Explore the vast range of titles available.

Haematoma expansion is a major cause of mortality in intracranial haemorrhage related to vitamin K antagonists (VKA-ICH). Normalisation of the international normalised ratio (INR) is recommended, but optimum haemostatic management is controversial. We assessed the safety and efficacy of fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with VKA-ICH. We did an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Patients aged at least 18 years with VKA-ICH who presented within 12 h after symptom onset with an INR of at least 2·0 were randomly assigned (1:1) by numbered sealed envelopes to 20 mL/kg of intravenous FFP or 30 IU/kg of intravenous four-factor PCC within 1 h after initial cerebral CT scan. The primary endpoint was the proportion of patients with INR 1·2 or lower within 3 h of treatment initiation. Masking of treatment was not possible, but the primary analysis was observer masked. Analyses were done using a treated-as-randomised approach. This trial is registered with EudraCT, number 2008-005653-37, and ClinicalTrials.gov, number NCT00928915. Between Aug 7, 2009, and Jan 9, 2015, 54 patients were randomly assigned (26 to FFP and 28 to PCC) and 50 received study drug (23 FFP and 27 PCC). The trial was terminated on Feb 6, 2015, after inclusion of 50 patients after a safety analysis because of safety concerns. Two (9%) of 23 patients in the FFP group versus 18 (67%) of 27 in the PCC group reached the primary endpoint (adjusted odds ratio 30·6, 95% CI 4·7–197·9; p=0·0003). 13 patients died: eight (35%) of 23 in the FFP group (five from haematoma expansion, all occurring within 48 h after symptom onset) and five (19%) of 27 in the PCC group (none from haematoma expansion), the first of which occurred on day 5 after start of treatment. Three thromboembolic events occurred within 3 days (one in the FFP group and two in the PCC group), and six after day 12 (one and five). 43 serious adverse events (20 in the FFP group and 23 in the PCC group) occurred in 26 patients. Six serious adverse events were judged to be FFP related (four cases of haematoma expansion, one anaphylactic reaction, and one ischaemic stroke) and two PCC related (ischaemic stroke and pulmonary embolism). In patients with VKA-related intracranial hemorrhage, four-factor PCC might be superior to FFP with respect to normalising the INR, and faster INR normalisation seemed to be associated with smaller haematoma expansion. Although an effect of PCC on clinical outcomes remains to be shown, our data favour the use of PCC over FFP in intracranial haemorrhage related to VKA. Octapharma.

•CRP-STEMI is an investigator-initiated, randomized, open-label, multicenter trial.•A total of 202 STEMI patients with elevated CRP post PCI enrolled at 5 centers.•The intervention group receives 3 sessions of selective CRP apheresis post-PCI.•The primary endpoint is infarct size assessed by CMR at 5 ± 2 days after PCI.•CRP-STEMI is the first randomized trial to evaluate CRP apheresis in STEMI. Despite the effectiveness of primary percutaneous coronary intervention (PCI) in treating ST-elevation myocardial infarction (STEMI), myocardial salvage is often incomplete, resulting in large infarct size and an increased risk of heart failure and mortality. Inflammation is involved in this process, with C-reactive protein (CRP) potentially contributing to infarct expansion. Whether selective CRP apheresis in addition to standard care can reduce infarct size in STEMI remains to be determined. Selective C-reactive protein apheresis in ST-elevation myocardial infarction (CRP-STEMI) is an investigator-initiated, randomized, open-label (outcome assessor blinded), multicenter trial investigating whether selective CRP apheresis using the PentraSorb-CRP system, in addition to standard care, can reduce infarct size in STEMI patients undergoing PCI within 12 hours of symptom onset. The trial will enroll 202 patients at 5 tertiary care centers in Austria and Germany, randomized 1:1 to either the intervention group (standard care + CRP apheresis) or the control group (standard care). In the intervention group, CRP apheresis will be performed on days 1, 2, and 3 post-PCI. The primary endpoint is infarct size as assessed by late gadolinium enhanced cardiac magnetic resonance at 5 ± 2 days after PCI. CRP-STEMI is the first randomized trial to investigate whether selective CRP apheresis, as an adjunct to standard care, can effectively reduce infarct size in acute STEMI patients. CRP-STEMI, NCT04939805, is registered at https://clinicaltrials.gov/study/NCT04939805. [Display omitted] This graphical abstract summarizes the design of the CRP-STEMI trial, a multicenter, investigator-initiated, randomized, open-label study. A total of 202 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) will be included, provided that high-sensitivity C-reactive protein (CRP) levels will be ≥7 mg/L within 6 to 16 hours post-PCI. Patients will be randomized 1:1 to receive either standard care alone (control group) or standard care + selective CRP apheresis on days 1, 2, and 3 (intervention group). The primary endpoint is infarct size, measured by cardiac magnetic resonance imaging (CMR) at 5 ± 2 days post-PCI. Created with Biorender.

