Post-sepsis syndrome - an evolving entity that afflicts survivors of sepsis.

BACKGROUND: The sequelae of sepsis were once thought to be independent of sepsis itself and assumed to be either comorbid to sick patients or complications of critical illness. Recent studies have reported consistent patterns of functional disabilities in sepsis survivors that can last from months to years after symptoms of active sepsis had resolved. BODY: Post-sepsis syndrome is an emerging pathological entity that has garnered significant interest amongst clinicians and researchers over the last two decades. It is marked by a significantly increased risk of death and a poor health-related quality of life associated with a constellation of long-term effects that persist following the patient's bout with sepsis. These include neurocognitive impairment, functional disability, psychological deficits, and worsening medical conditions. CONCLUSION: This "post-sepsis syndrome" has been the subject of active preclinical and clinical research providing new mechanistic insights and approaches linked to survivor well-being. Here we review important aspects of these research efforts and goals of care for patients who survive sepsis.

Reuniting overnutrition and undernutrition, macronutrients, and micronutrients.

Over-nutrition and its late consequences are a dominant theme in medicine today. In addition to the health hazards brought on by over-nutrition, the medical community has recently accumulated a roster of health benefits with obesity, grouped under "obesity paradox." Throughout the world and throughout history until the 20th century, under-nutrition was a dominant evolutionary force. Under-nutrition brings with it a mix of benefits and detriments that are opposite to and continuous with those of over-nutrition. This continuum yields J-shaped or U-shaped curves relating body mass index to mortality. The overweight have an elevated risk of dying in middle age of degenerative diseases while the underweight are at increased risk of premature death from infectious conditions. Micronutrient deficiencies, major concerns of nutritional science in the 20th century, are being neglected. This "hidden hunger" is now surprisingly prevalent in all weight groups, even among the overweight. Because micronutrient replacement is safe, inexpensive, and predictably effective, it is now an exceptionally attractive target for therapy across the spectrum of weight and age. Nutrition-related conditions worthy of special attention from caregivers include excess vitamin A, excess vitamin D, and deficiency of magnesium.

Fasting Serum IGFBP-1 as a Marker of Insulin Resistance in Diverse School Age Groups.

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures. Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected. Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels. Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified.

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

Ghrelin as an Anti-Sepsis Peptide: Review.

Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.

Effects of parental origins and length of residency on adiposity measures and nutrition in urban middle school students: a cross-sectional study.

BACKGROUND: The prevalence of obesity in U.S. has been rising at an alarming rate, particularly among Hispanic, African, and Asian minority groups. This trend is due in part to excessive calorie consumption and sedentary lifestyle. We sought to investigate whether parental origins influence eating behaviors in healthy urban middle school students. METHODS: A multiethnic/racial population of students (N = 182) enrolled in the ROAD (Reduce Obesity and Diabetes) Study, a school-based trial to assess clinical, behavioral, and biochemical risk factors for adiposity and its co-morbidities completed questionnaires regarding parental origins, length of US residency, and food behaviors and preferences. The primary behavioral questionnaire outcome variables were nutrition knowledge, attitude, intention and behavior, which were then related to anthropometric measures of waist circumference, BMI z-scores, and percent body fat. Two-way analysis of variance was used to evaluate the joint effects of number of parents born in the U.S. and ethnicity on food preference and knowledge score. The Tukey-Kramer method was used to compute pairwise comparisons to determine where differences lie. Analysis of covariance (ANCOVA) was used to analyze the joint effects of number of parents born in the US and student ethnicity, along with the interaction term, on each adiposity measure outcome. Pearson correlation coefficients were used to examine the relationships between maternal and paternal length of residency in the US with measures of adiposity, food preference and food knowledge. RESULTS: African Americans had significantly higher BMI, waist circumference and body fat percentage compared to other racial and ethnic groups. Neither ethnicity/race nor parental origins had an impact on nutrition behavior. Mothers' length of US residency positively correlated with students' nutrition knowledge, but not food attitude, intention or behavior. CONCLUSIONS: Adiposity measures in children differ according to ethnicity and race. In contrast, food behaviors in this middle school sample were not influenced by parental origins. Longer maternal US residency benefited offspring in terms of nutrition knowledge only. We suggest that interventions to prevent obesity begin in early childhood.

Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children.

OBJECTIVE: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults. DESIGN AND METHODS: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other). RESULTS: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance. CONCLUSIONS: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.

The obesity pandemic: where have we been and where are we going?

Obesity, a new pandemic, is associated with an increased risk of death, morbidity, and accelerated aging. The multiple therapeutic modalities used to promote weight loss are outlined with caution, especially for patients who are very young or old. Except for very rare single gene defects, the inheritance of obesity is complex and still poorly understood, despite active investigations. Recent advances that have shed light on the pathophysiology of obesity are the recognition that 1) excess fat is deposited in liver, muscle, and pancreatic islets; 2) fat tissue secretes a large number of active signaling molecules including leptin, adiponectin, and resistin, as well as free fatty acids; and 3) activated macrophages colonize the adipose tissue. Other candidates for key roles in the causes and consequences of obesity include 1) metabolic programming, where food acts as a developmental regulator; 2) the constellation of defects known as the "metabolic syndrome;" 3) cortisol overproduction in the adipose tissue; and especially, 4) insulin resistance. The possible etiologies of insulin resistance include cytokine excess, elevated free fatty acids, and hyperinsulinemia itself, as with transgenic overproduction of insulin in mice.