Necrosis retinal aguda. Dos casos clínicos / Acute retinal necrosis. A report of two clinical cases

La necrosis retinal aguda es una afección grave que amenaza la visión. Es frecuente en adultos, tanto inmunocompetentes como inmunocomprometidos. Se presentan dos pacientes, uno de 38 años, con antecedentes de salud anterior que acude a consulta con síntomas y signos de necrosis retinal aguda en el ojo izquierdo, la que fue diagnosticada luego; y otro de 48 años de edad con antecedentes de infección por herpes zóster, tres meses antes de los síntomas oculares, que concluyó con igual diagnóstico. No existió evolución satisfactoria, a pesar del tratamiento adecuado, lo que demostró que independientemente de datos estadísticos y estudios realizados que demuestran lo infrecuente de esta enfermedad, se diagnosticaron dos casos en el periodo de un año, dato que nos exhorta al estudio y práctica de alternativas diagnósticas y terapéuticas para minimizar las consecuencias devastadoras de esta afección.

Acute retinal necrosis is a serious vision-threatening condition. It is common in both immunocompetent and immunocompromised adults. We present two male patients; one aged 38 years, with a previous health history who comes to consultation with symptoms and signs of acute retinal necrosis in his left eye, which was later diagnosed; and another one aged 48 years with a history of herpes zoster infection three months before the ocular symptoms, which concluded with the same diagnosis. Regardless of the statistical data and research carried out on this rare disease, there was no satisfactory evolution despite adequate treatment. Two cases were diagnosed in a period of one year, data that urges us to study and practice diagnostic and therapeutic alternatives to minimize the devastating consequences of this condition.

COVID-19 infection and vaccines: potential triggers of Herpesviridae reactivation

Abstract Since the onset of the COVID-19 outbreak, numerous articles have highlighted a possible link between COVID-19 vaccination or infection and Herpesviridae co-infection or reactivation. The authors conducted an exhaustive literature review on this topic, the results of which are presented individually for each member of the Herpesviridae family: Herpes Simplex Virus (HSV) types-1 (HSV-1) and 2 (HSV-2); Varicella-Zoster Virus (VZV); Epstein-Barr Virus (EBV); Cytomegalovirus (CMV); HHV-6; HHV-7; and HHV-8. These human herpesviruses can serve as prognostic markers for the COVID-19 infection and may even underlie some of the clinical manifestations initially attributed to SARS-CoV-2. In addition to SARS-CoV-2 infection, all corresponding vaccines approved to date in Europe appear capable of inducing herpesvirus reactivation. It is important to consider all viruses of the Herpesviridae family when managing patients infected with or recently vaccinated against COVID-19.

Correlation between peak viral load and liver function damage in children with infectious mononucleosis induced by Epstein-Barr virus / 中国基层医药

Objective:To investigate the relationship between the peak load of Epstein-Barr virus (EPV) and live function damage in children with infectious mononucleosis caused by EPV.Methods:Eighty children with infectious mononucleosis caused by EPV who received treatment in Pingxiang People's Hospital from January 2018 to December 2021 were included in this study. Five mL of venous blood was taken from each child for detecting the peak load of EBV-DNA and liver function indicators. These children were divided into a low-load group ( n = 25, EBV-DNA load < 10 4 copies/mL), a medium-load group ( n = 34, EBV-DNA load of 10 4-10 5 copies/mL), and a high-load group ( n = 21, EBV-DNA load > 10 5 copies/mL) according to the peak EBV-DNA load. The relationships between different peak loads of EBV-DNA and live function, age, and sex were analyzed. Results:The rate of liver dysfunction in the high-load group [85.71% (18/21)] was significantly higher than [38.24% (13/34)] in the medium-load group and [20.00% (5/25)] in the low-load group ( χ2 = 11.90, 19.71, P = 0.001, P < 0.001). Alanine aminotransferase and aspartate aminotransferase levels in the high-load group were (156.24 ± 13.21) U/L and (171.69 ± 13.49) U/L, respectively, which were significantly higher than (125.89 ± 10.54) U/L and (143.26 ± 10.29) U/L in the medium-load group and (89.64 ± 6.75) U/L and (64.89 ± 5.74) U/L] in the low-load group (all P < 0.001). There was no significant difference in the peak load of EBV-DNA between children of different ages and between children of different sexes (both P > 0.05). Conclusion:Children with infectious mononucleosis caused by EPV have a high EBV-DNA peak load. A higher peak load of EVB-DNA indicates a higher risk of liver function damage. More attention should be paid in clinical practice. Effective diagnosis and treatment should be performed in time to control the patient's condition as early as possible.

Predictive indicators of a prolonged course of fever in children with infectious mononucleosis / 中国基层医药

Objective:To explore the relevant predictive indicators of fever course > 7 days in children with infectious mononucleosis.Methods:The clinical data of 163 children with infectious mononucleosis who received treatment in Xi'an Children's Hospital from January 2018 to October 2020 were retrospectively analyzed. According to the heat duration, the children were divided into the fever course > 7 days group ( n = 55) and the fever course ≤ 7 days group ( n = 108). The clinical manifestations and laboratory indexes on admission were compared between the two groups. A logistic regression model was used to analyze the influential factors of fever course in children. A receiver operating curve was used to evaluate the predictive value of heat course > 7 days for infectious mononucleosis. Results:The majority of children with infectious mononucleosis had a heat course of 7 days (21.5%). There were no significant differences in clinical manifestations between the fever course > 7 days group and the fever course ≤ 7 days group (all P > 0.05). Neutrophil count, the proportion of monocytes, aspartate aminotransferase, and the proportion of suppressor T (Ts) cells in the fever course > 7 days group were (15.97 ± 7.60) × 10 9/L, 7.75 (4.93, 10.75)%, 53.00 (22.00, 91.50) U/L, 70.00 (57.00, 75.00)%, respectively, which were significantly higher than (15.21 ± 5.29) × 10 9/L, 5.40 (3.40, 9.60)%, 40.00 (30.00, 63.75) U/L, 63.50 (55.00,70.75)% in the fever course ≤ 7 days group ( t = -5.10, Z = -2.31, Z = -2.26, Z = -2.12, all P < 0.05). The proportion of helper T (Th) cells and the ratio of Th/Ts cells in the fever course > 7 days group were 13.00 (9.00, 17.00)% and 0.19 (0.12, 0.30)%, respectively, which were significantly lower than 16.00 (12.25, 20.75)%, 0.26 (0.18, 0.37)% in the fever course ≤ 7 days group ( Z = 2.44, 2.48, both P < 0.05). Multivariate logistic regression analysis showed that the increased proportion of Ts cells ( OR = 0.96, 95% CI 0.922-0.978, P < 0.05) was an influential factor of the prolonged course of fever. The area under the receiver operating characteristic curve of the proportion of Ts cells was 0.637. The cut-off value, sensitivity, and specificity were 67.50%, 61.3%, and 64.3%, respectively. Conclusion:Children with infectious mononucleosis with a longer heat course have more severe immune responses. The proportion of Ts cells > 67.5% can be used as a risk factor for the fever course > 7 days in children with infectious mononucleosis.

Research progress of primary pulmonary lymphoepithelioma-like carcinoma / 国际肿瘤学杂志

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a distinct type of lung cancer with histological profiles similar to nasopharyngeal carcinoma. The development is associated with EBV and plasma EBV DNA has predictive value in the progression and prognosis of PPLELC. PPLELC is different from some other types of lung cancer in that it has a low mutation rate of the classical lung cancer driver genes and targeted therapy is ineffective for it. Chemotherapy combined with immunotherapy may be the best first-line treatment option for patients with advanced PPLELC.

Neurophilic herpesvirus: a powerful tool for neuroscience research / 生物工程学报

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.

Etiología de las infecciones de transmisión sexual (ITS) diagnosticadas por la técnica de PCR múltiple-hibridación en población colombiana de la ciudad de Medellín atendida en el Laboratorio Clínico VID / Etiology of sexually transmitted infections (STIs) diagnosed by multiplex PCR-hibridization assay technique in a Colombian population attending the VID Clinical Laboratory in Medellin

Introducción. Las infecciones de transmisión sexual (ITS) son y seguirán siendo un serio problema de salud pública en todo el mundo según los datos de la OMS, con el agravante que la mayoría de los casos son asintomáticos y, además, no existe otro reservorio distinto al humano. El diagnóstico se puede realizar con pruebas tradicionales y moleculares, estas últimas incluyen la reacción en cadena de la polimerasa (PCR), de las cuales existen varios tipos, entre ellas, la PCR múltiple que tiene la capacidad de detectar ITS polimicrobianas a partir de una sola muestra. El objetivo de este estudio fue establecer cuáles fueron las infecciones de transmisión sexual más frecuentes en diferentes grupos de pacientes, así como determinar la utilidad del uso de la técnica de PCR múltiple en el diagnóstico de las ITS. Metodología. Se trata de un estudio observacional de corte transversal realizado entre los años 2021 y 2022 con pacientes que acudieron al servicio de diagnóstico del Laboratorio Clínico VID por sospecha de ITS. Las muestras recolectadas fueron evaluadas utilizando una prueba comercial basada en la técnica de PCR múltiple e hibridación. Las muestras procesadas fueron: orina e hisopados de endocérvix, uretra, recto, faringe y úlceras. Resultados. Se estudiaron 1.027 pacientes, de estos, 228 (22,2 %) fueron positivos para diferentes agentes de trasmisión sexual, distribuidos así: 50 (21,9 %) mujeres, 129 (56,6 %) hombres heterosexuales y 49 (21,5 %) hombres que tenían sexo con hombres (HSH). La edad promedio de las mujeres fue 30 años, y la de ambos grupos de hombres fue 36 años. Los microorganismos más frecuentemente identificados en mujeres fueron: C. trachomatis (A-K) en 28,6 %, seguido de virus herpes simplex tipo 2 (VHS-2) en 26,8 % y N. gonorrhoeae en 17,9 %. En hombres heterosexuales fueron C. trachomatis (A-K) en 37,5 %, N. gonorrhoeae en 21,5 % y VHS-2 en 18,7 %. En HSH fueron C. trachomatis (L1-L3) en 32,7 %, seguido de N. gonorrhoeae en 27,6 %, y de C. trachomatis (A-K) y VHS-2, ambos en 13,8 %. En 11 hombres heterosexuales, 8 HSH y en 6 mujeres, se identificó infección polimicrobiana. Conclusiones. C. trachomatis (A-K) fue el microorganismo más prevalente causante de ITS, seguido de N. gonorrhoeae en ambos grupos de hombres, y de VHS-2 en las mujeres, muy similar a lo reportado a nivel mundial. La prueba de PCR múltiple permite la detección de infecciones polimicrobianas comúnmente asociadas a ITS y el diagnóstico es preciso y confiable, incluso en pacientes asintomáticos

Sexually transmitted infections (STIs) are and will continue to be a serious public health problem throughout the world according to WHO data, with the aggravating factor that most cases are asymptomatic and, furthermore, there is no other reservoir other than humans. The diagnosis can be made with traditional and molecular tests, the latter include the polymerase chain reaction (PCR), of which there are several types, among them, multiplex PCR that has the capacity to detect polymicrobial STIs from a single sample. The objective of this study was to establish which were the most frequent sexually transmitted infections in different groups of patients, as well as to determine the usefulness of the multiplex PCR technique in the diagnosis of STIs. Methodology. This is an observational, cross-sectional study carried out between 2021 and 2022 with patients who attended the VID Clinical Laboratory for suspected STIs. The collected samples were evaluated using a commercial test based on the multiplex PCR technique and hybridization. The samples processed were: urine and swabs from endocervix, urethra, rectum, pharynx, and ulcers. Results. The study included 1,027 patients, of these, 228 (22.2%) were positive for different sexually transmitted agents, distributed as follows: 50 (21.9%) women, 129 (56.6%) heterosexual men and 49 (21.5%) men who had sex with men (MSM). The average age of the women was 30 years, and that of both groups of men was 36 years. The microorganisms most frequently identified in women were: C. trachomatis (A-K) in 28.6%, followed by herpes simplex virus type 2 (HSV-2) in 26.8% and N. gonorrhoeae in 17.9%. In heterosexual men they were C. trachomatis (A-K) in 37.5%, N. gonorrhoeae in 21.5% and HSV-2 in 18.7%. In MSM they were C. trachomatis (L1-L3) in 32.7%, followed by N. gonorrhoeae in 27.6%, and C. trachomatis (A-K) and HSV-2, both in 13.8%. Polymicrobial infection was identified in 11 heterosexual men, 8 MSM, and 6 women. Conclusions. C. trachomatis (A-K) was the most prevalent STI-causing microorganism, followed by N. gonorrhoeae in both groups of men, and HSV-2 in women, very similar to that reported worldwide. The multiplex PCR test allows the detection of polymicrobial infections commonly associated with STIs and the diagnosis is accurate and reliable, even in asymptomatic patients

Epstein-Barr virus in gastric cancer and association with 30 bp del-latent membrane protein 1 polymorphism

SUMMARY OBJECTIVE: This study aimed to determine the frequencies of Epstein-Barr virus, types 1 and 2 infection, and 30 bp del-latent membrane protein 1 viral polymorphism in gastric adenocarcinomas, as well as to investigate the association between Epstein-Barr virus infection and tumor location, type, and the patient's sex. METHODS: Samples were collected from 38 patients treated at a university hospital in Rio de Janeiro, Brazil. Epstein-Barr virus detection and genotyping were performed by polymerase chain reaction, followed by polyacrylamide gel electrophoresis and staining by the silver nitrate method. RESULTS: Overall, 68.4% of patients had Epstein-Barr virus-positive tumors. Of these, 65.4% presented infection by Epstein-Barr virus type 1, 23.1% by Epstein-Barr virus type 2, and 11.5% had coinfection with types 1 and 2. The 30 bp del-latent membrane protein 1 polymorphism was found in 42.3% of Epstein-Barr virus-positive tumors, 23.1% had the wild-type virus, and 23.1% had the wild-type and the polymorphism concomitantly. In 11.5% of Epstein-Barr virus-positive tumors, it was impossible to determine whether there was polymorphism or not. Tumor location in the antrum (22 of 38) and diffuse type (27 of 38) were predominant. There was no significant difference in Epstein-Barr virus infection or the 30 bp del-latent membrane protein 1 polymorphism between men and women. CONCLUSION: Epstein-Barr virus infection was found in 68.4% of tumors investigated in this study. To the best of our knowledge, this is the first article showing the coinfection of Epstein-Barr virus types 1 and 2 in gastric carcinoma in Brazil.

Clinical characteristics and treatment of eight cases of pemphigus/bullous pemphigoid complicated by herpes simplex virus infection / 中华皮肤科杂志

Objective:To retrospectively analyze clinical characteristics and treatment of pemphigus/bullous pemphigoid (BP) complicated by herpes simplex virus (HSV) infection.Methods:Inpatients with pemphigus/BP complicated by HSV infection were collected from Wuhan No.1 Hospital from 2016 to 2021, and their clinical characteristics, treatment and follow-up results were retrospectively analyzed.Results:Among the 8 patients with pemphigus/BP complicated by HSV infection, there were 2 males and 6 females, and their age was 50.6 ± 8.3 years. Five of them were diagnosed with pemphigus vulgaris (PV), 1 with pemphigus foliaceus (PF), and 2 with BP. Seven were infected with HSV-1, and 1 with HSV-2. All the 8 patients were given systemic glucocorticoids and immunosuppressive agents for the treatment of pemphigus or BP, and were admitted to the hospital due to resistance to the treatment. Seven patients presented with exacerbation or recurrence of primary lesions, and 1 presented with enlarged lesions all over the body. HSV infection-induced lesions were located on the trunk in 4 cases, on the oral mucosa in 4, on the scalp in 3, and on the face in 2; lesions mainly manifested as irregular erosions with blood crusts, and some centrally umbilicated pustules; 7 patients had obvious pain at the lesional sites. During HSV infection, anti-desmoglein 1 antibody levels decreased in all the 6 patients with pemphigus, and anti-desmoglein 3 antibody levels decreased in 4 of the 5 patients with pemphigus vulgaris; anti-BP180 antibody levels decreased in 1 patient with BP, but increased in the other one with BP. After antiviral therapy at adequate doses for adequate durations (7- to 14-day treatment with valacyclovir alone or in combination with ganciclovir), HSV infection was controlled, the autoimmune bullous skin disorder intensity scores decreased compared with those before the antiviral therapy, and pain was significantly relieved in all the patients. No dose adjustment of glucocorticoids or other immunosuppressive agents was made during antiviral therapy in all patients.Conclusion:HSV infection should be considered when patients with pemphigus/BP suffer from recurrence or exacerbation and poorly respond to conventional treatment; for patients with pemphigus/BP complicated by HSV infection, systemic antiviral therapy at adequate doses can be used to control the disease condition without modifying the conventional immunosuppressive regimen.

Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction / Avaliação de membros da família Herpesviridae na admissão hospitalar de pacientes com lúpus eritematoso sistêmico mostra maior frequência do vírus Epstein-Barr e sua disfunção renal associada

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

Treatment-related fluctuations in Guillain-Barré syndrome​: clinical features and predictors of recurrence / Fluctuaciones relacionadas al tratamiento en el Síndrome de Guillain-Barré: características clínicas y predictores de recurrencia

ABSTRACT Background: A treatment-related fluctuation (TRF) in a patient with Guillain-Barré syndrome (GBS) is defined as clinical deterioration within two months of symptom onset following previous stabilization or improvements with treatment. Objective: To investigate the clinical characteristics and factors that could increase the risk of relapse of GBS in patients with and without TRFs. Methods: Retrospective review of medical records of patients (>18 years) with GBS evaluated between January/2006 and July/2019. Demographic and clinical characteristics, ancillary studies, treatment received, and the clinical course of patients with and without TRFs were analyzed. Results: Overall, 124 cases of GBS were included; seven (5.6%) presented TRFs. GBS-TRF cases were triggered more frequently by infectious mononucleosis (28.57 vs. 8.55%; p=0.01). GBS-TRF were initially treated with plasmapheresis more frequently than those without TRF (14.29 vs. 1.70%; p=0.0349). Combined treatment (71.43 vs. 4.27%; p<0.001) and corticosteroids (42.86 vs. 1.71%; p<0.001) were more commonly used in the GBS-TRF group. GBS-TRF patients presented a higher median initial disability score (4 vs. 2; p=0.01). Conclusions: Patients with GBS triggered by infectious mononucleosis and a high degree of initial disability have higher chances of developing TRFs. Although patients with TRF were treated with plasmapheresis more often, the total number was too low to suggest a link between plasma exchange and TRF.

RESUMEN Antecedentes: Una fluctuación relacionada al tratamiento (FRT) en un paciente con síndrome de Guillain-Barré (SGB) se define como un deterioro clínico dentro de los dos meses posteriores al inicio de los síntomas después de una estabilización previa o mejoría con el tratamiento. Objetivo: Investigar las características clínicas y los factores que podrían incrementar el riesgo de recaída, comparando pacientes con SGB, con y sin FRT. Métodos: Revisión retrospectiva de historias clínicas de pacientes (>18 años) con SGB evaluados entre enero/2006 y julio/2019. Se analizaron las características demográficas y clínicas, los estudios complementarios, el tratamiento recibido y la evolución clínica de los pacientes con y sin FRT. Resultados: Se incluyeron 124 casos de SGB en el total; 7 (5,6%) presentaron FRT. Los casos de SGB con FRT se desencadenaron con mayor frecuencia por mononucleosis infecciosa (28,57 vs. 8,55%; p=0,01). Los casos de SGB con FRT se trataron inicialmente con plasmaféresis con más frecuencia que aquellos sin FRT (14,29 vs. 1,70%; p=0,0349). El tratamiento combinado (71,43 vs. 4,27%; p<0,001) y los corticosteroides (42,86 vs. 1,71%; p<0,001) se utilizaron con mayor frecuencia en el grupo de SGB con FRT. Los pacientes con FRT presentaron una escala de discapacidad inicial mediana más alta (4 vs. 2; p=0,01). Conclusiones: Aquellos SGB desencadenados por mononucleosis infecciosa y un alto grado de discapacidad inicial tienen una mayor probabilidad de desarrollar FRT. Aunque los pacientes con FRT fueron tratados con plasmaféresis con mayor frecuencia, el número total fue demasiado bajo para sugerir un vínculo entre la plasmaféresis y FRT.

Effects of autophagy on viral structures and expression of functional proteins in dorsal root ganglia in a guinea pig model of varicella-zoster virus infection / 中华皮肤科杂志

Objective:To investigate effects of the autophagy inducer rapamycin and autophagy inhibitor 3-methyladenine on viral structures and biosynthesis of functional proteins in dorsal root ganglia in a guinea pig model of varicella-zoster virus (VZV) infection, and to explore their possible mechanisms.Methods:VZV was cultured and proliferated in human embryonic lung fibroblasts (HELFs) , and peripheral blood mononuclear cells (PBMCs) were isolated from guinea pigs. VZV-HELFs and PBMCs were co-cultured for 18-20 hours, and VZV-PBMCs were collected by centrifugation. Thirty-two guinea pigs were randomly and equally divided into 4 groups (8 mice in each group) : blank control group was injected with autologous PBMCs via the medial canthal venous plexus; autophagy inhibition group, autophagy induction group, and VZV infection group were intraperitoneally injected with 3 mg/kg 3-methyladenine solution, 0.5 mg/kg rapamycin solution, and the same volume of 0.9% NaCl solution respectively, followed 2 hours later by injections with 50 μl of VZV-PBMCs via the medial canthal venous plexus. Fourteen days later, the guinea pigs in each group were sacrificed, and dorsal root ganglion tissues were collected. The transmission electron microscope was used to observe the morphology of virus particles, as well as the morphology and number of autophagic vesicles, Western blot analysis was performed to determine the expression of VZV nucleocapsid protein (NCP) , immediate-early protein 62 (IE62) , and autophagy-related proteins Beclin-1 and p62, and immunohistochemical study to determine the expression of anti-VZV antibodies in VZV-infected dorsal root ganglia. Statistical analysis was carried out by using two-independent-sample t test, one-way analysis of variance, least significant difference- t test or Kruskal-Wallis H test. Results:Nucleocapsid-containing virions and scattered autophagosomes were seen in the dorsal root ganglia in the VZV infection group under the transmission electron microscope. The number of autophagic vesicles significantly differed among the blank control group, VZV infection group, autophagy induction group and autophagy inhibition group ( M[ Q1, Q3]: 0, 5[4, 6], 7[5, 9], 0, respectively; H = 135.60, P < 0.01) , and was significantly higher in the VZV infection group than in the blank control group and autophagy inhibition group (both P < 0.05) , as well as in the autophagy induction group than in the autophagy inhibition group ( P<0.05) , but there was no significant difference between the VZV infection group and autophagy induction group ( P>0.05) . Western blot analysis showed that the expression level of IE62 protein was significantly higher in the VZV infection group (1.49 ± 0.06) than in the blank control group (0.50 ± 0.09, t = 9.17, P < 0.05) ; the expression of anti-VZV antibodies was significantly lower in the autophagy inhibition group than in the autophagy induction group and VZV infection group ( t = 9.24, 7.78, respectively, both P < 0.01) , while there was no significant difference between the autophagy induction group and VZV infection group ( P > 0.05) . Conclusion:Autophagy occurred in the dorsal root ganglia of guinea pigs after VZV infection; the inhibition of autophagy could affect the structure of VZV and decrease the expression of VZV functional proteins in the dorsal root ganglia of guinea pigs.

Pemphigus complicated by herpes simplex virus infection / 中华皮肤科杂志

Virus infection is one of the common complications of pemphigus. In recent years, related studies on pemphigus complicated by virus infection have mainly focused on the herpes simplex virus (HSV) . Studies have shown that HSV infection can affect the course of disease, therapeutic effect, and even the morphology of skin lesions in patients with pemphigus. However, due to considerable differences in sample sizes and test methods, the incidence and clinical characteristics of HSV infection in patients with pemphigus markedly differ among different studies. This review summarizes the incidence and clinical characteristics of pemphigus complicated by HSV infection, aiming to improve clinicians′ understanding of the disease and provide a basis for its diagnosis and treatment.

Application of metagenomic next-generation sequencing in patients with Herpes simplex pneumonia mixed infection / 中国医师杂志

Objective:To explore the application value of next-generation sequencing (mNGS) technology in patients with Herpes simplex pneumonia mixed infection.Methods:The clinical data of pneumonia patients who underwent alveolar lavage fluid mNGS technology and traditional pathogen detection in the Affiliated Hospital of Yangzhou University from June 2018 to January 2021 were retrospectively collected.Results:A total of 41 patients with mNGS Herpes simplex type 1 (HSV-1) test (4 HSV-1 carriers, 37 HSV-1 infections) were enrolled in this study, including 22 males and 19 females. The age ranged from 46 to 83 years old, with a median age of 67 years. The higher proportion of pathogens in 25 cases of HSV-1 co-infection detected by mNGS were Pneumocystis jiroveci (6 cases, 24.0%), Acinetobacter baumannii (4 cases, 16.0%), and Klebsiella pneumoniae (4 cases, 16.0%), and Aspergillus fumigatus (3 cases, 12.0%). The difference in the Simpson's diversity index in the HSV-1carrier group, HSV-1 single infection group and HSV-1 mixed infection group was statistically significant ( P<0.05). Compared with 12 cases of HSV-1 single infection, the time for body temperature to return to normal for 25 cases of HSV-1 mixed infection was [(5.16±2.04)days vs (3.75±1.29)days], and course of antibiotic treatment was longer [(10.60±2.18)d vs (8.92±1.98)d]. Conclusions:The mNGS technology has obvious advantages in identifying HSV-1 mixed infections, which is beneficial to physicians to treat them accurately.

Detection of varicella-zoster virus in different specimens from patients with acute herpes zoster / 中华皮肤科杂志

Objective:To investigate positive rates of varicella-zoster virus (VZV) DNA in blood and saliva samples, as well as in swab samples from lesions and clothes in contact with lesions in patients with acute herpes zoster, and to explore their clinical significance.Methods:Patients with confirmed herpes zoster were collected from Department of Dermatology, Shenzhen Hospital, Southern Medical University from April 2019 to August 2020. Fluorescence-based quantitative PCR was performed to detect VZV DNA in blood and saliva samples, lesion and cloth swab samples from the patients before and after antiviral treatment. Chi-square test was used to compare the positive rate of VZV DNA in saliva samples between patients with herpes zoster on the head, face and neck and those without involvement of the head, face or neck, and changes in the positive rate of VZV DNA in different specimens were analyzed before and after treatment.Results:A total of 86 patients with herpes zoster were collected, including 26 males and 60 females aged 52.65 ± 14.83 years, with a disease duration being 5.23 ± 2.10 days. The positive rate of VZV DNA in the saliva samples was significantly higher in the 24 patients with herpes zoster on the head, face and neck (41.67%, 10/24) than in the 62 patients without involvement of the head, face or neck (12.90%, 8/62; χ2 = 7.63, P < 0.05) . Both pre- and post-treatment blood samples were collected from 37 patients, saliva samples from 35, lesion swab samples from 28, and cloth swab samples from 27. Before the treatment, the positive rates of VZV DNA in the blood, saliva, lesion and cloth swab samples were 86.49% (32/37) , 22.86% (8/35) , 92.86% (26/28) and 88.89% (24/27) respectively, which decreased to 51.35%, 8.57%, 89.29% and 85.18%, respectively, after 6.82 ± 2.23 days of treatment. The positive rate of VZV DNA significantly differed before and after treatment only in the blood samples ( χ2 = 9.60, P = 0.003) , while showed no significant difference in the other specimens (all P > 0.05) . Conclusion:The positive rate of VZV DNA in the saliva samples was significantly higher in the patients with acute herpes zoster on the head, face and neck than in those without involvement of the head, face or neck, and that in the cloth swab samples was relatively high before and after antiviral treatment.

Clinical characteristics and misdiagnosis analysis of infectious mononucleosis in children / 中国医师进修杂志

Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.

The risk factors for hemophagocytic syndrome in childhood Epstein-Barr virus-associated infectious mononucleosis / 中国医师进修杂志

Objective:To explore the risk factors for hemophagocytic syndrome (HPS) in childhood Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM).Methods:From January 2013 to December 2017, the medical charts of all children who were diagnosed with EBV-associated IM and HPS in Children′s Hospital of Soochow University were analyzed retrospectively. Statistical analyses were performed using SPSS version 22.0.Results:A total of 316 IM and 59 HPS were enrolled. The age was (4.26 ± 2.95) years old with a male-to-female ratio of 1.2∶1. In addition to the diagnostic criteria of HPS, there were significantly lower rates of fever >10 d, hepatomegaly, jaundice, alanine aminotransferase >500 U/L, aspartate aminotransferase >500 U/L, LDH >1 000 U/L, C-reactive protein >50 mg/L and hypoalbuminemia in children with EBV-associated IM compared to those with HPS, and the differences were statistically significant ( P<0.05). Multivariate Logistic regression analysis showed that fever >10 d, eyelid edema, lymphadenopathy and purulent tonsils were independent predictors of HPS in children with EBV-associated IM ( P<0.05). Hepatomegaly and fever >10 d were risk factors ( OR = 16.079 and 12.138, 95% CI 2.788 to 92.744 and 2.878 to 51.180). Eyelid edema, lymphadenopathy and purulent tonsils were protective factors ( OR = 0.087, 0.006 and 0.031; 95% CI 0.010 to 0.723, 0.001 to 0.058 and 0.007 to 0.146). Conclusions:Hepatomegaly and fever >10 d are the risk factors for hemophagocytic syndrome in childhood EBV-associated infectious mononucleosis.

Family Herpesviridae and neuroinfections: current status and research in progress

This article addresses the relationship between human herpesviruses (HHVs) and neuroinfections. Alphaherpesviruses, betaherpesviruses and gammaherpesviruses are neurotropic viruses that establish latency and exhibit reactivation capacity. Encephalitis and meningitis are common in cases of HHV. The condition promoted by HHV infection is a purported trigger for certain neurodegenerative diseases. Ongoing studies have identified an association between HSV-1 and the occurrence of Alzheimer's disease, multiple sclerosis and infections by HHV-6 and Epstein-Barr virus. In this review, we highlight the importance of research investigating the role of herpesviruses in the pathogenesis of diseases that affect the nervous system and describe other studies in progress.

Enfermedad de Castleman. Reporte de caso / Castleman Disease. Case report and literature review

Resumen INTRODUCCIÓN: La enfermedad de Castleman, o hiperplasia angiofolicular de los ganglios linfáticos, es todo un reto diagnóstico y terapéutico para la mayoría de los médicos. Puede estar asociada con infecciones virales, como el herpes virus tipo 8 (HHV-8), o ser idiopática. A su vez, puede localizarse en una sola región (unicéntrica) o afectar varias (multicéntrica). Suele diagnosticarse en la cuarta década de la vida y ser un hallazgo cuando se trata de la variante unicéntrica. CASO CLÍNICO: Paciente de 19 años que acudió a consulta debido a la aparición de un nódulo en la mama derecha. En el ultrasonido mamario y axilar se encontraron fibroadenomas bilaterales y adenomegalias en el lado izquierdo, con alta vascularidad. Se catalogó como BIRADS 3. El reporte histopatológico de la biopsia, con aguja de corte, del ganglio axilar izquierdo fue de: proliferación linfoide atípica. La inmunohistoquímica reportó positividad para: CD20, CD3, CD21 en células dendríticas interfoliculares, Ki-67 y negatividad para HHV-8 en centros germinales residuales. CONCLUSIÓN: La extirpación quirúrgica de una masa unicéntrica de tipo hialino-vascular-plasmático es curativa. La evaluación de pacientes con sospecha de esta enfermedad debe incluir, además de la evaluación patológica con inmunotinción, estudios de laboratorio y de imágenes sistémicas con PET-TAC para determinar la extensión de la enfermedad (unicéntrica o multicéntrica) y para los marcadores de seguimiento.

Abstract BACKGROUND: Castleman's disease, or angiofollicular lymph node hyperplasia, is a diagnostic and therapeutic challenge for most physicians. It may be associated with viral infections, such as herpes virus type 8, or be idiopathic. In turn, it can be localized in a single region (unicentric) or affect several (multicentric). It is usually diagnosed in the fourth decade of life and is a finding when it is the unicentric variant. CLINICAL CASE: 19 year old patient who came to consult due to the appearance of a nodule in the right breast. Breast and axillary ultrasound showed bilateral fibroadenomas and adenomegaly on the left side, with high vascularity. It was classified as BIRADS 3. The histopathological report of the biopsy, with cutting needle, of the left axillary node was: atypical lymphoid proliferation. Immunohistochemistry reported positivity for: CD20, CD3, CD21 on interfollicular dendritic cells, Ki-67 and negativity for HHV-8 in residual germinal centers. CONCLUSION: Surgical removal of a unicentric hyaline-vascular-plasmic type mass is curative. Evaluation of patients with suspected disease should include, in addition to pathologic evaluation with immunostaining, laboratory and systemic imaging studies with PET-CT to determine the extent of disease (unicentric or multicentric) and for follow-up markers.

Prevalence of epstein-barr virus infection in palatine tonsils hyperplasia through the immunoexpression of the LMP-1 marker / Avaliação da prevalência de infecção por epstein-barr vírus na hiperplasia de tonsilas palatinas através da imunoexpressão do marcador LMP-1

Introduction: LMP-1 (latent membrane protein 1) is a membrane protein found in EBV and can be identified through immunohistochemistry. Objectives: To evaluate the prevalence of EBV virus in tonsillar tissue samples correlating with tonsil size, age and gender. Methods: An LMP-1 immunohistochemical study was performed in slides from patients with tonsil hyperplasia. Results: The sample consisted of 120 slides, 66 were from male. The average tonsillar size was 6.0 cm2 (1.5-14.0) and the average age was 6.5 years (2-18). Overall, 72 patients were positive for the virus, the majority being male (51%) and preschoolers (51.4%). For comparative analysis, the sample was divided: group 1 (positive immunohistochemistry) and group 2 (negative immunohistochemistry). The average age was 6.74 years (± 4.14) and 6.19 years (± 3.82) for group 1 and 2, respectively. Group 1 had 37 preschoolers, 23 school-age children and 12 adolescents. Group 2 had 28 preschoolers, 14 school-age children and 6 adolescents (p=0.71). To evaluate the presence of virus, the slides were divided according to area: G (≥6cm²) and P (<6cm²). In G group, 54 slides were positive, while in P group, 18 were positive. Group 1 presented 54 of G group slides and 18 of P group slides, with no statistical difference, but with a tendency to positivity (p=0.09). Conclusion: Most of the sample was positive for the presence of Epstein-Barr virus. There was no difference in the virus presence or absence when correlated with the tonsillar size, age or sex

Introdução: LMP-1 (proteína latente de membrana-1) é uma proteína de membrana encontrada no Epstein-Barr vírus (EBV) e que pode ser identificadaatravés da imunoistoquímica. Objetivo: Avaliar a prevalência do EBV em amostras de tecido tonsilar correlacionando com o tamanho da tonsila, idade e sexo. Método: Realizou-se um estudo imunoistoquímico de LMP-1 para EBV em lâminas de pacientes com hiperplasia de tonsilas. Resultados: A amostra foi composta por 120 lâminas, sendo 66 (55%) de pacientes do sexo masculino. O tamanho médio tonsilar foi 6,0 cm2 (1,5-14,0) e a idade média 6,5 anos (2-18). Ao todo, 72 pacientes (60%) tiveram positividade para o vírus, a maioria meninos (51%) e pré-escolares (51,4%). A amostra foi dividida em: grupo 1 (imunoistoquímica positiva) e grupo 2 (imunoistoquímica negativa). A idade média foi de 6,74 anos (±4,14) e 6,19 anos (±3,82), para o grupo 1 e 2, respectivamente. O grupo 1 apresentou 37 pré-escolares, 23 escolares e 12 adolescentes. O grupo 2 foi composto por 28 pré-escolares, 14 escolares e 6 adolescentes, sem diferença estatística (p=0,71). Para avaliar a presença do EBV, as lâminas foram divididas de acordo com a área: G (≥6 cm²) e P (<6 cm²). No grupo G, 54 lâminas foram positivas, enquanto no grupo P, 18, sem diferença estatística, mas com tendência a positividade (p=0,09). Conclusão: A maior parte da amostra foi positiva para o Epstein-Barr vírus. Não houve diferença significante na positividade ou não do vírus quando correlacionada com o tamanho tonsilar, a idade e o sexo dos pacientes.