A Dried Blood Spot protocol for high-throughput quantitative analysis of SARS-CoV-2 RBD serology based on the Roche Elecsys system.

SARS-CoV-2 spreads pandemically since 2020; in 2021, effective vaccinations became available and vaccination campaigns commenced. Still, it is hard to track the spread of the infection or to assess vaccination success in the broader population. Measuring specific anti-SARS-CoV-2 antibodies is the most effective tool to track the spread of the infection or successful vaccinations. The need for venous-blood sampling however poses a significant barrier for large studies. Dried-blood-spots on filter-cards (DBS) have been used for SARS-CoV-2 serology in our laboratory, but so far not to follow quantitative SARS-CoV-2 anti-spike reactivity in a longitudinal cohort. We developed a semi-automated protocol or quantitative SARS-CoV-2 anti-spike serology from self-sampled DBS, validating it in a cohort of matched DBS and venous-blood samples (n = 825). We investigated chromatographic effects, reproducibility, and carry-over effects and calculated a positivity threshold as well as a conversion formula to determine the quantitative binding units in the DBS with confidence intervals. Sensitivity and specificity reached 96.63% and 97.81%, respectively, compared to the same test performed in paired venous samples. Between a signal of 0.018 and 250 U/mL, we calculated a correction formula. Measuring longitudinal samples during vaccinations, we demonstrated relative changes in titers over time in several individuals and in a longitudinal cohort over four follow-ups. DBS sampling has proven itself for anti-nucleocapsid serosurveys in our laboratory. Similarly, anti-spike high-throughput DBS serology is feasible as a complementary assay. Quantitative measurements are accurate enough to follow titer dynamics in populations also after vaccination campaigns. This work was supported by the Bavarian State Ministry of Science and the Arts; LMU University Hospital, LMU Munich; Helmholtz Center Munich; University of Bonn; University of Bielefeld; German Ministry for Education and Research (proj. nr.: 01KI20271 and others) and the Medical Biodefense Research Program of the Bundeswehr Medical Service. Roche Diagnostics provided kits and machines for analyses at discounted rates. The project is funded also by the European-wide Consortium ORCHESTRA. The ORCHESTRA project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 101016167. The views expressed in this publication are the sole responsibility of the author, and the Commission is not responsible for any use that may be made of the information it contains.IMPORTANCESARS-CoV-2 has been spreading globally as a pandemic since 2020. To determine the prevalence of SARS-CoV-2 antibodies among populations, the most effective public health tool is measuring specific anti-SARS-CoV-2 antibodies induced by infection or vaccination. However, conducting large-scale studies that involve venous-blood sampling is challenging due to the associated feasibility and cost issues. A more cost-efficient and less invasive method for SARS-CoV-2 serological testing is using Dried-Blood-Spots on filter cards (DBS). In this paper, we have developed a semi-automated protocol for quantifying SARS-CoV-2 anti-spike antibodies from self-collected DBS. Our laboratory has previously successfully used DBS sampling for anti-nucleocapsid antibody surveys. Likewise, conducting high-throughput DBS serology for anti-spike antibodies is feasible as an additional test that can be performed using the same sample preparation as the anti-nucleocapsid analysis. The quantitative measurements obtained are accurate enough to track the dynamics of antibody levels in populations, even after vaccination campaigns.

Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

BACKGROUND: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). METHODS: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. RESULTS: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). CONCLUSIONS: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.

The representative COVID-19 cohort Munich (KoCo19): from the beginning of the pandemic to the Delta virus variant.

