Enhanced recovery after surgery protocols following emergency intra-abdominal surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to evaluate whether Enhanced Recovery After Surgery (ERAS) protocols for patients undergoing emergency intra-abdominal surgery improve postoperative outcomes as compared to conventional care. METHODS: MEDLINE, EMBASE, WoS, CENTRAL, and Pubmed were searched from inception to December 2022. Articles were eligible if they were randomized controlled trials (RCT) or non-randomized studies comparing ERAS protocols to conventional care for patients undergoing emergency intra-abdominal surgery. The outcomes included postoperative length of stay (LOS), postoperative morbidity, prolonged postoperative ileus (PPOI), and readmission. An inverse variance random effects meta-analysis was performed. A risk of bias was assessed with Cochrane tools. Certainty of evidence was assessed with GRADE. RESULTS: After screening 1018 citations, 20 studies with 1615 patients in ERAS programs and 1933 patients receiving conventional care were included. There was a reduction in postoperative LOS in the ERAS group for patients undergoing upper gastrointestinal (GI) surgery (MD3.35, 95% CI 2.52-4.17, p < 0.00001) and lower GI surgery (MD2.80, 95% CI 2.62-2.99, p < 0.00001). There was a reduction in postoperative morbidity in the ERAS group for patients undergoing upper GI surgery (RR0.56, 95% CI 0.30-1.02, p = 0.06) and lower GI surgery (RR 0.66, 95%CI 0.52-0.85, p = 0.001). In the upper and lower GI subgroup, there were nonsignificant reductions in PPOI in the ERAS groups (RR0.59, 95% CI 0.30-1.17, p = 0.13; RR0.49, 95% CI 0.21-1.14, p = 0.10). There was a nonsignificant increased risk of readmission in the ERAS group (RR1.60, 95% CI 0.57-4.50, p = 0.50). CONCLUSION: There is low-to-very-low certainty evidence supporting the use ERAS protocols for patients undergoing emergency intra-abdominal surgery. The currently available data are limited by imprecision.

Demographic differences in Canadian medical students' motivation and confidence to promote physical activity.

BACKGROUND: Physical activity (PA) remains under prescribed by physicians. Motivation and confidence are clear drivers of frequency of promoting PA. Research shows demographic differences in physicians' preventive practices, yet none have included medical students who form habits during training. OBJECTIVES: Study objectives were to (i) examine how Canadian medical students' motivation to recommend PA to future patients differs according to six demographic variables (i.e. gender, ethnicity, year of study, university, proposed specialty and academic background) and (ii) examine how Canadian medical students' confidence to recommend PA to future patients differs according to these same demographic variables. METHODS: A cross-sectional design was used. First to fourth year medical students from three medical schools responded to an online survey (N = 221). RESULTS: Female participants were more motivated to counsel patients on PA and refer to an exercise specialist compared to males (P < 0.01). Second year students were more motivated to assess a patients' level of PA compared to third and fourth year students (P < 0.01). Students pursuing family medicine were more confident to assess and counsel compared to students pursuing paediatrics (P < 0.01). CONCLUSION: Given that motivation and confidence have a positive influence on frequency-promoting PA, these results suggest where future efforts should focus, to improve PA promotion in medical practice. Physical inactivity continues to be a major issue worldwide, and medical students as future physicians have a unique opportunity to enhance PA amongst the population.

Canadian medical students' perceived motivation, confidence and frequency recommending physical activity.

Despite the evidence supporting the benefits of physical activity in the prevention and treatment of most medical conditions, physical activity remains under-prescribed by physicians. Medical students will form habits during training that they are likely to maintain as future physicians. The overall purpose of this study was to investigate the underlying mechanism(s) contributing to frequency in recommending physical activity, to provide insight into how we can increase physical activity recommendations in future practice as physicians. First to fourth year medical students at three Canadian universities responded to an online survey (N = 221; 12% response rate) between November 2017 and January 2018. Results revealed that engaging in strenuous physical activity was a strong predictor for frequency in recommending physical activity to patients (p < .001). Confidence in recommending physical activity mediated the relationship between strenuous physical activity and frequency recommending physical activity (p = .005); motivation did not mediate this relationship. Students were more motivated, than they were confident, to assess, advise, counsel, prescribe and refer patients regarding physical activity (p < .05). While 70% of students stated they are aware of the Canadian physical activity guidelines, only 52% accurately recalled them. Findings suggest that increased training related to physical activity should be included in the medical school curriculum to increase students' confidence to recommend physical activity. Another way to increase confidence and frequency in recommending physical activity is to help students engage in more strenuous physical activity themselves, which will ultimately benefit both medical students and their future patients.

Regenerative cell therapy for pulmonary arterial hypertension in animal models: a systematic review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary arterial pressures leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. The objective of this systematic review was to compare the efficacy of regenerative cell therapies in preclinical models of PAH. METHODS: A systematic search strategy was developed and executed. We included preclinical animal studies using regenerative cell therapy in experimental models of PAH. Primary outcomes were right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP). The secondary outcome was right ventricle/left ventricle + septum weight ratio (RV/LV+S). Pooled effect sizes were undertaken using random effects inverse variance models. Risk of bias and publication bias were assessed. RESULTS: The systematic search yielded 1285 studies, of which 44 met eligibility criteria. Treatment with regenerative cell therapy was associated with decreased RVSP (SMD - 2.10; 95% CI - 2.59 to - 1.60), mPAP (SMD - 2.16; 95% CI - 2.97 to - 1.35), and RV/LV+S (SMD - 1.31, 95% CI - 1.64 to - 0.97). Subgroup analysis demonstrated that cell modification resulted in greater reduction in RVSP. The effects on RVSP and mPAP remained statistically significant even after adjustment for publication bias. The majority of studies had an unclear risk of bias. CONCLUSIONS: Preclinical studies of regenerative cell therapy demonstrated efficacy in animal models of PAH; however, future studies should consider incorporating design elements to reduce the risk of bias. SYSTEMATIC REVIEW REGISTRATION: Suen CM, Zhai A, Lalu MM, Welsh C, Levac BM, Fergusson D, McIntyre L and Stewart DJ. Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol. Syst Rev. 2016;5:89. TRIAL REGISTRATION: CAMARADES-NC3Rs Preclinical Systematic Review & Meta-analysis Facility (SyRF). http://syrf.org.uk/protocols/ . Syst Rev 5:89, 2016.

The impact of an acute oral phosphate load on endothelium dependent and independent brachial artery vasodilation in healthy males.

Serum phosphate levels are associated with cardiovascular morbidity and mortality in the general population and endothelial dysfunction may be mechanistically involved. The purpose of this study was to investigate the effects of acute phosphate supplementation on endothelial-dependent (flow-mediated dilation; FMD) and -independent (glyceryl trinitrate; GTN)) vasodilation in young, healthy males. Seventeen healthy male participants (age, 23 ± 3 years) were exposed to an oral load of phosphate (PHOS; liquid supplement containing 1200 mg of phosphorous) and placebo (PLAC) over 2 experimental days. A brachial artery FMD test was performed pre-ingestion and at 20 min, 60 min, and 120 min following the ingestion of the phosphate load or the placebo. GTN tests were performed pre- and 140 min post-ingestion. Serum phosphate was not impacted differently by phosphate versus placebo ingestion (p = 0.780). In contrast, urinary phosphate excretion was markedly increased in the PHOS (p < 0.001) but not in the PLAC condition (p = 0.130) (Δ fractional excretion of phosphate in PHOS (29.2%) vs. PLAC (9.3%)). This indicates that circulating phosphate levels were homeostatically regulated. GTN-mediated vasodilation was not significantly affected by phosphate ingestion. In primary analysis no impact of phosphate ingestion on FMD was detected. However, when the shear stress stimulus was added as a covariate in a subset of participants, exploratory pairwise comparisons revealed a significantly lower FMD 20 min post-phosphate ingestion versus placebo (p = 0.024). The effects of phosphate ingestion on FMD and serum phosphate are in contrast with previous findings and the mechanisms that underlie the disparate results require further investigation.

Efficacy and safety of regenerative cell therapy for pulmonary arterial hypertension in animal models: a preclinical systematic review protocol.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease (15 cases per million) that is characterized by widespread loss of the pulmonary microcirculation and elevated pulmonary vascular resistance leading to pathological right ventricular remodeling and ultimately right heart failure. Regenerative cell therapies (i.e., therapies involving cells with stem or progenitor-like properties) could potentially restore the effective lung microcirculation and provide a curative therapy for PAH. Preclinical evidence suggests that regenerative cell therapy using endothelial progenitor cells or mesenchymal stem cells may be beneficial in the treatment of PAH. These findings have led to the completion of a small number of human clinical trials, albeit with modest effect compared to animal studies. The objective of this systematic review is to compare the efficacy and safety of regenerative cell therapies in preclinical models of PAH as well as assess study quality to inform future clinical studies. METHODS: We will include preclinical studies of PAH in which a regenerative cell type was administered and outcomes compared to a disease control. The primary outcome will be pulmonary hemodynamics as assessed by measurement of right ventricular systolic pressure and/or mean pulmonary arterial pressure. Secondary outcomes will include mortality, survival, right ventricular remodeling, pulmonary vascular resistance, cardiac output, cardiac index, pulmonary acceleration time, tricuspid annular systolic excursion, and right ventricular wall thickness. Electronic searches of MEDLINE and EMBASE databases will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool, and individual study reporting will be assessed according to an itemized checklist based on the Animal Research: Reporting of In vivo Experiments (ARRIVE) guidelines. DISCUSSION: This systematic review will examine the efficacy and safety of regenerative cell therapy in preclinical models of PAH. As well, the literature will be assessed for study quality and risk of bias. The results will guide the design of future clinical trials and preclinical animal studies. SYSTEMATIC REVIEW REGISTRATION: CAMARADES ( http://www.dcn.ed.ac.uk/camarades/SyRF/Protocols.htm ).

The combined influence of fat consumption and repeated mental stress on brachial artery flow-mediated dilatation: a preliminary study.

Experienced separately, both acute mental stress and high-fat meal consumption can transiently impair endothelial function, and the purpose of the present study was to investigate their combined impact. On four separate days, 10 healthy men (23 years old) underwent brachial artery flow-mediated dilatation (FMD) tests, before and hourly for 4 h post-consumption of a high-fat (HFM; 54 g fat) or low-fat meal (LFM; 0 g fat; each meal ∼ 1000 calories), with hourly mental stress (mental arithmetic, speech) or control (counting) tasks (conditions HFM+S, LFM+S, HFM and LFM). Data are presented as means ± SD. Plasma triglycerides increased and remained elevated after the high-fat but not the low-fat meal (P = 0.004) and were not affected by mental stress (P = 0.329). Indices of stress reactivity increased during mental stress tasks (mean arterial pressure, ∼ 20 mmHg; heart rate, ∼ 22 beats min(-1); salivary cortisol, ∼ 2.37 nmol l(-1); and plasma noradrenaline, ∼ 0.17 ng ml(-1)) and were not influenced by meal (P > 0.05). There was no effect of the type of meal on FMD (P = 0.562); however, FMD was 4.5 ± 0.5% in the control conditions and 5.8 ± 0.6% in the mental stress conditions (P = 0.087), and this difference was significant when normalized for the shear stress stimulus (FMD/area under the curve of shear stress, P = 0.045). Overall, these preliminary data suggest that postprandial FMD was augmented with mental stress irrespective of meal type. These results are contrary to previous reports of impaired endothelial function after mental stress or fat consumption independently and highlight the need to further investigate the mechanisms underlying the interactions between these factors.

Ringer's lactate is compatible with saline-adenine-glucose-mannitol preserved packed red blood cells for rapid transfusion.

PURPOSE: Guidelines state that Ringer's lactate (RL) should not be co-administered with packed red blood cells (PRBC) due to a potential risk of clotting. The purpose of this study was to determine whether RL causes clotting in PRBC with the currently used preservative, saline-adenine-glucose-mannitol (SAGM). METHODS: Phase 1: Samples from 12 units of SAGM-PRBC were diluted from 0-97.5% with RL and normal saline (NS), incubated for 30 min, and passed through 40 µm filters. Additional samples were frozen and batch analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure prothrombin activation fragment 1 + 2 (F1 + 2), indicative of thrombin generation. Packed red blood cells were also diluted, flushed with crystalloid using a rapid transfusion model, and filtered. Phase 2: Eight further units were serially diluted with RL and incubated for 30, 60, 120, 180, and 240 min. Fresh samples were analyzed by filtration and ELISA. RESULTS: Phase 1: No clotting was seen during filtration or using the transfusion model with NS or RL. The F1 + 2 ranged from 2.28 to 154.37 pmol·L⁻¹ in NS dilutions and from 2.80 to 1675.93 pmol·L⁻¹ in RL dilutions, indicating coagulation in some samples. Phase 2: No clotting was observed within 60 min by filtration or ELISA. However, 4 of the 8 units showed clots in the filters of some dilutions between 120 and 240 min. CONCLUSIONS: No clotting was detected at any dilution of RL with SAGM- preserved PRBC within 60 min, but clotting was detected with extended incubation. The results indicate RL can be safely co-administered with PRBC during rapid transfusion (< 60 min).