Rendimiento diagnóstico de la prueba Genexpert MTB/RIF para el diagnóstico de tuberculosis extrapulmonar. Hospital III Emergencias Grau, 2019-2020

La enfermedad de la tuberculosis a nivel mundial es un problema de salud pública. La Organización Mundial de la Salud (OMS) estadísticamente a informado de 10 millones de personas afectados por tuberculosis como nuevos casos y también 1,2 millones de personas muertas (incluidos 678 000 coinfectados por el VIH) en el año 2020 (1). Donde el 90% de los diagnosticados con tuberculosis fueron adultos (65% sexo masculino y 35% sexo femenino), y el 10% de niños (1,2). Es así que, entre los nuevos casos de tuberculosis registrados, el 10% de las personas viven con la enfermedad del VIH y el 74% son africanos. La tuberculosis extrapulmonar notificadas por la OMS en el año 2020 en todo el mundo se estimó estadísticamente en un 16%, pero el 50% presenta coinfección entre VIH-tuberculosis (2,3). Además, las tasas porcentuales van a variar según la región y la endemicidad. A nivel mundial el diagnóstico de tuberculosis extrapulmonar es un desafío tanto para los médicos en general como para los patólogos clínicos. Es así por un lado, la tuberculosis extrapulmonar no siempre es obvia de sospechar durante los exámenes clínicos sintomatológicos debido a la variabilidad de sus presentaciones clínicas (4). Por otro lado, la dificultad o el no acceso a sitios difíciles de muestreo específicos da como resultado muestras paucibacilares, lo que reduce la sensibilidad de las pruebas diagnósticas laboratoriales convencionales (4,5)

Biomarker Associations with Insomnia and Secondary Sleep Outcomes in Persons with and without HIV in the POPPY-Sleep Sub-study: a cohort study

STUDY OBJECTIVES: We investigated associations between inflammatory profiles/clusters and sleep measures in people living with HIV and demographically-/lifestyle-similar HIV-negative controls in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY)-Sleep sub-study. METHODS: Primary outcome was insomnia (Insomnia Severity Index [ISI]≥15). Secondary sleep outcomes included 7-day actigraphy (e.g. mean/standard deviation of sleep duration/efficiency), overnight oximetry (e.g. oxygen desaturation index [ODI]) and patient-reported measures (Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires). Participants were grouped using Principal Component Analysis of 31 biomarkers across several inflammatory pathways followed by cluster analysis. Between-cluster differences in baseline characteristics and sleep outcomes were assessed using Kruskal-Wallis/logistic regression/Chi-squared/Fisher's exact tests. RESULTS: Of the 465 participants included (74% people with HIV, median [interquartile range] age 54 [50-60] years), only 18% had insomnia and secondary sleep outcomes suggested generally good sleep (e.g. ODI 3.1/hr [1.5-6.4]). Three clusters with distinct inflammatory profiles were identified: 'gut/immune activation' (n=47), 'neurovascular' (n=209), and 'reference' (relatively lower inflammation; n=209). The 'neurovascular' cluster included higher proportions of people with HIV, obesity (BMI≥30 kg/m 2), and previous cardiovascular disease, mental health disorder, and arthritis of knee/hip relative to the other two clusters. No clinically relevant between-cluster differences were observed in proportions with insomnia (17%, 18%, 20%) before (p=0.76) or after (p=0.75) adjustment for potential confounders. Few associations were observed among actigraphy, oximetry and PROMIS measures. CONCLUSIONS: Although associations could exist with other sleep measures or biomarker types not assessed, our findings do not support a strong association between sleep and inflammation in people with HIV

Endoscopic ultrasound-guided transvascular needle biopsy of thoracic and abdominal lesions: a multicenter experience

Background and study aims Traditionally in the case of a vascular interposition, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been contraindicated. A transvascular route (TV) is feasible and probably a safe alternative approach in selected patients, but data are scarce. The primary aim of this study was to analyze the diagnostic yield and safety of EUS-TV-FNA in thoracic and abdominal lesions. Secondary aims included evaluation of the clinical impact and technical aspects. Patients and methods A retrospective multicenter study was conducted with inclusion of all consecutive patients that underwent EUS-TV-FNA from July 2007 to January 2020. Feasibility, cytopathology, procedure details, and safety were evaluated. Univariate analysis was performed to identify variables associated with incidents, cytopathological diagnosis, and clinical impact. Results Data were collected from a total of 49 cases and 50 EUS-TV-FNAs. The aorta (n = 19) and portal system (n = 17) were the most frequently punctured. The most frequent lesions were mediastinal lymph nodes (n = 13) and pancreatic tumors (n = 11). The diagnostic yield was 86 %, and there were nondiagnostic samples in seven cases. Overall sensitivity, specificity, and accuracy were 88% (95 % CI, 0.74-0.96), 100% (95 % CI, 0.59-1), and 90% (95 % CI, 0.78-0.96), respectively. Only three incidents were detected: two mural hematomas and a self-limited bleeding of gastroduodenal artery. In most patients, there was a significant impact on clinical management (88%). Arterial vessel and ASA-III had a trend with incidents (both, P < 0.08). Rapid on-site evlauation was found to be an independent predictor for obtaining a conclusive sample (OR 6.2; 95%CI, 1.06-36.73, P < 0.04). Conclusions EUS-TV-FNA is feasible, seems to be safe, and can be recommended when no other targets are available, and the information obtained would impact on the clinical plan

Specific genetic markers for detecting subtypes of dengue virus serotype-2 in isolates from the states of Oaxaca and Veracruz, Mexico

<p>Abstract</p> <p>Background</p> <p>Dengue (DEN) is an infectious disease caused by the DEN virus (DENV), which belongs to the <it>Flavivirus </it>genus in the family <it>Flaviviridae</it>. It has a (+) sense RNA genome and is mainly transmitted to humans by the vector mosquito <it>Aedes aegypti</it>. Dengue fever (DF) and dengue hemorrhagic fever (DHF) are caused by one of four closely related virus serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). Epidemiological and evolutionary studies have indicated that host and viral factors are involved in determining disease outcome and have proved the importance of viral genotype in causing severe epidemics. Host immune status and mosquito vectorial capacity are also important influences on the severity of infection. Therefore, an understanding of the relationship between virus variants with altered amino acids and high pathogenicity will provide more information on the molecular epidemiology of DEN. Accordingly, knowledge of the DENV serotypes and genotypes circulating in the latest DEN outbreaks around the world, including Mexico, will contribute to understanding DEN infections.</p> <p>Results</p> <p>1. We obtained 88 isolates of DENV, 27 from Oaxaca and 61 from Veracruz. 2. Of these 88 isolates, 16 were serotype 1; 62 serotype 2; 7 serotype 3; and 2 serotype 4. One isolate had 2 serotypes (DENV-2 and -1). 3. Partial nucleotide sequences of the genes encoding C- prM (14 sequences), the NS3 helicase domain (7 sequences), the NS5 S-adenosyl methionine transferase domain (7 sequences) and the RNA-dependent RNA polymerase (RdRp) domain (18 sequences) were obtained. Phylogenetic analysis showed that DENV-2 isolates belonged to the Asian/American genotype. In addition, the Asian/American genotype was divided into two clusters, one containing the isolates from 2001 and the other the isolates from 2005–2006 with high bootstrap support of 94%.</p> <p>Conclusion</p> <p>DENV-2 was the predominant serotype in the DF and DHF outbreak from 2005 to 2006 in Oaxaca State as well as in the 2006 outbreak in Veracruz State, with the Asian/American genotype prevalent in both states. Interestingly, DENV-1 and DENV-2 were the only serotypes related to DHF cases. In contrast, DENV-3 and DENV-4 were poorly represented according to epidemiological data reported in Mexico. We found that isoleucine was replaced by valine at residue 106 of protein C in the isolates from these 2005–2006 outbreaks and in those from the 1997, 1998 and 2001 outbreaks in the Caribbean islands. We suggested that this amino acid change may be used as a signature for isolates arising in the Caribbean islands and pertaining to the Asian/American genotype. Other amino acid changes are specific for the Asian/American, Asian and American strains.</p

Lower expression of plasma-derived exosome miR-21 levels in HIV-1 elite controllers with decreasing CD4 T cell count

Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137-0.994, p = 0.049). Also, a negative correlation between miR-21 expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found

Análisis de los espectros de absorción de las películas radiocrómicas EBT2 y EBT3

Objetivo: Analizar los espectros de absorción neta de las películas radiocrómicas EBT2 y EBT3 para describir su influencia en el comportamiento de las curvas de dosis-respuesta. Metodología: Las películas se irradiaron en un acelerador lineal de 6 MV. La obtención de los espectros de absorción neta se realizó con espectrofotómetro UV/VIS. Las curvas de dosis-respuesta se obtuvieron con un escáner, un láser He-Ne y un espectrofotómetro. Resultados: El espectro de absorción de las EBT2 muestra tres bandas de absorción centradas que conservan la posición y aumentan su intensidad en función de la dosis, sin embargo, este comportamiento no se observa en las películas EBT3. La curva dosis-respuesta muestra la máxima sensibilidad utilizando el espectrofotómetro, pero no muestra un comportamiento definido. Implicaciones: Generación de nuevos conocimientos para la creación de nuevos sistemas ópticos capaces de amplificar la sensibilidad de la respuesta de las películas. Originalidad: Mostrar la correlación entre los espectros de absorción neta y su influencia en las curvas dosis-respuesta en tres diferentes sistemas ópticos. Conclusiones: El comportamiento de los espectros de absorción aunado al comportamiento de las curvas dosis-respuesta nos ayuda a descartar el uso de sistemas ópticos que no garanticen un uso clínico confiable

Platelet Count in First Trimester of Pregnancy as a Predictor of Perinatal Outcome

AIM: To rule out maternal and pregnancy factors that may contribute to platelet count (PLT) changes in the first trimester of gestation and examine if there is any association between its levels and adverse perinatal outcome.METHODS: The study population included all patients from the first-trimester visit between 2013-2015 with pregnancy results. Linear multiple regression was constructed to rule out variables that may have a significant contribution to PLT. For each adverse outcome at birth, multiple logistic regression analysis was implemented to estimate the PLT effect.RESULTS: PLT was measured in 6092 patients. There was the significant contribution on PLT in the first trimester from maternal weight, the presence of rheumatologic disease, BHCG levels and MPV. There was a significant association between PLT and abnormal cardiotocography at delivery (OR 1.004; IC95% 1.001 to 1.007) and C-Section due to abnormal CTG (OR 1.005; IC95% 1.002 to 1.008). When adjusted for factors that interact with PLT there was also a significant association with pH at birth &lt; 7.10 and gestational diabetes.CONCLUSIONS: Maternal and pregnancy factors can poorly predict relevant changes in PLT at the first trimester of gestation. PLT at first trimester of pregnancy might predict adverse perinatal outcome in combination with other markers

Individuals with obesity who survive SARS‐CoV‐2 infection have preserved antigen‐specific T cell frequencies

Objective: Obesity is a major risk factor for severe disease in COVID-19, with increased hospitalization, intensive care unit admission, and mortality. This increased impact of COVID-19 in people with obesity (PWO) is likely driven, in part, by the well-described obesity-induced immune dysregulation. Obesity has also been associated with impaired immune memory in many settings, including weakened responses to hepatitis B, tetanus, rabies, and influenza vaccination. Recently, it was reported that PWO who have COVID-19 have reduced IgG antibody titers with defective neutralizing capabilities. However, it remains unknown whether PWO generate durable T cell immunity to SARS-CoV-2. Methods: This study investigated SARS-CoV-2-specific T cell responses in a cohort of 40 patients (n = 20 PWO and n = 20 matched control individuals) who had recovered from COVID-19. T cell (CD4+, CD8+) cytokine responses (IFNγ, TNFα) to SARS-CoV-2 peptide pools (spike, membrane) were determined using multicolor flow cytometry. Results: Circulating T cells specific for SARS-CoV-2 were readily detected in the total cohort. PWO displayed comparable levels of SARS-CoV-2 spike- and membrane-specific T cells, with both T cell subsets responding. Conclusions: These data indicate that PWO who survive COVID-19 generate robust and durable SARS-CoV-2-specific T cell immunity that is equivalent to that seen in those without obesity

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

The Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis