Economic effects of next-generation sequencing diagnostics in unspecific sepsis patients - a budget impact analysis from the healthcare providers' perspective in Germany.

PURPOSE: Next-generation sequencing (NGS) tools have clinical advantages over blood culture but are more expensive. This study assesses the budget impact and break-even point of NGS testing costs from a healthcare provider's perspective in Germany. METHODS: The budget impact was calculated based on aggregated data of German post-operative surgery cases. Simulated cost savings were calculated based on a simulated reduction in hospital length of stay (LOS) of four or eight days with a positivity rate of 71% and compared to the costs of one (scenario A) or two tests (scenario B) per case. Furthermore, the break-even point of the cost of two tests compared to saved costs through shortened LOS was conducted. RESULTS: For 9,450 cases, an average budget impact for scenario A and scenario B of €1,290.41 [95% CI €1,119.64 - €1,461.19] and - €208.59 [95% CI - €379.36 - - €37.81] was identified for gastrointestinal and kidney surgery cases, and €1,355.58 [95% CI €1,049.62 - €1,661.55] and €18.72 [95% CI - €324.69 - €287.24] for vascular artery surgery cases, respectively. The break-even analysis showed that using two tests per case could achieve a minimum positive contribution margin with an average of 1.9 tests per case across the study population. CONCLUSION: The results revealed a positive budget impact for one NGS test and a slightly negative budget impact for two NGS tests per case. Findings suggest that largest cost savings are generated for more severe cases and are highly dependent on the patient population.

Butyricimonas faecihominis: an atypically resistant bacterium implicated in abscess formation - a case report.

BACKGROUND: This case report presents a unique instance of abscesses with an uncommon pathogen isolated from blood cultures. CASE PRESENTATION: We present the case of a perianal abscess in a 50-year-old man with a history of cocaine abuse and bilateral hip replacements. The rapid progression led to septic shock and multi-organ failure, requiring intensive care unit admission, surgery including protective transversostomy. Blood cultures showed growth of Butyricimonas spp. with resistance to penicillin and piperacillin-tazobactam. The immediate switch to meropenem led to a significant improvement in the patient's condition. The patient was discharged after 40 days of hospitalization in good general condition and the reversal of the transversostomy was performed six months later. CONCLUSION: The identification of Butyricimonas faecihominis, a rarely reported pathogen, emphasizes the challenges of diagnosing and treating unusual infections. This case emphasizes the importance of rapid microbiological diagnosis, interdisciplinary collaboration, and targeted antibiotic therapy in the treatment of abscesses and sepsis.

Comparing Simulation Training of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy Using Conventional Versus 3D Printed Simulators (TRAC-Sim Study).

Background: Individual implementation rate of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) varies among intensivists. Simulation training (ST) can increase the safety of medical procedures by reducing stress levels of the performing team. The aim of this study was to evaluate the benefit of ST in PDT regarding procedural time, quality of performance, and percepted feelings of safety of the proceduralist and to compare conventional simulators (CSIM) with simulators generated from 3D printers (3DSIM). Methods: We conducted a prospective, single-center, randomized, blinded cross-over study comparing the benefit of CSIM versus 3DSIM for ST of PDT. Participants underwent a standardized theoretical training and were randomized to ST with CSIM (group A) or 3DSIM (group B). After ST, participants' performance was assessed by two blinded examiners on a porcine trachea regarding time required for successful completion of PDT and correct performance (assessed by a performance score). Percepted feelings of safety were assessed before and after ST. This was followed by a second training and second assessment of the same aspects with crossed groups. Results: 44 participants were included: 24 initially trained with CSIM (group A) and 20 with 3DSIM (group B). Correctness of the PDT performance increased significantly in group B (p < .01) and not significantly in group A (p = .14). Mean procedural time required for performing a PDT after their second ST compared to the first assessment (p < .01) was lower with no difference between group A and group B and irrespective of the participants' previous experience regarding PDT, age, and sex. Moreover, percepted feelings of safety increased after the first ST in both groups (p < .001). Conclusions: ST can improve procedural skills, procedural time, and percepted feelings of safety of the proceduralist in simulated PDT.

Weaning failure due to isolated residual diaphragmatic paralysis after cervical spinal cord ischemia following aortic surgery- a case report.

BACKGROUND: Bilateral diaphragmatic dysfunction can lead to dyspnea and recurrent respiratory failure. In rare cases, it may result from high cervical spinal cord ischemia (SCI) due to anterior spinal artery syndrome (ASAS). We present a case of a patient experiencing persistent isolated diaphragmatic paralysis after SCI at level C3/C4 following thoracic endovascular aortic repair (TEVAR) for Kommerell's diverticulum. This is, to our knowledge, the first documented instance of a patient fully recovering from tetraplegia due to SCI while still exhibiting ongoing bilateral diaphragmatic paralysis. CASE PRESENTATION: The patient, a 67-year-old male, presented to the Vascular Surgery Department for surgical treatment of symptomatic Kommerell's diverticulum in an aberrant right subclavian artery. After successful surgery in two stages, the patient presented with respiratory insufficiency and flaccid tetraparesis consistent with anterior spinal artery syndrome with maintained sensibility of all extremities. A computerized tomography scan (CT) revealed a high-grade origin stenosis of the left vertebral artery, which was treated by angioplasty and balloon-expandable stenting. Consecutively, the tetraparesis immediately resolved, but weaning remained unsuccessful requiring tracheostomy. Abdominal ultrasound revealed a residual bilateral diaphragmatic paralysis. A repeated magnetic resonance imaging (MRI) 14 days after vertebral artery angioplasty confirmed SCI at level C3/C4. The patient was transferred to a pulmonary clinic with weaning center for further recovery. CONCLUSIONS: This novel case highlights the need to consider diaphragmatic paralysis due to SCI as a cause of respiratory failure in patients following aortic surgery. Diaphragmatic paralysis may remain as an isolated residual in these patients.

Completeness of the operating room to intensive care unit handover: a matter of time?

BACKGROUND: Handovers of post-anesthesia patients to the intensive care unit (ICU) are often unstructured and performed under time pressure. Hence, they bear a high risk of poor communication, loss of information and potential patient harm. The aim of this study was to investigate the completeness of information transfer and the quantity of information loss during post anesthesia handovers of critical care patients. METHODS: Using a self-developed checklist, including 55 peri-operative items, patient handovers from the operation room or post anesthesia care unit to the ICU staff were observed and documented in real time. Observations were analyzed for the amount of correct and completely transferred patient data in relation to the written documentation within the anesthesia record and the patient's chart. RESULTS: During a ten-week study period, 97 handovers were included. The mean duration of a handover was 146 seconds, interruptions occurred in 34% of all cases. While some items were transferred frequently (basic patient characteristics [72%], surgical procedure [83%], intraoperative complications [93.8%]) others were commonly missed (underlying diseases [23%], long-term medication [6%]). The completeness of information transfer is associated with the handover's duration [B coefficient (95% CI): 0.118 (0.084-0.152), p<0.001] and increases significantly in handovers exceeding a duration of 2 minutes (24% ± 11.7 vs. 40% ± 18.04, p<0.001). CONCLUSIONS: Handover completeness is affected by time pressure, interruptions, and inappropriate surroundings, which increase the risk of information loss. To improve completeness and ensure patient safety, an adequate time span for handover, and the implementation of communication tools are required.

COVID-19 associated pulmonary aspergillosis.

OBJECTIVES: Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID-19) associated invasive aspergillosis at a single centre in Cologne, Germany. METHODS: A retrospective chart review of all patients with COVID-19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. RESULTS: COVID-19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. CONCLUSION: Clinicians caring for patients with ARDS due to COVID-19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co-infection.

Apneic laryngeal oxygenation during elective fiberoptic intubation - a technical simulation.

