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Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients.This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery.On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36-55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28-75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (91 %) than postoperatively (46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine.Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).

BACKGROUND The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown. OBJECTIVE To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation. DESIGN Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818). SETTING Eighteen sites between February 2011 and February 2021. PATIENTS Patients with isolated subsegmental pulmonary embolism. INTERVENTION At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy. MEASUREMENTS The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period. RESULTS Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism. LIMITATION The study was restricted to patients with low-risk subsegmental pulmonary embolism. CONCLUSION Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism. PRIMARY FUNDING SOURCE Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.

Objective To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer. Design Multicentre, open label, randomised controlled trial. Settings 12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020. Participants 614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection. Interventions Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only. Main outcome measures Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population. Results The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person ( Conclusions Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups. Trial registration ClinicalTrials.gov NCT01455831 .

Study of Caffeine in Patients with Supraventricular TachycardiaIntroduction Patients with cardiac arrhythmias are generally instructed to avoid caffeine intake. A comprehensive evaluation of the electrophysiological effects of caffeine on atrial and ventricular tissues in humans has not previously been performed. Methods and Results Eighty patients (31 men, mean age 49 ± 14 years) with symptomatic supraventricular tachycardia (SVT) undergoing an electrophysiologic study (EPS) prior to catheter ablation were randomized to receive oral caffeine or placebo. Caffeine at a dosage of 5 mg/kg (moderate intake) or placebo tablets were administered orally at a mean time of 57 ± 13 minutes prior to the EPS. The median (IQR) caffeine level in patients receiving caffeine was 7.4 μg/mL (4.7–8.7), as compared with 0.15 (0.00–0.61) in patients receiving placebo, P

Patients with cardiac arrhythmias are generally instructed to avoid caffeine intake. A comprehensive evaluation of the electrophysiological effects of caffeine on atrial and ventricular tissues in humans has not previously been performed.Eighty patients (31 men, mean age 49 ± 14 years) with symptomatic supraventricular tachycardia (SVT) undergoing an electrophysiologic study (EPS) prior to catheter ablation were randomized to receive oral caffeine or placebo. Caffeine at a dosage of 5 mg/kg (moderate intake) or placebo tablets were administered orally at a mean time of 57 ± 13 minutes prior to the EPS. The median (IQR) caffeine level in patients receiving caffeine was 7.4 μg/mL (4.7-8.7), as compared with 0.15 (0.00-0.61) in patients receiving placebo, P 0.0001. Caffeine was associated with a significant increase in resting systolic and diastolic blood pressures as compared with placebo, while the resting heart rate was not significantly different between both groups. Caffeine was not associated with significant effects on the effective refractory period of the atrium or ventricle, as well as on AV node conduction. SVT was induced in all but 3 patients; there was no significant difference between groups receiving placebo or caffeine on SVT inducibility or the cycle length of induced tachycardias.Caffeine, at moderate intake, was associated with significant increases in systolic and diastolic blood pressures, but had no evidence of a significant effect on cardiac conduction and refractoriness. Furthermore, no effect of caffeine on SVT induction or more rapid rates of induced tachycardias was found.