Exploring the relationship between malnutrition and the systemic immune-inflammation index in older inpatients: a study based on comprehensive geriatric assessment.

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.

The mediating role of dietary inflammatory index on the association between eating breakfast and depression: Based on NHANES 2007-2018.

BACKGROUND: Depression is a significant, pervasive, global public health problem, associated with many factors, such as diet, social factors, and lifestyle habits. We aimed to evaluate the association between eating breakfast, dietary inflammatory index (DII) and depression, and to verify the mediating role of DII on the effect of eating breakfast on depression. METHODS: 21,865 participants from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were included in this study. Binary logistic regression and mediated effect analysis were conducted to analyze the associations between eating breakfast, DII and depression. Dietary inflammation was divided into pro-inflammatory diet and anti-inflammatory diet according to the DII. RESULTS: Both pro-inflammatory diet and skipping breakfast were risk factors for depression. After adjusting for covariables, compared with participants reporting breakfast in both recalls, reporting breakfast in one recall had a higher OR 95%CI (1.54(1.20, 1.98)) of depression. These associations in stratified analysis and sensitivity analysis without cardiovascular diseases (CVD) and diabetes were robust. DII mediated the association between eating breakfast and depression, the proportion of participants who reported breakfast in one recall and no recall was 26.15 % and 26.67 %, respectively. LIMITATIONS: This was a cross-sectional study that couldn't argue for the cause-effect relationship. Moreover, the confounding factor regarding medication use was not accounted for due to limited data. CONCLUSIONS: Skipping breakfast may increase the risk of depression by raising DII. And our study supported the essential role of regular breakfast and the anti-inflammatory diet in reducing the risk of depression.

The potential of intervening on childhood adversity to reduce socioeconomic inequities in body mass index and inflammation among Australian and UK children: A causal mediation analysis.

BACKGROUND: Lower maternal education is associated with higher body mass index (BMI) and higher chronic inflammation in offspring. Childhood adversity potentially mediates these associations. We examined the extent to which addressing childhood adversity could reduce socioeconomic inequities in these outcomes. METHODS: We analysed data from two early-life longitudinal cohorts: the Longitudinal Study of Australian Children (LSAC; n=1873) and the UK Avon Longitudinal Study of Parents and Children (ALSPAC; n=7085). EXPOSURE: low/medium (below university degree) versus high maternal education, as a key indicator of family socioeconomic position (0-1 year). OUTCOMES: BMI and log-transformed glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Mediator: multiple adversities (≥2/<2) indicated by family violence, mental illness, substance abuse and harsh parenting (LSAC: 2-11 years; ALSPAC: 1-12 years). A causal mediation analysis was conducted. RESULTS: Low/medium maternal education was associated with up to 1.03 kg/m2 higher BMI (95% CI: 0.95 to 1.10) and up to 1.69% higher GlycA (95% CI: 1.68 to 1.71) compared with high maternal education, adjusting for confounders. Causal mediation analysis estimated that decreasing the levels of multiple adversities in children with low/medium maternal education to be like their high maternal education peers could reduce BMI inequalities by up to 1.8% and up to 3.3% in GlycA. CONCLUSIONS: Our findings in both cohorts suggest that slight reductions in socioeconomic inequities in children's BMI and inflammation could be achieved by addressing childhood adversities. Public health and social policy efforts should help those affected by childhood adversity, but also consider underlying socioeconomic conditions that drive health inequities.

Characterization of tungiasis infection and morbidity using thermography in Kenya revealed higher disease burden during COVID-19 school closures.

BACKGROUND: Tungiasis is a neglected tropical skin disease caused by the sand flea Tunga penetrans. Female fleas penetrate the skin, particularly at the feet, and cause severe inflammation. This study aimed to characterize disease burden in two highly affected regions in Kenya, to test the use of thermography to detect tungiasis-associated inflammation and to create a new two-level classification of disease severity suitable for mapping, targeting, and monitoring interventions. METHODS: From February 2020 to April 2021, 3532 pupils age 8-14 years were quasi-randomly selected in 35 public primary schools and examined for tungiasis and associated symptoms. Of the infected pupils, 266 were quasi-randomly selected and their households visited, where an additional 1138 family members were examined. Inflammation was assessed using infra-red thermography. A Clinical score was created combining the number of locations on the feet with acute and chronic symptoms and infra-red hotspots. RESULTS: The overall prevalence of tungiasis among all the school pupils who were randomly selected during survey rounds 1 and 3 was 9.3% [95% confidence interval (CI): 8.4-10.3]. Based on mixed effects logistic models, the odds of infection with tungiasis among school pupils was three times higher in Kwale (coastal Kenya) than in Siaya [western Kenya; adjusted odds ratio (aOR) = 0.36, 95% CI: 0.18-0.74]; three times higher in males than in females (aOR = 3.0, 95% CI: 2.32-3.91) and three times lower among pupils sleeping in a house with a concrete floor (aOR = 0.32, 95% CI: 0.24-0.44). The odds of finding an infected person among the household population during surveys before the COVID-19 pandemic was a third (aOR = 0.32, 95% CI: 0.19-0.53) of that when schools were closed due to COVID-19 restrictions and approximately half (aOR = 0.44, 95% CI: 0.29-0.68) in surveys done after school re-opening (round 3). Infection intensity was positively correlated with inflammation as measured by thermography (Spearman's rho = 0.68, P < 0.001) and with the clinical score (rho = 0.86, P < 0.001). Based on the two-level classification, severe cases were associated with a threefold higher level of pain (OR = 2.99, 95% CI: 2.02-4.43) and itching (OR = 3.31, 95% CI: 2.24-4.89) than mild cases. CONCLUSIONS: Thermography was a valuable addition for assessing morbidity and the proposed two-level classification of disease severity clearly separated patients with mild and severe impacts. The burden of tungiasis was considerably higher in households surveyed during COVID-19 restrictions suggesting underlying risks are found in the home environment more than in school.

Socioeconomic determinants of inflammation and neuroendocrine activity: A longitudinal analysis of compositional and contextual effects.

Socioeconomic determinants are well-established modulators of inflammation and neuroendocrine activity. Less clear is whether neighbourhood-contextual or individual-compositional factors are more closely associated with gradients in these biomarkers. Here, we examine how immune and neuroendocrine activity are cross-sectionally and longitudinally nested in meso-level socioeconomic characteristics. Participants, male and female, aged ≥50, were recruited from the English Longitudinal Study of Ageing (ELSA). Neighbourhood (Index of Multiple Deprivation [IMD]) and individual (Wealth/Education/Occupational Social Class [Occupation]) factors were drawn from wave 4 (baseline; 2008). Immune and neuroendocrine biomarkers (indexed by C-reactive protein [CRP; n = 3,968]; fibrinogen [n = 3,932]; white blood cell counts [WBCC; n = 4,022]; insulin-like growth factor-1 [IGF-1; n = 4,056]) were measured at baseline and 4-years later (wave 6; 2012). Covariates at baseline included demographic, clinical, and lifestyle variables. Lower socioeconomic status was associated with heighted inflammation and lower neuroendocrine activity unadjusted both cross-sectionally and longitudinally. With few exceptions, cross-sectional associations remained significant after full adjustment. Prospectively, low IMD remained associated with higher CRP and WBCC; wealth with WBCC; and education and occupation with fibrinogen and WBCC. IMD-biomarker associations were reduced when wealth was simultaneously taken into account. Lifestyle accounted for the greatest variance in associations between socioeconomic indicators and inflammation (≤42.11%), but demographics were more salient to neuroendocrine activity (≤88.46%). Neighbourhood-contextual factors were stronger indicators of aberrant biomarker activity than individual-compositional factors in cross-sectional analyses but were largely explained by wealth differences prospectively. Therefore, immune and neuroendocrine changes depended on the composition of the population living in an area, rather than the area itself.

Propensity score weighted associations between financial strain and subsequent inflammatory biomarkers of aging among a representative sample of U.S. older adults.