Thrombin generation (TG) is reduced after cardiac surgery using cardiopulmonary bypass (CPB), contributing to coagulopathy and bleeding. Plasma transfusion or four-factor prothrombin complex concentrate (PCC) are commonly used to treat coagulopathic bleeding after CPB without knowledge of how each may restore TG. To determine the effect of PCC infusion on restoration of thrombin generation compared with plasma transfusion, we performed a laboratory-based secondary analysis of a randomized, controlled trial of adult patients undergoing cardiac surgery to assess efficacy and safety of 4 F-PCC versus plasma for treatment of perioperative coagulopathic bleeding after CPB. Participants were randomized to receive either PCC (15 IU/kg) or plasma (10–15 ml/kg) after separation from CPB. Participant blood samples were obtained at pre-specified serial timepoints, with laboratory assays for TG and factor levels subsequently performed. The primary outcome was change in thrombin generation (TG) parameters after each randomized treatment through postoperative day 5. Secondary outcomes included serially derived clotting factor levels. Of 100 randomized participants, 99 were included in this laboratory analysis (PCC group, N  = 51; plasma group, N  = 48). After treatment, participants in the PCC group compared with those in the plasma group showed higher endogenous thrombin potential (ETP, Median, Interquartile range, IQR: 688 [371–1069] vs. 1088 [550–1691] nM minutes, P  = 0.01), a greater increase din ETP ( P  = 0.002) and peak TG ( P  = 0.01) in the timepoints between heparin reversal and after treatment administration. Both groups demonstrated similar values in all TG assays by postoperative day 1 ( P  > 0.05). The PCC group also demonstrated higher levels of proteins C, S, and Factors II, VII, IX and X, early after treatment ( P  < 0.001 for all comparisons). Antithrombin levels were initially higher in the plasma group after treatment (Median, IQR: 66% [61-71%] vs. 56% [51-65%], P  = 0.002) but differences did not persist beyond postoperative day 3. In this laboratory analysis from a recent randomized trial in adult cardiac surgery, PCC administration restored thrombin generation more rapidly than plasma in the early postoperative period without laboratory evidence of hypercoagulability. ClinicalTrials.gov identifier: NCT02557672 [1]. Key points Question How does prothrombin complex concentrate (PCC) compare with plasma to restore thrombin generation (TG) in patients with coagulopathic bleeding after cardiopulmonary bypass? Findings In this subanalysis of a randomized clinical trial in 99 adult cardiac surgical patients, TG was restored more rapidly in the PCC group compared with the plasma group after treatment: endogenous thrombin potential (PCC, 688 [371–1069] vs. plasma, 1088 [550–1691], P  = 0.01nM minutes). Both groups displayed similar post-treatment TG by postoperative day one. Meaning These results support PCC administration to restore TG while avoiding acquired hypercoagulability in the early period after cardiac surgery.

