OBJECTIVE:To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock.
DESIGN:Single center, ...randomized, double-blind controlled trial.
SETTING:Teaching hospital.
PATIENTS:Adult cancer patients with septic shock in the first 6 hours of ICU admission.
INTERVENTIONS:Patients were randomized to the liberal (hemoglobin threshold, < 9g/dL) or to the restrictive strategy (hemoglobin threshold, < 7g/dL) of RBC transfusion during ICU stay.
MEASUREMENTS AND MAIN RESULTS:Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 0–3 vs 0 0–2 unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03).
CONCLUSIONS:We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.
Objective Although hyperlactatemia after cardiac surgery is common, the implications of raised levels remain controversial. The aim of this study was to evaluate whether high lactate levels after ...cardiac surgery are predictors of major complications including mortality. Patients and Methods This was a substudy of TRACS (Transfusion Requirements After Cardiac Surgery), which was designed as a prospective, randomized, controlled trial evaluating the effects of a transfusion strategy on morbidity and mortality. Results Of the 502 patients enrolled, 52 (10%) had at least 1 major complication. Patients with complications were older, had a higher EuroSCORE, lower left ventricular ejection fraction, lower preoperative hemoglobin, a higher prevalence of renal disease, and received more blood transfusions than the group without complications. Lactate levels were higher in the group with complications at the end of surgery (3.6 mmol/L 2.8-5.1 vs 3.3 mmol/L 2.2-4.8; P = .018), immediately after intensive care unit (ICU) admission (0 hour) (4.4 mmol/L 3.1-8.4 vs 4 mmol/L 2.6-6.4; P = .048); 6 hours (4 mmol/L 2.7-5.8 vs 2.6 mmol/L 2-3.6, P < .001), and 12 hours after admission (2.3 mmol/L 1.8-3.2 vs 1.7 mmol/L 1.3-2; P < .001). In a multivariate model, higher age (odds ratio OR, 1.048, 95% confidence interval CI, 1.011-1.086; P = .010), left ventricular ejection fraction (LVEF) lower than 40% (OR, 3.03; 95% CI, 1.200-7.510; P = .019 compared with LVEF of 40%-59%; OR, 3.571; 95% CI, 1.503-8.196; P = .004 compared with LVEF higher than 60%), higher EuroSCORE (OR, 1.138; 95% CI; 1.007-1.285; P = .038), red blood cell transfusion (OR, 1.230; 95% CI, 1.086-1.393; P = .001), and lactate levels 6 hours after ICU admission (OR, 3.28, 95% CI; 1.61-6.69; P = .001) are predictors of major complications. Conclusions Hyperlactatemia 6 hours after ICU admission is an independent risk factor for worse outcomes in adult patients after cardiac surgery.
CONTEXT Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding ...optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. OBJECTIVE To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. DESIGN, SETTING, AND PATIENTS The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n = 502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. INTERVENTION Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit ≥30%) or to a restrictive strategy (hematocrit ≥24%). MAIN OUTCOME MEASURE Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at −8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). RESULTS Hemoglobin concentrations were maintained at a mean of 10.5 g/dL (95% confidence interval CI, 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.0-9.2) in the restrictive-strategy group (P < .001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P < .001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% 95% CI, −6% to 4%; P = .85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 95% CI, 1.1-1.4; P = .002). CONCLUSION Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01021631
Objectives Acute acquired hypofibrinogenemia in children undergoing cardiac surgery is a major concern because it often results in perioperative bleeding and high rates of allogeneic blood ...transfusion. Fibrinogen concentrate has been proposed as an alternative to cryoprecipitate (the gold standard therapy), with minimal infectious and immunologic risks. Our objective was to investigate the efficacy and safety of fibrinogen concentrate in children undergoing cardiac surgery. Methods In this randomized pilot study, patients were allocated to receive fibrinogen concentrate (60 mg/kg) or cryoprecipitate (10 mL/kg) if bleeding was associated with fibrinogen levels <1 g/dL after cardiopulmonary bypass weaning. The primary outcome was postoperative blood losses during the 48 hours after surgery. Results A total of 63 patients were included in the study, 30 in the fibrinogen concentrate group and 33 in the cryoprecipitate group. The median 48-hour blood loss was not significantly different between the 2 groups (320 mL interquartile range, 157-750 vs 410 mL interquartile range, 215-510, respectively; P = .672). After treatment, plasma fibrinogen concentration increased similarly following administration of both products. There were no differences in allogeneic blood transfusion after intervention treatment. Conclusions A large trial comparing fibrinogen concentrate and cryoprecipitate in the management of children with acute acquired hypofibrinogenemia during heart surgery is feasible. The preliminary results of our study showed that the use of fibrinogen concentrate was as efficient and safe as cryoprecipitate in the management of bleeding children undergoing cardiac surgery.
Patients undergoing abdominal surgery for solid tumours frequently develop major postoperative complications, which negatively affect quality of life, costs of care and survival. Few studies have ...identified the determinants of perioperative complications in this group.
We performed a prospective observational study including all patients (age > 18) undergoing abdominal surgery for cancer at a single institution between June 2011 and August 2013. Patients undergoing emergency surgery, palliative procedures, or participating in other studies were excluded. Primary outcome was a composite of 30-day all-cause mortality and infectious, cardiovascular, respiratory, neurologic, renal and surgical complications. Univariate and multiple logistic regression analyses were performed to identify predictive factors for major perioperative adverse events.
Of a total 308 included patients, 106 (34.4%) developed a major complication during the 30-day follow-up period. Independent predictors of postoperative major complications were: age (odds ratio OR 1.03 95% CI 1.01-1.06, p = 0.012 per year), ASA (American Society of Anesthesiologists) physical status greater than or equal to 3 (OR 2.61 95% CI 1.33-5.17, p = 0.003), a preoperative haemoglobin level lower than 12 g/dL (OR 2.13 95% CI 1.21-4.07, p = 0.014), intraoperative use of colloids (OR 1.89, 95% CI 1.03-4.07, p = 0.047), total amount of intravenous fluids (OR 1.22 95% CI 0.98-1.59, p = 0.106 per litre), intraoperative blood losses greater than 500 mL (2.07 95% CI 1.00-4.31, p = 0.043), and hypotension needing vasopressor support (OR 4.68 95% CI 1.55-27.72, p = 0.004). The model had good discrimination with the area under the ROC curve being 0.80 (95% CI 0.75-0.84, p < 0.001).
Our findings suggest that a perioperative strategy aimed at reducing perioperative complications in cancer surgery should include treatment of preoperative anaemia and an optimal fluid strategy, avoiding fluid overload and intraoperative use of colloids.
Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA ...has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated
in vivo
in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected
ex vivo
by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.
OBJECTIVES:To evaluate the effects of goal-directed therapy on outcomes in high-risk patients undergoing cardiac surgery.
DESIGN:A prospective randomized controlled trial and an updated metaanalysis ...of randomized trials published from inception up to May 1, 2015.
SETTING:Surgical ICU within a tertiary referral university-affiliated teaching hospital.
PATIENTS:One hundred twenty-six high-risk patients undergoing coronary artery bypass surgery or valve repair.
INTERVENTIONS:Patients were randomized to a cardiac output–guided hemodynamic therapy algorithm (goal-directed therapy group, n = 62) or to usual care (n = 64). In the goal-directed therapy arm, a cardiac index of greater than 3 L/min/m was targeted with IV fluids, inotropes, and RBC transfusion starting from cardiopulmonary bypass and ending 8 hours after arrival to the ICU.
MEASUREMENTS AND MAIN RESULTS:The primary outcome was a composite endpoint of 30-day mortality and major postoperative complications. Patients from the goal-directed therapy group received a greater median (interquartile range) volume of IV fluids than the usual care group (1,000 625–1,500 vs 500 500–1,000 mL; p < 0.001, with no differences in the administration of either inotropes or RBC transfusions. The primary outcome was reduced in the goal-directed therapy group (27.4% vs 45.3%; p = 0.037). The goal-directed therapy group had a lower occurrence rate of infection (12.9% vs 29.7%; p = 0.002) and low cardiac output syndrome (6.5% vs 26.6%; p = 0.002). We also observed lower ICU cumulative dosage of dobutamine (12 vs 19 mg/kg; p = 0.003) and a shorter ICU (3 3–4 vs 5 4–7 d; p < 0.001) and hospital length of stay (9 8–16 vs 12 9–22 d; p = 0.049) in the goal-directed therapy compared with the usual care group. There were no differences in 30-day mortality rates (4.8% vs 9.4%, respectively; p = 0.492). The metaanalysis identified six trials and showed that, when compared with standard treatment, goal-directed therapy reduced the overall rate of complications (goal-directed therapy, 47/410 11% vs usual care, 92/415 22%; odds ratio, 0.40 95% CI, 0.26–0.63; p < 0.0001) and decreased the hospital length of stay (mean difference, –5.44 d; 95% CI, –9.28 to –1.60; p = 0.006) with no difference in postoperative mortality9 of 410 (2.2%) versus 15 of 415 (3.6%), odds ratio, 0.61 (95% CI, 0.26–1.47), and p = 0.27.
CONCLUSIONS:Goal-directed therapy using fluids, inotropes, and blood transfusion reduced 30-day major complications in high-risk patients undergoing cardiac surgery.
The rapid spread of SARS-CoV-2 caused a global pandemic. Due to the lack of treatment and vaccines, safety strategies must be found to stop the virus dissemination. The objective of this study was to ...evaluate the virucidal activity of ozonated water, a powerful oxidizing agent, against SARS-CoV-2. A special faucet was the source of ozonated water at a low concentration (0.2-0.8 ppm). At this concentration, tests with SARS-Cov-2 in Vero CCL81 lineage showed two log
10
reduction in virus infectivity upon 1 min exposure to ozonated water, in comparison to controls. It shows the potential as an efficient and rapid alternative for controlling viral spread in hospitals and other environments.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and ...prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.
•Dynamic cerebral blood flow autoregulation is impaired on the first day following cardiac surgery.•Autoregulation index before and after surgery is predictive of post-operative delirium.•Patients ...with impaired dynamic cerebral autoregulation at 24 h and 7 days after surgery had a higher incidence of delirium.
We investigated the potential association of cerebral autoregulation (CA) with postoperative delirium (PD), a common complication of cardiac surgery with cardiopulmonary bypass (CPB).
In patients undergoing coronary artery bypass graft (CABG) surgery with CPB, cerebral blood flow velocity (CBFV) and blood pressure (BP) were continuously recorded during 5-min preoperatively (T1), after 24 h (T2), and 7 days after procedure (T3). Prospective multivariate logistic regression analysis was performed to determine the independent risk factors of PD. Autoregulation index (ARI) was calculated from the CBFV response to a step change in BP derived by transfer function analysis.
In 67 patients, mean age 64.3 ± 9.5 years, CA was depressed at T2 as shown by values of ARI (3.9 ± 1.7), compared to T1 (5.6 ± 1.7) and T3 (5.5 ± 1.8) (p < 0.001). Impaired CA was found in 37 (55%) patients at T2 and in 7 patients (20%) at T3. Lower ARI at T1 and T2 were predictors of PD (p = 0.003).
Dynamic CA was impaired after CABG surgery with CPB and was a significant independent risk factor of PD.
Assessment of CA before and after surgery could have considerable potential for early identification of patients at risk of PD, thus reducing poor outcomes and length of stay.
Clinical trials registration: www.clinicaltrials.gov (NCT02143544, April 30, 2014).
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