BACKGROUND: Sedation during elective fiberoptic intubation for difficult airway can cause respiratory depression, apnea and periods of desaturation. During apneic episodes, hypoxemia can be prevented by insufflation of oxygen in the deep laryngeal space. The aim of this study was to evaluate an oropharyngeal oxygenation device (OOD) designed for deep laryngeal insufflation during fiberoptic intubation. METHODS: The OOD is split in the front to form a path for the bronchoscope. An external lumen delivers oxygen in the deep laryngeal space. In this experimental study, air application (as control group), oxygen application via nasal prongs, oxygen application via the OOD, and oxygen application via the working channel of a bronchoscope were compared in a technical simulation. In a preoxygenated test lung of a manikin, decrease of the oxygen saturation was measured over 20 min for each method. RESULTS: Oxygen saturation in the test lung dropped from 97 ± 1% (baseline in all groups) to 58 ± 3% in the control-group (p < 0.001 compared to all other groups) and to 78 ± 1% in the nasal prong group (p < 0.001 compared to all other groups). Oxygen saturation remained at 95 ± 2% in both the OOD group and the bronchoscopy group (p = 0.451 between those two groups). CONCLUSION: Simulating apneic laryngeal oxygenation in a preoxygenated manikin, both oxygen insufflation via the OOD and the bronchoscope kept oxygen saturation in the test lung at 95% over 20 min. Both methods significantly were more effective than oxygen insufflation via nasal prongs.

[S3-Guideline Intensive Care Therapy of Cardiac Surgery Patients - a Practical Approach]. / Leitlinien in der Praxis: der herzchirurgische Patient in der intensivmedizinischen Versorgung.

The current S3-Guideline for intensive care therapy in patients after cardiac surgery provides a wealth of information and recommendations ranging from monitoring to treatment options for various perioperative clinical situations. This article focuses on the most relevant information applicable to every-day critical care practice, covering important aspects of general and advanced monitoring, goal directed hemodynamic therapy and treatment principles for perioperative left and right heart failure.

Multiplex polymerase chain reaction to diagnose bloodstream infections in patients after cardiothoracic surgery.

BACKGROUND: Sepsis and other infectious complications are major causes of mortality and morbidity in patients after cardiac surgery. Whereas conventional blood culture (BC) suffers from low sensitivity as well as a reporting delay of approximately 48-72 h, real-time multiplex polymerase chain reaction (PCR) based technologies like "SeptiFast" (SF) might offer a fast and reliable alternative for detection of bloodstream infections (BSI). The aim of this study was to compare the performance of SF with BC testing in patients suspected of having BSI after cardiac surgery. METHODS: Two hundred seventy-nine blood samples from 169 individuals with suspected BSI were analyzed by SF and BC. After excluding results attributable to contaminants, a comparison between the two groups were carried out. Receiver operating characteristic (ROC) curves were generated to determine the accuracy of clinical and laboratory values for the prediction of positive SF results. RESULTS: 14.7% (n = 41) of blood samples were positive using SF and 17.2% (n = 49) using BC (n.s. [p > 0.05]). In six samples SF detected more than one pathogen. Among the 47 microorganisms identified by SF, only 11 (23.4%) could be confirmed by BC. SF identified a higher number of Gram-negative bacteria than BC did (28 vs. 12, χ2 = 7.97, p = 0.005). The combination of BC and SF increased the number of detected microorganisms, including fungi, compared to BC alone (86 vs. 49, χ2 = 13.51, p < 0.001). C-reactive protein (CRP) (21.7 ± 11.41 vs. 16.0 ± 16.9 mg/dl, p = 0.009), procalcitonin (28.7 ± 70.9 vs. 11.5 ± 30.4 ng/dl, p = 0.015), and interleukin 6 (IL 6) (932.3 ± 1306.7 vs. 313.3 ± 686.6 pg/ml, p = 0.010) plasma concentrations were higher in patients with a positive SF result. Using ROC analysis, IL-6 (AUC 0.836) and CRP (AUC 0.804) showed the best predictive values for positive SF results. CONCLUSION: The SF test represent a valuable method for rapid etiologic diagnosis of BSI in patients after cardiothoracic surgery. In particular this method applies for individuals with suspected Gram-negative blood stream. Due to the low performance in detecting Gram-positive pathogens and the inability to determine antibiotic susceptibility, it should be used in addition to BC only (Pilarczyk K, et al., Intensive Care Med Exp ,3(Suppl. 1):A884, 2015).

