Vaccination against COVID-19 in Ukraine. Safety of Vaccines

COVID-19 is a life-threatening disease that can be asymptomatic in the form of a common ARVI, or in extremely severe forms, with serious long-term consequences. Vaccination against COVID-19 is critically important to restrain the pandemic. The purpose of the study was to analyze and systematize the data of pharmacological supervision of the use of vaccines against COVID-19. For this, methods of analysis, systematization and generalization of information were used using the databases of the State Expert Center of the Ministry of Health of Ukraine, Food and Drug Administration, World Health Organisation in the period from February 24, 2021 to October 31, 2021. Currently, such vaccines are registered and approved for use in Ukraine as AstraZeneca (Covishield, SKBio), Comirnaty / Pfizer-BioNTech, Moderna, CoronaVac / Sinovac Biotech. According to official data, the effectiveness of all these vaccines is quite high. They are especially effective in preventing severe course of disease, hospitalization, and death. Sometimes the vaccination process can be with the development of a number of side effects. Responsibility for the risks associated with the production and use of vaccines dictates the need for constant monitoring of these side effects. That is why we analyzed the data of the State Expert Center of the Ministry of Health of Ukraine about adverse events after immunization from COVID-19 in Ukraine. Thus, the analysis of adverse events reported showed that they took place in 0.018% cases of the total number of vaccine doses that were administered. In the context, for each vaccine separately, the number of adverse events reported were: Covishield – 1128 cases (0.23%), CoronaVac – 419 (0.008%), Comirnaty – 854 (0.02%), AstraZeneca – 540 (0.02%), Moderna – 393 (0.02%), respectively. It should be noted that most of the reported cases of adverse events reported in Ukraine during vaccination against COVID-19 are mild predictable reactions (88.72 – 93.38%). This result allows us to speak of a fairly high predictability of the adverse events reported after COVID-19 vaccination. This is confirmed by the data of world literature. After analyzing the presented data of the State Expert Center of the Ministry of Health of Ukraine, we found that the most of adverse events reported after COVID-19 vaccination are so-called general disorders and disorders at the injection site (fever, fatigue, chills, redness, pain and swelling at the injection site). Neurological disorders ranked second in terms of the number of adverse events reported, and musculoskeletal disorders ranked third. Adverse events reported manifestations from other organs and systems had isolated cases. After using all of the above vaccines, the percentage of adverse events reported was significantly higher in women than in men, which coincides with the data of the world literature. Conclusion. Thus, the analysis of the safety of vaccines against COVID-19, registered and authorized for use in Ukraine, shows that the risks of adverse events reported after COVID-19 vaccination are rare; the most of them are mild and predictable. At the same time, these manifestations of adverse events reported cannot be compared with the health and life risks associated with the COVID-19 disease itself. Ensuring continuous monitoring of the safety of vaccine use and identifying potential side effects will further reduce and manage the risks associated with vaccine use

Algorithms for the diagnosis and treatment of idiopathic pulmonary arterial hypertension

