inflammation Following the College Transition

PurposeTo examine whether emotional support moderates the association between college generation status and concurrent and prospective levels of systemic inflammation during the college transition among a sample of older U.S. adolescents. MethodsAt an undergraduate tertiary institution, 41 first-generation college students (first-gens) and 46 continuing-generation college students (continuing-gens) in their first semester of college reported on basic demographic information and perceived emotional support. They also had their blood drawn midway through both the first and second semester to measure C-reactive protein and interleukin-6. An inflammatory composite for each semester was created by averaging the standardized scores for log-transformed C-reactive protein and interleukin-6. ResultsCompared to continuing-gens, first-gens had greater systemic inflammation in the first semester regardless of their level of emotional support (B = 0.515, p = .003). However, emotional support moderated the association between college generation status and prospective systemic inflammation in the second semester (B = −0.525, p = .007) such that first-gens had greater systemic inflammation compared to continuing-gens, but only if they reported lower levels of emotional support (B = 0.826, p = .002). This moderation effect held after further adjusting for systemic inflammation in the first semester (B = −0.374, p = .022). Also discussed are results of secondary analyses examining sources of support. DiscussionCompared to continuing-gens, first-gens had greater systemic inflammation in the first semester irrespective of emotional support, suggesting all first-gens may stand to benefit from college resources provided early in the college transition. Furthermore, first-gens who reported lower levels of emotional support may benefit from additional college resources provided beyond the first semester.

Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.

AimsWe evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants.Methods and resultsWe extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.ConclusionWe demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.

Blood Neutrophil Counts Define Specific Clusters of Bronchiectasis Patients: A Hint to Differential Clinical Phenotypes.

We sought to investigate differential phenotypic characteristics according to neutrophil counts, using a biostatistics approach in a large-cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 1034 patients who met the inclusion criteria were clustered into two groups on the basis of their blood neutrophil levels. Using the Mann–Whitney U test to explore potential differences according to FACED and EFACED scores between the two groups, a neutrophil count of 4990 cells/µL yielded the most balanced cluster sizes: (1) above-threshold (n = 337) and (2) below-threshold (n = 697) groups. Patients above the threshold showed significantly worse lung function parameters and nutritional status, while systemic inflammation levels were higher than in the below-threshold patients. In the latter group, the proportions of patients with mild disease were greater, while a more severe disease was present in the above-threshold patients. According to the blood neutrophil counts using biostatistics analyses, two distinct clinical phenotypes of stable patients with non-CF bronchiectasis were defined. Patients falling into the above-threshold cluster were more severe. Severity was characterized by a significantly impaired lung function parameters and nutritional status, and greater systemic inflammation. Phenotypic profiles of bronchiectasis patients are well defined as a result of the cluster analysis of combined systemic and respiratory variables.

First-generation College Students Have Greater Systemic Inflammation than Continuing-Generation College Students Following the Initial College Transition: A Brief Report.

First-generation college students ("first-gens") are often at a disadvantage socially and academically; whether they are at risk physiologically is unknown despite the well-established link between greater education and better long-term health. To examine whether first-gens have higher levels of cardiovascular disease (CVD) risk markers relative to continuing-generation college students ("continuing-gens"). A panel of CVD risk markers was assessed among 87 emerging adults (41 first-gens) twice over their first year of college. Compared to continuing-gens, first-gens had greater systemic inflammation (composite of averaged z-scores for C-reactive protein and interleukin-6; B = 0.515, SE = 0.171, p = .003) during the fall but not spring semester (p > .05). Associations were independent of family home ownership and childhood adversity, even though first-gens were more likely to live in rental homes and reported riskier home environments. Lower childhood subjective social status (SSS) accounted for greater systemic inflammation among first-gens as evidenced by an indirect effect of college generation status on systemic inflammation through childhood SSS (a1b1 = 0.261, bootstrapped SE = 0.103, 95% boot CI [0.078, 0.482]). There were no differences in metabolic risk and latent virus regulation by college generation status in either semester (p > .10). This is the first study to find that first-gens have higher levels of systemic inflammation than continuing-gens following the college transition and that childhood SSS may be one explanatory pathway. First-gens may benefit from university resources that address social class differences, which should be provided early on so that first-gens can reap the health-relevant benefits of higher education, at least in the short term.

Response to Hypoxia and the Ensuing Dysregulation of Inflammation Impacts Mycobacterium tuberculosis Pathogenicity.

Rationale: Different Mycobacterium tuberculosis (Mtb) strains exhibit variable degrees of virulence in humans and animal models. Differing stress response strategies used by different strains of Mtb could influence virulence. Objectives: We compared the virulence of two strains of Mtb with use in animal model research: CDC1551 and Erdman. Methods: Rhesus macaques, which develop human-like tuberculosis attributes and pathology, were infected with a high dose of either strain via aerosol, and virulence was compared by bacterial burden and pathology. Measurements and Main Results: Infection with Erdman resulted in significantly shorter times to euthanasia and higher bacterial burdens and greater systemic inflammation and lung pathology relative to those infected with CDC1551. Macaques infected with Erdman also exhibited significantly higher early inflammatory myeloid cell influx to the lung, greater macrophage and T cell activity, and higher expression of lung remodeling (extracellular matrix) genes, consistent with greater pathology. Expression of NOTCH4 (neurogenic locus notch homolog 4) signaling, which is induced in response to hypoxia and promotes undifferentiated cellular state, was also higher in Erdman-infected lungs. The granulomas generated by Erdman, and not CDC1551, infection appeared to have larger regions of necrosis, which is strongly associated with hypoxia. To better understand the mechanisms of differential hypoxia induction by these strains, we subjected both to hypoxia invitro. Erdman induced higher concentrations of DosR regulon relative to CDC1551. The DosR regulon is the global regulator of response to hypoxia in Mtb and critical for its persistence in granulomas. Conclusions: Our results show that the response to hypoxia is a critical mediator of virulence determination in Mtb, with potential impacts on bacillary persistence, reactivation, and efficiency of therapeutics.

Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years

BackgroundNeurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years. MethodsPWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor – type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Aβ)-42, soluble amyloid precursor protein-α (sAPPα)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline. ResultsParticipants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/μL (19,205), current CD4 568/μL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPα). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r ​= ​−0.168, p ​= ​0.0205 and r ​= ​−0.156, p ​= ​0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r ​= ​−0.154, p ​= ​0.0332), while IL-6 did not (r ​= ​−0.109, p ​= ​0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r ​= ​−0.1734, p ​= ​0.0006). Together BDI-II (p ​= ​0.0290), F1 (p ​= ​0.0484) and F3 (p ​= ​0.0309) contributed independently to NC decline (p ​= ​0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression. ConclusionsPWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation.

Racial disparities in mortality among patients with prurigo nodularis: A multi-center cohort study

Racial disparities in mortality among patients with prurigo nodularis: A multi-center cohort study

Frailty subtypes and recovery in older survivors of acute respiratory failure: a pilot study

BackgroundIdentifying subtypes of acute respiratory failure survivors may facilitate patient selection for post-intensive care unit (ICU) follow-up clinics and trials.MethodsWe conducted a single-centre prospective cohort study of 185 acute respiratory...

Relationship between body mass index and neuropsychiatric symptoms: Evidence and inflammatory correlates

ObjectiveNeuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI). MethodsThe study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m2), 50 severely obese (BMI: 35–39.99 kg/m2), 21 overweight or moderately obese (BMI: 25–34.9 kg/m2), and 24 lean (BMI < 25 kg/m2). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA. ResultsSeverely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP. ConclusionObesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity.

COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: A post-hoc analysis of a prospective cohort study

Background & aimsCoronavirus disease 2019 (COVID-19) may associate with clinical manifestations, ranging from alterations in smell and taste to severe respiratory distress requiring intensive care, that might associate with weight loss and malnutrition. We aimed to assess the incidence of unintentional weight loss and malnutrition in COVID-19 survivors.MethodsIn this post-hoc analysis of a prospective observational cohort study, we enrolled all adult (age ≥18 years) patients with a confirmed diagnosis of COVID-19 who had been discharged home from either a medical ward or the Emergency Department of San Raffaele University Hospital, and were re-evaluated after remission at the Outpatient COVID-19 Follow-Up Clinic of the same Institution from April 7, 2020, to May 11, 2020. Demographic, anthropometric, clinical and biochemical parameters upon admission were prospectively collected. At follow-up, anthropometrics, the mini nutritional assessment screening and a visual analogue scale for appetite were assessed.ResultsA total of 213 patients were included in the analysis (33% females, median age 59.0 [49.5–67.9] years, 70% overweight/obese upon initial assessment, 73% hospitalised). Sixty-one patients (29% of the total, and 31% of hospitalised patients vs. 21% of patients managed at home, p = 0.14) had lost >5% of initial body weight (median weight loss 6.5 [5.0–9.0] kg, or 8.1 [6.1–10.9]%). Patients who lost weight had greater systemic inflammation (C-reactive protein 62.9 [29.0–129.5] vs.48.7 [16.1–96.3] mg/dL; p = 0.02), impaired renal function (23.7% vs. 8.7% of patients; p = 0.003) and longer disease duration (32 [27–41] vs. 24 [21–30] days; p = 0.047) as compared with those who did not lose weight. At multivariate logistic regression analysis, only disease duration independently predicted weight loss (OR 1.05 [1.01–1.10] p = 0.022).ConclusionsCOVID-19 might negatively impact body weight and nutritional status. In COVID-19 patients, nutritional evaluation, counselling and treatment should be implemented at initial assessment, throughout the course of disease, and after clinical remission.Clinicaltrials.gov registrationNCT04318366.

Cocaine Use and Inflammation Is Associated with Diet Quality in People Living with HIV (PLWH) from the MASH Cohort

Abstract Objectives Cocaine use is one of the most widely used illicit drugs in Miami, FL and especially among PLWH. Cocaine use is associated with greater systemic inflammation and poor dietary intake. Lifestyle factors such as diet may influence inflammation and further exacerbate the effects of substance use and HIV infection on systemic inflammation. This study examined the relationships of cocaine use, inflammation and diet quality in PLWH from the Miami Adult Studies on HIV (MASH) cohort. Methods After obtaining informed consent, data on demographics, socioeconomic status, substance use and parameters of HIV disease progression (CD4 cell count and HIV viral load) were collected from 50 participants enrolled in the MASH cohort in Miami, FL. A total of 4 to 5 24-hour recalls were collected for each participant. Diet quality was assessed using the USDA Healthy Eating Index (HEI)-2015. Interleukin 6 (IL-6) was measured using the Quantikine ELISA kit (R&amp;D Systems, Minneapolis, MN). Statistical analyses used descriptive statistics, Spearman's correlations, Mann-Whitney U and logistic regression. Results The participants’ mean age was 55 ± 6.81, 58% were male, and 68% were African Americans. Overall the diet quality was low with a total median HEI-2015 score of 44.5 (IQR = 38.8–53.8), lower than the general US population score of 59 (P &amp;lt; 0.001) and it was not significantly correlated with IL-6 scores (r = −0.212, P = 139). Cocaine users had significantly lower total median HEI scores [41 (IQR = 35–48) vs.45 (IQR = 41–57.50), P = 0.048] than cocaine non-users. Component HEI scores of whole fruit (r = −0.280, P = 0.049) and saturated fat (r = −0.341, P = 0.015) were correlated with IL-6. Moreover, lower saturated fat intake reduced odds of having IL-6 above the median (OR = 0.710, 95% CI: 0.544–0.928, P = 0.012), after controlling for age, sex, income, education, and cocaine use. Conclusions Diet quality was low for all the participants and significantly lower for those who used cocaine compared to non-users. Higher inflammation was associated with lower fruit and higher saturated fat intakes. Larger studies are needed to elucidate these relationships in order to develop appropriate interventions for PLWH. These results highlight the need for nutritional counseling for PLWH, especially if the condition is associated with cocaine use. Funding Sources NIDA and NIMHD.

