The Barker hypothesis

The Barker hypothesis proposed that adverse nutrition in early life, including prenatally as measured by birth weight, increased susceptibility to the metabolic syndrome which includes obesity, diabetes, insulin insensitivity, hypertension, and hyperlipidemia and complications that include coronary heart disease and stroke. Periods of rapid postnatal growth associated with high-energy intake seem to be risk factors, along with a high-energy western diet. Theories proposing the mechanism of this association include the thrifty gene, bet-hedging, fetal predictive adaptive response, and drifty phenotype hypotheses. The cause of metabolic syndrome is likely to be multifactorial, with many nuclear DNA and cellular RNA sequences acting in concert with environmental influences. Epidemiological data in humans and experimental data indicate that transgenerational epigenetic inheritance is a possible mechanism where a history of starvation or deprivation during early life is seen in a grandparent and transgenerational effects are seen in their grandchildren. It remains to be seen whether this is mediated by heritable RNA sequences, or by acquired, possibly mosaic mutations in DNA coding for example for regulatory RNAs. Recent research has raised the possibility that the nature and quantity of gastrointestinal microorganisms (microbiota) can be modified by diet and conversely can modify an animal's metabolic program. As the microbiota is inherited largely from the mother, modification of her nutrition, health before and during pregnancy, and mode of delivery could influence the child's microbiota, introducing further potential avenues to improve the prevention, reduction of complications, and treatment of malnutrition and metabolic syndrome

Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis. Setting Prospective, international, multicentre, observational cohort study. Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative). Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality. Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787). Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups. Trial registration number NCT0432364