Human Circovirus is not detected in plasma pools for fractionation.

BACKGROUND: Human Circovirus 1 and 2 were recently described in a French hepatitis case and in two Chinese drug users. Because of its small size and presumable high resistance to both inactivation and removal by nanofilters, such viruses-if determined to be even pathogenic-should be considered with respect to the safety of plasma derivatives. We, therefore, investigated the prevalence and titer of these viruses in plasma pools before fractionation. METHODS AND MATERIALS: We tested for the presence of Human Circovirus 1 and 2 by qPCR in 48 plasma pools derived from healthy donors from Europe, USA, and Japan, corresponding to more than 200,000 plasma donations. RESULTS: We did not detect the presence of Human Circovirus 1 and 2 in any of the plasma pools, with a limit of detection of 300-600 genome copies per mL of plasma. CONCLUSIONS: These results indicate that high levels of circovirus are not widely prevalent in such donations.

Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients.

BACKGROUND: Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset posttreatment manifestations (such as persistent hepatitis) are not uncommon. OBJECTIVE: We sought to characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments. METHODS: We used various techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from patients in the SCIDH+ group and corresponding asymptomatic similarly transplanted SCID patients without hepatitis (SCIDH-). RESULTS: Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus, and sapovirus) in liver and/or stools, which were not found in stools from the SCIDH- group (n = 12). Multiomics analysis identified an expansion of effector memory CD8+ T cells with high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism, and defective B-cell function, representing 25% of the 44 patients with SCID having these characteristics. Partially myeloablative retransplantation or GT of patients with this condition (which we have named as "enteric virus infection associated with hepatitis") led to the reconstitution of T- and B-cell immunity and remission of hepatitis in 5 patients, concomitantly with viral clearance. CONCLUSIONS: Enteric virus infection associated with hepatitis is related to chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B-cell function.

Chronic Aichi Virus Infection As a Cause of Long-Lasting Multiorgan Involvement in Patients With Primary Immune Deficiencies.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation. METHODS: Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis. RESULTS: AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3). CONCLUSIONS: The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality.

Circovirus Hepatitis Infection in Heart-Lung Transplant Patient, France.

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Performance of clinical metagenomics in France: a prospective observational study.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) allows untargeted identification of a broad range of pathogens, including rare or novel microorganisms. Despite the recognition of mNGS as a valuable diagnostic tool for infections, the most relevant indications for this innovative strategy remain poorly defined. We aimed to assess the determinants of positivity and clinical utility of mNGS. METHODS: In this observational study, we prospectively performed short-read shotgun metagenomics analysis as a second-line test (in cases of negative first-line test or when the symptoms were not fully explained by initial positive results) or as a first-line test in life-threatening situations requiring urgent non-targeted pathogen identification at the Necker-Enfants Malades Hospital (Paris, France). All sample types, clinical indications, and patient populations were included. Samples were accompanied by a mandatory form completed by the senior clinician or pathologist, on which the clinical level of suspected infection (defined as high or low) was indicated. We assessed the variables (gender, age, immune status, initial suspicion of infection, indication, and sample type) associated with mNGS pathogen detection using odds ratios (ORs) from multivariate logistic regression. Additional investigations were carried out using specific PCR or culture techniques, to confirm positive mNGS results, or when infectious suspicion was particularly high despite a negative mNGS result. FINDINGS: Between Oct 29, 2019, and Nov 7, 2022, we analysed 742 samples collected from 523 patients. The initial suspicion of infection was either high (n=470, 63%) or low (n=272, 37%). Causative or possibly causative pathogens were detected in 117 (25%) samples from patients with high initial suspicion of infection, versus nine (3%) samples analysed to rule out infection (OR 9·1, 95% CI 4·6-20·4; p<0·0001). We showed that mNGS had higher odds of detecting a causative or possibly causative pathogenic virus on CNS biopsies than CSF samples (4·1, 1·7-10·7; p=0·0025) and in samples from immunodeficient compared with immunocompetent individuals (2·4, 1·4-4·1; p=0·0013). Concordance with conventional confirmatory tests results was 103 (97%) of 106, when mNGS detected causative or possibly causative pathogens. Altogether, among 231 samples investigated by both mNGS and subsequent specific tests, discordant results were found in 69 (30%) samples, of which 58 (84%) were mNGS positive and specific tests negative, and 11 (16%) mNGS negative and specific tests positive. INTERPRETATION: Major determinants of pathogen detection by mNGS are immune status and initial level of suspicion of infection. These findings will contribute, along with future studies, to refining the positioning of mNGS in diagnostic and treatment decision-making algorithms. FUNDING: Necker-Enfants Malades Hospital and Institut Pasteur. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Renal arcuate vein thrombosis-induced acute kidney injury: a rare multiple-Hit-mediated disease.

Background: Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive. Methods: This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis. Results: We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption. Conclusions: In conclusion, RAVT-induced AKI appears to be a multiple hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

A influência das práticas de lazer na saúde mental da população brasileira durante a pandemia da COVID-19 / The influence of leisure practices on the mental health of the brazilian population during the COVID-19 pandemic

A pandemia da COVID-19 afetou as pessoas de diferentes maneiras. Diversas mudanças aconteceram nas atividades de trabalho e de lazer, impactando na saúde física e mental. Este estudo de revisão bibliográfica analisou as adaptações referente às práticas de lazer ativo e social que ocorreram durante a pandemia da COVID-19 e sua influência na saúde mental da população brasileira. Foram selecionados os artigos mais relevantes que foram publicados nos últimos 4 anos (2020-2023). Os resultados apresentaram que as práticas de lazer durante o período pandêmico foram adaptadas aos pequenos espaços, e que pessoas que já praticavam algum tipo de atividade anteriormente possuem melhor capacidade de adaptação as adversidades. O acesso a internet e as plataformas de entretenimento aumentaram consideravelmente e as práticas de lazer social foram substituídas pelo lazer artístico, virtual, manual e intelectual.

The COVID-19 pandemic has affected people in different ways. Several changes have occurred in work and leisure activities, impacting physical and mental health. This literature review study analyzed the adaptations regarding active and social leisure practices that occurred during the COVID-19 pandemic and their influence on the mental health of the Brazilian population. The most relevant articles that were published in the last 4 years (2020-2023) were selected. The results showed that leisure practices during the pandemic period were adapted to small spaces, and that people who already practiced some type of activity previously have a better ability to adapt to adversities. Access to the internet and entertainment platforms increased considerably and social leisure practices were replaced by artistic, virtual, manual and intellectual leisure.

Aspectos gerais do retículo peritonite traumática em bovinos / General aspects of traumatic reticulum peritonitis in cattle / Aspectos generales de la peritonitis del retículo traumático en ganado

A Retículo Peritonite Traumática está diretamente ligada à ingestão de objetos metálicos perfuro cortantes, como pregos e pedaços de arame, que podem penetrar ou perfurar a parede do retículo. Embora a ocorrência de corpos estranhos de alumínio seja rara, outros elementos, como fios de pneus usados para fixar lonas em silagens e até cerdas de arame de escovas utilizadas em pequenos aeroportos, têm sido registrados como causas dessa afecção. A ingestão desses objetos pode resultar em lesões no retículo, desencadeando episódios de retículo peritonite traumática e suas sequelas, como pericardite traumática, inflamação do fígado, abscessos no baço e muito mais. Os sinais clínicos podem variar, mas incluem comportamento anormal, motilidade reduzida do rúmen, fezes mal digeridas, febre e sinais de dor. O diagnóstico baseia-se na avaliação dos sinais clínicos do animal, juntamente com exames complementares, como hemograma, bioquímico, ultrassom e radiografia. É importante considerar as alterações hematológicas, como leucocitose e hiperfibrinogenemia, como indicadores-chave desta afecção. O diagnóstico também envolve testes de dor ao corpo estranho. O tratamento pode ser conservativo ou cirúrgico. A abordagem conservativa envolve a administração de antibióticos, anti-inflamatórios e soluções intravenosas, além do tratamento de deficiências nutricionais subjacentes. A opção cirúrgica exige a remoção do corpo estranho do retículo, seguida de cuidados pós-operatórios.

Traumatic Reticulum Peritonitis this directly linked to the ingestion of sharp metallic objects, such as nails and pieces of wire, which can penetrate or pierce the wall of the reticulum. Although the occurrence of aluminum foreign bodies is rare, other elements, such as tire wires used to attach tarpaulins to silage and even wire bristles from brushes used in small airports, have been recorded as causes of this condition. Ingestion of these objects can result in damage to the reticulum, triggering episodes of traumatic reticulum peritonitis and its sequelae, such as traumatic pericarditis, liver inflammation, spleen abscesses and more. Clinical signs may vary but include abnormal behavior, reduced rumen motility, poorly digested feces, fever and signs of pain. The diagnosis is based on the evaluation of the animal's clinical signs, together with complementary tests, such as blood count, biochemistry, ultrasound and radiography. It is important to consider hematological changes, such as leukocytosis and hyperfibrinogenemia, as key indicators of this condition. Diagnosis also involves foreign body pain testing. Treatment can be conservative or surgical. The conservative approach involves administering antibiotics, anti-inflammatories and intravenous solutions, in addition to treating underlying nutritional deficiencies. The surgical option requires removal of the foreign body from the reticulum, followed by post-operative care.

La peritonitis traumática del retículo esto directamente ligada a la ingestión de objetos metálicos punzantes, como clavos y trozos de alambre, que pueden penetrar o perforar la pared del retículo. Aunque la aparición de cuerpos extraños de aluminio es rara, se han registrado como causas de esta afección otros elementos, como los alambres de neumáticos utilizados para fijar las lonas al ensilaje e incluso las cerdas de alambre de los cepillos utilizados en los aeropuertos pequeños. La ingestión de estos objetos puede provocar daños en el retículo, desencadenando episodios de peritonitis traumática del retículo y sus secuelas, como pericarditis traumática, inflamación del hígado, abscesos del bazo y más. Los signos clínicos pueden variar, pero incluyen comportamiento anormal, motilidad ruminal reducida, heces mal digeridas, fiebre y signos de dolor. El diagnóstico se basa en la evaluación de los signos clínicos del animal, junto con pruebas complementarias, como hemograma, bioquímica, ecografía y radiografía. Es importante considerar los cambios hematológicos, como la leucocitosis y la hiperfibrinogenemia, como indicadores clave de esta afección. El diagnóstico también implica la prueba del dolor por cuerpo extraño. El tratamiento puede ser conservador o quirúrgico. El enfoque conservador implica la administración de antibióticos, antiinflamatorios y soluciones intravenosas, además de tratar las deficiencias nutricionales subyacentes. La opción quirúrgica requiere la extracción del cuerpo extraño del retículo, seguida de cuidados postoperatorios.

[Outbreaks of human rabies transmitted by vampire bats in Alto Baudó and Bajo Baudó municipalities, department of chocó, Colombia, 2004-2005]. / Brotes de rabia humana transmitida por vampiros en los municipios de Bajo y Alto Baudó, departamento del Chocó, Colombia 2004-2005.

INTRODUCTION: During months May to July 2004, a rabies outbreak in the Embera community of Birrinchao, in the Purricha river basin department of Choc6 was reported with 14 human deaths. Another rabies outbreak was reported in January 2005 in the black communities of Pató and Nauca in the neighboring municipality of Alto Baudó with 3 human deaths. OBJECTIVES: To describe the largest outbreaks of human rabies transmitted by vampire bats reported in Colombia to date. To describe the diagnostic laboratory techniques used, and the activities undertaken for the control of rabies in the area. To discuss the epidemiologic significance and public health implications of these rabies outbreaks. MATERIALS AND METHODS: Rabies diagnosis was achieved by direct immunofluorescence, inoculation of mice and immunohistochemistry. Typing of the virus was achieved by indirect immunofluorescence using monoclonal antibodies. Rabies control activities were undertaken in Bajo Baudó consisting in a population census, human vaccination and application of antirabies sera, vaccination of dogs and cats, and application of anticoagulant to bats. RESULTS: Four human cases were confirmed as positive for rabies in both rabies outbreaks. Another 13 rabies cases in humans were inferred by strong epidemiological links. Rabies antigenic variant 3 was identified in the samples studied. Rabies control activities were conducted for a human rabies outbreak caused by vampire bats. CONCLUSIONS: The human rabies outbreak in Bajo Baudó has been the largest reported in Colombia. It was caused by vampire bats, showing that these animals are a threat for human health. The implementation of control strategies for this kind of epizootic outbreaks is needed in South America. It remains unknown whether there is a link between this outbreak and one reported 6 months later in the neighboring municipality of Alto Baudó.

Correlación de los hallazgos endoscópicos e histológicos en el diagnóstico de metaplasia intestinal gástrica en pacientes referidos para endoscopia digestiva alta en la Clínica Colombia / Correlation of endoscopic and histological findings in diagnosis of gastrointestinal metaplasia in patients referred to the Clinica Colombia for upper endoscopies

Introducción: La metaplasia intestinal es un paso más hacia el proceso final conocido del cáncer gástrico. Su correcta identificación endoscópica con toma de biopsia es vital para su confirmación histológica. No conocemos en nuestro medio la relación entre los hallazgos endoscópicos sospechosos de metaplasia intestinal y su confirmación histológica. El presento estudio busca determinar la verdadera correlación entre los hallazgos endoscópicos sugestivos de metaplasia y su contraparte histológica. Métodos: Estudio observacional analítico, realizado en la Clínica Colombia donde se incluyeron pacientes con sospecha endoscópica de metaplasia intestinal, excluyendo pacientes con antecedente previo de metaplasia y con cáncer gástrico previo. La evaluación estadística se realizó con el software estadístico STATA 11. Resultados: Se identificaron un total de 766 pacientes con sospecha endoscópica de metaplasia intestinal. En 543 de ellos se encontró confirmación histológica equivalente a un 70% del total de la muestra. Los hallazgos histológicos más frecuentes en el grupo en el que no se encontró correlación fueron gastritis crónica, gastropatía reactiva e hiperplasia foveolar entre otros. El valor predictivo positivo de los hallazgos endoscópicos fue cercano al 71%. Conclusiones: Aunque la correlación fue cercana al 70%, se requieren de estudios prospectivos, multicéntricos y con cromoendoscopia, con el fin de evaluar la concordancia respectiva entre los dos métodos y determinar variables endoscópicas predictoras de severidad, y tipo de metaplasia para determinar protocolos de seguimiento para este tipo de pacientes.

Introduction: Intestinal metaplasia is one step towards the final process known as gastric cancer. Correct identification through a biopsy taken endoscopically is vital for histological confirmation. In our surroundings the relationship between endoscopic findings when intestinal metaplasia is suspected and histological confirmation are not understood. This study aims to determine the true correlation between endoscopic findings suggestive of metaplasia and their histological counterparts. Methods: This was an observational and analytical study undertaken at the Clinica Colombia. Patients who were suspected of having intestinal metaplasia following endoscopic examinations were included. Patients with prior histories of metaplasia and gastric cancer were excluded. Statistical evaluation was performed using STATA 11. Results: A total of 766 patients suspected of having intestinal metaplasias following endoscopic examination were included. 543 (70%) were confirmed histologically. Patients who most frequently had no correlation between suspicion following endoscopy and histological findings included those with chronic gastritis, foveolar hyperplasia, and reactive gastropathy. The positive predictive value of endoscopic findings was close to 71%. Conclusions: Although the correlation was close to 70%, prospective and multicenter studies, as well as studies using chromoendoscopy, are needed in order to evaluate agreement between the two methods, to determine predictive endoscopic variables for severity and for types of metaplasia, and to determine protocols for monitoring these patients.

Quemadura de vía digestiva por ácido muriático: Reporte de caso y revisión de la literatura / Muriatic acid: digestive exposure, case report and literature review

Las quemaduras del tracto digestivo generan gran comorbilidad en el paciente expuesto, por su capacidad de lesión y dependen si se genera por álcali o por ácido. El momento ideal de endoscopia aún es debatido y las secuelas de estos pacientes pueden ser devastadoras. Presentamos el caso de una paciente con intento suicida tras ingerir ácido muriático, sus hallazgos endoscópicos, complicaciones y manejo de estos.

Digestive tract burns can create high levels of comorbidity in an exposed patient although these levels depend on the different capacities to cause harm of alkalis and acids. The ideal moment for endoscopy in these cases is currently being debated as a patient’s post burn reactions may be devastating. We present the case of a patient who attempted to commit suicide by ingesting muriatic acid including clinical findings, complications and management.

Un enfoque práctico de disnea / A practical approach of dyspnea

Revisamos la disnea, aguda y crónica, ya que es el más común de los síntomas de las enfermedades cardiopulmonares y motivo de consulta muy frecuente en los servicios de urgencias. Tenemos en cuenta definición, clasificación, patrones clínicos de presentación así como repercusión hemodinámica, tratamiento y pronóstico. Se revisan algoritmos de enfoque clínico para un óptimo manejo de los pacientes afectados por las múltiples entidades que pueden producir o deteriorar la clase funcional de la disnea.

Revisión semiologica respiratoria Tos: acercamiento a la fisiopatología, enfoque y tratamiento / Review respiratory semiology: cough approach to the pathophysiology, diagnosis and treatment

La tos es uno de los síntomas respiratorios más amplios y comunes dentro de la consulta médica, encontrándose, en la práctica clínica diaria, grandes dificultades para un adecuado abordaje diagnóstico, clasificación y tratamiento. Puede ser subestimada en la mayoría de los casos, por lo que se hace prioritaria la revisión de este síntoma, abarcando fisiopatología, orientación diagnóstica y aproximación terapéutica.

Proteinosis alveolar pulmonar: reporte de caso y revisión de la literatura / Alveolar pulmonary proteinosis: case report and literature review

Se describe el caso de una mujer joven con proteinosis alveolar primaria, con cuadro clínico poco frecuente dado la corta duración de la sintomatología, sin factores de riesgo para la entidad, con su evolución clínica y algunas complicaciones relacionadas con el tratamiento. Se realiza además una breve revisión de la literatura sobre la entidad.

Embolismo pulmonar por silicona: reporte de caso y revisión de literatura / Silicone pulmonary embolism: report of a case and review of the literature

Presentamos el caso de un paciente de 24 años, con disnea súbita progresiva y antecedentes de inyecciones de silicona en regio glútea 24 horas antes del ingreso hospitalario. Al examen físico se encontraron disminuidos los ruidos respiratorios, taquipnea, en la gasimetria arterial trastorno de la oxigenación; los hallazgos de la tomografía computarizada de tórax y del lavado bronco alveolar fueron compatibles con embolismo pulmonar por silicona. La mortalidad en esta entidad es elevada debido al trastorno severo en la oxigenación y perfusión. El uso de este compuesto para fines cosméticos es, en la mayoría de los casos, practicado de manera ilegal, poniendo en riesgo la vida de los usuarios de este tipo de terapia. La evolución de este caso fue favorable.