Introduction Much controversy exists on the effect of a fresh frozen plasma (FFP) transfusion on systemic inflammation and endothelial damage. Adverse effects of FFP have been well described, including acute lung injury. However, it is also suggested that a higher amount of FFP decreases mortality in trauma patients requiring a massive transfusion. Furthermore, FFP has an endothelial stabilizing effect in experimental models. We investigated the effect of fresh frozen plasma transfusion on systemic inflammation and endothelial condition. Methods A prospective predefined substudy of a randomized trial in coagulopathic non-bleeding critically ill patients receiving a prophylactic transfusion of FFP (12 ml/kg) prior to an invasive procedure. Levels of inflammatory cytokines and markers of endothelial condition were measured in paired samples of 33 patients before and after transfusion. The statistical tests used were paired t test or the Wilcoxon signed-rank test. Results At baseline, systemic cytokine levels were mildly elevated in critically ill patients. FFP transfusion resulted in a decrease of levels of TNF-α (from 11.3 to 2.3 pg/ml, P  = 0.01). Other cytokines were not affected. FFP also resulted in a decrease in systemic syndecan-1 levels (from 675 to 565 pg/ml, P  = 0.01) and a decrease in factor VIII levels (from 246 to 246%, P <0.01), suggestive of an improved endothelial condition. This was associated with an increase in ADAMTS13 levels (from 24 to 32%, P <0.01) and a concomitant decrease in von Willebrand factor (vWF) levels (from 474 to 423%, P <0.01). Conclusions A fixed dose of FFP transfusion in critically ill patients decreases syndecan-1 and factor VIII levels, suggesting a stabilized endothelial condition, possibly by increasing ADAMTS13, which is capable of cleaving vWF. Trial registrations Trialregister.nl NTR2262 , registered 26 March 2010 and Clinicaltrials.gov NCT01143909 , registered 14 June 2010.

Objectives Activated granulocytes and monocytes may contribute to the pathogenesis of Crohn's disease (CD). In small, uncontrolled studies, granulocyte/monocyte apheresis (GMA) has shown promise in treating CD. We conducted a randomised, double-blind study to compare GMA with a sham procedure in patients with moderate to severe CD. Design Patients with active CD as defined by a Crohn's Disease Activity Index (CDAI) of 220–450 were randomly allocated in a 2:1 ratio to treatment with GMA using the Adacolumn Apheresis System (JIMRO, Takasaki, Japan) or sham apheresis. Ten apheresis sessions were scheduled over a 9-week period, and efficacy was evaluated at week 12. The primary end point was the proportion of patients achieving clinical remission (CDAI score ≤150 without use of prohibited drugs). Results Clinical remission was achieved by 17.8% of patients in the GMA group (n=157) compared with 19.2% of those in the sham control group (n=78) (absolute difference −1.4% (95% CI−12.8% to 8.5%), p=0.858). Clinical response (defined as a ≥100-point decrease in CDAI) was achieved by 28.0% and 26.9% of patients in the GMA and sham groups, respectively (p=1.000). The two treatments produced similar changes from baseline in CDAI and quality of life, as well as in disease severity assessed endoscopically. The incidence and types of adverse events did not differ between groups. Conclusions GMA was well tolerated, but this study did not demonstrate its effectiveness over a sham procedure in inducing clinical remission or response in patients with moderate to severe CD. Clinical trial registration number Clinical Trials.gov identifier NCT00162942.

