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Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (Fon), is a soilborne disease that significantly limits yield in watermelon ( Citrullus lanatus) and occasionally causes the loss of an entire year's harvest. Reference-quality de novo genomic assemblies of pathogenic and nonpathogenic strains were generated using a combination of next-generation and third-generation sequencing technologies. Chromosomal-level genomes were produced with representatives from three Fon races, facilitating comparative genomic analysis and the identification of chromosomal structural variation. Syntenic analysis between isolates allowed for differentiation of the core and lineage-specific portions of their genomes. This research will support future efforts to refine the scientific understanding of the molecular and genetic factors underpinning the Fon host range, develop diagnostic assays for each of the four races, and decipher the evolutionary history of race 3. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Background We aimed to describe the effectiveness and safety of inhaled antibiotics in chronic obstructive pulmonary disease (COPD) patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment. Methods Multicentre retrospective observational cohort study in COPD patients who had received ≥1 dose of inhaled antibiotics in the last 5 years. Clinical data from the two years prior to and subsequent to the start of the treatment were compared. Primary outcome: COPD exacerbations. Secondary outcomes: side effects, symptomatology (sputum purulence, dyspnoea), microbiological profile and pathogen eradication. Results Of 693 COPD patients analyzed (aged 74.1; 86.3% men; mean FEV1 = 43.7%), 71.7% had bronchiectasis and 46.6% presented chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). After 1 year of treatment with inhaled antibiotics, there was a significant decrease in the number of exacerbations (−33.3%; P Conclusions In COPD patients with multiple exacerbations and/or CBI by any PPM (especially PA), inhaled antibiotics appear to be an effective and safe treatment, regardless of the presence of bronchiectasis.

AIM Surgical site infections (SSIs) are common after colonic surgery. SSIs can cause relevant morbidity and increase costs of care. Preoperative oral antibiotics can reduce the incidence of SSIs after resection of the colon, but the role of mechanical bowel preparation (MBP) is debated. This study aims to assess the impact of a combined regimen of oral antibiotics and MBP on SSIs after colonic surgery. METHODS An international, multicentre, pragmatic, adaptive, parallel-group, randomized controlled trial will be conducted across Europe. Adult patients scheduled to undergo elective colonic resection will be assessed for inclusion. Patients will be randomized into one of two treatment arms: (1) preoperative oral antibiotics without MBP (control); (2) preoperative oral antibiotics with MBP (experimental). All patients will receive intravenous antibiotics at anaesthetic induction. The primary aim will be 30-day SSI, assessed by a blinded nurse. Additional end-points include safety, morbidity and mortality, satisfaction with the preparation, time to return of bowel function, time to complete recovery and time to discharge, long-term results. Analyses will be performed with a modified intention-to-treat approach. Interim analyses are planned. DISCUSSION This will be the first randomized clinical trial to assess the efficacy and safety of preoperative oral antibiotics plus MBP versus preoperative oral antibiotics only, before colonic surgery. The knowledge obtained could help to establish the ideal preparation for patients scheduled to undergo resection of the colon. Full protocol NCT04161599.

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

International audience; Extracellular glutamate levels are maintained low by efficient transporters, whose dysfunction can cause neuronal hyperexcitability, excitotoxicity, and neurological disease. While many methods estimate glutamate uptake in vitro/ex vivo, a limited number of techniques address glutamate transport in vivo. Here, we used in vivo microdialysis in a two-in-one approach combining reverse dialysis of isotopic glutamate to measure uptake ability and zero-flow (ZF) methods to quantify extracellular glutamate levels. The complementarity of both techniques is discussed on methodological and anatomical basis. We used a transgenic mouse model of human disease, expressing low levels of the EAAT-2/GLT1 glutamate transporter, to validate our approach in a relevant animal model. As expected, isotopic analysis revealed an overall decrease in glutamate uptake, while the ZF method unveiled higher extracellular glutamate levels in these mice. We propose a sensitive and expedite two-in-one microdialysis approach that is sufficiently robust to reveal significant differences in neurotransmitter uptake and extracellular levels through the analysis of a relatively low number of animals.