BACKGROUND: Despite known socioeconomic disparities in aging-related outcomes, the underlying physiologic mechanisms are understudied. This study applied propensity score weighting to estimate the effect of financial strain on inflammation-related aging biomarkers among a national sample of older adults. METHODS: Financial strain severe enough to lack money for housing, utilities, medical/prescription bills or food was measured among 4,593 community-dwelling National Health and Aging Trends Study participants aged ≥ 65 years in 2016. Inverse probability propensity score weights were generated based on 2015 background characteristics, including age, gender, race/ethnicity, income to poverty ratio, education, occupation, home ownership, retirement, Sect. 8 housing, Medicaid, food/energy assistance, childhood health, marital status, and U.S. region. Sampling weights additionally accounted for study design and non-response. RESULTS: In propensity score-weighted analyses adjusting for age, gender, race/ethnicity, 2017 income to poverty ratio and education, those with 2016 financial strain had 15% higher IL-6 (p = 0.026) and 20% higher CRP levels (p = 0.002) in 2017 than those who were not strained, but did not differ with regard to hemoglobin A1c or CMV. In weighted comparisons, those with financial strain did not differ from those without with regard any 2015 background characteristics. CONCLUSIONS: These results strengthen the etiologic evidence suggesting that financial strain increases inflammatory biomarkers among older adults. Importantly, inflammation is likely a key physiologic pathway contributing to socioeconomic disparities. Therefore, research is needed to address financial strain.

Early-life stress, depressive symptoms, and inflammation: the role of social factors.

OBJECTIVE: To identify modifiable, social factors that moderate the relationship between early-life stress (ELS) and health outcomes as measured by depressive symptoms and inflammation. METHODS: Data were from 3,416 adults (58.28% female), ages 36 - 97 (Mage = 68.41; SDage = 10.24) who participated in the 2006 wave of the Health and Retirement Study, a nationally representative sample of older adults in the United States. This study used hierarchical regression analyses to first test the main effects of ELS on depressive symptoms and inflammation (high-sensitivity C-reactive protein). Four social factors (perceived support, frequency of social contact, network size, and volunteer activity) were assessed as moderators of the ELS-depression and ELS-inflammation relationships. RESULTS: There was a small, positive association between ELS and depressive symptoms (B = 0.17, SE = 0.05, p = .002), which was moderated by social contact and perceived support. Specifically, ELS was only associated with elevated depressive symptoms for participants with limited social contact (B = 0.24, SE = 0.07, p < .001) and low perceived support (B = 0.24, SE = 0.07, p < .001). These associations remained after accounting for potential confounds (age, body-mass index, adulthood stress, and marital status). CONCLUSIONS: Increased social contact and perceived support may be protective for individuals at a higher risk of developing depressive symptoms as a result of ELS. Future interventions may benefit from leveraging these social factors to improve quality of life in adults with ELS.

The epidemiology, pathophysiological mechanisms, and management toward COVID-19 patients with Type 2 diabetes: A systematic review.

This review comprehensively summarizes epidemiologic evidence of COVID-19 in patients with Type 2 diabetes, explores pathophysiological mechanisms, and integrates recommendations and guidelines for patient management. We found that diabetes was a risk factor for diagnosed infection and poor prognosis of COVID-19. Patients with diabetes may be more susceptible to adverse outcomes associated with SARS-CoV-2 infection due to impaired immune function and possible upregulation of enzymes that mediate viral invasion. The chronic inflammation caused by diabetes, coupled with the acute inflammatory reaction caused by SARS-CoV-2, results in a propensity for inflammatory storm. Patients with diabetes should be aware of their increased risk for COVID-19.

Inflammatory pathways amongst people living with HIV in Malawi differ according to socioeconomic status.

BACKGROUND: Non-communicable diseases (NCDs) are increased amongst people living with HIV (PLWH) and are driven by persistent immune activation. The role of socioeconomic status (SES) in immune activation amongst PLWH is unknown, especially in low-income sub-Saharan Africa (SSA), where such impacts may be particularly severe. METHODS: We recruited Malawian adults with CD4<100 cells/ul two weeks after starting ART in the REALITY trial (NCT01825031), as well as volunteers without HIV infection. Clinical assessment, socioeconomic evaluation, blood draw for immune activation markers and carotid femoral pulse wave velocity (cfPWV) were carried out at 2- and 42-weeks post-ART initiation. Socioeconomic risk factors for immune activation and arterial stiffness were assessed using linear regression models. RESULTS: Of 279 PLWH, the median (IQR) age was 36 (31-43) years and 122 (44%) were female. Activated CD8 T-cells increased from 70% amongst those with no education to 88% amongst those with a tertiary education (p = 0.002); and from 71% amongst those earning less than 10 USD/month to 87% amongst those earning between 100-150 USD/month (p = 0.0001). Arterial stiffness was also associated with higher SES (car ownership p = 0.003, television ownership p = 0.012 and electricity access p = 0.029). Conversely, intermediate monocytes were higher amongst those with no education compared to a tertiary education (12.6% versus 7.3%; p = 0.01) and trended towards being higher amongst those earning less than 10 USD/month compared to 100-150 USD/month (10.5% versus 8.0%; p = 0.08). Water kiosk use showed a protective association against T cell activation (p = 0.007), as well as endothelial damage (MIP1ß, sICAM1 and sVCAM1 p = 0.047, 0.026 and 0.031 respectively). CONCLUSIONS: Socioeconomic risk factors for persistent inflammation amongst PLWH in SSA differ depending on the type of inflammatory pathway. Understanding these pathways and their socioeconomic drivers will help identify those at risk and target interventions for NCDs. Future studies assessing drivers of inflammation in HIV should include an SES assessment.

Systemic inflammation as a driver of health disparities among sexually-diverse and gender-diverse individuals.

Sexually-diverse individuals (those who seek sexual or romantic relationships with the same and/or multiple genders) and gender-diverse individuals (those whose gender identity and/or expression differs from their birth-assigned sex/gender) have disproportionately high physical health problems, but the underlying biological causes for these health disparities remain unclear. Building on the minority stress model linking social stigmatization to health outcomes, we argue that systemic inflammation (the body's primary response to both physical and psychological threats, indicated by inflammatory markers such as C-reactive protein and proinflammatory cytokines) is a primary biobehavioral pathway linking sexual and gender stigma to physical health outcomes. Expectations and experiences of social threat (i.e., rejection, shame, and isolation) are widespread and chronic among sexually-diverse and gender-diverse individuals, and social threats are particularly potent drivers of inflammation. We review research suggesting that framing "minority stress" in terms of social safety versus threat, and attending specifically to the inflammatory consequences of these experiences, can advance our understanding of the biobehavioral consequences of sexual and gender stigma and can promote the development of health promoting interventions for this population.

Adiposity and pathogen exposure: An investigation of response to iron supplementation and hypothesized predictors in anemic pre-school-aged children living in a dual burden environment.

OBJECTIVES: Peruvians are experiencing rapid dietary and lifestyle changes, resulting in a phenomenon known as the "dual burden of disease." A common manifestation of the dual burden in individuals is the co-occurrence of overweight and anemia. Despite recent initiatives introduced to address these concerns, rates continue to be public health concerns. This study investigates the relationship between immune activation and lack of response to iron supplementation after 1 month of treatment and explores variation in body fat stores as a potential moderator between immune function and response to treatment. METHODS: Data come from children, aged 2-5 years (n = 50) from a peri-urban community in Lima, Peru. Multivariate logistic regression models were used to explore the associations between response to treatment (Hb > =11.0 g/dl) after 1 month of treatment), markers of immune activation (C-reactive protein [CRP] and reported morbidity symptoms), and measures of body fat (waist-to-height ratio, triceps skinfold thickness, and body mass index [BMI]). RESULTS: We found that high CRP is associated with a lack of response to iron supplementation after 1 month of treatment and that BMI z-score may moderate this association. Generally, larger body size is associated with response to iron supplementation whether or not the children in this sample have high immune activation. However, the probability of anemic children responding to iron supplementation treatment differed across adiposity measures. CONCLUSIONS: Our finding suggesting that adiposity and CRP influence response to iron supplementation, furthers our understanding of the relationship between inflammation and anemia treatment in children and has both theoretical and public health implications.

The CASSIOPEA Study (Economic Crisis and Adherence to the Mediterranean diet: poSSIble impact on biOmarkers of inflammation and metabolic PhEnotypes in the cohort of the Moli-sAni Study): Rationale, design and characteristics of participants.

BACKGROUND AND AIMS: The CASSIOPEA Study was designed to evaluate whether the economic downturn during the late 2000s was a contributing factor to the observed decrease in adherence to Mediterranean diet (MD). METHODS AND RESULTS: The study protocol consists of two steps: A) recall of 7406 men and women who, between 2005 and 2006, had been randomly recruited in the Moli-sani Study from the general population of Molise, to assess possible economic hardship (EH) related to the economic crisis initiated in 2007; B) re-examination, between 2017 and 2020, of available subjects identified in Step 1 as poorly or harder hit by EH to test the hypothesis that EH is associated with a decrease in MD adherence, possibly resulting in increased inflammation. The results of Step 1 are reported here. From the initial sample of individuals re-examined after 12.6 years (median; IQR = 12.1-13.0 y), 3646 were finally analysed. An Economic Hardship Score (EHS; range 0-14) was obtained by scoring three domains: 1) change in employment status; 2) financial hardship and 3) financial hardship for health expenditures. Overall, 37.8% of the sample reported high EHS (≥3), whilst 32% scored 0 (no EH). Those with high EHS were prevalently women and younger, with low socioeconomic status. CONCLUSIONS: High economic hardship was prevalently reported by weaker socioeconomic groups. Longitudinal analysis (step 2) will examine whether the economic crisis had an effect on adherence to Mediterranean diet with consequent potential impact on inflammation, one of the main biological pathways linking MD to health outcomes. CLINICALTRIALS. GOV IDENTIFIER: NCT03119142.

Early origins of socioeconomic inequalities in chronic inflammation: Evaluating the contributions of low birth weight and short breastfeeding.

The United States is characterized by persistent and widening social inequities in a wide range of adult health outcomes. A life course approach challenges us to consider if, and how, these inequities trace back to early life conditions, and chronic inflammation represents a potentially important mechanism through which early environments may have lasting effects on health in adulthood. Low birth weight (LBW) and shorter durations of breastfeeding both predict increased inflammation in adulthood, which is associated with increased risk for cardiovascular disease, metabolic syndrome, and all-cause mortality. Using data from a large representative sample of young adults in the US (National Longitudinal Study of Adolescent to Adult Health (Add Health)), we document the socioeconomic status (SES) gradient in chronic inflammation, as indicated by concentrations of C-reactive protein (CRP). Using a nested set of structural equation models and marginal standardization techniques, we investigate the extent to which this gradient is explained by patterns of LBW and breastfeeding in infancy. Findings reveal a particularly important role for breastfeeding duration: Based on model predictive margins, increasing breastfeeding duration to three or more months corresponds to a flattening of the SES gradient by 80%, and 83% when LBW is eliminated. This study expands current understandings of the consequential role of developmental environments for population health and for addressing health inequities in future generations.

A multi-omics approach to investigate the inflammatory response to life course socioeconomic position.

Aim: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & methods: We analyzed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 European Prospective Investigation into Cancer and Nutrition-Italy participants. Results & conclusion: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis-acting regulatory methylation sites individually and jointly using several scores. Less-advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.

COVID-19 mortality in Lombardy: the vulnerability of the oldest old and the resilience of male centenarians.

Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences.We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females.

Updates on the epidemiology, pathogenesis, diagnosis, and management of postinfectious irritable bowel syndrome.

PURPOSE OF REVIEW: With its impact on quality of life and increasing awareness, postinfectious irritable bowel syndrome (PI-IBS) is now gaining attention as one of the major health problems commonly encountered in gastrointestinal practice. Literature investigating the various pathogenic mechanisms involved is rapidly emerging. The objective of the current review is to provide an update on recent evidence published in the past 2 years describing advances in our understanding of the epidemiology, pathogenesis, diagnosis, and treatment of PI-IBS. RECENT FINDINGS: Significant proportion of research in the recent past was preclinical in nature. Epidemiological studies continue to highlight the risk of IBS after infection, with recent studies documenting postprotozoal effects. Advances in pathogenic mechanisms included clinical studies, which documented micro-RNA down-regulation and Peroxiredoxin-1 up-regulation in colonic mucosa of PI-IBS patients. Protease-activated receptor-2 (PAR-2) activation in PI-IBS mice models resulted in increase in epithelial permeability, mucosal inflammation, visceral hypersensitivity. Moxibustion and rifamycin reduced intestinal inflammation by inhibiting cytokine and chemokine release via different mechanisms. Miltefosine reduced mast cell degranulation and TRPV1 activation, thereby reducing visceral hypersensitivity. SUMMARY: At present, generalization of limited diagnostic and therapeutic strategies across a heterogeneous prevalent patient population impedes the ability to provide effective personalized care in PI-IBS. Further development in pathogenesis discovery, diagnostic tool development are needed in order to design well tolerated and effective therapies that guide treatments based on distinct pathways of disease.

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management.

The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.

Criminal Justice Contacts and Psychophysiological Functioning in Early Adulthood: Health Inequality in the Carceral State.

