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.
Aim To evaluate clinical efficacy of the proactive anti-inflammatory therapy in patients hospitalized for COVID-19 with pneumonia and a risk of "cytokine storm".Material and methods The COLORIT ...study was a comparative study with randomization into 4 groups: colchicine (n=21) 1 mg for the first 3 days followed by 0.5 mg/day through day 12 or discharge from the hospital; secukinumab 300 mg/day, s.c., as a single dose (n=20); ruxolitinib 5 mg, twice a day (n=10); and a control group with no anti-inflammatory therapy (n=22). The effect was evaluated after 12±2 days of inpatient treatment or upon discharge, what comes first. For ethical reasons, completely randomized recruitment to the control group was not possible. Thus, for data analysis, 17 patients who did not receive any anti-inflammatory therapy for various reasons not related with inclusion into the study were added to the control group of 5 randomized patients. Inclusion criteria: presence of coronavirus pneumonia (positive PCR test for SARS-CoV-2 RNA or specific clinical presentation of pneumonia; IDC-10 codes U07.1 and U07.2); C-reactive protein (CRP) concentration >60 mg/l or its threefold increase from baseline; at least 2 of 4 symptoms (fever >37.5 °C, persistent cough, shortness of breath with inspiratory rate >20 per min or blood saturation with oxygen <94 % by the 7th-9th day of disease. The study primary endpoint was changes in COVID Clinical Condition Scale (CCS-COVID) score. The secondary endpoints were the dynamics of CRP and changes in the area of lung lesion according to data of computed tomography (CT) of the lungs from the date of randomization to 12±2 days.Results All three drugs significantly reduced inflammation, improved the clinical course of the disease, and decreased the disease severity as evaluated by the CCS score: in the ruxolitinib group, by 5.5 (p=0.004); in the secukinumab group, by 4 (p=0.096); in the colchicine group, by 4 (p=0.017), and in the control group, by 2 (р=0.329). In all three groups, the CCS-COVID score was 2-3 by the end of observation period, which corresponded to a mild process, while in the control group, the score was 7 (р=0.005). Time-related changes in CRP were significant in all three anti-inflammatory treatment groups with no statistical difference between the groups. By the end of the study, changes in CT of the lungs were nonsignificant.Conclusion In severe СOVID-19 with a risk of "cytokine storm", the proactive therapy with ruxolitinib, colchicine, and secukinumab significantly reduces the inflammation severity, prevents the disease progression, and results in clinical improvement.
Relevance The brachial plexus is a complex anatomical structure the passes through three narrow anatomical spaces including the interscalene space, the space between the first rib and the clavicle ...(thoracic aperture), the space between the anterior chest wall and the pectoralis minor muscle. Compression of the brachial plexus and the vascular band can occur at the sites. Endoscopic approach to the brachial plexus is a promising surgical trend to allow neurolysis and decompression of the plexus with minimal trauma and blood loss and a good cosmetic result. The purpose was to explore topographic anatomy of the brachial plexus and surrounding structures and determine the possibility of endoscopic approach to the brachial plexus. Material and methods The shoulder and neck were dissected in 5 fresh cadavers. The study was performed at Trauma and Orthopaedics department of the Russian Peoples Friendship University and Department of pathological anatomy at the Buyanov’s Moscow State City Hospital between 2021 and 2022. Results The pectoralis minor muscle was detached from the coracoid process to endoscopically approach to the subclavian part of plexus. The lateral aspect of the subclavian muscle was detached from the clavicle to endoscopically approach to the thoracic aperture. Portals were produced at the supraclavicular fossa to endoscopically approach to the supraclavicular part of the plexus in the interscalene space considering the topographic anatomy of the jugularis external vein and accessory veins. The mean distance from the coracoid tip to the penetration point of the musculo-cutaneous nerve to the conjoint tendon was 3 cm. The mean distance between the anterior chest wall and the clavicle (width of thoracic aperture) was 1.86 cm. The mean distance between the sternal end of the clavicle to the point of passage of the subclavian artery under the clavicle was 5.7 cm. The mean width of the interscalene space was 1.4 cm. Discussion Aspects of topographic anatomy of the brachial plexus were examined in cadaveric studies of Sidorovich R.R. (2011), Chembrovich V.V. (2019), Anokhina Z.A. (2021), but endoscopic approach to the brachial plexus and possibility with endoscopic surgery were not discussed in the studies. Foreign cadaveric studies of Akaslan I. (2021), Koyyalamudi V. (2021), Costabeber I. (2010), Akboru (2010) were performed to examine topographic anatomy of the brachial plexus. The only study reporting the possibility of endoscopic approach to the brachial plexus and endoscopic anatomy was performed by Lafosse T. (2015). Our cadaveric series reported the possibility of endoscopic approach to the brachial plexus at the three levels for the first time in Russian literature. Conclusion Topographic anatomy of the supraclavicular and infraclavicular portions of the brachial plexus was examined in our series. The study showed the possibility of endoscopic approach to the brachial plexus at the interscalene space, thoracic aperture and subclavian area.