BACKGROUND: Population-based serological studies allow to estimate prevalence of SARS-CoV-2 infections despite a substantial number of mild or asymptomatic disease courses. This became even more relevant for decision making after vaccination started. The KoCo19 cohort tracks the pandemic progress in the Munich general population for over two years, setting it apart in Europe. METHODS: Recruitment occurred during the initial pandemic wave, including 5313 participants above 13 years from private households in Munich. Four follow-ups were held at crucial times of the pandemic, with response rates of at least 70%. Participants filled questionnaires on socio-demographics and potential risk factors of infection. From Follow-up 2, information on SARS-CoV-2 vaccination was added. SARS-CoV-2 antibody status was measured using the Roche Elecsys® Anti-SARS-CoV-2 anti-N assay (indicating previous infection) and the Roche Elecsys® Anti-SARS-CoV-2 anti-S assay (indicating previous infection and/or vaccination). This allowed us to distinguish between sources of acquired antibodies. RESULTS: The SARS-CoV-2 estimated cumulative sero-prevalence increased from 1.6% (1.1-2.1%) in May 2020 to 14.5% (12.7-16.2%) in November 2021. Underreporting with respect to official numbers fluctuated with testing policies and capacities, becoming a factor of more than two during the second half of 2021. Simultaneously, the vaccination campaign against the SARS-CoV-2 virus increased the percentage of the Munich population having antibodies, with 86.8% (85.5-87.9%) having developed anti-S and/or anti-N in November 2021. Incidence rates for infections after (BTI) and without previous vaccination (INS) differed (ratio INS/BTI of 2.1, 0.7-3.6). However, the prevalence of infections was higher in the non-vaccinated population than in the vaccinated one. Considering the whole follow-up time, being born outside Germany, working in a high-risk job and living area per inhabitant were identified as risk factors for infection, while other socio-demographic and health-related variables were not. Although we obtained significant within-household clustering of SARS-CoV-2 cases, no further geospatial clustering was found. CONCLUSIONS: Vaccination increased the coverage of the Munich population presenting SARS-CoV-2 antibodies, but breakthrough infections contribute to community spread. As underreporting stays relevant over time, infections can go undetected, so non-pharmaceutical measures are crucial, particularly for highly contagious strains like Omicron.

The Prospective COVID-19 Post-Immunization Serological Cohort in Munich (KoCo-Impf): Risk Factors and Determinants of Immune Response in Healthcare Workers.

Antibody studies analyze immune responses to SARS-CoV-2 vaccination and infection, which is crucial for selecting vaccination strategies. In the KoCo-Impf study, conducted between 16 June and 16 December 2021, 6088 participants aged 18 and above from Munich were recruited to monitor antibodies, particularly in healthcare workers (HCWs) at higher risk of infection. Roche Elecsys® Anti-SARS-CoV-2 assays on dried blood spots were used to detect prior infections (anti-Nucleocapsid antibodies) and to indicate combinations of vaccinations/infections (anti-Spike antibodies). The anti-Spike seroprevalence was 94.7%, whereas, for anti-Nucleocapsid, it was only 6.9%. HCW status and contact with SARS-CoV-2-positive individuals were identified as infection risk factors, while vaccination and current smoking were associated with reduced risk. Older age correlated with higher anti-Nucleocapsid antibody levels, while vaccination and current smoking decreased the response. Vaccination alone or combined with infection led to higher anti-Spike antibody levels. Increasing time since the second vaccination, advancing age, and current smoking reduced the anti-Spike response. The cumulative number of cases in Munich affected the anti-Spike response over time but had no impact on anti-Nucleocapsid antibody development/seropositivity. Due to the significantly higher infection risk faced by HCWs and the limited number of significant risk factors, it is suggested that all HCWs require protection regardless of individual traits.

Impact of Omicron Variant Infection on Assessment of Spike-Specific Immune Responses Using the EUROIMMUN Quan-T-Cell SARS-CoV-2 Assay and Roche Elecsys Anti-SARS-CoV-2-S.

The currently prevailing variants of SARS-CoV-2 are subvariants of the Omicron variant. The aim of this study was to analyze the effect of mutations in the Spike protein of Omicron on the results Quan-T-Cell SARS-CoV-2 assays and Roche Elecsys anti-SARS-CoV-2 anti-S1. Omicron infected subjects ((n = 37), vaccinated (n = 20) and unvaccinated (n = 17)) were recruited approximately 3 weeks after a positive PCR test. The Quan-T-Cell SARS-CoV-2 assays (EUROIMMUN) using Wuhan and the Omicron adapted antigen assay and a serological test (Roche Elecsys anti-SARS-CoV-2 anti-S1) were performed. Using the original Wuhan SARS-CoV-2 IGRA TUBE, in 19 of 21 tested Omicron infected subjects, a positive IFNy response was detected, while 2 non-vaccinated but infected subjects did not respond. The Omicron adapted antigen tube resulted in comparable results. In contrast, the serological assay detected a factor 100-fold lower median Spike-specific RBD antibody concentration in non-vaccinated Omicron infected patients (n = 12) compared to patients from the pre Omicron era (n = 12) at matched time points, and eight individuals remained below the detection threshold for positivity. For vaccinated subjects, the Roche assay detected antibodies in all subjects and showed a 400 times higher median specific antibody concentration compared to non-vaccinated infected subjects in the pre-Omicron era. Our results suggest that Omicron antigen adapted IGRA stimulator tubes did not improve detection of SARS-CoV-2-specific T-cell responses in the Quant-T-Cell-SARS-CoV-2 assay. In non-vaccinated Omicron infected individuals, the Wuhan based Elecsys anti-SARS-CoV-2 anti-S1 serological assay results in many negative results at 3 weeks after diagnosis.

Is there a real risk of bacterial infection in patients receiving targeted and biological therapies?

Over the past decades, the advent of targeted and biological therapies has revolutionized the management of cancer and autoimmune, hematological and inflammatory conditions. Although a large amount of information is now available on the risk of opportunistic infections associated with some of these agents, the evidence regarding the susceptibility to bacterial infections is more limited. Biological agents have been shown to entail a variable risk of bacterial infections in pivotal randomized clinical trials and post-marketing studies. Recommendations on risk minimization strategies and therapeutic interventions are therefore scarce and often based on expert opinion, with only a few clear statements for some particular agents (i.e. meningococcal vaccination for patients receiving eculizumab). In the present review the available information regarding the incidence of and risk factors for bacterial infection associated with the use of different groups of biological agents is summarized according to their mechanisms of action, and recommendations based on this evidence are provided. Additional information coming from clinical research and real-world studies is required to address unmet questions in this emerging field.

Mortalidad y desenlaces clínicos en pacientes críticamente enfermos con infecciones por bacterias productoras de carbapenemasas en un hospital de alta complejidad en Bogotá, Colombia / Mortality and clinical outcomes in critically ill patients with carbapenemase-producing bacteria in a tertiary-care hospital in Bogotá, Colombia

Resumen Introducción: Los microorganismos capaces de producir carbapenemasas vienen incrementándose a nivel mundial y se han convertido en un problema de salud pública global. En Colombia actualmente la resistencia a carbapenémicos en las unidades de cuidado intensivo está aumentando y se desconoce su impacto en desenlaces clínicos. Objetivos: Determinar las características demográficas, clínicas, y los desenlaces de los pacientes adultos en estado crítico con infección por microorganismos productores de carbapenemasas en una unidad de cuidado intensivo polivalente de una institución de alta complejidad. Métodos: Estudio observacional, descriptivo y retrospectivo, incluyendo pacientes con infección por bacterias resistentes a carbapenémicos, ingresados a la unidad de cuidado intensivo entre el 1 de Enero de 2014 y el 1 de Enero de 2018. Se excluyeron los pacientes colonizados. Se evaluaron complicaciones clínicas, estancia en UCI y hospitalaria, así como la mortalidad en UCI y hospitalaria. Resultados: Se incluyó 58 pacientes. La mortalidad global fue de 67,2%, de los cuales 55,17% murió durante su estancia en la unidad de cuidado intensivo y 12.06% en hospitalización. La mediana de estancia en la unidad de cuidado intensivo fue de 18 días (RIQ 4-28). La causa más frecuente de mortalidad fue choque séptico en 51% y las complicaciones más comunes fueron lesión renal aguda y delirium en un 55,2% y 43,1%, respectivamente. La mediana de estancia en la UCI fue de 18 días (RIQ 4-28). Conclusiones: Las infecciones por bacterias resistentes a carbapenémicos en pacientes críticamente enfermos se relacionan con altas tasas de mortalidad, complicaciones y estancia prolongada en UCI

Abstract Introduction: Microorganisms able to produce carbapenemases are spreading worldwide and have become a concerning global public-health problem. In Colombia, the Gram-negative resistance to carbapenems at intensive care units is currently increasing and its impact on clinical outcomes is not well known. Objectives: To determine the demographic, clinical characteristics and outcomes of critically ill adult patients with infection by carbapenemase producing bacteria in a polyvalent intensive care unit of a highly complex institution. Methods: Single-center retrospective, descriptive observational study including critically ill adult patients infected by carbapenemase-producing bacteria and transferred to a polyvalent intensive care unit from January 1th 2014 to January 1th 2018. Known colonized patients were excluded. Clinical complications, ICU and in-hospital days of stay were evaluated, as ICU and in-hospital mortality. Results: A total of 58 patients were included. Overall mortality was 67.2%, of which 55.17% died during their stay in the intensive care unit and 12.06% in hospitalization. The median stay in the intensive care unit was 18 days (IQR 4-28). The most frequent cause of death was septic shock in 51% and the most common complications were acute renal injury and delirium in 55.2% and 43.1%, respectively. The median stay in the ICU was 18 days (RIQ 4-28). Conclusions: Infections caused by carbapenem-resistant bacteria in critically ill patients are associated with high mortality rates, complications and long stay in ICU.

Is there a real risk of bacterial infection in patients receiving targeted and biological therapies?

Over the past decades, the advent of targeted and biological therapies has revolutionized the management of cancer and autoimmune, hematological and inflammatory conditions. Although a large amount of information is now available on the risk of opportunistic infections associated with some of these agents, the evidence regarding the susceptibility to bacterial infections is more limited. Biological agents have been shown to entail a variable risk of bacterial infections in pivotal randomized clinical trials and post-marketing studies. Recommendations on risk minimization strategies and therapeutic interventions are therefore scarce and often based on expert opinion, with only a few clear statements for some particular agents (i.e. meningococcal vaccination for patients receiving eculizumab). In the present review the available information regarding the incidence of and risk factors for bacterial infection associated with the use of different groups of biological agents is summarized according to their mechanisms of action, and recommendations based on this evidence are provided. Additional information coming from clinical research and real-world studies is required to address unmet questions in this emerging field.

Proceedings from the CIHLMU Symposium 2020 on "eHealth: Trends and innovations".

Electronic Health (eHealth) is the use of information and communication technologies for health and plays a significant role in improving public health. The rapid expansion and development of eHealth initiatives allow researchers and healthcare providers to connect more effectively with patients. The aim of the CIHLMU Symposium 2020 was to discuss the current challenges facing the field, opportunities in eHealth implementation, to share the experiences from different healthcare systems, and to discuss future trends addressing the use of digital platforms in health. The symposium on eHealth explored how the health and technology sector must increase efforts to reduce the obstacles facing public and private investment, the efficacy in preventing diseases and improving patient quality of life, and the ethical and legal frameworks that influence the proper development of the different platforms and initiatives related to the field. This symposium furthered the sharing of knowledge, networking, and patient/user and practitioner experiences in low- and middle-income countries (LMIC) in both public and private sectors.

Miocarditis por gram negativos / Gram-Negative Myocarditis

Resumen Objetivo: describir las características epidemiológicas, clínicas y microbiológicas de los pacientes que cursan con miocarditis por Enterobacterias. Métodos: se realizó una revisión sistemática de la literatura, en la que se incluyeron Pubmed, Ovid, Scopus, SciELO y LILACS sin exclusión por tipo de idioma. La población objetivo de estudio fueron los pacientes con diagnóstico de infección bacteriana por bacilo gram negativo mediante cultivo, técnicas moleculares o histopatología, y quienes presentaban biopsia de miocardio o, en su defecto, resonancia magnética cardiaca con hallazgos sugestivos de miocarditis. Resultados: se encontraron 742 artículos, de los cuales se incluyeron 24; en estos se reportaron 27 pacientes. La edad promedio fue de 31 años. El 81% de los pacientes eran de sexo masculino. El síntoma principal fue diarrea (80%), seguido de fiebre (53%) y dolor torácico (38%). El 37% de los pacientes fallecieron. El hallazgo más común en el electrocardiograma fue la elevación del segmento ST (36,7%). En quienes se realizó ecocardiograma se encontraron anormalidades en 50% de los casos, siendo más frecuente la disminución en la fracción de eyección. El microorganismo más común fue el Campylobacter jejuni, seguido por Salmonela sp. Conclusiones: la miocarditis causada por enterobacterias es más frecuente en pacientes adultos jóvenes de sexo masculino. Los síntomas gastrointestinales suelen estar presentes al momento de la presentación clínica. El diagnóstico requiere de alta sospecha clínica teniendo en cuenta que las anormalidades eléctricas y en ecocardiograma no se encuentran en todos los pacientes.

Abstract Objective: To describe the epidemiological, clinical, and microbiological characteristics of patients with myocarditis due to Enterobacteria. Methods: A systematic review was carried out on the literature, which included Pubmed, Ovid, Scopus, SciELO, and LILACS, with no exclusions due to language. The target population of the study were patients with a diagnosis of bacterial infection due to gram negative bacillus by means of a culture, or using molecular or histopathology technique. They also had to have had a myocardial biopsy or, if not, a cardiac magnetic resonance scan with findings suggestive of myocarditis. Results: Out of a total of 742 articles found, 24 of these, in which 27 patients were described, were included. The mean age was 31 years, and 81% were male. The main symptom was diarrhoea (80%), followed by fever (53%), and chest pain (38%). More than one-third (37%) of the patients died. The most common finding on the electrocardiogram (ECG) was elevation of the ST segment (36.7%). Abnormalities were found in 50% of the cases, on whom a cardiac ultrasound was performed, with a decrease in the ejection fraction being the most common. The most common microorganism was Campylobacter jejuni, followed by Salmonella spp. Conclusions: Myocarditis caused by enterobacteria is most common in young male patients. The gastrointestinal symptoms are usually present from the clinical onset. The diagnosis requires a high clinical suspicion, taking into account that the abnormalities in the ECG and cardiac ultrasound are not found in all patients.

Perfil de resistencia de la Salmonella sp durante un periodo de tres años en un hospital de Colombia / Resistance Profile of Salmonella SP During a Period of Three Years in a Hospital of Colombia / Perfil de resistência de Salmonella SP durante um período de três años em um hospital da Colômbia

Resumen Introducción: en Colombia, del 2000 al 2012, se describió un aumento progresivo en la resistência a betalactámicos y quinolonas en los aislamientos de Salmonella sp. A partir de esta fecha se desconoce la evolución de las tasas de resistencia en el país. El objetivo de este estúdio fue describir el perfil de suscep tibilidad durante el periodo 2014-2017 así como evaluar la asociación entre las características clínicas y sociodemográficas de la población con los patrones de resistencia de Salmonella sp. Materiales y méto dos: estudio de corte transversal del 2014 al 2017, realizado en la Fundación Cardioinfantil en mayores de 18 años, con aislamiento de Salmonella sp en cualquier tipo de muestra biológica. Resultados: se encontraron sesenta casos, ningún aislamiento fue resistente a quinolonas, uno mostró resistencia a ampicilina y uno se caracterizó como ; el 95 % tenia perfil de susceptibilidad usual. No se encontró asociación entre las variables estudiadas y la presencia de resistencia. Conclusión: los resultados pueden reflejar un cambio en el perfil de susceptibilidad de Salmonella sp en Colombia, con una disminución en la resistencia a betalactámicos y quinolonas a partir del 2014. Sin embargo, se requiere una mayor muestra poblacional para corroborar esta hipótesis.

Abstract Objective: In Colombia, from 2000 to 2012, a progressive increase in resistance to beta-lactams and quinolones was described in isolates of Salmonella As of this date, the evolution of resistance rates in the country is unknown. The objective of this study is to describe the susceptibility profile from 2014 to 2017, as well as to evaluate the association between the clinical and sociodemographic characteristics of the population with the resistance patterns of Salmonella Materials and methods: The study is a cross-sectional study between 2014 and 2017 at the Fundación Cardioinfantil, in patients over 18 years of age with Salmonella in any type of biologic sample. Results: The authors found 60 cases, no isolate was resistant to quinolones. One showed resistant to ampicillin, and añother one was characterized as amp-C; 95% had a usual susceptibility profile. No association was found between the variables studied and the presence of resistance. Conclusion: The results may reflect a change in the susceptibility profile of Salmonella in Colombia, with a decrease in resistance to beta-lactams and quinolones as of 2014; however, a larger population sample is required to corroborate this hypothesis.