Tumor Mutation Burden and Depression in Lung Cancer: Association With Inflammation.

Patients with lung cancer with greater systemic inflammation have higher rates of depression. Tumor mutation burden (TMB) predicts immunotherapy response in patients with lung cancer and is associated with intratumoral inflammation, which may contribute to systemic inflammation and depression. This study evaluated whether higher TMB was associated with increased depression and systemic inflammation in patients with lung cancer. Patients with metastatic lung cancers were evaluated for depression severity using the Hospital Anxiety and Depression Scale. TMB was measured using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Inflammation was evaluated using C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR). A total of 96 patients with adequate TMB testing were evaluated. The average number of mutations (TMB) was 10.8 (SD, 10.9). A total of 19% of patients endorsed clinically significant depression symptoms. TMB was significantly correlated with depression severity (r = 0.34; P=.001) and NLR (r = 0.37; P=.002) but not CRP level (r = 0.19; P=.07). TMB was also higher in patients receiving chemotherapy (mean, 12.0) and immunotherapy (mean, 14.4) versus targeted therapy (mean, 4.8). A multivariate model found that TMB (β = 0.30; P=.01) and CRP level (β = 0.31; P=.01) were independently associated with depression; there was no significant interaction effect of TMB × CRP and depression. A similar multivariate model showed no independent effect for NLR and depression (β = 0.16; P=.17) after accounting for TMB. These data provide evidence for biologic depression risk in patients with lung cancer who have high levels of TMB. The underlying mechanism of the association is not clearly related to inflammation but warrants further analysis to broadly elucidate the mechanism of biologically derived depression in cancer.

Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study

ObjectiveTo characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort. Patients and MethodsThis was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m2) and nonobese (BMI<30 kg/m2) for comparison. ResultsObese patients with HFpEF (n=81) were younger (median age, 64 [interquartile range (IQR), 67-79] years vs 73 [IQR, 56-70] years; P<.001) but had greater peripheral edema (31% [25] vs 9% [6]; P<.001), more orthopnea (76% [56] vs 53% [35]; P=.005), worse New York Heart Association class (P=.006), and more impaired quality of life (P<.001) as compared with nonobese patients with HFpEF (n=70). Despite more severe signs and symptoms, obese patients with HFpEF had lower N-terminal pro B-type natriuretic peptide level (median, 481 [IQR, 176-1183] pg/mL vs 825 [IQR, 380-1679] pg/mL [to convert to pmol/L, multiply by 0.118]; P=.007) and lower left atrial volume index (median, 38 [IQR, 31-47] mL/m2 vs 54 [IQR, 41-63] mL/m2; P<.001). Serum C-reactive protein (median, 5.0 [IQR, 2.4-9.9] mg/dL vs 2.7 [IQR, 1.6-5.4] mg/dL [to convert to mg/L, multiply by 10−3]; P<.001) and uric acid (median, 7.8 [IQR, 6.1-8.7] mg/dL vs 6.8 [IQR, 5.5-8.3] mg/dL; P=.03) levels were higher in obese HFpEF, indicating greater systemic inflammation, than in nonobese HFpEF. Peak oxygen consumption was impaired in obese HFpEF (median, 11.1 [IQR, 9.6-14.4] mL/kg per minute vs 13.1 [IQR, 11.3-14.7] mL/kg per minute; P=.008), as was submaximal exercise capacity (6-minute walk distance, 272 [IQR, 200-332] m vs 355 [IQR, 290-415] m; P<.0001). ConclusionObese HFpEF is associated with decreased quality of life, worse symptoms of heart failure, greater systemic inflammation, worse exercise capacity, and higher metabolic cost of exertion as compared with nonobese HFpEF. Further study is required to understand the pathophysiology and potential distinct treatments for patients with the obese phenotype of HFpEF. Trial Registrationclinicaltrials.gov Identifier: NCT00763867