Análisis de la inmunidad de las mujeres infectadas por el virus del papiloma humano y su relación con la lesión intraepitelial cervical / Immunity analysis in women infected with human papillomavirus and its link with cervical intraepithelial lesion (IMVIR study)

Introducción: El objetivo principal es estudiar los marcadores de NK memoria presentes en sangre periférica en pacientes con lesiones cervicales intraepiteliales de alto grado CIN2/3 frente a mujeres sin lesiones o con lesiones de bajo grado. Los objetivos secundarios son estudiar la relación entre el perfil de las células NK memoria y la infección o no por VPH, así como la persistencia viral en las mujeres infectadas por VPH. Material y métodos: Se trata de un estudio observacional prospectivo de una cohorte de mujeres reclutadas desde el año 2019, durante un periodo de 2años, en la unidad del tracto genital inferior en las consultas de ginecología general del Instituto de Salud de la Mujer del Hospital Clínico San Carlos. Los grupos de pacientes incluidos en el estudio son el grupo de estudio: mujeres con infección por VPH y con lesión cervical de alto grado (CIN2+); el grupo control1: mujeres con infección por el VPH sin lesión cervical de alto grado, y el grupo control2: mujeres sin infección por el VPH y sin lesión. Resultados: Durante el estudio se han reclutado 115 pacientes. Nos encontramos con un mayor número de NK «memoria» en pacientes infectadas, tanto en el grupo control1 como en el grupo de estudio, en comparación con el grupo control2. Además, cuando se analizan las pacientes no fumadoras, la expresión de NKp30 es significativamente menor en el grupo control1. Conclusiones: Los resultados ponen de manifiesto una probable menor capacidad para desarrollar funciones adaptativas por parte de las células NK en estas pacientes fumadoras frente a las no fumadoras. Un mejor conocimiento de la biología de las células NK y su papel en la infección por el VPH podría permitir el desarrollo de estrategias para manipular su funcionamiento (inmunoterapias) con un propósito pronóstico y terapéutico.(AU)

Introduction: The main objective is to study the NK markers present in circulating blood in patients with high grade intraepithelial cervical lesions compared with women without lesions or low grade lesions. The secondary objectives of the study are to understand the relationship between the NK memory like cells and the infection with HPV, as well as the persistence of the infection. Methods and materials: It is an observational prospective study that studies women from 2019 for 2years seen in ginecology rooms in Hospital Clínico San Carlos. The group of patients studied are: women with infection by HPV and high grade lesions, women with infection by HPV but no lesion or low grade lesion and women without lesion or infection. Results: We have recruited 115 patients. We have found more memory like NK cells in patients infected by HPV. And when we analyze the non-smoking patients, the expression of NKp30 is lower in patients infected without lesion. Conclusions: The results show that there could be less capacity to generate an adaptative function by NK in smoking patients than in non-smoking. A better knowledge of the NK cells biology and its role in the infection by HPV could allow us to manipulate with a therapeutic and prognostic end.(AU)

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Synergistic impact of N-antigenemia profiled by a rapid antigen test and low anti-S1 antibodies on the risk of hospitalization in COVID-19.

OBJECTIVES: Identifying patients with COVID-19 who are at risk of poor evolution is key to early decide on their hospitalization. We evaluated the combined impact of nucleocapsid (N)-antigenemia profiled by a rapid test and antibodies against the S1 subunit of the SARS-CoV S protein (S1) on the hospitalization risk of patients with COVID-19. METHODS: N-antigenemia and anti-S1 antibodies were profiled at admission to the emergency department in 146 patients with COVID-19 using the Panbio® antigen Rapid Test and the SARS-CoV-2 immunoglobulin G II Quant/SARS-CoV-2 immunoglobulin G assay from Abbott. A multivariable analysis was used to evaluate the impact of these factors on hospitalization. RESULTS: Patients with a positive N-antigen test in plasma and anti-S1 levels <2821 arbitrary units/mL needed hospitalization more frequently (20 of 23, 87%). A total of 20 of 71 (28.2%) of those showing a negative N-antigen test and anti-S1 ≥2821 arbitrary units/mL were hospitalized for 18 of 52 (34.6%) of the patients with only one of these conditions. Patients with a positive N-antigen test and low antibody levels showed an odds ratio, 95% confidence interval, and P-value for hospitalization of 18.21, 2.74-121.18, and 0.003, respectively, and exhibited the highest mortality (30.4%). CONCLUSIONS: Simultaneous profiling of a rapid N-antigen test in plasma and anti-S1 levels could help to early identify patients with COVID-19 needing hospitalization.

Exploring gastric cancer genetics: A turning point in common variable immunodeficiency.

Background: Gastric cancer (GC) stands as a prominent cause of cancer-related mortality and ranks second among the most frequently diagnosed malignancies in individuals with common variable immunodeficiency (CVID). Objective: We sought to conduct a comprehensive, large-scale genetic analysis to explore the CVID-associated germline variant landscape within gastric adenocarcinoma samples and to seek to delineate the transcriptomic similarities between GC and CVID. Methods: We investigated the presence of CVID-associated germline variants in 1591 GC samples and assessed their impact on tumor mutational load. The progression of GC was evaluated in patients with and without these variants. Transcriptomic similarities were explored by matching differentially expressed genes in GC to healthy gastric tissue with a CVID transcriptomic signature. Results: CVID-associated germline variants were found in 60% of GC samples. Our analysis revealed a significant association between the presence of CVID-related genetic variants and higher tumor mutational load in GC (P < .0001); high GC mutational load seems to be linked to immunotherapy response and worse prognosis. Transcriptomic similarities unveiled key genes and pathways implicated in innate immune responses and tumorigenesis. We identified upregulated genes related to oncogene drivers, inflammation, tumor suppression, DNA repair, and downregulated immunomodulatory genes shared between GC and CVID. Conclusions: Our findings contribute to a deeper understanding of potential molecular modulators of GC and shed light on the intricate interplay between immunodeficiency and cancer. This study underscores the clinical relevance of CVID-related variants in influencing GC progression and opens avenues for further exploration into novel therapeutic approaches.

[Addressing sexual violence in health services]. / La violencia sexual y su abordaje en el sistema de salud.

Sexual violence is a very underdetected public health problem, with important short and long-term consequences on physical, mental, social, sexual and reproductive health, which must be taken into account by health services. Health systems are part of the set of resources necessary for a comprehensive approach from the ecological model: prevention and promotion of healthy sexuality with equality, adequate and coordinated care in the event of sexual assault and subsequent support to prevent sequelae. All sexual violence has health consequences, even those that may seem less serious such as sexual harassment or sexual cyberviolence. We must know the needs of the victim and their possible emotional reactions. A risk assessment will be carried out, the victim will be referred to a hospital if necessary and comprehensive and integrated care will be provided. Care and follow-up must focus on the survivor and with professionals trained in trauma to understand the consequences of sexual violence, offer a safe and trusting environment and know how to reinforce their qualities and support.

Sex- and age-related patterns in the use of analgesics in older patients in the emergency department.

BACKGROUND: Treatment of acute pain in older patients is a common challenge faced in emergency departments (EDs). Despite many studies that have investigated chronic analgesic use in the elderly, data on patterns of acute use, especially in EDs, of analgesics according to patient characteristics is scarce. OBJECTIVE: To investigate sex- and age-related patterns of analgesic use in the Spanish EDs and determine differences in age-related patterns according to patient sex. DESIGN: A secondary analysis of the Emergency Department and Elderly Needs (EDEN) multipurpose cohort. SETTING: Fifty-two Spanish EDs (17% of Spanish EDs covering 25% of Spanish population). PARTICIPANTS: All patients' ≥65 years attending ED during 1 week (April 1-7, 2019). Patient characteristics recorded included age, sex, chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and opiates, comorbidity, dependence, dementia, depression, ability to walk and previous falls. Analgesics used in the ED were categorized in three groups: non-NSAID non-opioids (mainly paracetamol and metamizole, PM), NSAIDs, and opiates. OUTCOME MEASURES: Frequency of analgesic use was quantified, and the relationship between sex and age and analgesic use (in general and for each analgesic group) was assessed by unadjusted and adjusted logistic regression and restricted cubic spline models. Interaction between sex and age was explored. MAIN RESULTS: We included 24 573 patients, and 6678 (27.2%) received analgesics in the ED: 5551 (22.6%) PM, 1661 (6.8%) NSAIDs and 937 (3.8%) opiates (1312 received combinations). Analgesics were more frequently used in women (adjusted OR = 1.076, 95%CI = 1.014-1.142), as well as with NSAID (1.205, 1.083-1.341). Analgesic use increased with age, increasing PM and decreasing NSAIDs use. Opiate use remained quite constant across age and sex. Interaction of sex with age was present for the use of analgesics in general ( P  = 0.006), for PM ( P  < 0.001) and for opiates ( P  = 0.033), with higher use of all these analgesics in women. CONCLUSION: Use of analgesics in older individuals in EDs is mildly augmented in women and increases with age, with PM use increasing and NSAIDs decreasing with age. Conversely, opiate use is quite constant according to sex and age. Age-related patterns differ according to sex, with age-related curves of women showing higher probabilities than those of men to receive any analgesic, PM or opiates.

Influence of income on in-hospital mortality in older adults during the first wave of the COVID-19 pandemic: results from the EDEN-33 study. / Influencia de la renta económica en la mortalidad intrahospitalaria de las personas mayores durante la primera ola de la pandemia por COVID-19: resultados del estudio EDEN-33.

OBJECTIVES: To determine whether income was associated with unexpected in-hospital mortality in older patients treated in Spanish public health system hospital emergency departments. MATERIAL AND METHODS: Fifty-one public health system hospital emergency departments in Spain voluntarily participated in the study. Together the hospitals covered 25% of the population aged 65 years or older included in all patient registers during a week in the pre-pandemic period (April 1-7, 2019) and a week during the COVID-19 pandemic (March 30 to April 5, 2020). We estimated a patient's gross income as the amount published for the postal code of the patient's address. We then calculated the standardized gross income (SGI) by dividing the patient's estimated income by the mean for the corresponding territory (Spanish autonomous community). The existence and strength of an association between the SGI and in-hospital mortality was evaluated by means of restricted cubic spline (RCS) curves adjusted for 10 patient characteristics at baseline. Odds ratios (ORs) for each income level were expressed in relation to a reference SGI of 1 (the mean income for the corresponding autonomous community). We compared the COVID-19 and pre-pandemic periods by means of first-order interactions. RESULTS: Of the 35 280 patients attended in the 2 periods, gross income could be ascertained for 21 180 (60%), 15437 in the pre-pandemic period and 5746 during the COVID-19 period. SGIs were slightly higher for patients included before the pandemic (1.006 vs 0.994; P = .012). In-hospital mortality was 5.6% overall and higher during the pandemic (2.8% pre-pandemic vs 13.1% during COVID-19; P .001). The adjusted RCS curves showed that associations between income and mortality differed between the 2 periods (interaction P = .004). Whereas there were no significant income-influenced differences in mortality before the pandemic, mortality increased during the pandemic in the lowest-income population (SGI 0.5 OR, 1.82; 95% CI, 1.32-3.37) and in higher-income populations (SGI 1.5 OR, 1.32; 95% CI, 1.04-1.68, and SGI 2 OR, 1.92; 95% CI, 1.14-3.23). We found no significant differences between patients with COVID-19 and those with other diagnoses (interaction P = .667). CONCLUSION: The gross income of patients attended in Spanish public health system hospital emergency departments, estimated according to a patient's address and postal code, was associated with in-hospital mortality, which was higher for patients with the lowest and 2 higher income levels. The reasons for these associations might be different for each income level and should be investigated in the future.

OBJETIVO: Determinar si el nivel económico durante la primera ola pandémica tuvo una influencia diferente a la esperable en la mortalidad intrahospitalaria de los pacientes mayores atendidos en los servicios de urgencias (SU) de los hospitales públicos españoles. METODO: Cincuenta y un SU públicos españoles que participaron voluntariamente y que dan cobertura al 25% de la población incluyeron todos los registros de pacientes de edad 65 años atendidos durante una semana del periodo preCOVID (1-4-2019 a 7-4-2019) y una semana del periodo COVID (30-3-2020 a 5-4-2020). Se identificó la renta bruta (RB) asignada al código postal de residencia de cada paciente y se calculó la RB normalizada (RBN) dividiendo aquella por la RB media de su comunidad autónoma. La existencia y fuerza de la relación entre RBN y mortalidad intrahospitalaria se determinó mediante curvas spline cúbicas restringidas (SCR) ajustadas por 10 características basales del paciente. Las OR para cada situación económica se expresó en relación con una RBN de 1 (referencia, renta correspondiente a la media de la comunidad autónoma). La comparación entre periodo COVID y no COVID se realizó mediante el estudio de interacción de primer grado. RESULTADOS: De los 35.280 registros de pacientes atendidos en ambos periodos, se disponía de la RB en 21.180 (60%): 15.437 del periodo preCOVID y 5.746 del periodo COVID. La RBN de los pacientes incluidos fue discretamente superior en el periodo preCOVID (1,006 versus 0,994; p = 0,012). La mortalidad intrahospitalaria fue del 5,6%, y fue superior durante el periodo COVID (2,8% versus 13,1%; p 0,001). Las curvas SCR ajustadas mostraron una asociación entre nivel económico y mortalidad diferente entre ambos periodos (p interacción = 0,004): en el periodo preCOVID no hubo diferencias significativas de mortalidad en función de la RBN, mientras que en el periodo COVID la mortalidad se incrementó en rentas bajas (OR = 1,82, IC 95% = 1,32-3,37 para RBN de 0,5) y en rentas altas (OR = 1,32, IC 95% = 1,04-1,68 y OR = 1,92, IC 95% = 1,14-3,23 para RBN de 1,5 y 2, respectivamente), sin diferencias significativas entre pacientes con COVID y con otros diagnósticos (p interacción = 0,667). CONCLUSIONES: Durante la primera ola de la pandemia COVID, la RB asignada al código postal de residencia de los pacientes atendidos en los SU públicos españoles se asoció con la mortalidad intrahospitalaria, que aumentó en pacientes de rentas bajas y altas. Las razones de estas asociaciones pueden ser distintas para cada segmento económico y deben ser investigadas en el fututo.

Inherited Human BCL10 Deficiencies.

Human BCL10 deficiency causes combined immunodeficiency with bone marrow transplantation as its only curative option. To date, there are four homozygous mutations described in the literature that were identified in four unrelated patients. Here, we describe a fifth patient with a novel mutation and summarize what we have learned about BCL10 deficiency. Due to the severity of the disease, accurate knowledge of its clinical and immunological characteristics is instrumental for early diagnosis and adequate clinical management of the patients.

Current Approach in the Management of Secondary Immunodeficiency in Patients with Hematological Malignancies: Spanish Expert Consensus Recommendations.

A Delphi-based survey was designed to assess the opinions of clinical hematologists (n = 17) and clinical immunologists (n = 18) from across Spain on secondary immunodeficiencies (SID) in the management of oncohematological patients. There was 100% agreement on the need to have available guidelines for the management of immunodeficiency in hematological patients; to perform a baseline immunological evaluation in patients with chronic lymphocytic leukemia (CLL), multiple myeloma (MM), lymphoma and hematopoietic stem cell transplantation (HSCT) recipients; and to quantify serum IgG, IgA and IgM levels when SID is suspected. More than 90% agreed on the need for active immunization against seasonal influenza and H1N1, pneumococcus and Haemophilus influenzae. There was a consensus on the monitoring of IgG levels every 3 months (83%) and the need to have available a clinical protocol for the use of IVIG in the management of SID (94%), to monitor trough IgG levels to determine the correct IVIG dose (86%) and to discontinue IVIG after the recovery of IgG levels after 12 months of follow-up (77%). The findings of the present survey may be useful recommendations for hematologists and immunologists to improve the management of SID in daily practice.

Myeloid-derived suppressor cells as a potential biomarker for recurrent pregnancy loss and recurrent implantation failure: Increased levels of MDSCs in recurrent reproductive failure.

PROBLEM: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) represent distinct clinical conditions with established definitions, both of which have been linked to an underlying pro-inflammatory state. This study aimed to explore the levels of monocytic-myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (TReg ) in a cohort of RPL and RIF women and their potential contribution to RPL and RIF. METHOD OF STUDY: One hundred and eight non-pregnant women were evaluated: 40 RPL, 41 RIF, and 27 fertile healthy controls (HC). A multiparametric flow cytometry approach was utilized to measure and quantify the frequency of M-MDSCs and TReg cells. Cytokine levels in plasma samples were evaluated through a multiplex assay. M-MDSCs levels were significantly higher in RPL and RIF patients compared to HC. RESULTS: M-MDSCs levels were significantly higher in RPL (9.4% [7-11.6]) and RIF (8.1% [5.9-11.6]) patients compared to HC (6% [4.2-7.6]). An optimal cut-off of 6.1% for M-MDSCs disclosed a sensitivity of 75.6% and 89.7% and a specificity of 57.7% and 57.7% in RIF and RPL groups, respectively. A significant negative correlation was observed between M-MDSCs and TReg (p = .002, r = -.51). CONCLUSIONS: Our preliminary data allowed us to build a predictive model that may aid as a potential diagnostic tool in the clinic. These findings could provide a better understanding of these pathologies and a better definition of patients that could benefit from personalized treatments to promote pregnancy. Additional exploration and confirmation in distinct study groups are needed to fully assess the diagnostic capabilities of this biomarker.

Specific Cellular and Humoral Response after the Third Dose of Anti-SARS-CoV-2 RNA Vaccine in Patients with Immune-Mediated Rheumatic Diseases on Immunosuppressive Therapy.

OBJECTIVE: Data on cellular and humoral immunogenicity after the third dose of anti-SARS-CoV-2 vaccines in patients with immune-mediated rheumatic diseases (IMRDs) are scarce. Herein, we evaluated the adaptive immune response in IMRD patients treated with different immunosuppressive therapies (conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], biological disease-modifying antirheumatic drugs [bDMARDs], and targeted synthetic disease-modifying antirheumatic drugs [tsDMARDs]) after the booster of the anti-SARS-CoV-2 vaccine to determine whether any drug reduced the vaccine's response. METHODS: A single-center prospective study was conducted, including patients presenting with IMRD and healthy controls (HC). Specific anti-SARS-CoV-2 interferon-gamma (IFN-γ) production was evaluated between 8-12 weeks after the third dose of the SARS-CoV-2 vaccine. In addition, anti-Spike IgG antibody titers were also measured. RESULTS: Samples were obtained from 79 IMRD patients (51 women, 28 men; mean age 57 ± 11.3 years old): 43 rheumatoid arthritis, 10 psoriatic arthritis, 14 ankylosing spondylitis, 10 undifferentiated spondyloarthritis, and 2 inflammatory bowel disease-associated spondyloarthritis (IBD-SpA). In total, 31 HC (mean age 50.9 ± 13.1 years old, 67.7% women) were included in the study. Post-vaccine results displayed positive T-cell immune responses in 68 out of 79 (86.1%) IMRD patients (82.3% of those without prior COVID-19). All HC and IMRDs patients had an antibody response against the SARS-CoV-2 receptor-binding domain; however, the HC response was significantly higher (median of 18,048 AU/mL) than in IMRDs patients (median of 6590.3 AU/mL, p < 0.001). MTX and leflunomide were associated with lower titers of IgG and IFN-γ responses. Among bDMARDs, adalimumab, etanercept, and guselkumab are associated with reduced cellular responses. CONCLUSION: Our preliminary data show that the majority of our IMRD patients develop cellular and humoral responses after the SARS-CoV-2 booster vaccination, emphasizing the relevance of vaccination in this group. However, the magnitude of specific responses was dependent on the immunosuppressive therapy administered. Specific vaccination protocols and personalized decisions about boosters are essential for these patients.

The PID Odyssey 2030: outlooks, unmet needs, hurdles, and opportunities - proceedings from the IPOPI global multi-stakeholders' summit (June 2022).

IPOPI held its first Global Multi-Stakeholders' Summit on 23-24 June 2022 in Cascais, Portugal. This IPOPI initiative was designed to set the stage for a stimulating forward-thinking meeting and brainstorming discussion among stakeholders on the future priorities of the PID community. All participants were actively engaged in the entire Summit, bringing provocative questions to ensure a high level of discussion and engagement, and partnered in identifying the outlooks, unmet needs, hurdles and opportunities of PIDs for 2030. The topics that were covered include diagnosis (e.g., newborn screening [NBS], genomic sequencing- including ethical aspects on the application of genomics on NBS, the role of more accurate and timely diagnostics in impacting personalized management), treatment (e.g., the therapeutic evolution of immunoglobulins in a global environment, new therapies such as targeted therapies, new approaches in curative therapies), the interactions of Primary ID with Secondary ID, Autoinflammatory Diseases and other diseases as the field experiences an incessant evolution, and also the avenues for research in the field of humanities and human sciences such as Patient-Reported Outcome Measures (PROMs), Patient-Reported Experience Measures (PREMs), and Health-Related Quality Of Life (HRQoL). During this meeting, all participants contributed to the drafting of recommendations based on our common understanding of the future opportunities, challenges, and scenarios. As a collection of materials, perspectives and summaries, they are succinct and impactful and may help determine some of the next key steps for the PID community.

Convergence insufficiencyCentral mini-plication of medial rectusDiplopiaConsecutive esotropiaSurgical overcorrection / Detection of anti-SARS-CoV-2 antibodies in tears: Ocular surface immunity to COVID-19

Objetivos Evaluar la presencia de anticuerpos IgA e IgG específicos del SARS-CoV-2 en lágrima de sujetos no vacunados y vacunados contra la COVID-19 con antecedentes de infección SARS-CoV-2. Correlacionar los resultados en lágrima con los de saliva y sangre, datos clínicos y regímenes de vacunación. Métodos Estudio transversal que incluyó a sujetos con antecedentes de infección SARS-CoV-2, tanto no vacunados como vacunados contra la COVID-19. Se recogieron 3muestras: lágrima, saliva y sangre. Se analizaron IgA e IgG frente a S-1 SARS-CoV-2 con ELISA semicuantitativo. Resultados Treinta sujetos, con una edad media 36,4±10, varones 13/30 (43,3%) con historia de infección SARS-CoV-2 leve; 13/30 (43,3%) habían recibido un régimen de 2 dosis y 13/30 (43,3%) un régimen de 3 dosis de vacunación anti-COVID-19, 4/30 (13,3%) no estaban vacunados. Todos los sujetos con vacunación completa presentaron IgA detectable en los 3biofluidos. Entre los no vacunados, se detectó IgA en 3/4 sujetos en lágrima y saliva, mientras que no se detectó IgG. No se observaron diferencias entre la pauta de vacunación de 2 y 3 dosis según los títulos IgA-IgG. Conclusiones Anticuerpos IgA e IgG del SARS-CoV-2 están presentes en lágrimas de pacientes con antecedentes de COVID-19 leve, lo que destaca el papel de la superficie ocular como primera línea de defensa frente a la infección. La mayoría de los sujetos no vacunados presentaron IgA a largo plazo en lágrima y saliva. La inmunización híbrida (infección natural más vacunación) parece potenciar las respuestas IgG mucosas y sistémicas. No se observaron diferencias entre la pauta de 2 y 3 dosis (AU)

Purpose To evaluate the presence of SARS-CoV-2 specific IgA and IgG antibodies in tears of unvaccinated and anti-COVID-19 vaccinated subjects with previous history of SARS-CoV-2 infection. To compare results in tears with those in saliva and serum and correlate with clinical data and vaccination regimens. Methods Cross-sectional study including subjects with a previous history of SARS-CoV-2 infection, both unvaccinated and vaccinated against COVID-19. Three samples were collected: tears, saliva and serum. IgA and IgG antibodies against S-1 protein of SARS-CoV-2 were analyzed with a semi-quantitative ELISA. Results Thirty subjects, mean age 36.4±10, males 13/30 (43.3%) with history of mild SARS-CoV-2 infection were included. 13/30 (43.3%) subjects had received a 2-dose regimen and 13/30 (43.3%) a 3-dose regimen of anti-COVID-19 vaccine, 4/30 (13.3%) subjects were unvaccinated. All the participants with full anti-COVID-19 vaccination (2-or 3-doses) presented detectable anti-S1 specific IgA in all 3biofluids, tears, saliva and serum. Among unvaccinated subjects, specific IgA was detected in 3/4 subjects in tears and saliva, whereas IgG was not detected. Considering IgA and IgG antibodies titers, no differences were observed between the 2- and 3-dose vaccination regimen. Conclusions SARS-CoV-2-specific IgA and IgG antibodies were detected in tears after mild COVID-19, highlighting the role of the ocular surface as a first line of defense against infection. Most naturally infected unvaccinated individuals exhibit long-term specific IgA in tears and saliva. Hybrid immunization (natural infection plus vaccination) appears to enhance mucosal and systemic IgG responses. However, no differences were observed between the 2- and 3-dose vaccination schedule (AU)

Consumo de fármacos anticolinérgicos en ancianos de entre sesenta y cinco y ochenta años consultantes de un servicio de Urgencias / Consumption of anticholinergic drugs in elderly people between 65 and 80 years of age consultants in an emergency service

Fundamentos: Con la edad aumenta el consumo de fármacos, entre ellos los anticolinérgicos. La carga anticolinérgica es predictora decaídas, deterioro cognitivo y mortalidad, y su cálculo resulta de utilidad. El objetivo de este trabajo fue conocer la prevalencia del consumode anticolinérgicos y la carga anticolinérgica según diferentes escalas, así como las variables que influyen en la prevalencia y en la carga.Métodos: Se llevó a cabo un estudio analítico y transversal. La muestra fue obtenida por muestreo por conglomerados (nivel de confianza del95%, precisión del 3%) de pacientes de sesenta y cinco-ochenta años consultantes de un servicio de Urgencias. Las variables dependientes fueronlos fármacos anticolinérgicos consumidos y la carga anticolinérgica calculada mediante diez escalas:Anticholinergic Activity Scale (AAS);Anticholinergic Burden Classification (ABC);Anticholinergic Cognitive Burden Scale (ACB);Anticholinergic Drug Scale (ADS);Anticholinergic Load Scale (ALS);Anticholinergic Risk Scale (ARS);Clinician-Rated Anticholinergic Scale (CrAS);Chew’s scale (Chew);Drug Burden Index (DBI); yDuran’s scale (Duran).Las variables independientes fueron demográficas, patologías crónicas y fármacos consumidos. Como análisis estadístico se realizó la descripciónde variables y el estudio analítico a través de un análisis multivariante (análisis de regresión) para evitar factores de confusión.Resultados: Participaron 456 pacientes, y el consumo medio fue de siete fármacos (IC 95% 6,81-7,59). El 75,2% (IC 95%; 71%-79%) tomaban al-gún anticolinérgico; la media de anticolinérgicos fue de 1,91 (IC 95%; 1,75%-2,08%). Utilizando las escalas simultáneamente, el 58,1%, (IC 95%; 53,4%-62,5%) tenían alta carga anticolinérgica. Las escalas que más riesgo anticolinérgico detectaron fueron DBI (50,7%) y ALS (45,8%) y las que másalta carga, ABC (19,1%) y DBI (17,3%)...

Background: With age increases the consumption of drugs, including anticholinergics. The anticholinergic load is a predictor of falls, cognitiveimpairment and mortality, and its calculation is useful. The objectives of this paper was to know the prevalence of anticholinergic consumption andanticholinergic load according to different scales, and the variables that influence the prevalence and load.Methods: An analytical and cross-sectional study was carried out. The sample was obtained by cluster sampling (95% confidence level, 3%precision) of patients aged sixty-five/eighty consulting an emergency department. Dependent variables were Anticholinergic drugs consumed andanticholinergic load calculated using 10 scales:Anticholinergic Activity Scale (AAS);Anticholinergic Burden Classification (ABC);AnticholinergicCognitive Burden Scale (ACB);Anticholinergic Drug Scale (ADS);Anticholinergic Load Scale (ALS);Anticholinergic Risk Scale (ARS);Clinician-RatedAnticholinergic Scale (CrAS);Chew’s scale (Chew);Drug Burden Index (DBI); andDuran’s scale (Duran). Independent variables were demographics,chronic pathologies and drugs consumed. Statistical analysis: description of variables and analytical study through a multivariate analysis (regres-sion analysis) to avoid confounding factors.Results: 456 patients participated, mean consumption was seven drugs (95% CI 6.81-7.59). 75.2% (95% CI 71%-79%) were taking someanticholinergic; mean of anticholinergics of 1.91 (95% CI 1.75%-2.08%). Using the scales simultaneously, 58.1% (95% CI 53.4%-62.5%) had a highanticholinergic load. The scales that detected the highest anticholinergic risk were DBI (50.7%) and ALS (45.8%), and those with the highest, ABCload (19.1%) and DBI (17.3%)...(AU)

Inherited human ezrin deficiency impairs adaptive immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a group of monogenic diseases that confer susceptibility to infection, autoimmunity, and cancer. Despite the life-threatening consequences of some IEI, their genetic cause remains unknown in many patients. OBJECTIVE: We investigated a patient with an IEI of unknown genetic etiology. METHODS: Whole-exome sequencing identified a homozygous missense mutation of the gene encoding ezrin (EZR), substituting a threonine for an alanine at position 129. RESULTS: Ezrin is one of the subunits of the ezrin, radixin, and moesin (ERM) complex. The ERM complex links the plasma membrane to the cytoskeleton and is crucial for the assembly of an efficient immune response. The A129T mutation abolishes basal phosphorylation and decreases calcium signaling, leading to complete loss of function. Consistent with the pleiotropic function of ezrin in myriad immune cells, multidimensional immunophenotyping by mass and flow cytometry revealed that in addition to hypogammaglobulinemia, the patient had low frequencies of switched memory B cells, CD4+ and CD8+ T cells, MAIT, γδ T cells, and centralnaive CD4+ cells. CONCLUSIONS: Autosomal-recessive human ezrin deficiency is a newly recognized genetic cause of B-cell deficiency affecting cellular and humoral immunity.

[Detection of anti-SARS-CoV-2 antibodies in tears: Ocular surface immunity to COVID-19]. / Detección de anticuerpos anti-SARS-CoV-2 en lágrimas: inmunidad de la superficie ocular frente a COVID-19.

Purpose: To evaluate the presence of SARS-CoV-2 specific IgA and IgG antibodies in tears of unvaccinated and anti-COVID-19 vaccinated subjects with previous history of SARS-CoV-2 infection. To compare results in tears with those in saliva and serum and correlate with clinical data and vaccination regimens. Methods: Cross-sectional study including subjects with a previous history of SARS-CoV-2 infection, both unvaccinated and vaccinated against COVID-19. Three samples were collected: tears, saliva and serum. IgA and IgG antibodies against S-1 protein of SARS-CoV-2 were analyzed with a semi-quantitative ELISA. Results: Thirty subjects, mean age 36.4 ± 10, males 13/30 (43.3%) with history of mild SARS-CoV-2 infection were included. 13/30 (43.3%) subjects had received a 2-dose regimen and 13/30 (43.3%) a 3-dose regimen of anti-COVID-19 vaccine, 4/30 (13.3%) subjects were unvaccinated. All the participants with full anti-COVID-19 vaccination (2-or 3-doses) presented detectable anti-S1 specific IgA in all 3 biofluids, tears, saliva and serum. Among unvaccinated subjects, specific IgA was detected in 3/4 subjects in tears and saliva, whereas IgG was not detected. Considering IgA and IgG antibodies titers, no differences were observed between the 2- and 3-dose vaccination regimen. Conclusions: SARS-CoV-2-specific IgA and IgG antibodies were detected in tears after mild COVID-19, highlighting the role of the ocular surface as a first line of defense against infection. Most naturally infected unvaccinated individuals exhibit long-term specific IgA in tears and saliva. Hybrid immunization (natural infection plus vaccination) appears to enhance mucosal and systemic IgG responses. However, no differences were observed between the 2- and 3-dose vaccination schedule.