Expressions and Clinical Significance of Notch1 and Hes1 in Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expressions of Notch1 and Hes1 in diffuse large B-cell lymphoma (DLBCL), and their correlations with clinical features.@*METHODS@#Immunohistochemistry (IHC) was performed on DLBCL samples (54 cases) and lymphadenitis tissues (20 cases) to evaluate the expressions of Notch1 and Hes1, and analyze their correlations with clinical characteristics of patients. Based on Oncomine database, the expressions of Notch1 and Hes1 mRNA and DNA were also explored.@*RESULTS@#IHC result showed that the positive expression rates of Notch1 and Hes1 in DLBCL patients were significantly higher than those in the control group (P <0.05). In DLBCL patients, the expression of Notch1 was closely associated with B symptoms, Ann Arbor stage, lymphocyte count and the level of lactate dehydrogenase (P <0.05), while the expression level of Hes1 was significantly higher in patients with B symptoms (P <0.05). Notch+/Hes1+ expression was found in 21 DLBCL tissues (38.9%), and there was a correlation between Notch1 and Hes1 expression (r =0.296, P <0.05). Bioinformatics analysis (Oncomine database) showed that the mRNA expressions of Notch1 and Hes1 in the Brune dataset were significantly higher than those in the control tissues (P <0.05).@*CONCLUSION@#The expressions of Notch1 and Hes1 in DLBCL are significantly higher than those in lymphadenitis, and correlated with B symptoms and Ann Arbor stage, suggesting that Notch1 and Hes1 play important roles in the occurrence and development of DLBCL.

Morganella sp. infection in scent gland of corn snake (Pantherophis guttatus) - case report / Infecção por Morganella sp. em glândula de cheiro de corn snake (Pantherophis guttatus) - relato de caso

The corn snake (Pantherophis guttatus) is a non-venomous snake from the Colubridae family. The pair of scent glands is indispensable in the physiology of reproduction and defense of the species. This structure is located caudal to the cloaca. It is responsible for releasing a thick material based on lipids containing pheromones that perform functions associated with animal behavior and survival. This work aims to report infection by Morganella sp. in a scent gland in a female corn snake, evidencing the diagnosis and treatment. An increase in volume was seen in the final third, proximal to the cloaca, firm consistency, immobile, and approximately 4 cm long and painful to touch. Samples of the material were collected for bacterial culture and antibiogram examination, being positive for bacteria of the genus Morganella. Based on the result of the antibiogram, it was possible to determine the most appropriate therapeutic protocol, with the referral to perform the surgical procedure to remove the tissue compromised by the infection, remaining stable until the removal of the stitches 40 days after the procedure, with total surgical wound healing.(AU)

A corn snake (Pantherophis guttatus) é uma serpente não peçonhenta, da família Colubridae. Na fisiologia da reprodução e defesa da espécie, o par de glândulas de cheiro é indispensável. Essa estrutura está localizada caudal à cloaca e é responsável pela liberação de um material espesso à base de lipídeos, contendo feromônios que exercem funções associadas ao comportamento animal e à sua sobrevivência. O objetivo desse trabalho é relatar uma infecção por Morganella sp. em glândula de cheiro em uma fêmea de corn snake, evidenciando o diagnóstico e tratamento. Observou-se um aumento de volume no terço final, proximal a cloaca, de consistência firme, imóvel e com aproximadamente 4 cm de comprimento e sensibilidade dolorosa ao toque. Foram coletadas amostras do material para cultura bacteriana e exame de antibiograma, sendo positivo para bactérias do gênero Morganella. Com base no resultado do antibiograma, foi possível determinar o protocolo terapêutico mais adequado, como o encaminhamento para realização do procedimento cirúrgico para remoção do tecido comprometido pela infecção, se mantendo estável até a remoção dos pontos, 40 dias após o procedimento, com total cicatrização da ferida cirúrgica.(AU)

Pathological significance of plasma cell infiltration in diagnosing lymph node diseases / 中华病理学杂志

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.

