Epidural analgesia and neonatal short-term outcomes during routine childbirth: a 10-year retrospective analysis from the national birth registry of Austria.

BACKGROUND: Epidural analgesia (EA) is well-accepted for pain relief during labor. Still, the impact on neonatal short-term outcome is under continuous debate. This study assessed the outcome of neonates in deliveries with and without EA in a nationwide cohort. METHODS: We analyzed the National Birth Registry of Austria between 2008 and 2017 of primiparous women with vaginal birth of singleton pregnancies. Neonatal short-term morbidity was assessed by arterial cord pH and base excess (BE). Secondary outcomes were admission to a neonatological intensive care unit, APGAR scores, and perinatal mortality. Propensity score-adjusted regression models were used to investigate the association of EA with short-term neonatal outcome. RESULTS: Of 247,536 included deliveries, 52 153 received EA (21%). Differences in pH (7.24 vs. 7.25; 97.5% CI -0.0066 to -0.0047) and BE (-5.89±3.2 vs. -6.15±3.2 mmol/L; 97.5% CI 0.32 to 0.40) with EA could be shown. APGAR score at five minutes <7 was more frequent with EA (OR 1.45; 95% CI: 1.29 to 1.63). Admission to a neonatological intensive care unit occurred more often with EA (4.7% vs. 3.4%) with an OR for EA of 1.2 (95% CI: 1.14 to 1.26). EA was not associated with perinatal mortality (OR 1.33; 95% CI: 0.79 to 2.25). CONCLUSIONS: EA showed no clinically relevant association with neonatal short-term outcome. Higher rates of NICU admission and APGAR score after five minutes <7 were observed with EA. The overall use of EA in Austria is low, and an investigation of causes may be indicated.

Drug-Drug Interactions in Patients with Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a potential life-threatening, heterogenous, inflammatory lung disease. There are no data available on potential drug-drug interactions (pDDIs) in critically ill patients with ARDS. This study analyzed pDDIs in this specific cohort and aimed to investigate possible associations of coronavirus disease 2019 (COVID-19) as an underlying cause of ARDS and treatment with extracorporeal membrane oxygenation (ECMO) with the occurrence of pDDIs. This retrospective study included patients ≥18 years of age diagnosed with ARDS between January 2010 and September 2021. The Janusmed database was used for the identification of pDDIs. A total of 2694 pDDIs were identified in 189 patients with a median treatment duration of 22 days. These included 323 (12%) clinically relevant drug combinations that are best avoided, corresponding to a median rate of 0.05 per day. There was no difference in the number of pDDIs between COVID-19- and non-COVID-19-associated ARDS. In patients treated with ECMO, the rate of the most severely graded pDDIs per day was significantly higher compared with those who did not require ECMO. PDDIs occur frequently in patients with ARDS. On average, each patient may encounter at least one clinically relevant drug combination that should be avoided during their intensive care unit stay.

Peripartum Maternal Admission to the Intensive Care Unit: An Observational Study over a 15-Year Period at a Tertiary Center in Austria.

Peripartum maternal admission to the intensive care unit is challenging for anesthesiologists, obstetricians, and all personnel involved. An understanding of altered maternal physiology, fetal considerations, and acute peripartum emergencies is required to ensure adequate maternal and neonatal outcomes. In this study, we analyzed data of peripartum maternal admissions to the intensive care unit at our large tertiary referral center in order to define trends and changes over time. This study retrospectively analyzed maternal morbidity, admission diagnoses, treatments, and outcomes of women with peripartum admission to the intensive care unit at our tertiary care center over a 15-year period. We found that patient characteristics and admission diagnoses remained remarkably consistent over the observational period; however, there was a significant increase in postpartum hemorrhage (r = 0.200, p < 0.001) and cesarean hysterectomy (r = 0.117, p = 0.027) over time. Moreover, we found a reduction in preterm births (r = -0.154, p = 0.004) and a decreased peripartum neonatal intensive care unit admission rate (r = -0.153, p = 0.006) among women who were transferred to the intensive care unit. Based on our long-term observational data, there is consistent need for intensive care in obstetrics due to a small number of different etiologies. Specialized training for the predominant diagnoses involved as well as multidisciplinary care of the affected patients are both warranted.

Sex differences in pediatric caudal epidural anesthesia under sedation without primary airway instrumentation.

STUDY OBJECTIVE: To identify sex differences associated with caudal epidurals, the most commonly used technique of pediatric regional anesthesia, based on individually validated data of ultrasound-guided blocks performed between 04/2014 and 12/2020. METHODS: Prospectively collected and individually validated data of a cohort of children aged between 0-15 years was analyzed in a retrospective observational study. We included pediatric surgeries involving a primary plan of caudal epidural anesthesia under sedation (without airway instrumentation) and a contingency plan of general anesthesia. Sex-specific rates were analyzed for overall failure of the primary anesthesia plan, for residual pain, for block-related technical complications and for critical respiratory events. We used Fisher´s exact tests and multivariable logistic regressions were used to evaluate sex-specific associations. RESULTS: Data from 487 girls and 2060 boys ≤15 years old (ASA status 1 to 4) were analyzed. The primary-anesthesia-plan failure rate was 5.5% (95%CI 3.8%-7.8%) (N = 27/487) among girls and 4.7% (95%CI 3.9%-5.7%) (N = 97/2060) among boys (p = 0.41). Residual pain was the main cause of failure, with rates of 4.5% (95%CI 2.9-6.6%) (N = 22/487) among girls and 3.0% (95%CI 2.3-3.8%) (N = 61/2060) among boys (p = 0.089). Block-related technical complications were seen at rates of 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls vs 2.5% (95%CI 0.5-2.7%) (N = 51/2060) among boys and, hence, significantly more often among male patients (p = 0.023). Male sex was significantly associated with higher odds (adjusted OR: 3.18; 95% CI: 1.12-9; p = 0.029) for such technical complications regardless of age, ASA status, gestational week at birth or puncture attempts. Critical respiratory events occurred at a 1.7% (95%CI 1.2%-2.3%) rate (N = 35/2060) twice as high among boys as 0.8% (95%CI 0.3%-1.9%) (N = 4/487) among girls (p = 0.21). CONCLUSIONS: While the the primary-anesthesia-plan failure rate was equal for girls and boys, technical complications and respiratory events are more likely to occur in boys.

Combined angiotensin-converting enzyme and aminopeptidase inhibition for treatment of experimental ventilator-induced lung injury in mice.

Introduction: Ventilator-induced lung injury (VILI) may aggravate critical illness. Although angiotensin-converting enzyme (ACE) inhibition has beneficial effects in ventilator-induced lung injury, its clinical application is impeded by concomitant hypotension. We hypothesized that the aminopeptidase inhibitor ALT-00 may oppose the hypotension induced by an angiotensin-converting enzyme inhibitor, and that this combination would activate the alternative renin-angiotensin system (RAS) axis to counteract ventilator-induced lung injury. Methods: In separate experiments, C57BL/6 mice were mechanically ventilated with low (LVT, 6 mL/kg) and high tidal volumes (HVT, 30 mL/kg) for 4 h or remained unventilated (sham). High tidal volume-ventilated mice were treated with lisinopril (0.15 µg/kg/min) ± ALT-00 at 2.7, 10 or 100 µg/kg/min. Blood pressure was recorded at baseline and after 4 h. Lung histology was evaluated for ventilator-induced lung injury and the angiotensin (Ang) metabolite profile in plasma (equilibrium levels of Ang I, Ang II, Ang III, Ang IV, Ang 1-7, and Ang 1-5) was measured with liquid chromatography tandem mass spectrometry at the end of the experiment. Angiotensin concentration-based markers for renin, angiotensin-converting enzyme and alternative renin-angiotensin system activities were calculated. Results: High tidal volume-ventilated mice treated with lisinopril showed a significant drop in the mean arterial pressure at 4 h compared to baseline, which was prevented by adding ALT-00 at 10 and 100 µg/kg/min. Ang I, Ang II and Ang 1-7 plasma equilibrium levels were elevated in the high tidal volumes group versus the sham group. Lisinopril reduced Ang II and slightly increased Ang I and Ang 1-7 levels versus the untreated high tidal volumes group. Adding ALT-00 at 10 and 100 µg/kg/min increased Ang I and Ang 1-7 levels versus the high tidal volume group, and partly prevented the downregulation of Ang II levels caused by lisinopril. The histological lung injury score was higher in the high tidal volume group versus the sham and low tidal volume groups, and was attenuated by lisinopril ± ALT-00 at all dose levels. Conclusion: Combined angiotensin-converting enzyme plus aminopeptidase inhibition prevented systemic hypotension and maintained the protective effect of lisinopril. In this study, a combination of lisinopril and ALT-00 at 10 µg/kg/min appeared to be the optimal approach, which may represent a promising strategy to counteract ventilator-induced lung injury that merits further exploration.

Usefulness and limitations of the acute respiratory distress syndrome definitions in non-intubated patients. A narrative review.

According to the Berlin Definition of acute respiratory distress syndrome (ARDS), a positive end-expiratory pressure (PEEP) of at least 5 cmH2O is required to diagnose and grade ARDS. While the Berlin consensus statement specifically acknowledges the role of non-invasive ventilation (NIV) in mild ARDS, this stratification has traditionally presumed a mechanically ventilated patient in the context of moderate to severe ARDS. This may not accurately reflect today's reality of clinical respiratory care. NIV and high-flow nasal cannula oxygen therapy (HFNO) have been used for managing of severe forms of acute hypoxemic respiratory failure with growing frequency, including in patients showing pathophysiological signs of ARDS. This became especially relevant during the COVID-19 pandemic. The levels of PEEP achieved with HFNO have been particularly controversial, and the exact FiO2 it achieves is subject to variability. Pinpointing the presence of ARDS in patients receiving HNFO and the severity in those receiving NIV therefore remains methodically problematic. This narrative review highlights the evolution of the ARDS definition in the context of non-invasive ventilatory support and provides an overview of the parallel development of definitions and ventilatory management of ARDS. It summarizes the methodology applied in clinical trials to classify ARDS in non-intubated patients and the respective consequences on treatment. As ARDS severity has significant therapeutic and prognostic consequences, and earlier treatment in non-intubated patients may be beneficial, closing this knowledge gap may ultimately be a relevant step to improve comparability in clinical trial design and outcomes.

[Radial head arthropolasty in unreconstructable comminuted fractures of the radial head: Long-term results and factors influencing the outcome]. / Langzeitverlauf und Einflussfaktoren auf das Outcome nach endoprothetischem Ersatz des Radiuskopfes bei nichtrekonstruierbaren Frakturen.

BACKGROUND: Radial head arthroplasty is recognized as the gold standard in the treatment of patients with unreconstructable radial head fractures. OBJECTIVE: The aim of this retrospective study was to investigate the long-term results after prosthetic replacement of the radial head and in a subgroup analysis to identify factors which influence the outcome. MATERIAL AND METHODS: A total of 48 patients with unreconstructable fractures of the radial head and neck were treated by cementless radial head arthroplasty between 05/2008 and 10/2018 (30 bipolar prosthesis type rHead Recon, 18 monopolar prosthesis type MoPyc). After a mean follow-up of 4.6 years 39 patients were assessed clinically and radiologically. RESULTS: The median MEP score was 95 points. Compared to the uninjured side the median range of motion was reduced by 10° for extension/flexion as well as for pronation/supination. In 36 of 39 cases an osseous integration of the prosthesis could be documented. One prosthesis had to be removed after 23 months because of painful loosening. Overlengthening was present in 11 cases (28%), 25 patients (64%) had subcollar bone resorption with a stable osteointegrated stem. Nonbridging heterotopic ossification was observed in 15 patients (38%), 16 patients (41%) showed posttraumatic arthrosis. Patients with sustained elbow dislocation had a significantly worse function in the MEP score and tended to develop an arthrosis more frequently. Ulnohumeral joint degeneration was significantly increased when overlengthening was present. CONCLUSION: Radial head arthroplasty is an effective treatment option for unreconstructable fractures of the radial head and can provide good to excellent mid-term to long-term results. Sustained elbow dislocation as well as overlengthening of the prosthesis had a negative impact on the clinical outcome.

Interactive contribution of hyperinsulinemia, hyperglycemia, and mammalian target of rapamycin signaling to valvular interstitial cell differentiation and matrix remodeling.

Diabetes and its major key determinants insulin resistance and hyperglycemia are known risk factors for calcific aortic valve disease (CAVD). The processes leading to molecular and structural alterations of the aortic valve are yet not fully understood. In previous studies, we could show that valvular interstitial cells (VIC) display canonical elements of classical insulin signaling and develop insulin resistance upon hyperinsulinemia and hyperglycemia accompanied by impaired glucose metabolism. Analyses of cultured VIC and aortic valve tissue revealed extracellular matrix remodeling and degenerative processes. Since PI3K signaling through mammalian target of rapamycin (mTOR) is involved in fibrotic processes of the heart, we aim at further functional investigation of this particular Akt-downstream signaling pathway in the context of diabetes-induced CAVD. Primary cultures of VIC were treated with hyperinsulinemia and hyperglycemia. Phosphorylation of mTOR(Ser2448) was determined by Western blot analysis after acute insulin stimulus. Inhibition of mTOR phosphorylation was performed by rapamycin. Phosphorylation of mTOR complex 1 (MTORC1) downstream substrates 4E-BP1(Thr37/46) and P70S6K(Thr389), and MTORC2 downstream substrate Akt(Ser473) as well as the PDK1-dependent phosphorylation of Akt(Thr308) was investigated. Markers for extracellular matrix remodeling, cell differentiation and degenerative changes were analyzed by Western blot analysis, semi-quantitative real-time PCR and colorimetric assays. Hyperinsulinemia and hyperglycemia lead to alterations of VIC activation, differentiation and matrix remodeling as well as to an abrogation of mTOR phosphorylation. Inhibition of mTOR signaling by rapamycin leads to a general downregulation of matrix molecules, but to an upregulation of α-smooth muscle actin expression and alkaline phosphatase activity. Comparison of expression patterns upon diabetic conditions and rapamycin treatment reveal a possible regulation of particular matrix components and key degeneration markers by MTORC1 downstream signaling. The present findings broaden the understanding of mitogenic signaling pathways in VIC triggered by hyperinsulinemia and hyperglycemia, supporting the quest for developing strategies of prevention and tailored treatment of CAVD in diabetic patients.

Applicability of Vasopressor Trials in Adult Critical Care: A Prospective Multicentre Meta-Epidemiologic Cohort Study.

Objective: To assess the applicability of evidence from landmark randomized controlled trials (RCTs) of vasopressor treatment in critically ill adults. Study Design and Setting: This prospective, multi-center cohort study was conducted at five medical and surgical intensive care units at three tertiary care centers. Consecutive cases of newly initiated vasopressor treatment were included. The primary end point was the proportion of patients (≥18 years) who met the eligibility criteria of 25 RCTs of vasopressor therapy in critically ill adults included in the most recent Cochrane review. Multilevel Poisson regression was used to estimate the eligibility proportions with 95% confidence intervals for each trial. Secondary end points included the eligibility criteria that contributed most to trial ineligibility, and the relationship between eligibility proportions and (i) the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) score, and (ii) the recruitment-to-screening ratio of each RCT. The PRECIS-2 score was used to assess the degree of pragmatism of each trial. Results: Between January 1, 2017, and January 1, 2019, a total of 1189 cases of newly initiated vasopressor therapy were included. The median proportion of cases meeting eligibility criteria for all 25 RCTs ranged from 1.3% to 6.0%. The eligibility criteria contributing most to trial ineligibility were the exceedance of a specific norepinephrine dose, the presence of a particular shock type, and the drop below a particular blood pressure value. Eligibility proportions increased with the PRECIS-2 score but not with the recruitment-to-screening ratio of the trials. Conclusion: The applicability of evidence from available trials on vasopressor treatment in critically ill adults to patients receiving vasopressors in daily practice is limited. Applicability increases with the degree of study pragmatism but is not reflected in a high recruitment-to-screening ratio. Our findings may help researchers design vasopressor trials and promote standardized assessment and reporting of the degree of pragmatism achieved.

Intravenous IgM-enriched immunoglobulins in critical COVID-19: a multicentre propensity-weighted cohort study.

BACKGROUND: A profound inflammation-mediated lung injury with long-term acute respiratory distress and high mortality is one of the major complications of critical COVID-19. Immunoglobulin M (IgM)-enriched immunoglobulins seem especially capable of mitigating the inflicted inflammatory harm. However, the efficacy of intravenous IgM-enriched preparations in critically ill patients with COVID-19 is largely unclear. METHODS: In this retrospective multicentric cohort study, 316 patients with laboratory-confirmed critical COVID-19 were treated in ten German and Austrian ICUs between May 2020 and April 2021. The primary outcome was 30-day mortality. Analysis was performed by Cox regression models. Covariate adjustment was performed by propensity score weighting using machine learning-based SuperLearner to overcome the selection bias due to missing randomization. In addition, a subgroup analysis focusing on different treatment regimens and patient characteristics was performed. RESULTS: Of the 316 ICU patients, 146 received IgM-enriched immunoglobulins and 170 cases did not, which served as controls. There was no survival difference between the two groups in terms of mortality at 30 days in the overall cohort (HRadj: 0.83; 95% CI: 0.55 to 1.25; p = 0.374). An improved 30-day survival in patients without mechanical ventilation at the time of the immunoglobulin treatment did not reach statistical significance (HRadj: 0.23; 95% CI: 0.05 to 1.08; p = 0.063). Also, no statistically significant difference was observed in the subgroup when a daily dose of ≥ 15 g and a duration of ≥ 3 days of IgM-enriched immunoglobulins were applied (HRadj: 0.65; 95% CI: 0.41 to 1.03; p = 0.068). CONCLUSIONS: Although we cannot prove a statistically reliable effect of intravenous IgM-enriched immunoglobulins, the confidence intervals may suggest a clinically relevant effect in certain subgroups. Here, an early administration (i.e. in critically ill but not yet mechanically ventilated COVID-19 patients) and a dose of ≥ 15 g for at least 3 days may confer beneficial effects without concerning safety issues. However, these findings need to be validated in upcoming randomized clinical trials. Trial registration DRKS00025794 , German Clinical Trials Register, https://www.drks.de . Registered 6 July 2021.

Tidal Volume-Dependent Activation of the Renin-Angiotensin System in Experimental Ventilator-Induced Lung Injury.

OBJECTIVES: Ventilator-induced lung injury (VILI) is a major contributor to morbidity and mortality in critically ill patients. Mechanical damage to the lungs is potentially aggravated by the activation of the renin-angiotensin system (RAS). This article describes RAS activation profiles in VILI and discusses the effects of angiotensin (Ang) 1-7 supplementation or angiotensin-converting enzyme (ACE) inhibition with captopril as protective strategies. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Anesthetized mice ( n = 12-18 per group) were mechanically ventilated with low tidal volume (LV T , 6 mL/kg), high tidal volume (HV T , 15 mL/kg), or very high tidal volume (VHV T , 30 mL/kg) for 4 hours, or killed after 3 minutes (sham). Additional VHV T groups received infusions of 60 µg/kg/hr Ang 1-7 or a single dose of 100 mg/kg captopril. MEASUREMENTS AND MAIN RESULTS: VILI was characterized by increased bronchoalveolar lavage fluid levels of interleukin (IL)-6, keratinocyte-derived cytokine, and macrophage inflammatory protein-2 (MIP2). The Ang metabolites in plasma measured with liquid chromatography tandem mass spectrometry showed a strong activation of the classical (Ang I, Ang II) and alternative RAS (Ang 1-7, Ang 1-5), with highest concentrations found in the HV T group. Although the lung-tissue ACE messenger RNA expression was unchanged, its protein expression showed a dose-dependent increase under mechanical ventilation. The ACE2 messenger RNA expression decreased in all ventilated groups, whereas ACE2 protein levels remained unchanged. Both captopril and Ang 1-7 led to markedly increased Ang 1-7 plasma levels, decreased Ang II levels, and ACE activity (Ang II/Ang I ratio), and effectively prevented VILI. CONCLUSIONS: VILI is accompanied by a strong activation of the RAS. Based on circulating Ang metabolite levels and tissue expression of RAS enzymes, classical ACE-dependent and alternative RAS cascades were activated in the HV T group, whereas classical RAS activation prevailed with VHV T ventilation. Ang 1-7 or captopril protected from VILI primarily by modifying the systemic RAS profile.

Duration of invasive mechanical ventilation prior to extracorporeal membrane oxygenation is not associated with survival in acute respiratory distress syndrome caused by coronavirus disease 2019.

BACKGROUND: Duration of invasive mechanical ventilation (IMV) prior to extracorporeal membrane oxygenation (ECMO) affects outcome in acute respiratory distress syndrome (ARDS). In coronavirus disease 2019 (COVID-19) related ARDS, the role of pre-ECMO IMV duration is unclear. This single-centre, retrospective study included critically ill adults treated with ECMO due to severe COVID-19-related ARDS between 01/2020 and 05/2021. The primary objective was to determine whether duration of IMV prior to ECMO cannulation influenced ICU mortality. RESULTS: During the study period, 101 patients (mean age 56 [SD ± 10] years; 70 [69%] men; median RESP score 2 [IQR 1-4]) were treated with ECMO for COVID-19. Sixty patients (59%) survived to ICU discharge. Median ICU length of stay was 31 [IQR 20.7-51] days, median ECMO duration was 16.4 [IQR 8.7-27.7] days, and median time from intubation to ECMO start was 7.7 [IQR 3.6-12.5] days. Fifty-three (52%) patients had a pre-ECMO IMV duration of > 7 days. Pre-ECMO IMV duration had no effect on survival (p = 0.95). No significant difference in survival was found when patients with a pre-ECMO IMV duration of < 7 days (< 10 days) were compared to ≥ 7 days (≥ 10 days) (p = 0.59 and p = 1.0). CONCLUSIONS: The role of prolonged pre-ECMO IMV duration as a contraindication for ECMO in patients with COVID-19-related ARDS should be scrutinised. Evaluation for ECMO should be assessed on an individual and patient-centred basis.

Lung transplantation for acute respiratory distress syndrome: A multicenter experience.

Acute respiratory distress syndrome (ARDS) is a rapidly progressive lung disease with a high mortality rate. Although lung transplantation (LTx) is a well-established treatment for a variety of chronic pulmonary diseases, LTx for acute lung failure (due to ARDS) remains controversial. We reviewed posttransplant outcome of ARDS patients from three high-volume European transplant centers. Demographics and clinical data were collected and analyzed. Viral infection was the main reason for ARDS (n = 7/13, 53.8%). All patients were admitted to ICU and required mechanical ventilation, 11/13 were supported with ECMO at the time of listing. They were granted a median LAS of 76 (IQR 50-85) and waited for a median of 3 days (IQR 1.5-14). Postoperatively, median length of mechanical ventilation was 33 days (IQR 17-52.5), median length of ICU and hospital stay were 39 days (IQR 19.5-58.5) and 54 days (IQR 43.5-127). Prolongation of peripheral postoperative ECMO was required in 7/13 (53.8%) patients with a median duration of 2 days (IQR 2-7). 30-day mortality was 7.7%, 1 and 5-year survival rates were calculated as 71.6% and 54.2%, respectively. Given the lack of alternative treatment options, the herein presented results support the concept of offering live-saving LTx to carefully selected ARDS patients.

Incidence and Etiology of System Exchanges in Patients Receiving Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has established as a cornerstone therapy in severe acute respiratory distress syndrome and refractory hemodynamic failure. As circuit integrity is crucial for adequate organ support, component failure may necessitate a system exchange. In this retrospective study, incidence and etiology of system exchanges during applications of venovenous, venoarterial ECMO, and extracorporeal CO2 removal were examined. Sixty-three (44.4%) of 142 patients were affected by one or more exchanges, totaling 105 replaced circuits. The predominant exchange reason was clotting (n = 20), followed by hemolysis (n = 19), systemic coagulation disorders (n = 13), reconfiguration (n = 13), impaired gas exchange (n = 10), mechanical complications (n = 8), bleeding (n = 6), failed weaning (n = 5), prophylactic exchange (n = 3), and undocumented/other (n = 8). Nineteen (18.1%) events were classified as acute and 70 (66.7%) events as elective exchanges. Patients with circuit exchanges more frequently underwent renal replacement therapy at ECMO initiation (49.2% vs. 29.1%; p = 0.023), had a longer ECMO treatment duration (18 vs. 7.5 days, p < 0.001), and lower hospital survival (29.5% vs. 57.1%; p = 0.002). Considering the high occurrence of coagulation complications, further optimization of coagulation management is deemed necessary.

The Renin-Angiotensin System as a Component of Biotrauma in Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a major concern in critical care medicine with a high mortality of over 30%. Injury to the lungs is caused not only by underlying pathological conditions such as pneumonia, sepsis, or trauma, but also by ventilator-induced lung injury (VILI) resulting from high positive pressure levels and a high inspiratory oxygen fraction. Apart from mechanical factors that stress the lungs with a specific physical power and cause volutrauma and barotrauma, it is increasingly recognized that lung injury is further aggravated by biological mediators. The COVID-19 pandemic has led to increased interest in the role of the renin-angiotensin system (RAS) in the context of ARDS, as the RAS enzyme angiotensin-converting enzyme 2 serves as the primary cell entry receptor for severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. Even before this pandemic, studies have documented the involvement of the RAS in VILI and its dysregulation in clinical ARDS. In recent years, analytical tools for RAS investigation have made major advances based on the optimized precision and detail of mass spectrometry. Given that many clinical trials with pharmacological interventions in ARDS were negative, RAS-modifying drugs may represent an interesting starting point for novel therapeutic approaches. Results from animal models have highlighted the potential of RAS-modifying drugs to prevent VILI or treat ARDS. While these drugs have beneficial pulmonary effects, the best targets and application forms for intervention still have to be determined to avoid negative effects on the circulation in clinical settings.

Recent advances in understanding acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by acute diffuse lung injury, which results in increased pulmonary vascular permeability and loss of aerated lung tissue. This causes bilateral opacity consistent with pulmonary edema, hypoxemia, increased venous admixture, and decreased lung compliance such that patients with ARDS need supportive care in the intensive care unit to maintain oxygenation and prevent adverse outcomes. Recently, advances in understanding the underlying pathophysiology of ARDS led to new approaches in managing these patients. In this review, we want to focus on recent scientific evidence in the field of ARDS research and discuss promising new developments in the treatment of this disease.

Case-based learning and multiple choice questioning methods favored by students.

BACKGROUND: Investigating and understanding how students learn on their own is essential to effective teaching, but studies are rarely conducted in this context. A major aim within medical education is to foster procedural knowledge. It is known that case-based questioning exercises drive the learning process, but the way students deal with these exercises is explored little. METHODS: This study examined how medical students deal with case-based questioning by evaluating 426 case-related questions created by 79 fourth-year medical students. The subjects covered by the questions, the level of the questions (equivalent to United States Medical Licensing Examination Steps 1 and 2), and the proportion of positively and negatively formulated questions were examined, as well as the number of right and wrong answer choices, in correlation to the formulation of the question. RESULTS: The evaluated case-based questions' level matched the United States Medical Licensing Examination Step 1 level. The students were more confident with items aiming on diagnosis, did not reject negatively formulated questions and tended to prefer handling with right content, while keeping wrong content to a minimum. CONCLUSION: These results should be taken into consideration for the formulation of case-based questioning exercises in the future and encourage the development of bedside teaching in order to foster the acquisition of associative and procedural knowledge, especially clinical reasoning and therapy-oriented thinking.