Etapa subaguda de pos-COVID-19 grave o crítico. Rehabilitación musculoesquelética, respiratoria y uso de corticoides. Experiencia de la Unidad de Rehabilitación del Hospital del Banco de Seguros del Estado (URHBSE)

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Introduction: In patients with severe or critical COVID-19, the use of prednisone and musculoskeletal and respiratory rehabilitation has been described. The role of these interventions and the optimal time for their initiation are not clearly established. This study presents the results of the Rehabilitation Unit of the Banco de Seguro del Estado Hospital, which implemented a comprehensive rehabilitation program and the use of corticosteroids in the subacute stage of patients with severe or critical post-COVID-19, with a systematic approach, working interdisciplinary and centered on the person being treated. Findings at admission, oxygen requirement, Barthel scale, tomographic patterns, use of corticosteroids, their response, and complications are reported. The results of this approach on clinical, respiratory, and functional variables are described. Method: Descriptive, retrospective study of post-COVID-19 patients who completed rehabilitation at the Rehabilitation Unit of the Banco de Seguros del Estado Hospital (URHBSE) in the period April-August 2021. Data obtained from review of medical records, statistical analysis with PRISM (v8.2.1). Results: Eighty-four patients completed the rehabilitation program. Upon admission to the URHBSE, 55% had total or severe dependence on the Barthel scale. Forty-eight percent were unable to walk. Eighty-nine-point two percent required oxygen, with a mean saturation of 90.3 ± 4.8. Twenty-five percent of patients were admitted requiring a reservoir mask. All patients who entered the program were in the subacute phase of the disease (4 to 12 weeks) and received a comprehensive and individualized rehabilitation plan. The objective was to achieve a functional situation similar to what they had before COVID-19. The length of stay at the URHBSE was 23.5 ± 13.8 days. A total of 76 patients (90.5%) underwent high-resolution chest tomography (HRCT), which was pathological in 96.1% of cases. The predominant findings were ground-glass opacity in 49.3% of cases, consolidation in 8.23%, and a fibrosis-like pattern in 30.13%. "Non-typical" post-COVID damage tomographic alterations were detected (pleural effusion, cavitary nodules, apical cavities, etc.) in 11.8% of the tomographies. In 2 patients (2.6%), pulmonary aspergillosis was found, and in 6.6%, pulmonary thromboembolism. Forty-four patients (52.3%) received prednisone. In 63.4% of cases, oxygen supplementation was discontinued within the first 15 days from the start of prednisone. We found an association between the ground-glass opacity tomographic pattern and early discontinuation of oxygen supplementation from the start of prednisone (p = 0.047). Despite the high degree of colonization, we did not observe infections by colonizing microorganisms, even in those who used prednisone. Comparing admission and discharge, statistically significant differences were found in the following parameters: degree of dyspnea, oxygen requirement (only one patient was discharged with oxygen), saturation, degree of instrumentation (tracheostomy, nasogastric tube, etc.), and the Barthel dependency scale. Regarding respiratory variables, we only have data on the presence of dyspnea in the first 35 patients. Of these, 83% had dyspnea at admission, while only 17% had it at discharge (p < 0.0001). There were also significant differences in the oxygen requirement between admission and discharge (p < 0.0001) and in the degree of dependency measured on the Barthel scale. Fifty-five percent of patients had total or severe dependence at admission, compared to only 3.4% at discharge. Conclusions: The interventions carried out in the subacute stage of the disease were associated with significant improvements in clinical variables of interest. More studies are needed to define the role and the exact timing of the initiation of corticosteroids and rehabilitation in this group of patients.

Introdução: O uso de prednisona e reabilitação musculoesquelética e respiratória foi descrito no tratamento de pacientes com COVID-19 grave ou crítico. O papel destas intervenções e o momento ideal para o seu início não estão claramente estabelecidos. Este trabalho mostra os resultados da Unidade de Reabilitação Hospitalar do Banco de Seguro del Estado que implementou um programa abrangente de reabilitação e uso de corticosteroides na fase subaguda de pacientes graves ou críticos pós-COVID-19, com uma abordagem sistematizada, trabalhando de forma interdisciplinar e centrada no paciente. São relatados os achados na admissão, a necessidade de oxigênio, a escala de Barthel, os padrões tomográficos, o uso de corticosteroides, a resposta ao tratamento e as complicações. Os resultados desta abordagem sobre variáveis clínicas, respiratórias e funcionais são descritos. Material e métodos: Estudo descritivo e retrospectivo de pacientes pós-COVID-19 que completaram reabilitação na Unidade de Reabilitação do Hospital Banco de Seguros del Estado (URHBSE) no período de abril a agosto de 2021. Os dados foram obtidos dos prontuários de pacientes com posterior análise estatísticas usando PRISM (v8.2.1). Resultados: 84 pacientes completaram o programa de reabilitação. No momento da admissão na URHBSE, 55% apresentavam dependência total ou grave da escala de Barthel. 48% não conseguiam se mover. 89,2% necessitaram oxigênio com saturação média de 90,3 ± 4,8. 25% dos pacientes foram internados necessitando máscara com reservatório. Todos os pacientes que ingressaram no programa estavam na fase subaguda da doença (4 a 12 semanas) e receberam um plano de reabilitação abrangente e individualizado. O objetivo era alcançar uma situação funcional semelhante à que apresentavam antes da COVID-19. O tempo de permanência na URHBSE foi de 23,5±13,8 dias. A tomografia de tórax de alta resolução (TCAR) foi realizada em 76 pacientes (90,5%); os resultados foram patológicos em 96,1%. O vidro fosco predominou em 49,3% deles, a consolidação em 8,23% e o padrão fibroso em 30,13%. Alterações tomográficas "atípicas" de danos pós-COVID (derrame pleural, nódulos cavitados, cavidades apicais, etc.) foram detectadas em 11,8% dos exames tomográficos. Aspergilose pulmonar foi encontrada em 2,6% dos pacientes e tromboembolismo pulmonar em 6,6%. 44 pacientes (52,3%) receberam prednisona. Em 63,4% a oferta de oxigênio foi suspensa nos primeiros 15 dias após o início da mesma. Encontramos associação entre o padrão tomográfico em vidro fosco e a suspensão precoce da oferta de oxigênio desde o início da administração da prednisona (p = 0,047). Apesar do alto grau de colonização, mesmo naqueles que usaram prednisona, não observamos infecções. Em relação às variáveis respiratórias, só temos dados sobre a presença de dispneia nos primeiros 35 pacientes; destes, 83% apresentavam dispneia na admissão, enquanto apenas 17% a apresentavam na alta (p< 0,0001). Observou-se também diferenças significativas na necessidade de O2 entre a admissão e a alta (p< 0,0001) e no grau de dependência medido pela escala de Barthel, com 55% dos pacientes apresentando dependência total ou grave na admissão e apenas 3,4% na alta. Conclusões: As intervenções realizadas na fase subaguda da doença foram associadas a melhorias significativas nas variáveis de interesse clínico. São necessários mais estudos para definir o papel e o momento exato do início dos corticosteroides e da reabilitação neste grupo de pacientes.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic / Fármacos y productos naturales para el tratamiento de la COVID-19 durante 2020, el primer año de la pandemia

Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Famotidina en el tratamiento de pacientes hospitalizados con COVID-19. Revisión sistemática y metaanálisis

Introducción: El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2), de alta morbimortalidad, carece a la fecha de preparar esta revisión, de una terapia específica altamente eficaz. Famotidina se ha postulado como una opción terapéutica viable, basado en trabajos de cohorte retrospectiva y modelos computacionales guiados por inteligencia artificial. Objetivo: Recopilar la mejor evidencia científica disponible para determinar la efectividad y eficacia de famotidina en el tratamiento de pacientes hospitalizados con COVID-19, para reducir el riesgo de progresión de la enfermedad, intubación, muerte y tiempo de estancia hospitalaria. Material y Métodos: Se realizó una búsqueda en PubMed, EBSCO, Scopus, Web of Science y Cochrane Central, de artículos originales que reporten las variables de interés asociadas al uso de famotidina en pacientes hospitalizados con COVID- 19. Los investigadores independientemente evaluaron y seleccionaron los estudios, se extrajeron los datos expuestos para las asociaciones de interés y se procesaron con el software Revman 5.3. Resultados: En la búsqueda se obtuvo un total de 126 artículos potenciales para la revisión, de los cuales 14 fueron seleccionados para el análisis. En el metaanálisis se incluyeron un total de 47.044 pacientes, de los cuales 6.647 fueron los usuarios de famotidina. El riesgo de intubación se vio reducido en el grupo no expuesto a famotidina, aunque sin significancia estadística, (RR 1,43 IC95% 0,42-4,83), en cuanto a la mortalidad no se evidenció reducción significativa en el grupo de famotidina (RR 0,95 IC 95% 0,70-1,29). Se observó reducción en el tiempo de estancia hospitalaria (DM -1,60 -2,89, -0,31) y finalmente se mostró que no hay presencia de asociación entre el uso de famotidina y el desenlace compuesto de reducción del riesgo de ingreso a UCI, intubación y muerte (RR 1,03 IC 95% 0,46-2,34). Conclusión: Famotidina no presenta efectividad ni eficacia en la reducción de riesgo de intubación o ingreso a UCI ni de mortalidad en pacientes hospitalizados por COVID-19. La eficacia en la reducción de la estancia hospitalaria no es consistente y se necesitan más ensayos clínicos con buena calidad metodológica para definirla.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high morbidity and mortality, lacks, at the time of preparing this review, a highly effective specific therapy. Famotidine has been postulated as a viable therapeutic option, based on retrospective cohort investigations and computational models guided by artificial intelligence. Aim: The objective of this study was to compile the best scientific evidence available to determine the effectiveness and efficacy of famotidine in the treatment of hospitalized patients with COVID-19, to reduce the risk of disease progression, intubation, death, and time to hospital stay. Methods: A search was carried out in PubMed, EBSCO, Scopus, Web of Science, and Central Cochrane, for original articles that report the variables of interest associated with the use of famotidine in hospitalized patients with COVID-19. The investigators independently evaluated and selected the studies, the exposed data for the associations of interest were extracted and processed with Revman 5.3 software. Results: The search yielded a total of 126 potential articles for the review, of which 14 were selected for analysis. A total of 47,044 patients were included in the meta-analysis of which 6,647 were famotidine users. The risk of intubation was reduced in the group not exposed to famotidine, although without statistical significance (RR 1.43 IC95% 0.42 - 4.83), regarding mortality there was no significant reduction in the famotidine group (RR 0.95 IC 95 % 0.70-1.29). A reduction in the length of hospital stay was observed (MD -1.60 -2.89, -0.31) and finally it was shown that there is no association between the use of famotidine and the composite outcome of reduced risk of ICU admission, intubation and death. (RR 1.03 95% CI 0.46-2.34). Conclusion: Famotidine does not show effectiveness or efficacy in reducing the risk of intubation or ICU admission or mortality in patients hospitalized for COVID-19. The efficacy in reducing hospital stay is not consistent and more clinical trials with good methodological quality are needed to define it.