Linfadenitis por Mycobacterium en pacientes inmunocompetentes y viviendo con VIH/sida / Lymphodenitis by Mycobacterium in immunocompetent and living with HIV/AIDS patients

Introducción: La coinfección del virus de inmunodeficiencia humana (VIH) y la tuberculosis ha alterado su presentación histológica, esto es particularmente frecuente en las linfadenitis. Objetivos: Realizar la caracterización etiológica de linfadenopatías producidas por el género Mycobacterium, destacar la importancia del diagnóstico precoz de esta enfermedad para evitar diseminación de la infección, tanto en pacientes inmunocompetentes como inmunodeficientes, específicamente con VIH/sida. Método: Se realizó estudio descriptivo-prospectivo entre enero de 2017 y enero de 2019. Durante este período se recibieron 5640 muestras, de estas 81 obtenidas a partir de tejido ganglionar; la toma de muestra mayoritariamente fue quirúrgica 74 (91,35 por ciento) y 7 (8,64 por ciento) por biopsia aspirativa (BAAF). Del total de muestras, 60 (74,07 por ciento) procedían de pacientes con VIH/sida, las muestras se descontaminaron por el método de ácido sulfúrico al 4 por ciento, se cultivaron en medio sólido Löwenstein-Jensen e incubaron a 37°C. Se realizaron lecturas semanalmente. Para identificar Mycobacterium tuberculosis se realizó la prueba rápida comercial inmunocromatográfica SD TB AgMPT64. Resultados: De 81 muestras analizadas se obtuvieron 22 (27,16 por ciento) aislamientos, 16 (72,72 por ciento) de Mycobacterium tuberculosis, y 6 (27,27 por ciento) de especies no tuberculosas. De estas, 18 (81,81 por ciento) procedían de pacientes con VIH/sida. Conclusión: Por todo lo antes expuesto es importante la vigilancia diagnóstica en este tipo de infección extrapulmonar, tanto para M. tuberculosis como para otras especies no tuberculosas y poder comenzar tempranamente el tratamiento específico evitando la diseminación de la infección, pues esta puede tener consecuencias fatales, sobre todo en pacientes con algún tipo de inmunosupresión, como aquellos con VHI/sida. Si un paciente mantiene fiebre prolongada, con linfadenopatías, sin síntomas respiratorios y no responde a los tratamientos con antibióticos, es necesario pensar en este tipo de infección(AU)

Introduction: The coinfection of human immunodeficiency virus (HIV) and tuberculosis has altered its histological presentation; this is particularly frequent in lymphadenitis. Objective: To carry out the etiological characterization of lymphadenopathies produced by the genus Mycobacterium, highlighting the importance of early diagnosis of this disease to avoid dissemination of the infection, both in immunocompetent and immunodeficient patients, specifically HIV / AIDS. Methods: A descriptive-prospective study was carried out between January 2017 - January 2019. During this period, 5640 samples were received, of these 81 obtained from lymph node tissue, the sample collection was mostly surgical 74 (91.35 percent) and 7 (8.64 percent) by aspiration biopsy (BAAF). Of the total samples, 60 (74.07 percent) were from HIV / AIDS patients, the samples were decontaminated by the 4 percent sulfuric acid method and cultured in solid Löwenstein-Jensen medium and incubated at 370C, the readings were made weekly. For the identification of Mycobacterium tuberculosis, the commercial SD TB AgMPT64 immunochromatographic rapid test was performed. Results: Of 81 samples analyzed, 22 (27.16 percent) isolates were obtained, 16 (72.72 percent) of Mycobacterium tuberculosis (MTB), and 6 (27.27 percent) of non-tuberculous species, of these 18 (81.81%) were from HIV / AIDS patients. Conclusion: For all the above, diagnostic surveillance is important in this type of extrapulmonary infection, both for M tuberculosis and for other non-tuberculous species and to be able to start specific treatment early, avoiding the spread of the infection, since it can have fatal consequences on all in patients with some type of immunosuppression, such as HIV/AIDS. If a patient maintains a prolonged fever, with lymphadenopathy, without respiratory symptoms and does not respond to antibiotic treatment, it is necessary to consider this type of infection(AU)

Estimation of economic burden of bacillus Calmette-Guérin lymphadenitis in Shandong Province based on compensation for abnormal reaction to vaccination / 中华预防医学杂志

