Cognitive reserve, depressive symptoms, obesity, and change in employment status predict mental processing speed and executive function after COVID-19

Post-COVID-19 condition; Mental speed processing; Logistic regressionCondición post-COVID-19; Procesamiento de velocidad mental; Regresión logísticaEstat post-COVID-19; Processament de velocitat mental; Regressió logísticaThe risk factors for post-COVID-19 cognitive impairment have been poorly described. This study aimed to identify the sociodemographic, clinical, and lifestyle characteristics that characterize a group of post-COVID-19 condition (PCC) participants with neuropsychological impairment. The study sample included 426 participants with PCC who underwent a neurobehavioral evaluation. We selected seven mental speed processing and executive function variables to obtain a data-driven partition. Clustering algorithms were applied, including K-means, bisecting K-means, and Gaussian mixture models. Different machine learning algorithms were then used to obtain a classifier able to separate the two clusters according to the demographic, clinical, emotional, and lifestyle variables, including logistic regression with least absolute shrinkage and selection operator (LASSO) (L1) and Ridge (L2) regularization, support vector machines (linear/quadratic/radial basis function kernels), and decision tree ensembles (random forest/gradient boosting trees). All clustering quality measures were in agreement in detecting only two clusters in the data based solely on cognitive performance. A model with four variables (cognitive reserve, depressive symptoms, obesity, and change in work situation) obtained with logistic regression with LASSO regularization was able to classify between good and poor cognitive performers with an accuracy and a weighted averaged precision of 72%, a recall of 73%, and an area under the curve of 0.72. PCC individuals with a lower cognitive reserve, more depressive symptoms, obesity, and a change in employment status were at greater risk for poor performance on tasks requiring mental processing speed and executive function.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was supported by the European Archives of Psychiatry and Clinical Neuroscience Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 2020PANDE00053), the La Marató de TV3 Foundation (202111–30-31–32), the Ministerio de Ciencia e Innovación (TED2021-130409B-C55)

Predictability of B cell clonal persistence and immunosurveillance in breast cancer

B cell; Immunosurveillance; Breast cancerCèl·lules B; Immunovigilància; Càncer de mamaCélulas B; Inmunovigilancia; Cáncer de mamaB cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy. Using immune receptor, RNA and whole-exome sequencing, we show that both B cell and T cell responses seem to coevolve with the metastatic cancer genomes and mirror tumor mutational and neoantigen architecture. B cell clones associated with metastatic immunosurveillance and temporal persistence were more expanded and distinct from site-specific clones. B cell clonal immunosurveillance and temporal persistence are predictable from the clonal structure, with higher-centrality B cell antigen receptors more likely to be detected across multiple metastases or across time. This predictability was generalizable across other immune-mediated disorders. This work lays a foundation for prioritizing antibody sequences for therapeutic targeting in cancer.The authors thank the late Nir Friedman at the Weizmann Institute for the many scientific discussions that contributed to the central idea that rooted this work. S-J.S. was supported by a Whitney Wood Scholarship awarded by the Royal College of Physicians (United Kingdom). C.C. was supported by funding from CRUK (grant numbers A17197, A27657 and A29580), an NIHR Senior Investigator Award (grant number NF-SI-0515-10090), and a European Research Council Advanced Award (grant number 694620). R.J.M.B.-R. was supported by the Wellcome Trust and University of Oxford. O.M.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (UK; MC_UU_00002/16). B.S. is supported by an NIHR Academic Clinical Lectureship (CL-2021-13-002), Academy of Medical Sciences (SGL028\1074) and The British Medical Association Vera Down Award. We thank Breast Cancer Now for funding this work as part of Programme Funding to the Breast Cancer Now Toby Robins Research Centre. We thank the Asociación Española contra el Cáncer, Cellex foundation, and the clinical team at the Breast Cancer Unit of Vall d’Hebron University Hospital/Institute of Oncology and the Cambridge Breast Cancer Research Unit for facilitating the collection and processing of biological samples. We are very grateful for the generosity of all the participants that donated samples for analysis

Vacuna anti-virus del papil·loma humà (vacuna VPH)

