[Vaskuläre Dyspnoe: Lungenembolie]. / Vaskuläre Dyspnoe: Lungenembolie.

INTRODUCTION: In clinical practice, the differentiation of pulmonary embolism from other entities often remains difficult. Of utmost importance is the estimation of the pretest probability of the disease: predictive scoring systems and the use of clinical gestalt are equally useful tools. Exclusion or confirmation of the disease requires the rationale use of additional investigations (laboratory, imaging). In this article, we provide clinical engrams and outline our diagnostic algorithm. Based on the latest recommendations, we summarize the therapeutic approach for patients with pulmonary embolism. The importance of follow-up visits after the initial event is discussed in the last part. The assessment of risk factors promoting the development of venous thromboembolism is crucial for estimating the risk of recurrence. Excessive screening (thrombophilia testing or tumor investigations) are of minor relevance.

External Validation of the Modified 4C Deterioration Model and 4C Mortality Score for COVID-19 Patients in a Swiss Tertiary Hospital.

Prognostic models to predict the deterioration and mortality risk in COVID-19 patients are utterly needed to assist in informed decision making. Most of these models, however, are at high risk of bias, model overfitting, and unclear reporting. Here, we aimed to externally validate the modified (urea was omitted) 4C Deterioration Model and 4C Mortality Score in a cohort of Swiss COVID-19 patients and, second, to evaluate whether the inclusion of the neutrophil-to-lymphocyte ratio (NLR) improves the predictive performance of the models. We conducted a retrospective single-centre study with adult patients hospitalized with COVID-19. Both prediction models were updated by including the NLR. Model performance was assessed via the models' discriminatory performance (area under the curve, AUC), calibration (intercept and slope), and their performance overall (Brier score). For the validation of the 4C Deterioration Model and Mortality Score, 546 and 527 patients were included, respectively. In total, 133 (24.4%) patients met the definition of in-hospital deterioration. Discrimination of the 4C Deterioration Model was AUC = 0.78 (95% CI 0.73-0.82). A total of 55 (10.44%) patients died in hospital. Discrimination of the 4C Mortality Score was AUC = 0.85 (95% CI 0.79-0.89). There was no evidence for an incremental value of the NLR. Our data confirm the role of the modified 4C Deterioration Model and Mortality Score as reliable prediction tools for the risk of deterioration and mortality. There was no evidence that the inclusion of NLR improved model performance.

Pulmonary Embolism and Heart Failure: A Reappraisal.

Acute heart failure and acute pulmonary embolism share many features, including epidemiological aspects, clinical presentation, risk factors and pathobiological mechanisms. As such, it is not surprising that diagnosis and management of these common conditions might be challenging for the treating physician, in particular when both are concomitantly present. While helpful guidelines have been elaborated for both acute heart failure and pulmonary embolism, not many studies have been published on the coexistence of these diseases. With a special focus on diagnostic tools and therapeutic options, the authors review the available literature and, when evidence is lacking, present their own approach to the management of dyspnoeic patients with acute heart failure and pulmonary embolism.

Right Ventricular Failure: Pathophysiology, Diagnosis and Treatment.

The prognostic significance of the right ventricle (RV) has recently been recognised in several conditions, primarily those involving the left ventricle, the lungs and their vascular bed, or the right-sided chambers. Recent advances in imaging techniques have created new opportunities to study RV anatomy, physiology and pathophysiology, and contemporary research efforts have opened the doors to new treatment possibilities. Nevertheless, the treatment of RV failure remains challenging. Optimal management should consider the anatomical and physiological particularities of the RV and include appropriate imaging techniques to understand the underlying pathophysiological mechanisms. Treatment should include rapid optimisation of volume status, restoration of perfusion pressure and improvement of myocardial contractility and rhythm, and, in case of refractory RV failure, mechanical circulatory support.

[Practical Evaluation of Patients with Syncopal Events]. / Synkope ­ Eine praktische Abklärungsstrategie.

Syncope is defined as a transient, self-limited loss of consciousness due to insufficient cerebral blood perfusion. In a clinical setting, syncopal events usually present a diagnostic dilemma due to its broad differential diagnosis ranging from banal to potentially harmful causes. In the absence of a working hypothesis, multiple tests are ordered that result in high costs but are of questionable diagnostic and therapeutic value. This article provides a practical overview and, based on international guidelines and selected studies, proposes a standardized approach to patients with syncope. Initial evaluation of these patients includes taking a careful medical history, physical examination and ECG. These tests result in an individual risk assessment that supports decision-making whether further analysis should be performed in an outpatient or inpatient setting. Additional tests including echocardiography, laboratory analysis, cardiac monitoring, CT-scans, are ordered according to prior evaluation. This article reviews the most common diagnostic tests, their indications and the clinical relevance for the evaluation of patients with syncopal events. Therapeutic options are not within the focus of this article.

First experience in Switzerland in Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease enrolled in a lumacaftor-ivacaftor therapy trial - preliminary results.

AIMS OF THE STUDY: Cystic fibrosis is the most common genetic disorder in Caucasians. The combination of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector lumacaftor / potentiator ivacaftor (LUM/IVA) has been shown to increase forced expiratory volume in 1 second (FEV1) moderately, but predominantly reduce acute exacerbation rate (AER) in Phe508del homozygous cystic fibrosis patients; however, patients with FEV1 <40% predicted were excluded from studies. We used LUM/IVA on a "compassionate use" basis in cystic fibrosis patients with end-stage pulmonary disease. Our aim was to evaluate if this patient cohort tolerates LUM/IVA treatment and if there is clinical stabilisation. Lung transplantation (LTX) is the ultimate treatment option for these patients despite maximal therapy. If LTX candidates stabilise clinically, conditions for LTX, when it is indicated, improve. This is particularly important in countries such as Switzerland with a low organ donation rate and long waiting times for suitable donor organs. METHODS: We included all patients from the Adult Cystic Fibrosis Centre at the University Hospital Zurich with Phe508del homozygous genotype and a predicted FEV1 <40% or being evaluated or already listed for LTX. Clinical outcome data comprised AER, 6-minute walking distance (6-MWD), FEV1, forced vital capacity (FVC), mid-expiratory flow (MEF 25-75%), sweat chloride, body mass index (BMI) and quality of life. Respiratory-related adverse events (RAEs) were recorded. LUM/IVA treatment was initiated at a low dose and the dose increased stepwise. RESULTS: Twenty patients were on trial with LUM/IVA; at the cut-off date, 6-month follow-up was complete for 10 patients. RAEs were severe and occurred early. The dropout rate due to RAE or lack of clinical success was 20%. Median AER decreased from 2.5 in the 6 months pre-treatment to 1 during the observation period. FEV1 increased from 32 to 34.5% predicted, p = 0.292. The 6-MWD increased by a median 33 m (p = 0.6086). Sweat chloride decreased significantly by a median of 25 mmol/l (p = 0.0003). Median BMI increased from 19 to 19.9 kg/m2 (p = 0.1488). At the cut-off, three previously listed patients were paused on the transplant waiting list. CONCLUSION: Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease tolerated LUM/IVA, although RAEs occurred early and were severe. This positive finding was probably due to the stepwise dose increases. There was clinical benefit mainly from reduction in AER and stabilisation of lung function. We propose that all suitable Phe508del homozygous cystic fibrosis patients with end-stage pulmonary disease should have a trial of LUM/IVA treatment in experienced centres.

[Lung auscultation--an overview]. / Die Lungenauskultation--Erkenntnisse und Irrtümer.

The auscultation of the lungs is - among anamnesis - the most important part in the assessment of patients presenting with pulmonary symptoms. The lung auscultation is reproducible, cost efficient and very helpful to distinguish between differential diagnoses, in particular in emergency situations. Detection and description of lung sounds requires experience and should be performed by strict adherence to the internationally accepted terminology.