RESUMO
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.
Assuntos
COVID-19 , Colchicina/uso terapêutico , Infecções por Coronavirus , SARS-CoV-2 , Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
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.
Assuntos
Colchicina , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticoagulantes/uso terapêutico , Betacoronavirus , COVID-19 , Colchicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Nitrilas , Estudos Prospectivos , Pirazóis , Pirimidinas , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
Cardiac amyloidosis is accumulation in the heart of a pathologic fibrillar protein amyloid. It represents a heterogeneous group of states from clinically insignificant amyloid accumulation in isolated atrial amyloidosis to severe involvement of the heart in primary amyloidosis when mean duration of life equals to 6 months. Insufficient awareness of physicians of this pathology leads to erroneous and belated diagnosis of cardiac amyloidosis. This paper contains contemporary data of pathophysiology, clinical manifestation, diagnosis, treatment, and prognosis of various variants of cardiac amyloidosis.
Assuntos
Amiloidose , Doenças Cardiovasculares , Miocárdio/patologia , Amiloide , Amiloidose/diagnóstico , Amiloidose/etiologia , Amiloidose/fisiopatologia , Amiloidose/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Diagnóstico Diferencial , Testes de Função Cardíaca/métodos , Humanos , PrognósticoRESUMO
The paper gives current general data on the structure of amyloid fibril and the principles in the classification of amyloidosis, information on the clinical course of cardiac and renal involvements in systemic AL and AA amyloidosis, and that on diagnostic and prognostic criteria and the specific features of cardiorenal links. The authors draw the conclusion that the identification of acute and chronic cardiorenal links is of practical value for systemic amyloidosis. Cardiorenal and renocardiac syndromes are not always differentiated clearly in the systemacy of involvement.
Assuntos
Amiloidose , Cardiopatias , Nefropatias , Adulto , Idoso , Amiloidose/classificação , Amiloidose/diagnóstico , Amiloidose/terapia , Diagnóstico Diferencial , Evolução Fatal , Cardiopatias/classificação , Cardiopatias/diagnóstico , Cardiopatias/terapia , Humanos , Nefropatias/classificação , Nefropatias/diagnóstico , Nefropatias/terapia , MasculinoRESUMO
It has been shown that the EEG of pregnant women with high anxiety level is characterized by a lower occipital alpha and theta rhythm spectral power if compared to the EEG of women with low anxiety level. The frequency of the alpha rhythm of their EEG was reliably higher. Pregnant women with high anxiety level with a pregnancy interruption threat diagnosis have an essentially lower occipital alpha rhythm spectral power than women of this group without such a diagnosis. And vice versa, the occipital alpha rhythm spectral power in the EEG of pregnant women with low anxiety level with a pregnancy interruption threat diagnosis is essentially higher and its frequency essentially lower than the EEG of women without that diagnosis. The data received are interpreted as a change in hormone regulation during the pregnancy period, as well as psychogenic influence on the pregnancy.
Assuntos
Ansiedade/fisiopatologia , Complicações na Gravidez/fisiopatologia , Ameaça de Aborto/complicações , Ameaça de Aborto/fisiopatologia , Adulto , Ritmo alfa , Ansiedade/complicações , Feminino , Humanos , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/fisiopatologia , Complicações do Trabalho de Parto/psicologia , Gravidez , Complicações na Gravidez/psicologia , Ritmo TetaRESUMO
A 14C study of chemobiokinetics of sarcolysin and its peptides of glutaminic acid, dosage and routes of administration was conducted in intact rats and those bearing Walker's carcinoma. Similar in shape for peptides, kinetic curves differed from those found for sarcolysin. The rates of absorption and excretion of sarcolysin peptides in intraperitoneal and, particularly, oral administration were lower than those of sarcolysin. Tumor appeared to play a role in a higher rate of peptide excretion. While sarcolysin and its peptides distribution in organs and tissues was generally identical, time of peak radioactive concentration build-up was different. Time needed for accumulation and excretion of peptides from tumor was much longer than from other organs or tissues. Sarcolysin went chiefly to urine while peptides--to faeces.
Assuntos
Antineoplásicos Alquilantes/farmacocinética , Carcinoma 256 de Walker/metabolismo , Glutamatos/farmacocinética , Melfalan/farmacocinética , Administração Oral , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/metabolismo , Área Sob a Curva , Radioisótopos de Carbono , Esquema de Medicação , Glutamatos/administração & dosagem , Glutamatos/metabolismo , Infusões Parenterais , Masculino , Melfalan/administração & dosagem , Melfalan/metabolismo , Peptídeos/farmacocinética , Ratos , Fatores de Tempo , Distribuição TecidualRESUMO
To study extrapulmonary tuberculosis, the authors analyzed deaths from that of the meninges and central nervous system over 5 years (1993-1997). The clinical and morphological variants of the disease, age-sex pattern, and the specific features of its course and outcomes are described.