Pathophysiology of COVID-19: Critical Role of Hemostasis.

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.

Pathophysiology of COVID-19: critical role of hemostasis

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2’s infection and to reduce the deaths.

Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom

Snakebite accidents are a public health problem that affects the whole world, causing thousands of deaths and amputations each year. In Brazil, snakebite envenomations are caused mostly by snakes from the Bothrops genus. The local symptoms are characterized by pain, swelling, ecchymosis, and hemorrhages. Systemic disturbances can lead to necrosis and amputations. The present treatment consists of intravenous administration of bothropic antivenom, which is capable of reversing most of the systemic symptoms, while presenting limitations to treat the local effects, such as hemorrhage and to neutralize the snake venom serine protease (SVSP). In this context, we aimed to evaluate the activity of selective serine protease inhibitors (pepC and pepB) in combination with the bothropic antivenom in vivo. Further, we assessed their possible synergistic effect in the treatment of coagulopathy and hemorrhage induced by Bothrops jararaca venom. For this, we evaluated the in vivo activity in mouse models of local hemorrhage and a series of in vitro hemostasis assays. Our results showed that pepC and pepB, when combinated with the antivenom, increase its protective activity in vivo and decrease the hemostatic disturbances in vitro with high selectivity, possibly by inhibiting botropic proteases. These data suggest that the addition of serine protease inhibitor to the antivenom can improve its overall potential.

Neumorraquis: un hallazgo en el neumomediastino espontaneo / Pneumorrhachis: A finding in spontaneous pneumomediastinum

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Urothelial papilloma: a rare cause of gross haematuria in childhood.

Bladder urothelial papilloma is extremely rare in the paediatric population. It usually presents as painless gross haematuria and its diagnosis implies a high index of suspicion as other causes of haematuria predominate in this age range. We describe a 9-year-old boy with two episodes of gross haematuria occurring 1 year apart with spontaneous resolution after 2 days. Bladder ultrasound revealed an endovesical papillary lesion of 24×24 mm suggestive of bladder tumour. The diagnosis was confirmed by histopathological examination of the specimen obtained by cystoscopy with transurethral resection. After 3 years of follow-up with ultrasound and cystoscopy, there are no signs of recurrence. Due to the low prevalence of urothelial papilloma, paediatric guidelines for appropriate management and follow-up are unavailable, making this a challenging entity.

Successful management of a patient with a C3 Glomerulonephritis and crescentic pattern: a case report.

BACKGROUND: Crescentic glomerulonephritis is a rare condition in children and is typically associated with renal insufficiency. Dysfunction of the alternative complement pathway is an unusual aetiology with an unknown mechanism. CASE PRESENTATION: We report a case of a previously healthy 12-year-old Caucasian girl who was examined on emergency owing to an asymptomatic gross haematuria. An active urinary sediment and nephrotic-range proteinuria were identified, and serologic examination showed a decreased serum C3 concentration not associated with any immunologic or infectious cause. Oedema, hypertension, and renal insufficiency were not observed. A renal biopsy was performed, and crescentic glomerulonephritis associated with C3 glomerulonephritis was diagnosed. Prompt treatment with intravenous steroids resulted in complete resolution of the gross haematuria. Further examination did not detect any underlying acquired cause. A combination of oral steroids and cyclophosphamide, followed by mycophenolate mofetil, was maintained and resulted in clinical remission during an 8-month follow-up. CONCLUSION: The presence of severe injury such as crescentic glomerulonephritis secondary to C3 glomerulonephritis is extremely unusual in children. This is the first known case of paediatric crescentic glomerulonephritis secondary to C3 glomerulonephritis that presented with gross haematuria and was treated early and effectively with immunosuppressive therapy based on its severe histologic features.

Epidermal nevus syndrome associated with hypophosphatemic rickets.

Epidermal Nevus Syndrome (ENS) is characterized by epidermal nevi associated with abnormalities involving the nervous, skeletal, and other systems. Rarely, hypophosphatemic rickets has been observed in association with epidermal nevi. A patient with ENS with right-sided serpiginous skin lesions, generalized weakness, and diffuse osteopenia associated with hypophosphatemic rickets is described. Medical management was enough to correct the clinical picture. The pathogenic mechanism involved in the onset of hypophosphatemic rickets in ENS is not fully clarified. Different studies suggest that phosphaturia, caused by circulating factor(s), called "phosphatonin(s)," may be secreted by an epidermal nevus. The nature of the phosphaturic factor(s) is not well understood, but elevated levels of circulating FGF-23 were recently reported in one patient with hypophosphatemic rickets. The authors suggest that serum FGF-23 measurement be included in the workup of this kind of rickets because there is growing evidence that in these situations the epidermal nevi produce a phosphaturic factor.

Increased mortality and morbidity due to acute myocardial infarction in a public hospital, in Feira de Santana, Bahia.

BACKGROUND: Factors related to socioeconomic status and health care quality and management may influence mortality and morbidity rates due to acute myocardial infarction (AMI). OBJECTIVE: To compare mortality and morbidity in patients with AMI hospitalized in public and private hospitals. METHODS: An observational study, with comparison groups. Clinical evaluation on admission, and recording of diagnostic, therapeutic and evolution data until discharge or death. Comparison of clinical characteristics by univariate analysis followed by bivariate analysis, evaluating the combination of predictors with death and morbidity (Killip> I), SPSS, version 13.0. RESULTS: 150 patients were evaluated, 63 (42.0%) of private hospitals and 87 (58.0%) of public hospitals, with 63.1% and 62.1% of males, aged 61.1 +/- 13.8 and 60.0 +/- 11.6 years, respectively. The mortality from AMI was 19.5% in public hospitals vs 4.8% in private hospitals (p = 0.001), and morbidity (Killip class> I) was 34.3% in public hospitals vs 15.0% in private hospitals (p = 0.012). There was a significant difference between public and private patients, due to lower family income and education (70.1% with one to two salaries vs 19.0%, p <0.001, and 49.4% of illiterates vs 6.3%, p <0.001, respectively ); late arrival at the hospital (HAT> 1 hour: 76.9% vs 48.6%, p = 0.003); and a longer period of time before being medicated (AMT > 15 minutes: 47.1% vs 8.0%; p <0.001); ICU for 8% of the patients in public hospitals vs 94% in private hospitals; and thrombolysis for 20.6% vs 54.0%, respectively (p <0.001). CONCLUSION: Mortality and morbidity were greater among public patients, which presented more serious conditions, arrived later at the hospital and received lower quality treatment.

Maior letalidade e morbidade por infarto agudo do miocárdio em hospital público, em Feira de Santana - Bahia / Mayor letalidad y morbilidad por infarto agudo de miocardio en hospital público, en Feira de Santana - Bahía / Increased mortality and morbidity due to acute myocardial infarction in a public hospital, in Feira de Santana, Bahia

FUNDAMENTO: Fatores relacionados ao nível sócio-econômico, à qualidade e à gestão assistencial podem influenciar na letalidade e morbidade por infarto agudo do miocárdio (IAM). OBJETIVO: Comparar letalidade e morbidade por IAM entre hospital público e privado. MÉTODOS: Estudo observacional, com grupos de comparação. Avaliação clínica na admissão e registro de dados diagnósticos, terapêuticos e evolutivos até a alta ou o óbito. Comparação das características clínicas por análise univariada seguida de análise bivariada, avaliando a associação de preditores com óbito e morbidade (Killip >I), SPSS, versão 13,0. RESULTADOS: Avaliados 150 pacientes, 63 (42,0 por cento) privados e 87 (58,0 por cento) públicos, com 63,1 por cento e 62,1 por cento de homens e idades de 61,1±13,8 e 60,0±11,6 anos, respectivamente. A letalidade por IAM foi de 19,5 por cento nos públicos vs 4,8 por cento nos privados (p=0,001) e a morbidade (Killip classe >1) de 34,3 por cento nos públicos vs 15,0 por cento nos privados (p=0,012). Houve diferença significativa nos públicos devido à menor renda familiar e escolaridade (70,1 por cento com um a dois salários vs 19,0 por cento, p<0,001, e 49,4 por cento de analfabetos vs 6,3 por cento, p<0,001, respectivamente), maior tempo de chegada ao hospital (TDH>1 hora: 76,9 por cento vs 48,6 por cento; p=0,003) e maior tempo para ser medicado (THM>15 minutos: 47,1 por cento vs 8,0 por cento, p<0,001), UTI para 8 por cento vs 94 por cento nos privados e trombólise para 20,6 por cento vs 54,0 por cento, respectivamente (p<0,001). CONCLUSÃO: Letalidade e morbidade maior no paciente público, que se apresentou mais grave, mais tardiamente e recebeu tratamento de menor qualidade.

BACKGROUND: Factors related to socioeconomic status and health care quality and management may influence mortality and morbidity rates due to acute myocardial infarction (AMI). OBJECTIVE: To compare mortality and morbidity in patients with AMI hospitalized in public and private hospitals. METHODS: An observational study, with comparison groups. Clinical evaluation on admission, and recording of diagnostic, therapeutic and evolution data until discharge or death. Comparison of clinical characteristics by univariate analysis followed by bivariate analysis, evaluating the combination of predictors with death and morbidity (Killip> I), SPSS, version 13.0. RESULTS: 150 patients were evaluated, 63 (42.0 percent) of private hospitals and 87 (58.0 percent) of public hospitals, with 63.1 percent and 62.1 percent of males, aged 61.1 ± 13.8 and 60.0 ± 11.6 years, respectively. The mortality from AMI was 19.5 percent in public hospitals vs 4.8 percent in private hospitals (p = 0.001), and morbidity (Killip class> I) was 34.3 percent in public hospitals vs 15.0 percent in private hospitals (p = 0.012). There was a significant difference between public and private patients, due to lower family income and education (70.1 percent with one to two salaries vs 19.0 percent, p <0.001, and 49.4 percent of illiterates vs 6.3 percent, p <0.001, respectively ); late arrival at the hospital (HAT> 1 hour: 76.9 percent vs 48.6 percent, p = 0.003); and a longer period of time before being medicated (AMT > 15 minutes: 47.1 percent vs 8.0 percent; p <0.001); ICU for 8 percent of the patients in public hospitals vs 94 percent in private hospitals; and thrombolysis for 20.6 percent vs 54.0 percent, respectively (p <0.001). CONCLUSION: Mortality and morbidity were greater among public patients, which presented more serious conditions, arrived later at the hospital and received lower quality treatment.

FUNDAMENTO: Factores relacionados al nivel socioeconómico, a la calidad y a la gestión asistencial pueden influir en la letalidad y la morbilidad por infarto agudo de miocardio (IAM). OBJETIVO: Comparar letalidad y morbilidad por IAM entre hospital público y privado. MÉTODOS: Estudio observacional, con grupos de comparación. Evaluación clínica al ingreso y registro de datos diagnósticos, terapéuticos y evolutivos hasta el alta u óbito. Comparación de las características clínicas por análisis univariado, seguida de análisis bivariado, evaluando la asociación de predictores con óbito y morbilidad (Killip >I), SPSS, versión 13,0. RESULTADOS: Se evaluaron a 150 pacientes, 63 pacientes privados (42,0 por ciento) y 87 públicos (58,0 por ciento), con un 63,1 por ciento y un 62,1 por ciento de varones y edades variando de 61,1±13,8 a 60,0±11,6 años, respectivamente. La letalidad por IAM fue de un 19,5 por ciento en los pacientes públicos vs. un 4,8 por ciento en los privados (P=0,001), y la morbilidad (Killip classe >1) de un 34,3 por ciento en los públicos vs. el 15 por ciento en los pacientes privados (P=0,012). Hubo diferencia significativa en los pacientes públicos por culpa de la menor renta familiar y de la baja escolaridad (un 70,1 por ciento con uno a dos salarios vs. el 19 por ciento, P<0,001, y un 49,4 por ciento de analfabetos vs. un 6,3 por ciento, P<0,001, respectivamente), mayor tiempo transcurrido hasta la llegada al hospital (TDH>1 hora: un 76,9 por ciento vs. un 48,6 por ciento; P=0,003) y un mayor tiempo transcurrido hasta la administración de los medicamentos (THM>15 minutos: 47,1 por ciento vs. 8,0 por ciento, P<0,001), UCI para el 8 por ciento vs. el 94 por ciento en los pacientes privados y trombólisis para un 20,6 por ciento vs. el 54 por ciento, respectivamente (P<0,001). CONCLUSIÓN: Letalidad y morbilidad mayor en el paciente público, que se presentó más severa más tardíamente, y recibió tratamiento de menor calidad.

Avaliaçäo da atividade terapêutica do albendazol sobre infecçöes experimental e human pela hymenolepis nana / Evaluation of the therapeutic activity of albendazole on experimental and human infections by hymenolepis nana

Com o intuito de demarcar convenientemente o espectro de atividade do albendazol, no que diz respeito às helmintíases intestinais, foram efetuadas observaçöes rferentes à himenolepíase causada por Hymenolepis nana. Nesse contexto, duas ordens de investigaçöes tiveram lugar: a) tratamento de camundongos, renovado depois de transcorridos dez dias, por meio de doses únicas de 25 mg/Kg ou 50 mg/Kg, sendo que 25 mg/Kg de praziquantel e animais que näo receberam os antiparasitários, serviram como controles; b) tratamento de crianças e adultos mediante uso de 400 mg cotidianamente, em três oportunidades consecutivas, com repetiçäo após intervalo com duraçäo de dez dias. O estudo concernente aos animais revelou ineficácia do albendazol, pois sistematicamente houve verificaçäo da persistência de vermes vivos no intestino. Por seu turno, só 10% dos indivíduos medificados puderam ser considerados curados. Portanto, pelo menos de acordo com a maneira como procedemos, o albendazol näo se afigurou capaz de debelar satisfatoriamente a himenolepíase