•Experimental models show autonomic regulation of systemic inflammation.•Autonomic measures, independent of heart rate variability, are required in humans.•Slower heart rate recovery after exercise ...quantifies vagal dysfunction.•Delayed heart rate recovery is associated with chronic inflammatory markers.
Experimental animal models demonstrate that autonomic activity regulates systemic inflammation. By contrast, human studies are limited in number and exclusively use heart rate variability (HRV) as an index of cardiac autonomic regulation. HRV measures are primarily dependent on, and need to be corrected for, heart rate. Thus, independent autonomic measures are required to confirm HRV-based findings. Here, the authors sought to replicate the findings of preceding HRV-based studies by using HRV-independent, exercise-evoked sympathetic and parasympathetic measures of cardiac autonomic regulation to examine the relationship between autonomic function and systemic inflammation.
Sympathetic function was assessed by measuring heart rate changes during unloaded pedaling prior to onset of exercise, divided into quartiles; an anticipatory heart rate (AHRR) rise during this period is evoked by mental stress in many individuals. Parasympathetic function was assessed by heart rate recovery (HRR) 60s after finishing cardiopulmonary exercise testing, divided into quartiles. Parasympathetic dysfunction was defined by delayed heart rate recovery (HRR) ≤12.beats.min−1, a threshold value associated with higher cardiovascular morbidity/mortality in the general population. Systemic inflammation was primarily assessed by neutrophil-lymphocyte ratio (NLR), where a ratio >4 is prognostic across several inflammatory diseases and correlates strongly with elevated plasma levels of pro-inflammatory cytokines. High-sensitivity C-reactive protein (hsCRP) was also measured.
In 1624 subjects (65±14y; 67.9% male), lower HRR (impaired vagal activity) was associated with progressively higher NLR (p=0.004 for trend across quartiles). Delayed HRR, recorded in 646/1624 (39.6%) subjects, was associated with neutrophil-lymphocyte ratio >4 (relative risk: 1.43 (95%CI: 1.18–1.74); P=0.0003). Similar results were found for hsCRP (p=0.045). By contrast, AHRR was not associated with NLR (relative risk: 1.24 (95%CI: 0.94–1.65); P=0.14).
Delayed HRR, a robust measure of parasympathetic dysfunction, is independently associated with leukocyte ratios indicative of systemic inflammation. These results further support a role for parasympathetic modulation of systemic inflammation in humans.
Systemic arterial pulse pressure (systolic minus diastolic pressure) ≤53 mm Hg in patients with cardiac failure is correlated with reduced stroke volume and is independently associated with ...accelerated morbidity and mortality. Given that deconditioned surgical and heart failure patients share similar cardiopulmonary physiology, we examined whether lower pulse pressure is associated with excess morbidity after major surgery.
This was a prospective observational cohort study of patients deemed by their preoperative assessors to be at higher risk of postoperative morbidity. Preoperative pulse pressure was calculated before cardiopulmonary exercise testing. The primary outcome was any morbidity (PostOperative Morbidity Survey) occurring within 5 days of surgery, stratified by pulse pressure threshold ≤53 mm Hg. The relationship between pulse pressure, postoperative morbidity, and oxygen pulse (a robust surrogate for left ventricular stroke volume) was examined using logistic regression analysis (accounting for age, sex, BMI, cardiometabolic co-morbidity, and operation type).
The primary outcome occurred in 578/660 (87.6%) patients, but postoperative morbidity was more common in 243/ 660 patients with preoperative pulse pressure ≤53 mm Hg{odds ratio (OR): 2.24 95% confidence interval (CI): 1.29–3.38; P<0.001). Pulse pressure ≤53 mm Hg OR:1.23 (95% CI: 1.03–1.46); P=0.02 and type of surgery were independently associated with all-cause postoperative morbidity (multivariate analysis). Oxygen pulse <90% of population-predicted normal values was associated with pulse pressure ≤ 53 mm Hg OR: 1.93 (95% CI: 1.32–2.84); P=0.007.
In deconditioned surgical patients, lower preoperative systemic arterial pulse pressure is associated with excess morbidity. These data are strikingly similar to meta-analyses identifying low pulse pressure as an independent risk factor for adverse outcomes in cardiac failure. Low preoperative pulse pressure is a readily available measure, indicating that detailed physiological assessment may be warranted.
ISRCT registry, ISRCTN88456378.
Abstract
Objective
Multimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic ...combinations are lacking.
Design
A retrospective study using the Premier Healthcare Database (2009–2014).
Subjects
Adults who underwent elective primary THA or TKA.
Methods
We categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs).
Results
Among 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio aOR = 1.35, 95% confidence interval CI = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.
Conclusions
Gabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.
Assessments of frailty in bladder cancer Grimberg, Dominic C.; Shah, Ankeet; Molinger, Jeroen ...
Urologic oncology,
September 2020, 2020-09-00, 20200901, Letnik:
38, Številka:
9
Journal Article
Recenzirano
•Frailty is increasingly common in bladder cancer, and associated with a spectrum of poor outcomes after radical cystectomy.•No universally agreed upon screening or diagnostic tool for frailty ...exists, but the 11-item modified Frailty Index is the most studied in radical cystectomy patients.•The gold standard frailty assessment is multidisciplinary care and a Comprehensive Geriatric Assessment performed by a geriatrician, but this is not universally available.