Despite increased attention to the links between the criminal justice system and health, how criminal justice contacts shape health and contribute to racial health disparities remains to be better understood. Using data from the National Longitudinal Study of Adolescent to Adult Health (N = 5,488) and several analytic techniques-including a quasi-treatment-control design, treatment-weighting procedures, and mediation analyses-this study examines how criminal justice contacts shape inflammatory and depressive risk and contribute to black-white health gaps. Findings revealed that incarceration is associated with increased C-reactive protein and depressive risk, particularly for individuals who experienced long durations of incarceration. Arrests are also associated with mental health, and mediation analyses showed that racial disparities in arrests and incarceration were drivers of black-white gaps in depressive symptoms. Together, this study provides new evidence of the role of the criminal justice system in shaping health and patterning black-white health gaps from adolescence through early adulthood.

How do early socioeconomic circumstances impact inflammatory trajectories? Findings from Generation XXI.

BACKGROUND: The association between socioeconomic position and markers of inflammation in adults, including C-reactive protein (CRP), is well-established. We hypothesized that children from families of less-advantaged socioeconomic circumstances may be at higher inflammatory risk during childhood and, consequently, throughout their life course. Thus, we aimed to investigate whether early socioeconomic circumstances impact CRP trajectories using repeated measures of data from a population-based birth cohort. METHODS: Data from 2510 participants of Generation XXI, a prospective Portuguese population-based birth cohort, were included in this study. Early socioeconomic circumstances comprised maternal education and occupation, paternal education and occupation, and household income at the child's birth. Venous blood samples were collected from the children at ages four, seven, and ten years, and high-sensitivity CRP (Hs-CRP) was quantified. Hs-CRP trajectories were computed using a linear mixed-model approach. RESULTS: Participants from less-advantaged socioeconomic circumstances presented higher levels of Hs-CRP by age of ten years. The higher the mother´s education and disposable household income, the lower the minimum value of the log Hs-CRP observed throughout childhood. Further, the age at which that minimum log Hs-CRP value was reached occurs later, meaning that children born in more-advantaged socioeconomic circumstances had lower levels of log Hs-CRP compared with children from less-advantaged families. CONCLUSIONS: Poor socioeconomic circumstances early in life are associated with increased inflammation levels throughout the first decade of life. This study demonstrates that social inequalities may impact population health beginning at very early ages.

Childhood socioeconomic status, comorbidity of chronic kidney disease risk factors, and kidney function among adults in the midlife in the United States (MIDUS) study.

BACKGROUND: There is a lack of empirical effort that systematically investigates the clustering of comorbidity among known risk factors (obesity, hypertension, diabetes, hypercholesterolemia, and elevated inflammation) of chronic kidney disease (CKD) and how different types of comorbidity may link differently to kidney function among healthy adult samples. This study modeled the clustering of comorbidity among risk factors, examined the association between the clustering of risk factors and kidney function, and tested whether the clustering of risk factors was associated with childhood SES. METHODS: The data were from 2118 participants (ages 25-84) in the Midlife in the United States (MIDUS) Study. Risk factors included obesity, elevated blood pressure (BP), high total cholesterol levels, poor glucose control, and increased inflammatory activity. Glomerular filtration rate (eGFR) was estimated from serum creatinine, calculated with the CKD-EPI formula. The clustering of comorbidity among risk factors and its association with kidney function and childhood SES were examined using latent class analysis (LCA). RESULTS: A five-class model was optimal: (1) Low Risk (class size = 36.40%; low probability of all risk factors), (2) Obese (16.42%; high probability of large BMI and abdominally obese), (3) Obese and Elevated BP (13.37%; high probability of being obese and having elevated BP), (4) Non-Obese but Elevated BP (14.95%; high probability of having elevated BP, hypercholesterolemia, and elevated inflammation), and (5) High Risk (18.86%; high probability for all risk factors). Obesity was associated with kidney hyperfiltration, while comorbidity between obesity and hypertension was linked to compromised kidney filtration. As expected, the High Risk class showed the highest probability of having eGFR < 60 ml/min/1.73 m2 (P = .12; 95%CI = .09-.17). Finally, higher childhood SES was associated with reduced probability of being in the High Risk rather than Low Risk class (ß = - 0.20, SE = 0.07, OR [95%CI] = 0.82 [0.71-0.95]). CONCLUSION: These results highlight the importance of considering the impact of childhood SES on risk factors known to be associated with CKD.