Hydrogenated fat diet intake during pregnancy and lactation modifies the PAI-1 gene expression in white adipose tissue of offspring in adult life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor

LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography

Abstract\ud \ud Background\ud Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients.\ud \ud \ud Methods\ud 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis.\ud \ud \ud Results\ud The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95% CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95% CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes.\ud \ud \ud Conclusions\ud We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association.PCJL Santos is recipient of fellowship from FAPESP, Proc. 2013-09295-3, and\ud Proc. 2013-20614-3, Brazil. We also thank the patients who participated in the\ud study. The technical assistance of the Laboratory of Genetics and Molecular\ud Cardiology group is gratefully acknowledged

Effect of combined β-Lactam/Macrolide therapy on mortality according to the microbial etiology and inflammatory status of patients with community-acquired pneumonia

Antibiotic combinations that include macrolides have shown lower mortality rates than β-lactams in monotherapy or combined with fluoroquinolones in patients with community-acquired pneumonia (CAP). However, this effect has not been studied according to the levels of C-reactive protein in CAP with identified microbial cause. In patients with CAP and known microbial cause we aimed to evaluate 30-day mortality of a β-lactam plus macrolide (BL + M) compared with a fluoroquinolone alone or with a β-lactam (FQ ± BL). METHODS: We analyzed a prospective observational cohort of patients with CAP admitted to the Hospital Clinic of Barcelona between 1996 and 2016. We included only patients with known microbial cause. RESULTS: Of 1,715 patients (29%) with known etiology, a total of 932 patients (54%) received BL + M. Despite lower crude mortality in the BL + M group in the overall population (BL + M, 5% vs FQ ± BL, 8%; P = .015), after adjustment by a propensity score and baseline characteristics, the combination of BL + M had a protective effect on mortality only in patients with high inflammatory response (C-reactive protein, > 15 mg/dL) and pneumococcal CAP (adjusted OR, 0.28; 95% CI, 0.09-0.93). No benefits on mortality were observed for the population without high inflammatory response and pneumococcal CAP or with other etiologies. CONCLUSIONS: The combination of a β-lactam with a macrolide was associated with decreased mortality in patients with pneumococcal CAP and in patients with high systemic inflammatory response. When both factors occurred together, BL + M was protective for mortality in the multivariate analysis

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background: Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings: Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10−7) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10−5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10−4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions: Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summar

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research