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Colorectal cancer is the third most common cancer worldwide both in men and women. Around one-third of patients with cancer will suffer from anxiety or depression symptoms. The aim of this study was to evaluate the effectiveness of a Mindfulness-based stress reduction intervention through a mobile application ("En Calma en el Quirófano").This study is a multicenter, single-blind (evaluator), controlled, randomised trial that compares the effectiveness of a mindfulness training through a mobile application (intervention group) and treatment as usual (control group) in three different moments (T0 or baseline, T1 or hospital discharge and T2 or one month after surgery). Anxiety and depression symptoms (HADS), quality of life (WHOQOL), pain, (VAS) and satisfaction (CSQ) were assessed.In all, there were 270 referred patients. Among them, 39 and 43 were assigned to the intervention and control groups respectively. 82 patients were analyzed: 39 patients used the app, and 43 patients continued with the treatment as usual. There were no significant changes between groups and time. We observed a slight trend in which intervention group had less depression and anxiety symptoms since T0 and T2 (B = -0.2; 95% CI between 8.8 and 9.2).The sample of this study had a high mean age (65 years old), and low levels of anxiety and depression and medium levels of pre-surgery quality of life in baseline. These factors could have influenced limiting the effectiveness of the app. Prospective research lines should focus on evaluating the effectiveness of mobile applications for younger patients with surgical pathologies.

We examined whether excess chronic medical comorbidity mediated excess COVID-19 inpatient mortality among people with mental disorders in the early phase of the pandemic, a question with important implications for public health and clinical decision-making. Using records of 2599 COVID-19 hospitalized patients, we conducted a formal causal mediation analysis to estimate the extent to which chronic comorbidity mediates the association between mental disorders and COVID-19 mortality. The Odds Ratio (95% CI) for Natural Indirect Effect and Controlled Direct Effect were 1.07(1.02, 1.14) and 1.40 (1.00, 1.95), respectively, suggesting that a large proportion of excess COVID-19 mortality among people with mental disorders may be explained by factors other than comorbidity.

Critical patients, despite initial recovery in the intensive care unit (ICU), may require readmission to the ICU or even die in the same hospital episode. The objectives are to determine the incidence and to identify risk factors for ICU readmission, and to determine hospital mortality.Observational cohort study of all patients admitted consecutively for more than 24hours to the ICU of the University Hospital of Getafe between April 1, 2018 and September 30, 2018 and discharged alive from their first ICU admission.Of the 164 patients alive at ICU discharge, 14 (8.5%) were readmitted to ICU (2.4% at≤48hours). The adjusted risk of ICU readmission was higher in patients with disabling neurological deficits prior to ICU admission [odds ratio (OR) 7.96, 95% confidence interval (CI) 1.55-40.92] or who received vasoactive drugs (OR 5.07, 95% CI 1.41-18.29) during their ICU stay. Readmitted patients had higher hospital mortality (4 of 14 [29%] versus 5 of 150 [3%], P.001) and longer hospital stay (74.5 [37.5-99.75] days versus 16 [9-34] days, median [interquartile range], P=.001).Patients with disabling neurological deficits prior to hospital admission or who received vasoactive drugs during their ICU stay have a higher risk of readmission to the ICU, which increases hospital stay and mortality.

International audience; ObjectivesThis study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).BackgroundCommon cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsREFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.ResultsWe included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.ConclusionsCAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

Objective This study explores whether social cognition and social functioning improve after a mindfulness-based social cognition training (SocialMIND). Methods Thirty-eight outpatients with psychosis completed an assessment with social cognition (Eyes Test, Ambiguous Intentions and Hostility Questionnaire [AIHQ], and Hinting Task) and social functioning tasks (Personal and Social Performance [PSP] scale) before and after eight SocialMIND weekly sessions. Mean differences between timepoints were standardized and 95% confidence intervals were obtained with a paired samples t-test. Results The scores of the Eyes Test (95% CI [.43, 3.32], d = .48), the Hostility Bias subscale (AIHQ) (95% CI [-.29, -.01], d = .44), and the self-care difficulties subscale (PSP) (95% CI [-.77, -.09], d = .45) improved after the intervention. Conclusions and Implications for practice: The results of SocialMIND-8 are very promising in terms of developing comprehensive rehabilitation programs. Further trials must address its effectiveness against a control group during longer follow-up periods. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background During the initial COVID-19 outbreak, organizational changes were required to ensure adequate staffing in healthcare facilities. The extent to which organizational changes impacted the mental wellbeing of healthcare workers (HCWs) remains unexplored. Here we analyzed the association between three work-related stressors (reported access to protective equipment, change in job functions, and patient prioritization decision-making) and mental health outcomes (depression symptoms, psychological distress, suicidal thoughts, and fear of infection) in a large sample of Spanish HCWs during the initial COVID-19 outbreak. Methods We conducted a cross-sectional study including HCWs from three regions of Spain between April 24th and June 22nd, 2020. An online survey measured sociodemographic characteristics, work-related stressors, fear of infection, and mental health outcomes (depression [PHQ-9], psychological distress [GHQ-12], death wishes [C-SSRS]). We conducted mixed-effects regression models to adjust all associations for relevant individual- and region-level sources of confounding. Results We recruited 2,370 HCWs. Twenty-seven percent screened positive for depression and 74% for psychological distress. Seven percent reported death wishes. Respondents were more afraid of infecting their loved ones than of getting infected themselves. All work-related stressors were associated with depression symptoms and psychological distress in adjusted models. Limitations Non-probabilistic sampling, potential reverse causation. Conclusions Modifiable work-related stressors are associated with worse mental health among HCWs. Our results suggest that workplace prevention strategies for HCWs should provide sufficient protective equipment, minimize changes in job functions, favor the implementation of criteria for patient triage and on-call bioethics committees, and facilitate access to stepped-care, evidence-based mental health treatment.

Examining the neutralizing capacity of monoclonal antibodies (MAbs) used to treat COVID-19, as well as antibodies recovered from unvaccinated, previously vaccinated, and infected individuals, against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) remains critical to study. Here, we report on a SARS-CoV-2 nosocomial outbreak caused by the SARS-CoV-2 R.1 variant harboring the E484K mutation in a 281-bed psychiatric facility in New Jersey among unvaccinated inpatients and health care professionals (HCPs). A total of 81 inpatients and HCPs tested positive for SARS-Cov-2 by reverse transcription (RT)-PCR from 29 October 9 to 30 November 2020. The R.1 variant exhibits partial or complete resistance to two MAbs in clinical use, as well as 2 receptor binding domain MAbs and 4 N-terminal domain (NTD) MAbs. NTD MAbs against pseudovirus harboring single characteristic R.1 mutations highlight the role of S255F in loss of activity. Additionally, we note dampened neutralization capacity by plasma from individuals with previous SARS-CoV-2 infection or sera from vaccinated individuals. The relative resistance of the R.1 variant is likely lower than that of B.1.351 and closer to that of P.1 and B.1.526. The R.1 lineage has been reported in 47 states in the United States and 40 countries. Although high proportions exhibited symptoms (26% and 61% among patients and HCPs, respectively) and relative antibody resistance, we detected only 10 R.1 variants from over 2,900 samples (~0.34%) collected from January to October 2021. Among 3 vaccinated individuals previously infected with R.1, we observed robust neutralizing antibody responses against SARS-CoV-2 wild type and VOCs.

BackgroundLow serum alkaline phosphatase levels are the hallmark of hypophosphatasia, a disorder due to pathogenic variants of the ALPL gene. However, some patients do not carry ALPL variants and the cause of low alkaline phosphatase remains unknown. We aimed to determine health-related quality of life in adults with low alkaline phosphatase and explore the differences between patients with and without ALPL mutations.MethodsWe studied 35 adult patients with persistently low alkaline phosphatase unrelated to secondary acquired causes who had ALPL sequenced, and 35 controls of similar age. Three questionnaires about body pain (Brief Pain Inventory, BPI), physical disability (Health Assessment Questionnaire Disability Index, HAQ-DI), and health-related quality of life (36-item Short-Form Health Survey, SF-36) were delivered by telephone interviews.ResultsThe mean BPI intensity and interference scores were higher in the patient group (p=0.04 and 0.004, respectively). All domains of the HAQ instrument tended to score better in the control group, with significant differences in the “reach” score (p=0.037) and the overall mean score (0.23 vs 0.09; p=0.029). Patients scored worse than controls in several SF-36 dimensions (Role physical, p=0.039; Bodily pain p=0.046; Role emotional, p=0.025). Patients with and without pathogenic variants scored similarly across all tests, without between-group significant differences.ConclusionsPatients with persistently low levels of alkaline phosphatase have significantly worse scores in body pain and other health-related quality of life dimensions, without differences between patients with and without pathogenic variants identified in ALPL gene. This is consistent with the latter ones carrying mutations in regulatory regions.

Objective: To characterize the evolution of healthcare workers’ mental health status over the 1-year period following the initial COVID-19 pandemic outbreak and to examine baseline characteristics associated with resolution or persistence of mental health problems over time.Methods: We conducted an 8-month follow-up cohort study. Eligible participants were healthcare workers working in Spain. Baseline data were collected during the initial pandemic outbreak. Survey-based self-reported measures included COVID-19-related exposures, sociodemographic characteristics, and three mental health outcomes (psychological distress, depression symptoms, and posttraumatic stress disorder symptoms). We examined three longitudinal trajectories in mental health outcomes between baseline and follow-up assessments (namely asymptomatic/stable, recovering, and persistently symptomatic/worsening).Results: We recruited 1,807 participants. Between baseline and follow-up assessments, the proportion of respondents screening positive for psychological distress and probable depression decreased, respectively, from 74% to 56% and from 28% to 21%. Two-thirds remained asymptomatic/stable in terms of depression symptoms and 56% remained symptomatic or worsened over time in terms of psychological distress.Conclusion: Poor mental health outcomes among healthcare workers persisted over time. Occupational programs and mental health strategies should be put in place.

BackgroundHealthcare workers (HCWs) from COVID-19 hotspots worldwide have reported poor mental health outcomes since the pandemic's beginning. The virulence of the initial COVID-19 surge in Spain and the urgency for rapid evidence constrained early studies in their capacity to inform mental health programs accurately. Here, we used a qualitative research design to describe relevant mental health problems among frontline HCWs and explore their association with determinants and consequences and their implications for the design and implementation of mental health programs.Materials and methodsFollowing the Programme Design, Implementation, Monitoring, and Evaluation (DIME) protocol, we used a two-step qualitative research design to interview frontline HCWs, mental health experts, administrators, and service planners in Spain. We used Free List (FL) interviews to identify problems experienced by frontline HCWs and Key informant (KI) interviews to describe them and explore their determinants and consequences, as well as the strategies considered useful to overcome these problems. We used a thematic analysis approach to analyze the interview outputs and framed our results into a five-level social-ecological model (intrapersonal, interpersonal, organizational, community, and public health).ResultsWe recruited 75 FL and 22 KI interviewees, roughly balanced in age and gender. We detected 56 themes during the FL interviews and explored the following themes in the KI interviews: fear of infection, psychological distress, stress, moral distress, and interpersonal conflicts among coworkers. We found that interviewees reported perceived causes and consequences across problems at all levels (intrapersonal to public health). Although several mental health strategies were implemented (especially at an intrapersonal and interpersonal level), most mental health needs remained unmet, especially at the organizational, community, and public policy levels.ConclusionsIn keeping with available quantitative evidence, our findings show that mental health problems are still relevant for frontline HCWs 1 year after the COVID-19 pandemic and that many reported causes of these problems are modifiable. Based on this, we offer specific recommendations to design and implement mental health strategies and recommend using transdiagnostic, low-intensity, scalable psychological interventions contextually adapted and tailored for HCWs.

Background Inconsistent doses and schemes are commonly used in older patients receiving cancer chemotherapy. We performed this study in patients with cancer and age ≥ 70 years to determine the frequency of undertreatment and overtreatment as well as factors influencing the decision to modify chemotherapy doses. Patients and Methods Patients aged ≥70 years starting new chemotherapy regimens were prospectively included in a multicentre study. The schedule and drug doses were determined by the treating oncologist. Pre-chemotherapy assessment included sociodemographics, treatment details and geriatric assessment (GA) variables. Association between these factors and undertreatment (use of less intensive cancer treatment [LICT] in a fit patient) or overtreatment (use of standard cancer treatment in an unfit older patient) were examined by multivariate logistic regression. Results Three- hundred ninety-seven patients were included, 43% of whom received LICT. If not adjusted for GA, toxicity did not differ between those receiving LICT (38%) or standard doses of chemotherapy (37%). If the dose of chemotherapy was analyzed according to the results of GA 61 (15%) patients had been undertreated and 133 (34%) had been overtreated. Undertreatment was related with increasing age and decreased renal function. Factors related with overtreatment were younger age, curative intention of treatment, prescription of G-CSF as primary prophylaxis and adequate cognitive status. Overtreated patients had more grade 3–4 toxicity than those receiving treatment adapted to fragility (42% vs 31%; p Conclusions The use of chemotherapy without considering GA leads to overtreatment more commonly than undertreatment in older patients with cancer. Oncologists should take into account the results of GA to stratify patients and to avoid under or overtreatment.

