Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the ...largest population of brainstem vagal preganglionic neurons residing in the brainstem's dorsal vagal motor nucleus dramatically impairs exercise capacity, while optogenetic recruitment of the same neuronal population enhances cardiac contractility and prolongs exercise endurance. These data provide direct experimental evidence that parasympathetic vagal drive generated by a defined CNS circuit determines the ability to exercise. Decreased activity and/or gradual loss of the identified neuronal cell group provides a neurophysiological basis for the progressive decline of exercise capacity with aging and in diverse disease states.
Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent ...infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection.
We conducted a prospective observational study of adult patients undergoing major elective gastrointestinal, gynecological, or maxillofacial surgery requiring planned admission to the post-anesthetic care unit. Patients were followed up to hospital discharge or death. Outcome data collected included mortality, length of stay, unplanned intensive care unit admission, and post-operative infections (using the standardized endpoints in perioperative medicine-core outcome measures for perioperative and anesthetic care criteria). Peripheral blood mononuclear cells were isolated prior to and 24 h following surgery from which cellular immune traits including activation and functional status were assessed by multi-parameter flow cytometry and serum immune analytes compared by enzyme-linked immunosorbent assay (ELISA).
Forty-eight patients were recruited, 26 (54%) of whom developed a post-operative infection. We observed reduced baseline pre- and post-operative monocyte CXCR4 and CD80 expression (chemokine receptors and co-stimulation markers, respectively) in patients who subsequently developed an infection as well as a profound and selective post-operative increase in CD4
lymphocyte IL-7 receptor expression in the infection group only. Higher post-operative monocyte count was significantly associated with the development of post-operative infection (false discovery rate < 1%; adjusted p-value = 0.001) with an area under the receiver operating characteristic curve of 0.84 (p < 0.0001).
Lower monocyte chemotaxis markers, higher post-operative circulating monocyte counts, and reduced co-stimulatory signals are associated with subsequent post-operative infections. Identifying the underlying mechanisms and therapeutics to reverse defects in immune cell function requires further exploration.
Morbidity after major surgery is associated with low oxygen delivery. Haemodynamic therapy aimed at increasing oxygen delivery in an effort to reduce oxygen debt, tissue injury, and morbidity, is ...controversial. The most appropriate target for this strategy is unclear and might have several off-target effects, including loss of neural (parasympathetic)-mediated cellular protection. We hypothesised that individualised oxygen delivery targeted haemodynamic therapy (goal-directed therapy) in high-risk surgical patients would reduce postoperative morbidity, while secondarily addressing whether goal-directed therapy affected parasympathetic function.
In this multicentre, randomised, double-blind, controlled trial, adult patients undergoing major elective surgery were allocated by computer-generated randomisation to a postoperative protocol (fluid, with and without dobutamine) targeted to achieve their individual preoperative oxygen delivery value (goal-directed therapy) or standardised care (control). Patients and staff were masked to the intervention. The primary outcome was absolute risk reduction (ARR) in morbidity (defined by Clavien-Dindo grade II or more) on postoperative day 2. We also assessed a secondary outcome focused on parasympathetic function, using time-domain heart rate variability measures. Analyses were done on an intention-to-treat basis. The trial was registered with Controlled Clinical Trials (number ISRCTN76894700).
We enrolled 204 patients between May 20, 2010, and Feb 12, 2014. Intention-to-treat analysis of the 187 (92%) patients who completed the trial intervention period showed that early morbidity was similar between goal-directed therapy (44 46% of 95 patients) and control groups (49 53% of 92 patients) (ARR -7%, 95% CI -22 to 7; p=0·30). Prespecified secondary analysis showed that 123 (66%) of 187 patients achieved preoperative oxygen delivery (irrespective of intervention). These patients sustained less morbidity (ARR 19%, 95% CI 3-34; p=0·016), including less infectious complications. Goal-directed therapy reduced parasympathetic activity postoperatively (relative risk 1·33, 95% CI 1·01-1·74).
Achievement of preoperative oxygen delivery values in the postoperative phase was associated with less morbidity, but this was not affected by the use of an oxygen delivery targeted strategy. Reduced parasympathetic activity after goal-directed therapy was associated with the failure of this intervention to reduce postoperative morbidity.
Academy of Medical Sciences and Health Foundation Clinician Scientist Award.
We present bespoke energy efficiency optimizations in high performance computing (HPC) environments using holistic approach to data collection, analysis and proactive management of resources and ...workloads. Our solution has three major components: (i) platform for collecting, storing and processing data from multiple sources across hardware and software stacks, (ii) collections of regression machine learning (ML) algorithms for making workloads classifications and energy usage predictions, (iii) agent‐based decision‐making framework for delivering control decisions to middle‐ware and infrastructure thus supporting real time or near real energy efficiency optimizations. We will provide some concrete examples of using our proposed approach in HPC environment.
Lower fitness is a predictor of adverse outcomes after radical cystectomy. Lockdown measures during the COVID-19 pandemic affected daily physical activity. We hypothesised that lockdown during the ...pandemic was associated with a reduction in preoperative aerobic fitness and an increase in postoperative complications in patients undergoing radical cystectomy.
We reviewed routine preoperative cardiopulmonary exercise testing (CPET) data collected prior to the pandemic (September 2018 to March 2020) and after lockdown (March 2020 to July 2021) in patients undergoing radical cystectomy. Differences in CPET variables, Postoperative Morbidity Survey (POMS) data, and length of hospital stay were compared.
We identified 267 patients (85 pre-lockdown and 83 during lockdown) who underwent CPET and radical cystectomy. Patients undergoing radical cystectomy throughout lockdown had lower ventilatory anaerobic threshold (9.0 7.9–10.9 vs 10.3 9.1–12.3 ml kg−1 min−1; P=0.0002), peak oxygen uptake (15.5 12.9–19.1 vs 17.5 14.4–21.0 ml kg−1 min−1; P=0.015), and higher ventilatory equivalents for carbon dioxide (34.7 31.4–38.5 vs 33.4 30.5–36.5; P=0.030) compared with pre-lockdown. Changes were more pronounced in males and those aged >65 yr. Patients undergoing radical cystectomy throughout lockdown had a higher proportion of day 5 POMS-defined morbidity (89% vs 75%, odds ratio OR 2.698, 95% confidence interval CI 1.143–6.653; P=0.019), specifically related to pulmonary complications (30% vs 13%, OR 2.900, 95% CI 1.368–6.194; P=0.007) and pain (27% vs 9%, OR 3.471, 95% CI 1.427–7.960; P=0.004), compared with pre-lockdown on univariate analysis.
Lockdown measures in response to the COVID-19 pandemic were associated with a reduction in fitness and an increase in postoperative morbidity among patients undergoing radical cystectomy.
Enhanced recovery after surgery (ERAS) pathways aim to standardize and integrate perioperative care, incorporating the best available evidence-based practice throughout the perioperative period ...targeted at attenuating the surgical stress response while optimizing physiologic function, with the goal of facilitating recovery. Radical cystectomy is associated with significant postoperative morbidity, but comprehensive ERAS pathways have not been well studied in this population.
This is a before and after cohort study of an ERAS pathway for radical cystectomy at a large academic medical center. Following introduction of the ERAS pathway and a wash in period, we prospectively collected data from the next 100 consecutive subjects undergoing radical cystectomy with the ERAS pathway. This cohort was compared to a retrospective cohort of 100 consecutive patients undergoing radical cystectomy with traditional care. The primary outcome was hospital length of stay. Secondary outcomes included perioperative management, time to recovery milestones, complications, and costs.
Implementation of an ERAS pathway for radical cystectomy was associated with reduced hospital length of stay (median LOS 10 days (IQR = 8-18) vs 7 days (IQR = 6-11);
< 0.0001), reduced time to key recovery milestones, including days to first stool (5.83 vs 3.99;
< 0.001) and days to first solid food (9.68 vs 3.2;
< 0.001), reductions in some complications, and a 26.6% reduction in overall costs (
< 0.001).
Our data support the use of an ERAS pathway for radical cystectomy and add to the increasing body of literature supporting enhanced recovery over a wide variety of procedures.
Not applicable.
Opioid use has come under increasing scrutiny, driven in part by the opioid crisis and growing concerns that up to 6% of opioid-naïve patients may become chronic opioid users. This has resulted in a ...revaluation of perioperative practice. For this reason, we implemented a multidisciplinary pathway to reduce perioperative opioid usage through education and standardization of practice.
A single-centre retrospective evaluation was performed after 1 year, comparing the outcomes to those of the 2 years prior to pathway implementation. Comparisons were made between pre- vs. post pathway change by 2:1 propensity matching between cohorts. Univariate linear regression models were created using demographic variables with those that were p < 0.15 included in the final model and using post-operative opioid use (in oral morphine equivalents, OME) as the primary outcome.
We found that intraoperative opioid use was significantly decreased 38.2 mg (28.3) vs. 18.0 mg (40.4) oral morphine equivalents (OME), p < .001, as was post-operative opioid use for the duration of the hospitalization, 46.3 mg (49.5) vs. 35.49 mg (43.7) OME, p = 0.002. In subgroup analysis of those that received some intraoperative opioids (n = 152) and those that received no opioids (n = 34), we found that both groups required fewer opioids in the post-operative period 47.0 mg (47.7) vs. 32.4 mg (40.6) OME, p = 0.001, + intraoperative opioids, 62.4 mg (62.9) vs. 35.8 mg (27.7) OME, p = 0.13, - intraoperative opioids. Time to discharge from the PACU was reduced in both groups 215 min (199) vs. 167 min (122), p < 0.003, + intraoperative opioids and 253 min (270) vs. 167 min (105), p = 0.028, - intraoperative opioids. The duration of time until meeting discharge criteria from PACU was 221 min (205) vs. 170 min (120), p = 0.001. Hospital length of stay (LOS) was significantly reduced 1.4 days (1.3) vs. 1.2 days (0.8), p = 0.005. Both sub-groups demonstrated reduced hospital LOS 1.5 days (1.4) vs. 1.2 days (0.8), p = 0.0047, + intraoperative opioids and 1.7 days (1.6) vs. 1.3 days (0.9), p = 0.0583, - intraoperative opioids. Average pain scores during PACU admission and post-PACU until discharge were not statistically different between cohorts.
These findings underscore the effectiveness of a multidisciplinary approach to reduce opioids. Furthermore, it demonstrates improved patient outcomes as measured by both shorter PACU and almost 50% reduction in perioperative opioid use whilst maintaining similar analgesia as indicated by patient-reported pain scores.
Ehrlichiosis is a tick-borne disease that ranges in severity from asymptomatic infection to fatal sepsis. Ehrlichiosis acquired from transfusion of blood products has not been documented in the ...literature to date. A case of Ehrlichia ewingii infection likely transmitted by transfusion of leukoreduced platelets is described, and public health implications are discussed.
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