Objective: To investigate the economic burden of bacillus Calmette-Guérin (BCG) lymphadenitis in Shandong Province. Methods: From May 2011 to December 2019, 304 patients applying for the province-level compensation of BCG lymphadenitis was selected from Shandong Province in this study. The basic situation, vaccination, outpatient (inpatient) records, cost and relevant information of those patients were collected to calculate the direct economic burden (including direct medical costs and direct non-medical costs), indirect economic burden and total economic burden. Comparison of the difference of economic burden of cases with different characteristics was taken. Results: The M(Q1,Q3) of age of BCG lymphadenitis patients was 3 (2, 4) months, among which 239 cases (78.6%) were male, 71 cases (23.4%) had lymphadenopathy, and 227 cases (74.7%) underwent surgery.The number of outpatient only, inpatient only and outpatient then inpatient was 25.7% (78 cases), 7.2% (22 cases) and 67.1% (204 cases), respectively. The M(Q1,Q3) of direct, indirect and total economic burden of single case after discount was 9 910 (5 713, 16 074), 2 081 (1 547, 3 122) and 12 262 (7 694, 18 571) yuan, respectively.The direct medical expenses accounted for 89.4% of the direct economic burden, the direct economic burden accounted for 84.9% of the total economic burden, the total economic burden of 80.0% cases accounted for only about 20.0% of the compensation amount, and the total economic burden of only 2.3% cases accounted for more than 60.0% of the compensation amount.The direct, indirect and total economic burden of patients with inpatient only and outpatient then inpatient was higher than that of patients with outpatient only; the direct, indirect and total economic burden of patients with operation was higher than that of patients with non-operation; the direct and total economic burden of patients with unulcerated lymph node was higher than that of patients with ulcerated lymph node(all P values<0.05). Conclusion: The economic burden of BCG lymphadenitis cases in Shandong Province is influenced by the mode of diagnosis and treatment, with direct medical expenses as the predominant component.

Síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenitis / Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome

Introducción: El síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenitis es un cuadro relativamente frecuente de curso autolimitado y buen pronóstico. Es la más común de las enfermedades autoinflamatorias que presentan fiebre recurrente y su etiología y fisiopatogenia permanecen inciertas. Objetivo: Describir el caso clínico de un niño que consultó por fiebre recurrente y faringitis y se arribó al diagnóstico de síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenitis. Presentación del caso: Se trata de un paciente de 5 años que consultó por un episodio febril acompañado de faringitis y adenitis, con antecedente de múltiples episodios previos. Conclusiones: El síndrome fiebre periódica, estomatitis aftosa, faringitis y adenitis, es una entidad de curso benigno y autolimitado que constituye la causa más común de fiebre recurrente con un gran impacto en la vida de los pacientes. La fisiopatogenia permanece incierta. Es destacable la sospecha clínica para arribar al diagnóstico ya que no existen en la actualidad exámenes complementarios específicos(AU)

Introduction: Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome is a relatively common picture of self-limiting course and good prognosis. It is the most common of self-inflammatory diseases with recurrent fever and its etiology and physiopathology remain uncertain. Objective: Describe the clinical case of a boy who was checked due recurrent fever and pharyngitis and being diagnosed with Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Case presentation: This is a 5-year-old patient who was consulted due to a febrile episode accompanied by pharyngitis and adenitis, with a history of multiple previous episodes. Conclusions: Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome is a benign, self-limiting course entity that is the most common cause of recurrent fever with a large impact on patients' lives. Its physiopathology remains uncertain. Clinical suspicion for diagnosis is noteworthy as there are currently no specific complementary test for it(AU)

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD – Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 – 4 μg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 μg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 μg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 μg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 μg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 μg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 μg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 μg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 μg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 μg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 μg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 μg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

Modelagem farmacocinética/farmacodinâmica do florfenicol para o tratamento da adenite equina por meio da simulação de Monte Carlo / Pharmacokinetic/pharmacodynamic modeling of florfenicol for the treatment of equine adenitis using Monte Carlo simulation

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD ­ Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 ­ 4 µg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 µg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 µg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 µg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 µg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 µg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.

The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 µg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 µg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 µg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 µg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 µg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 µg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.

Clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: an analysis of 13 cases / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis.@*METHODS@#A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome.@*RESULTS@#All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the @*CONCLUSIONS@#For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.

Sarcoidose como diagnóstico diferencial de mieloma múltiplo / Sarcoidosis as a differential diagnosis of multiple myeloma

A sarcoidose caracteriza-se como doença granulomatosa que acomete diferentes órgãos humanos, especialmente os pulmões, sendo sua patogênese pouco conhecida. No caso em questão, a paciente iniciou com sintomas inespecíficos, como fraqueza, perda ponderal e tosse seca esporádica, sendo internada para extensão da propedêutica. Sugeriu-se como hipótese diagnóstica inicial possível quadro de mieloma múltiplo, tendo em vista a anemia, a disfunção renal, a hipercalcemia e, sobretudo, as lesões osteolíticas apresentadas pela paciente. Todavia, o diagnóstico de sarcoidose foi selado a partir das biópsias de medula óssea e de linfonodo inguinal, que evidenciaram mielite e linfadenite granulomatosas, respectivamente. A terapêutica instituída baseou-se na administração de corticosteroides e em medidas de redução da calcemia. A paciente recebeu alta, com melhora do quadro clínico, para acompanhamento ambulatorial da doença. Conclui-se que a sarcoidose não possui tratamento curativo, mas a terapêutica imunossupressora é eficaz no controle da progressão da enfermidade, fazendo com que o paciente tenha um prognóstico favorável.

Sarcoidosis is characterized as a granulomatous disease that affects different human organs, especially the lungs, and its pathogenesis is little known. In this case, the patient started with nonspecific symptoms, such as weakness, weight loss, and sporadic dry cough, being hospitalized for extension of the propaedeutics. The initial diagnostic hypothesis suggested was a possible case of multiple myeloma, based on the anemia, renal dysfunction, hypercalcemia and, above all, the osteolytic lesions presented by the patient. However, the diagnosis of sarcoidosis was made after bone marrow and inguinal lymph node biopsies that showed granulomatous myelitis and lymphadenitis, respectively. The therapy instituted was based on the administration of corticosteroids and on measures to reduce the level of calcium. The patient was discharged, with clinical improvement, for outpatient follow-up of the disease. It is concluded that sarcoidosis has no curative treatment, but immunosuppressive therapy is effective in controlling the progression of the disease, giving the patient a favorable prognosis.

Adenomegalia dolorosa: doença de Kikuchi entre os diagnósticos diferenciais / Painful adenomegaly: Kikuchi disease among differential diagnoses

RESUMO: A doença de Kikuchi-Fujimoto ou linfadenite histiocítica necrosante, de curso benigno, é prevalente em mulheres jovens, e associada à febre e leucopenia. Estudos recentes têm demostrado que sua etiologia ainda é incerta, sendo uma doença rara, com incidência de 0,5 a 5% de todas as adenopatias analisadas histologicamente. O diag-nóstico diferencial por imunohistoquímica foi decisivo, descartando outras hipóteses diagnósticas como: linfoma, tuberculose ganglionar e lúpus eritematoso sistêmico. Este relato de caso mostra as características da apresentação da doença em uma mulher, caucasiana e todas as etapas da investigação, destacando a importância dos diagnósticos diferenciais em adenopatias dolorosas e as dificuldades quando avaliamos portadores de doenças raras. (AU)

ABSTRACT: Kikuchi-Fujimoto disease or benign necrotizing histiocytic lymphadenitis is prevalent in young women and associated with fever and leukopenia. Recent studies have shown that its etiology is still uncertain, being a rare disease, with an incidence of 0.5 to 5% of all histologically analyzed adenopathies. Differential diagnosis by immunohistochemistry was decisive, ruling out other diagnostic hypotheses such as lymphoma, ganglion tuberculosis, and systemic lupus erythematosus. This case report shows the characteristics of the presentation of the disease in a Caucasian woman and all stages of the investigation, highlighting the importance of differential diagnoses in painful adenopathies and the difficulties when evaluating rare-disease patients. (AU)

Assessment of the acid phosphatase CP01850 from Corynebacterium pseudotuberculosis in DNA and subunit vaccine formulations against caseous lymphadenitis / Avaliação da fosfatase ácida recombinante CP01850 de Corynebacterium pseudotuberculosis em formulações vacinais de subunidade e de DNA contra a linfadenite caseosa

The target cp1002_RS01850 from Corynebacterium pseudotuberculosis was used to construct a DNA and recombinant subunit vaccine against caseous lymphadenitis. Recombinant protein rCP01850 was expressed in Escherichia coli using pAE vector, and DNA vaccine was engineered with pTARGET vector. BALB/c mice were divided in five groups containing eight animals each, inoculated with: pTARGET/cp01850 as DNA vaccine (G1); rCP01850 plus Al (OH)3 as recombinant subunit vaccine (G2); pTARGET/cp01850 and a boost with rCP01850 plus Al (OH)3 (G3); pTARGET (G4); or Al (OH)3 (G5). Mice were inoculated and blood samples were collected on days 0, 21, and 42 for the analysis of total IgG, IgG1 and IgG2a by ELISA. In each group, five animals were challenged with Mic-6 C. pseudotuberculosis strain, and three were used for cytokine quantification by qPCR. Although no group has been protected by vaccines against lethal challenge, G2 showed an increase in the survival rate after challenge. Significantly higher levels of IL-4, IL-12, IFN-γ, total IgG, IgG1 and IgG2a were also detected for G2, evidencing a mixed Th1/Th2 immunological profile. In conclusion, despite no protection level provided by different vaccinal strategies using cp1002_RS01850 from C. pseudotuberculosis, G2 developed a Th1/Th2 immune response with an increase in survival rate.(AU)

O alvo cp1002_RS01850 de Corynebacterium pseudotuberculosis foi utilizado para construir uma vacina recombinante de subunidade e de DNA contra a linfadenite caseosa. A proteína recombinante rCP01850 foi expressa em Escherichia coli usando o vetor pAE, e a vacina de DNA foi construída com o vetor pTARGET. Camundongos BALB/c foram divididos em grupos de oito animais, inoculados com: pTARGET/cp01850 como vacina de DNA (G1); rCP01850 e Al (OH)3 como vacina recombinante de subunidade (G2); pTARGET/cp01850 e um boost com rCP01850 e Al (OH)3 (G3); pTARGET (G4); ou Al (OH)3 (G5). Os animais foram inoculados e amostras de sangue foram coletadas nos dias 0, 21, e 42 do experimento para a análise de IgG total, IgG1 e IgG2a por ELISA. De cada grupo, cinco animais foram desafiados com a cepa Mic-6 de C. pseudotuberculosis, e três foram usados para a quantificação de citocinas por qPCR. Apesar de nenhum grupo ter sido protegido pelas vacinas testadas contra o desafio letal, G2 apresentou taxa de sobrevida e níveis de IL-4, IL-12, IFN-γ, IgG total, IgG1 e IgG2a significativamente mais altos, evidenciando um perfil imunológico misto Th1/Th2. Conclui-se que apesar das diferentes estratégias vacinais utilizando cp1002_RS01850 de C. pseudotuberculosis não terem sido capazes de gerar proteção, G2 desenvolveu uma resposta Th1/Th2 e elevou a taxa de sobrevida.(AU)

Síndrome PFAPA: reporte de un caso clínico / PFAPA syndrome: a case report

El síndrome PFAPA es la entidad más frecuente dentro de los síndromes de fiebres periódicas que pueden manifestarse desde la infancia. Es un síndrome autoinflamatorio caracterizado por una disfunción en las citoquinas, de carácter autolimitado y de etiología desconocida, aunque se han reportado casos de presentación familiar; lo que sugiere la existencia de una base genética de la enfermedad. Se presenta con episodios febriles que suelen acompañarse de aftas orales, adenopatías cervicales, faringoamigdalitis y síntomas constitucionales. En los exámenes de laboratorio es frecuente encontrar elevación marcada de la proteína C reactiva, leucocitosis y aumento de IgG, IgA e IgM. El diagnóstico se realiza utilizando los criterios modificados de Thomas, que incluyen parámetros clínicos, antecedentes y diagnósticos de exclusión. Se presenta el caso de un paciente de 4 años de edad que consultó a un hospital por un cuadro febril, movimientos tónico-clónicos generalizados, desviación de la mirada, sialorrea y relajación de esfínteres. También presentó cefalea de localización frontal y odinofagia. En la cavidad oral se observaron lesiones tipo aftas, y se evidenciaron adenopatías cervicales. El paciente no respondió al manejo con antibióticos, y se observó que cumplía con los criterios de diagnóstico para síndrome PFAPA, luego de descartarse un proceso infeccioso. Se inició terapia con corticoides con respuesta favorable y se concluyó que el paciente tenía un cuadro compatible con síndrome PFAPA.