New Approaches to Airway Management in Tracheal Resections-A Systematic Review and Meta-analysis.

OBJECTIVES: Although endotracheal intubation, surgical crossfield intubation, and jet ventilation are standard techniques for airway management in tracheal resections, there are also reports of new approaches, ranging from regional anesthesia to extracorporeal support. The objective was to outline the entire spectrum of new airway techniques. DESIGN: The literature databases PubMed/Medline and the Cochrane Library were searched systematically for prospective and retrospective trials as well as case reports on tracheal resections. SETTING: No restrictions applied to hospital types or settings. PARTICIPANTS: Adult patients undergoing surgical resections of noncongenital tracheal stenoses with end-to-end anastomoses. INTERVENTIONS: Airway management techniques were divided into conventional and new approaches and analyzed regarding their potential risks and benefits. MEASUREMENTS AND MAIN RESULTS: A total of 59 publications (n = 797 patients) were included. The majority of publications (71.2%) describe conventional airway techniques. Endotracheal tube placement after induction of general anesthesia and surgical crossfield intubation after incision of the trachea were used most frequently without major complications. A total of 7 new approaches were identified, including 4 different regional anesthetic techniques (25 cases), supraglottic airways (4 cases), and new forms of extracorporeal support (25 cases). Overall failure rates of new techniques were low (1.8%). Details on patient selection and procedural specifics are provided. CONCLUSIONS: New approaches have several theoretical benefits, yet further research is required to establish criteria for patient selection and evaluate procedural safety. Given the low level of evidence, it currently is impossible to compare methods of airway management regarding outcome-related risks and benefits.

Early prediction of acute kidney injury after transapical and transaortic aortic valve implantation with urinary G1 cell cycle arrest biomarkers.

BACKGROUND: Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) leading to increased mortality and morbidity. Urinary G1 cell cycle arrest proteins TIMP-2 and IGFBP7 have recently been suggested as sensitive biomarkers for early detection of AKI in critically ill patients. However, the precise role of urinary TIMP-2 and IGFBP7 in patients undergoing TAVI is unknown. METHODS: In a prospective observational trial, 40 patients undergoing TAVI (either transaortic or transapical) were enrolled. Serial measurements of TIMP-2 and IGFBP7 were performed in the early post interventional course. The primary clinical endpoint was the occurrence of AKI stage 2/3 according to the KDIGO classification. RESULTS: Now we show, that ROC analyses of [TIMP-2]*[IGFBP7] on day one after TAVI reveals a sensitivity of 100 % and a specificity of 90 % for predicting AKI 2/3 (AUC 0.971, 95 % CI 0.914-1.0, SE 0.0299, p = 0.001, cut-off 1.03). In contrast, preoperative and postoperative serum creatinine levels as well as glomerular filtration rate (GFR) and perioperative change in GFR did not show any association with the development of AKI. Furthermore, [TIMP-2]*[IGFBP7] remained stable in patients with AKI ≤1, but its levels increased significantly as early as 24 h after TAVI in patients who developed AKI 2/3 in the further course (4.77 ± 3.21 vs. 0.48 ± 0.68, p = 0.022). Mean patients age was 81.2 ± 5.6 years, 16 patients were male (40.0 %). 35 patients underwent transapical and five patients transaortic TAVI. 15 patients (37.5 %) developed any kind of AKI; eight patients (20 %) met the primary endpoint and seven patients required renal replacement therapy (RRT) within 72 h after surgery. CONCLUSION: Early elevation of urinary cell cycle arrest biomarkers after TAVI is associated with the development of postoperative AKI. [TIMP-2]*[IGFBP7] provides an excellent diagnostic accuracy in the prediction of AKI that is superior to that of serum creatinine.

Tracheostomy After Cardiac Surgery With Median Sternotomy and Risk of Deep Sternal Wound Infections: Is It a Matter of Timing?

OBJECTIVE: To assess the impact of timing of percutaneous dilatational tracheotomy (PDT) on incidence of deep sternal wound infections (DSWI) after cardiac surgery with median sternotomy. DESIGN: Retrospective study between 2003 and 2013. SETTING: Single-center university hospital. PARTICIPANTS: Eight hundred seventy-nine patients after cardiac surgery with extracorporeal circulation and median sternotomy. INTERVENTIONS: PDT using the Ciaglia-technique with direct bronchoscopic guidance. MEASUREMENT AND MAIN RESULTS: Mean time from surgery and (re)intubation to PDT was 6.7±9.9 and 3.8±3.3 days, respectively. Incidence of DSWI was 3.9% (34/879). The incidence of DSWI was comparable between patients with PDT performed before postoperative day (POD) 10 and those with PDT after POD 10 (29/755 [3.8%] v 5/124 [4.0%], p = n.s.). However, the authors observed an association of timing of PDT and DSWI: The incidence of DSWI was significantly higher in patients with PDT performed≤POD 1 compared to those with PDT after POD 2 (12/184 [6.52%] v 22/695 [3.16%], p = 0.046). In multivariate analysis, obesity, use of bilateral internal mammary arteries, ICU stay>30 days and PDT<48 hours after surgery (OR 3.519, 95% CI 1.242-9.976, p = 0.0018) were independent predictors of DSWI. In 15/34 patients (44.1%), similarity of microorganisms between sternotomy site and tracheal cultures was observed, indicating a possible cross-contamination. CONCLUSIONS: PDT within the first 10 postoperative days after cardiac surgery with median sternotomy can be performed safely without an increased risk of DSWI. In contrast, very early PDT within 48 hours after surgery is associated with an increased risk of mediastinitis and should, therefore, be avoided.

Impact of Inhaled Nitric Oxide (iNO) on the Outcome of COVID-19 Associated ARDS.

Background: Inhaled nitric oxide (iNO) can improve oxygenation in acute respiratory syndrome (ARDS), has anti-inflammatory and antithrombotic effects, and can inhibit coronavirus- replication. The study aim was to investigate the impact of iNO in COVID-19 associated ARDS (CARDS) on oxygenation, the length of mechanical ventilation (MV), the level of inflammatory markers and the rate of thrombotic events during ICU stay. Methods: This was a retrospective, observational, monocentric study analyzing the effect of INO (15 parts per million) vs. non-iNO in adult ventilated CARDS patients on oxygenation, the level of inflammatory markers, and the rate of thrombotic events during ICU stay. Within the iNO group, the impact on gas exchange was assessed by comparing arterial blood gas results obtained at different time points. Results: Overall, 19/56 patients were treated with iNO, with no difference regarding sex, age, body mass index, and SOFA-/APACHE II- score between the iNO and non-iNO groups. iNO improved oxygenation in iNO-responders (7/19) and had no impact on inflammatory markers or the rate of thrombotic events but was associated with an increased MV length. Conclusions: iNO was able to improve oxygenation in CARDS in iNO-responders but did not show an impact on inflammatory markers or the rate of thrombotic events, while it was associated with an increased MV length.

Alternative techniques for cardiopulmonary resuscitation in extreme environments - A scoping review.