IIntroduction Sciatic nerve neuropathy is common pathology. Development of endoscopic method of decompression and neurolysis is extremely prospective. Objective Analyze the results of endoscopic ...decompression of sciatic nerve at a 1-year follow-up. Material and methods 15 patients (11 females – 79 %, 4 males – 21 %) were included into the study and were treated in the period from 2018 to 2022. Endoscopic sciatic nerve neurolysis and decompression were performed. Mean age of the patients was 47 ± 16 years. The severity of pain according to VAS was 8 ± 1. Motor dysfunction according to the BMRC scale was 2.6 ± 1.7 points. Degree of sensitive dysfunction according to Seddon scale was 2.9 ± 0.9 points. Functional activity of the lower limb according to LEFS scale was 49 ± 7 points. Results The severity of pain one year after surgery according to VAS scale decreased to 2.8 ± 2.6 cm. Degree of motor dysfunction according to BMRC scale became 4.4 ± 0.8 points. Degree of sensitive dysfunction according to Seddon scale became 3.7 ± 0.4 points. Functional activity of the lower limb according to LEFS scale increased to 68 ± 8.7 points. Efficacy of surgery in our study was 80 % (12 patients), there was one complication after surgery (6.7 %). Discussion Our study obtained clinical results that are comparable with the data of domestic and world literature. Conclusion Endoscopic decompression of sciatic nerve is an effective and low-traumatic method with a low rate of complications, which allows for pain relief, promotes restoration of function of the sciatic nerve and lower extremity.
Background: Thoracic outlet syndrome compression of the brachial plexus in the area between the clavicle and the first rib is a commonly spread and important pathology. It occurs, as usual, after a ...trauma or due to an anatomical malformation of this area. Thoracic outlet syndrome can be combined with a shoulder joint pathology. In the case of a conservative treatment's failure, the standard surgical procedure is decompression of the brachial plexus in the thoracic aperture. This procedure is usually done via an open approach. The development of the endoscopic surgical technique of decompression allows reducing the risk of complications and recurrences, improving the cosmetic result and relieving the rehabilitation period. Clinical case description: A 73-year-old female patient with a clinical picture of posttraumatic brachial plexopathy and a massive shoulder rotator cuff tear. The patient underwent a conservative treatment for 6 months after the trauma without a significant improvement. To confirm the diagnosis, ENMG and an ultrasound investigation of the brachial plexus, as well as MRI of the shoulder joint were performed. Simultaneous shoulder joint arthroscopy with subacromial spacer implantation and brachial plexus decompression in the thoracic aperture were performed to the patient. According to the VAS-scale (Visual Analogue Scale), the severity of pain syndrome before the surgery was 10 cm, while 6 months after the surgery, it decreased to 1 cm. According to the DASH scale (Disabilities of the Arm, Shoulder, and Hand), the dysfunction of the of shoulder joint before the surgery was 76 points, while 6 months after the surgery, it decreased to 12 points. The range of motion in the shoulder joint before the surgery was as follows: flexion 105, abduction 95, external rotation 15, which increased to 160, 165, and 45, respectively, 6 months after the surgery. Conclusion: The results allow us to characterize the method of simultaneous shoulder joint arthroscopy and endoscopic decompression of the brachial plexus in the thoracic aperture as a low-traumatic and effective technique. The technique provides complete brachial plexus decompression in the thoracic aperture which promotes restoration of the function of the upper extremity and shoulder joint, and elimination of pain syndrome from the upper extremity area.
The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 ...with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.
The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to ...prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.
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).
To clarify the indications for surgical treatment of malignant cerebellar infarction (CI).
Eighty patients with CI were studied. The malignancy of CI was understood as the development of mass effect ...in the posterior cranial fossa, accompanied by the decrease in consciousness due to compression of the brain stem and/or the development of occlusive hydrocephalus. The patients were divided into 2 groups. The group of malignant CI included 55 patients (68.75%) (group I), the group of benign CI included 25 patients (31.25%) (group II). Patients of group I were divided into subgroups, one of them underwent surgical treatment (surgical subgroup), and another only conservative (conservative subgroup) treatment. Surgery efficacy criteria were: restoration of consciousness to 15 points according to GCS and/or restoration of the fourth ventricle and the quadrigeminal cistern configurations. Results of treatment were assessed according to the Glasgow outcome scale.
Malignant CI occurred more frequently in patients with the volume of ischemia exceeding 20 cm
(p<0.05) in the first day of the disease. The threshold value of mass effect, which can cause further a malignant CI, was 3 points according to the M. Jauss scale. In the group of patients with malignant CI, surgical treatment reduced the mortality rate from occlusion and dislocation syndrome by 35.8%. The most effective type of intervention was a combination of decompressive trepanation of the posterior cranial fossa and external ventricular drainage.
In patients with CI with the volume more than 20 cm
and signs of mass effect in the posterior cranial fossa on the scale of M. Jauss 3 points or more, the malignant course of the disease develops in 67% of cases. These patients require careful monitoring, and, in case of development of malignant CI, surgical treatment is necessary.
INTRODUCTION
Posttraumatic axillary nerve neuropathy is a widely spread pathology, more often seen after shoulder joint trauma. It can also occur as a complication after orthopaedic surgeries, for ...example, after Latarjet procedure for shoulder stabilization. The technique of open axillary nerve decompression is very popular but has a number of disadvantages: large trauma of soft tissue, severe bleeding, high rate of complications, poor cosmetic effect. Endoscopic surgical technique of decompression is an effective, less traumatic alternative to open procedures.
AIM
To improve the outcomes of treatment of patients with axillary nerve neuropathy.
MATERIAL AND METHODS
We present the outcomes of endoscopic transcapsular axillary nerve decompression in 5 patients with a clinical picture of neuropathic pain syndrome, hypoesthesia in the deltoid area, hypotrophy of the deltoid muscle, who were operated from 2018 to 2021. The mean age of the patients was 44.4±14.9. An original surgical technique of decompression, which included arthroscopy of the shoulder joint with diagnostic and treatment components and transcapsular endoscopic axillary nerve decompression in the beach-chair position, was developed and applied to all the patients. Statistical analysis was performed using the MannWhitney U test.
RESULTS
According to VAS-scale, the severity of pain syndrome before the surgery was 6±4.6 points, 6 months after surgery it decreased to 1.4±0.5 points (p<0.05). According to DASH scale, the function of the of shoulder joint before surgery was 77,6±6,9 points, 6 months after surgery it increased to 12±5,2 points (p<0.05). According to BMRC scale (M0–M5), strength of the deltoid muscle before surgery was 2±0,4 points, after surgery it increased to 4,4±0,5 points (p<0.05). Range of motion in the shoulder joint before surgery was as follows: flexion 107±45,6°, extension 102±49°, external rotation 22±13,6°; 6 months after surgery: flexion 154±25,6°, extension 156±22,4°, external rotation 50±8° (p<0,05). The thickness of the middle portion of the deltoid muscle according to ultrasound examination before the surgery was 7.2±1.04 mm, after surgery 11.8±1.44 mm (p<0.05). All the patients (100%) during long follow-up noticed complete relief of pain and regression of neurological symptoms.
CONCLUSION
The achieved results allow us to characterize the method of endoscopic transcapsular decompression as a reproducible, minimally invasive and highly effective technique providing pain relief to patients, curing neurological and intraarticular pathology, thus promoting early restoration of the upper limb function in the treated group of patients.