PFAPA syndrome is the most frequent illness within the syndromes of periodic fevers manifesting during childhood. It is an auto-inflammatory syndrome characterized by cytokine dysfunction, a self-limiting nature, and unknown etiology; family cases have been reported, suggesting the existence of a genetic basis for the disease. PFAPA syndrome is manifested with febrile episodes that are usually accompanied by oral aphthae, cervical adenopathy, pharyngotonsillitis and constitutional symptoms. In laboratory tests, it is common to find marked elevation of C reactive protein, leukocytosis and increased IgG, IgA and IgM levels. Diagnosis is reached by means of the modified Thomas criteria that include clinical parameters, personal and family history, and exclusion diagnoses. The case of a 4-year-old patient who visited the hospital with fever, generalized tonic-clonic seizures and sphincter relaxation is presented. The patient reported frontal headache and odynophagia. Aphthous stomatitis was observed, and cervical adenopathies were evident. The patient did not respond to antibiotic therapy, and met the diagnostic criteria for PFAPA syndrome after an infectious process was ruled out. Corticosteroid therapy was initiated with a favorable response. It was concluded that the patient had a diagnosis compatible with PFAPA syndrome

Corynebacterium pseudotuberculosis biovar ovis: evaluación de la sensibilidad antibiótica in vitro / Corynebacterium pseudotuberculosis biovar ovis: Evaluation of antibiotics susceptibility in vitro

Resumen Los objetivos de este trabajo fueron estudiar la sensibilidad antibiótica de aislamientos de Corynebacterium pseudotuberculosis procedentes de pequeños rumiantes e investigar la presencia de integrones que contienen genes de resistencia. Se estudiaron 15 aislamientos de diferentes fuentes por los métodos de difusión y dilución. Por el método de difusión, amoxicilina-clavulánico, ampicilina, cefotaxima, cefoxitina, ciprofloxacina, cloranfenicol, eritromicina, estreptomicina, gentamicina, imipenem, kanamicina, norfloxacina, penicilina, rifampicina, tetraciclina, trimetroprima-sulfametoxazol y vancomicina fueron activos frente al 100% de los aislamientos, mientras que amicacina presentó resultados variables. En los aislamientos que desarrollaron frente a amicacina se investigó la presencia de integrones de clase 1. El resultado fue negativo, sugiriendo la ausencia del integrón. Utilizando el método de dilución, los antibióticos más activos correspondieron a los grupos de cefalosporinas, gluco-péptidos, macrólidos, quinolonas y tetraciclinas. Se demostró menor actividad de p-lactámicos y aminoglucósidos. No se registró variabilidad en los perfiles antibióticos en los aislamientos procedentes de diferentes fuentes.

Abstract The aims of this work were to study the antibiotic susceptibility in Corynebacterium pseudotuberculosis isolated from small ruminants and to determine the presence of integrons that contain resistance genes. Fifteen isolates of different sources were analysed using the diffusion and the dilution methods. When the diffusion method was performed, amoxicillin-clavulanic, ampicillin, cefotaxime, cefoxitin, ciprofloxacin, chloramphenicol, erythromycin, streptomycin, gentamicin, imipenem, kanamycin, norfloxacin, penicillin, rifampicin, tetracycline, trimethoprim-sulfamethoxazole and vancomycin were effective against the 100% of isolates, while amikacin showed variable results. The isolates that were able to grow with amikacin, were studied in relation to the presence of integron class 1. The result was negative, suggesting the absence of integron. Using dilution method, the antibiotics belonging to the cephalosporin, glycopeptide, macrolide, quinolone, and tetracycline groups were the most active ones for the C. pseudotuberculosis biovar ovis isolates. Less activity of p-lactam and aminoglycosides were observed. There was no observation of variability in the antibiotic patterns in the strains coming from different sources.

Interesting post-mortem findings in a H1N1 influenza-positive pneumonia patient

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) em crianças e adultos / PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome in children and adults

A síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) é a forma mais comum das doenças autoinflamatórias. Trata-se de uma doença rara, não genética, bimodal, usualmente com início dos sintomas antes dos 5 anos de vida, que também pode prolongar-se ou iniciar-se na vida adulta. A prevalência é variável em todo o mundo, e não há dados estatísticos da doença no Brasil. Diversos pontos da doença são discutíveis, como os critérios diagnósticos, as avaliações laboratoriais, a ausência de mutações genéticas específicas e a abordagem terapêutica e prognóstica. Este trabalho tem como objetivo rever, de forma narrativa e crítica, aspectos relacionados ao diagnóstico e tratamento da síndrome PFAPA em adultos e crianças. Foram feitas buscas nas redes de dados PubMed, Bireme e Cochrane, utilizando o acrônimo PFAPA sem auxílio de qualquer filtro. Quanto ao diagnóstico, os critérios pediátricos foram adaptados para os adultos, com análises variadas e divergentes. Há a necessidade pujante de desenvolver um consenso com diretrizes de diagnóstico de pacientes em populações bem caracterizadas para melhor diagnosticar a doença. Já em relação ao tratamento, a cirurgia com remoção das tonsilas é considerada curativa, com necessidade de se manter acompanhamento após o procedimento para confirmação da remissão da doença. As drogas poupadoras de corticoide ainda são incertas, e o uso de imunobiológicos deve ser reservado somente para pacientes refratários ao tratamento cirúrgico e com grande impacto na qualidade de vida.

PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is the most common form of autoinflammatory disease. It is a rare, non-genetic, bi-modal disease, usually with onset of symptoms before the age of 5 years, which may also be prolonged or start in adult life. The prevalence varies worldwide and there are no specific statistical data in Brazil. Several aspects of the disease are debatable, such as diagnostic criteria, laboratory evaluations, absence of specific genetic mutations, and therapeutic and prognostic approach. This paper aims to review in a narrative and critical manner aspects related to diagnosis and treatment of PFAPA syndrome in adults and children. PubMed, Bireme and Cochrane databases were searched using the acronym PFAPA without any filter. Regarding diagnosis, pediatric criteria were adapted for use in adults, with varied and divergent analyses. There is a strong need to develop consensus diagnostic guidelines for patients in well-characterized populations to better diagnose the disease. Regarding treatment, tonsillectomy is considered curative, requiring follow-up after the procedure to confirm remission of the disease. Corticosteroid-sparing agents remain uncertain, and the use of immunobiological agents should be reserved only for patients who are refractory to surgical treatment and experience a great impact on quality of life.

Long-term follow-up of tonsillectomy efficacy in children with PFAPA syndrome / Acompanhamento em longo prazo da eficácia da tonsilectomia em crianças com síndrome de PFAPA

Abstract Introduction: The role of tonsillectomy in the periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, is controversial. Although some studies reported high success rates with tonsillectomy, further investigations are needed with larger numbers of patients. Objective: To seek the long-term outcomes of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Methods: Case series; multi-center study. The study comprised 23 patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome who underwent surgery (tonsillectomy with or without adenoidectomy) between January 2009 and November 2014. Results: 21 (91%) of 23 patients had complete resolution immediately after surgery. One patient had an attack 24 h after surgery, but has had no further attacks. One patient had three attacks with various intervals, and complete remission was observed after 3 months. Conclusions: Tonsillectomy is a good option for the treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

Resumo Introdução: O papel da tonsilectomia na síndrome da febre periódica, estomatite aftosa, faringite e adenite é controverso. Embora alguns estudos tenham relatado altas taxas de sucesso com a tonsilectomia, são necessárias mais pesquisas com um número maior de pacientes. Objetivo: Avaliar os resultados em longo prazo da tonsilectomia na síndrome de febre periódica, estomatite aftosa, faringite e adenite. Método: Série de casos; estudo multicêntrico. O estudo avaliou 23 pacientes com síndrome de febre periódica, estomatite aftosa, faringite e adenite submetidos a cirurgia (tonsilectomia com ou sem adenoidectomia) entre janeiro de 2009 e novembro de 2014. Resultados: Dos 23 pacientes, 21 (91%) apresentaram resolução completa imediatamente após a cirurgia. Um paciente apresentou um episódio 24 horas após a cirurgia, mas sem recorrência posterior. Um paciente teve três episódios com vários intervalos e a remissão completa foi observada após 3 meses. Conclusões: A tonsilectomia é uma boa opção para o tratamento da síndrome de febre periódica, estomatite aftosa, faringite e adenite.