Background: Cardiopulmonary resuscitation (CPR) is essential for saving lives during cardiac arrest, but performing CPR in extreme environments poses unique challenges. In scenarios ranging from hypogravity or microgravity to confined spaces like aeroplanes and underwater scenarios, traditional CPR techniques may be inadequate. This scoping review aims to identify alternative chest compression techniques, synthesise current knowledge, and pinpoint research gaps in resuscitation for cardiac arrest in extreme conditions. Methods: PubMed and the Cochrane Register of Controlled Trials as well as the website of ResearchGate was searched to identify relevant literature. Studies were eligible for inclusion if they evaluated alternative chest compression techniques, including manual or mixed CPR approaches, whilst assessing feasibility and effectiveness based on compression depth, rate, and/or impact on rescuer effort. Results: The database search yielded 9499 references. After screening 26 studies covering 6 different extreme environments were included (hypogravity: 2; microgravity: 9, helicopter: 1, aeroplane: 1, confined space: 11; avalanche: 2). 13 alternative chest compression techniques were identified, all of which tested using manikins to simulate cardiac arrest scenarios. Conclusion: To address the unique challenges in extreme environments, novel CPR techniques are emerging. However, evidence supporting their effectiveness remains limited.

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study.

Bloodstream infection (BSI), a frequent cause of severe sepsis, is a life-threatening complication in critically ill patients and still associated with a high mortality rate. Rapid pathogen identification from blood is crucial for an early diagnosis and the treatment of patients with suspected BSI. For this purpose, novel diagnostic tools on the base of genetic analysis have emerged for clinical application. The aim of this study was to assess the diagnostic value of additional next-generation sequencing (NGS) pathogen test for patients with suspected BSI in a surgical ICU and its potential impact on antimicrobial therapy. In this retrospective single-centre study, clinical data and results from blood culture (BC) and NGS pathogen diagnostics were analysed for ICU patients with suspected BSI. Consecutive changes in antimicrobial therapy and diagnostic procedures were evaluated. Results: 41 cases with simultaneous NGS and BC sampling were assessed. NGS showed a statistically non-significant higher positivity rate than BC (NGS: 58.5% (24/41 samples) vs. BC: 21.9% (9/41); p = 0.056). NGS detected eight different potentially relevant bacterial species, one fungus and six different viruses, whereas BC detected four different bacterial species and one fungus. NGS results affected antimicrobial treatment in 7.3% of cases. Conclusions: NGS-based diagnostics have the potential to offer a higher positivity rate than conventional culture-based methods in patients with suspected BSI. Regarding the high cost, their impact on anti-infective therapy is currently limited. Larger randomized prospective clinical multicentre studies are required to assess the clinical benefit of this novel diagnostic technology.

Predictive enrichment for the need of renal replacement in sepsis-associated acute kidney injury: combination of furosemide stress test and urinary biomarkers TIMP-2 and IGFBP-7.

BACKGROUND: In sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice. Both the Furosemide Stress Test (FST) and measurements of the urinary biomarkers TIMP-2*IGFBP-7, if applied solely, do not provide sufficient guidance. We tested the hypothesis that a combination of two tests, i.e., an upstream FST combined with downstream measurements of urinary TIMP-2*IGFBP-7 concentrations improves the accuracy in predicting RRT necessity. METHODS: In this prospective, multicenter study 100 patients with sepsis (diagnosed < 48h), AKI stage ≥ 2, and an indication for negative fluid balance were included between 02/2020 and 12/2022. All patients received a standardized FST and urinary biomarkers TIMP-2*IGFBP-7 were serially measured immediately before and up to 12 h after the FST. The primary outcome was the RRT requirement within 7 days after inclusion. RESULTS: 32% (n = 32/99) of SA-AKI patients eventually required RRT within 7 days. With the FST, urine TIMP-2*IGFBP-7 decreased within 2 h from 3.26 ng2/mL2/1000 (IQR: 1.38-5.53) to 2.36 ng2/mL2/1000 (IQR: 1.61-4.87) in RRT and 1.68 ng2/mL2/1000 (IQR: 0.56-2.94) to 0.27 ng2/mL2/1000 (IQR: 0.12-0.89) and non-RRT patients, respectively. While TIMP-2*IGFBP-7 concentrations remained low for up to 12 h in non-RRT patients, we noted a rebound in RRT patients after 6 h. TIMP-2*IGFBP-7 before FST (accuracy 0.66; 95%-CI 0.55-0.78) and the FST itself (accuracy 0.74; 95%-CI: 0.64-0.82) yielded moderate test accuracies in predicting RRT requirement. In contrast, a two-step approach, utilizing FST as an upstream screening tool followed by TIMP-2*IGFBP-7 quantification after 2 h improved predictive accuracy (0.83; 95%-CI 0.74-0.90, p = 0.03) compared to the FST alone, resulting in a positive predictive value of 0.86 (95%-CI 0.64-0.97), and a specificity of 0.96 (95%-CI 0.88-0.99). CONCLUSIONS: The combined application of an upstream FST followed by urinary TIMP-2*IGFBP-7 measurements supports highly specific identification of SA-AKI patients requiring RRT. Upcoming interventional trials should elucidate if this high-risk SA-AKI subgroup, identified by our predictive enrichment approach, benefits from an early RRT initiation.

Next-Generation Sequencing in Critically Ill COVID-19 Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study.

BACKGROUND: Rapid pathogen identification and appropriate antimicrobial therapy are crucial in critically ill COVID-19 patients with bloodstream infections (BSIs). This study aimed to evaluate the diagnostic performance and potential therapeutic benefit of additional next-generation sequencing (NGS) of microbial DNA from plasma in these patients. METHODS: This monocentric descriptive retrospective study reviewed clinical data and pathogen diagnostics in COVID-19 ICU patients. NGS (DISQVER®) and blood culture (BC) samples were obtained on suspicion of BSIs. Data were reviewed regarding the adjustment of antimicrobial therapy and diagnostic procedures seven days after sampling and analyzed using the Chi²-test. RESULTS: Twenty-five cases with simultaneous NGS and BC sampling were assessed. The NGS positivity rate was 52% (13/25) with the detection of 23 pathogens (14 bacteria, 1 fungus, 8 viruses), and the BC positivity rate was 28% (7/25, 8 bacteria; p = 0.083). The NGS-positive patients were older (75 vs. 59.5 years; p = 0.03) with a higher prevalence of cardiovascular disease (77% vs. 33%; p = 0.03). These NGS results led to diagnostic procedures in four cases and to the commencement of four antimicrobial therapies in three cases. Empirical treatment was considered appropriate and continued in three cases. CONCLUSIONS: In COVID-19 patients with suspected BSIs, NGS may provide a higher positivity rate than BC and enable new therapeutic approaches.

The GNB3 C825T polymorphism influences platelet aggregation in human whole blood.

BACKGROUND: Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G-protein ß-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation. METHODS: Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.2 years ±11.7 SD). Genotypes were determined using pyrosequencing and restriction analysis. Data were analyzed by linear one-way analysis of variance and Student's t-test, linear and multiple regression, and the χ(2)-test, as appropriate. RESULTS: Homozygous carriers of the GNB3 825C-allele showed significantly (P≤0.022) increased maximum aggregation for EC(75) dosages compared with CT and TT genotypes [e.g. ADP: CC 150±36 vs. TT 126±33 aggregation unit (AU); thrombin receptor activating peptide: CC 175±46 vs. TT 150±38 AU; U46619: CC 164±33 vs. 149±32 AU; epinephrine: CC 66±41 vs. TT 48±34 AU]. In contrast, genotypes of glycoprotein IIb/IIIa PI(A)-polymorphism had no effect. Regression analysis revealed the GNB3 C825T polymorphism as an independent factor for enhanced platelet aggregation, besides factors such as female sex and blood cell values. CONCLUSION: In human whole blood, the GNB3 825CC genotype is associated with enhanced platelet aggregation.

Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood.