Background. Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition characteri-zed by an increase in the average pressure in the pulmonary artery > 20 mm Hg and is evaluated according to the data of the right heart catheterization (RHC). In most cases, PH is not an independent disease but is a manifestation of other diseases. Idiopathic pulmonary arterial hypertension (IPAH) is a diagnosis that it is established by excluding all other causes of PH (damage to the left heart, connective tissue diseases, HIV infection, lung diseases, portal hypertension, congenital heart defects, a history of pulmonary thromboembolism, etc.). In IPAH, the etiology of the disease is unknown. Pathogenesis and symptoms of PH. Vasoconstriction, microthrombosis, and vascular remodeling are the three main pathophysiological elements in PH. Symptoms of PH are non-specific: shortness of breath, rapid fatigue, chest pain during physical exertion, and sometimes syncopal states are observed. Decompensated patients have signs of right-sided heart failure (edemas, ascites, bloating, pulsation of the jugular veins). Diagnosis. The diagnostic algorithm for РH consists of two stages. The first one is located outside the expert сenter, and the second one is located directly in the PH expert center. When this disease is suspected and there are typical symptoms and signs, all patients undergo an echocardiographic examination. Then, under certain conditions (for example, the absence of the underlying cause of PH), the patient is referred to the PH expert center, where it is possible to conduct RHC. Evaluating the prognosis. Evaluation of patients with IPAH is necessary to improve disease control and transition from a higher risk to a lower one. Prognosis assessment is comprehensive and is determined based on clinical status, symptom progression, syncope, results of a 6-minute walk test and NT-proBNP, results of examination methods (cardiopulmonary exercise test, echocardiography or MRI of the heart, hemodynamic assessment). Treatment. The main objectives of IPAH treatment are reducing the severity of symptoms, slowing the progression of the disease, improving the quality and increasing the life expectancy of patients. First of all, these are general measures (physical activity, prevention and management of pregnancy), prevention of infectious diseases, social and psychological assistance, monitoring compliance with the regime, recommendations for travel/journey, maintenance therapy (oral anticoagulants, diuretics, digoxin, oxygen therapy). Patients with a positive vasoreactive test are prescribed with calcium channel blockers. In all other patients, specific PH therapy may include prostaglandins (inhaled, intravenous, and subcutaneous forms), prostacyclin receptor antagonists, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and soluble guanylate cyclase stimulants. Surgical treatment. One of the options for surgical treatment of IPAH is atrial septostomy — the creation of a perforation in the atrial septum. This leads to decompression of the right chambers of the heart and increases the preload on the left ventricle, which leads to an increase in cardiac output. In case of ineffectiveness of all the above methods of treatment and significant progression of the disease, patients are indicated for lung transplantation or heart — lung complex.

Bilateral Renal Tumors in Children: The First 5 Years’ Experience of National Centralization in The Netherlands and a Narrative Review of the Literature

Survival of unilateral Wilms tumors (WTs) is exceeding 90%, whereas bilateral WTs have an inferior outcome. We evaluated all Dutch patients with bilateral kidney tumors, treated in the first five years of national centralization and reviewed relevant literature. We identified 24 patients in our center (2015–2020), 23 patients had WT/nephroblastomatosis and one renal cell carcinoma. Patients were treated according to SIOP-RTSG protocols. Chemotherapy response was observed in 26/34 WTs. Nephroblastomatosis lesions were stable (n = 7) or showed response (n = 18). Nephron-sparing surgery was performed in 11/22 patients undergoing surgery (n = 2 kidneys positive margins). Local stage in 20 patients with ≥1 WT revealed stage I (n = 7), II (n = 4) and III (n = 9). Histology was intermediate risk in 15 patients and high risk in 5. Three patients developed a WT in a treated nephroblastomatosis lesion. Two of 24 patients died following toxicity and renal failure, i.e., respectively dialysis-related invasive fungal infection and septic shock. Genetic predisposition was confirmed in 18/24 patients. Our literature review revealed that knowledge is scarce on bilateral renal tumor patients with metastases and that radiotherapy seems important for local stage III patients. Bilateral renal tumors are a therapeutic challenge. We describe management and outcome in a national expert center and summarized available literature, serving as baseline for further improvement of care.

Improved BEC SMOS Arctic Sea Surface Salinity product v3.1

Measuring salinity from space is challenging since the sensitivity of the brightness temperature (TB) to sea surface salinity (SSS) is low (about 0.5 K / psu), while the SSS range in the open ocean is narrow (about 5 psu, if river discharge areas are not considered). This translates into a high accuracy requirement of the radiometer (about 2–3 K). Moreover, the sensitivity of the TB to SSS at cold waters is even lower (0.3 K / psu), making the retrieval of the SSS in the cold waters even more challenging. Due to this limitation, ESA launched a specific initiative in 2019, the Arctic+Salinity project (AO/1-9158/18/I-BG), to produce an enhanced Arctic SSS product with better quality and resolution than the available products. This paper presents the methodologies used to produce the new enhanced Arctic SMOS SSS product (Martínez et al., 2020) . The product consists of 9-day averaged maps in an EASE 2.0 grid of 25 km. The product is freely distributed from the Barcelona Expert Center (BEC, http://bec.icm.csic.es/) with the DOI number: 10.20350/digitalCSIC/12620. The major change in this new product is its improvement of the effective spatial resolution that permits better monitoring of the mesoscale structures (larger than 50 Km), which benefits the river discharges monitoring.

