Tranexamsäure zur Prophylaxe der postpartalen Hämorrhagie nach Schnittentbindung. Ein Kommentar zur TRAAP2-Studie

Die Anaesthesiologie -     

The Current UK Consensus on the Management of Weber B and Posterior Ankle Fractures: A Questionnaire Study as Part of the Acute Management of Ankle Fractures (AUGMENT) Audit

Ankle fractures are common conditions which are associated with significant morbidity when managed incorrectly. With the incidence due to triple by 2030, standards of practice were created by the British Orthopaedic Association and the British Orthopaedic Foot and Ankle Society to ensure optimal treatment. In spite of this, anecdotally there is still a variation in practice and therefore a questionnaire study was designed to explore clinician decision-making around Weber B and Posterior Malleolus ankle fractures. Five scenarios explored management regarding minimally and grossly displaced injuries, as well as the use of further imaging. The questionnaires were distributed via AUGMENT collaborators at their sites and at the British Orthopaedic Foot and Ankle Society congress 2018. About 315 questionnaires were completed and included in analysis. For Weber B injuries, overall there was a consensus across all respondents with minimally displaced and grossly displaced fractures being treated conservatively and operatively respectively. For Posterior Malleolus injuries, there was variation in practice between Foot and Ankle specialists and their non-Foot and Ankle colleagues. Computed tomography (CT) was more likely to be used to assess these injuries by specialists (97.50 vs 69.79%) and these injuries were more likely to be treated operatively across the board. This study identified key variation in practice of the management of Posterior Malleolar ankle fractures, including the use of imaging to further define the anatomy and the decision to operate. Foot and Ankle surgeons were more likely to organize CT scans and to surgically manage these injures.     

Novel approach to an early assessment of a patient’s potential for neurological remission after acute spinal cord injury: Analysis of hemoglobin concentration dynamics

Context/objective: Examining hemoglobin (Hb) dynamics with regard to the potential of neurological remission in patients with traumatic spinal cord injury (TSCI).Design: Prospective Clinical Observational Study.Setting: BG Trauma Centre Ludwigshafen, Department of Paraplegiology, Rhineland-Palatinate, Germany.Methods: From 2011 to 2017 a total of 80 patients with acute spinal injury were enrolled and divided into three groups: initial neurological impairment either with (G1; n = 33) or without subsequent neurological remission (G0; n = 35) and vertebral fractures without initial neurological impairment as control group (C; n = 12). Blood samples were taken for 3 months at 11 time-points after injury. Analyses were performed using routine diagnostics.Outcome measures: Multiple logistic regression was used to determine the prognostic value of Hb regarding neurological remission respecting clinical covariates.Results: Data showed elevated mean Hb concentrations in G1 from the third day to 1 month compared to G0, Hb levels were significantly higher in G1 after 3 days (P = 0.03, G1 > G0). The final multiple logistic regression model based on this data predicting the presence of neurological remission resulted in an AUC (area under the curve) of 80.5% (CI: 67.8%–93.2%) in the ROC (receiver operating characteristic) analysis.Conclusion: Elevated Hb concentrations are associated with a higher likelihood of neurological remission. Elevated concentrations of Hb in G1 compared to G0 over time might be linked to both a better initial oxygen supply response and a decreased ECM (extracellular matrix) degradation highlighting the role of Hb as a valuable biomarker for neural regeneration after TSCI.     

Unequal rates of postoperative complications in relatively healthy bariatric surgical patients of white and black race

BackgroundRacial disparities in postsurgical complications are often presumed to be due to a higher preoperative co-morbidity burden among patients of black race, although being relatively healthy is not a prerequisite for a complication-free postoperative course.ObjectivesTo examine the association of race with short-term postbariatric surgery complications in seemingly healthy patients.SettingsMetabolic and Bariatric Surgery Accreditation and Quality Improvement Program database (2015–2018).MethodsWe studied a relatively healthy (American Society of Anesthesiologists physical status 1 or 2), propensity score–matched cohort of adult non-Hispanic black and non-Hispanic white bariatric surgery patients. We compared the risk-adjusted incidences of postoperative complications, serious adverse events, and measures of postoperative resource utilization across racial groups.ResultsWe identified 44,090 matched pairs of relatively healthy black and white bariatric surgery patients. Patients of black race were 72% more likely than those of white race to develop 1 or more postoperative complications (.7% versus .4%, respectively; odds ratio [OR], 1.72; 95% confidence interval [CI], 1.32–2.24; P < .01). Measures of postbariatric resource utilization were significantly higher in patients of black race than those of white race, including unplanned reoperations (1.3% versus 1.0%, respectively; OR, 1.28; 95% CI, 1.07–1.52; P = .01), unplanned readmissions (4.5% versus 3.0%, respectively; OR, 1.53; 95% CI, 1.38–1.69; P < .01), unplanned interventions (1.6% versus 1.2%, respectively; OR, 1.36; 95% CI, 1.16–1.60; P < .01), and extended hospital lengths of stay (51.2% versus 42.7%, respectively; OR, 1.41; 95% CI, 1.36–1.46; P < .01).ConclusionEven among relatively healthy patients, race appears to be an important determinant of postbariatric surgery complications and resource utilization. Research and interventions aimed at narrowing the racial disparities in bariatric surgery outcomes may need to broaden the focus beyond the racial variation in the preoperative co-morbidity burden.     

