Eficacia y seguridad de la vacunación antigripal pediátrica: una revisión sistemática / Efficacy and safety of pediatric flu vaccination: a systematic review

Introducción. Los a corren un mayor riesgo de infección por influenza en comparación con la población general. La Organización Mundial la Salud y las recomendaciones del Comité Asesor de Vacunas de la Asociación Española de Pediatría contemplan la vacunación anual como la forma más eficaz de prevenir la enfermedad. Por lo tanto, el propósito de esta revisión fue actualizar la información sobre eficacia y seguridad en la vacuna antigripal en niños y adolescentes. Material y métodos. Una búsqueda en cuatro bases de datos electrónicas (Scopus, Cumulative Index to Nursing and Allied Health Literature, MedLine / PubMed, Google Scholar y Cochrane), así como una búsqueda manual para identificar investigaciones originales publicadas entre 2012 y 2022. Se adoptaron las directrices de análisis (PRISMAcR) como elemento de informe preferido para revisiones sistemáticas. Resultados. Se incluyeron siete artículos de investigación originales donde se identificaron dos temas de la vacunación antigripal en niños/adolescentes sanos y con patologías. La eficacia (entre un 30% y un 80% aproximadamente) varió en función de la vacuna utilizada y los subtipos circulantes. La mayoría de las reacciones adversas fueron de intensidad leve y el evento adverso local más común informado fue dolor en el sitio de la inyección. Conclusiones. Destacamos positivamente la seguridad de la vacunación antigripal pediátrica en los estudios analizados, por el contrario, con respecto a la eficacia de la vacunación antigripal, observamos una amplia variabilidad de resultados. Existe una clara necesidad de seguir realizando estudios de eficacia y seguridad en el niño. (AU)

Introduction. Children are at a higher risk of influenza infection compared to the general population. The World Organization Health and recommendations of the Vaccine Advisory Committee of the Spanish Association of Pediatrics contemplate annual vaccination as the most effective way to prevent the disease. Therefore, the purpose of this review was to update information on efficacy and safety in the anti -shed vaccine in children and adolescents. Material and methods. A search in four electronic databases (Scopus, Cumulative Index to Nursing and Allied Health Literature, Medline / Pubmed, Google Scholar and Cochrane), as well as a manual search to identify original research published between 2012 and 2022. The guidelines of ANALYSIS (PRISMACR) as a preferred report element for systematic reviews. Results. Seven original research articles were included where two issues of antigripal vaccination were identified in healthy children/adolescents and with pathologies. The efficacy (between approximately 30% and 80%) varied depending on the vaccine used and circulating subtypes. Most adverse reactions were mild intensity, and the most common local adverse event was pain in the injection site. Conclusions. We positively highlight the safety of pediatric flu vaccination in analyzed studies, on the contrary, with respect to the efficacy of flu vaccination, we observe a wide variability of results. There is a clear need to continue conducting efficacy and safety studies in the child. (AU)

Community-based models of care for adolescent and adult depression, suicidal behavior, anxiety, trauma, and substance use in Africa: a scoping review.

Background: Community-based care (CBC), where care is delivered outside of the traditional health facility setting, has been proposed to narrow the mental health (MH) and substance use (SU) treatment gap in Africa. Objective: This scoping review aims to comprehensively summarize CBC models addressing adolescent and adult MH (depression, anxiety, trauma, suicidal behavior) and (non-tobacco) SU problems in Africa. Methods: We searched PsycINFO, Embase, Scopus, CINAHL, and Medline Ovid. Studies and protocols were included if they reported on CBC intervention's effects on MH or SU symptoms/ diagnoses, acceptability, feasibility, or patient engagement in care, regardless of whether the intervention itself was designed specifically for MH or SU. Results: Among 11,477 screened publications, 217 were eligible. Of the unique intervention studies (n = 206), CBC models were classified into the following approaches (non-mutually exclusive): psychotherapeutic (n = 144), social (n = 81), lifestyle/physical health (n = 55), economic (n = 26), and psychopharmacological (n = 2). While quantitative results suggest possible efficacy of CBC models, description of CBC location was often poor. Fewer interventions addressed suicidal behavior (n = 12), the needs of adolescents (n = 49), or used traditional healers or religious figures as providers (n = 3). Conclusion: Many CBC models have been tested on MH and SU in Africa and should be critically appraised and meta-analyzed in subsequent reviews, where possible.

Effect of an intensive tobacco cessation program on the smoker narrative: A content analysis and grounded theory.

INTRODUCTION: The smoker's narrative during smoking quitting provides insight into aspects not fully explored in daily clinical practice. The aim of the study was to analyze the smoker narrative using two types of methodologies: content analysis and grounded theory, before and after smoking cessation intervention, provided to the smoker in a specialized Smoking Cessation Unit accredited by the Spanish Society of Pneumology and Thoracic Surgery. METHODS: A prospective observational study of current smokers included in a tobacco cessation program between 2017 and 2020 was conducted at the Smoking Cessation Unit of Santiago de Compostela Health Area, Spain. Routine clinical variables and patient narrative data were collected. A descriptive analysis of the sample, the content of the textual corpus, and a grounded theory were performed in semi-structured interviews at baseline and at follow-up at 6 months. RESULTS: A total of 116 patients were included (mean age 55.6 ± 10.6 years; 56.9% male; mean nicotine dependence score 5.7 ± 1.6). Quantitative analysis of the narrative shows that the most frequent phrases and words are associated with smoking, nicotine craving, and predisposition for smoking cessation. After the intervention, phrases related to the manifestation of abstinence, response to pharmacological treatment, and self-perception of smoking cessation were predominant. In the qualitative analysis, the most frequent categories in the smoker's textual corpus were dependence, motivation, and emotionality, which decreased after the intervention (11.4%, 21.4%, and 9.9%, respectively) accompanied by increased satisfaction (19.2%) and the manifestation of abstinence (21.5%). CONCLUSIONS: Motivation, nicotine dependence, and sensitivity to emotions are all closely intertwined in the current smoker narrative and can be modified as a consequence of treatment.

Prevalence of virulence- and antibiotic resistance-associated genotypes and phenotypes in Staphylococcus aureus strains from the food sector compared to clinical and cow mastitis isolates.

Background: Infections by the pathogen Staphylococcus aureus currently represent one of the most serious threats to human health worldwide, especially due to the production of enterotoxins and the ability to form biofilms. These structures and the acquisition of antibiotic resistance limit the action of antibiotics and disinfectants used to combat this microorganism in the industry and the clinic. Methods: This work reports a comparative phenotypic and genotypic study of 18 S. aureus strains from different origins: clinical samples, milk from mastitic cows and food industry surfaces, most of which were isolated in Northern Spain. Results: Genetically, the strains were very diverse but, in most cases, a closer proximity was observed for those from the same source. Notably, the average number of virulence genes was not significantly different in strains from the food sector. Of the 18 strains, 10 coded for at least one enterotoxin, and four of them carried 6 or 7 enterotoxin genes. The latter were all veterinary or clinical isolates. Most strains carried prophages, plasmids and/or pathogenicity islands. Regarding antibiotic resistance, although phenotypically all strains showed resistance to at least one antibiotic, resistance genes were only identified in 44.5% of strains, being mastitis isolates those with the lowest prevalence. Virulence-related phenotypic properties such as haemolytic activity, staphyloxanthin production, biofilm-forming capacity and spreading ability were widely distributed amongst the isolates. Conclusions: Our results indicate that production of virulence factors, antibiotic resistance and biofilm formation can be found in S. aureus isolates from diverse environments, including the food industry, although some of these traits are more prevalent in strains isolated from infections in cows or humans. This emphasizes on the importance of monitoring the spread of these determinants not only in samples from the clinical environment, but also along the food chain, a strategy that falls under the prism of a one-health approach.

Prevalence and clinical characteristics of patients with rheumatoid arthritis with interstitial lung disease using unstructured healthcare data and machine learning.

OBJECTIVES: Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR). METHODS: Observational case-control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared. RESULTS: From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001). CONCLUSIONS: We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality.

Photobiomodulation increases brain metabolic activity through a combination of 810 and 660 wavelengths: a comparative study in male and female rats.

Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to benefit the nervous system by modifying the mitochondrial cytochrome c-oxidase (CCO) enzyme, which has red (620-680 nm) or infrared (760-825 nm) spectral absorption peaks. The effect of a single 810-nm wavelength with a combination of 810 nm and 660 nm lights in the brain metabolic activity of male and female rats was compared. PBM, with a wavelength of 810 nm and a combination of 810 nm and 660 nm, was applied for 5 days on the prefrontal cortex. Then, brain metabolic activity in the prefrontal area, hippocampus, retrosplenial, and parietal cortex was explored. Sex differences were found in cortical and subcortical regions, indicating higher male brain oxidative metabolism, regardless of treatment. CCO activity in the cingulate and prelimbic area, dentate gyrus, retrosplenial and parietal cortex was enhanced in both treatments (810 + 660 nm and 810 nm). Moreover, using the combination of waves, CCO increased in the infralimbic area, and in CA1 and CA3 of the hippocampus. Thus, employment of a single NIR treatment or a combination of red to NIR treatment led to slight differences in CCO activity across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.

Phage Lytic Protein CHAPSH3b Encapsulated in Niosomes and Gelatine Films.

Antimicrobial resistance (AMR) has emerged as a global health challenge, sparking worldwide interest in exploring the antimicrobial potential of natural compounds as an alternative to conventional antibiotics. In recent years, one area of focus has been the utilization of bacteriophages and their derivative proteins. Specifically, phage lytic proteins, or endolysins, are specialized enzymes that induce bacterial cell lysis and can be efficiently produced and purified following overexpression in bacteria. Nonetheless, a significant limitation of these proteins is their vulnerability to certain environmental conditions, which may impair their effectiveness. Encapsulating endolysins in vesicles could mitigate this issue by providing added protection to the proteins, enabling controlled release, and enhancing their stability, particularly at temperatures around 4 °C. In this work, the chimeric lytic protein CHAPSH3b was encapsulated within non-ionic surfactant-based vesicles (niosomes) created using the thin film hydrating method (TFH). These protein-loaded niosomes were then characterized, revealing sizes in the range of 30-80 nm, zeta potentials between 30 and 50 mV, and an encapsulation efficiency (EE) of 50-60%. Additionally, with the objective of exploring their potential application in the food industry, these endolysin-loaded niosomes were incorporated into gelatine films. This was carried out to evaluate their stability and antimicrobial efficacy against Staphylococcus aureus.

Association Between Speech Reception Threshold in Noise and Multimorbidity: The UK Biobank Study.

OBJECTIVE: To investigate the association between hearing function, as approached with the functional auditory capacity, and multimorbidity. STUDY DESIGN: Cross-sectional study. SETTING: The UK Biobank was established from 2006 to 2010 in the United Kingdom. This cross-sectional analysis included 165,524 participants who provided baseline information on hearing function. METHODS: Functional auditory capacity was measured with a digit triplet test. Three categories were defined according to the speech reception threshold in noise (SRTn): normal (SRTn < -5.5 dB signal-to-noise ratio [SNR]), insufficient (SRTn ≥ -5.5 to ≤ -3.5 dB SNR) and poor hearing function (SRTn > -3.5 dB SNR). To define multimorbidity, 9 chronic diseases were considered, including chronic obstructive pulmonary disease, dementia, Parkinson's disease, stroke, cancer, depression, osteoarthritis, coronary heart disease, and diabetes; multimorbidity was defined as the coexistence of 2 or more in the same individual. Analyses were conducted using logistic models adjusted for relevant confounders. RESULTS: Among the study participants, 54.5% were women, and the mean (range) age was 56.7 (39-72) years. The prevalence of insufficient and poor hearing function and multimorbidity was 13% and 13.2%, respectively. In comparison with having a normal SRTn, the odds ratio (95% confidence interval) of multimorbidity associated with insufficient SRTn was 1.13 (1.08-1.18), and with poor SRTn was 1.25 (1.14-1.37). CONCLUSION: Insufficient and poor hearing function was associated with multimorbidity. This association suggests common biological pathways for many of the considered morbidities.

Content Validity of the Spanish Adaptation of the Premature Infant Pain Profile Revised.

BACKGROUND: To the best of our knowledge, there are no validated neonatal pain assessment scales in Spanish. Given the need for such a scale, a study was undertaken to adapt and validate the Premature Infant Pain Profile-Revised (PIPP-R) scale. After translation and back-translation, content validity was addressed, a crucial phase in validation studies, in which researchers examine whether the items that make up the scale represent the content that the scale is intended to assess. AIMS: The aim was to provide evidence for the content validity of the Spanish adaptation of the PIPP-R scale. METHOD: The study used the Delphi technique with 10 experts. Data collection was anonymous and was conducted through an online platform. It was an ad hoc survey consisting of four questions, with a five-point Likert scale for each item on the scale and for the instruction table. An item-content validity index (I-CVI) and a scale-content validity index (S-CVI) were calculated for the analysis. RESULTS: After two rounds of the survey, all items exceeded an I-CVI of 0.9. The S-CVI value was 0.98 (±0.03) for the scale, and 1 for its instruction table. The kappa index yielded values indicating an excellent degree of agreement. CONCLUSIONS: The Spanish version of the PIPP-R obtained a high degree of content validity according to the expert group and the Delphi technique.

A pulmonary rehabilitation program reduces hospitalizations in chronic obstructive pulmonary disease patients: A cost-effectiveness study.

BACKGROUND: Although pulmonary rehabilitation (PR) is recommended in patients with chronic obstructive pulmonary disease (COPD), there is a scarcity of data demonstrating the cost-effectiveness and effectiveness of PR in reducing exacerbations. METHODS: A quasi-experimental study in 200 patients with COPD was conducted to determine the number of exacerbations 1 year before and after their participation in a PR program. Quality of life was measured using the COPD assessment test and EuroQol-5D. The costs of the program and exacerbations were assessed the year before and after participation in the PR program. The incremental cost-effectiveness ratio (ICER) was estimated in terms of quality-adjusted life years (QALYs). RESULTS: The number of admissions, length of hospital stay, and admissions to the emergency department decreased after participation in the PR program by 48.2%, 46.6%, and 42.5%, respectively (P < 0.001 for all). Results on quality of life tests improved significantly (P < 0.001 for the two tests). The cost of PR per patient and the cost of pre-PR and post-PR exacerbations were €1867.7 and €7895.2 and €4201.9, respectively. The PR resulted in a cost saving of €1826 (total, €365,200) per patient/year, and the gain in QALYs was+0.107. ICER was -€17,056. The total cost was <€20,000/QALY in 78% of patients. CONCLUSIONS: PR contributes to reducing the number of exacerbations in patients with COPD, thereby slowing clinical deterioration. In addition, it is cost-effective in terms of QALYs.

Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

Host cell cAMP-Epac-Rap1b pathway inhibition by hawthorn extract as a potential target against Trypanosoma cruzi infection.

Although the two drugs currently available for the treatment of Chagas disease, Benznidazole and Nifurtimox, have proven to be effective in the acute phase of the disease, the 60-90-day treatment leads to high toxicity and unwanted side effects, presenting, in addition, a low efficacy in the chronic phase of the disease. For this reason, new therapies that are more effective are needed. In this regard, we have recently shown that the inhibition of the Epac-Rap1b pathway suppressed the cAMP-mediated host cell invasion by Trypanosoma cruzi. Interestingly, it has been described that vitexin, a natural flavone that protects against ischemia-reperfusion damage, acts by inhibiting the expression of Epac and Rap1 proteins. Vitexin can be found in plants of the genus Crataegus spp., traditionally known as hawthorn, which are of great interest considering their highly documented use as cardio-protectors. Pre-treating cells with an extract of Crataegus oxyacantha produced levels of T. cruzi invasion comparable to the ones observed for the commercially available Epac1-specific inhibitor, ESI-09. In addition, extract-treated cells exhibited a decrease in the activation of Rap1b, suggesting that the effects of the extract would be mediated by the inhibition of the cAMP-Epac-Rap1 signaling pathway. Using HPLC-HRMS2, we could confirm the presence of vitexin, and other flavones that could act as inhibitors of Epac/Rap1b, in the extracts of C. oxyacantha. Most significantly, when cells were treated with the extract of C. oxyacantha in conjunction with Nifurtimox, an increased modulation of invasion was observed.

Identification of Reference Genes for Precise Expression Analysis during Germination in Chenopodium quinoa Seeds under Salt Stress.

Chenopodium quinoa Willd. (quinoa), a member of the Amaranthaceae family, is an allotetraploid annual plant, endemic to South America. The plant of C. quinoa presents significant ecological plasticity with exceptional adaptability to several environmental stresses, including salinity. The resilience of quinoa to several abiotic stresses, as well as its nutritional attributes, have led to significant shifts in quinoa cultivation worldwide over the past century. This work first defines germination sensu stricto in quinoa where the breakage of the pericarp and the testa is followed by endosperm rupture (ER). Transcriptomic changes in early seed germination stages lead to unstable expression levels in commonly used reference genes that are typically stable in vegetative tissues. Noteworthy, no suitable reference genes have been previously identified specifically for quinoa seed germination under salt stress conditions. This work aims to identify these genes as a prerequisite step for normalizing qPCR data. To this end, germinating seeds from UDEC2 and UDEC4 accessions, with different tolerance to salt, have been analyzed under conditions of absence (0 mM NaCl) and in the presence (250 mM NaCl) of sodium chloride. Based on the relevant literature, six candidate reference genes, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Monensin sensitivity1 (MON1), Polypyrimidine tract-binding protein (PTB), Actin-7 (ACT7), Ubiquitin-conjugating enzyme (UBC), and 18S ribosomal RNA (18S), were selected and assessed for stability using the RefFinder Tool encompassing the statistical algorithms geNorm, NormFinder, BestKeeper, and ΔCt in the evaluation. The data presented support the suitability of CqACT7 and CqUBC as reference genes for normalizing gene expression during seed germination under salinity stress. These recommended reference genes can be valuable tools for consistent qPCR studies on quinoa seeds.

COVID-19 screening in low resource settings using artificial intelligence for chest radiographs and point-of-care blood tests.

Artificial intelligence (AI) systems for detection of COVID-19 using chest X-Ray (CXR) imaging and point-of-care blood tests were applied to data from four low resource African settings. The performance of these systems to detect COVID-19 using various input data was analysed and compared with antigen-based rapid diagnostic tests. Participants were tested using the gold standard of RT-PCR test (nasopharyngeal swab) to determine whether they were infected with SARS-CoV-2. A total of 3737 (260 RT-PCR positive) participants were included. In our cohort, AI for CXR images was a poor predictor of COVID-19 (AUC = 0.60), since the majority of positive cases had mild symptoms and no visible pneumonia in the lungs. AI systems using differential white blood cell counts (WBC), or a combination of WBC and C-Reactive Protein (CRP) both achieved an AUC of 0.74 with a suggested optimal cut-off point at 83% sensitivity and 63% specificity. The antigen-RDT tests in this trial obtained 65% sensitivity at 98% specificity. This study is the first to validate AI tools for COVID-19 detection in an African setting. It demonstrates that screening for COVID-19 using AI with point-of-care blood tests is feasible and can operate at a higher sensitivity level than antigen testing.

Real world data on the demographic and clinicopathological profile and management of patients with early-stage HER2-positive breast cancer and residual disease treated with adjuvant trastuzumab emtansine (KARMA study).

INTRODUCTION: Trastuzumab emtansine (T-DM1) significantly improves invasive disease-free survival and reduces the risk of recurrence in patients with HER2-positive early breast cancer (EBC) with residual disease (RD). The KARMA study aimed to describe the characteristics and management of these patients in clinical practice in Spain. MATERIAL AND METHODS: We conducted a multicentre retrospective study in patients with HER2-positive EBC with RD following neoadjuvant treatment (NeoT) and who had received ≥1 dose of T-DM1 as adjuvant treatment. The primary endpoint was the evaluation of sociodemographic and clinicopathological characteristics of these patients. RESULTS: A total of 114 patients were included (March-July 2020). At diagnosis, most tumours were infiltrating ductal carcinoma (IDC) (93.9 %), grade 2 (56.1 %), and hormone receptor (HR)-positive (79.8 %). Over 75 % of patients had disease in operable clinical stages (T1-3 N0-1). In the neoadjuvant setting, 86.8 % of patients received trastuzumab plus pertuzumab, and 23.6 % achieved radiological complete response. Breast-conserving surgery was performed in 55.8 % of patients. Surgical specimens showed that 89.5 % of patients had IDC, 49.1 % grade 2, 84.1 % HR-positive, and 8.3 % HER2-negative disease. Most patients had RD classified as RCB-II and Miller/Payne grade 3/4. Grade 3 treatment-related adverse events (trAEs) occurred in 5.3 % of patients. No grade 4/5 AEs occurred. Over 95 % of patients were free of invasive-disease during T-DM1 adjuvant treatment. CONCLUSION: The KARMA study describes the characteristics of patients with HER2-positive EBC with RD after NeoT and the real-life management of a T-DM1 adjuvant regimen, which showed a manageable safety profile in line with the KATHERINE trial data.

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.