Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study.

AIMS: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria. METHODS AND RESULTS: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI. CONCLUSION: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care.

ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.

SARS-CoV-2 rapid antigen test: Fast-safe or dangerous? An analysis in the emergency department of an university hospital.

The use of Antigen point of care tests (AgPOCT) might be an essential tool to fight the coronavirus disease 2019 (COVID-19) pandemic. Manufacturer information indicates a specificity of about 95% and there is a growing interest to use these tests area-wide. Therefore, it is necessary to clarify whether AgPOCT can be used safely for "rule-in" (detection of positive patients) and for "rule-out" (valid negative testing). Two thousand three hundred and seventy-five patients received polymerase chain reaction (PCR) testing and AgPOCT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms. The positive predictive value of symptomatic and asymptomatic patients was compared with a cut-off threshold cycle (C t ) value of ≤30 and in total. Five hundrded and fifty-one patients tested positive for the SARS-CoV-2 virus by PCR, of whom 35.2% presented without symptoms. In all patients, regardless of their symptoms or C t values, a sensitivity of 68.9% and a specificity of 99.6% were calculated for AgPOCT. In patients with C t values ≤30, a sensitivity of 80.5% (95% confidence interval: ±1.62) and a specificity of 99.6% were shown for all tests (symptomatic/asymptomatic). Highly infectious patients (C t ≤ 20), regardless of symptoms, were reliably detected by the AgPOCT. In infectious patients with C t values ≤30, the test has a sensitivity of about 80% regardless of COVID-19 typical symptoms, which is apparently less than the 96.52% specificity indicated by the manufacturer. Relevant improvement in test sensitivity by querying the patients who are symptomatic and asymptomatic is also not feasible. We strongly suggest that we critically question the use of AgPOCT for "rule-out," as they only provide a supposed safety.

The influence of IFITM3 polymorphisms on susceptibility to SARS-CoV-2 infection and severity of COVID-19.

BACKGROUND AND AIMS: The interferon-induced transmembrane protein 3 (IFITM3) plays an important role in the adaptive and innate immune response by inhibiting viral membrane hemifusion between the host and viral cell cytoplasm. Single nucleotide polymorphisms (SNPs) in the gene IFITM3 have been associated with susceptibility and severity of influenza or other viral infections. We aimed to analyze the role of SNPs in the gene IFITM3 in SARS-CoV-2 infection. METHODS: We performed genotyping of the SNPs rs12252 and rs34481144 in the gene IFITM3 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics. Neither IFITM3 rs12252 nor rs34481144 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. Interestingly, we observed the putative deleterious rs12252 CC genotype only in SARS-CoV-2-positive patients (N = 2). Also, we found a non-significant higher frequency of rs34481144 A-allele carriers in the patients with 'serious' COVID-19. CONCLUSIONS: In summary, we could not confirm the recently reported influence of polymorphisms in the gene IFITM3 on SARS-CoV-2 infection risk or severity of COVID-19 in a German cohort. Additional studies are needed to clarify the influence of the rs12252 CC genotype on SARS-CoV-2 infection risk and the rs34481144 A-allele on course of COVID-19.

What about the others: differential diagnosis of COVID-19 in a German emergency department.

BACKGROUND: The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. METHOD: We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. RESULTS: Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). CONCLUSION: For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. TRIAL REGISTRATION: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

Effective intranasal cooling in an 80 year old patient with heatstroke.

Intranasal cooling by the evaporation of perflourcarbon is almost exclusively used for the induction of therapeutic hypothermia in post-resuscitation care. This method has proven to be effective and safe. This case presents a successful application to a patient with external heatstroke. The 80 year old male patient was found in deep coma (GCS 4) by emergency medical services (EMS) showing a core temperature around 42 °C. Despite of preclinical physical cooling, the patient showed a persistent temperature of 41.5 °C upon reaching the emergency department. After endotracheal intubation intranasal evaporation cooling was performed and the patient's core temperature was reduced efficiently. We recorded an excellent cooling rate of 2.8 °C per hour. 16 h later the patient was successfully extubated with a good neurological outcome. This case shows that although intranasal cooling is mostly known for post-resuscitation care, there is a sensible application in heatstroke with imminent cerebral oedema.