Background Plasma transfusion is recommended as an initial intervention in most major haemorrhage protocols for trauma resuscitation. With availability of newer blood components, therapeutic agents and investigations for coagulopathy, the marginal benefits of high ratios of plasma to red cells is uncertain. The aim of this study was to report the association of high ratios of plasma: red cells and 28-day mortality in patients with major trauma. Methods The PATCH-Trauma trial enrolled critically bleeding patients at high risk of trauma induced coagulopathy and randomised them to receive prehospital tranexamic acid or placebo. The sub-group of patients who were managed with massive transfusions in hospital (> 4 units of red cells in first 4 h) were included for this post-hoc analysis. Associations of high ratios of plasma (more than 1 unit of plasma for every 2 units of red cells) and 28-day mortality were reported using multivariable logistic regression analysis after adjustment for potential confounders including age, neurological injury, injury severity, coagulopathy and administration of platelets, fibrinogen concentrates, cryoprecipitate and tranexamic acid. Results Among 1310 patients enrolled in the PATCH-trauma trial, 372 patients were included for this analysis; 213 (57.3%) received high ratios of plasma: red cells and 116 (31.4%) deaths were recorded at 28 days. High ratios of plasma: red cells were associated with lower mortality (adjusted odds ratio; aOR 0.50; 95%CI: 0.26–0.96). Older age (aOR 1.02; 95%CI: 1.01–1.03), initial Glasgow Coma Scale 3–8 (aOR 6.57; 95%CI: 2.92–14.80) and trauma induced coagulopathy (aOR 5.64; 95%CI: 2.87–11.1) on hospital arrival were associated with higher mortality. Conclusions Among patients with critical bleeding managed with massive transfusions, high ratios of plasma: red cells were associated with lower mortality, after controlling for potential confounders. Ongoing provision of early plasma for management of critical bleeding is indicated with consideration to prehospital plasma. Registration ClinicalTrials.gov number, NCT02187120 (Registered 09 July 2014).

The debate on replacing coagulation factors and its effect on the final outcome of the patients with acute traumatic coagulopathy (ATC) in need of transfusion is still ongoing. Therefore, the present study is designed with the aim of comparing the outcome of patients with acute traumatic coagulopathies receiving fibrinogen and fresh frozen plasma (FFP). In this quasi-experimental randomized controlled study, patients with severe blunt trauma (ISS>16) and in need of packed cells transfusion were divided into 3 groups of receiving fibrinogen, receiving FFP, and control, and their final outcome was compared. 90 patients with the mean age of 33.16±16.32years were randomly allocated to one of the 3 study groups (82.2% male). The 3 groups were similar regarding baseline characteristics. Patients receiving fibrinogen needed significantly less packed cells (p=0.044) and intravenous fluid in the initial 24h of hospitalization (p=0.022). In addition, mortality rate (p=0.029), need for admission to intensive care unit (p=0.020) and duration of hospitalization (p=0.045) were also lower in the group receiving fibrinogen. The number of sepsis cases in patients receiving fibrinogen and control group was lower than those who received FFP (p=0.001). The number of multiple organ failure cases in patients receiving fibrinogen was about one fourth of the other 2 groups (p=0.106), and a fewer number of them needed mechanical ventilation (p=0.191). No case of venous thrombosis was detected in any of the 3 groups. Multiple trauma patients in need of transfusion who received fibrinogen along with packed cells had significantly better outcomes regarding mortality, sepsis, need for admission to the intensive care unit, need for receiving packed cells, need for receiving intravenous fluids in the initial 24h, and duration of hospitalization.

Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Non–vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement.

Age-specific population forecasts for small areas or subnational regions are a valuable tool for local governments. However, typical population projection methods based on the cohort-component approach are difficult to apply on a smaller subnational scale. We introduce Bayesian methods suitable for obtaining reliable age-specific population forecasts for small regions using the cohort-component method. Our approach improves fertility forecasting by extending the Lee--Carter model with an age-region interaction term. We propose to forecast net-migration counts using skewed error terms, and introduce a Dirichlet regression to model migration age patterns as well as age proportions of fertility. We run our model to produce age-specific population forecasts for a set of 13 heterogeneous regions in Bavaria, Germany. We compare our method with other standard approaches and find that it produces superior out-of-sample forecasts according to both point measures and scoring rules. The findings suggest that the proposed Bayesian methods offer good predictive accuracy and are suitable in obtaining precise forecasts of age-specific population for smaller geographical regions.