A 29-mRNA host-response classifier identifies bacterial infections following liver transplantation - a pilot study.

PURPOSE: Infections are common complications in patients following liver transplantation (LTX). The early diagnosis and prognosis of these infections is an unmet medical need even when using routine biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Therefore, new approaches are necessary. METHODS: In a prospective, observational pilot study, we monitored 30 consecutive patients daily between days 0 and 13 following LTX using the 29-mRNA host classifier IMX-BVN-3b that determine the likelihood of bacterial infections and viral infections. True infection status was determined using clinical adjudication. Results were compared to the accuracy of CRP and PCT for patients with and without bacterial infection due to clinical adjudication. RESULTS: Clinical adjudication confirmed bacterial infections in 10 and fungal infections in 2 patients. 20 patients stayed non-infected until day 13 post-LTX. IMX-BVN-3b bacterial scores were increased directly following LTX and decreased until day four in all patients. Bacterial IMX-BVN-3b scores detected bacterial infections in 9 out of 10 patients. PCT concentrations did not differ between patients with or without bacterial, whereas CRP was elevated in all patients with significantly higher levels in patients with bacterial infections. CONCLUSION: The 29-mRNA host classifier IMX-BVN-3b identified bacterial infections in post-LTX patients and did so earlier than routine biomarkers. While our pilot study holds promise future studies will determine whether these classifiers may help to identify post-LTX infections earlier and improve patient management. CLINICAL TRIAL NOTATION: German Clinical Trials Register: DRKS00023236, Registered 07 October 2020, https://drks.de/search/en/trial/DRKS00023236.

Direct oral anticoagulants in trauma patients.

PURPOSE OF REVIEW: Direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. Thus, trauma care providers are facing a steadily raising number of injured patients on DOACs. RECENT FINDINGS: Despite a predictable pharmacokinetic profile, the resulting plasma levels of trauma patients upon admission and bleeding risks remain uncertain. Therefore, recent guidelines recommend the measurement of DOAC plasma concentrations in injured patients. Alternatively, DOAC specific visco-elastic tests assays can be applied to identify DOAC patients at bleeding risk.Bleeding complications in trauma patients on DOACs are generally higher compared to nonanticoagulated subjects, but comparable to vitamin K antagonists (VKAs). In particular, a traumatic brain injury does not carry an increased risk of intracranial bleeding due to a DOAK intake compared to VKAs. Current studies demonstrated that up to 14% of patients with a hip fracture are on DOACs prior to surgery. However, the majority can be operated safely within a 24h time window without an increased bleeding rate.Specific antagonists facilitate rapid reversal of patients on DOACs. Idarucizumab for dabigatran, and andexanet alfa for apixaban and rivaroxaban have been approved for life threatening bleeding. Alternatively, prothrombin complex concentrate can be used. Dialysis is a potential treatment option for dabigatran and haemoabsorption with special filters can be applied in patients on FXa-inhibitors. SUMMARY: Current guidelines recommend the measurement of DOAC plasma levels in trauma patients. Compared to VKAs, DOACs do not carry a higher bleeding risk. DOAC specific antagonists facilitate the individual bleeding management.

Point-of-care, goal-directed management of bleeding in trauma patients.

PURPOSE OF REVIEW: The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). RECENT FINDINGS: Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. SUMMARY: POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

Evaluation of the Novel Sepsis Biomarker Host-Derived Delta-like Canonical Notch Ligand 1-A Secondary Analysis of 405 Patients Suffering from Inflammatory or Infectious Diseases.

Sepsis is defined as organ failure caused by dysregulated host response to infection. While early antibiotic treatment in patients with acute infection is essential, treating non-infectious patients must be avoided. Current guidelines recommend procalcitonin (PCT) to guide discontinuation of antibiotic treatment. For initiation of therapy, there is currently no recommended biomarker. In this study, we evaluated Host-Derived Delta-like Canonical Notch Ligand 1 (DLL1), a monocyte membrane ligand that has shown promising results in differentiating infectious from non-infectious critically ill patients. Soluble DLL1 levels were measured in plasma samples of six different cohorts. The six cohorts comprise two cohorts with non-infectious inflammatory auto-immune diseases (Hidradenitis Suppurativa, Inflammatory Bowel Disease), one cohort of bacterial skin infection, and three cohorts of suspected systemic infection or sepsis. In total, soluble DLL1 plasma levels of 405 patients were analyzed. Patients were divided into three groups: inflammatory disease, infection, and sepsis (defined according to the Sepsis-3 definition), followed by the evaluation of its diagnostic performance via Area Under the Receiver Operating Characteristics (AUROC) analyses. Patients of the sepsis group showed significantly elevated plasma DLL1 levels compared to patients with uncomplicated infections and sterile inflammation. However, patients with infections had significantly higher DLL1 levels than patients with inflammatory diseases. Diagnostic performance was evaluated and showed better performance for DLL1 for the recognition of sepsis (AUC: 0.823; CI 0.731-0.914) than C-reactive protein (AUC 0.758; CI 0.658-0.857), PCT (AUC 0.593; CI 0.474-0.711) and White Blood Cell count (AUC 0.577; CI 0.46-0.694). DLL1 demonstrated promising results for diagnosing sepsis and was able to differentiate sepsis from other infectious and inflammatory diseases.

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Identification of an optimized 2'-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8.

Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between "host" and "foreign" RNA. Ribose 2'-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-O-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2'-O-methylated RNA sequence, we performed a systematic permutation of the methylated nucleotide as well as adjacent bases and hereby identify two minimal trinucleotide motifs within a 9-mer oligoribonucleotide that are necessary and sufficient to antagonize TLR7 and TLR8 activation, respectively. Given the growing interest in the development of inhibitors of nucleic acid-sensing TLRs for therapeutic purposes, these results will facilitate the rational design of such antagonists in the future.

Gut microbiome patterns correlate with higher postoperative complication rates after pancreatic surgery.

BACKGROUND: Postoperative complications are of great relevance in daily clinical practice, and the gut microbiome might play an important role by preventing pathogens from crossing the intestinal barrier. The two aims of this prospective clinical pilot study were: (1) to examine changes in the gut microbiome following pancreatic surgery, and (2) to correlate these changes with the postoperative course of the patient. RESULTS: In total, 116 stool samples of 32 patients undergoing pancreatic surgery were analysed by 16S-rRNA gene next-generation sequencing. One sample per patient was collected preoperatively in order to determine the baseline gut microbiome without exposure to surgical stress and/or antibiotic use. At least two further samples were obtained within the first 10 days following the surgical procedure to observe longitudinal changes in the gut microbiome. Whenever complications occurred, further samples were examined. Based on the structure of the gut microbiome, the samples could be allocated into three different microbial communities (A, B and C). Community B showed an increase in Akkermansia, Enterobacteriaceae and Bacteroidales as well as a decrease in Lachnospiraceae, Prevotella and Bacteroides. Patients showing a microbial composition resembling community B at least once during the observation period were found to have a significantly higher risk for developing postoperative complications (B vs. A, odds ratio = 4.96, p < 0.01**; B vs. C, odds ratio = 2.89, p = 0.019*). CONCLUSIONS: The structure of the gut microbiome is associated with the development of postoperative complications.

New approaches for the detection of invasive fungal diseases in patients following liver transplantation-results of an observational clinical pilot study.

PURPOSE: Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses. METHODS: Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX. RESULTS: A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD. CONCLUSION: Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005480 .

Cell cycle arrest and cell death correlate with the extent of ischaemia and reperfusion injury in patients following kidney transplantation - results of an observational pilot study.

A prolonged cold ischaemia time (CIT) is suspected to be associated with an increased ischaemia and reperfusion injury (IRI) resulting in an increased damage to the graft. In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end products (sRAGE), tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP7) were measured. As a result of prolonged CIT and increased IRI, deceased donor transplantations were shown to suffer from a more distinct cell cycle arrest and necrotic cell death. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 were therefore demonstrated to be of value for the detection of a delayed graft function (DGF), as they improved the diagnostic performance of a routinely used clinical scoring system. Plasmatic total K18 and urinary TIMP-2 and IGFBP7 measurements are potentially suitable for early identification of patients at high risk for a DGF following kidney transplantation from deceased or living donors.

Pathophysiology of Trauma-Induced Coagulopathy.

Trauma-induced coagulopathy (TIC) is a complex hemostatic disturbance that can develop early after a major injury. There is no universally accepted definition of TIC. However, TIC primarily refers to the inability to achieve sufficient hemostasis in severely injured trauma patients, resulting in diffuse microvascular and life-threatening bleeding. Endogenous TIC is driven by the combination of hypovolemic shock and substantial tissue injury, resulting in endothelial damage, glycocalyx shedding, upregulated fibrinolysis, fibrinogen depletion, altered thrombin generation, and platelet dysfunction. Exogenous factors such as hypothermia, acidosis, hypokalemia, and dilution due to crystalloid and colloid fluid administration can further exacerbate TIC. Established TIC upon emergency room admission is a prognostic indicator and is strongly associated with poor outcomes. It has been shown that patients with TIC are prone to higher bleeding tendencies, increased requirements for allogeneic blood transfusion, higher complication rates such as multi-organ failure, and an almost fourfold increase in mortality. Thus, early recognition and individualized treatment of TIC is a cornerstone of initial trauma care. However, patients who survive the initial insult switch from hypocoagulability to hypercoagulability, also termed "late TIC," with a high risk of developing thromboembolic complications.

[Update on point-of-care-based coagulation treatment : Systems, reagents, device-specific treatment algorithms]. / Update der Point-of-care-basierten Gerinnungstherapie : Systeme, Reagenzien, gerätespezifische Behandlungsalgorithmen.

Viscoelastic test (VET) procedures suitable for point-of-care (POC) testing are in widespread clinical use. Due to the expanded range of available devices and in particular due to the development of new test approaches and methods, the authors believe that an update of the current treatment algorithms is necessary. The aim of this article is to provide an overview of the currently available VET devices and the associated reagents. In addition, two treatment algorithms for the VET devices most commonly used in German-speaking countries are presented.

A Comparison of Two Transport Monitor Systems With Regard to Efficiency and Staff Satisfaction in the Perioperative Setting.

BACKGROUND: Medical research aims to improve patient safety and efficiency in the perioperative setting. One critical aspect of patient safety is the intrahospital transfer of patients. Also, reliable monitoring of vital signs is crucial to support the medical staff. This study was conducted to assess two monitoring systems in terms of the handover time and staff satisfaction. METHODS: To assess several aspects, two monitoring systems were compared: an organizational unit-related monitoring system that needs to be changed and brought back to the initial organizational unit after the patient transfer and a patient-specific monitoring system that accompanies the patient during the whole perioperative process. RESULTS: In total, 243 patients were included, and 375 transfers were examined to analyze economic factors, including differences in handover times and user-friendliness. To this end, 30 employees of the Heidelberg University Hospital were asked about their satisfaction with the two monitoring systems based on a systematic questionnaire. It could be shown that, especially during transfers from the operating theater to the intensive care unit or the recovery room, the time from arrival to fully centralized monitoring and the total handover time were significantly shorter with the patient-specific monitoring system (p < 0.001). Furthermore, the staff was more satisfied with the patient-specific monitor system in terms of flexibility, cleanability and usability. CONCLUSION: The increased employee satisfaction and significant time benefits during intrahospital transports may increase patient safety and efficiency of patient care, reduce employee workload, and reduce costs in the overall context of patient care.

Biomarker-guided detection of acute kidney injury in abdominal aortic surgery: the new and the old.

Introduction: Acute kidney injury (AKI) is a common complication in patients undergoing major vascular surgery. Despite significant research efforts in this area, the incidence of AKI remains high, posing a significant challenge to healthcare systems, especially in situations where resources are limited. Early prediction of AKI severity and individualized postoperative care is therefore essential. Methods: The primary objective of this exploratory study was to assess the diagnostic value of urine cell-cycle arrest biomarkers [(TIMP-2) × (IGFBP7)] and soluble urokinase plasminogen activator receptor (suPAR) for predicting moderate or severe AKI within 24 h after open aortic surgery, and compared to routine kidney biomarkers. Seventy-five patients undergoing elective aortic surgery were included. Clinical parameters, urine and blood samples were collected preoperatively, immediately postoperatively, and 24 h later. AKI was defined using KDIGO criteria. Individual and combined diagnostic performance of biomarkers were evaluated. Results: Of the 75 patients, 61% developed AKI, of which 28% developed moderate or severe AKI within 24 h of surgery. Baseline demographics, comorbidities and kidney parameters did not differ between patients with moderate or severe AKI (AKI II/III) and none or mild AKI (AKI 0/I), except for higher preoperative suPAR levels in later AKI II/III patients. Urine osmolality, Cystatin C and serum creatinine had the highest predictive power for AKI II/III with AUCs of 0.75-0.72. (TIMP-2) × (IGFBP7), and neither (TIMP-2) × (IGFBP7) nor suPAR individually showed superior diagnostic value. Combining CysC or SCr with urine osmolality and 6 h urine output gave the best performance with AUCs of 0.86 (95% CI, 0.74-0.96) and 0.85 (95% CI, 0.75-0.95) respectively. Conclusion: Our study suggests that routine parameters like urine osmolality, CysC, SCr and 6 h urine output perform best in predicting postoperative AKI after aortic surgery compared to the new biomarkers (TIMP-2) × (IGFBP7) and suPAR. Combining biomarkers, particularly CysC or SCr with urine output, urine osmolality, may enhance diagnostic accuracy. Further validation in larger cohorts and clinical settings is warranted to establish their clinical utility.

Comparison of Two Viscoelastic Testing Devices in a Parturient Population.

Background: Viscoelastic hemostatic assays (VHAs) have become an integral diagnostic tool in guiding hemostatic therapy, offering new opportunities in personalized hemostatic resuscitation. This study aims to assess the interchangeability of ClotPro® and ROTEM® delta in the unique context of parturient women. Methods: Blood samples from 217 parturient women were collected at three timepoints. A total of 631 data sets were eligible for our final analysis. The clotting times were analyzed via extrinsic and intrinsic assays, and the clot firmness parameters A5, A10, and MCF were analyzed via extrinsic, intrinsic, and fibrin polymerization assays. In parallel, the standard laboratory coagulation statuses were obtained. Device comparison was assessed using regression and Bland-Altman plots. The best cutoff calculations were used to determine the VHA values corresponding to the established standard laboratory cutoffs. Results: The clotting times in the extrinsic and intrinsic assays showed notable differences between the devices, while the extrinsic and intrinsic clot firmness results demonstrated interchangeability. The fibrinogen assays revealed higher values in ClotPro® compared to ROTEM®. An ROC analysis identified VHA parameters with high predictive values for coagulopathy exclusion and yet low specificity. Conclusions: In the obstetric setting, the ROTEM® and ClotPro® parameters demonstrate a significant variability. Device- and indication-specific transfusion algorithms are essential for the accurate interpretation of measurements and adequate hemostatic therapy.

[Central anticholinergic, neuroleptic malignant and serotonin syndromes : Important differential diagnoses in postoperative impairment of consciousness]. / Zentrales anticholinerges, malignes neuroleptisches und Serotoninsyndrom : Wichtige Differenzialdiagnosen bei postoperativen Bewusstseinsstörungen.

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day-1) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day-1) is the recommended treatment.

[Central anticholinergic, neuroleptic malignant and serotonin syndromes]. / Zentrales anticholinerges, malignes neuroleptisches und Serotoninsyndrom: Wichtige Differenzialdiagnosen bei postoperativen Bewusstseinsstörungen.

Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day-1) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day-1) is the recommended treatment.

Case report: Resuscitative endovascular balloon occlusion after iatrogenic injury of the common iliac artery during neurosurgical dorsal lumbar microdiscectomy.

Introduction and importance: This case report describes resuscitative endovascular balloon occlusion (REBOA) of the aorta in a patient with life-threatening iatrogenic bleeding of the right common iliac artery during elective dorsal lumbar spine surgery. REBOA is an emergency procedure for temporary intra-aortic balloon occlusion being increasingly reported and published since its inauguration in 1954. The interdisciplinary management of hemorrhage and technical notes for a successful REBOA procedure will be presented. Case presentation: A 53-year-old female patient was admitted to the neurosurgery clinic suffering from left-sided L5 radiculopathy. During surgery, the anterior longitudinal ligament was perforated and an arterial vessel was lacerated. The patient became hemodynamically unstable demanding prompt supine repositioning and cardiopulmonary resuscitation (CPR). REBOA enabled cardiovascular stabilization after 90 min of CPR and laparotomy with vascular reconstruction and contributed to the survival of the patient without major clinical deficits. The patient was discharged from the ICU after 7 days. Clinical discussion: Resuscitative endovascular balloon occlusion of the aorta is an emergency procedure to control life-threatening hemorrhage. REBOA should be available on-scene and applied by well-trained vascular surgery personnel to control vascular complications or extend to emergency laparotomy and thoracotomy with aortic cross-clamping in case of in-hospital non-controllable hemorrhages. In case of ongoing CPR, we recommend surgical groin incision, open puncture of the pulseless common femoral artery, and aortic balloon inflation in REBOA zone I. Hereby, fast access and CPR optimization for heart and brain perfusion are maintained. Conclusion: Training for REBOA is the decisive factor to control selected cases of in-house and outpatient massive arterial abdominal bleeding complications.

Liver-Support Therapies in Critical Illness-A Comparative Analysis of Procedural Characteristics and Safety.

Extracorporeal liver-support therapies remain controversial in critically ill patients, as most studies have failed to show an improvement in outcomes. However, heterogeneous timing and inclusion criteria, an insufficient number of treatments, and the lack of a situation-dependent selection of available liver-support modalities may have contributed to negative study results. We retrospectively investigated the procedural characteristics and safety of the three liver-support therapies CytoSorb, Molecular Adsorbent Recirculating System (MARS) and therapeutic plasma exchange (TPE). Whereas TPE had its strengths in a shorter treatment duration, in clearing larger molecules, affecting platelet numbers less, and improving systemic coagulation and hemodynamics, CytoSorb and MARS were associated with a superior reduction in particularly small protein-bound and water-soluble substances. The clearance magnitude was concentration-dependent for all three therapies, but additionally related to the molecular weight for CytoSorb and MARS therapy. Severe complications did not appear. In conclusion, a better characterization of disease-driving as well as beneficial molecules in critically ill patients with acute liver dysfunction is crucial to improve the use of liver-support therapy in critically ill patients. TPE may be beneficial in patients at high risk for bleeding complications and impaired liver synthesis and hemodynamics, while CytoSorb and MARS may be considered for patients in whom the elimination of smaller toxic compounds is a primary objective.

[Principles of the perioperative management of direct oral anticoagulants]. / Grundlagen des perioperativen Umgangs mit direkten oralen Antikoagulanzien.

Within the approved indications direct oral anticoagulants (DOAC) are increasingly gaining acceptance instead of vitamin K antagonists (VKA). In the last 12 months 5 guidelines relevant to the perioperative management of DOACs have been updated. This article summarizes the current recommendations for the perioperative management of treatment with DOACs. The available substances and their pharmacological properties as well as the possibilities for specific laboratory diagnostics of the effect of DOAC are explained. Special focus is placed on anesthesiologically important aspects of substance-specific preoperative and postoperative intermission intervals, the procedure for neuraxial regional anesthesia and antagonization with specific antidotes in cases of life-threatening bleeding.

Pediatric cardiopulmonary resuscitation in infant and children with chronic diseases: A simple approach?

Infants and children with complex chronic diseases have lifelong, life-threatening conditions and for many, early death is an unavoidable outcome of their disease process. But not all chronic diseases in children are fatal when treated well. Cardiopulmonary resuscitation is more common in children with chronic diseases than in healthy children. Resuscitation of infants and children presents significant challenges to physicians and healthcare providers. Primarily, these situations occur only rarely and are therefore not only medically demanding but also associated with emotional stress. In case of resuscitation in infants and children with chronic diseases these challenges become much more complex. The worldwide valid Pediatric Advanced Life Support Guidelines do not give clear recommendations how to deal with periarrest situations in chronically ill infants and children. For relevant life-limiting illnesses, a "do not resuscitate" order should be discussed early, taking into account medical, ethical, and emotional considerations. The decision to terminate resuscitative efforts in cardiopulmonary arrest in infants and children with chronic illnesses such as severe lung disease, heart disease, or even incurable cancer is complex and controversial among physicians and parents. Judging the "outcome" of resuscitation as a "good" outcome becomes complex because for some, life extension itself and for others, quality of life is a goal. Physicians often decide that a healthy child is more likely to have a reversible condition and thereby have a better outcome than a child with multiple comorbidities and chronic health care needs. Major challenges in resuscitation infants and children are that clinicians need to individualize resuscitation strategies in light of each chronic disease, anatomy and physiology. This review aims to highlight terms of resuscitation infants and children with complex chronic diseases, considering resuscitation-related factors, parent-related factors, patient-related factors, and physician-related factors.