Here, we present a small Russian family, where the index patient received a diagnosis of left-ventricular non-compaction cardiomyopathy (LVNC) in combination with a skeletal myopathy. Clinical follow-up analysis revealed a LVNC phenotype also in her son. Therefore, we applied a broad next-generation sequencing gene panel approach for the identification of the underlying mutation. Interestingly, DES-p.A337P was identified in the genomes of both patients, whereas only the index patient carried DSP-p.L1348X. DES encodes the muscle-specific intermediate filament protein desmin and DSP encodes desmoplakin, which is a cytolinker protein connecting desmosomes with the intermediate filaments. Because the majority of DES mutations cause severe filament assembly defects and because this mutation was found in both affected patients, we analyzed this DES mutation in vitro by cell transfection experiments in combination with confocal microscopy. Of note, desmin-p.A337P forms cytoplasmic aggregates in transfected SW-13 cells and in cardiomyocytes derived from induced pluripotent stem cells underlining its pathogenicity. In conclusion, we suggest including the DES gene in the genetic analysis for LVNC patients in the future, especially if clinical involvement of the skeletal muscle is present.

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later. Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy. Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1]. Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge. Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.

Introduction The aim of this study was to assess the efficacy and safety of a combination of bromhexine at a dose of 8 mg 4 times a day and spironolactone 50 mg per day in patients with mild and moderate COVID 19. Material and methods It was an open, prospective comparative non-randomized study. 103 patients were included (33 in the bromhexine and spironolactone group and 70 in the control group). All patients had a confirmed 2019 novel coronavirus infection (COVID 19) based on a positive polymerase chain reaction (PCR) for SARS-CoV-2 virus RNA and/or a typical pattern of viral pneumonia on multispiral computed tomography. The severity of lung damage was limited to stage I-II, the level of CRP should not exceed 60 mg / dL and SO2 in the air within 92-98%. The duration of treatment is 10 days. Results The decrease in scores on the SHOKS-COVID scale, which, in addition to assessing the clinical status, the dynamics of CRP (a marker of inflammation), D-dimer (a marker of thrombus formation), and the degree of lung damage on CT (primary endpoint) was statistically significant in both groups and differences between them was not identified. Analysis for the group as a whole revealed a statistically significant reduction in hospitalization time from 10.4 to 9.0 days (by 1.5 days, p=0.033) and fever time from 6.5 to 3.9 days (by 2.5 days, p<0.001). Given the incomplete balance of the groups, the main analysis included 66 patients who were match with using propensity score matching. In matched patients, temperature normalization in the bromhexine/spironolactone group occurred 2 days faster than in the control group (p=0.008). Virus elimination by the 10th day was recorded in all patients in the bromhexine/spironolactone group; the control group viremia continued in 23.3% (p=0.077). The number of patients who had a positive PCR to the SARS-CoV-2 virus on the 10th day of hospitalization or longer (≥10 days) hospitalization in the control group was 20/21 (95.2%), and in the group with bromhexine /spironolactone -14/24 (58.3%), p=0.012. The odds ratio of having a positive PCR or more than ten days of hospitalization was 0.07 (95% CI: 0.008 - 0.61, p=0.0161) with bromhexine and spironolactone versus controls. No side effects were reported in the study group. Conclusion The combination of bromhexine with spironolactone appeared effective in treating a new coronavirus infection by achieving a faster normalization of the clinical condition, lowering the temperature one and a half times faster, and reducing explanatory combine endpoint the viral load or long duration of hospitalization (≥ 10 days).

Pelvic organ prolapse is a chronic disease resulting from a weakening of the musculoskeletal apparatus of the pelvic organs. For the diagnosis of this pathology, it is insufficient to conduct only a clinical examination. An effective diagnostic tool is the method of dynamic magnetic resonance imaging (MRI) of the pelvic floor, which allows a comprehensive assessment of the anatomical and functional characteristics of the walls of the pelvis and pelvic organs. The aim of the study was to analyze the literature data on the possibilities and limitations of using dynamic MRI in pelvic organ prolapse. The widespread use of the dynamic MRI method is due to the high quality of the resulting image, good reproducibility, and the maximum ability to display the characteristics of the pelvic floor. Dynamic MRI of the small pelvis allows a comprehensive assessment of the anatomical and functional features of the pelvis, excluding the effect of ionizing radiation on the body. The method is characterized by good visualization with high resolution and excellent soft tissue contrast. The method allows for assessing the state of the evacuation function of visualized structures in dynamics. Simultaneous imaging of all three parts of the pelvic floor using dynamic MRI makes it possible to assess multicompartment disorders. The anatomical characteristics of the state of the pelvic organs in the norm and in the event of prolapse are considered. The technique for performing the method and the procedure for analyzing the resulting images are described. The possibilities of diagnosing a multicomponent lesion are considered, while it is noted that dynamic MRI of the pelvic organs provides visualization and functional analysis of all three parts of the pelvis and often allows the choice and correction of tactics for the surgical treatment of pelvic organ prolapse. It is noted that dynamic MRI is characterized by a high resolution of the obtained images, and the advantage of the method is the ability to detect functional changes accompanying the pathology of the pelvic floor.