Síndrome PFAPA: Diagnóstico e Tratamento na Atenção Primária à Saúde / PFAPA Syndrome: Diagnosis and Treatment in Primary Health Care / Síndrome PFAPA: Diagnóstico y Tratamiento en la Atención Primaria a la Salud

Objetivo: Apresentar informações sobre o diagnóstico e tratamento da síndrome PFAPA na Atenção Primária à Saúde. Métodos: Revisão sistemática de literatura baseada na recomendação PRISMA e realizada nas bases de dados Scielo, Lilacs, Medline, IBECS e PubMed, incluindo estudos publicados no período de 2004 a 2018, além da consulta a outros documentos específicos da síndrome PFAPA. Resultados: Após busca e seleção, foram incluídos 31 artigos. Avaliação e Diagnóstico: A síndrome PFAPA acomete principalmente crianças, sendo caracterizada por febre periódica acompanhada por faringite, estomatite aftosa e/ou adenite cervical. Seu diagnóstico é clínico e por exclusão, baseado em critérios estabelecidos. Recomendações: Os episódios costumam responder a prednisona e, em graus variáveis, a cimetidina e colchicina. Casos refratários e acompanhados de hipertrofia tonsilar são candidatos a tonsilectomia, devendo ser encaminhados à avaliação otorrinolaringológica.

Objective: To present information about the diagnosis and treatment of PFAPA syndrome in Primary Health Care. Methods: Systematic review of literature based on the PRISMA recommendation and carried out in the Scielo, Lilacs, Medline, IBECS and PubMed databases, including studies published from 2004 to 2018, in addition to consulting other PFAPA syndrome specific documents. Results: After search and selection, 31 articles were included. Assessment and Diagnosis: PFAPA syndrome affects mainly children and is characterized by periodic fever accompanied by pharyngitis, aphthous stomatitis and/or cervical adenitis. Its diagnosis is clinical and by exclusion, based on established criteria. Recommendations: The episodes usually respond to prednisone and, in varying levels, cimetidine and colchicine. Refractory cases and accompanied by tonsillar hypertrophy are candidates for tonsillectomy, and should be referred to otorhinolaryngological evaluation.

Objetivo: Presentar informaciones sobre el diagnóstico y tratamiento del síndrome PFAPA en la Atención Primaria a la Salud. Métodos: Revisión sistemática de literatura basada en la recomendación PRISMA y realizada en las bases de datos Scielo, Lilacs, Medline, IBECS y PubMed, incluyendo estudios publicados en el período 2004 a 2018, además de la consulta a otros documentos específicos del síndrome PFAPA. Resultados: Después de la búsqueda y selección, se incluyeron 31 artículos. Evaluación y Diagnóstico: El síndrome PFAPA acomete principalmente niños, siendo caracterizada por fiebre periódica acompañada por faringitis, estomatitis aftosa y/o adenitis cervical. Su diagnóstico es clínico y por exclusión, basado en criterios establecidos. Recomendaciones: Los episodios suelen responder a la prednisona y, en grados variables, a la cimetidina y colchicina. Los casos refractarios y acompañados de hipertrofia tonsilar son candidatos a tonsilectomía, debiendo ser encaminados a la evaluación otorrinolaringológica.

Síndrome PFAPA ­ A propósito de um caso clínico nos Cuidados Primários / PFAPA Syndrome - About a clinical case in Primary Health Care / Síndrome PFAPA - A propósito de un caso clínico en los Cuidados Primarios

Objetivo: Apresentar informações sobre o diagnóstico e tratamento da síndrome PFAPA na Atenção Primária à Saúde. Métodos: Revisão sistemática de literatura baseada na recomendação PRISMA e realizada nas bases de dados Scielo, Lilacs, Medline, IBECS e PubMed, incluindo estudos publicados no período de 2004 a 2018, além da consulta a outros documentos específicos da síndrome PFAPA. Resultados: Após busca e seleção, foram incluídos 31 artigos. Avaliação e Diagnóstico: A síndrome PFAPA acomete principalmente crianças, sendo caracterizada por febre periódica acompanhada por faringite, estomatite aftosa e/ou adenite cervical. Seu diagnóstico é clínico e por exclusão, baseado em critérios estabelecidos. Recomendações: Os episódios costumam responder a prednisona e, em graus variáveis, a cimetidina e colchicina. Casos refratários e acompanhados de hipertrofia tonsilar são candidatos a tonsilectomia, devendo ser encaminhados à avaliação otorrinolaringológica.