Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

Prognostic Model for Vasopressor Requirement After Retroperitoneal Adrenalectomy for Pheochromocytoma: A Retrospective Study.

OBJECTIVES: To evaluate the risk factors for postoperative vasopressor requirement among patients with pheochromocytoma undergoing retroperitoneal adrenalectomy. The primary outcome was postoperative hypotension requiring vasopressor support. DESIGN: A single-center retrospective observational study. SETTING: At a university hospital. PARTICIPANTS: Adults who underwent unilateral adrenalectomy for pheochromocytoma between October 2015 and February 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 201 patients were included. Postoperative vasopressor requirements were observed in 39 (19.4%) patients, and were associated with baseline coronary artery disease (CAD) (odds ratio [OR] 6.21, 95% CI) 2.48-15.52; p = 0.0001), maximal systolic blood pressure (maxSBP) >195 mmHg (OR 3.71, 95% CI 1.53-8.95; p = 0.0035), and >5.1-fold increase in the upper limit of normal values for baseline adrenergic activity (OR 4.9, 95% CI 1.93-12.55; p = 0.0008). The area under the receiver operating characteristic curve of the predictive model was 0.804 (95% CI 0.742-0.856). CONCLUSION: A MaxSBP >195 mmHg, baseline adrenergic activity >5.1-fold increase in the upper limit of normal values, and baseline CAD could predict postresection requirements for vasoactive support. Prospective multicenter international studies are required to develop and validate universally accepted predictive models for postoperative complications in patients after adrenalectomy for pheochromocytoma.

Combined Cytotoxic Effect of Inhibitors of Proteostasis on Human Colon Cancer Cells.

Despite significant progress in the diagnosis and treatment of colorectal cancer, drug resistance continues to be a major limitation of therapy. In this regard, studies aimed at creating combination therapy are gaining popularity. One of the most promising adjuvants are inhibitors of the proteostasis system, chaperone machinery, and autophagy. The main HSP regulator, HSF1, is overactivated in cancer cells and autophagy sustains the survival of malignant cells. In this work, we focused on the selection of combination therapy for the treatment of rectal cancer cells obtained from patients after tumor biopsy without prior treatment. We characterized the migration, proliferation, and chaperone status in the resulting lines and also found them to be resistant to a number of drugs widely used in the clinic. However, these cells were sensitive to the autophagy inhibitor, chloroquine. For combination therapy, we used an HSF1 activity inhibitor discovered earlier in our laboratory, the cardenolide CL-43, which has already been proven as an auxiliary component of combined therapy in established cell lines. CL-43 effectively suppressed HSF1 activity and Hsp70 expression in all investigated cells. We tested the autophagy inhibitor, chloroquine, in combination with CL-43. Our results indicate that the use of an inhibitor of HSF1 activity in combination with an autophagy inhibitor results in effective cancer cell death, therefore, this therapeutic approach may be a promising treatment regimen for certain patients.

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

BACKGROUND: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. OBJECTIVE: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. DESIGN: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). INTERVENTION: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. CONTROL: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. SETTING: Recruitment from 108 centers in 22 countries from 2018 to 2021. PATIENTS: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. MEASUREMENTS: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 µmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. METHODS: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Substudy results will be analyzed in 2022. LIMITATIONS: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. CONCLUSIONS: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

CONTEXTE: La plupart des patients qui prennent des médicaments antihypertenseurs continuent de les prendre le matin d'une intervention chirurgicale et pendant la période périopératoire. De plus en plus de preuves suggèrent que cette pratique pourrait entraîner l'hypotension périopératoire et augmenter le risque de complications. Ce protocole décrit une sous-étude sur l'insuffisance rénale aiguë (IRA) découlant de l'essai Perioperative Ischemic Evaluation-3 (POISE-3). Cet essai teste l'effet d'une stratégie d'évitement de l'hypotension périopératoire par rapport à une stratégie d'évitement de l'hypertension chez des patients qui subissent une chirurgie non cardiaque. OBJECTIFS: Cette sous-étude de l'essai POISE-3 vise à déterminer si une stratégie d'évitement de l'hypotension périopératoire réduit le risque d'IRA comparativement à la stratégie d'évitement de l'hypertension. TYPE D'ÉTUDE: Essai clinique randomisé à répartition 1:1 au groupe intervention (stratégie d'évitement de l'hypotension périopératoire) ou au groupe témoin (stratégie d'évitement de l'hypertension). GROUPE INTERVENTION: Si la pression artérielle systolique (PAS) avant l'opération est <130 mmHg, tous les médicaments antihypertenseurs sont suspendus le matin de la chirurgie. Si la PAS est ≥130 mmHg, certains médicaments (excluant les inhibiteurs de l'enzyme de conversion de l'angiotensine [IECA], les antagonistes du récepteur de l'angiotensine [ARA] ou les inhibiteurs de la rénine) peuvent être poursuivis de façon graduelle. Pendant la chirurgie, la pression artérielle moyenne (PAM) du patient est maintenue à ≥80 mmHg. Dans les 48 heures suivant l'intervention chirurgicale, certains médicaments antihypertenseurs (excluant les IECA, les ARA ou les inhibiteurs de la rénine) peuvent être réintroduits par étapes si la PAS est ≥130 mmHg. GROUPE TÉMOIN: Les patients reçoivent leurs médicaments antihypertenseurs habituels avant et après la chirurgie. La PAM du patient est maintenue à ≥60 mmHg de l'induction de l'anesthésie à la fin de l'intervention chirurgicale. CADRE: Recrutement à partir de 108 centres dans 22 pays entre 2018 à 2021. SUJETS: Des patients (~6 800) âgés de 45 ans et plus atteints d'athérosclérose, ou présentant un risque de l'être, devant subir une chirurgie non cardiaque et prenant des médicaments antihypertenseurs sur une base régulière. MESURES: Le principal critère d'évaluation de cette sous-étude est une IRA postopératoire définie par une hausse d'au moins 26,5 µmol/L (≥0,3 mg/dL) de la créatinine sérique dans les 48 heures suivant la randomisation ou d'au moins 50 % dans les 7 jours suivant la randomisation. MÉTHODOLOGIE: L'analyse primaire (par intention de traiter) examinera le risque relatif d'une IRA et l'intervalle de confiance à 95 % dans le groupe intervention par rapport au groupe témoin. Nous répéterons l'analyse primaire en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante (définie par un DFGe prérandomisation <60 ml/min/1,73 m2). RÉSULTATS: Les résultats de cette sous-étude seront analysés en 2022. LIMITES: Il n'est pas possible de procéder à l'insu des patients ou des prestataires de soins pour cette intervention; des mesures objectives seront toutefois utilisées pour évaluer l'IRA. CONCLUSION: Cette sous-étude fournira des estimations généralisables de l'effet d'une stratégie visant à éviter l'hypotension périopératoire sur le risque d'insuffisance rénale aiguë.

Predictors of Perioperative Vasoactive Drug Requirement During Retroperitoneal Adrenalectomy for Pheochromocytoma: A Retrospective Exploratory Study.

The aim of the present study was to test a hypothesis that baseline systemic vascular resistance index (SVRI) assessed by method of transpulmonary thermodilution predicts perioperative requirement for vasoactive drugs. The primary outcomes were: (1) peak vasoactive-inotropic score (VIS) and (2) peak dose of hypotensive drugs at any stage of surgery. The main exposure variable was baseline SVRI. Hemodynamics were retrospectively assessed by transpulmonary thermodilution in 50 adults who had undergone posterior retroperitoneal surgery for pheochromocytoma. Univariate linear regression analysis showed predictive value of SVRI on VIS [regression coefficient, 95% CI; 0.024 (0.005, 0.4), p=0.015]. Other significant factors were the history of peak diastolic pressure, baseline MAP, baseline betablocker therapy, and history of coronary artery disease (CAD). After adjustment of SVRI for the history of CAD, its prognostic value became non-significant [0.018 (0.008, 0.03), p=0.063 and 29.6 (19, 40.2), p=0.007 for SVRI and history of CAD, respectively]. Requirements of vasodilators were predicted by baseline adrenergic activity [0.37 (0.005, 0.74), p=0.047]. In conclusion, baseline SVRI is associated with perioperative requirement of vasopressor drugs, but history of CAD is a stronger prognostic factor for vasopressor support. Perioperative requirement in vasodilators is associated with baseline adrenergic activity.

Calcium administration In patients undergoing CardiAc suRgery under cardiopulmonary bypasS (ICARUS trial): Rationale and design of a randomized controlled trial.

INTRODUCTION: Weaning from cardiopulmonary bypass (CPB) is a critical step of any cardiac surgical procedure and often requires pharmacologic intervention. Calcium ions are pivotal elements for the excitation-contraction coupling process of cardiac myocytes. Thus, calcium administration might be helpful during weaning from CPB. METHODS: We describe a multicenter, placebo-controlled, double blind randomized clinical trial to assess the effect of calcium chloride on the need for inotropic support among adult patients during weaning from CPB. The experimental group (409 patients) will receive 15 mg/kg of calcium chloride. The control group (409 patients) will receive an equivalent volume of 0.9% sodium chloride. Both drugs will be administered intravenously as a bolus at the beginning of weaning from CPB. RESULTS: The primary outcome will be the need for inotropic support between termination of CPB and completion of surgery. Secondary outcomes will be: duration of inotropic support, vasoactive-inotropic score 30 min after transfer to intensive care unit and on postoperative day 1, plasma alpha-amylase on postoperative day 1, plasma Ca2+ concentration immediately before and 10-15 min after calcium chloride administration, non-fatal myocardial infarction, blood loss on postoperative day 1, need for transfusion of red blood cells, signs of myocardial ischemia on electrocardiogram after arrival to intensive care unit, all-cause mortality at 30 days or during hospital stay if this is longer than 30 days. DISCUSSION: This trial is designed to assess whether intravenous calcium chloride administration could reduce the need for inotropic support after cardiopulmonary bypass weaning among adults undergoing cardiac surgery.

Prevention of High Glucose-Mediated EMT by Inhibition of Hsp70 Chaperone.

Hyperglycemia may contribute to the progression of carcinomas by triggering epithelial-to-mesenchymal transition (EMT). Some proteostasis systems are involved in metastasis; in this paper, we sought to explore the mechanism of Hsp70 chaperone in EMT. We showed that knockdown of Hsp70 reduced cell migration capacity concomitantly with levels of mRNA of the Slug, Snail, and Twist markers of EMT, in colon cancer cells incubated in high glucose medium. Conversely, treatment of cells with Hsp70 inducer U-133 were found to elevate cell motility, along with the other EMT markers. To prove that inhibiting Hsp70 may reduce EMT efficiency, we treated cells with a CL-43 inhibitor of the HSF1 transcription factor, which lowered Hsp70 and HSF1 content in the control and induced EMT in carcinoma cells. Importantly, CL-43 reduced migration capacity, EMT-linked transcription factors, and increased content of epithelial marker E-cadherin in colon cancer cells of three lines, including one derived from a clinical sample. To prove that Hsp70 chaperone should be targeted when inhibiting the EMT pathway, we treated cancer cells with 2-phenylethynesulfonamide (PES) and demonstrated that the compound inhibited substrate-binding capacity of Hsp70. Furthermore, PES suppressed EMT features, cell motility, and expression of specific transcription factors. In conclusion, the Hsp70 chaperone machine efficiently protects mechanisms of the EMT, and the safe inhibitors of the chaperone are needed to hamper metastasis at its initial stage.

Impact of malnutrition on survival in adult patients after elective cardiac surgery: Long-term follow up data.

The data article refers to the paper titles "Impact of malnutrition on long-term survival in adult patients after elective cardiac surgery" [1]. The data refer to the analysis of the relationship between baseline malnutrition and long-term mortality after cardiac surgery. Baseline demographic, nutritional, and medical history data were collected for each enrolled patient. Baseline serum albumin and C-reactive (CRP) protein levels were also obtained. Surgical risk was assessed in accordance with the logistic EuroSCORE. Intraoperative data including cardiopulmonary bypass (CPB) time and postoperative characteristics, such as postoperative complications, number of days in the ICU, and hospitalization duration, were also collected. Data on nutritional status were collected using four nutritional screening tools: (1) malnutrition universal screening tool (MUST), (2) short nutritional assessment questionnaire (SNAQ), (3) mini-nutritional assessment (MNA), and (4) nutritional risk screening 2002 (NRS-2002). Both electronic medical records and phone interviews were used for survival data collection. ROC analysis was performed to analyze prognostic value of baseline and perioperative variables on long-term mortality. Univariate and multivariate logistic regression analysis of predictors of 3- and 8-year mortality were performed. Kaplan-Meyer curves, describing the impact of baseline and perioperative characteristics on 3- and 8-year survival were also performed.

Effects of malnutrition on long-term survival in adult patients after elective cardiac surgery.

OBJECTIVES: The aim of this study was to investigate the relationship between malnutrition and long-term survival in patients who underwent cardiopulmonary bypass (CPB). METHODS: This study analyzed the long-term survival data of a mixed cohort of 1187 cardiac patients previously enrolled in a prospective observational study of nutritional screening in cardiac surgery. Nutritional status was assessed using the Malnutrition Universal Screening Tool (MUST). The mean age of patients was 58.86 ± 10.07 y (95% confidence interval [CI], 58.2-59.4). The median time of follow-up was 73.4 mo (25th-75th percentiles, 18.3-101.3). RESULTS: In all, 449 patients (37.8%) were lost to follow-up after hospitalization. For the remaining participants, the overall 8-y survival was 68% (95% CI, 59-76) and 77% (95% CI, 73-80; log-rank, P = 0.12) in patients with and without malnutrition risk, respectively. Statistically significant differences in survival were found during the 3-y follow-up of patients with heart valve disease: 83% (95% CI, 74-92) with malnutrition versus 93% (95% CI, 90-96) without malnutrition (log-rank, P = 0.03). The final multivariate Cox regression model revealed logistic EuroSCORE (hazard ratio (HR), 1.337; 95% CI, 1.110-1.612), cardiopulmonary bypass time <110.5 min (HR 0.463, 95% CI 0.255-0.842), preoperative albumin (HR 0.799, 95% CI 0.691-0.924), and C-reactive protein (HR, 1.106; 95% CI, 1.018-1.202) as independent predictors of 3-y survival. CONCLUSION: Preoperative malnutrition is not associated with 8-y mortality in a mixed cardiac surgery cohort. However, it may be associated with worse 3-y outcomes in patients with heart valve disease.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey.

OBJECTIVES: To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. DESIGN: Multiple-choice survey on current practice of CPB weaning. SETTING: Online survey using the SurveyMonkey platform. PARTICIPANTS: Departments of cardiac anesthesiology worldwide. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). CONCLUSION: This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Lung Ultrasonography and Cardiac Surgery: A Narrative Review.

Pulmonary complications are common after cardiac surgery and are closely related to postoperative heart failure and adverse outcomes. Lung ultrasonography (LUS) is currently a widely accepted diagnostic approach with well-established methodology, nomenclature, accuracy, and prognostic value in numerous clinical conditions. The advantages of LUS are universally recognized and include bedside applicability, high diagnostic sensitivity and reproducibility, no radiation exposure, and low cost. However, routine perioperative ultrasonography during cardiac surgery generally is limited to echocardiography, diagnosis of pleural effusion, and as a diagnostic tool for postoperative complications in different organs, and few studies have explored the clinical outcomes in relation to LUS among cardiac patients. This narrative review presents the clinical evidence regarding LUS application in intensive care and during the perioperative period for cardiac surgery. Furthermore, this review describes the methodology and the diagnostic and prognostic accuracies of LUS. A summary of ongoing clinical trials evaluating the clinical outcomes related to LUS also is provided. Finally, this review discusses the rationale for upcoming clinical research regarding whether routine use of LUS can modify current intensive care practice and potentially affect the clinical outcomes after cardiac surgery.

The immunosuppressive effects of volatile versus intravenous anesthesia combined with epidural analgesia on kidney cancer: a pilot randomized controlled trial.

BACKGROUND: The aim of this study was to test the hypothesis that the use of inhalational anesthesia leads to higher suppression of the cell-mediated immunity compared to total intravenous anesthesia in patients undergoing kidney cancer surgery under combined low thoracic epidural analgesia and general anesthesia. METHODS: Patients were randomly allocated to either propofol-based (intravenous anesthetic) or sevoflurane-based (volatile anesthetic) anesthesia group with 10 patients in each group, along with epidural analgesia in both groups. Amounts of natural killer (NK) cells, total T lymphocytes, and T lymphocyte subpopulations in the blood samples collected from the patients before surgery, at the end of the surgery and postoperative days 1, 3 and 7 were determined by flow cytometric analysis. The NK cell count served as the primary endpoint of the study, whereas the total T lymphocyte count and cell counts for T lymphocyte subpopulations were used as the secondary endpoint. RESULTS: Our study showed that there were no significant differences in the amount of NK cells, total T lymphocytes, regulatory T cells, and T-helper cells, cytotoxic T lymphocytes, and their subpopulations between the propofol- and sevoflurane-based anesthesia groups when the anesthesia was administered in combination with epidural analgesia. CONCLUSIONS: The results of this pilot study did not support the hypothesis that the use of inhalational anesthesia leads to higher suppression of the cell-mediated immunity than that of total intravenous anesthesia in patients undergoing kidney cancer surgery under combined low thoracic epidural analgesia and general anesthesia.

Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial).

OBJECTIVE: To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. DESIGN: Randomized, placebo-controlled, pilot feasibility trial. SETTING: Cardiac surgery department of a tertiary hospital. PARTICIPANTS: Forty patients undergoing combined valvular and coronary artery bypass surgery. INTERVENTIONS: Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. MEASUREMENTS AND MAIN RESULTS: The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). CONCLUSIONS: A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

Study of Data Transfer in a Heterogeneous LoRa-Satellite Network for the Internet of Remote Things.

In the absence of traditional communication infrastructures, the choice of available technologies for building data collection and control systems in remote areas is very limited. This paper reviews and analyzes protocols and technologies for transferring Internet of Things (IoT) data and presents an architecture for a hybrid IoT-satellite network, which includes a long range (LoRa) low power wide area network (LPWAN) terrestrial network for data collection and an Iridium satellite system for backhaul connectivity. Simulation modelling, together with a specialized experimental stand, allowed us to study the applicability of different methods of information presentation for the case of transmitting IoT data over low-speed satellite communication channels. We proposed a data encoding and packaging scheme called GDEP (Gateway Data Encoding and Packaging). It is based on the combination of data format conversion at the connection points of a heterogeneous network and message packaging. GDEP enabled the reduction of the number of utilized Short Burst Data (SBD) containers and the overall transmitted data size by almost five times.

History and Current Status of Cardiac Anesthesiology in Russia.

Anesthesiology, the branch of medicine concerning anesthesia and management of the vital functions of patients undergoing surgery, has played an important role in the development of cardiac surgery. In the middle of the last century, medical professionals had little experience in the treatment of congenital and acquired heart diseases. Progress of cardiac anesthesiology in Russia, as well as in countries across the globe, was due to requests to increase the safety of surgical procedures and to improve survival rates for the increasing number of patients with complex heart diseases. The development of cardiac surgery and anesthesiology in Russia evolved in 2 directions simultaneously in the mid-1950s. Some surgeons widely accepted the use of perfusionless hypothermia (hypothermia caused by surface cooling without perfusion); others were in favor of cardiopulmonary bypass technology. This review focuses on major historic milestones of cardiac anesthesiology in Russia, including its current status and the major problems it faces today.