Administration of fibrinogen concentrate combined with prothrombin complex maintains hemostasis in children undergoing congenital heart repair (a long-term propensity score-matched study).

BACKGROUND: Bleeding is a common problem in children with congenital heart disease undergoing major cardiac surgery requiring cardiopulmonary bypass (CPB). Little is known about optimal management with blood products. OBJECTIVE: To investigate clinical outcome and hemostatic effects of fibrinogen concentrate (FC) in combination with prothrombin complex concentrate (PCC) versus standard treatment with fresh frozen plasma (FFP) in children undergoing cardiac surgery. METHODS: For this single-institution cohort study, data on 525 children were analyzed. Propensity score matching in 210 children was applied to reduce the impact of various baseline characteristics. RESULTS: Three children treated with FC/PCC developed surgical site bleeding requiring surgical revision. One child developed central venous line-related thrombosis. Blood loss through chest tube drainage was independent of FC/PCC. Coagulation abnormalities were not present in any of these children. Time to extubation and ICU stay did not differ. In the FC/PCC group, children received (median, Q1, Q3) 52 mg/kg (32, 83) FC and 28IU/kg (13, 44) PCC. Fibrinogen concentration was comparable at baseline. On admission to the ICU, fibrinogen was higher in children receiving FC/PCC, namely, 232 mg/dL (196, 280), than in children receiving FFP (186 mg/dL, 149, 224; P < .001). On discharge from the ICU, values did not differ ((FC/PCC 416 mg/dL (288, 501)), non-FC/PCC 418 mg/dL (272, 585; P = 1.000)). CONCLUSION: FC/PCC was well tolerated and permitted hemostasis to be maintained, even in the very young. We were not able to detect a signal for inferiority of this treatment. We conclude that FC/PCC can safely replace FFP.

Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial.

BACKGROUND: Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transfusion requirements, and consequently the development of multiple organ failure. METHODS: This single-centre, parallel-group, open-label, randomised trial was done at the Level 1 Trauma Center in Innsbruck Medical University Hospital (Innsbruck, Austria). Patients with trauma aged 18-80 years, with an Injury Severity Score (ISS) greater than 15, bleeding signs, and plasmatic coagulopathy identified by abnormal fibrin polymerisation or prolonged coagulation time using rotational thromboelastometry (ROTEM) were eligible. Patients with injuries that were judged incompatible with survival, cardiopulmonary resuscitation on the scene, isolated brain injury, burn injury, avalanche injury, or prehospital coagulation therapy other than tranexamic acid were excluded. We used a computer-generated randomisation list, stratification for brain injury and ISS, and closed opaque envelopes to randomly allocate patients to treatment with FFP (15 mL/kg of bodyweight) or CFC (primarily fibrinogen concentrate [50 mg/kg of bodyweight]). Bleeding management began immediately after randomisation and continued until 24 h after admission to the intensive care unit. The primary clinical endpoint was multiple organ failure in the modified intention-to-treat population (excluding patients who discontinued treatment). Reversal of coagulopathy and need for massive transfusions were important secondary efficacy endpoints that were the reason for deciding the continuation or termination of the trial. This trial is registered with ClinicalTrials.gov, number NCT01545635. FINDINGS: Between March 3, 2012, and Feb 20, 2016, 100 out of 292 screened patients were included and randomly allocated to FFP (n=48) and CFC (n=52). Six patients (four in the FFP group and two in the CFC group) discontinued treatment because of overlooked exclusion criteria or a major protocol deviation with loss of follow-up. 44 patients in the FFP group and 50 patients in the CFC group were included in the final interim analysis. The study was terminated early for futility and safety reasons because of the high proportion of patients in the FFP group who required rescue therapy compared with those in the CFC group (23 [52%] in the FFP group vs two [4%] in the CFC group; odds ratio [OR] 25·34 [95% CI 5·47-240·03], p<0·0001) and increased needed for massive transfusion (13 [30%] in the FFP group vs six [12%] in the CFC group; OR 3·04 [0·95-10·87], p=0·042) in the FFP group. Multiple organ failure occurred in 29 (66%) patients in the FFP group and in 25 (50%) patients in the CFC group (OR 1·92 [95% CI 0·78-4·86], p=0·15). INTERPRETATION: Our results underline the importance of early and effective fibrinogen supplementation for severe clotting failure in multiple trauma. The available sample size in our study appears sufficient to make some conclusions that first-line CFC is superior to FFP. FUNDING: None.

Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community.

BACKGROUND: Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinson's disease (PD), but to date their predictive value has not yet been tested in population-based cohorts. METHODS: We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable. RESULTS: After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of "probable prodromal PD" status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%). CONCLUSIONS: Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease-prevention trials. © 2016 International Parkinson and Movement Disorder Society.

Probable RBD and association with neurodegenerative disease markers: A population-based study.

BACKGROUND: The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined. METHODS: We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older. RESULTS: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety. CONCLUSIONS: Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD.