Effectiveness of Mepolizumab in Patients with Severe Eosinophilic Asthma with/without Nasal Polyposis: A Real-Life Study.

INTRODUCTION: Asthma is one of the most common chronic diseases and affects around 334 million people worldwide. The estimated prevalence of severe asthma is 3-10% of the asthmatic population. Mepolizumab has demonstrated efficacy in reducing exacerbations, oral corticosteroid use, and improving quality of life, asthma control, and lung function in patients with severe eosinophilic asthma (SEA). Our study aimed to check the response to mepolizumab in a series of severe asthma patients regarding exacerbations, oral corticosteroid use, asthma control, quality of life, and lung function and to compare the response between patients with and without nasal polyps. METHOD: This is a retrospective, multicenter study of RE-ASGRAMUR (Register of Severe Asthma of the Region of Murcia) performed in eight hospitals of the Region of Murcia (Spain) under routine clinical practice conditions. We included patients diagnosed with SEA who completed at least 1 year of treatment with mepolizumab. We analyzed clinical characteristics, drug tolerance, and effectiveness: exacerbations, ACT, miniAQLQ, forced expiratory volume in 1 s (FEV1), and use of oral corticosteroids. We also compared the results between patients with and without nasal polyps. RESULTS: The median of exacerbations before treatment was 3 and decreased to 0 after treatment (mean decrease of 77.4%). The median diary oral prednisone intake was 15 mg before treatment and 5 mg after treatment (mean 56% reduction). We have obtained a significant improvement in other variables: ED visits and hospitalizations, asthma control (ACT), quality of life (miniAQLQ), and lung function (FEV1). Thirty-four out of 70 patients (48.57%) fulfilled the criteria of super-responder, and 17 out of 70 (24.29%) had a complete response. More patients in the group with nasal polyps fulfilled the criteria of super-responder and complete response to mepolizumab. CONCLUSIONS: Mepolizumab is a safe and effective treatment for SEA patients, improving exacerbations, oral corticosteroid intake, asthma control, quality of life, and lung function. In patients with associated nasal polyposis, there is a statistically significant higher proportion of super-responders and complete responders.

Screening blood donors for malaria, can we increase the number of eligible donors? An observational retrospective study.

BACKGROUND: In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. METHODS: An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015-2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. RESULTS: During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33-48); median time to consultation was 32 months (IQR:12.5-110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). CONCLUSIONS: None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

Sex estimation by CT image analysis of the rib cage in a Mediterranean population.

Sexual dimorphism in the human species is key to the development of sex estimation techniques in the human skeleton. This dimorphism is manifested, as in other regions of the skeleton, in the bones that constitute the thoracic cage, according to the existing bibliography. In this aspect, the study of the human skeleton through 3D images has also proved to be useful for the development and validation of sex estimation methodologies for the reconstruction of the osteobiological profile.For this purpose, a sample of 240 thoracic CT scans of adult individuals was selected from a collection of 3D images belonging to the University of Granada, provided by the Castilla-La Mancha Health Service (SESCAM). Different measurements of the thoracic bones (ribs R2 to R5 width, sternum length and width, and clavicles width) have been taken with OsiriX software, with the aim of developing discriminant functions for sex estimation.The obtained results are positive, allowing sex estimation through 3D images of the thorax with up to 89.6% accuracy through discriminant functions, which shows the usefulness of image analysis for the reconstruction of the osteobiological profile.

Cognitive reserve and executive functions in dual task gait performance in Parkinson's disease.

A higher level of education was correlated with less severe motor impairment in Parkinson's Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study's findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD.

Author Correction: Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.

In this Article, the sentence: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent coding mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).", should have read: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).". This has been corrected online. In Extended Data Fig. 6a and b, which show the number of point mutations identified per sample and the mutational signatures, all sequence variants (including non-coding mutations) are shown. Fig. 2d also presents all variants compared to human mutations. In the Supplementary Information to this Amendment, we now provide the comparisons of all variants and coding variants to human mutations.

Nonequilibrium relaxation of soft responsive colloids.