Caso de dengue grave en un niño de 5 años de la ciudad de Lima / A case of severe dengue in a 5-year-old boy in the city of Lima

RESUMEN El dengue es una infección viral transmitida a través del mosquito Aedes aegypti y presenta cuatro serotipos (DENV-1 a DENV-4). La enfermedad desencadena una variedad de manifestaciones clínicas, desde formas leves sin signos de alarma hasta formas graves, potencialmente mortales. Se presenta el caso de un niño de cinco años, procedente de la provincia del Callao, cuyos síntomas iniciales fueron fiebre, cefalea y malestar general. Al tercer día, el niño manifiestó dolor abdominal leve y vómitos escasos; posteriormente, distensión abdominal, ictericia y coluria. Fue hospitalizado en la unidad de cuidados intensivos pediátricos con deshidratación moderada, ictericia, edemas, abdomen distendido y doloroso, matidez desplazable, hígado a 2 cm debajo del reborde costal derecho y lúcido. Por exámenes complementarios, se evidenció falla hepática, hepatoesplenomegalia y derrame pleural en bases. Se diagnosticó dengue grave a través de una prueba de ELISA Ig M reactivo más sobreinfección por probable peritonitis bacteriana espontánea. Se inició el tratamiento con antibióticos, furosemida, plasma fresco congelado, crioprecipitado y metamizol. Al no observarse mejoría, se optimizó el diurético y se administró albúmina humana. Mostró mejoría con disminución de ascitis, edemas, ictericia y efusión pleural; también mejora del perfil hepático y de la coagulación, además de encontrarse afebril. Presentó inesperadamente dificultad respiratoria por insuficiencia cardiaca congestiva debido a miocardiopatía dilatada según ecocardiografía; se manejó con diuréticos. Fue dado de alta en estado afebril, sin edemas y con resolución de falla hepática y trastorno de coagulación.

ABSTRACT Dengue is a viral infection which is transmitted by the Aedes aegypti mosquito and has four serotypes (DENV-1 to DENV-4). The disease triggers a variety of clinical manifestations, ranging from mild forms without warning signs to severe lifethreatening forms. We present the case of a 5-year-old boy, from the province of Callao, whose first symptoms were fever, headache and general malaise. On the third day, the child had mild abdominal pain and little vomiting; subsequently, abdominal distension, jaundice and choluria. He was admitted to the pediatric intensive care unit being alert and with moderate dehydration, jaundice, edema, distended and tender abdomen, shifting dullness and liver 2 cm below the right costal margin. Complementary tests revealed liver failure, hepatosplenomegaly and pleural effusion in the bases. Using a reactive IgM ELISA, severe dengue was diagnosed, as well as a superinfection due to probable spontaneous bacterial peritonitis. He started treatment with antibiotics, furosemide, fresh frozen plasma, cryoprecipitate and metamizole. As the child did not get better, the diuretic was optimized, and human albumin was administered. Thereafter, he got better showing decreased ascites, edema, jaundice and pleural effusion; improvement of the liver and coagulation profile; and being afebrile. He unexpectedly presented respiratory distress due to congestive heart failure caused by dilated cardiomyopathy diagnosed by echocardiography; thus, he was treated with diuretics. The patient was discharged afebrile, without edema and with resolution of liver failure and coagulation disorder.

Manejo clínico quirúrgico de la necrosis pancreática infectada en adultos: experiencia en un hospital especializado, Paraguay / Surgical clinical management of necrotizing pancreatitis in adults: experience in a specialized hospital, Paraguay

Introducción: la necrosis pancreática se presenta entre 10 y 20 % de los pacientes con pancreatitis aguda, tiene una mortalidad de 10 a 25 % y si se agrega infección a la necrosis entre 40 y 70 %. Objetivo: describir el manejo clínico quirúrgico de la necrosis pancreática infectada en el Servicio de Cirugía General del Hospital Nacional entre el periodo 2021-2022. Metodología: estudio observacional descriptivo de corte temporal transversal. En pacientes internados en el Servicio de Cirugía General del Hospital Nacional por pancreatitis aguda grave con necrosis pancreática infectada. Resultados: se analizaron un total de 30 pacientes. La media de edad fue de 39 años. Predominó en nuestra población pacientes de sexo masculino en el 56.67 %. En cuanto a las comorbilidades asociadas un 33.3 % los pacientes presentaron principalmente Diabetes mellitus tipo 2 e Hipertensión arterial; en menor medida Obesidad en un 23.3 %. De la población en estudio 76.6 % recibieron tratamiento quirúrgico y 23.33% tratamiento médico principalmente antibiótico terapia. De los pacientes sometidos a tratamiento quirúrgico 9 fueron a necrosectomia abierta, 7 a drenaje percutáneo, y en menor medida drenaje biliar y endoscópico. En cuanto a la mortalidad por necrosis pancreática infectada encontramos un 10 % de mortalidad. Discusión: la mayor parte de los pacientes con pancreatitis aguda grave sufren de necrosis pancreática; la necrosis pancreática infectada se asocia con mayor riesgo de mortalidad y en su mayoría requieren tratamientos invasivos. Conclusión: el manejo mínimamente invasivo en el tratamiento inicial de la necrosis pancreática infectada podría resolver la mayoría de los casos sin necesidad de realizar necrosectomia; reservando esta última solo a los que fracasan en el tratamiento inicial.

Introduction: pancreatic necrosis occurs between 10 and 20 % of patients with pancreatitis, has a mortality of 10 to 25 % and if infection is added to the necrosis between 40 and 70 %. Objective: to describe the surgical and clinical management of infected necrotizing pancreatitis in patients admitted to the General Surgery Service of the Hospital Nacional between the period 2021-2022. Methodology: this was an observational, descriptive and cross-section study with a temporal cut. We included patients admitted to the general surgery service of the National Hospital with severe acute pancreatitis with infected necrotizing pancreatitis. Results: a total of 30 patients were included. The mean age was 39 years. Male patients prevailed in our population in 56.67 %. Regarding the associated comorbidities, 33.3 % of the patients presented mainly type 2 diabetes mellitus and arterial hypertension; to a lesser extent Obesity in 23.3 %. In the study population, 76.6 % received surgical treatment and 23.33 % medical treatment, mainly antibiotic therapy. Of the patients who underwent surgical treatment, 9 were open necrosectomy, 7 had percutaneous drainage, and to a lesser extent biliary and endoscopic drainage. Regarding mortality due to infected necrotizing pancreatitis, we found a 10% mortality. Discussion: most of the patients with severe acute pancreatitis suffer from necrotizing pancreatitis; infected necrotizing pancreatitis is associated with increased risk of mortality and most require invasive treatment. Conclusion: minimally invasive management in the initial treatment of infected necrotizing pancreatitis, which could resolve most cases without the need to perform necrosectomy; the latter should be reserved for those who fail the initial treatment.

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma

Abstract Objectives The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. Methods A total of 1066 adults were evaluated. Asthma and chronic⁄allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. Results Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p= 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). Conclusion Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. Level of evidence: Level 3.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Management of critical bleeding

Abstract The management of major bleeding is a critical aspect of modern healthcare and it is imperative to emphasize the importance of applying Patient Blood Management (PBM) principles. Although transfusion support remains a vital component of bleeding control, treating severe bleeding goes beyond simply replacing lost blood. A more comprehensive, multidisciplinary approach is essential to optimize patient outcomes and minimize the risks associated with excessive transfusions.

Dengue Burden and Factors Influencing Severity in Honduras: A Descriptive and Analytical Study

ABSTRACT Background: Dengue is a disease that accounts for a major morbidity and mortality in Honduras. Methods: This descriptive study used an analytical component based on the data from the National Virology Laboratory between 2016-2022. Ordinal logistic regression was used to identify the factors associated with the classification of dengue without warning signs (DWOS), dengue with warning signs (DWS), and severe dengue (SD). Results: Overall, 14,687 dengue cases were included; 50.1% had DWOS, 36.5% had DWS, and 13.4% had SD. Patients that were more associated with a higher probability of DWS and SD were patients in the age groups 1-4 years (DWS OR 1.61; 95%CI:1.33-1.94), (SD OR 1.52; 95% CI:1.26-1.84), 5-9 years (DWS OR 2.01; 95% CI:1.68-2.40), (SD OR 2.00; 95% CI:1.67-2.40), and 10-19 years (DWS OR 1.55; 95% CI:1.30-1.85) (SD OR 1.57; 95% CI:1.31-1.88). The departments that were associated with a higher probability of DWS and SD were La Paz (OR 6.35; 95% CI:3.53-11.42), (OR 10.94; 95% CI:5.96-20.08), Copán (OR 6.94; 95% CI:5.05-9.53) (OR 7.33; 95% CI: 5.35-10.03), Valle (OR 5.22; 95% CI:1.25-21.82) (OR 10.71; 95% CI:2.21-51.88). Conclusions: During the study period, dengue presented endemic behavior, with peaks consistent with the last two epidemics in Honduras in 2015 and 2019. The main factors associated with dengue severity were age< 19 years, male sex, and being from La Paz, Copán, or Valle.

Aspectos clínico-epidemiológicos en pacientes con malaria grave del Hospital Municipal de Cuimba, Angola

Introducción: El Plasmodium falciparum es el causante de más del 90 % de los casos de malaria en el mundo. Objetivo: Describir aspectos clínico-epidemiológicos de pacientes con malaria grave, atendidos en el Hospital Municipal de Cuimba, provincia de Zaire, República de Angola. Método: Estudio observacional, descriptivo, de corte transversal y retrospectivo, durante el periodo comprendido entre enero-junio de 2023, en pacientes con diagnóstico de malaria grave. El universo fue conformado por 452 pacientes positivos de malaria, la muestra quedó conformada por 97 pacientes que desarrollaron malaria grave. Se estudiaron variables asociadas como: anemia severa, convulsiones, hiperparasitemia, entre otras. Resultados: La media de edad fue de 14,8 años, el 43,3 % menor de cinco años, con predominio del sexo masculino (53,9 %). El Plasmodium falciparum estuvo presente en 59 casos (60,8 %), con elevadas tasas de parasitemia. Las manifestaciones de disfunción cerebral en asociación con la anemia severa resultaron estar en el cuadro clínico del 31 % de los pacientes. El 40,2 % de los enfermos no presentó complicaciones en su estadía hospitalaria. El síndrome de dificultad respiratoria aguda (18,6 %) fue la complicación más frecuente que sobrellevó al fallecimiento del 12,4 % de los pacientes. El artesunato fue usado en 77,3 % de los pacientes. Conclusiones: El paludismo representa un problema de salud en el Hospital Municipal de Cuimba, con mayor frecuencia en los menores de cinco años. Prevalece la infección por Plasmodium falciparum en pacientes con anemia severa.

Introduction: Plasmodium falciparum is responsible for more than 90 % of malaria worldwide. Objective: Characterization of Clinical-epidemiological aspects of severe malaria in patients treated at the Municipal Hospital of Cuimba, Zaire, Angola. Method: An observational, descriptive, cross-sectional and retrospective study was conducted, during the period January - June 2023, in patients reported with severe malaria. The study involved a total of 452 patients with positive malaria but only 97 of them, who presented a complication of severe malaria, were selected as sample. The variables used were as follow: severe anemia, convulsions, hyperparasitemia, among others. Results: Male sex was predominant, with an average age of 14.8% and 43.3% of patients under five years of age. Plasmodium falciparum was found in 59 patients (60.8%) with a high parasitaemia prevalence. Manifestations of cerebral dysfunction in association with severe anemia were found in the clinical picture of 31% of patients. The 40.2% of patients had no complications in admission period. Acute Respiratory Distress Syndrome was the most frequent complication (18.6%), and it was the leading cause of death in 12.4% of patients. Artesunate was used in 77.3% of patients. Conclusions: Malaria is a health problem in Municipal Hospital of Cuimba, with a higher incidence in children under five years of age; Plasmodium falciparum infection prevailed in patients with severe anemia.

Introdução: O Plasmodium falciparum é responsável por mais de 90 % da malária em todo o mundo. Objetivo: Caracterização dos aspectos clínico-epidemiológicos da malária grave em pacientes atendidos no Hospital Municipal de Cuimba, Zaire, Angola. Método: Foi realizado um estudo observacional, descritivo, transversal e retrospetivo, durante o período de janeiro a junho de 2023, em doentes notificados com malária grave. O estudo envolveu um total de 452 doentes com malária positiva, mas apenas 97 deles, que apresentavam uma complicação de malária grave, foram seleccionados como amostra. As variáveis utilizadas foram as seguintes: anemia grave, convulsões, hiperparasitemia, entre outras. Resultados: O sexo masculino foi predominante, com uma idade média de 14,8 anos e 43,3 % dos doentes com menos de cinco anos de idade. O Plasmodium falciparum foi encontrado em 59 doentes (60,8 %) com uma elevada prevalência de parasitemia. Manifestações de disfunção cerebral em associação com anemia grave foram encontradas no quadro clínico de 31 % dos doentes. Os 40,2 % dos doentes não tiveram complicações no período de admissão. A Síndrome de Angústia Respiratória Aguda foi a complicação mais frequente (18,6 %) e foi a principal causa de morte em 12,4 % dos doentes. O artesunato foi utilizado em 77,3 % dos doentes. Conclusões: A malária é um problema de saúde em Hospital Municipal de Cuimba, com uma maior incidência em crianças com menos de cinco anos de idade; a infeção por Plasmodium falciparum prevaleceu em pacientes com anemia grave.

Vaccine effectiveness in preventing deaths in people with severe acute respiratory syndrome due to COVID-19 in Blumenau, Brazil, 2021 / Efectividad de las vacunas en la prevención de la muerte por síndrome respiratório agudo grave por covid-19 en Blumenau, Brasil, 2021 / Efetividade vacinal na prevenção de óbitos em pessoas com síndrome respiratória aguda grave por covid-19 em Blumenau, 2021

ABSTRACT Objective to analyze the vaccine effectiveness in preventing deaths attributed to severe acute respiratory syndrome due to COVID-19 (SARS/COVID-19) in adults and the elderly, in Blumenau, state of Santa Catarina, Brazil, 2021. this was a population-based study conducted among individuals aged 20 years and older hospitalized with SARS/COVID-19; each death due to SARS/COVID-19 was considered a "case", and every survivor was considered a "control"; the association between vaccination status and the outcome of "death" was estimated using logistic regression, and vaccine effectiveness was estimated as (1-OR)*100. The study included 1,756 cases of SARS/COVID-19 (59.2% male, mean age of 56 years, 50.4% with elementary education, 68.4% with comorbidities and 39.1% in intensive care), of whom 398 died (cases) and 1,358 survived (controls); vaccine effectiveness was 74% and 85% (20-59 years old) and 72% and 75% (≥ 60 years old), respectively, for those who were partially vaccinated and fully vaccinated. Conclusion vaccines proved to be effective in reducing case fatality ratio due to SARS/COVID-19 in individuals ≥ 20 years old.

RESUMEN Objetivo analizar la efectividad de la vacuna para prevención de muertes por SRAG-COVID en adultos y ancianos de Blumenau, Santa Catarina, Brasil, 2021. Método estudio de base poblacional con personas hospitalizadas por SRAG-COVID mayores de 20 años; las muertes por SRAG-COVID se consideraron casos y todos los supervivientes, controles; la asociación entre el estado de vacunación y la muerte se estimó mediante regresión logística; la efectividad de la vacuna se estimó por (1-OR)*100. Resultados participaram do estudo 1.756 casos de SRAG-COVID (59,2% del sexo masculino, edad media de 56 años, 50,4% con estudios primarios, 68,4% con comorbilidades y 39,1% en cuidados intensivos), dos quais 398 foram a óbito (casos) e 1.358 sobreviveram (controles); la efectividad de la vacuna fue del 74% y el 85% (20 a 59 años) y del 72% y el 75% (60 y más años), entre los que tenían vacunación parcial y completa, respectivamente. Conclusión las vacunas fueran efectivas para reducir la letalidad del SRAG-covid.

RESUMO Objetivo Analisar a efetividade vacinal na prevenção de óbitos atribuídos a síndrome respiratória aguda grave por covid-19 (SRAG-covid) em adultos e idosos, em Blumenau, Santa Catarina, Brasil, 2021. Métodos Estudo populacional, entre maiores de 20 anos de idade internados por SRAG-covid; considerou-se "caso" cada óbito por SRAG-covid, e "controle", todo sobrevivente; estimou-se a associação entre a condição vacinal e o desfecho "óbito" por regressão logística, e a efetividade vacinal, por (1-OR)*100. Resultados Participaram do estudo 1.756 casos de SRAG-covid (59,2% do sexo masculino, idade média de 56 anos, 50,4% com ensino fundamental, 68,4% com comorbidades e 39,1% em cuidado intensivo), dos quais 398 foram a óbito (casos) e 1.358 sobreviveram (controles); a efetividade vacinal foi de 74% e 85% (20-59 anos) e de 72% e 75% (≥ 60 anos), respectivamente, para quem possuía vacinação parcial e vacinação completa. Conclusão Vacinas mostraram-se efetivas na redução da letalidade por SRAG-covid em indivíduos com idade ≥ 20 anos.

Machine learning in predicting severe acute respiratory infection outbreaks / Aprendizado de máquina na previsão de surtos de síndrome respiratória aguda grave / Aprendizaje automático en la predicción de brotes de síndrome respiratorio agudo grave

Abstract: Severe acute respiratory infection (SARI) outbreaks occur annually, with seasonal peaks varying among geographic regions. Case notification is important to prepare healthcare networks for patient attendance and hospitalization. Thus, health managers need adequate resource planning tools for SARI seasons. This study aims to predict SARI outbreaks based on models generated with machine learning using SARI hospitalization notification data. In this study, data from the reporting of SARI hospitalization cases in Brazil from 2013 to 2020 were used, excluding SARI cases caused by COVID-19. These data were prepared to feed a neural network configured to generate predictive models for time series. The neural network was implemented with a pipeline tool. Models were generated for the five Brazilian regions and validated for different years of SARI outbreaks. By using neural networks, it was possible to generate predictive models for SARI peaks, volume of cases per season, and for the beginning of the pre-epidemic period, with good weekly incidence correlation (R2 = 0.97; 95%CI: 0.95-0.98, for the 2019 season in the Southeastern Brazil). The predictive models achieved a good prediction of the volume of reported cases of SARI; accordingly, 9,936 cases were observed in 2019 in Southern Brazil, and the prediction made by the models showed a median of 9,405 (95%CI: 9,105-9,738). The identification of the period of occurrence of a SARI outbreak is possible using predictive models generated with neural networks and algorithms that employ time series.

Resumo: Surtos de síndrome respiratória aguda grave (SRAG) ocorrem anualmente, com picos sazonais variando entre regiões geográficas. A notificação dos casos é importante para preparar as redes de atenção à saúde para o atendimento e internação dos pacientes. Portanto, os gestores de saúde precisam ter ferramentas adequadas de planejamento de recursos para as temporadas de SRAG. Este estudo tem como objetivo prever surtos de SRAG com base em modelos gerados com aprendizado de máquina usando dados de internação por SRAG. Foram incluídos dados sobre casos de hospitalização por SRAG no Brasil de 2013 a 2020, excluindo os casos causados pela COVID-19. Estes dados foram preparados para alimentar uma rede neural configurada para gerar modelos preditivos para séries temporais. A rede neural foi implementada com uma ferramenta de pipeline. Os modelos foram gerados para as cinco regiões brasileiras e validados para diferentes anos de surtos de SRAG. Com o uso de redes neurais, foi possível gerar modelos preditivos para picos de SRAG, volume de casos por temporada e para o início do período pré-epidêmico, com boa correlação de incidência semanal (R2 = 0,97; IC95%: 0,95-0,98, para a temporada de 2019 na Região Sudeste). Os modelos preditivos obtiveram uma boa previsão do volume de casos notificados de SRAG; dessa forma, foram observados 9.936 casos em 2019 na Região Sul, e a previsão feita pelos modelos mostrou uma mediana de 9.405 (IC95%: 9.105-9.738). A identificação do período de ocorrência de um surto de SRAG é possível por meio de modelos preditivos gerados com o uso de redes neurais e algoritmos que aplicam séries temporais.

Resumen: Brotes de síndrome respiratorio agudo grave (SRAG) ocurren todos los años, con picos estacionales que varían entre regiones geográficas. La notificación de los casos es importante para preparar las redes de atención a la salud para el cuidado y hospitalización de los pacientes. Por lo tanto, los gestores de salud deben tener herramientas adecuadas de planificación de recursos para las temporadas de SRAG. Este estudio tiene el objetivo de predecir brotes de SRAG con base en modelos generados con aprendizaje automático utilizando datos de hospitalización por SRAG. Se incluyeron datos sobre casos de hospitalización por SRAG en Brasil desde 2013 hasta 2020, salvo los casos causados por la COVID-19. Se prepararon estos datos para alimentar una red neural configurada para generar modelos predictivos para series temporales. Se implementó la red neural con una herramienta de canalización. Se generaron los modelos para las cinco regiones brasileñas y se validaron para diferentes años de brotes de SRAG. Con el uso de redes neurales, se pudo generar modelos predictivos para los picos de SRAG, el volumen de casos por temporada y para el inicio del periodo pre-epidémico, con una buena correlación de incidencia semanal (R2 = 0,97; IC95%: 0,95-0,98, para la temporada de 2019 en la Región Sudeste). Los modelos predictivos tuvieron una buena predicción del volumen de casos notificados de SRAG; así, se observaron 9.936 casos en 2019 en la Región Sur, y la predicción de los modelos mostró una mediana de 9.405 (IC95%: 9.105-9.738). La identificación del periodo de ocurrencia de un brote de SRAG es posible a través de modelos predictivos generados con el uso de redes neurales y algoritmos que aplican series temporales.

Spatial analysis of hospital-related mortality due to COVID-19 among children and adolescents in Brazil / Análise espacial da mortalidade hospitalar por COVID-19 em crianças e adolescentes no Brasil

Abstract The objective was to perform a spatial analysis of the hospital mortality rate (HMR) due to severe acute respiratory syndrome (SARS) attributed to COVID-19 among children and adolescents in Brazil from 2020 to 2021. A cluster method was used to group federal units (FUs) based on HMR. In 2020, clusters with high HMRs were formed by north/northeast FUs. In 2021, there was a reduction in HMR. Clusters with higher rates remained in the N/NE region. Regional differences were observed in the HMR. The findings may reflect social inequalities and access to hospital care, especially in the under 1-year-old age group due to the severity of the disease in this group.

Resumo Objetivou-se realizar uma análise espacial da taxa de mortalidade hospitalar (TMH) por síndrome respiratória aguda grave (SRAG) atribuída à COVID-19 em crianças e adolescentes no Brasil no período de 2020 a 2021. Utilizou-se o método de cluster para agrupar as unidades federativas (UFs) com base na TMH. Em 2020, clusters com altas TMHs foram formados por UFs Norte/Nordeste. Em 2021, houve redução na TMH. Os clusters com maiores taxas permaneceram na região N/NE. Diferenças regionais foram observadas nas TMHs. Os achados podem refletir as desigualdades sociais e o acesso à atenção hospitalar, principalmente na faixa etária de menores de 1 ano pela gravidade da doença neste grupo.

Evaluation of Severe Acute Respiratory Syndrome surveillance caused by respiratory viruses in a pediatric unit, 2013 to 2019 / Avaliação da vigilância da Síndrome Respiratória Aguda Grave causada por vírus respiratórios em uma unidade pediátrica, 2013 a 2019

ABSTRACT Objective: To evaluate severe acute respiratory syndrome surveillance in a pediatric unit. Methods: Descriptive study of reported severe acute respiratory syndrome cases with the detection of respiratory viruses in the nasopharyngeal sample of patients hospitalized between 2013 and 2019, in a reference hospital in the Federal District, Brazil. Results: A total of 269 children had one or more viruses detected, resulting in 280 viruses, of which 152 (54%) were respiratory syncytial virus. The detection of respiratory syncytial virus was higher during the autumn-winter period. Children´s median age was 6.9 months, 156 (58%) were male, 104 (39%) had comorbidity, 197 (73%) required mechanical ventilation, 241 (90%) received antibiotics, and 146 (54%) oseltamivir. There were 19 (7%) deaths. The median time from symptom onset to sample collection was 5 days and the median time from sample collection to final results was 6 days. Conclusions: The system needs to reduce the time to deliver results so that inappropriate use of antibiotics and antivirals can be avoided. Moreover, the burden of viral pneumonia was relevant and the system must be flexible enough to include emerging viruses in order to be useful in responding to public health emergencies caused by respiratory viruses.

RESUMO Objetivo: Avaliar a vigilância da síndrome respiratória aguda grave em uma unidade pediátrica. Métodos: Estudo descritivo dos casos de síndrome respiratória aguda grave, notificados e com a detecção de vírus respiratório em amostra de nasofaringe de pacientes internados entre 2013 e 2019, em um hospital de referência do Distrito Federal. Resultados: Um total de 269 crianças tiveram algum vírus detectado, resultando em 280 vírus, sendo 152 (54%) vírus sincicial respiratório. A detecção do vírus sincicial respiratório foi maior durante o período de outono-inverno. A mediana da idade das crianças foi de 6,9 meses, 156 (58%) eram do sexo masculino, 104 (39%) tinham comorbidade, 197 (73%) necessitaram de ventilação mecânica, 241 (90%) receberam antibióticos e 146 (54%) oseltamivir. Ocorreram 19 (7%) óbitos. A mediana do tempo desde o início dos sintomas até a coleta da amostra foi de 5 dias, e do tempo da coleta até o resultado foi de 6 dias. Conclusões: O sistema necessita reduzir o tempo do resultado final para que seja possível evitar o uso inadequado de antibióticos e antivirais. Ademais, o impacto das pneumonias virais foi relevante e o sistema deve ser flexível suficiente para incluir vírus emergentes, para ser útil na resposta às emergências de saúde pública causada por vírus respiratórios.

Compatibility Theory of Yiqi Zengmian Prescription as Vaccine Adjuvant / 中国实验方剂学杂志

ObjectiveThis study explored the application of Yiqi Zengmian prescription as a vaccine adjuvant， aiming to provide a new scheme for the prevention and control of corona virus disease 2019（COVID-19） with traditional Chinese medicine （TCM）. By analyzing the compatibility and efficacy， this paper examines the compatibility effect of Yiqi Zengmian prescription， which is modified from the classic tonifying agent Si Junzitang， as a vaccine adjuvant. MethodUsing the Database of Ancient Classical Prescriptions， this paper analyzed the composition of Yiqi Zengmian prescription and probed into the theoretical basis for the compatibility of this prescription from the properties， medicine combination， and efficacy. Furthermore， the compatibility effect of this prescription with vaccines was analyzed. ResultAs a TCM prescription， Yiqi Zengmian prescription focuses on the lung and spleen and enhances the Qi in the two organs. The lung governs Qi movement. The body breathes fresh air through the lungs and exchanges the turbid gas in the lungs， and the gas circulates alternately in the lungs to ensure the normal breathing of the human body. The spleen governing transportation and transformation is the hub for Qi movement， and Qi is the embodiment of metabolic function. By regulating qi movement and enhancing the functions of Qi and blood， Yiqi Zengmian prescription can enhance the immunogenicity of the vaccine， which provides a theoretical basis for enhancing the immune effects of vaccines. ConclusionYiqi Zengmian prescription has the effects of replenishing Qi and invigorating spleen， regulating Qi and drying dampness， and enhancing immunity. The in-depth analysis of the TCM theory of Yiqi Zengmian prescription as a vaccine adjuvant and the results of clinical and laboratory studies suggest that Yiqi Zengmian prescription may enhance the induction of immune response after vaccination and maintain the immune memory. However， the mechanism of Yiqi Zengmian prescription in regulating the complex immune network remains to be elucidated.

Compound anisodine combined with retinal laser photocoagulation for the treatment of severe non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of the compound anisodine combined with retinal laser photocoagulation in the treatment of severe non-proliferative diabetic retinopathy(NPDR). METHODS: According to the retrospective study, totally 120 eyes of patients with severe NPDR who admitted to Daxing Teaching Hospital Affiliated to Capital Medical University from May 2023 to July 2023 were selected. The patients were divided into the observation group and the control group according to treatment methods, with 60 eyes in each group. The observation group was treated with panretinal photocoagulation combined with the compound anisodine injection. The control group was only treated with panretinal photocoagulation. The optical coherence tomography angiography(OCTA)and optical coherence tomography(OCT)were used to quantitatively analyze the fundus retinal structure and blood flow. Furthermore, the best corrected visual acuity(BCVA), superficial vascular density(SVD), deep vascular density(DVD), choroidal blood flow density and central macular foveal retinal thickness(CMT)were compared before treatment and at 1 d, 1 and 2 mo after treatment.RESULTS:At 2 mo postoperatively, the rate of visual improvement and the BCVA in the observation group of patients were significantly better than those of the control group, and the incidence of macular edema in the observation group was significantly lower than the control group(P&#x003C;0.05). The BCVA at 1 and 2 mo after treatment were significantly higher than those before treatment in both groups(P&#x003C;0.05). The SVD in the observation group was better than the control group at 1 d, 1 and 2 mo after treatment(all P&#x003C;0.05). The DVD and choroidal flow density in the observation group were better than those of the control group at 1 d after treatment(all P&#x003C;0.05). The CMT of the observation group was smaller than that of the control group at 1 d after treatment(P&#x003C;0.05).CONCLUSION:Compound anisodine can effectively improve the fundus microcirculation after panretinal photocoagulation and reduce the incidence of macular edema, thus promoting the visual function.

Epidemiological characteristics of patients with severe fever with thrombocytopenia syndrome in Dongyang City / 预防医学

Objective @#To investigate the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Dongyang City, Zhejiang Province from 2017 to 2022, so as to provide insights into SFTS prevention and control. @*Methods@#Data pertaining to patients with SFTS in Dongyang City from 2017 to 2022 were collected from Notifiable Infectious Disease Reporting System of Chinese Disease Prevention and Control Information System. The epidemiological and clinical characteristics of patients with SFTS were descriptively analyzed, and the trends in incidence of SFTS was evaluated using annual percent change (APC). @*Results@#A total of 32 SFTS cases were reported in Dongyang City from 2017 to 2022, with mean annual incidence of 0.63/105, and 8 cases died, with a fatality rate of 25.00%. The incidence of SFTS appeared a tendency towards a rise from 2017 to 2022 (APC=40.697%, P<0.05). The male to female ratio of SFTS cases was 0.78∶1, and farmer was the predominant occupation (31 cases, 96.88%). SFTS predominantly occurred among individuals at ages of 51 to 69 years (20 cases, 62.50%), and the incidence peaked during the period between March and May and between July and August (28 cases, 87.50%). SFTS cases were reported in 11 out of the 18 townships (streets) in Dongyang City, with the highest number found in Zuocun Township (8 cases, 28.13%), and had the lowest platelet count of (41.46±5.19)×109 platelets/L, with the lowest count of (3.00 to 67.00) ×109 platelets/L. All the SFTS cases had a history of mountain forest and farmland activities 2 weeks prior to onset of the disease, and 5 cases (15.63%) had a history of tick bites.@*Conclusions@#The incidence of SFTS appeared a tendency towards a rise in Dongyang City from 2017 to 2022, and SFTS was highly prevalent in spring and summer, with high incidence among farmers. Intensified health education of SFTS is recommended among residents in high-incidence areas.

Immunologic characteristics and management and prospects of targeted biological therapy in adults with severe asthma / 中国临床药理学与治疗学

Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.

Rare and severe adverse reaction diabetic ketoacidosis induced by bevacizumab：one case report / 中国药房

OBJECTIVE To provide reference for the safe use of bevacizumab in cancer patients. METHODS The diagnosis and treatment of a 65-year-old female lung adenocarcinoma patient with diabetic ketoacidosis （DKA） induced by bevacizumab was retrospectively analyzed， and the possible mechanisms and causes were analyzed based on literature review. RESULTS & CONCLUSIONS The diagnosis and treatment process of patients were analyzed， and DKA caused by other drugs and disease factors were excluded. DKA was considered to be caused by the use of bevacizumab according to Naranjo’s ADR evaluation scale； the acidosis of the patient improved rapidly after one hemodialysis treatment. DKA caused by bevacizumab is rare in clinic， clinicians should be aware that bevacizumab may affect pancreatic function and induce DKA， and early detection and treatment should be achieved to improve the prognosis.

Expression of Gn protein of severe fever with thrombocytopenia syndrome virus and its immunogenicity / 中国生物制品学杂志

@#Objective To express the Gn protein of severe fever with thrombocytopenia syndrome virus(SFTSV) through adeno-associated virus 9(AAV9) expression system and evaluate its immunogenicity.Methods SFTSV Gn gene was inserted into viral vector pAAV-CMV-FH and the recombinant plasmid was transfected into HEK293T cells to obtain recombinant virus AAV9-Gn.The expression of Gn protein was determined by immunofluorescence and Western blot.Eighteen fernale BALB/c mice were randomly divided into three groups:Mock group(serum-free DMEM),AAV9-GFP group(1 × 10~(11) vg) and AAV9-Gn group(1 × 10~(11) vg),all of which were injected intramuscularly into the right hind limb at a dose of 100 μL per mouse.The body mass,diet,behavior and mental state of mice in each group were monitored continuously for 21 d,and the change rate of body mass was calculated;At 2,4,8 and 16 weeks after immunization,the levels of SFTSV neutralizing antibody in serum of mice in each group were detected by fluorescent reduction neutralization test(FRNT),and the levels of specific IgGl and IgG2a in serum of mice in AAV9-Gn group were detected by ELISA.Results After incubation with specific antibody,Vero cells transfected with AAV9-Gn showed specific green fluorescence under fluorescence microscope,and had specific binding to mouse anti-SFTSV Gn monoclonal antibody,and the specific binding bands were found at a relative molecular mass of about 61 000.The body mass of the three groups showed an increasing trend,there was no significant difference between the three groups(F=0.158—2.621,P> 0.05),and the diet,behavior and mental state were normal.At 2,4,8 and 16 weeks after immunization,the titer of SFTSV neutralizing antibody in serum of mice in AAV9-Gn group was significantly higher than that of Mock group and AAV9-GFP group(H=13.332—14.538,each P <0.001),and the titer peak appeared at 8 weeks;The level of specific IgG1 in serum of mice was significantly higher than that of IgG2a(F=4.373—12.975,each P <0.05) at different time points.Conclusion SFTSV Gn protein can be expressed correctly through AAV9 expression system,and has low toxicity to mice with good immunogenicity,which is expected to be a candidate component of SFTSV vaccine.