Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study.

BACKGROUND: Several anti-cytokine therapies were tested in the randomized trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Previously, dexamethasone demonstrated a reduction of case-fatality rate in hospitalized patients with respiratory failure. In this matched control study we compared dexamethasone to a Janus kinase inhibitor, ruxolitinib. METHODS: The matched cohort study included 146 hospitalized patients with COVID-19 and oxygen support requirement. The control group was selected 1:1 from 1355 dexamethasone-treated patients and was matched by main clinical and laboratory parameters predicting survival. Recruitment period was April 7, 2020 through September 9, 2020. RESULTS: Ruxolitinib treatment in the general cohort of patients was associated with case-fatality rate similar to dexamethasone treatment: 9.6% (95% CI [4.6-14.6%]) vs 13.0% (95% CI [7.5-18.5%]) respectively (p = 0.35, OR = 0.71, 95% CI [0.31-1.57]). Median time to discharge without oxygen support requirement was also not different between these groups: 13 vs. 11 days (p = 0.13). Subgroup analysis without adjustment for multiple comparisons demonstrated a reduced case-fatality rate in ruxolitnib-treated patients with a high fever (≥ 38.5 °C) (OR 0.33, 95% CI [0.11-1.00]). Except higher incidence of grade 1 thrombocytopenia (37% vs 23%, p = 0.042), ruxolitinib therapy was associated with a better safety profile due to a reduced rate of severe cardiovascular adverse events (6.8% vs 15%, p = 0.025). For 32 patients from ruxolitinib group (21.9%) with ongoing progression of respiratory failure after 72 h of treatment, additional anti-cytokine therapy was prescribed (8-16 mg dexamethasone). CONCLUSIONS: Ruxolitinib may be an alternative initial anti-cytokine therapy with comparable effectiveness in patients with potential risks of steroid administration. Patients with a high fever (≥ 38.5 °C) at admission may potentially benefit from ruxolitinib administration. Trial registration The Ruxolitinib Managed Access Program (MAP) for Patients Diagnosed With Severe/Very Severe COVID-19 Illness NCT04337359, CINC424A2001M, registered April, 7, 2020. First participant was recruited after registration date.

[Homoarginine level and methionine-homocysteine balance in patients with ischemic heart disease.]

The level of homoarginine (hArg) in terms of prognostic significance may exceed the natriuretic peptides and other well-known markers according to the latest data about the progression of cardiovascular diseases. The lack of data on the association of hArg levels with levels of other metabolites makes it difficult to understand its role in the pathogenesis of cardiovascular diseases. Relationships of hArg and other amino acids, including methionine (Met) and total homocysteine (tHcy), and their ratio in patients with ischemic heart disease were evaluated. The study included 74 patients with coronary heart disease (57 men and 17 women) aged 62 (57 - 67) years before coronary artery bypass surgery and 27 healthy people of similar age. In patients, the level of hArg was almost 2 times lower (p < 0.05) than in healthy individuals and rates lower than 1.4 µM were in half of them. The statistically significant decrease (p = 0.0025) of the Met/tHcy ratio corresponded to a decrease in the level of hArg. This ratio did not correlate with glucose level or body mass index. Less statistical significance of hArg correlation with levels of Met or tHcy separately was observed. In the subgroup of patients with hAarg level above 2.1 µM, a lower incidence of myocardial infarction was noted. Thus, a low hArg level is associated with impaired metabolism of sulfur-containing amino acids involved in transmethylation reactions, in patients with ischemic heart disease. The Met/tHcy ratio, closely correlating with the level of hArg, apparently reveals a link between the reactions of creatine formation and transmethylation, highlighting a cohort of patients with the most profound and dangerous changes in tissue metabolism.

[The level of circulating humanin in patients with ischemic heart disease.]

At present, great interest is caused with evaluation of new markers in blood circulation for the estimation a tissue oxidative metabolism disturbance due to the presence of secondary mitochondrial dysfunction in patients with coronary heart disease. Сoronary heart disease is generally accompanied with a decline in mitochondrial respiration and represents the root cause of metabolic abnormalities in tissues. To gain insight into rate of decline of mitochondrial oxidative metabolism in tissues there were proposed humanin as a new marker. The content of humanin in compare with other markers of energy metabolism in 59 patients with coronary heart disease was studied. In the examined patients, a decrease in the level of humanin up to 250 ng/l was observed when compared with its level of 1110 (800 to 1500) ng/l in healthy individuals. In most of the patients increased level of lactic acid from 1.0 to 2.2 mM accompanied in 45 % cases with elevation of pyruvic acid concentration above 99.1 µM was observed. Also, it was found a significant decrease of homoarginine level down to 1.40 (1.0-2.0) versus 2.3 (1.8-3.1) µM in healthy individuals. We found an inverse correlation between the level of humanin and the age of patients (R = -0.35, p = 0.048). It can be concluded that patients with coronary heart disease are characterized by a lower level of humanin and homoarginine in the blood, as well as an increased content of lactic acid, indicators that are the criteria for inhibiting aerobic pathways and reducing mitochondriogenesis.

[PAIN AFTER CHILDBIRTH AND ITS IMPACT ON QUALITY OF LIFE].

BACKGROUND: Public attitude towards labor pain and pain relief in labor is not fully formed. PURPOSE: To study the frequency of formation of acute and chronic pain during delivery. MATERIALS AND METHODS: Retrospectively we surveyed 300 women 18-48 years old, who had childbirth naturally or by caesarean section for 4-6 months before the survey and analyzed the history of their childbirth. RESULTS: The obtained data showed that the problem with generic pain has real medical and social consequences, significantly altering the quality of life of women as during childbirth and the postpartum period. Of those surveyed, 74.9% of women in childbirth experienced severe pain during labor; which had 16.7% of women had led to a complete loss of mobility. With approximately 20% of women believed the use of methods of anaesthesia was dangerous and 63% thought that anaesthesia is possible only under strict obstetric indications. Only 20% of pregnant women expected to give birth without pain. In 3-6 months. after labor representation mothers opinion was not changed significantly. In 1 month or more after delivery or cesarean section pain was presented in 21% of women, in 2-3 months--13.7%, in more than 3 months--7%. In 4.3% of the patients the pain persistedfor 5-6 months. CONCLUSIONS: Significant relationship between persistent for a long time after childbirth pain and the way the urgency of delivery, the method of anesthesia for caesarean section, the expression of acute pain during childbirth was not revealed.

[OLD AND NEW PROBLEMS IN THE TRAINING OF ANAESTHESIOLOGISTS].

In connection with the upcoming changes in the professional education in Russia, there is a need to adapt the existing system of training of anesthesiologists. We sent questionnaires to 831 anesthesiologists to identify their opinion about the planned transition to continuous medical education. We found that the majority of respondents do not object to the implementation in practice of this system, especially if the educational model will be adapted to the specific requests of practitioners. Reorganization of the system of higher and additional professional education requires state educational and medical institutions, and public organizations of the effective interaction. Public professional organizations should play the more active role of facilitators of the educational process.