BACKGROUND: Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis. METHODS: Hyperfibrinolysis was induced by addition of recombinant tissue plasminogen activator (r-tPA) (final concentration: 100 ng · mL(-1)) to citrated whole blood obtained from 13 healthy volunteers. To assess inhibition of fibrinolysis, we added to the assays FXIII-A(2)B(2) (0.42 U · mL(-1)), PCC (0.42 U · mL(-1)), rFVIIa (final concentration: 1.6 µg · mL(-1)), TA (final concentration: 0.33 mg · mL(-1)), or saline. Coagulation was analyzed by rotational thromboelastometry (ROTEM®) using the clot lysis index (CLI) after 45 and 60 minutes in extrinsically activated assays, with (FIBTEM®) and without (EXTEM®) inhibition of platelet function by cytochalasin D. RESULTS: After r-tPA-evoked fibrinolysis (CLI45: median 78%; 72/85.5, 25th/75th percentile), FXIII (90%; 82.5/96, P = 0.025), PCC (89%; 74/91, P = 0.0465), and TA (94%; 92/96, P = 0.001) but not rFVIIa (79%; 72/86.5, P = 1.0) significantly attenuated the decrease in CLI. Similarly, CLI60 increased only with FXIII (66%; 33/90.5, P = 0.017) and TA (90%; 89/92, P = 0.001) compared with r-tPA alone (21%; 7/59). After abolition of platelet function by cytochalasin D, only TA (95%; 89/97.5, P = 0.0025) and PCC (84%; 70.5/90, P = 0.0305) but not FXIII or rFVIIa significantly increased CLI45 and CLI60 (TA: 89%; 84.5/96, P = 0.01 and PCC: 55%; 29.5/60, P = 0.0405) compared with r-tPA alone (CLI45: 59%; 40.5/72.5 and CLI60: 10%; 0/30). CONCLUSION: In thromboelastometric assays using whole blood, only TA, FXIII, and PCC significantly inhibited r-tPA-evoked hyperfibrinolysis whereas rFVIIa had no effect. We also found that the effects of exogenous FXIII were dependent on the presence of functional platelets.

Effectiveness of CPR in Hypogravity Conditions-A Systematic Review.

(1) Background: Cardiopulmonary resuscitation (CPR), as a form of basic life support, is critical for maintaining cardiac and cerebral perfusion during cardiac arrest, a medical condition with high expected mortality. Current guidelines emphasize the importance of rapid recognition and prompt initiation of high-quality CPR, including appropriate cardiac compression depth and rate. As space agencies plan missions to the Moon or even to explore Mars, the duration of missions will increase and with it the chance of life-threatening conditions requiring CPR. The objective of this review was to examine the effectiveness and feasibility of chest compressions as part of CPR following current terrestrial guidelines under hypogravity conditions such as those encountered on planetary or lunar surfaces; (2) Methods: A systematic literature search was conducted by two independent reviewers (PubMed, Cochrane Register of Controlled Trials, ResearchGate, National Aeronautics and Space Administration (NASA)). Only controlled trials conducting CPR following guidelines from 2010 and after with advised compression depths of 50 mm and above were included; (3) Results: Four different publications were identified. All studies examined CPR feasibility in 0.38 G simulating the gravitational force on Mars. Two studies also simulated hypogravity on the Moon with a force of 0.17 G/0,16 G. All CPR protocols consisted of chest compressions only without ventilation. A compression rate above 100/s could be maintained in all studies and hypogravity conditions. Two studies showed a significant reduction of compression depth in 0.38 G (-7.2 mm/-8.71 mm) and 0.17 G (-12.6 mm/-9.85 mm), respectively, with nearly similar heart rates, compared to 1 G conditions. In the other two studies, participants with higher body weight could maintain a nearly adequate mean depth while effort measured by heart rate (+23/+13.85 bpm) and VO2max (+5.4 mL·kg-1·min-1) increased significantly; (4) Conclusions: Adequate CPR quality in hypogravity can only be achieved under increased physical stress to compensate for functional weight loss. Without this extra effort, the depth of compression quickly falls below the guideline level, especially for light-weight rescuers. This means faster fatigue during resuscitation and the need for more frequent changes of the resuscitator than advised in terrestrial guidelines. Alternative techniques in the straddling position should be further investigated in hypogravity.