IMPORTANCE Excessive bleeding is a common complication of cardiac surgery. An important cause of bleeding is acquired hypofibrinogenemia (fibrinogen level <1.5-2.0 g/L), for which guidelines recommend fibrinogen replacement with cryoprecipitate or fibrinogen concentrate. The 2 products have important differences, but comparative clinical data are lacking.OBJECTIVE To determine if fibrinogen concentrate is noninferior to cryoprecipitate for treatment of bleeding related to hypofibrinogenemia after cardiac surgery. DESIGN, SETTING, AND PARTICIPANTSRandomized clinical trial at 11 Canadian hospitals enrolling adult patients experiencing clinically significant bleeding and hypofibrinogenemia after cardiac surgery (from February 10, 2017, to November 1, 2018). Final 28-day follow-up visit was completed on November 28, 2018.INTERVENTIONS Fibrinogen concentrate (4 g; n = 415) or cryoprecipitate (10 units; n = 412) for each ordered dose within 24 hours after cardiopulmonary bypass. MAIN OUTCOMES AND MEASURESPrimary outcome was blood components (red blood cells, platelets, plasma) administered during 24 hours post bypass. A 2-sample, 1-sided test for the ratio of the mean number of units was conducted to evaluate noninferiority (threshold for noninferiority ratio, <1.2). RESULTSOf 827 randomized patients, 735 (372 fibrinogen concentrate, 363 cryoprecipitate) were treated and included in the primary analysis (median age, 64 [interquartile range, 53-72] years; 30% women; 72% underwent complex operations; 95% moderate to severe bleeding; and pretreatment fibrinogen level, 1.6 [interquartile range, 1.3-1.9] g/L). The trial met the a priori stopping criterion for noninferiority at the interim analysis after 827 of planned 1200 patients were randomized. Mean 24-hour postbypass allogeneic transfusions were 16.3 (95% CI, 14.9 to 17.8) units in the fibrinogen concentrate group and 17.0 (95% CI, 15.6 to 18.6) units in the cryoprecipitate group (ratio, 0.96 [1-sided 97.5% CI, −ϱ to 1.09; P < .001 for noninferiority] [2-sided 95% CI, 0.84 to 1.09; P = .50 for superiority]). Thromboembolic events occurred in 26 patients (7.0%) in the fibrinogen concentrate group and 35 patients (9.6%) in the cryoprecipitate group. CONCLUSIONS AND RELEVANCEIn patients undergoing cardiac surgery who develop clinically significant bleeding and hypofibrinogenemia after cardiopulmonary bypass, fibrinogen concentrate is noninferior to cryoprecipitate with regard to number of blood components transfused in a 24-hour period post bypass. Use of fibrinogen concentrate may be considered for management of bleeding in patients with acquired hypofibrinogenemia in cardiac surgery.

Records of 487 patients in long-term follow-up after Ro resection of colorectal carcinomas between January 1, 1980 and December 31, 1989 were analyzed. Every patient underwent regular examinations according to a defined schedule after curative resection of colorectal carcinoma. The date of evaluation was June 31, 1991. During a median observation time of 48 months (range, 15-132 months), tumor recurrence was observed in 149 patients (30.6 percent), with 56.4 percent of these suffering from tumor-associated symptoms. As the primary manifestation of tumor recurrence, only distant metastases (DM) were found in 76 patients (51 percent), only local recurrence (LR) in 46 patients (30.9 percent), and both DM and LR in 27 patients (18.1 percent). Patients with rectal carcinoma developed LR more frequently (P < 0.05) (19.5 percent) than patients with colon carcinoma (11.8 percent). The probability of developing distant metastases was not different (P < 0.05) for colon or rectal carcinoma but depended on primary tumor stage (P < 0.05). Only 36 patients (24.2 percent) with recurrence could undergo further curative resection. Fifty patients (33.5 percent) were given palliative therapy, and 63 patients (42.3 percent) were given no oncologic treatment. Only 9 of the 36 patients (6 percent of all recurrence patients) undergoing Ro resection were free of tumor for more than two years. In no case was a third Ro resection possible. The survival time of these patients was increased significantly after Ro resection of tumor recurrence (P = 0.03). Our study suggests that only a very few patients may live longer as a result of regular follow-up programs after curative resection for colorectal carcinoma.

Key Points Question Can 4-factor prothrombin complex concentrate (PCC) be used as a substitute for frozen plasma (FP) for treatment of bleeding related to coagulation factor deficiency in cardiac surgery? Findings In this pilot trial, 101 adult patients were successfully randomized to receive PCC or FP for bleeding during cardiac surgery. In exploratory analyses, the PCC group had significantly lower chest tube blood loss and received fewer allogeneic blood transfusions, whereas the number of thromboembolic events was similar. Meaning Four-factor PCC may be a suitable alternative to FP for management of cardiac surgery–associated coagulopathy, pending assessment by adequately powered multicenter trials.

Use of the stapling technique facilitates the performance of anastomoses, particularly in regions with difficult anatomy. The rate of local complications is low, and protective colostomy can thus be dispensed with in most cases

IntroductionAcute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.Methods and analysisThe factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.Ethics and disseminationThe study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.Trial registration numberNCT04534751, pre results.