Diagnostic Accuracy of Vascular Ultrasonography for Postanesthesia Induction Hypotension: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Arterial hypotension commonly occurs after anesthesia induction and is associated with negative clinical outcomes. Point-of-care ultrasound examination has emerged as a modality to predict postinduction hypotension (PIH). We performed a systematic review and network meta-analysis of the predictive performance of point-of-care ultrasound tests for PIH in noncardiac, nonobstetrical routine adult surgery. METHODS: Online databases were searched for diagnostic test accuracy studies of point-of-care ultrasound for predicting PIH up to March 30, 2023. The systematic review followed the Cochrane methodology. A Bayesian diagnostic test accuracy network meta-analysis model was used, with PIH as defined by study authors as the main outcome. Risk of bias and applicability were examined through the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) score. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess evidence certainty. RESULTS: A total of 32 studies with 2631 participants were eligible for systematic review. Twenty-six studies with 2258 participants representing 8 ultrasound tests were included in the meta-analysis. Inferior vena cava collapsibility index (22 studies) sensitivity was 60% (95% credible interval [CrI], 49%-72%) and specificity was 83% (CrI, 74%-89%). Carotid artery corrected flow time (2 studies) sensitivity was 91% (CrI, 76%-98%) and specificity was 90% (CrI, 59%-98%). There were serious bias and applicability concerns due to selection bias and inappropriate blinding. The certainty of evidence was very low for all tests. CONCLUSIONS: The predictive performance of point-of-care ultrasound for PIH is uncertain. There is a need for high-quality randomized controlled trials with appropriate blinding and void of selection bias.

The Effect of CytoSorb on Inflammatory Markers in Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The effectiveness of CytoSorb at removing inflammatory mediators in critically ill patients is controversial. DATA SOURCES: Electronic databases were searched from inception to May 2023. STUDY SELECTION: Randomized controlled trials reporting the effects of CytoSorb therapy on inflammatory parameters in critically ill patients with hyperinflammatory conditions were included. DATA EXTRACTION: Two authors screened articles for eligibility, extracted data, and assessed the risk of bias, conflicts of interest, and certainty of evidence (CoE). The primary outcome was interleukin (IL)-6 at 1 day after initiation of the therapy. Secondary outcomes included various inflammatory markers at 1, 2, 3, and 5 days and mortality. Data were pooled if at least three trials reported the outcome of interest. We conducted meta-analyses of the data using a random-effects model. DATA SYNTHESIS: Seventeen trials ( n = 855) were included. Fourteen trials were judged to have notable concern about conflicts of interest. Seven trials were performed in medical ICU patients with hyperinflammatory conditions and 10 in complex cardiovascular surgery under cardiopulmonary bypass. Hemoadsorption with CytoSorb was not associated with lower IL-6 at 1 day (mean difference -5.98 [95% CI, -30.44 to 18.48] pg/mL), 2 days, 3 days, or 5 days after initiation of the treatment, as well as the concentration of procalcitionin. The levels of C-reactive protein were not lower with CytoSorb at 1, 2, and 3 days. The use of CytoSorb was associated with higher mortality at latest follow-up (relative risk = 1.22 [95% CI, 1.02-1.45]) and at 30 days. CoE ranged from low to very low. CONCLUSIONS: The use of CytoSorb hemoadsorption in a mixed population of critically ill patients with hyperinflammatory conditions does not exhibit a consistent decrease in IL-6 and other inflammatory parameters within the first 5 days of treatment. The significant uncertainty surrounding these findings highlights the need for further investigations.

Impact of pharmacological interventions on intrapulmonary shunt during one-lung ventilation in adult thoracic surgery: a systematic review and component network meta-analysis.

BACKGROUND: Intrapulmonary shunt is a major determinant of oxygenation in thoracic surgery under one-lung ventilation. We reviewed the effects of available treatments on shunt, Pao2/FiO2 and haemodynamics through systematic review and network meta-analysis. METHODS: Online databases were searched for RCTs comparing pharmacological interventions and intrapulmonary shunt in thoracic surgery under one-lung ventilation up to March 30, 2022. Random-effects (component) network meta-analysis compared 24 treatments and 19 treatment components. The Confidence in Network Meta-Analysis (CINeMA) framework assessed evidence certainty. The primary outcome was intrapulmonary shunt fraction during one-lung ventilation. RESULTS: A total of 55 RCTs were eligible for systematic review (2788 participants). The addition of N2O (mean difference [MD]=-15%; 95% confidence interval [CI], -25 to -5; P=0.003) or almitrine (MD=-13%; 95% CI, -20 to -6; P<0.001) to propofol anaesthesia were efficient at decreasing shunt. Combined epidural anaesthesia (MD=3%; 95% CI, 1-5; P=0.005), sevoflurane (MD=5%; 95% CI, 2-8; P<0.001), isoflurane (MD=6%; 95% CI, 4-9; P<0.001), and desflurane (MD=9%; 95% CI, 4-14; P=0.001) increased shunt vs propofol. Almitrine (MD=147 mm Hg; 95% CI, 58-236; P=0.001), dopexamine (MD=88 mm Hg; 95% CI, 4-171; P=0.039), and iloprost (MD=81 mm Hg; 95% CI, 4-158; P=0.038) improved Pao2/FiO2. Certainty of evidence ranged from very low to moderate. CONCLUSIONS: Adding N2O or almitrine to propofol anaesthesia reduced intrapulmonary shunt during one-lung ventilation. Halogenated anaesthetics increased shunt in comparison with propofol. The effects of N2O, iloprost, and dexmedetomidine should be investigated in future research. N2O results constitute a research hypothesis currently not backed by any direct evidence. The clinical availability of almitrine is limited. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022310313.

Cardioprotective Effects of Glucose-Insulin-Potassium Infusion in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.

The infusion of glucose-insulin-potassium (GIK) has yielded conflicting results in terms of cardioprotective effects. We conducted a meta-analysis to examine the impact of perioperative GIK infusion in early outcome after cardiac surgery. Randomized controlled trials (RCTs) were eligible if they examined the efficacy of GIK infusion in adults undergoing cardiac surgery. The main study endpoint was postoperative myocardial infarction (MI) and secondary outcomes were hemodynamics, any complications and hospital resources utilization. Subgroup analyses explored the impact of the type of surgery, GIK composition and timing of administration. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated with a random-effects model. Fifty-three studies (n=6129) met the inclusion criteria. Perioperative GIK infusion was effective in reducing MI (k=32 OR 0.66[0.48, 0.89] P=0.0069), acute kidney injury (k=7 OR 0.57[0.4, 0.82] P=0.0023) and hospital length of stay (k=19 MD -0.89[-1.63, -0.16] days P=0.0175). Postoperatively, the GIK-treated group presented higher cardiac index (k=14 MD 0.43[0.29, 0.57] L/min P<0.0001) and lesser hyperglycemia (k=20 MD -30[-47, -13] mg/dL P=0.0005) than in the usual care group. The GIK-associated protection for MI was effective when insulin infusion rate exceeded 2 mUI/kg/min and after coronary artery bypass surgery. Certainty of evidence was low given imprecision of the effect estimate, heterogeneity in outcome definition and risk of bias. Perioperative GIK infusion is associated with improved early outcome and reduced hospital resource utilization after cardiac surgery. Supporting evidence is heterogenous and further research is needed to standardize the optimal timing and composition of GIK solutions.

Contralateral Pneumonectomy 27 Years After Right Single-Lung Transplantation for Emphysema: A Case Report.

BACKGROUND Following single-lung transplantation, native lung inflation can progressively develop in patients with emphysema. CASE REPORT A 74-year-old female patient presented with worsening dyspnea during daily activities. She underwent a right single-lung transplantation for emphysema 27 years ago. Despite recurrent episodes of acute rejection of the grafted lung, the patient had satisfactory recovery of physical fitness during that period and did not report any serious complications or respiratory symptoms. Her recent dyspnea was due to hyperinflation of the native emphysematous lung with mediastinal shift, reduction of venous blood return, and compression of the grafted lung. Although surgical lung volume reduction had resulted in temporary functional improvement 2 years ago, a completion contralateral pneumonectomy was deemed necessary to allow re-expansion of the grafted lung. After anesthesia induction and placement of a double-lumen tube, selective ventilation of the left emphysematous native lung confirmed the absence of gas exchange based on near-zero end-expiratory carbon dioxide fraction. During selective ventilation of the grafted lung, satisfactory gas exchange was achieved and pneumonectomy proceeded uneventfully under minimally-invasive thoracotomy. Immediately after anesthesia emergence and tracheal extubation, the patient experienced respiratory improvement. Continuous thoracic epidural blockade allowed pain-free mobilization and respiratory therapy to facilitate re-expansion of the grafted lung. CONCLUSIONS After single-lung transplantation in COPD patients, native lung hyperinflation is a well-described rare complication. Lung volume reduction including pneumonectomy can be considered a valuable treatment option.

Patent foramen ovale and perioperative stroke in noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Patent foramen ovale (PFO) is associated with perioperative stroke in noncardiac surgery. The magnitude of this association was assessed in a systematic review and meta-analysis. METHODS: Electronic databases were searched up to June 2022 for studies assessing the association between patent foramen ovale and perioperative stroke in adult patients undergoing noncardiac surgery. The primary analysis was limited to studies reporting effect estimates adjusted for significant clinical confounders. We calculated the adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: We included nine retrospective and two prospective observational studies, including 21 257 082 patients. The presence of a patent foramen ovale was independently associated with stroke at 30 days after surgery (aOR=6.68 [95% CI: 3.51-12.73]; P<0.001) and at longest follow-up available (aOR=7.36 [95% CI: 3.56-15.21]; P<0.001). The odds of stroke at 30 days varied according to surgical specialty: neurosurgery (aOR=4.52 [95% CI: 3.17-6.43]), vascular surgery (aOR=7.15 [95% CI: 2.52-20.22]), thoracic surgery (aOR=10.64 [95% CI: 5.97-18.98]), orthopaedic surgery (aOR=11.85 [95% CI: 5.38-26.08]), general surgery (aOR=14.40 [95% CI: 10.88-19.06]), and genitourinary surgery (aOR=17.28 [95% CI: 10.36-28.84]). CONCLUSIONS: The presence of a patent foramen ovale is associated with a large and consistent increase in odds of stroke across all explored surgical settings. Prospective trials should further explore this association by systematically assessing patent foramen ovale and stroke prevalence and identifying a specific population at risk. This is crucial for the elaboration of prevention plans and may improve perioperative outcomes.

Mortality and adverse events of hemoadsorption with CytoSorb® in critically ill patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The effects and safety of extracorporeal hemoadsorption with CytoSorb® in critically ill patients with inflammatory conditions are controversial. METHODS: We performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized-controlled trials to assess the mortality and safety of CytoSorb® therapy in critically ill patients with inflammatory conditions. Electronic databases were searched up to April 2022. The primary outcome was mortality at longest follow-up and secondary outcomes included various adverse event (AE) outcomes. Conflict of interest and funding of each trial were assessed. We calculated relative risk (RR) and 95% confidence interval (CI). RESULTS: Fourteen published (n = 764) and 4 unpublished (n = 111) trials were included. Eight trials were performed in medical ICU patients and 10 in complex cardiac surgery. Ten trials had significant industrial funding or an author conflict of interest. Hemoadsorption with CytoSorb® was associated with higher mortality at latest follow-up (16 trials, n = 807, 120 of 402 [29.85%] patients in the CytoSorb® group vs. 98 of 405 [24.20%] patients in the control group, RR = 1.24 [95% CI, 1.04-1.49], p = .02, [TSA-adjusted CI, 0.92-1.68]) and at 30-days or in-hospital (11 trials, n = 727; RR = 1.41 [95% CI, 1.06-1.88], p = .02, [TSA-adjusted CI, 0.44-4.62]). Only one trial reported the definition of adverse event, while detailed results were reported in 3 trials; the risk of adverse events was not higher with CytoSorb®. Certainty of evidence ranged from low to very low. CONCLUSION: Low certainty of evidence showed that the use of CytoSorb® might increase mortality in critically ill patients with inflammatory conditions. Adverse events were frequent but underreported and not systematically evaluated. Industrial funding and conflict of interest were common. Considerable uncertainty about the findings does not allow firm conclusions and suggests a need for high-quality randomized trials to clarify mortality and adverse events related to CytoSorb®. EDITORIAL COMMENT: Hemoadsorption with CytoSorb® have been used in critically ill patients despite lack of high quality data from RCTs suggesting any patient-important benefits. The findings from this systematic review and meta-analysis suggests an increased risk of adverse events including mortality. With no apparent benefits and at the same time risk of harm, use of hemoadsorption with CytoSorb® in daily clinical practice cannot be recommended at this time.

Myocardial injury after major noncardiac surgery: A secondary analysis of a randomized controlled trial.

BACKGROUND: Myocardial injury after noncardiac surgery frequently occurs and may influence survival. The aims of this study were to examine the association between myocardial injury after noncardiac surgery and patient and procedural factors as well as its impact on postoperative clinical outcome. METHODS: A retrospective analysis was conducted from data collected in adults enrolled in a randomized trial in elective major open abdominal surgery. Preoperative patient characteristics, intraoperative hemodynamic changes, and postoperative adverse events were analyzed, and Kaplan-Meier curves were built for postoperative survival probability. After adjustment for baseline patient and procedural characteristics, the effect of myocardial injury after noncardiac surgery on postoperative outcomes was analyzed in a propensity score matched cohort. RESULTS: Among 394 patients, myocardial injury after noncardiac surgery was reported in 109 (27.7%) and was associated with a higher cardiovascular risk profile, prolonged surgery (333 ± 111 min vs 295 ± 134 min, P = .010), greater need for transfusions (41.3% vs 19.3%, P < .001), higher incidence of major adverse cardiac events (22.9% vs 6.7%, P < .001), pulmonary complications (31.2% vs 17.9%, P = .004) , acute kidney injury (30.3% vs 18.2%, P = .009), and systemic inflammatory syndrome (28.4% vs 13.0%, P < .001). After propensity score matching, the operative time and the need for blood transfusion remained higher among myocardial injury after noncardiac surgery patients who experienced more frequent major adverse cardiac events and acute kidney injury. In both the entire and matched cohorts, survival up to 30 months after surgery was determined mainly by the presence of cancer. CONCLUSION: The burden of cardiovascular disease and operative stress surgery is predictive of myocardial injury after noncardiac surgery and, in turn, with a higher incidence of cardiac adverse events, whereas the presence of cancer is associated with poor survival in patients undergoing major open abdominal surgery. Further studies are needed to determine whether myocardial injury after noncardiac surgery can be prevented by better control of the patient's cardiovascular condition and implementation of less invasive of surgical procedures.

The hypoxic pulmonary vasoconstriction: From physiology to clinical application in thoracic surgery.

More than 70 years after its original report, the hypoxic pulmonary vasoconstriction (HPV) response continues to spark scientific interest on its mechanisms and clinical implications, particularly for anesthesiologists involved in thoracic surgery. Selective airway intubation and one-lung ventilation (OLV) facilitates the surgical intervention on a collapsed lung while the HPV redirects blood flow from the "upper" non-ventilated hypoxic lung to the "dependent" ventilated lung. Therefore, by limiting intrapulmonary shunting and optimizing ventilation-to-perfusion (V/Q) ratio, the fall in arterial oxygen pressure (PaO2) is attenuated during OLV. The HPV involves a biphasic response mobilizing calcium within pulmonary vascular smooth muscles, which is activated within seconds after exposure to low alveolar oxygen pressure and that gradually disappears upon re-oxygenation. Many factors including acid-base balance, the degree of lung expansion, circulatory volemia as well as lung diseases and patient age affect HPV. Anesthetic agents, analgesics and cardiovascular medications may also interfer with HPV during the perioperative period. Since HPV represents the homeostatic mechanism for regional ventilation-to-perfusion matching and in turn, for optimal pulmonary oxygen uptake, a clear understanding of HPV is clinically relevant for all anesthesiologists.

How can we minimize the risks by optimizing patient's condition shortly before thoracic surgery?

The "moderate-to-high-risk" surgical patient is typically older, frail, malnourished, suffering from multiple comorbidities and presenting with unhealthy life style such as smoking, hazardous drinking and sedentarity. Poor aerobic fitness, sarcopenia and "toxic" behaviors are modifiable risk factors for major postoperative complications. The physiological challenge of lung cancer surgery has been likened to running a marathon. Therefore, preoperative patient optimization or " prehabilitation " should become a key component of improved recovery pathways to enhance general health and physiological reserve prior to surgery. During the short preoperative period, the patients are more receptive and motivated to adhere to behavioral interventions (e.g., smoking cessation, weaning from alcohol, balanced food intake and active mobilization) and to follow a structured exercise training program. Sufficient protein intake should be ensured (1.5-2 g/kg/day) and nutritional defects should be corrected to restore muscle mass and strength. Currently, there is strong evidence supporting the effectiveness of various modalities of physical training (endurance training and/or respiratory muscle training) to enhance aerobic fitness and to mitigate the risk of pulmonary complications while reducing the hospital length of stay. Multimodal interventions should be individualized to the patient's condition. These bundle of care are more effective than single or sequential intervention owing to synergistic benefits of education, nutritional support and physical training. An effective prehabilitation program is necessarily patient-centred and coordinated among health care professionals (nurses, primary care physician, physiotherapists, nutritionists) to help the patient regain some control over the disease process and improve the physiological reserve to sustain surgical stress.

Restricted, optimized or liberal fluid strategy in thoracic surgery: A narrative review.

Perioperative fluid balance has a major impact on clinical and functional outcome, regardless of the type of interventions. In thoracic surgery, patients are more vulnerable to intravenous fluid overload and to develop acute respiratory distress syndrome and other complications. New insight has been gained on the mechanisms causing pulmonary complications and the role of the endothelial glycocalix layer to control fluid transfer from the intravascular to the interstitial spaces and to promote tissue blood flow. With the implementation of standardized processes of care, the preoperative fasting period has become shorter, surgical approaches are less invasive and patients are allowed to resume oral intake shortly after surgery. Intraoperatively, body fluid homeostasis and adequate tissue oxygen delivery can be achieved using a normovolemic therapy targeting a "near-zero fluid balance" or a goal-directed hemodynamic therapy to maximize stroke volume and oxygen delivery according to the Franck-Starling relationship. In both fluid strategies, the use of cardiovascular drugs is advocated to counteract the anesthetic-induced vasorelaxation and maintain arterial pressure whereas fluid intake is limited to avoid cumulative fluid balance exceeding 1 liter and body weight gain (~1-1.5 kg). Modern hemodynamic monitors provide valuable physiological parameters to assess patient volume responsiveness and circulatory flow while guiding fluid administration and cardiovascular drug therapy. Given the lack of randomized clinical trials, controversial debate still surrounds the issues of the optimal fluid strategy and the type of fluids (crystalloids versus colloids). To avoid the risk of lung hydrostatic or inflammatory edema and to enhance the postoperative recovery process, fluid administration should be prescribed as any drug, adapted to the patient's requirement and the context of thoracic intervention.

Goal-directed hemodynamic therapy versus restrictive normovolemic therapy in major open abdominal surgery: A randomized controlled trial.

BACKGROUND: The aim of this study was to compare the occurrence of postoperative complications in patients undergoing elective open abdominal surgery and receiving intraoperative goal-directed hemodynamic therapy or restrictive normovolemic therapy. METHODS: A total of 401 patients were randomized in the goal-directed hemodynamic therapy or restrictive normovolemic therapy groups. A cardiac output monitor was used in all goal-directed hemodynamic therapy patients and was left at the discretion of anesthetists in charge of patients in the restrictive normovolemic therapy group. The primary outcome was a composite morbidity endpoint (30-day mortality and complications grade 2-4 according to Dindo-Clavien classification). Secondary outcomes were the hospital duration of stay, the incidence of pulmonary, cardiovascular, and renal complications up to 30 days after surgery, and midterm survival. RESULTS: Intraoperatively, the goal-directed hemodynamic therapy group received higher intravenous fluid volumes (mean of 10.8 mL/kg/h and standard deviation of 4.0) compared with the restrictive normovolemic therapy group (mean of 7.2 mL/kg/h and standard deviation of 2.0; P < .001). On the first postoperative day, similar fluid volumes were infused in the 2 groups. The primary outcome occurred in 57.7% of goal-directed hemodynamic therapy and 53.0% of restrictive normovolemic therapy (relative risk, 1.09 [95% confidence interval, 0.91-1.30]), and there was no significant difference between groups for any secondary outcomes. CONCLUSION: Among patients undergoing major open abdominal surgery, the goal-directed hemodynamic therapy and the restrictive normovolemic therapy were associated with similar incidence of moderate-to-severe postoperative complications and hospital resource use.

Preoperative Exercise Training to Prevent Postoperative Pulmonary Complications in Adults Undergoing Major Surgery. A Systematic Review and Meta-analysis with Trial Sequential Analysis.

Rationale: Poor preoperative physical fitness and respiratory muscle weakness are associated with postoperative pulmonary complications (PPCs) that result in prolonged hospital length of stay and increased mortality.Objectives: To examine the effect of preoperative exercise training on the risk of PPCs across different surgical settings.Methods: We searched MEDLINE, Web of Science, Embase, the Physiotherapy Evidence Database, and the Cochrane Central Register, without language restrictions, for studies from inception to July 2020. We included randomized controlled trials that compared patients receiving exercise training with those receiving usual care or sham training before cardiac, lung, esophageal, or abdominal surgery. PPCs were the main outcome; secondary outcomes were preoperative functional changes and postoperative mortality, cardiovascular complications, and hospital length of stay. The study was registered with PROSPERO (International Prospective Register of Systematic Reviews).Results: From 29 studies, 2,070 patients were pooled for meta-analysis. Compared with the control condition, preoperative exercise training was associated with a lower incidence of PPCs (23 studies, 1,864 patients; relative risk, 0.52; 95% confidence interval [CI], 0.41 to 0.66; grading of evidence, moderate); Trial Sequential Analysis confirmed effectiveness, and there was no evidence of difference of effect across surgeries, type of training (respiratory muscles, endurance or combined), or preoperative duration of training. At the end of the preoperative period, exercise training resulted in increased peak oxygen uptake (weighted mean difference [WMD], +2 ml/kg/min; 99% CI, 0.3 to 3.7) and higher maximal inspiratory pressure (WMD, +12.2 cm H2O; 99% CI, 6.3 to 18.2). Hospital length of stay was shortened (WMD, -2.3 d; 99% CI, -3.82 to -0.75) in the intervention group, whereas no difference was found in postoperative mortality.Conclusions: Preoperative exercise training improves physical fitness and reduces the risk of developing PPCs while minimizing hospital resources use, regardless of the type of intervention and surgery performed.Systematic review registered with https://www.crd.york.ac.uk/prospero/ (CRD 42018096956).

Blood pressure measurements with the OptiBP smartphone app validated against reference auscultatory measurements.

Mobile health diagnostics have been shown to be effective and scalable for chronic disease detection and management. By maximizing the smartphones' optics and computational power, they could allow assessment of physiological information from the morphology of pulse waves and thus estimate cuffless blood pressure (BP). We trained the parameters of an existing pulse wave analysis algorithm (oBPM), previously validated in anaesthesia on pulse oximeter signals, by collecting optical signals from 51 patients fingertips via a smartphone while simultaneously acquiring BP measurements through an arterial catheter. We then compared smartphone-based measurements obtained on 50 participants in an ambulatory setting via the OptiBP app against simultaneously acquired auscultatory systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) measurements. Patients were normotensive (70.0% for SBP versus 61.4% for DBP), hypertensive (17.1% vs. 13.6%) or hypotensive (12.9% vs. 25.0%). The difference in BP (mean ± standard deviation) between both methods were within the ISO 81,060-2:2018 standard for SBP (- 0.7 ± 7.7 mmHg), DBP (- 0.4 ± 4.5 mmHg) and MBP (- 0.6 ± 5.2 mmHg). These results demonstrate that BP can be measured with accuracy at the finger using the OptiBP smartphone app. This may become an important tool to detect hypertension in various settings, for example in low-income countries, where the availability of smartphones is high but access to health care is low.

Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. METHODS: Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. RESULTS: Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. CONCLUSIONS: Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.

Short-Term Preoperative High-Intensity Interval Training in Patients Awaiting Lung Cancer Surgery: A Randomized Controlled Trial.

INTRODUCTION: Impairment in aerobic fitness is a potential modifiable risk factor for postoperative complications. In this randomized controlled trial, we hypothesized that a high-intensity interval training (HIIT) program enhances cardiorespiratory fitness before lung cancer surgery and therefore reduces the risk of postoperative complications. METHODS: Patients with operable lung cancer were randomly assigned to usual care (UC) (n = 77) or preoperative rehabilitation based on HIIT (Rehab) (n = 74). Maximal cardiopulmonary exercise testing and the 6-minute walk test were performed twice before surgery. The primary outcome measure was a composite of death and in-hospital postoperative complications. RESULTS: The groups were well balanced in terms of patient characteristics. During the preoperative waiting period (median 25 days), the peak oxygen consumption and the 6-minute walking distance increased (median +15%, interquartile range, 25th to 75 percentile [IQR25%-75%, %] = +9% to +22%, p = 0.003 and +15%, IQR25%-75% = +8% to +28%, p < 0.001, respectively) in the Rehab group, whereas peak oxygen consumption declined in the UC group (median -8%, IQR25%-75% = -16% to 0%], p = 0.005). The primary end point did not differ significantly between the two groups: at least one postoperative complication developed in 27 of the 74 patients (35.5%) in the Rehab group and 39 of 77 patients (50.6%) in the UC group (p = 0.080). Notably, the incidence of pulmonary complications was lower in the Rehab compared with in the UC group (23% versus 44%, p = 0.018), owing to a significant reduction in atelectasis (12.2% versus 36.4%, p < 0.001), and this decrease was accompanied by a shorter length of stay in the postanesthesia care unit (median -7 hours, IQR25%-75% = -4 to -10). CONCLUSIONS: In this randomized controlled trial, preoperative HIIT resulted in significant improvement in aerobic performances but failed to reduce early complications after lung cancer resection.

Fluvastatin inhibits regulated secretion of endothelial cell von Willebrand factor in response to diverse secretagogues.

Regulated secretion of EC (endothelial cell) vWF (von Willebrand factor) is part of the haemostatic response. It occurs in response to secretagogues that raise intracellular calcium or cAMP. Statins are cholesterol-lowering drugs used for the treatment of cardiovascular disease. We studied the effect of fluvastatin on regulated secretion of vWF from HUVEC (human umbilical-vein ECs). Secretion in response to thrombin, a protease-activated receptor-1 agonist peptide, histamine, forskolin and adrenaline (epinephrine) was inhibited. This inhibition was reversed by mevalonate or geranylgeranyl pyrophosphate, and mimicked by a geranylgeranyl transferase inhibitor, demonstrating that the inhibitory mechanism includes inhibition of protein geranylgeranylation. To investigate this mechanism further, calcium handling and NO (nitric oxide) regulation were studied in fluvastatin-treated HUVEC. Intracellular calcium mobilization did not correlate with vWF secretion. Fluvastatin increased eNOS [endothelial NOS (NO synthase)] expression, but NOS inhibitors failed to reverse the effect of fluvastatin on vWF secretion. Exogenous NO did not inhibit thrombin-induced vWF secretion. Many small GTPases are geranylgeranylated and some are activated by secretagogues. We overexpressed DN (dominant negative) Rho GTPases, RhoA, Rac1 and Cdc42 (cell division cycle 42), in HUVEC. DNCdc42 conferred inhibition of thrombin- and forskolin-induced vWF secretion. We conclude that, via inhibition of protein geranylgeranylation, fluvastatin is a broadspectrum inhibitor of regulated vWF secretion. Geranylgeranylated small GTPases with functional roles in regulated secretion, such as Cdc42, are potential targets for the inhibitory activity of fluvastatin.