Letermovir in lung transplant recipients with cytomegalovirus infection: A retrospective observational study

Letermovir is a new antiviral drug approved for the prophylaxis of CMV infection in allogeneic stem cell transplants. The aim of the study was to assess the therapeutic efficacy of letermovir in difficult to treat CMV infections in lung transplant recipients. All lung transplant recipients between March 2018 and August 2020, who have been treated with letermovir for ganciclovir-resistant or refractory CMV infection were included in the study and analysed retrospectively. In total, 28 patients were identified. CMV disease was present in 15 patients (53.6%). In 23 patients (82.1%), rapid response was noticed, and CMV-viral load could be significantly decreased (>1 log₁₀) after a median of 17 [14–27] days and cleared subsequently in all of these patients. Five patients (17.9%) were classified as non-responder. Thereof, development of a mutation of the CMV UL56 terminase (UL-56-Gen: C325Y) conferring letermovir resistance could be observed in three patients (60%). Common side effects were mild and mostly of gastrointestinal nature. Mild adjustments of the immunosuppressive drugs were mandatory upon treatment initiation with letermovir. In addition to other interventions, letermovir was effective in difficult to treat CMV infections in lung transplant recipients. However, in patients with treatment failure mutation conferring letermovir, resistance should be taken into account.     

Inhibition of uptake1 by (+)-oxaprotiline reveals a differential central regulation of noradrenaline and adrenaline release

Summary Inhibition of uptake, in the central nervous system leads to a decrease of sympathetic outflow to many tissues; central a2-adrenoceptors are involved in this decrease. The aim of the present study was to compare the effects of the selective uptake, inhibitor (+)-oxaprotiline on the plasma kinetics of noradrenaline and adrenaline in anaesthetized and in conscious rabbits. [³H]Noradrenaline and [^3H]adrenaline were infused iv. The arterial plasma concentrations of endogenous and radiolabelled noradrenaline and adrenaline were measured, and the clearance from and spillover into the plasma of noradrenaline and adrenaline were calculated.Results obtained in conscious and anaesthetized rabbits were similar. (+)-Oxaprotiline 0.2, 0.6 and 1.8 mg kg^–1 iv. dose-dependently reduced the clearance of [³H]noradrenaline from the plasma. The clearance of [³H]adrenaline was reduced less. The spillover of endogenous noradrenaline was decreased by up to 35%. In contrast, the spillover of adrenaline tended to be enhanced. Prazosin 0.1 and 1 mg kg^–1 was injected iv. in a second part of each experiment. It lowered the blood pressure and caused a marked increase in noradrenaline spillover but no increase or even a decrease in adrenaline spillover.The results are compatible with the following hypothesis. The sympathetic outflow from the central nervous system is subject to a twofold a-adrenoceptor-mediated modulation: -adrenoceptor-mediated inhibition and ₁-adrenoceptor-mediated excitation. In the control of the sympathetic outflow to many extra-adrenal tissues, the ₂-adrenergic inhibition prevails. Uptake₁ inhibitors depress sympathetic outflow to such tissues by enhancing the ₂-adrenergic inhibition. In the regulation of the sympathetic outflow to the adrenal medulla, in contrast, ₂-adrenergic inhibition and ₁-adrenergic excitation have a similar impact. Uptake, inhibitors, hence, cause little change in adrenaline release: the two opposing influences cancel out. Prazosin produces an increase in noradrenaline but not adrenaline release because the loss of the central ₁ sympathoexcitation attenuates at best slightly the baroreflex to most extra-adrenal tissues but dampens markedly the baroreflex to the adrenal medulla. Correspondence to B. Szabo at the above address     

Continuous regional anaesthesia in infants

Physiological immaturity of the respiratory musculature and central respiratory control centres leads to an increased risk of apnoea and respiratory complications following general anaesthesia in neonates. Regional anaesthetic techniques may obviate the need for general anaesthesia and lessen the risks of perioperative morbidity. Although these techniques have been described in infants, previous reports have dealt with singleshot techniques for brief surgical procedures (< 60 min). Experience with prolonged operative cases using regional anaesthesia via indwelling catheters in infants is limited. We present our experience with four infants in whom either caudal epidural or spinal anaesthesia was administered via indwelling catheters for operative procedures that lasted 90 to 180 min. We believe this technique is an alternative to general anaesthesia in these patients. A cause de l’immaturité physiologique de sa musculature et de son centre respiratoires, le nouveau-né est plus sujet à l’apnée et aux complications après une anesthésie générale. L’anesthésie régionale peut remplacer en partie l’anesthésie générale et diminuer ainsi la morbidité périopératoire. Les techniques régionales sont bien décrites pour l’enfant mais elles sont utilisées en doses uniques pour des interventions brèves (< 60 min). L’expérience d’interventions sous régionale avec des cathéters en place est limitée. Nous présentons ici notre expérience avec quatre enfants auxquels on a administré une caudale ou une rachianesthésie continue pour des interventions de 90 à 180 min. Nous croyons que ces techniques sont des alternatives valables à l’anesthésie générale chez ces patients.     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.