Impact of temporary mechanical circulatory support on mortality in cardiogenic shock: an emulated target trial with a prospective, multicenter, French cohort study

Background The field of temporary mechanical circulatory support (TMCS) has advanced in last decade justifying that TMCS is increasingly used for treatment of refractory cardiogenic shock (CS). Nevertheless, the efficacy of TMCS (extracorporeal life support (ECLS) and Impella) in CS remains controversial due to the lack of high-quality evidence. The aim of this prospective multicenter observational study simulating a randomized trial was to assess the impact of TMCS on the hospital mortality in patients with CS. Methods This study (ClinicalTrials.gov ID: NCT03528291) was conducted at 3 TMCS centers organized in a cardiac assistance network, one as a level 1 TMCS center (expert center), and 2 as level 2 centers (hub centers). The study was designed and led by the heart team of the expert center with input from the hub centers. All patients admitted to an intensive care unit between July 2017 and May 2020 either directly at the TMCS centers or after transfer from a non-specialized hospital, were screened for TMCS indication provided they were admitted for CS. CS was defined according to the European Society of Cardiology criteria. Were excluded patients younger than 18 years, CS after cardiac surgery, or after cardiac arrest if it was refractory or with a no flow >3 min and/or out-of-hospital cardiac arrest with non-shockable rhythm, or CS in the context of myocardial infarction complications, massive pulmonary embolism, and if TMCS was contraindicated TMCS indication was decided after a multidisciplinary discussion carried out by the “heart team”. Implantation of TMCS resulted from an agreement of the heart team within the first 24 hours after admission mainly based on the initial severity of the CS, or if CS was refractory to the medical treatment. The primary outcome was in-hospital survival. A propensity score-weighted analysis was done for treatment-effect estimation. This method, which weights each patient according to their propensity score, includes all participants in the analysis. Results 246 patients with CS were included in the study: 121 in TMCS group (72% ECLS, 14% Impella, 14% both ECLS and Impella) and 125 in control group. After adjustment by a propensity score, hospital mortality was comparable in the two groups (32% TMCS group vs 27% control group; Odds ratio with TMCS, 1.28; 95% confidence interval, 0.87 to 1.88; p=0.21). Mortality at D180 was also similar in the two group (33% vs 30% respectively; p=0.51). Thromboembolic events were significantly higher in the TCMS group (14% vs 4%; p<0.01) as well as the transfusion rate ((median (IQR); 4.0 (0.0; 9.0) vs 0.0 (0.0; 0.0); p<0.01). Conclusion In our study, the use of TMCS does not seem to improve hospital survival in patients with cardiogenic shock. Thus, TMCS, which are iatrogenic side effects providers, should be reserved for the most severe patient and discussed by a multidisciplinary team. FUNDunding Acknowledgement Type of funding sources: None. Flow chart

Oromandibular Dystonia: A Clinical Examination of 2,020 Cases

Objective: The goal of this study is to better characterize the phenotypic heterogeneity of oromandibular dystonia (OMD) for the purpose of facilitating early diagnosis.Methods: First, we provide a comprehensive summary of the literature encompassing 1,121 cases. Next, we describe the clinical features of 727 OMD subjects enrolled by the Dystonia Coalition (DC), an international multicenter cohort. Finally, we summarize clinical features and treatment outcomes from cross-sectional analysis of 172 OMD subjects from two expert centers.Results: In all cohorts, typical age at onset was in the 50s and 70% of cases were female. The Dystonia Coalition cohort revealed perioral musculature was involved most commonly (85%), followed by jaw (61%) and tongue (17%). OMD more commonly appeared as part of a segmental dystonia (43%), and less commonly focal (39%) or generalized (10%). OMD was found to be associated with impaired quality of life, independent of disease severity. On average, social anxiety (LSA score: 33 ± 28) was more common than depression (BDI II score: 9.7 ± 7.8). In the expert center cohorts, botulinum toxin injections improved symptom severity by more than 50% in ~80% of subjects, regardless of etiology.Conclusions: This comprehensive description of OMD cases has revealed novel insights into the most common OMD phenotypes, pattern of dystonia distribution, associated psychiatric disturbances, and effect on QoL. We hope these findings will improve clinical recognition to aid in timely diagnosis and inform treatment strategies.