Objectives: To assess whether initial fluid resuscitation with lactated Ringer’s solution compared with 0.9% saline is associated with improved clinical outcomes in patients with sepsis-induced hypotension. Design: Secondary analysis of the randomized controlled Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial. Setting: ICUs and emergency departments in 60 U.S. centers from March 2018 to January 2022. Patients: Participants from the CLOVERS trial. Adult patients with a suspected or confirmed infection and hypotension caused by sepsis. Interventions: Participants received 1–3 L of crystalloid fluid for initial fluid resuscitation before randomization. In this analysis, participants were categorized into a lactated Ringer’s group and a 0.9% saline group based on the fluid type predominantly used for the initial fluid resuscitation (i.e., ≥ 95% of pre-randomization fluid). Measurements and Main Results: Of 1563 participants with sepsis-induced hypotension included in the CLOVERS trial, 622 (39.8%) received lactated Ringer’s solution and 690 (44.1%) received 0.9% saline as solution for the initial fluid bolus. Death before discharge home by day 90 occurred in 76 of 622 participants (12.2%) in the lactated Ringer’s group and in 110 of 690 participants (15.9%) in the 0.9% saline group, resulting in an adjusted hazard ratio of 0.71 (95% CI, 0.51–0.99; p = 0.043). Patients receiving lactated Ringer’s solution had more hospital-free days at 28 days than those receiving 0.9% saline (16.6 ± 10.8 vs. 15.4 ± 11.4, respectively; adjusted mean difference, 1.6 d [95% CI, 0.4–2.8 d; p = 0.009]). Treatment with 0.9% saline was associated with higher levels of serum chloride and decreased levels of serum bicarbonate. Conclusions: Initial fluid resuscitation with lactated Ringer’s solution, compared with 0.9% saline, might be associated with improved survival in patients with sepsis-induced hypotension.

Microcirculatory alterations are predictive of poor outcomes in patients with shock and after cardiac arrest in animal models. However, microcirculatory alterations during human cardiac arrest have not yet been studied. We prospectively included adult patients receiving resuscitation after witnessed out-of-hospital cardiac arrest. Exclusion criteria were hypovolemia, hypo- or hyperthermia (< 34.0 °C, > 37.5 °C), peripheral arterial disease, Raynaud’s disease, and logistical issues (e.g., shortage of space). Capillary refill time was measured on the finger (CRT-F) and the earlobe (CRT-E) every other minute until return of spontaneous circulation (any ROSC) or termination of resuscitation. The primary endpoint was any ROSC, secondary endpoints were 30-day-mortality and good neurological outcome (defined as cerebral performance category 1–2). Based on the data structure, CRT-F and CRT-E values were grouped post-hoc into quartiles and tertiles. A cluster-robust standard error logistic regression was performed for the primary outcome. Trend analyses were made for each individual. After screening of 141 patients, 50 were included in the analysis (median age 75 years, 28

BACKGROUND:The optimal systolic blood pressure (SBP) target in patients with increased cardiovascular risk remains uncertain. This study evaluated the efficacy and safety of intensive SBP control (<120 mm Hg) compared to standard SBP control (<140 mm Hg) in patients with increased cardiovascular risk. METHODS:We conducted a systematic search of PubMed, Embase, Web of Science, and Cochrane Library for RCTs published from database inception through November 2024 that compared intensive SBP control (<120 mm Hg) with standard SBP control (<140 mm Hg) in adults with high cardiovascular risk. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (MACE), cardiovascular death, stroke, myocardial infarction (MI), and heart failure. Safety outcomes included hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities. RESULTS:Five RCTs comprising 39,434 patients were included. The all-cause mortality was significantly lower in the intensive SBP control group (672 of 19,712 [3.4%]) compared to the standard SBP control group (778 of 19,722 [3.9%]) (risk ratio 0.87 [95% confidence interval, 0.76-0.99, p = 0.03]). The incidence of MACE, cardiovascular death, MI, stroke, and heart failure was significantly lower in the intensive SBP control group as compared to standard SBP control group. The treatment effect (MACE) was consistent across all subgroups. Conversely, intensive SBP control was associated with an increased risk of hypotension, syncope, arrhythmia, acute kidney injury, and electrolyte abnormalities. CONCLUSIONS:Targeting intensive SBP control to less than 120 mm Hg was associated with a lower incidence of all-cause mortality and MACE but a higher incidence of adverse events.

OBJECTIVE: We aimed to investigate the association of electrocardiogram (ECG) findings with outcomes in patients with chronic coronary syndrome. METHODS: This secondary analysis of the ISCHEMIA and ISCHEMIA-CKD trials divided patients with chronic coronary syndrome into two groups, those with a normal ECG tracing and abnormal ECG tracing. Repolarization abnormalities included ST-segment depression >= 0.5 mm and T-wave inversion >= 1 mm; conduction abnormalities included left and right bundle branch block (LBBB and RBBB). The primary endpoint was cardiovascular death. Outcomes were assessed using a covariate-adjusted Cox-regression model. RESULTS: Of 5876 patients, 2901 (49.4%) had a normal and 2975 (50.6%) an abnormal ECG tracing. An abnormal ECG tracing at baseline, compared with a normal ECG tracing, was associated with an increased risk of cardiovascular death (257 of 2975 [8.6%] vs. 97 of 2901 [3.3%], adjusted hazard ratio [aHR] 2.01, 95% CI 1.58-2.55) over a median follow-up period of 3.1 years (IQR 2.1-4.2). This finding was consistent across subgroups except for patients with black skin color and current smokers, in whom an abnormal ECG was not significantly associated with increased risk of cardiovascular death. Individual ECG abnormalities (ST-segment depression [aHR 2.0, 95% CI 1.52-2.63], T-wave inversion [aHR 1.89, 95% CI 1.40-2.54], LBBB [aHR 1.74, 95% CI 1.05-2.90], and RBBB [aHR 1.52, 95% CI 1.04-2.22]) were independently associated with an increased risk of cardiovascular death. CONCLUSION: In patients with chronic coronary syndrome, an abnormal ECG tracing was associated with an increased risk of cardiovascular death. Our findings underscore the importance of the ECG in cardiovascular risk stratification and prognostication. TRIAL REGISTRATION: NCT01471522, BioLINCC ID 14539. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) center dot The American Journal of Medicine (2025) 138:61-69

BACKGROUND:Amiodarone is used in shockable out-of-hospital cardiac arrest (OHCA), but the ideal dose is unknown. METHODS:This was an analysis from the Resuscitation Outcomes Consortium Cardiac Epidemiologic Registry (2011-2015). Patients with shockable OHCA who received 5 or more defibrillation attempts and treatment with 300 or 450 mg of amiodarone were included. Outcomes were ROSC at ED arrival, survival at hospital discharge, and favorable neurologic function at discharge. Group-differences were adjusted for using inverse probability weighting and a multiple logistic regression model. RESULTS:The present study included 910 patients; 426 received amiodarone 300 mg and 484 received amiodarone 450 mg. The amiodarone 300 mg group had a higher estimated probability of ROSC at ED arrival as compared with the amiodarone 450 mg group (30.8% [95% CI, 26.6-35.1] vs 24.2% [95% CI, 20.5-27.9], respectively; adjusted probability difference, 6.6% (0.9-12.3), p = 0.0234). The group differences in survival at hospital discharge (21.3% [95% CI, 17.2-25.4] vs 18.0% [95% CI, 14.6-21.5]; adjusted probability difference, 3.3% [-2.3-8.8]) and favorable neurologic outcome at discharge (16.5% [95% CI, 12.9-20.2] vs 12.7% [95% CI, 9.5-16.0]; adjusted probability difference, 3.8% [95% CI, -1.2-8.7]) did not reach statistical significance. CONCLUSION:In patients with shockable OHCA who received 5 or more defibrillation attempts, a dose of amiodarone 300 mg was associated with a similar survival compared with a total dose of amiodarone 450 mg. Further study is needed to evaluate the need for a second administration of amiodarone in patients with shockable OHCA.

Background Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus that causes the life-threatening toxic shock syndrome. The development of a safe and immunogenic vaccine against TSST-1 remains an unmet medical need. We investigated the safety, tolerability and immunogenicity of a recombinant TSST-1 variant vaccine (rTSST-1v) after 1-3 injections in healthy volunteers. Methods In this randomised, double-blind, adjuvant-controlled, parallel-group, phase 2 trial, healthy adults aged 18-64 were randomly allocated to undergo 1-3 injections of either 10 or 100 mu g rTSST-1v or Al(OH)3. The primary endpoint was safety and tolerability of rTSST-1v in the intention-to-treat population. The per-protocol population was used for the immunogenicity analysis. The trial is registered with EudraCT#: 2015-003714-24; ClinicalTrials.gov#: NCT02814708. Findings Between April and November 2017,140 subjects were enrolled and 126 completed the trial. rTSST-1v showed a good safety and tolerability profile. A total of 855 systemic adverse events occurred, 280 of which were suspected related adverse events, without dose dependency. Two participants were discontinued early because of allergic reactions. Seroconversion occurred in >81% of subjects within 3 months of the first immunisation which was sustained until 18 months after the third immunisation in over 70% of subjects in the pooled low-dose group and in over 85% in the pooled high-dose group. Interpretation rTSST-1v in cumulative doses of up to 300 mu g was safe, well-tolerated and highly immunogenic. Two immunisations with 100 mu g rTSST-1v provided the most persistent immune response and may be evaluated in future trials. Funding Biomedizinische Forschung & Bio-Produkte AG funded this study.

Anaphylaxis is a life-threatening condition that involves severe cutaneous, respiratory, and cardiovascular symptoms. Disseminated intravascular coagulation (DIC) is an acquired, widespread activation of coagulation that can be caused by infectious conditions (e.g., sepsis) and noninfectious conditions. The onset of DIC following anaphylaxis is not commonly known, and information regarding the pathomechanism linking anaphylaxis to DIC is scarce. Further, demographic and clinical data in anaphylaxis-induced DIC are still missing to this day. Triggered by a case of anaphylaxis-induced DIC that seamlessly transitioned to lethal sepsis-induced DIC, we aimed to characterize the patient population affected by anaphylaxis-induced DIC by performing a review of existing literature and expand the discussion to underlying mechanisms. The overall mortality of the patient cohort (n = 30) identified by the literature review was 50%. All patients that died either suffered a bleeding event or a thrombotic event. The majority of patients (n = 25/30; 83%) had bleeding events; thrombotic events were only reported in nonsurvivors (n = 9/15 or 60% of nonsurvivors; vs. n = 0/15 in survivors; p < 0.001). Nonsurvivors of anaphylaxis-induced DIC were on average 25 years older than survivors (p = 0.068). In conclusion, DIC can complicate anaphylaxis and is expected to contribute to poor microvascular perfusion after anaphylaxis. Particularly, elderly patients with known cardiovascular disease and patients who develop thrombotic events are susceptible to lethal outcomes. As a rare and largely uncharacterized disease entity, further research is needed to investigate the link between DIC and anaphylaxis and to potentially identify better treatment strategies.

Background: Recombinant tissue plasminogen activator (rt-PA) is a thrombolytic agent and essential in emergency medical care. Given recent supply shortages, the availability of biosimilar products is an urgent medical need. However, biosimilarity trials are difficult to perform in critically ill patients. Objectives: The aim of this pilot study was to investigate the pharmacokinetics and pharmacodynamics of low rt-PA doses to establish a model for testing proposed biosimilars in healthy volunteers. Methods: Eight healthy volunteers received 0.02 to 0.05 mg/kg rt-PA on 3 study days; blood samples were obtained every 4 minutes after the end of the bolus infusion to measure rt-PA antigen levels by enzyme immunoassay, and the pharmacodynamics were assessed with rotational thromboelastometry. Results: Bolus infusion of low rt-PA doses was safe and well tolerated. Maximal plasma concentrations and the area under the curve increased dose-dependently. Time-concentration curves were clearly separated between the lower and the higher doses. As expected, the half-live of rt-PA was short (4.5-5 min), and representative for therapeutic doses. The intrasubject coefficient variations were moderate (<25%). Bolus infusion of rt-PA dose-dependently shortened lysis time and lysis onset time in both dose groups and caused maximum clot lysis of 100% in all participants. Conclusion: In conclusion, the pharmacokinetics of rt-PA was dose linear and displayed limited intrasubject variability even at subtherapeutic doses. The half-life and thus clearance of rt-PA was representative of full therapeutic doses. The lysis time was shortened in a dose and time-dependent fashion and was clearly distinguishable between doses. Thus, the model appears to be suitable and sensitive to test biosimilarity.

Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD. This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90. Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45

Abstract Background There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. Methods This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7–6.4% [40–47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. Results Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1–4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95–2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29–2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15–10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. Conclusions In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Severe burn injuries are often accompanied by infections and associated with high morbidity and mortality. This study aimed to compare the prevalence and clinical impact of bacteremia between patients receiving intensive care with and without burns. This single-center retrospective cohort study at the University Hospital Vienna, Austria, analyzed blood cultures from intensive care unit (ICU) patients with and without burns (2012–2022) to assess the prevalence of bacteremia, the associated pathogen distribution and the 60-day all-cause mortality. In 1170 ICU patients, 303 with burns and 867 without, the prevalence of bacteremia was similar among patients with at least one blood culture (31/157 [19.7

Background: : Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1- receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF. Methods: : In this randomized, double-blind, placebo-controlled pilot trial, patients with OHCA and recurrent or refractory VF (at least 3 defibrillation attempts and last rhythm shockable), pretreated with epinephrine and amiodarone, were allocated to receive add-on treatment with landiolol or placebo. Landiolol was given as a 20 mg bolus infusion. The primary efficacy outcome was time from trial drug infusion to sustained return of spontaneous circulation (ROSC). Safety outcomes included the onset of bradycardia and asystole. Results: : A total of 36 patients were enrolled, 19 were allocated to the landiolol group and 17 to the placebo group. Time from trial drug infusion to sustained ROSC was similar between treatment groups (39 min [landiolol] versus 41 min [placebo]). Sustained ROSC was numerically lower in the landiolol group compared with the placebo group (7 patients [36.8%] versus 11 patients [64.7%], respectively). Asystole within 15 min of trial drug infusion occurred significantly more often in the landiolol group than in the placebo group (7 patients [36.8%] and 0 patients [0.0%], respectively). Conclusion: : In patients with OHCA and refractory VF who are pretreated with epinephrine and amiodarone, add-on bolus infusion of landiolol 20 mg did not lead to a shorter time to sustained ROSC compared with placebo. Landiolol might be associated with bradycardia and asystole.

INTRODUCTION:Cold agglutinin disease (CAD) is a difficult-to-treat autoimmune hemolytic anemia and B cell lymphoproliferative disorder associated with fatigue, acrocyanosis, and a risk of thromboembolic events. Cold-induced binding of autoantibody agglutinates red blood cells and triggers the classical complement pathway, leading to predominantly extravascular hemolysis.AREAS COVERED:This review summarizes clinical and experimental antibody-based treatments for CAD and analyzes the risks and benefits of B cell and complement directed therapies, and discusses potential future treatments for CAD.EXPERT OPINION:Conventional treatment of CAD includes a B cell targeted treatment approach with rituximab, yielding only limited treatment success. The addition of a cytotoxic agent (e.g. bendamustine) increases efficacy, but this is accompanied by an increased risk of neutropenia and infection. Novel complement directed therapies have emerged and were shown to have good efficacy against hemolysis and safety profiles but are expensive and unable to address circulatory symptoms. Complement inhibition with sutimlimab may be used as a bridging strategy until B cell directed therapy with rituximab takes effect or continued indefinitely if needed. Future antibody-based treatment approaches for CAD involve the further development of complement directed antibodies, a combination of rituximab and bortezomib, and daratumumab. Non-antibody based prospective treatments may include the use of Bruton tyrosine kinase inhibitors.

Background: Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus that causes the life-threatening toxic shock syndrome. The development of a safe and immunogenic vaccine against TSST-1 remains an unmet medical need. We investigated the safety, tolerability and immunogenicity of a recombinant TSST-1 variant vaccine (rTSST-1v) after 1-3 injections in healthy volunteers. Methods: In this randomised, double-blind, adjuvant-controlled, parallel-group, phase 2 trial, healthy adults aged 18-64 were randomly allocated to undergo 1-3 injections of either 10 or 100µg rTSST-1v or Al(OH)3. The primary endpoint was safety and tolerability of rTSST-1v in the intention-to-treat population. The per-protocol population was used for the immunogenicity analysis. The trial is registered with EudraCT#: 2015-003714-24; ClinicalTrials.gov#: NCT02814708. Findings: Of 140 enrolled subjects, 126 completed the trial (per-protocol analysis). rTSST-1v showed a good safety and tolerability profile. A total of 855 systemic adverse events occurred, 280 of which were suspected related adverse events, without dose dependency. Two participants were discontinued early because of allergic reactions. Seroconversion occurred in >81% of subjects within 3 months of the first immunisation which was sustained until 18 months after the third immunisation in over 70% of subjects in the pooled low-dose group and in over 85% in the pooled high-dose group. Interpretation: rTSST-1v in cumulative doses of up to 300 µg was safe, well-tolerated and highly immunogenic. Two immunisations with 100 µg rTSST-1v provided the most persistent immune response and may be evaluated in future trials.Trial Registration: EudraCT 2015-003714-24, clinicaltrials.gov (NCT02814708).Funding: This research was funded by Biomedizinische Forschung & Bio-Produkte AG.Declaration of Interest: GG, CS, CF, MMS, NB, UD, AT, and BJ declare no competing interests. Martha M. Eibl was the owner of Biomedizinische Forschung & Bio-Produkte AG. DH, LS, NM, and AR are employees of the study funder Biomedizinische Forschung & Bio- Produkte AG, a biotechnology company engaged in the development of BioMed rTSST-1v.Ethical Approval: The study was approved by the local ethics committee (Ethics Committee of the Medical University of Vienna, European Research Council Number 1810/2015) and was conducted in compliance with the Declaration of Helsinki, the Good Clinical Practice guidelines and with the Note for Guidance on Clinical Evaluation of New Vaccines. Oral and written informed consent was obtained prior to any trial-related procedure.

Background: It is unclear whether thrombectomy alone is non-inferior to thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion.Purpose: To perform a comprehensive, trial-level data, non-inferiority meta-analysis of randomised controlled trials comparing endovascular thrombectomy with and without intravenous thrombolysis in patients with ischemic stroke due to large-vessel occlusion of anterior circulation.Methods: The prespecified primary efficacy outcome was functional independence, defined as a modified Rankin scale (mRS)score of 0 to 2 at 90 days. The two prespecified non-inferiority margins were risk differences of-10% and -5%. The study was registered in PROSPERO (CRD42022361110) and conducted according to PRISMA guidelines.Results: Six trials were included in this analysis (DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, DIRECT-SAFE and SWIFT DIRECT) comprising a total of 2334 patients. Functional independence at 90 days was achieved by 570 (49.0%) of 1164 patients in the thrombectomy alone group and 595 (50.9%) of 1170 patients in the throm-bectomy with thrombolysis group (pooled risk difference -0.02, [95% CI-0.06-0.02]). Combined thrombec-tomy and thrombolysis were associated with significantly higher rates of successful reperfusion (pooled risk ratio 0.96 [95% CI, 0.93-0.99], p = 0.006) but at the expense of a significantly increased risk of overall -but not symptomatic -intracranial haemorrhage (pooled risk ratio 0.87 [95% CI, 0.77-0.98], p = 0.02).Conclusions: Compared with a combined treatment approach, thrombectomy alone was non-inferior at-10% non-inferiority margin, but not at a -5% inferiority margin for functional independence. Current evidence cannot exclude clinically important differences between the two treatment approaches.

Factor VIII (FVIII) circulates in a noncovalent complex with von Willebrand Factor (VWF), the latter determining FVIII half-life. The VWF-binding aptamer rondaptivon pegol (BT200) increases plasma levels of VWF/FVIII in healthy volunteers. This trial assessed its safety, pharmacokinetics, and pharmacodynamics in hemophilia A. Nineteen adult patients (ages 20-62 years, 4 women) with hemophilia A (8 mild, 2 moderate, and 9 severe) received subcutaneous injections of rondaptivon pegol. After an initial fixed dose of 3 mg on days 0 and 4, patients received weekly doses of 2 to 9 mg until day 28. Severe hemophilia A patients underwent sparse-sampling population pharmacokinetics individual profiling after the final dose of rondaptivon pegol. Adverse events, pharmacokinetics, and pharmacodynamics were assessed. FVIII activity and VWF levels were measured. All patients tolerated rondaptivon pegol well. The geometric mean half-life of rondaptivon pegol was 5.4 days and rondaptivon pegol significantly increased VWF levels. In severe hemophilia A, 6 doses of rondaptivon pegol increased the half-lives of 5 different FVIII products from a median of 10.4 hours to 31.1 hours (range, 20.8-56.0 hours). Median FVIII increased from 22% to 48% in mild hemophilia A and from 3% to 7.5% in moderate hemophilia A. Rondaptivon pegol is a first-in-class prohemostatic molecule that extended the half-life of substituted FVIII approximately 3-fold and increased endogenous FVIII levels approximately 2-fold in hemophilia patients. This trial was registered at www.clinicaltrials.gov as #NCT04677803.

Background Bacterial co-infections are believed to be less frequent in patients with Covid-19 than influenza, but frequencies varied between studies. Methods This single-center retrospective, propensity score-matched analysis included adult patients with Covid-19 or influenza admitted to normal-care wards between 02/2014 and 12/2021. Covid-19 cases were propensity score matched to influenza cases at a 2:1 ratio. Community-acquired and hospital-acquired bacterial co-infections were defined as positive blood or respiratory cultures ≤ 48 h or > 48 h after hospital admission, respectively. The primary outcome was comparison of community-acquired and hospital-acquired bacterial infections between patients with Covid-19 and influenza in the propensity score-matched cohort. Secondary outcomes included frequency of early and late microbiological testing. Results A total of 1337 patients were included in the overall analysis, of which 360 patients with Covid-19 were matched to 180 patients with influenza. Early (≤ 48 h) microbiological sampling was performed in 138 (38.3%) patients with Covid-19 and 75 (41.7%) patients with influenza. Community-acquired bacterial co-infections were found in 14 (3.9%) of 360 patients with Covid-19 and 7 (3.9%) of 180 patients with influenza (OR 1.0, 95% CI 0.3–2.7). Late (> 48 h) microbiological sampling was performed in 129 (35.8%) patients with Covid-19 and 74 (41.1%) patients with influenza. Hospital-acquired bacterial co-infections were found in 40 (11.1%) of 360 patients with Covid-19 and 20 (11.1%) of 180 patients with influenza (OR 1.0, 95% CI 0.5–1.8). Conclusion The rate of community-acquired and hospital-acquired bacterial co-infections was similar in hospitalized Covid-19 and influenza patients. These findings contrast previous literature reporting that bacterial co-infections are less common in Covid-19 than influenza.

While the initial minutes of acute emergencies significantly influence clinical outcomes, prehospital research often receives inadequate attention due to several challenges. Retrospective chart reviews carry the risk of incomplete and inaccurate data. Furthermore, prehospital intervention trials frequently encounter difficulties related to extensive training requirements, even during the planning phase. Consequently, we have implemented prospective research concepts involving additional paramedics and physicians directly at the scene during major emergency calls. Three concepts were used: (I) Paramedic field supervisor units, (II) a paramedic + physician field supervisor unit, (III) a special physician-based research car. This paper provides insights into our historical perspective, the current situation, and the lessons learned while overcoming certain barriers and using existing and novel facilitators. Our objective is to support other research groups with our experiences in their planning of upcoming prehospital trials.