The incidence of frailty is increasing as the population ages, which has important clinical implications given the associations between frailty and poor outcomes in the bladder cancer population. Due to a multi-organ system decline and decreased physiologic reserve, frail patients are vulnerable to stressors of disease and have poorer mortality and morbidity rates than their nonfrail peers. The association between frailty and poor outcomes has been documented across multiple populations, including radical cystectomy, creating a need for frailty assessments to be used preoperatively for risk stratification. We aim to provide a review of the common frailty assessments and their relevance to radical cystectomy patients.
A variety of assessments for frailty exist, from short screening items to comprehensive geriatric assessments. The syndrome spans multiple organ systems, as do the potential diagnostic instruments. Some instruments are less practical for use in clinical practice by urologists, such as the Canadian Study of Health and Aging Frailty Index and Comprehensive Geriatric Assessment. The tool most studied in radical cystectomy is the modified Frailty Index, associated with high grade complications and 30-days mortality. Frailty often coexists with malnutrition and sarcopenia, stressing the importance of screening for and addressing these syndromes to improve patient's perioperative outcomes.
There is no universally agreed upon frailty assessment, but the most studied in radical cystectomy is the modified Frailty Index, providing valuable data with which to counsel patients preoperatively. Alterations in immune phenotypes provide potential future diagnostic biomarkers for frailty.
Featured Cover Tracey, Robert; Elisseev, Vadim; Smyrnakis, Michalis ...
Applied AI letters,
12/2023, Letnik:
4, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The cover image is based on the Letter T
owards bespoke optimizations of energy efficiency in HPC environments
by Robert Tracey et al.,
https://doi.org/10.1002/ail2.87
.
image
Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This ...series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of
. The following article describes a project at an academic tertiary-care medical center aimed at identifying surgical patients with uncontrolled diabetes early in the preoperative process to improve their perioperative glycemic control and surgical outcomes.
Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) ...equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations.
This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition – Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients.
The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic mREE at 21.3 kcal/kg/d or 110% of predicted by the HB equation over the first week of mechanical ventilation (MV). This progressed to significant and uniquely prolonged hypermetabolism over successive weeks to 28.1 kcal/kg/d or 143% of HB predicted by MV week 3, with hypermetabolism persisting to MV week 7. Obese individuals displayed a more truncated response with significantly lower mREE versus non-obese patients in MV week 1 (19.5 ± 1.0 kcal/kg/d vs 25.1 ± 1.8 kcal/kg/d, respectively; p < 0.01), with little change in weeks 2–3 (19.5 ± 1.5 kcal/kg/d vs 28.0 ± 2.0 kcal/kg/d; p < 0.01). Both ASPEN-SCCM upper range and PSU pREE equations provided close approximations of mREE yet, like all pREE equations, occasionally over- and under-predicted energy needs and typically did not predict late hypermetabolism.
Study results show a truly unique metabolic response in COVID-19 ICU patients, characterized by significant and prolonged, progressive hypermetabolism peaking at 3 weeks’ post-intubation, persisting for up to 7 weeks in ICU. This pattern was more clearly demonstrated in non-obese versus obese patients. This response is unique and distinct from any previously described model of ICU stress response in its prolonged hypermetabolic nature. This data reaffirms the need for routine, longitudinal IC measures to provide accurate energy targets in COVID-19 ICU patients. The PSU and ASPEN-SCCM equations appear to yield the most reasonable estimation to IC-derived mREE in COVID-19 ICU patients, yet still often over-/under-predict energy needs. These findings provide a practical guide for caloric prescription in COVID-19 ICU patients in the absence of IC.
Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac ...impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein-coupled receptor kinase 2, a key negative regulator of cardiac function.
Laboratory/clinical investigations.
University laboratory/medical centers.
Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2-deficient mice; elective surgical patients.
Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein-coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of <6 ms mm Hg). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed.
Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein-coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein-coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein-coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in patients was also associated with impaired intraoperative cardiac contractility. Critical illness and mortality were more frequent in surgical patients with baroreflex dysfunction (relative risk, 1.66 95% CI, 1.16-2.39; p = 0.006).
Reduced baroreflex sensitivity is associated with nicotinamide adenine dinucleotide phosphate oxidase subunit-2-mediated upregulation of G-protein-coupled receptor kinase 2 expression in cardiomyocytes and impaired cardiac contractility. Autonomic dysfunction predisposes patients to the development of critical illness and increases mortality.
Complications after major surgery account for a disproportionate amount of in-hospital morbidity and mortality. Recent efforts have focused on preoperative optimization in an attempt to modify the ...risk associated with major surgery. Underaddressed, but important, modifiable risk factors are physical fitness and nutritional status. Surgical patients are particularly at risk of 3 related, but distinct, conditions: frailty, sarcopenia, and reduced physical fitness. Exercise-based prehabilitation strategies have shown promise in terms of improving aerobic fitness, although their impact on key clinical perioperative outcome measures have not been fully determined. Preoperative nutritional status also has a strong bearing on perioperative outcome.
PDF
