Efficacy and safety of in-hospital treatment of Covid-19 infection with low-dose hydroxychloroquine and azithromycin in hospitalized patients: A retrospective controlled cohort study.

Objectives: In this study we evaluate the efficacy and safety of a treatment protocol with standard dose of hydroxychloroquine plus azithromycin in patients hospitalized with COVID-19 infection. Methods: We conducted a retrospective analysis to compare the 28-day mortality rate in 352 patients treated with hydroxychloroquine with or without azithromycin (HCQ-group) in our hospital with a contemporary control group of 3533 patients receiving standard of care from the Belgian Collaborative Group on COVID-19 Hospital Surveillance. Results: All patients who received at least one dose of treatment were included in the analysis. A statistically significant reduction in crude mortality rate at 28 days was observed in the HCQ-group compared to standard of care (16.8% vs 25.9%,p â€‹= â€‹0.001).Patients in the treatment group were on average younger (69,7 vs73,1 years, p â€‹= â€‹0,0002), were less likely to smoke or to have malignancy and more likely to be male. Patients in the treatment group were more likely to be obese, immunocompromised or to have arterial hypertension, liver disease and lung disease.After adjustment for these variables the OR for mortality was 0.635 (95%CI 0.464-0.875). Patients who did not receive HCQ had a 57% higher risk of mortality. A survival benefit in the treatment group was consistent across all age groups. 13 patients discontinued treatment due to side effects (4 with QTc-prolongation>60msec (1.1%) and 9 because of gastro-intestinal symptoms (2.55%)). No episodes of ventricular arrhythmia or torsade de pointes were recorded during treatment. Conclusion: Treatment of COVID-19 using a combination of hydroxychloroquine plus azithromycin was safe and was associated with a statistically significant mortality benefit in the treatment of COVID-19 infection in hospitalized patients. Our findings do not support the current negative recommendations regarding this treatment.

A case of myocarditis following ChAdOx1 nCov-19 vaccination.

Introduction: Myocarditis is an inflammatory disease of the myocardium, that might lead to reduced cardiac function and in the most severe cases to mortality. Although uncommon, it is a known adverse event after vaccination with coronavirus disease 2019 (COVID-19) mRNA vaccines. Here, we report the case of myocarditis following vaccination with a viral vector vaccine, ChAdOX1 nCoV-19.Case presentation: A 50-year-old male presented at the emergency department with shortness of breath, general malaise and fever, 5 days after receiving a second dose of the ChAdOx1 vaccine. Biochemical analysis revealed elevated serum CRP and troponin levels. Two weeks after initial presentation, a cardiac MRI showed belated contrast capitation in the left ventricle, confirming the diagnosis of myocarditis.Conclusions: To our knowledge, this is the first report of myocarditis following ChAdOx1 vaccination. Except for some case of myocarditis upon the Ad26COVS1 vaccine, no other cases were reported upon vaccination with the ChAdOX1 viral vector vaccines. With this report we would like to raise awareness about myocarditis as an adverse event following ChAdOx1 vaccination.

How to Choose the Right Inhaler Using a Patient-Centric Approach?

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient. Indeed, to date, no ideal device exists that fits all patients, and a personalized approach needs to be considered. Several useful choice-guiding algorithms have been developed in the recent years to improve inhaler-patient matching, but a comprehensive tool that translates the multifactorial complexity of inhalation therapy into a user-friendly algorithm is still lacking. To address this, a multidisciplinary expert panel has developed an evidence-based practical treatment tool that allows a straightforward way of choosing the right inhaler for each patient.

Early high antibody titre convalescent plasma for hospitalised COVID-19 patients: DAWn-plasma.

BACKGROUND: Several randomised clinical trials have studied convalescent plasma for coronavirus disease 2019 (COVID-19) using different protocols, with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralising antibody titres, at different time-points and severities of illness. METHODS: In the prospective multicentre DAWn-plasma trial, adult patients hospitalised with COVID-19 were randomised to 4 units of open-label convalescent plasma combined with standard of care (intervention group) or standard of care alone (control group). Plasma from donors with neutralising antibody titres (50% neutralisation titre (NT50)) ≥1/320 was the product of choice for the study. RESULTS: Between 2 May 2020 and 26 January 2021, 320 patients were randomised to convalescent plasma and 163 patients to the control group according to a 2:1 allocation scheme. A median (interquartile range) volume of 884 (806-906) mL) convalescent plasma was administered and 80.68% of the units came from donors with neutralising antibody titres (NT50) ≥1/320. Median time from onset of symptoms to randomisation was 7 days. The proportion of patients alive and free of mechanical ventilation on day 15 was not different between both groups (convalescent plasma 83.74% (n=267) versus control 84.05% (n=137)) (OR 0.99, 95% CI 0.59-1.66; p=0.9772). The intervention did not change the natural course of antibody titres. The number of serious or severe adverse events was similar in both study arms and transfusion-related side-effects were reported in 19 out of 320 patients in the intervention group (5.94%). CONCLUSIONS: Transfusion of 4 units of convalescent plasma with high neutralising antibody titres early in hospitalised COVID-19 patients did not result in a significant improvement of clinical status or reduced mortality.

Incremental Experience in In Vitro Primary Culture of Human Pulmonary Arterial Endothelial Cells Harvested from Swan-Ganz Pulmonary Arterial Catheters.

Pulmonary arterial hypertension (PAH) is a devastating condition affecting the pulmonary microvascular wall and endothelium, resulting in their partial or total obstruction. Despite a combination of expensive vasodilatory therapies, mortality remains high. Personalized therapeutic approaches, based on access to patient material to unravel patient specificities, could move the field forward. An innovative technique involving harvesting pulmonary arterial endothelial cells (PAECs) at the time of diagnosis was recently described. The aim of the present study was to fine-tune the initial technique and to phenotype the evolution of PAECs in vitro subcultures. PAECs were harvested from Swan-Ganz pulmonary arterial catheters during routine diagnostic or follow up right heart catheterization. Collected PAECs were phenotyped by flow cytometry and immunofluorescence focusing on endothelial-specific markers. We highlight the ability to harvest patients' PAECs and to maintain them for up to 7-12 subcultures. By tracking the endothelial phenotype, we observed that PAECs could maintain an endothelial phenotype for several weeks in culture. The present study highlights the unique opportunity to obtain homogeneous subcultures of primary PAECs from patients at diagnosis and follow-up. In addition, it opens promising perspectives regarding tailored precision medicine for patients suffering from rare pulmonary vascular diseases.

Uveitis as a window to diagnosis of sarcoidosis - case report and review of the literature.

Sarcoidosis is a multisystem disease of unclear etiology with a variable clinical profile characterized by the presence of non-caseating granuloma in involved organs. The diagnosis is often challenging and based on clinical, radiological and anatomopathological data. Sarcoidosis can be benign and self-limiting, but some cases may follow a chronic, progressive course and result in severe morbidity. The disease has a predilection for the lungs and thoracic lymph nodes but can involve nearly any part of the body, possible more commonly in areas with contact to the external environment, such as the eyes and the skin. This paper is based on a case in which a recurrent uveitis led to the diagnosis of an underlying sarcoidosis.

Balloon Pulmonary Angioplasty for the Treatment of Nonoperable Chronic Thromboembolic Pulmonary Hypertension: Single-Center Experience with Low Initial Complication Rate.

PURPOSE: To evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH) patients during the initial experience of a single center. METHODS: A total of 18 CTEPH patients (5 with residual pulmonary hypertension after pulmonary endarterectomy) were treated with BPA during the period 2014-2018 and were retrospectively reviewed. Mean age was 61 ± 19 years; 55% were female; mean pulmonary artery pressure was 44 ± 12 mmHg; cardiac output was 4.3 ± 1.0 l/min; and pulmonary vascular resistance was 8.4 ± 3.6 WU. Patients were evaluated by New York Heart Association functional class, 6-minute walk distance, N-terminal pro b-type natriuretic peptide, echocardiography, right heart catheterization, and before and after completions of BPA. RESULTS: A total of 91 procedures were performed, with a median number of 4 BPA sessions per patient (range, 2-8). There were no deaths or major complications requiring extracorporeal support or (non)invasive ventilation. The most common complication was self-limiting hemoptysis (3%). According to Society of Interventional Radiology classification, 4 mild, 4 moderate, and 1 severe adverse events were noted. Invasive hemodynamics significantly improved, with a cardiac index increase of 15% (P = .0333), decrease of mean pulmonary artery pressure of 30% (P = .0013), and decrease of pulmonary vascular resistance of 45% (P = .0048). Stroke volume index (P = .0171) and pulmonary arterial compliance (P = .0004) were also significantly enhanced. CONCLUSIONS: BPA significantly improves cardiopulmonary hemodynamics with an acceptable safety profile. Further studies assessing the long-term efficacy of BPA are required.

Hypocalcemia after Denosumab in a Pulmonary Hypertension Patient Receiving Epoprostenol.

We report the case of a 50-year-old woman with anorexigen-induced pulmonary arterial hypertension treated with epoprostenol, who presented with Trousseau's sign, leading to the diagnosis of severe hypocalcemia for which substitution was started (initially orally, followed by intravenous substitution). After further analysis, we assume that epoprostenol-induced diarrhea caused malabsorption (as other reasons were excluded), leading to nutritional osteomalacia with secondary hyperparathyroidism. We discovered that even more severe hypocalcemia was induced by the treatment with the anti-osteoporotic drug denosumab, which was started after the diagnosis of osteoporosis on bone densitometry. In our opinion, clinicians have to be aware that in patients with malabsorption, antiresorptive therapy can induce dangerous and even life-threatening hypocalcemia, even in patients with normal renal function.

A 64-year-old woman with interstitial lung disease and positive antibodies against aminoacyl-transfer RNA synthetases in the absence of myositis: presentation of an anti-PL-12 positive antisynthetase syndrome.

Introduction The antisynthetase syndrome is a rare autoimmune disease described by the presence of inflammatory myositis, interstitial lung disease and antibodies against aminoacyl-transfer RNA synthetases. Interstitial lung disease can be the only manifestation in the absence of an inflammatory myositis. Other clinical signs are Raynaud phenomenon, hyperkeratotic skin lesions, fever and inflammatory polyarthritis. Case presentation We report the case of a 64-year old woman who complained of a dry cough, progressive dyspnea and arthralgia since 2 years, with no other systemic symptoms. High resolution computed tomography (HRCT) of the thorax showed the presence of bilateral ground glass opacities, reticular opacities and some traction bronchiectasis. Further biochemical testing revealed the presence of anti-PL12 antibodies. Management The diagnosis of antisynthetase syndrome was made and the patient was treated with steroids and azathioprine with a good response. Conclusion The search for antisynthetase antibodies should always be considered in patients with an interstitial lung disease without any other clinical symptoms or signs of an underlying connective tissue disease.