The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were “conceptual disorganization”, “emotional withdrawal”, “lack of spontaneity and flow of conversation”, “delusions”, “unusual thought content”, “dealing with strangers” and “poor rapport”. Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population, This work was supported by the Madrid Regional Government (R&D activities in Biomedicine (grant number S2017/BMD-3740 - AGES-CM 2-CM)) and Structural Funds of the European Union. Ana Izquierdo’s work is supported by the PFIS predoctoral program (FI17/00138) from the Instituto de Salud Carlos III (Spain) and co-funded by the European Union (ERDF/ESF, "A way to make Europe”/ “Investing in your future”) and The Biomedical Research Foundation of La Princesa University Hospital. Angela Ib´a˜nez thanks the support of CIBERSAM and of the Spanish Ministry of Science, Innovation and Universities. Instituto de Salud Carlos III (PI16/00834 and PI19/01295) co-financed by ERDF Funds from the European Commission. Covadonga M. Díaz-Caneja holds a Juan Rod´es Grant from Instituto de Salud Carlos III (JR19/00024). Celso Arango was supported by the Spanish Ministry of Science and Innovation. Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/ 024), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM. Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds. European Union Seventh Framework Program under grant agreements FP7-4-HEALTH-2009-2.2.1-2-241909 (Project EU-GEI), FP7- HEALTH- 2013-2.2.1-2-603196 (Project PSYSCAN) and FP7- HEALTH-2013- 2.2.1-2-602478 (Project METSY); and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No 115916, Project PRISM, and grant agreement No 777394, Project AIMS-2-TRIALS), Fundaci´on Familia Alonso, Fundaci´on Alicia Koplowitz and Fundaci´on Mutua Madrile˜na

Background We studied the determinants of hemodynamics and analyzed the incidence, risk factors, and clinical impact of pulmonary homograft dysfunction following Ross surgery, after a 20-year follow-up at our referral center. Methods From 1997 to 2017, a total of 142 patients underwent surgery using the Ross procedure. The development of moderate-severe stenosis (peak transhomograft pressure gradient 36 mm Hg or greater) and surgical or percutaneous Ross homograft reinterventions were evaluated by echocardiography in the immediate postoperative period and at annual intervals. Results After 20 years of follow-up, 31% of patients had moderate-severe homograft stenosis, and 9.1% had had to undergo one or two reinterventions, of which, six were valve replacements and seven were percutaneous interventions. At 1, 5, and 20 years, 89.4%, 74.6%, and 69% of these patients, respectively, were free from moderate-severe stenosis; and 99.3%, 95.7%, and 90.9%, respectively, had freedom from homograft reintervention. The pediatric group had a higher risk factor for homograft stenosis (hazard ratio 3.70; 95% confidence interval, 1.56 to 7.20, P = .002), whereas donor age behaved as a protective factor (hazard ratio 0.98; 95% confidence interval, 0.95 to 0.99; P = .044). Pulmonary homograft stenosis tended to appear in the first year (10.6%) or at 5 years (25.4%). Conclusions Pulmonary homografts implanted in the Ross procedure offer satisfactory long-term results, but the level of homograft dysfunction is not negligible. Young recipient and donor age were associated with a higher rate of homograft stenosis during follow-up. Moreover, homograft dysfunction usually occurred during the first few years of follow-up, and may have been related to immune responses.

Background: The Covid-19 pandemic caused a shutdown of healthcare systems in many countries. We explored the impact on hypertension care in the Excellence Center (EC) network of the European Society of Hypertension. Methods: We conducted a 17-question electronic survey among ECs. Results: Overall, 52 ECs from 20 European and three non-European countries participated, providing hypertension service for a median of 1500 hypertensive patients per center per year. Eighty-five percent of the ECs reported a shutdown lasting for 9 weeks (range 0–16). The number of patients treated per week decreased by 90%: from a median of 50 (range 10–400) before the pandemic to a median of 5.0 (range 0–150) during the pandemic (P < 0.0001). 60% of patients (range 0–100%) declared limited access to medical consultations. The majority of ECs (57%) could not provide 24-h ambulatory BP monitoring, whereas a median of 63% (range 0–100%) of the patients were regularly performing home BP monitoring. In the majority (75%) of the ECs, hypertension service returned to normal after the first wave of the pandemic. In 66% of the ECs, the physicians received many questions regarding the use of renin–angiotensin system (RAS) blockers. Stopping RAS-blocker therapy (in a few patients) either by patients or physicians was reported in 27 and 36.5% of the ECs. Conclusion: Patient care in hypertension ECs was compromised during the Covid-19-related shutdown. These data highlight the necessity to develop new strategies for hypertension care including virtual clinics to maintain services during challenging times.

Summary Background Genome-edited donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T cells offer a novel form of CAR-T-cell product that is available for immediate clinical use, thereby broadening access and applicability. UCART19 is one such product investigated in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Two multicentre phase 1 studies aimed to investigate the feasibility, safety, and antileukaemic activity of UCART19 in children and adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Methods We enrolled paediatric or adult patients in two ongoing, multicentre, phase 1 clinical trials to evaluate the safety and antileukaemic activity of UCART19. All patients underwent lymphodepletion with fludarabine and cyclophosphamide with or without alemtuzumab, then children received UCART19 at 1·1–2·3 × 106 cells per kg and adults received UCART19 doses of 6 × 106 cells, 6–8 × 107 cells, or 1·8–2·4 × 108 cells in a dose-escalation study. The primary outcome measure was adverse events in the period between first infusion and data cutoff. These studies were registered at ClinicalTrials.gov, NCT02808442 and NCT02746952. Findings Between June 3, 2016, and Oct 23, 2018, seven children and 14 adults were enrolled in the two studies and received UCART19. Cytokine release syndrome was the most common adverse event and was observed in 19 patients (91%); three (14%) had grade 3–4 cytokine release syndrome. Other adverse events were grade 1 or 2 neurotoxicity in eight patients (38%), grade 1 acute skin graft-versus-host disease in two patients (10%), and grade 4 prolonged cytopenia in six patients (32%). Two treatment-related deaths occurred; one caused by neutropenic sepsis in a patient with concurrent cytokine release syndrome and one from pulmonary haemorrhage in a patient with persistent cytopenia. 14 (67%) of 21 patients had a complete response or complete response with incomplete haematological recovery 28 days after infusion. Patients not receiving alemtuzumab (n=4) showed no UCART19 expansion or antileukaemic activity. The median duration of response was 4·1 months with ten (71%) of 14 responders proceeding to a subsequent allogeneic stem-cell transplant. Progression-free survival at 6 months was 27%, and overall survival was 55%. Interpretation These two studies show, for the first time, the feasibility of using allogeneic, genome-edited CAR T cells to treat patients with aggressive leukaemia. UCART19 exhibited in-vivo expansion and antileukaemic activity with a manageable safety profile in heavily pretreated paediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. The results this study are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR-T-cell therapy is unavailable. Funding Servier.

The integrity of the perirhinal cortex (PRh) is essential for object recognition memory (ORM) function, and damage to this brain area in animals and humans induces irreversible ORM deficits. Here, we show that activation of area V2, a brain area interconnected with brain circuits of ventral stream and medial temporal lobe that sustain ORM, by expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned rats and nonhuman primates. Furthermore, this treatment was sufficient for full recovery of ORM in rodent models of aging and Alzheimer's disease, conditions thought to affect multiple brain areas. Thus, RGS14414-mediated activation of area V2 has therapeutic relevance in the recovery of recognition memory, a type of memory that is primarily affected in patients or individuals with symptoms of memory dysfunction. These findings suggest that area V2 modulates the processing of memory-related information through activation of interconnected brain circuits formed by the participation of distinct brain areas.

This work analyzed the use of Microsoft HoloLens 2 in orthopedic oncological surgeries and compares it to its predecessor (Microsoft HoloLens 1). Specifically, we developed two equivalent applications, one for each device, and evaluated the augmented reality (AR) projection accuracy in an experimental scenario using phantoms based on two patients. We achieved automatic registration between virtual and real worlds using patient-specific surgical guides on each phantom. They contained a small adaptor for a 3D-printed AR marker, the characteristic patterns of which were easily recognized using both Microsoft HoloLens devices. The newest model improved the AR projection accuracy by almost 25%, and both of them yielded an RMSE below 3 mm. After ascertaining the enhancement of the second model in this aspect, we went a step further with Microsoft HoloLens 2 and tested it during the surgical intervention of one of the patients. During this experience, we collected the surgeons’ feedback in terms of comfortability, usability, and ergonomics. Our goal was to estimate whether the improved technical features of the newest model facilitate its implementation in actual surgical scenarios. All of the results point to Microsoft HoloLens 2 being better in all the aspects affecting surgical interventions and support its use in future experiences. This work was supported by projects PI18/01625, AC20/00102-3 and Era Permed PerPlanRT (Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, Asociación Española Contra el Cáncer and European Regional Development Fund "Una manera de hacer Europa") and IND2018/TIC-9753 (Comunidad de Madrid).

The prognosis for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia remains poor. UCART19, an allogeneic genome-edited anti-CD19 chimeric antigen receptor (CAR) T-cell product derived from healthy donors and available for immediate clinical use, offers a potential therapeutic option for such patients. The CALM trial is a first-in-human study evaluating the safety and antileukaemic activity of UCART19 in adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia.This phase 1, open-label study was conducted at eight centres across France, the UK, the USA, and Japan. Adult patients aged 16-70 years with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukaemia who had morphological relapse or a minimal residual disease level of at least 1 × 10Between Aug 1, 2016, and June 30, 2020, 25 patients were enrolled in the study and treated with UCART19. Median duration of follow-up was 12·8 months (IQR 2·8-24·8). Median age was 37 years (IQR 28-45). 14 (56%) patients were male and 11 (44%) female. 17 (68%) patients were White, two (8%) Black, two (8%) Asian, and four (16%) from other racial or ethnic groups. Three patients developed dose-limiting toxicities (one at each dose level); one had grade 4 cytokine release syndrome and two had grade 4 prolonged cytopenias. Grade 3 or higher cytokine release syndrome was reported in six (24%) patients and grade 3 or higher neurological toxicity in one (4%) patient. Grade 3 or higher infections occurred in seven (28%) patients, and grade 4 prolonged cytopenia in four (16%) patients. Two (8%) patients developed grade 1 acute cutaneous graft-versus-host disease. 14 patients died, nine from progressive disease and five from infections or other complications, of which four were considered to be related to UCART19 or lymphodepletion, or both. After a median of follow-up of 12·8 months (IQR 2·8-24·8), overall response rate was 48% (95% CI 28-69; 12 of 25 patients), duration of response and median relapse-free survival were 7·4 months (95% CI 1·8 to not calculable), progression-free survival was 2·1 months (95% CI 1·2-2·8), and overall survival was 13·4 months (95% CI 4·8-23·0).UCART19 had a manageable safety profile, and showed evidence of antileukaemic activity in heavily pretreated adult patients with relapsed or refractory B-cell acute lymphoblastic leukaemia. This study shows that allogeneic off-the-shelf CAR T cells can be used safely to treat patients with relapsed B-cell acute lymphoblastic leukaemia.Servier.

The free fatty acid FFA3 receptor (FFA3R) belongs to the superfamily of G-protein-coupled receptors (GPCRs). In the intestine and adipose tissue, it is involved in the regulation of energy metabolism, but its function in the brain is unknown. We aimed, first, to investigate the expression of the receptor in the hippocampus of Alzheimer disease (AD) patients at different stages of the disease and, second, to assess whether genetic inactivation of the Ffar3 gene could affect the phenotypic features of the APP

ObjectivesSARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients.DesignWe evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 hours after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors.ResultsWe included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404–433), and after treatment QTc was prolonged to 423 ms (405–438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14,1 %) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation.ConclusionsAmbulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.What is already known about this subject?Treatment for COVID 19 with empirical drugs hydroxicloroquine, azitromycin and protease inhibitors affects ventricular repolarization by prolonging the QT interval in a variable degree basing upon heterogeneous studiesWhat does this study add?Not critically ill patients with COVID 19 develop a non relevant QT interval prolongation, leading to a modest arrhythmic risk increase, overall in patients with normal basal ECGHow might this impact on clinical practice?Our findings are significant as ECG monitoring of COVID 19 patients is costly and difficult. Ambulatory and stable patients with normal basal ECG might nor benefit from QT assessment afeter treatment initiation

We assessed the outcomes associated with thiotepa, busulfan and fludarabine (TBF) conditioning regimen in a cohort of 29 consecutive patients allografted for myelofibrosis (MF). The median age was 56 (range 42-70) years. According to the refined Dynamic International Prognostic Scoring System (DIPSS-plus), 15 (52%) patients were classified as high risk. Graft source was peripheral blood stem cells in 27 patients. Donor type was HLA-matched related (

The in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly characterized. Here, we report the effects of idelalisib, duvelisib, and umbralisib on regulatory T cells (Tregs) on normal human T cells, T cells from CLL patients, and T cells in an Eμ-TCL1 adoptive transfer mouse CLL model. Ex vivo studies revealed differential effects of these PI3K inhibitors; only umbralisib treatment sustained normal and CLL-associated FoxP3+ human Tregs. Further, although all 3 inhibitors exhibit antitumor efficacy in the Eμ-TCL1 CLL model, idelalisib- or duvelisib-treated mice displayed increased immune-mediated toxicities, impaired function, and reduced numbers of Tregs, whereas Treg number and function were preserved in umbralisib-treated CLL-bearing mice. Finally, our studies demonstrate that inhibition of CK1ε can improve CLL Treg number and function. Interestingly, CK1ε inhibition mitigated impairment of CLL Tregs by PI3K inhibitors in combination treatment. These results suggest that the improved safety profile of umbralisib is due to its role as a dual PI3Kδ/CK1ε inhibitor that preserves Treg number and function.

Background Standard oncology tools are inadequate to distinguish which older patients are at higher risk of developing chemotherapy-related complications. Materials and Methods Patients over 70 years of age starting new chemotherapy regimens were prospectively included in a multicenter study. A prechemotherapy assessment that included sociodemographics, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and the development of grade 3–5 toxicity was examined by using logistic regression. Results A total of 551 patients were accrued. Chemotherapy doses (odds ratio [OR] 1.834; 95% confidence interval [CI] 1.237–2.719) and creatinine clearance (OR 0.989; 95% CI 0.981–0.997) were the only factors independently associated with toxicity. Only 19% of patients who received reduced doses of chemotherapy and had a creatinine clearance ≥40 mL/minute had grade 3–4 toxicity, compared with 38% of those who received standard doses or had a creatinine clearance Conclusion Chemotherapy doses and renal function were identified as the major risk factors for developing severe toxicity in the older patient. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up in these patients.

The mutational profile of plasmablastic lymphoma has not been described. We performed a targeted, exonic next-generation sequencing analysis of 30 plasmablastic lymphoma cases with a Bcell lymphoma-dedicated panel and fluorescence in situ hybridization for the detection of MYC rearrangements. Complete phenotyping of the neoplastic and microenvironmental cell populations was also performed. We identified an enrichment in recurrent genetic events in MYC (69% with MYC translocation or amplification and three cases with missense point mutations), PRDM1/Blimp1 and STAT3 mutations. These gene mutations were more frequent in Epstein-Barr virus (EBV)-positive disease. Other genetic events included mutations in BRAF, EP300, BCR (CD79A and CD79B), NOTCH pathway (NOTCH2, NOTCH1 and SGK1) and MYD88pL265P. Immunohistochemical analysis showed consistent MYC expression, which was higher in cases with MYC rearrangements, together with phospho-STAT3 (Tyr705) overexpression in cases with STAT3 SH2 domain mutations. Microenvironmental cell populations were heterogeneous and unrelated to EBV, with enrichment of tumor-associated macrophages (TAM) and PD1-positive T cells. PD-L1 was expressed in all cases in the TAM population but only in the neoplastic cells in five cases (4 of 14 EBV-positive cases). HLA expression was absent in the majority of cases of plasmablastic lymphoma. In summary, the mutational profile of plasmablastic lymphoma is heterogeneous and related to EBV infection. Genetic events in MYC, STAT3 and PRDM1/Blimp1 are more frequent in EBV-positive disease. An enrichment in TAM and PD1 reactive T lymphocytes is found in the microenvironment of plasmablastic lymphoma and a fraction of the neoplastic cells express PD-L1.

Resumen: Introducción y objetivo: El objetivo del presente estudio es describir los errores de medicación (EM) notificados en atención primaria analizando el ámbito, el daño y las causas, y orientando el análisis a las medidas para prevenir estos errores. Material y métodos: Ámbito: Atención primaria. Servicio Madrileño de Salud. 2016. Diseño: Estudio descriptivo transversal. Participantes: Todas las notificaciones de EM realizadas desde los centros de salud en el sistema de notificación de incidentes de seguridad entre el 1 de enero y el 17 de noviembre de 2016 (n = 1.839). Mediciones principales: Ámbito donde ocurrió el error, daño real, daño potencial y causa del error. Fueron clasificadas por un investigador. Se comprobó la concordancia con otro investigador. Resultados: En el ámbito del centro de salud ocurrieron el 47% (IC95%: 44,8-49,3%) de los EM y en el entorno del paciente el 26,5% (IC95%: 24,5-28,6%). El 27,5% (IC95%: 24,1-30,8%) de los EM tenían potencialidad de daño grave. En el ámbito del centro de salud, la causa más frecuente fue la prescripción inadecuada: 27,4% (IC95%: 24,4-30,4%). En el entorno del paciente, la causa más frecuente fue el fallo en la comunicación profesional-paciente: 66% (IC95%: 61,8-70,2%), seguida por equivocaciones y despistes del paciente. Conclusiones: La mitad de los errores de medicación notificados desde atención primaria tiene lugar en el centro de salud mientras que los EM del paciente son la cuarta parte. Uno de cada 4 es un error potencialmente grave. Las causas más importantes son la prescripción inadecuada (incluyendo indicación o dosis incorrecta, interacciones, contraindicaciones y alergias), los fallos en la comunicación profesional-paciente y los despistes en la autoadministración del paciente. Parece prioritario implantar sistemas de ayuda a la prescripción, prácticas seguras efectivas en comunicación profesional-paciente y ayudas que eviten los despistes en la autoadministración del paciente. Abstract: Introduction and objectives: Aim of this study is to determine the setting, causes, and the harm of medication errors (ME) which are notified by Primary Health Care. Material and methods: Setting: Primary Care Regional Health Service of Madrid. 2016. Design: Descriptive and cross-sectional study. Participants: All ME (1,839) which were notified by Primary Care Centres by notification system of safety incidents between January 1 st 2016 and November 17th 2016. Main measurements: Setting, real harm, potential harm, and cause of error. These items were classified by one researcher. Concordance was checked with another researcher. Results: Just under half (47%) (95% CI: 44.8%-49.3%) of ME occurred in Primary Care Centre, 26.5% (95% CI: 24.5%-28.6%) of ME were patient medication errors, and 27.5% (95% CI: 24.1%-30.8%) of ME were potential severe harm errors. Prescribing errors were the cause of most ME in Primary Care Centre [27.4% (95% CI: 24.4%-30.4%)]. Communication between patients and doctors were the cause of most patient medication errors [66% (95% CI: 61.8%-70.2%)]. Patient mistakes and forgetfulness were also causes of patient medication errors. Conclusions: Half of all mediation errors hppened at Primary Care Center while one quarter of them were patient medication errors.One quarter of all ME were potential severe harm errors. The main causes were prescribing errors, failure of communication between patients and doctors, and patient mistakes and forgetfulness. Prescribing aid systems, communication improvements and patients aids should be implemented. Palabras clave: Seguridad del paciente, Errores de medicación, Atención primaria, Keywords: Patient safety, Medication errors, Primary care

Aim Cardiotoxicity (CTox) is a major side effect of cancer therapies, but uniform diagnostic criteria to guide clinical and research practices are lacking. Methods and results We prospectively studied 865 patients, aged 54.7 ± 13.9; 16.3% men, scheduled for anticancer therapy related with moderate/high CTox risk. Four groups of progressive myocardial damage/dysfunction were considered according to current guidelines: normal, normal biomarkers (high-sensitivity troponin T and N-terminal natriuretic pro-peptide), and left ventricular (LV) function; mild, abnormal biomarkers, and/or LV dysfunction (LVD) maintaining an LV ejection fraction (LVEF) ≥50%; moderate, LVD with LVEF 40–49%; and severe, LVD with LVEF ≤40% or symptomatic heart failure. Cardiotoxicity was defined as new or worsening of myocardial damage/ventricular function from baseline during follow-up. Patients were followed for a median of 24 months. Cardiotoxicity was identified in 37.5% patients during follow-up [95% confidence interval (CI) 34.22–40.8%], 31.6% with mild, 2.8% moderate, and 3.1% with severe myocardial damage/dysfunction. The mortality rate in the severe CTox group was 22.9 deaths per 100 patients-year vs. 2.3 deaths per 100 patients-year in the rest of groups, hazard ratio of 10.2 (95% CI 5.5–19.2) (P Conclusions The majority of patients present objective data of myocardial injury/dysfunction during or after cancer therapy. Nevertheless, severe CTox, with a strong prognostic relationship, was comparatively rare. This should be reflected in protocols for clinical and research practices.

Objective Increasing evidence has shown the involvement of the innate immune system and inflammatory response in osteoarthritis (OA) pathogenesis; however, anterior cruciate ligament (ACL) tears are recognized risk factors for development of post-traumatic OA. We investigated (1) whether inflammatory mediators involved in OA pathogenesis are also present at significant concentrations in the knee joint sometime after ACL complete tear and may be considered as prognostic biomarkers of progression to secondary OA; and (2) whether quantification in serum may surrogate synovial fluid (SF) measurements in both cases. Methods Thirty-seven end-stage OA patients and 33 patients with ACL complete tear that were included on the waiting list for knee surgery were consecutively recruited. Serum and SF samples were taken before surgery, and tumor necrosis factor-alpha, (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinase-1 (TIMP1), bone morphogenetic protein-7 (BMP7), regulated upon activation normal t-cell expressed and secreted (RANTES), cytokine interferon-γ-induced protein 10 (IP-10) and heat shock protein family A (Hsp70) member 1A (HSPA1A) were quantified by enzyme-linked immunosorbent assay (ELISA.) Normally distributed data were compared using a one-way analysis of variance (ANOVA) test. Data not normally distributed were analyzed using a nonparametric Mann–Whitney rank sum test. Differences in means were compared using a Student's t-test. Correlations were analyzed using Pearson's coefficient of variation. Results Eighty-seven percent of patients with OA and 86% of those with ACL tear had quantifiable levels of biomarkers in SF. SF levels of IL-6, IL-8, MMP1, MMP3, RANTES, IP-10, BMP7 and HSPA1A were significantly lower in ACL injury knees compared with those with OA, but much higher than those reported in control subjects. Serum levels of IL-6, IP-10, and MMP1 were also lower in patients with ACL tears, who had, however, significantly higher TNF-α, HSPA1A, and TIMP1 levels when compared with OA patients. Levels of biomarkers tested in serum and SF samples were significantly different. Conclusions Our data propose that cytokines IL-6 and IL-8 and the chemokines RANTES, IP-10, MMP1, MMP3, and HSPA1A may be involved in the inflammatory process leading to synovitis, the central lesion in OA onset and development; persistent high levels of these substances sometime after ACL injury suggest that they could play an etiopathogenic role in the maintenance of the inflammatory environment leading to post-traumatic OA. Serum biomarker levels do not appear to faithfully reflect what occurs inside the joint. Thus, most biomarkers cannot yet be considered as useful inflammatory biomarkers of knee joint diseases.

The ability of MALDI-TOF for the identification of nontuberculous mycobacteria (NTM) has improved recently thanks to updated databases and optimized protein extraction procedures. Few multicentre studies on the reproducibility of MALDI-TOF have been performed so far, none on mycobacteria. The aim of this study was to evaluate the reproducibility of MALDI-TOF for the identification of NTM in 15 laboratories in 9 European countries. A total of 98 NTM clinical isolates were grown on Löwenstein-Jensen. Biomass was collected in tubes with water and ethanol, anonymized and sent out to the 15 participating laboratories. Isolates were identified using MALDI Biotyper (Bruker Daltonics). Up to 1330 MALDI-TOF identifications were collected in the study. A score ≥ 1.6 was obtained for 100% of isolates in 5 laboratories (68.2–98.6% in the other). Species-level identification provided by MALDI-TOF was 100% correct in 8 centres and 100% correct to complex-level in 12 laboratories. In most cases, the misidentifications obtained were associated with closely related species. The variability observed for a few isolates could be due to variations in the protein extraction procedure or to MALDI-TOF system status in each centre. In conclusion, MALDI-TOF showed to be a highly reproducible method and suitable for its implementation for NTM identification.

Background Healthcare workers (HCWs) from COVID-19 pandemic hotspots across the globe have reported mental health problems, including anxiety, depression, or sleep problems. Many studies have focused on identifying modifiable risk factors, such as being afraid of getting infected or reporting shortage of personal protective equipment, but none have explored the role of protective factors. Method This cross-sectional study used an online survey to describe the association between three potentially protective factors (self-reported resilience, self-perceived social support from colleagues at work, and self-perceived social support from relatives and friends) and three mental health outcomes, namely psychological distress, depression symptoms, and death thoughts in a large sample of Spanish HCWs during the first wave of the COVID-19 pandemic. Results We recruited 2372 respondents between April 26th and June 22nd, 2020. Resilience and self-perceived social support were inversely associated with mental health problems (psychological distress, depression symptoms, and death thoughts), after adjusting for potential sources of confounding. Conclusions Resilience and self-perceived social support might protect HCWs against negative mental health outcomes. Public health strategies targeting these modifiable determinants might help to reduce the impact of the pandemic on HCWs’ mental health.

Emergence of SARS-CoV-2 with high transmission and immune evasion potential, the so-called variants of concern (VOC), is a major concern. We describe the early genomic epidemiology of SARS-CoV-2 recovered from vaccinated health care professionals (HCP). Our postvaccination COVID-19 symptoms-based surveillance program among HCPs in a 17-hospital network identified all vaccinated HCPs who tested positive for COVID-19 after routine screening or after self-reporting. From 1 January 2021 to 30 April 2021, 23,687 HCPs received either mRNA-1273 or BNT162b2 mRNA vaccine. All available postvaccination SARS-CoV-2 samples and a random collection from nonvaccinated patients during the similar time frame were subjected to VOC screening and whole-genome sequencing (WGS). Sixty-two percent (23,697/37,500) of HCPs received at least one vaccine dose, with 60% (22,458) fully vaccinated. We detected 138 (0.58%, 138/23,697) COVID-19 cases, 105 among partially vaccinated and 33 (0.15%, 33/22,458) among fully vaccinated. Five partially vaccinated required hospitalization, four with supplemental oxygen. VOC screening from 16 fully vaccinated HCPs identified 6 (38%) harboring N501Y and 1 (6%) with E484K polymorphisms; percentage of concurrent nonvaccinated samples was 37% (523/1,404) and 20% (284/1,394), respectively. There was an upward trend from January to April for E484K/Q (3% to 26%) and N501Y (1% to 49%). WGS analysis from vaccinated and nonvaccinated individuals indicated highly congruent phylogenies. We did not detect an increased frequency of any receptor-binding domain (RBD)/N-terminal domain (NTD) polymorphism between groups (P > 0.05). Our results support robust protection by vaccination, particularly among recipients of both doses. Despite VOCs accounting for over 40% of SARS-CoV-2 from fully vaccinated individuals, the genomic diversity appears to proportionally represent VOCs among nonvaccinated populations. IMPORTANCE A number of highly effective vaccines have been developed and deployed to combat the COVID-19 pandemic. The emergence and epidemiological dominance of SARS-CoV-2 mutants with high transmission potential and immune evasion properties, the so-called variants of concern (VOC), continue to be a major concern. Whether these VOCs alter the efficacy of the administered vaccines is of great concern and a critical question to study. We describe the initial genomic epidemiology of SARS-CoV-2 recovered from partial/fully vaccinated health care professionals and probe specifically for VOC enrichment. Our findings support the high level of protection provided by full vaccination despite a steep increase in the prevalence of polymorphisms associated with increased transmission potential (N501Y) and immune evasion (E484K) in the nonvaccinated population. Thus, we do not find evidence of VOC enrichment among vaccinated groups. Overall, the genomic diversity of SARS-CoV-2 recovered postvaccination appears to proportionally represent the observed viral diversity within the community.

Cupressus sempervirens L., Juniperus communis L. and Cistus ladanifer L. are Mediterranean arboreal and shrub species that possess essential oils (EO) in their leaves and branches. This study aimed at characterizing the EOs obtained by steam distillation from the three species collected in different locations from Spain (Almazán, Andévalo, Barriomartín, Cerezal, Ermitas and Huéscar). For this purpose, volatiles composition was determined by GC-MS, and different bioactivities were evaluated. The highest content in terpenes was observed in C. sempervirens (Huéscar origin) followed by J. communis (Almazán origin), corresponding to 92% and 91.9% of total compounds, respectively. With exception of C. ladanifer from Cerezal that presented viridiflorol as the most abundant compound, all the three species presented in common the -pinene as the major compound. The EOs from C. ladanifer showed high antibacterial potential, presenting MIC values from 0.3 to 1.25 mg/mL. Concerning other bioactivities, C. ladanifer EO revealed an oxidation inhibition of 83%, while J. communis showed cytotoxicity in the MCF-7 cell line, and C. sempervirens and C. ladanifer EOs exhibited the highest potential on NCI-H460 cell lines. Nevertheless, some EOs revealed toxicity against non-tumoral cells but generally presented a GI50 value higher than that of the tumor cell lines. Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to the CIMO (UIDB/00690/2020). L. Barros, R. Calhelha and S.A. Heleno (CEEC-IND/03040/2017) thank the national funding by FCT, P.I., through the institutional and individual scientific employment program-contract for their contracts. This project has received funding from the Bio Based Industries Joint Undertaking (JU) under grant agreement No 887917 BeonNAT. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and the Bio Based Industries Consortium. info:eu-repo/semantics/publishedVersion

SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig Cardells, The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re, This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.

Aims Knowledge of the features of patients with familial hypercholesterolaemia (FH) who are protected from atherosclerotic cardiovascular disease (ASCVD) is important for the clinical and prognostic care of this apparently high-risk condition. Our aim was to investigate the determinant and characteristics of patients with FH who are protected from ASCVD and have normal life expectancy, so-called ‘resilient’ FH (R-FH). Methods and results Spanish Familial Hypercholesterolaemia cohort study (SAFEHEART) is an open, multicentre, nation-wide, long-term prospective cohort study in genetically defined patients with heterozygous FH in Spain. Patients in the registry who at the time of analysis were at least 65 years or those who would have reached that age had they not died from an ASCVD event were analysed as a case–control study. Resilient FH was defined as the presence of a pathogenic mutation causative of FH in a patient aged ≥65 years without clinical ASCVD. Nine hundred and thirty registrants with FH met the study criteria. A defective low-density lipoprotein (LDL)-receptor mutation, higher plasma level of high-density lipoprotein cholesterol (HDL-C), younger age, female gender, absence of hypertension, and lower plasma lipoprotein (a) [Lp(a)] concentration were independently predictive of R-FH. In a second model, higher levels of HDL-C and lower 10-year score in SAFEHEART-RE were also independently predictive of R-FH. Conclusion Resilient FH may be typified as being female and having a defective LDL-receptor mutation, higher levels of plasma HDL-C, lower levels of Lp(a), and an absence of hypertension. The implications of this type of FH for clinical practice guidelines and the value for service design and optional care of FH remains to be established. Trial registration ClinicalTrials.gov number NCT02693548.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), harboring spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) mutations, exhibit reduced in vitro susceptibility to convalescent-phase serum, commercial antibody cocktails, and vaccine neutralization and have been associated with reinfections. The accumulation of these mutations could be the consequence of intrahost viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on steroids and convalescent plasma therapy and identify the emergence of multiple NTD and RBD mutations. SARS-CoV-2 genomes from the first swab (day 0) and from three tracheal aspirates (days 7, 21, and 27) were compared at the sequence level. We identified a mixed viral population with five different S protein mutations (141 to 144 deletion, 243 to 244 deletion, E484K, Q493K, and Q493R) at the NTD or RBD region from the second tracheal aspirate sample (day 21) and a predominance of the S protein 141 to 144 LGVY deletion and E484K mutant on day 27. The neutralizing antibodies against various S protein lentiviral pseudovirus mutants, as well as the anti-SARS-CoV-2 total Ig and IgG, showed “U” shape dynamics, in support of the endogenous development of neutralizing antibodies. The patient’s compromised immune status, the antirejection regiment, convalescent plasma treatment, and the development of neutralizing antibodies may have resulted in unique selective pressures on the intrahost genomic evolution, and this observation supports the hypotheses that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune escape mutants. IMPORTANCE Over a year of the COVID-19 pandemic, distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages have arisen in multiple geographic areas around the world. SARS-CoV-2 variants of concern (VOCs), i.e., B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.2 (delta), harboring mutations and/or deletions in spike protein N-terminal domain (NTD) or receptor-binding domain (RBD) regions showed evidence of increased transmissibility and disease severity and possible reduced vaccine efficacy. In this study, we report the emergence of five different NTD and RBD mutations in an uncommon SARS-CoV-2 B.1.369 lineage from an immunosuppressed patient undergoing steroid and convalescent plasma therapy. The observation highlighted that VOCs can independently arise in immunocompromised populations undergoing anti-SARS-CoV-2 therapy, and enhanced measures will be required to reduce the transmission.

Background Autobiographical memory is an important component of declarative memory, which refers to the ability to recall personal events that happened in the past. This requires that the person senses or experiences himself/herself in the past (i.e., conscious recollection). For people with schizophrenia, conscious recollection can be particularly difficult, resulting in difficulty accessing detailed, specific autobiographical information. Our hypothesis is that the ability to monitor and think about one's cognitive processes (metacognition) is a requisite for conscious recollection, and that it mediates the association between having schizophrenia and recalling fewer specific, personal memories. Methods Participants were 30 adults with schizophrenia and 30 matched healthy controls. The main assessment instruments were the Metacognition Assessment Scale-Abbreviated (MAS-A) and the Autobiographical Memory Test (AMT). Severity of symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Cognitive performance was measured with the Screen for Cognitive Impairment in Psychiatry (SCIP). Mediation analysis was conducted following Baron and Kenny's procedure. Results People with schizophrenia had more semantic associations and fewer specific memories than controls in the AMT. Metacognition (MAS-A total score) partially mediated the association between having schizophrenia and recalling fewer specific past events, even after controlling for cognitive impairment as a potential confounding source. Conclusions Metacognitive ability, which can be improved with available programs, intervenes in the process of accessing autobiographical memories in people with schizophrenia. Practical implications of this finding are discussed.

International audience; Background aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD.

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days. The median days to neutrophil engraftment was 17 (range, 12-34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

Previous research has consistently evidenced that children with speech and language difficulties suffer more bullying victimisation during middle school years, whereas other educative stages remain less explored. Moreover, there are divergent results in previous evidence about the types of victimisation (physical, verbal, relational) youths may experience.To examine the retrospective developmental trajectories of bullying victimisation in adults with and without self-reported oral language difficulties across seven educational stages (preschool to university). Special attention was given to the prevalence and types of victimisation.A total of 336 participants (ages between 18 and 65, M = 30.3) from a sample of 2259 participants that fully answered an online survey were classified as having experienced oral language difficulties (LD) not associated with a biomedical condition. A comparable control group (n = 336; ages between 18 and 72, M = 30.0) was randomly selected for statistical between-groups contrasts. Responses to the California Bullying Victimization Scale-Retrospective (CBVS-R) were analysed by generalised estimating equations (GEE) including language groups, types of bullying, and educational stages as explanatory variables. Specific language group comparisons in terms of percentages were conducted using chi-square tests.GEE results suggested that experiencing LD was associated with an overall increase in the likelihood of bullying victimisation, Wald's χPeople with oral language difficulties experience more bullying victimisation behaviours than their typically developing peers. Heightened bullying prevalence in children with language difficulties seems to emerge as early as 6-9 years old and persists along the rest of schooling. Not all victimisation forms seem to show differential increased rates in people with speech/language difficulties, evidencing important implications for bullying assessment. Results highlight the need to provide particular support to individuals with language difficulties against bullying during the entire schooling.

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.

Treatment of chronic myeloid leukaemia (CML) is based on tyrosine kinase inhibitors (TKI), whose introduction in 2001 improved the survival rate after 5 years from 40 to 90%. The longevity increase has been accompanied by a higher incidence of cardiovascular events (CVE) that can be explained due to the sum of cardiovascular risk factors (CVRF) together with the secondary effects of the TKI. The effect of the TKI over the blood pressure control is still unknown. An observational cross-sectional study of patients with CML under treatment with TKI (imatinib, dasatinib and nilotinib) was conducted. Blood pressure was analyzed through sphygmomanometer and 24-h ambulatory blood pressure monitoring (ABPM). A total of 73 patients were included, 57 treated with a single line of treatment. 32.9% of the total of individuals under this study showed uncontrolled blood pressure according to the ABPM. The factors related to uncontrolled BP were overweight, dyslipidemia, alcohol use, pulse wave velocity a high/very high cardiovascular risk. The subjects who received treatment with nilotinib did present worse control of their blood pressure in ABPM than those treated with imatinib and dasatinib (p = 0.041). This finding could indicate that an uncontrolled blood pressure is implied in the pro-inflammatory and pro-atherogenic mechanism underlying the development of the cardiovascular disease in those patients under treatment with nilotinib. The ABPM is a useful tool in the diagnosis and treatment of HT, being the reason why it should be included in the assessment of patients with CML whose HT diagnosis proves uncertain.

To evaluate the association of neuthophyl/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) with BCG intravesical responses in patients with initial diagnosis of non/muscle invasive bladder tumor high-risk (NMIBC).Retrospective multicenter study on patients with initial diagnosis of high-grade NMIBC treated with BCG between January 2016 and December 2017. Initially a total of 74 patients were collected. Those patients with mixt pathology, cis, chronic corticoid usage and lost to follow-up, were excluded. Induction BCG (x6) and BCG maintenance schedules were administered (x9) over 1 year. Demographic variables (sex, age, BMI) and blood variables (NLR, PLR) before BCG instillation were collected. Response to treatment was defined as absence of recurrence and/ or progression. A statistical analysis with T-student, Chi square, ANOVA and ROC curves was performed.Final study cohort included a total of 50 patients. 10 females and 40 males. Median age was 70 year old. All patients had pure urothelial carcinoma, 12 with pTa and 38 with pT1. Median follow-up was 24 months. A total of 28% had a recurrence. No correlation between NLR or PLR and BCG response was observed (p=0.738; p= 0.768). Neither a cut off was established through ROC curves. At multivariate analysis, there was no significative relationship between recurrence and the clinical and blood samples analyzed (sec, age, BMI, NLR, PLR)CONCLUSION: No correlation between NLR and PLR has been reported with BCG response on high-grade NMIBC.Evaluar la asociación de la ratio neutrófilo/linfocito (RNL) y ratio plaqueta/linfocito (RPL) con la respuesta al tratamiento mediante instilaciones de Bacilo Calmette Guerin (BCG) intravesical, en pacientes con diagnóstico inicial de tumor vesical no músculo-invasivos (TVNMI) de alto riesgo.MATERIAL Y MÉTODOS: Estudio retrospectivo multicéntrico con pacientes diagnosticados de tumor vesical inicial de alto riesgo y sometidos a instilaciones endovesicales con BCG entre enero 2016 y diciembre 2017. Inicialmente se recogieron 74 pacientes con tumor vesical inicial. Se excluyeron aquellos sin estirpe urotelial pura, con carcinoma in situ (Cis) asociado, con tratamientos corticoideos crónicos y perdidos durante el seguimiento. Instilamos dosis completa de BCG (81mg) con pauta de inducción (6 dosis) y mantenimiento (9 dosis) durante un año. Se recogieron variables demográficas (sexo, edad e índice de masa corporal) y analíticas (RNL y RPL) previas al inicio del tratamiento con BCG. Definimos respuesta al tratamiento como ausencia de recidiva y/o progresión. Se realizó análisis estadístico mediante t de student, Chi cuadrado, ANOVA y curvas ROC.La cohorte del estudio incluyó finalmente 50 pacientes: 10 mujeres y 40 varones, con una edad media de 70 años. Todos estos pacientes tenían tumor urotelial puro alto grado, 12 de ellos estadio Ta y 38 estadio T1. El seguimiento mínimo fue de 24 meses, presentando recidiva tumoral un 28% de los pacientes. No se encontró relación entre RNL y éxito de la BCG (p=0,738) ni entre RPL y éxito de BCG (p=0,768). Tampoco pudimos establecer un punto de corte mediante curvas ROC. En el análisis multivariante, no encontramos significación estadística entre la recidiva tumoral y los datos analizados (Variables demográficas: Edad, sexo, índice de masa corporal y variables analíticas: RNL/RPL).CONCLUSIÓN: Pese a lo descrito en la literatura, no hemos encontrado asociación entre la RNL ni la RPL con la respuesta al tratamiento con BCG en TVNMI de alto riesgo.

Resumen Introduccion Las manifestaciones cutaneas se han incluido en el espectro clinico de los pacientes con COVID-19. Nuestro objetivo fue determinar la asociacion entre las lesiones cutaneas observadas en ninos durante la primera ola de la pandemia y la infeccion por SARS-CoV-2, analizando otras posibles etiologias infecciosas o autoinmunes. Material y metodos Estudio observacional, multicentrico, de corte transversal, desarrollado en ninos con manifestaciones cutaneas desde abril hasta mayo de 2020. La determinacion de SARS-CoV-2 se realizo mediante PCR en exudado nasofaringeo y/o serologia. Resultados Se selecciono a 62 ninos; 9 (14,5%) presentaron serologia positiva para SARS-CoV-2, siendo la PCR negativa en todos los casos en los que se realizo. Los pacientes con serologia positiva para SARS-CoV-2 presentaron con mas frecuencia lesiones pernioticas y/o vesiculosas (66,7 vs. 24,5%; p = 0,019). El exantema generalizado, urticarial y maculopapuloso fue mas habitual en el grupo de pacientes con serologia negativa (37,7 vs. 0%; p = 0,047); se aislaron otros patogenos en el 41,5%. No hubo diferencias significativas en cuanto a la positividad de autoanticuerpos entre ambos grupos. Conclusion En nuestro estudio, las lesiones de tipo perniosis o vesiculosas se relacionaron significativamente con el contacto previo con SARS-CoV-2.

Out of 956, there were 95 (10%) CD56+ APL patients treated with PETHEMA ATRA and chemotherapy. CD56+ expression was associated with high WBC, BCR3 isoform, and co-expression of CD2, CD34, CD7, HLA-DR, CD15, and CD117 antigens. CD56+ vs CD56- APL presented higher induction death rate (16% vs 8%, p = .02) and 5-years cumulative incidence of relapse (33% versus 10%, p = .006), irrespectively of the Sanz score (low-risk 47% versus 5%, p