Vacuna anti-virus; Malalties prevenibles; Papil·loma humàVacuna antivirus; Enfermedades prevenibles; Papiloma humanoAnti-virus vaccine; Preventable diseases; Human papillomaCapítol 4 del Manual de vacunacions de Catalunya dedicat a la vacuna del papil·loma humà (vacuna VPH). Es tracta d'una vacuna constituïda per partícules no infeccioses similars al virus del papil·loma humà (partícules similivíriques o VLP), produïdes mitjançant l’autoassemblatge de les proteïnes L1 de la càpsida del virus de diferents tipus, obtingudes per tècniques de recombinació genètica. En l’actualitat, hi ha dues vacunes disponibles: la vacuna anti-virus del papil ·loma humà tipus 16 i 18 (vacuna VPH2), la nonavalent (vacuna VPH9). La vacuna VPH2 és bivalent i conté VLP dels tipus 16 i 18, causants de més del 70% dels casos de càncer de coll uterí i d’una fracció variable dels càncers de vulva, vagina, penis, anus i orofaringe associats al VPH. La vacuna nonavalent, a més de VLP dels 4 tipus de VPH inclosos en la tetravalent 6, 11, 16 i 18 conté VLP dels tipus 31, 33, 45, 52 i 58, responsables d’un 20% addicional dels casos de càncer de coll uterí.Capítulo 4 del Manual de vacunacions de Catalunya dedicado a la vacuna del papiloma humano (vacuna VPH). Se trata de una vacuna constituida por partículas no infecciosas similares al virus del papiloma humano (partículas similivíricas o VLP), producidas mediante el autoensamblaje de las proteínas L1 de la cápsida del virus de diferentes tipos, obtenidas por técnicas de recombinación genética . En la actualidad, existen dos vacunas disponibles: la vacuna antivirus del papiloma humano tipo 16 y 18 (vacuna VPH2), la nonavalente (vacuna VPH9). La vacuna VPH2 es bivalente y contiene VLP de los tipos 16 y 18, causantes de más del 70% de los casos de cáncer de cuello uterino y de una fracción variable de los cánceres de vulva, vagina, pene, ano y orofaringe asociados al VPH. La vacuna nonavalente, además de VLP de los 4 tipos de VPH incluidos en la tetravalente 6, 11, 16 y 18 contiene VLP de los tipos 31, 33, 45, 52 y 58, responsables de un 20% adicional de los casos de cáncer de cuello uterino.Chapter 4 of the Manual de vacunacions de Catalunya dedicated to the human papilloma vaccine (HPV vaccine). It is a vaccine made up of non-infectious particles similar to the human papillomavirus (viral-like particles or VLPs), produced through the self-assembly of the L1 proteins of the virus capsid of different types, obtained by genetic recombination techniques . Currently, there are two vaccines available: the human papillomavirus type 16 and 18 vaccine (HPV2 vaccine), the nonavalent (HPV9 vaccine). The HPV2 vaccine is bivalent and contains VLPs of types 16 and 18, which cause more than 70% of cervical cancer cases and a variable fraction of cancers of the vulva, vagina, penis, anus and oropharynx associated with HPV. The nonavalent vaccine, in addition to VLPs from the 4 types of HPV included in the tetravalent 6, 11, 16 and 18 contains VLPs of types 31, 33, 45, 52 and 58, responsible for an additional 20% of cancer cases cervix

Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure

Antibody; Immunogenicity; Metastatic melanomaAnticuerpos; Inmunogenicidad; Melanoma metastásicoAnticossos; Immunogenicitat; Melanoma metastàticIntroduction: Although checkpoint inhibitors (CPIs) have improved outcomes for patients with metastatic melanoma, those progressing on CPIs have limited therapeutic options. To address this unmet need and overcome CPI resistance mechanisms, novel immunotherapies, such as T-cell engaging agents, are being developed. The use of these agents has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs), which is challenging to predict preclinically and can lead to neutralization of the drug and loss of efficacy. Methods: TYRP1-TCB (RO7293583; RG6232) is a T-cell engaging bispecific (TCB) antibody that targets tyrosinase-related protein 1 (TYRP1), which is expressed in many melanomas, thereby directing T cells to kill TYRP1-expressing tumor cells. Preclinical studies show TYRP1-TCB to have potent anti-tumor activity. This first-in-human (FIH) phase 1 dose-escalation study characterized the safety, tolerability, maximum tolerated dose/optimal biological dose, and pharmacokinetics (PK) of TYRP1-TCB in patients with metastatic melanoma (NCT04551352). Results: Twenty participants with cutaneous, uveal, or mucosal TYRP1-positive melanoma received TYRP1-TCB in escalating doses (0.045 to 0.4 mg). All participants experienced ≥1 treatment-related adverse event (TRAE); two participants experienced grade 3 TRAEs. The most common toxicities were grade 1–2 cytokine release syndrome (CRS) and rash. Fractionated dosing mitigated CRS and was associated with lower levels of interleukin-6 and tumor necrosis factor-alpha. Measurement of active drug (dual TYPR1- and CD3-binding) PK rapidly identified loss of active drug exposure in all participants treated with 0.4 mg in a flat dosing schedule for ≥3 cycles. Loss of exposure was associated with development of ADAs towards both the TYRP1 and CD3 domains. A total drug PK assay, measuring free and ADA-bound forms, demonstrated that TYRP1-TCB-ADA immune complexes were present in participant samples, but showed no drug activity in vitro. Discussion: This study provides important insights into how the use of active drug PK assays, coupled with mechanistic follow-up, can inform and enable ongoing benefit/risk assessment for individuals participating in FIH dose-escalation trials. Translational studies that lead to a better understanding of the underlying biology of cognate T- and B-cell interactions, ultimately resulting in ADA development to novel biotherapeutics, are needed.The author(s) declare financial support was received for the research, authorship, and/or publication of this article

Editorial: Virology today in Spain. Selected topics from Spanish virology

Adeno associated virus; African swine fever virus; West Nile virusVirus adenoasociados; Virus de la peste porcina africana; Virus del Nilo occidentalVirus adenoassociats; Virus de la pesta porcina africana; Virus del Nil occidenta

Actualització de les actuacions per a la prevenció i el control de la tos ferina

Preguntes freqüents; Tos ferina; CatalunyaPreguntas frecuentes; Tos ferina; CataluñaFrequently asked questions; Whooping cough; CataloniaAquest document recull les preguntes formulades en el seminari web "Actualització de les actuacions per a la prevenció i el control de la tos ferina" del dia 24 d’abril de 2024.This document collects the questions asked in the webinar "Actualització de les actuacions per a la prevenció i el control de la tos ferina" on April 24, 2024.Este documento recoge las preguntas formuladas en el seminario web "ctualització de les actuacions per a la prevenció i el control de la tos ferina" del día 24 de abril de 2024

A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial

Minor stroke; ThrombolysisIctus lleu; TrombolisiIctus leve; TrombólisisBackground: Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. Design: TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0–1, mRS 0–2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. Conclusion: Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion.This study was supported by the Heart and Stroke Foundation of Canada, Canadian Institute for Health Research, Alberta Innovates and British Heart Foundation. Intravenous Tenecteplase is off-the-shelf and supported by Boehringer Ingelheim

Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy

Liquid biopsy; Cholangiocarcinoma; Targeted therapyBiopsia líquida; Colangiocarcinoma; Terapia dirigidaBiòpsia líquida; Colangiocarcinoma; Teràpia dirigidaPurpose: FGFR2 fusions occur in 10% to 15% of patients with intrahepatic cholangiocarcinoma (iCCA), potentially benefiting from FGFR inhibitors (FGFRi). We aimed to assess the feasibility of detecting FGFR2 fusions in plasma and explore plasma biomarkers for managing FGFRi treatment. Experimental design: We conducted a retrospective study in 18 patients with iCCA and known FGFR2 fusions previously identified in tissue samples from prior FGFRi treatment. Both tissue and synchronous plasma samples were analyzed using a custom hybrid capture gene panel with next-generation sequencing (VHIO-iCCA panel) and validated against commercial vendor results. Longitudinal plasma analysis during FGFRi was performed. Subsequently, we explored the correlation between plasma biomarkers, liver enzymes, tumor volume, and clinical outcomes. Results: Sixteen patients (88.9%) were positive for FGFR2 fusion events in plasma. Remarkably, the analysis of plasma suggests that lower levels of ctDNA are linked to clinical benefits from targeted therapy and result in improved progression-free survival and overall survival. Higher concentrations of cell-free DNA before FGFRi treatment were linked to worse overall survival, correlating with impaired liver function and indicating compromised cell-free DNA removal by the liver. Additionally, increased ctDNA or the emergence of resistance mutations allowed earlier detection of disease progression compared with standard radiologic imaging methods. Conclusions: VHIO-iCCA demonstrated accurate detection of FGFR2 fusions in plasma. The integration of information from various plasma biomarkers holds the potential to predict clinical outcomes and identify treatment failure prior to radiologic progression, offering valuable guidance for the clinical management of patients with iCCA.This study was supported by Incyte Corporation (Wilmington, DE; project title: “Identification of FGFR2 alterations by liquid biopsy and correlation with tissue biopsies in patients with cholangiocarcinoma”), the Asociación Española contra el Cáncer (AECC, Spain), and the FERO Foundation. A. Gonzalez-Medina is supported by the grant FJC2019-039770-I funded by Agencia Estatal de Investigación of Ministerio de Ciencia e Innovación (MCIN/AEI/10.13039/501100011033, Spain). R. Pérez-López. is supported by LaCaixa Foundation, a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigación en Salud (PI18/01395 and PI21/01019), the Prostate Cancer Foundation (18YOUN19), and the Asociación Española Contra el Cáncer (AECC; PRYCO211023SERR, funding CM). A. Vivancos is supported by the Instituto de Salud Carlos III-investigación en Salud (PI20/01112). Some pictures were created with BioRender

Usefulness of real-time PCR for urogenital schistosomiasis diagnosis in preschool children in a high-prevalence area in Angola

Urogenital schistosomiasis; Diagnosis; AngolaDiagnòstic; Esquistosomiasi urogenital; AngolaDiagnóstico; Esquistosomiasis urogenital; AngolaBackground Urogenital schistosomiasis caused by Schistosoma haematobium is highly endemic in the municipality of Cubal in Angola. Currently, diagnosis is based on the observation of S. haematobium eggs in urine samples by microscopy but this method has low sensitivity. Few studies have been performed using molecular techniques in high-prevalence areas for the detection of S. haematobium. The objective of this study is to evaluate the usefulness of real-time PCR as a diagnostic technique for urogenital schistosomiasis among preschool-age children and its correlation with morbidity data. Methods A cross-sectional study was conducted in Cubal, Angola, involving 97 urine samples from preschool-age children analyzed by the dipstick test, microscopic examination of filtered urine, and real-time PCR. The diagnosis of urogenital schistosomiasis was based on microscopy and/or real-time PCR results. Clinical and ultrasonography evaluation was performed to rule out complications of schistosomiasis. Results We detected a total of 64.95% of samples positive by real-time PCR and 37.11% by microscopy. The sensitivity of parasitological diagnosis of urogenital schistosomiasis by real-time PCR and microscopy was 95.45% and 54.55%, respectively, and the sensitivity of real-time PCR compared with microscopy was 91.67%. A positive real-time PCR result was significantly related to older age (mean = 3.22 years), detection of eggs by microscopy, and abnormal urine dipstick results (18.56% with proteinuria, 31.96% with leukocyturia, and 31.96% with microhematuria) (p-value<0.05). Ultrasound analysis showed that 23.94% of children had urinary tract abnormalities, and it was significantly related to the real-time PCR diagnosis (p-value<0.05). Conclusions Real-time PCR is a more sensitive technique than microscopy for urinary schistosomiasis diagnosis in preschool-age children in Cubal. This increase in sensitivity would allow earlier diagnosis and treatment, thus reducing the morbidity associated with schistosomiasis in its early stages

Unraveling wasp sensitization in a patient with systemic mastocytosis by CAP-inhibition assay

Hymenoptera venom allergy; Indolent systemic mastocytosis; Venom immunotherapyAlergia al veneno de himenópteros; Mastocitosis sistémica indolente; Inmunoterapia con venenoAl·lèrgia al verí dels himenòpters; Mastocitosi sistèmica indolent; Immunoteràpia con veríSystemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity