Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple’s (RAW) study

Background Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. Method Data were extracted from the Recurrence After Whipple’s (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012–2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien–Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. Results Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). Conclusion In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Wheat Grain and Forage Yields are Affected by Planting and Harvest Dates in the Central Great Plains

Although grazing of winter wheat (Triticum aestivum L.) is a common practice in the southern Great Plains, little is known about the efficacy of wheat as a dual-purpose crop in the Nebraska Panhandle. The objective of this study was to evaluate the effects of establishment and harvest times on forage and grain production of wheat cultivars adapted to the region. Six cultivars were planted at four dates (very early, recommended early, recommended late, and very late) in each of 3 yr. Forage samples were taken from a previously non-harvested area late in the fall, at jointing, and at the boot stage. Grain yield at maturity was measured from each forage harvest treatment and from a full-season unharvested control. In 2 of 3 yr, grain yield was reduced an average of 25% compared with the full-season check when plants were harvested for forage at the joint stage. No grain was produced when forage was removed at the boot stage. Forage removal during the fall averaged 1300 kg ha-1 dry matter and resulted in insignificant losses in grain yield. While most of the fall growth was too low to the ground for clipping, it could provide high- value supplemental grazing on account of the high crude protein (310 g kg-1) and in vitro organic matter digestibility (800 g kg-1) levels. Spring grazing in this region is limited to the time prior to jointing if market conditions favor grain production

Moderate continuous- and high-intensity interval training elicit comparable cardiovascular effect among middle-aged men regardless of recovery mode

To assess the effect of active and passive intra-interval recovery modes in time-efficient high-intensity interval training (HIT) on cardiorespiratory fitness, autonomic function, and endothelial function in sedentary middle-aged men. Participants (n = 62; age: 49.5 ± 5.8 y; BMI: 29.7 ± 3.7 kg·m−2) completed the assessments of cardiorespiratory fitness, flow-mediated dilation (FMD) and heart rate variability before being randomly allocated to control (CON; n = 14), moderate intensity continuous training (MICT; n = 15), HIT with passive (P-HIT; n-15), or active recovery (A-HIT; n = 15). Participants performed thrice weekly exercise sessions for 12 weeks. MICT completed 50–60 min of continuous cycling at 60–70% heart rate (HR) maximum. HIT completed 30-s work intervals (∼85% HR) interspaced with 2.5 min of active or passive recovery. All exercise modalities increased oxygen uptake (V̇O2) (MD: ≥ 3.1 ml·kg−1·min−1, 95%CI: 1.5–4.7 ml·kg−1·min−1; P < 0.001), power output (MD: ≥ 26 W, 95%CI: 15–37 W; P < 0.001) and cycle duration (MD: ≥ 62 s, 95%CI: 36–88 s; P < 0.001) at 85% HRM. Significant pre-to-post differences were observed among all exercise groups for FMD (MD: ≥ 3.4%, 95%CI: 0.3–6.5%; P < 0.05), while MICT and P-HIT significantly increased the standard deviation of all NN intervals (SDNN) pre-to-post intervention (MD: ≥ 7 ms, 2–13 ms; P ≤ 0.05). Time-efficient HIT elicits significant improvements in cardiorespiratory fitness, FMD and autonomic modulation following a thrice weekly 12-week exercise intervention among sedentary middle-aged men. Active recovery between successive high-intensity intervals provided no additional benefit among this deconditioned cohort.</p

Role of D

Chemotaxis enables bacteria to move towards an optimal environment in response to chemical signals. In the case of plant-pathogenic bacteria, chemotaxis allows pathogens to explore the plant surface for potential entry sites with the ultimate aim to prosper inside plant tissues and to cause disease. Chemoreceptors, which constitute the sensory core of the chemotaxis system, are usually transmembrane proteins which change their conformation when sensing chemicals in the periplasm and transduce the signal through a kinase pathway to the flagellar motor. In the particular case of the soft-rot pathogen Dickeya dadantii 3937, jasmonic acid released in a plant wound has been found to be a strong chemoattractant which drives pathogen entry into the plant apoplast. In order to identify candidate chemoreceptors sensing wound-derived plant compounds, we carried out a bioinformatics search of candidate chemoreceptors in the genome of Dickeya dadantii 3937. The study of the chemotactic response to several compounds and the analysis of the entry process to Arabidopsis leaves of 10 selected mutants in chemoreceptors allowed us to determine the implications of at least two of them (ABF-0020167 and ABF-0046680) in the chemotaxis-driven entry process through plant wounds. Our data suggest that ABF-0020167 and ABF-0046680 may be candidate receptors of jasmonic acid and xylose, respectively.Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaUniversidad Complutense de MadridTRUEpu