Stimuli-responsive macromolecules display large conformational changes during their dynamics, sometimes switching between states. Such a multi-stability is useful for the development of soft functional materials. Here, we introduce a mean-field dynamical density functional theory for a model of responsive colloids to study the nonequilibrium dynamics of a colloidal dispersion in time-dependent external fields, with a focus on the coupling of translational and conformational dynamics during their relaxation. Specifically, we consider soft Gaussian particles with a bimodal size distribution between two confining walls with time-dependent (switching-on and off) external gravitational and osmotic fields. We find a rich relaxation behavior of the systems in excellent agreement with particle-based Brownian dynamics computer simulations. In particular, we find time-asymmetric relaxations of integrated observables (wall pressures, mean size, and liquid center-of-mass) for activation/deactivation of external potentials, respectively, which are tunable by the ratio of translational and conformational diffusion time scales. Our work thus paves the way for studying the nonequilibrium relaxation dynamics of complex soft matter with multiple degrees of freedom and hierarchical relaxations.

Sexuality and self-concept of morbidly obese women who are sexually attracted to men after bariatric surgery: a phenomenological study.

BACKGROUND: Morbid Obesity (MO) is a public health problem that affects a person's physical, psychological and sexual well-being. Women with MO are affected by their body image and self-concept, and obesity stigma may affect women in social and sexual relationships. OBJECTIVE: To describe and understand the experiences of morbidly obese heterosexual women (who are sexually attracted to men) in relation to their body image and sexuality after bariatric surgery. METHODOLOGY: Qualitative study using Merleau-Ponty's hermeneutic phenomenology as a philosophical framework. Data collection took place between 2020 and 2021 in a southern Spanish province. A total of 22 in-depth interviews were conducted using open-ended questions until data saturation was reached. RESULTS: Two main themes were identified: (1) "Escaping from a cruel environment": weight loss to increase self-esteem; with the sub-themes: 'I love myself now', and 'Body image and social relationships; a vicious circle; (2) "Now, I am truly me": accepting my body to reclaim my sexuality, with the sub-themes: 'The body as the focal point of sexuality', and 'When regaining your sex drive reignites your sex life and relationship'. CONCLUSION: Weight loss and body acceptance radically change morbidly obese women's sex lives after bariatric surgery. They rediscover their bodies, have increased self-esteem, and see improvements in their social relationships and sexuality. These women feel seen, loved and desired, and now value their body image and femininity. As they go through continuous improvements following bariatric surgery, they gradually regain self-esteem, acceptance of their bodies and control over their sex life. Even though the women's partners benefit from these improvements, they seem to be afraid of being left.

Obesity is a problem that affects women's physical, psychological and sexual well-being, as well as their social relationships. It is important to explore and understand the experiences of heterosexual women regarding their body and sexuality. After other treatments, women undergo surgery to reduce their obesity. After bariatric surgery women feel happier about themselves, experience less stigma and progressively recover their social and sex lives.

Allosteric couplings upon binding of RfaH to transcription elongation complexes.

In every domain of life, NusG-like proteins bind to the elongating RNA polymerase (RNAP) to support processive RNA synthesis and to couple transcription to ongoing cellular processes. Structures of factor-bound transcription elongation complexes (TECs) reveal similar contacts to RNAP, consistent with a shared mechanism of action. However, NusG homologs differ in their regulatory roles, modes of recruitment, and effects on RNA synthesis. Some of these differences could be due to conformational changes in RNAP and NusG-like proteins, which cannot be captured in static structures. Here, we employed hydrogen-deuterium exchange mass spectrometry to investigate changes in local and non-local structural dynamics of Escherichia coli NusG and its paralog RfaH, which have opposite effects on expression of xenogenes, upon binding to TEC. We found that NusG and RfaH regions that bind RNAP became solvent-protected in factor-bound TECs, whereas RNAP regions that interact with both factors showed opposite deuterium uptake changes when bound to NusG or RfaH. Additional changes far from the factor-binding site were observed only with RfaH. Our results provide insights into differences in structural dynamics exerted by NusG and RfaH during binding to TEC, which may explain their different functional outcomes and allosteric regulation of transcriptional pausing by RfaH.

Online Media Use and COVID-19 Vaccination in Real-World Personal Networks: Quantitative Study.

BACKGROUND: Most studies assessing the impact of online media and social media use on COVID-19 vaccine hesitancy predominantly rely on survey data, which often fail to capture the clustering of health opinions and behaviors within real-world networks. In contrast, research using social network analysis aims to uncover the diverse communities and discourse themes related to vaccine support and hesitancy within social media platforms. Despite these advancements, there is a gap in the literature on how a person's social circle affects vaccine acceptance, wherein an important part of social influence stems from offline interactions. OBJECTIVE: We aimed to examine how online media consumption influences vaccination decisions within real-world social networks by analyzing unique quantitative network data collected from Romania, an Eastern European state and member of the European Union. METHODS: We conducted 83 face-to-face interviews with participants from a living lab in Lerești, a small rural community in Romania, using a personal network analysis framework. This approach involved gathering data on both the respondents and individuals within their social circles (referred to as alters). After excluding cases with missing data, our analysis proceeded with 73% (61/83) of the complete personal networks. To examine the hierarchical structure of alters nested within ego networks, we used a mixed multilevel logistic regression model with random intercepts. The model aimed to predict vaccination status among alters, with the focal independent variable being the respondents' preferred source of health and prevention information. This variable was categorized into 3 types: traditional media, online media (including social media), and a combination of both, with traditional media as the reference category. RESULTS: In this study, we analyzed 61 personal networks, encompassing between 15 and 25 alters each, totaling 1280 alters with valid data across all variables of interest. Our primary findings indicate that alters within personal networks, whose respondents rely solely on online media for health information, exhibit lower vaccination rates (odds ratio [OR] 0.37, 95% CI 0.15-0.92; P=.03). Conversely, the transition from exclusive traditional media use to a combination of both traditional and online media does not significantly impact vaccination rate odds (OR 0.75, 95% CI 0.32-1.78; P=.52). In addition, our analysis revealed that alters in personal networks of respondents who received the vaccine are more likely to have received the vaccine themselves (OR 3.75, 95% CI 1.79-7.85; P<.001). CONCLUSIONS: Real-world networks combine diverse human interactions and attributes along with consequences on health opinions and behaviors. As individuals' vaccination status is influenced by how their social alters use online media and vaccination behavior, further insights are needed to create tailored communication campaigns and interventions regarding vaccination in areas with low levels of digital health literacy and vaccination rates, as Romania exposes.

Key aspects in the development of gender identity and sexual orientation according to trans and gender diverse people: a qualitative approach.

For decades, the sexuality of trans and gender diverse people has been researched from a pathologising and medical perspective. This approach makes assumptions about the experiences of trans people, limiting concern for unique and individual experiences, especially for those with non-binary or gender diverse identities. A growing number of articles however are beginning to take the viewpoints of trans people seriously, taking into consideration their unique experiences and insights within the context of sexual and romantic relationships. This study examines the development of gender identity and sexual orientation of a group of trans individuals in Spain. Thirteen self-identified trans participants were interviewed about their sexual orientation, gender identity and the interplay between both those aspects. A constructivist grounded theory methodology was employed to analyse the data. Five major categories were identified: reinterpreting experiences through identification with gender identity and sexual orientation; questioning gender identity and sexual orientation norms; understanding the interplay between gender identity and sexual orientation; developing as a couple; and building a community. Findings highlight the dynamic and relational nature of gender identity and sexual orientation and provide further insight into the interaction of these aspects in the development of trans and gender diverse identities.

Optical Flow-Based Obstacle Detection for Mid-Air Collision Avoidance.

The sky may seem big enough for two flying vehicles to collide, but the facts show that mid-air collisions still occur occasionally and are a significant concern. Pilots learn manual tactics to avoid collisions, such as see-and-avoid, but these rules have limitations. Automated solutions have reduced collisions, but these technologies are not mandatory in all countries or airspaces, and they are expensive. These problems have prompted researchers to continue the search for low-cost solutions. One attractive solution is to use computer vision to detect obstacles in the air due to its reduced cost and weight. A well-trained deep learning solution is appealing because object detection is fast in most cases, but it relies entirely on the training data set. The algorithm chosen for this study is optical flow. The optical flow vectors can help us to separate the motion caused by camera motion from the motion caused by incoming objects without relying on training data. This paper describes the development of an optical flow-based airborne obstacle detection algorithm to avoid mid-air collisions. The approach uses the visual information from a monocular camera and detects the obstacles using morphological filters, optical flow, focus of expansion, and a data clustering algorithm. The proposal was evaluated using realistic vision data obtained with a self-developed simulator. The simulator provides different environments, trajectories, and altitudes of flying objects. The results showed that the optical flow-based algorithm detected all incoming obstacles along their trajectories in the experiments. The results showed an F-score greater than 75% and a good balance between precision and recall.

Promoting the empowerment and emancipation of community-dwelling older adults with chronic multimorbidity through a home visiting programme: a hermeneutical study.

INTRODUCTION: Nurse-led preventive home visiting programmes can improve health-related outcomes in community-dwelling older adults, but they have not proven to be cost-effective. Home visiting programmes led by nursing students could be a viable alternative. However, we do not know how community-dwelling older adults with chronic multimorbidity experience home visiting programmes in which nursing students carry out health promotion activities. The aim of the study is to understand how community-dwelling older adults with chronic multimorbidity experience a home visiting programme led by nursing students. METHODS: A qualitative study based on Gadamer's hermeneutics. Thirty-one community-dwelling older adults with chronic multimorbidity were interviewed in-depth. Fleming's method for conducting hermeneutic, Gadamerian-based studies was followed and ATLAS.ti software was used for data analysis. RESULTS: Two main themes were generated: (1) 'The empowering experience of a personalised health-promoting intervention', and (2) 'The emancipatory effect of going beyond standardised self-care education'. CONCLUSIONS: The home visiting programme contributed to the community-dwelling older adults feeling more empowered to engage in health-promoting self-care behaviours. It also improved the older adults' sense of autonomy and self-efficacy, while reducing their loneliness and addressing some perceived shortcomings of the healthcare system. CLINICAL RELEVANCE: Older adults participating in a home visiting programme led by nursing students feel empowered to implement self-care behaviours, which has a positive impact on their perceived health status. Nurse leaders and nursing regulatory bodies could collaborate with nursing faculties to integrate preventive home visiting programmes led by nursing students into the services offered to community-dwelling older adults with chronic multimorbidity.

Caspofungin formulations for buccal and sublingual mucosae anti-fungal infections: physicochemical characterization, rheological analysis, release and ex vivo permeability profiles.

AIM: Oral candidiasis is often challenging due to limited effectiveness of topical treatments. This study aimed to develop novel caspofungin formulations for administration onto the oral mucosa to enhance drug retention and efficacy. METHOD: Five caspofungin (2%, w/v) formulations were developed to assess their permeability, retention and mucoadhesiveness. Ex vivo permeability assays were performed on buccal and sublingual mucosae, and histological analyses conducted to evaluate tissue tolerance. RESULTS: Formulation composed of chitosan demonstrated the highest retention in both buccal (5183.24 ± 587.32 µg/cm2) and sublingual (1090.72 ± 110.26 µg/cm2) mucosae. Other formulations exhibited significantly lower retention, ranging from 7.53 ± 0.81 to 1852.10 ± 193.24 µg/cm2 in buccal mucosa and 1.64 ± 0.14 to 317.74 ± 31.78 µg/cm2 in sublingual mucosa. Chitosan-based formulation exhibited the highest mucoadhesive strength, with values of 5179.05 ± 31.99 mN/cm2 for buccal and 7026.10 ± 123.41 mN/cm2 for sublingual mucosae, and also superior extensibility, which facilitates application in the oral cavity. All formulations showed antifungal activity against Candida spp., and histological analyses revealed minor epithelial alterations. CONCLUSION: The developed formulations offer distinct advantages for treating oral candidiasis, with chitosan formulation emerging as the most promising due to its superior retention, mucoadhesion force, and spreadability, making it a potential candidate for further clinical investigation.

Contribution of Low CD4 Cell Counts and High Human Immunodeficiency Virus (HIV) Viral Load to the Efficacy of Preferred First-Line Antiretroviral Regimens for Treating HIV Infection: A Systematic Review and Meta-Analysis.

We assessed whether low CD4 count and high viral load (VL) affect the response to currently preferred ART. We performed a systematic review of randomized, controlled clinical trials that analyzed preferred first-line ART and a subgroup analysis by CD4 count (≤ or >200 CD4/µL) or VL (≤ or >100 000 copies/mL). We computed the odds ratio (OR) of treatment failure (TF) for each subgroup and individual treatment arm. Patients with ≤200 CD4 cells or VL ≥100 000 copies/mL showed an increased likelihood of TF at 48 weeks: OR, 1.94; 95% confidence interval (CI): 1.45-2.61 and OR, 1.75; 95% CI: 1.30-2.35, respectively. A similar increase in the risk of TF was observed at 96 weeks. There was no significant heterogeneity regarding integrase strand transfer inhibitor or nucleoside reverse transcriptase inhibitor backbone. Our results show that CD4 <200 cells/µL and VL ≥100,000 copies/mL impair ART efficacy in all preferred regimens.

Safety of early oral ambulatory treatment of adult patients with bloodstream infections discharged from the emergency department.

This study evaluates the safety of early oral ambulatory treatment of adult patients diagnosed with bacteremia after their discharge from the emergency department. A cohort of 206 febrile ambulatory patients was assessed. Bacteremic low-risk patients were recommended an oral treatment and were compared with matched febrile non-bacteremic outpatients. Rates of 14-day mortality and unplanned re-consultations were similar and below 5% in both cohorts, highlighting the safety of oral therapy of low-risk bacteremia, even from its onset.

Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

What is essential remains invisible to the eyes? Blood pressure cuffs colonized by bacterial diversity.

Using sphygmomanometers to measure blood pressure is a common practice in the healthcare context. The disinfection and maintenance of these devices is essential in clinical practice to prevent the proliferation of microorganisms. The aim of this study was to determine the presence of pathogenic microorganisms in sphygmomanometer cuffs in the clinical setting. A cross-sectional study was carried out. Five types of healthcare centers, selected through convenience sampling, participated in this study. Samples were collected from the inside of sphygmomanometer cuffs, and labeled and delivered to the laboratory for analysis. The samples were incubated in an oven at 35.5 °C for 24 h. A total CFU count was carried out on the plates that were cataloged as positive. Colonies that showed growth were identified using the matrix-assisted laser desorption/ionization-mass spectrometry technology. Of the total sample, (N = 372), 69.1% were positive and were isolated. In 30.9% (n = 115), no bacterial development was found within 48 h. A total of 257 microorganisms were found. The mean number of colony-forming units was 29.62 (SD = 32.33). The socio-health centers had the highest amount of bacterial contamination in the cuffs. In regards to the type of microorganisms, 31.5% (n = 81) found were Bacillus cereus, followed by 26.8% (n = 69) of Staphylococcus hominis and 9.7% (n = 25) were Pantoea agglomerans, among others. Statistically significant differences were found between the type of microorganism and the hours elapsed since the last disinfection (X2(19) = 44.582; p = 0.001). Statistically significant differences were found between the time elapsed since the last disinfection and the type of sphygmomanometer (X2 (2) = 117.752; p = 0.000). Despite the fact that most hospitals and health centers have established infection control policies and protocols, the results of this study indicate the presence of pathogenic microorganisms in blood pressure cuffs in the clinical setting.

Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS.

BACKGROUND: People living with HIV have an increased risk of anal cancer. OBJECTIVE: To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. DESIGN: Prospective multicenter cohort study. SETTINGS: Multicenter study including patients from the Spanish HIV Research Network. PATIENTS: We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. MAIN OUTCOMES MEASURES: The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. RESULTS: Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). LIMITATIONS: Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. CONCLUSIONS: Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. INCIDENCIA DEL CNCER DE ANO Y LOS FACTORES DE RIESGO RELACIONADOS CON PACIENTES INFECTADOS POR VIH INCLUIDOS EN LA COHORTE PROSPECTIVA NACIONAL ESPAOLA CORIS: ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).

Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.

The role of adaptive immunity in early cancer development is controversial. Here we show that chronic inflammation and fibrosis in humans and mice with non-alcoholic fatty liver disease is accompanied by accumulation of liver-resident immunoglobulin-A-producing (IgA+) cells. These cells also express programmed death ligand 1 (PD-L1) and interleukin-10, and directly suppress liver cytotoxic CD8+ T lymphocytes, which prevent emergence of hepatocellular carcinoma and express a limited repertoire of T-cell receptors against tumour-associated antigens. Whereas CD8+ T-cell ablation accelerates hepatocellular carcinoma, genetic or pharmacological interference with IgA+ cell generation attenuates liver carcinogenesis and induces cytotoxic T-lymphocyte-mediated regression of established hepatocellular carcinoma. These findings establish the importance of inflammation-induced suppression of cytotoxic CD8+ T-lymphocyte activation as a tumour-promoting mechanism.

Erratum: Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.

This corrects the article DOI: 10.1038/nature24302.