Resumo Objetivo: Na Colômbia do ao 2000 ao 2012 se descreveu um aumento progressivo na resistência a beta-lactâmicos e quinolonas nos isolamentos de Salmonella sp. A partir desta data se desconhece a evolução das taxas de resistência no país. O objetivo deste estudo é descrever o perfil de susceptibilidade do ao 2014 ao 2017, assim como avaliar a associação entre as características clínicas e sociodemográficas da população com os patrões de resistência Salmonella sp. Materiais e métodos: Estudo de corte transversal do ano 2014 ao ao 2017 realizado na Fundación Cardioinfantil em maiores de 18 ao anos com isolamento de Salmonella sp, em qualquer tipo de amostra biológica. Resultados: se encontraram 60 casos, nenhum isolamento foi resistente a quinolonas, um mostrou resistência a ampicilina e um se caracterizou como AMP-C, o 95 % tinha perfil de susceptibilidade usual. Não se encontrou associação entre as variáveis estudadas e a presença de resistência. Conclusão: Os resultados podem refletir uma mudança no perfil de susceptibilidade de Salmonella sp. Na Colômbia, com uma diminuição na resistência a beta-lactâmicos e quinolonas a partir do año 2014, no entanto se requere uma maior amostra populacional para corroborar esta hipótese.

A Patient With Human Herpesvirus 8-Positive Multicentric Castleman's Disease Who Met Criteria for TAFRO Syndrome: Controversy in Practice?

Multicentric Castleman's disease (MCD) is a known entity with characteristics of lymphoproliferative syndrome, characterized by cytokine activation. Its association with human immunodeficiency virus (HIV) is frequently described, as well as its positivity for human herpesvirus 8 (HHV-8). However, some negative patients for the latter (called idiopathic MCD), may have an aggressive spectrum of the disease (characterized by the presence of cytopenia, renal failure, anasarca and organomegaly), known as TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly). We present the case of a young patient recently diagnosed with HIV infection, in whom MCD was found, and with an aggressive course despite treatment, who met criteria for TAFRO syndrome despite HHV-8 positivity.

First Case of Acquired Hemophilia B in a Patient with HIV Infection: Case Report and Literature Review.

Acquired hemophilia B is a rare bleeding disorder in which circulating specific antibodies inhibit the coagulation factors. Usually, it is associated with autoimmune diseases, malignancy and some infections such as hepatitis B (HBV) and C (HCV) viruses. The association with the human immunodeficiency virus (HIV) is rare. We present the first case of hemophilia B acquired in a patient with HIV. A 36-year-old woman with a history of HIV infection stage 3 acquired immunodeficiency syndrome (AIDS) (CDC 2014) and glomerulopathy secondary to HIV. She consulted for subacute non-dysenteric diarrhea. During her hospitalization, bacteremia by methicillin-sensitive Staphylococcus aureus (S.aureus) was documented, requiring hemodialysis catheter replacement with profuse bleeding during the procedure. The coagulation tests showed prolonged activated partial thromboplastin time (aPTT), normal prothrombin time (PT), mixing test with Rosner index: 8.8%, negative lupus anticoagulant, and specific tests for normal factor VIII and XI. The activity of factor IX was <50% and the inhibitor was increased, which confirms the diagnosis of hemophilia B. Acquired hemophilia B in a patient with HIV infection is not a frequent association; it should be suspected in the context of bleeding with prolonged aPTT.

Viral infections in the biologic therapy era.

INTRODUCTION: The development of biologic therapies for treating patients with rheumatic, hematologic, or oncological diseases has increased in the last few years, spreading their use in clinical practice. Areas covered: Clinical experience has evidenced substantial risks for some viral infections and/or reactivations such as viral hepatitis, herpetic infections, and other viruses, as a consequence of specific immune pathway blockages. Biological therapies produce a variable risk of reactivation of viral infections, which is particularly uncertain in the case of the most recently introduced agents. Here we make an extensive review of the viral infections associated with the use of biological drugs and provide a series of recommendations for its prevention and management. Expert commentary: To prevent these infections/reactivations, the practitioner must be aware of the infection-risk profile, performing accurate screening during and after the use of any biologic agent. In some instances, expert recommendations are made for some therapies, while in other scenarios recommendations have not yet been defined making experimental and clinical research an essential approach to elucidate multiple issues yet not resolved in this field.

Endocarditis por Lactobacillus rhamnosus en un paciente con válvula aórtica bicúspide: ¿implicación potencial del consumo de probióticos? / Endocarditis due to Lactobacillus rhamnosus in a patient with bicuspid aortic valve: Potential role for the consumption of probiotics?

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