Point-of-care PCR testing of SARS-CoV-2 in the emergency department: Influence on workflow and efficiency.

PROBLEM: Regarding transmissible viral diseases such as those caused by SARS-CoV-2 virus, one of the key challenges is isolation management until final diagnosis. This study investigates the influence of SARS-CoV-2 point-of-care (POC) PCR on workflow and efficiency in an emergency department (ED) of a tertiary university hospital. METHOD: An analysis of 17,875 ED patients receiving either SARS-CoV-2 POC PCR (rapid PCR, 11,686 patients) or conventional laboratory SARS-CoV-2 PCR (conventional PCR, 6,189 patients) was performed. The pathways for both groups were mapped and compared, and process times from admission to diagnosis were measured. Effects on resource management within the ED were quantified. Direct costs due to isolation, loss of capacities, and revenues were calculated for inpatients. RESULTS: The mean time from admission to result was 1.62 h with rapid PCR and 16.08 h with conventional PCR (p < 0.01), reducing the isolation time by 14.46 h. In the first 2 h after testing, test results were available for > 75% of the rapid PCR group and none of the conventional PCR group. Ninety percent of the results were available within 3 h for the rapid PCR and within 21 h for the conventional PCR group. For the conventional PCR group, an increase in direct costs of €35.74 and lost revenues of €421.06 for each inpatient case was detected. CONCLUSION: Rapid PCR significantly reduces the time-to-results and time for isolation relative to conventional PCR. Although testing costs for rapid PCR are higher, it benefits workflow, reduces total costs, and frees up ward capacity.

Effect of video laryngoscopy for non-trauma out-of-hospital cardiac arrest on clinical outcome: A registry-based analysis.

AIM: Videolaryngoscopy (VL) is a promising tool to provide a safe airway during cardiopulmonary resuscitation (CPR) and to ensure early reoxygenation. Using data from the German Resuscitation Registry, we investigated the outcome of non-traumatic out-of-hospital cardiac arrest (OHCA) patients treated with VL versus direct laryngoscopy (DL) for airway management. METHODS: We analysed retrospective data of 14,387 patients from 1 January 2018 until 31 December 2021 (VL group, n = 2201; DL group, n = 12186). Primary endpoint was discharge with cerebral performance categories one and two (CPC1/2). Secondary endpoints were the rate of return of spontaneous circulation (ROSC), hospital admission, hospital admission with ongoing cardiopulmonary resuscitation, 30-day survival/ hospital discharge and airway management complications. We used multivariate binary logistic regression analysis to identify the effects on outcome of known influencing variables and of VL vs DL. RESULTS: The multivariate regression model revealed that VL was an independent predictor of CPC1/2 survival (OR = 1.34, 95% CI = 1.12-1.61, p = 0.002) and of hospital discharge/30-day survival (OR = 1.26, 95% CI = 1.08-1.47, p = 0,004). CONCLUSION: VL for endotracheal intubation (ETI) at OHCA was associated with better neurological outcome in patients with ROSC. Therefore, the use of VL for OHCA offers a promising perspective. Further prospective studies are required.

[Risk management in the triage of emergency room patients to outpatient care : Manchester Triage System and CEReCo-blue as a tool for low-risk patient management in integrated emergency centers]. / Risikomanagement in der Triage ambulanter Notfallpatienten : Manchester Triage System und CEReCo-blue als Instrument zur risikoarmen Patientensteuerung in integrierten Notfallzentren.

BACKGROUND: So-called "integrated emergency centers (IEC)" are going to be implemented in German hospitals and will be the first contact point in the emergency care setting. For early decision-making whether outpatient care or inpatient admission in the emergency department is indicated, it would be helpful to have a system to identify patients for outpatient treatment. In this study, we investigated whether the Manchester Triage System (MTS) is suitable for identifying patients who can be safely referred to emergency room patients to outpatient care. METHODS: Patients in the emergency department of the "blue" MTS level were examined for the endpoint inpatient admission and were compared with the next higher MTS category "green". In a second step, the "blue" MTS category was examined for the most common criteria leading to inpatient admission. RESULTS: After excluding patients who were presented by the emergency medical services (EMS) or after prior medical consultation, the rate of inpatient admissions in the blue MTS category was significantly lower than in the green category (10.8% vs 29.0%). The rate could be reduced to 0.9% by establishing a subgroup with the additional exclusion criteria chronic disorder and readmission after prior inpatient treatment (CEReCo-blue group: Chronic Disorder (C), Emergency Medical Service (E), Readmission (R), Prior Medical Consultation (Co)). CONCLUSION: The blue MTS category does not appear to be suitable for the selection of patients with indication for outpatient treatment. We propose the introduction of a subgroup, the so-called CEReCo-blue group, which could be helpful for the selection of this patient group.

Streamlining Patient Management of Suspected COVID-19 Patients in the Emergency Department: Incorporation of Pulmonary CT Angiography into the Triaging Algorithm.

Purpose: To evaluate the use of pulmonary computed tomography (CT) angiography during initial admission at an emergency department (ED), to identify COVID-19 patients with accompanying pulmonary embolism (PE) and its impact on clinical management. Methods: We performed a retrospective analysis of COVID-19 patients that underwent pulmonary CT angiography at the ED. CT scans were evaluated for the presence and extent of PE and for imaging changes suspicious of COVID-19. Patients were subdivided into two groups: (1) Group A consisted of patients with proven COVID-19 based on real-time polymerase chain reaction (RT-PCR), and (2) Group B of patients suspected for COVID-19, comprising patients positive on RT-PCR and/or COVID-19-suspicious CT findings. To assess the differences between patients with and without pulmonary embolism, Fisher's exact test was used. Results: A total of 308 patients were admitted to the ED for diagnostic work-up of dyspnea and suspected COVID-19, and 95 patients underwent pulmonary CT angiography. PE was detected in 13.6% (3/22) of patients in Group A and 20.7% (6/29) in Group B. No significant differences were observed between patients with and without PE concerning hospitalization (Group B: 100% (6/6) vs. 91.3% (21/23)), the necessity of oxygen therapy (Group B: 66% (4/6) vs. 43.5% (10/23)), and death (Group B: 33% (2/6) vs. 4.3% (1/23) p > 0.05, respectively). Conclusions: In 20.7% of COVID-19 patients, PE was detected upon admission to the ED. Although the incorporation of early pulmonary CT angiography in patients suspicious of COVID-19 may be beneficial to identify concomitant PE, further studies are necessary to corroborate these findings.

[Wave riding - 12 months of COVID-19 in a German tertiary care center]. / Wellenreiten ­ 12 Monate COVID-19 im Maximalversorger.

INTRODUCTION: With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. METHODS: Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. RESULTS: Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. CONCLUSIONS: The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.

Evaluation of a new COVID-19 triage algorithm in the emergency department including combined antigen and PCR-testing: A case-control study.

The coronavirus disease 2019 (COVID-19) pandemic is a major challenge for global healthcare systems. Early and safe triage in the emergency department (ED) is crucial for proper therapy. However, differential diagnosis remains challenging. Rapid antigen testing (RAT) may help to improve early triage and patient safety. We performed a retrospective study of 234 consecutive patients with suspected COVID-19 who presented to our ED in November 2020. All underwent SARS-CoV-2-nasopharyngeal swab testing using both RAT and reverse transcription polymerase chain reaction (RT-PCR). The inpatient treatment was established according to an empirically developed triage algorithm. The accuracy of the suggested algorithm was analyzed based on the rate of outpatients returning within 7 days and inpatients staying for less than 48 hours. COVID-19 inpatients and outpatients were compared for symptoms, vital signs, and C-reactive protein levels. Of the 221 included patients with suspected COVID-19 infection, the diagnosis could be confirmed in 120 patients (54.3%) by a positive RT-PCR result, whereas only 72% of those had a positive antigen test. Of the 56 COVID-19 outpatients, three returned within 7 days with the need for hospital treatment due to clinical deterioration. Among the 64 COVID-19 inpatients, 4 were discharged within 48 hours, whereas 60 stayed longer (mean duration 10.2 days). The suggested triage algorithm was safe and efficient in the first 234 consecutive patients. RAT can confirm a diagnosis in 72% of PCR proven COVID-19 patients and allows early cohort isolation as an important way to save hospital capacity.

Transmembrane serine protease 2 Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection: A German Case-Control Study.

The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.

Separating the wheat from the chaff-COVID-19 in a German emergency department: a case-control study.

BACKGROUND: COVID-19 pandemia is a major challenge to worldwide health care systems. Whereas the majority of disease presents with mild symptoms that can be treated as outpatients, severely ill COVID-19 patients and patients presenting with similar symptoms cross their ways in the emergency department. Especially, the variety of symptoms is challenging with primary triage. Are there parameters to distinguish between proven COVID-19 and without before? How can a safe and efficient management of these inpatients be achieved? METHODS: We conducted a retrospective analysis of 314 consecutive inpatient patients who presented with possible symptoms of COVID-19 in a German emergency department between March and April 2020 and were tested with a SARS-Cov-2 nasopharyngeal swab. Clinical parameters, Manchester Triage System categories, and lab results were compared between patients with positive and negative test results for SARS-Cov-2. Furthermore, we present the existing COVID-19 workflow model of the university hospital in Essen which proved to be efficient during pandemia. RESULTS: Forty-three of the 314 patients (13.7%) were tested positive for COVID-19 by SARS-Cov-2 nasopharyngeal swab. We did not find any laboratory parameter to distinguish safely between patients with COVID-19 and those with similar symptoms. Dysgeusia was the only clinical symptom that was significantly more frequent among COVID-19 patients. CONCLUSION: Dysgeusia seems to be a typical symptom for COVID-19, which occurred in 14% of our COVID-19 patients. However, no valid parameters could be found to distinguish clinically between COVID-19 and other diseases with similar symptoms. Therefore, early testing, a strict isolation policy, and proper personal protection are crucial to maintain workflow and safety of patients and ED staff for the months to come. TRIAL REGISTRATION: German Clinical Trials registry, DRKS00021675.

[COVID-19 Triage: Who is an inpatient? The Essen triage model]. / COVID-19-Triage: Wer bleibt stationär? Das Modell Essen.

INTRODUCTION: Data about optimal initial assessment in patients with suspicion for COVID19-infection or already confirmed infection are sparse. Especially, in preparation for expected mass casualty incident it is necessary to distinguish early and efficiently between outpatient and inpatient treatment including the need for intensive care therapy. METHODS: We present a model for a safe and efficient triage, which is established and used in the university hospital of Essen, Germany. It is intended for a non-disaster situation. This model is a combination of clinical assessment by using vital parameters and Manchester triage scale (MTS). Possible additional parameters are POCT (point-of-care-testing) values, electrocardiogram, CT pulmonary angiography, SARS-Cov2-PCR as well as detailed diagnostic of laboratory values. The model was validated by 100 consecutive patients. We demonstrate three patients to illustrate this model. RESULTS: During the first two weeks after implementing this model in our normal operation at the emergency department, we had an efficient selectivity between need for inpatient and outpatient treatment. 16 patients were classified as "inpatients" according to initial assessment. Among 84 patients who were initially classified as "outpatients", 7 patients returned to our emergency department within 14 days. Three of these patients returned due to complaints other than COVID19. One female patient had to be admitted due to progressive dyspnea. CONCLUSIONS: This introduced triage-model seems to be an efficient concept. Adjustment might be necessary after further experience and after a growing number of patients.

Decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018.

In June 2016, members of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) met for a Consensus Conference in Cologne, Germany. Aim of this Conference was to compile consensus based practice recommendations based on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. This article summarizes the results and updated recommendations 2018 of the working group on decompensated right heart failure (RHF), intensive care and perioperative management in patients with pulmonary hypertension. The RHF section comprises definition and pathophysiology, diagnosis and monitoring, identification of triggering factors and supportive therapy of RHF, volume management as well as PAH targeting therapy, therapy with inotropic, inodilator and vasopressor drugs, extracorporeal support and transplantation. The second part of this article summarizes preoperative management, perioperative monitoring and choice of anesthesia.