Resumen Introduccion Nuestro objetivo ha sido informar de los resultados oncologicos de pacientes con ERET y antecedentes de neoplasias urologicas que fueron sometidos posteriormente a un trasplante renal (TR). Material y metodo Estudio retrospectivo llevado a cabo en el registro de la Fundacion Puigvert (Barcelona) con 1.200 TR realizados entre 1988 y 2018. Se identificaron 85 neoplasias urologicas que recibieron tratamiento previo al TR en 81 pacientes: 15 (18%) canceres de prostata, 49 (58%) carcinoma de celulas renales (CCR), 19 (22%) carcinomas uroteliales y 2 (2%) canceres de testiculo. Se registraron datos de las caracteristicas basales, la estadificacion del cancer, el tratamiento y el seguimiento, y sobre la cronologia del inicio de dialisis, la inscripcion en la lista de espera y el TR. Los criterios de valoracion fueron la recidiva del cancer, la progresion metastasica, la muerte especifica por cancer y la supervivencia global. Resultados En una mediana de seguimiento de 13,1 anos (2,2-32), se registraron 16/85 (19%) recidivas del cancer, con 3 (4%) progresiones a metastasis y muerte por cancer. La mediana de supervivencia global tras el tratamiento del cancer fue de 25,3 anos y la supervivencia por cancer especifica fue del 95% a los 25 anos. La mediana de tiempo desde el tratamiento del cancer hasta el trasplante de rinon fue de 4,8 anos: 3,7 anos en el cancer de prostata, 3,9 anos en el CCR y 8,8 anos en el cancer vesical. La mediana de tiempo desde el inicio de dialisis hasta el TR fue de 1,8 anos en los pacientes con antecedentes de neoplasia urologica, frente a 0,5 anos en la cohorte total de 1.200 trasplantes renales durante el mismo periodo. Conclusiones Los pacientes con antecedentes de neoplasias urologicas bien seleccionados se pueden beneficiar enormemente del trasplante de rinon con una recidiva del cancer tardia y poco frecuente. Para el cancer de prostata de bajo riesgo y el CCR, podria optimizarse el tiempo de espera, pero se necesitan datos mas solidos en este contexto.

Background We assess the effect of Coronavirus disease 2019 (COVID-19) on UK oral and maxillofacial (OMF) trauma services and patient treatment during the first wave of the pandemic. Materials and Methods From April 1st 2020 until July 31st 2020, OMF Surgery units in the UK were invited to prospectively record all patients presenting with OMF trauma. Information gathered included clinical presentation, mechanism of injury, and how it was managed and whether or not treatment included surgery. Participants were also asked to compare the patient’s care with the treatment, which would have usually been given prior to the crisis. Results Twenty-nine units across the UK contributed with 2229 entries. The most common aetiology was mechanical fall (39%). The most common injuries were soft tissue wounds (52%) and mandible fractures (13%) for hard tissues. Of 876 facial fractures, 79 patients had treatment, which differed from that which would be normal pre-COVID and 33 had treatment deferred meaning 112 (14%) patients received care at variance to normal practice because of COVID restrictions. Conclusions The pattern of OMFS injuries changed during the first COVID-19 lockdown period. For the majority, best practice and delivery of quality trauma care continued in spite on-going operational challenges. Changes to treatment affected only a small proportion of patients. The lessons learnt from the first wave combined with adequate resources and pre-operative patient testing should allow those facial injuries in the second wave to receive best practice care.

The authors of Cardenas et al. 111:1893-1896 (2021) retracted this article because posterior analyses have identified that the assembled genomes contained a substantial proportion of other fungi beyond the orange rust Puccinia kuehnii, mainly Ascomycetes for one isolate and Ustilaginales for the other (metagenomes). This article was retracted on 11 March 2022. Puccinia kuehnii is an obligate biotrophic fungal pathogen that causes orange rust of sugarcane, which is prevalent in many countries around the globe. In the United States, orange rust was first detected in sugarcane in Florida in 2007 and poses a persistent and economically damaging threat to the sugarcane industry in this region. Here, we generated the first genome assemblies for two isolates of P. kuehnii (1040 and 2143) collected in Florida in 2017 from two sugarcane cultivars, CL85-1040 and CP89-2143, respectively. These two rust genome resources will be of immense value for future genomic studies, particularly further exploration of the predicted secretomes that may help define key pathogenicity determinants for this economically important pathogen.

Purpose: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. Material and methods: Longitudinal matched exposed–unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. Results: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (−25.5% vs −3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication ( p < 0.0001). Conclusions: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.

Dominant optic atrophy (DOA) is genetically heterogeneous and most commonly caused by mutations in OPA1. To distinguish between the classical OPA1-related and the recently identified SSBP1-related DOAs, the retina and fovea of 27 patients carrying the SSBP1 p.Arg38Gln variant were scrutinized using 20° × 20° macular cube and 30° and 55° field fundus autofluorescence photographs. Age of onset, visual acuity, retinal nerve fiber layer and macular thicknesses were recorded. Three SSBP1-patients were asymptomatic, 10 had isolated DOA, and 12 had a combined DOA plus foveopathy. The foveopathy, with a tiny defect of the ellipsoid and interdigitation lines, was similar in all patients, independent of age. There were no significant statistical differences in terms of visual acuity and SD-OCT measurements between patients with isolated DOA (mean visual acuity in decimals: 0.54 ± 0.41) and those with combined foveopathy (0.50 ± 0.23). Two patients over 50 years of age developed a progressive rod-cone dystrophy, leading to severe visual impairment. SSBP1-related DOA shares similarities with OPA1-related DOA with an incomplete penetrance and an early childhood visual impairment. Nevertheless, the presence of a congenital foveopathy with no impact on visual acuity is a major criterion to distinguish SSBP1 cases and orient the appropriate genetic analysis.

Supplemental Digital Content is available in the text., Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (

Purpose The aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial. Patients and methods We identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse. Results 39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes. Conclusions Lowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines.

Purpose The LAP07 multicenter randomized study assessed whether chemoradiation therapy increases overall survival versus continuation chemotherapy in patients whose locally advanced pancreatic cancer was controlled after 4 months of induction chemotherapy. This analysis investigated whether failure to adhere to radiation therapy (RT) guidelines influenced survival and toxicity. Methods and Materials This is a planned analysis of secondary objectives in the framework of a randomized international phase 3 trial. The protocol included detailed written RT guidelines. All participating institutions undertook an initial benchmark case to check adherence to protocol guidelines. Centers with major deviation were not allowed to include patients until they achieved a significant improvement and rigorously followed the guidelines. On-trial RT quality assurance consisted of a central review of treatment plan with dose-volume histograms for each patient. Adherence to guidelines was graded as per protocol (PP), minor deviation (MiD), or major deviation (MaD). Results Fifty-seven benchmark cases were evaluated, 26% were classified as PP, 60% were MiD, and 14% were MaD. Among the 442 included patients, 133 patients were randomized in the chemoradiation therapy arm, and 117 patients were assessable for RT quality analysis. RT quality was graded as PP in 38.5% of patients, MiD in 43.6% of patients, and MaD in 17.9% of patients. The most frequent protocol violations were dose distribution heterogeneities. Median overall survival was 17 months with PP and MiD versus 13.4 months with MaD (hazard ratio [HR], 1.63; 95% confidence interval [CI], 0.99-2.71; P = .055). There was no difference in terms of progression-free survival (HR, 1.09; 95% CI, 0.66-1.8; P = .72). Patients with MaD had more nausea than patients treated PP or with MiD (P = .0045). Conclusions MaD was associated with a trend for worst survival. There was no difference in terms of progression-free survival. Because of the low rate of major deviations, their effects on the LAP07 trial results may be negligeable.

Introduction Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Material and methods Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Results Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. Conclusion International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

International audience; The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.

Background The long-term outcome of patients after antitumour necrosis factor alpha (anti-TNF) discontinuation is not well known. Aims To assess the risk of relapse in the long-term after anti-TNF discontinuation. Methods This was an extension of the evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (EVODIS) study (Crohn's disease or ulcerative colitis patients treated with anti-TNFs in whom these drugs were withdrawn after achieving clinical remission) based in the same cohort of patients whose outcome was updated. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn's disease, a partial Mayo score ≤2 in ulcerative colitis and the absence of fistula drainage despite gentle finger compression in perianal disease. Results This was an observational, retrospective, multicenter study. A total of 1055 patients were included. The median follow-up time was 34 months. The incidence rate of relapse was 12% per patient-year (95% confidence interval [CI] = 11-14). The cumulative incidence of relapse was 50% (95% CI = 47-53): 19% at one year, 31% at 2 years, 38% at 3 years, 44% at 4 years and 48% at 5 years of follow-up. Of the 60% patients retreated with the same anti-TNF after relapse, 73% regained remission. Of the 75 patients who did not respond, 48% achieved remission with other therapies. Of the 190 patients who started other therapies after relapse, 62% achieved remission with the new treatment. Conclusions A significant proportion of patients who discontinued the anti-TNF remained in remission. In case of relapse, retreatment with the same anti-TNF was usually effective. Approximately half of the patients who did not respond after retreatment achieved remission with other therapies.

Inhibition of hydroxy acid oxidase 1 (HAO1) is a strategy to mitigate the accumulation of toxic oxalate that results from reduced activity of alanine-glyoxylate aminotransferase (AGXT) in primary hyperoxaluria 1 (PH1) patients. DNA-Encoded Chemical Library (DECL) screening provided two novel chemical series of potent HAO1 inhibitors, represented by compounds 3-6. Compound 5 was further optimized via various structure-activity relationship (SAR) exploration methods to 29, a compound with improved potency and absorption, distribution, metabolism, and excretion (ADME)/pharmacokinetic (PK) properties. Since carboxylic acid-containing compounds are often poorly permeable and have potential active glucuronide metabolites, we undertook a brief, initial exploration of acid replacements with the aim of identifying non-acid-containing HAO1 inhibitors. Structure-based drug design initiated with Compound 5 led to the identification of a nonacid inhibitor of HAO1, 31, which has weaker potency and increased permeability.

Resumen Introduccion El instrumento NECPAL es una herramienta para la identificacion de personas en situacion de enfermedad cronica avanzada con necesidades paliativas. El objetivo del estudio es conocer la prevalencia de pacientes con necesidades paliativas en un Servicio de Neumologia de un hospital terciario mediante la herramienta NECPAL. Como objetivo secundario se plantea conocer la mortalidad al ano de estos pacientes. Material y metodos Estudio trasversal y seguimiento prospectivo de la cohorte de los pacientes identificados como paliativos con la herramienta NECPAL durante 12 meses. La identificacion se realiza en pacientes ingresados > 3 dias en una planta de Neumologia. Hemos evaluado el estatus vital (fallecido o no fallecido) al ano, asi como datos demograficos clinicos, funcionales y uso de recursos sanitarios. Resultados Se analizaron 363 pacientes. De ellos, 87 (24,3%) (IC 95%, 19-30) fueron identificados como NECPAL positivos. En el seguimiento durante un ano fallecieron 54 pacientes, un 60%. No hubo diferencias en mortalidad entre diagnosticos oncologicos y no oncologicos. En el analisis multivariante, la mortalidad se asocio a la demanda de paciente o familiares de atencion paliativa y a la presencia de indicadores especificos de progresion de la enfermedad. Conclusiones La prevalencia de pacientes con necesidades paliativas en una planta de hospitalizacion de agudos de Neumologia es alta (uno de cada cuatro pacientes). El 60% de los identificados como NECPAL positivos en nuestra serie fallece en los primeros 12 meses. Son necesarios formacion y recursos para atender a estos pacientes.

Introduction NECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients. Materials and methods Cross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources. Results We monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19–30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators. Conclusions prevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population.

Background Language delay is one of the major referral criteria for an autism evaluation. Once an autism spectrum diagnosis is established, the language prognosis is among the main parental concerns. Early language regression (ELR) is observed by 10–50% of parents but its relevance to late language level and socio-communicative ability is uncertain. This study aimed to establish the predictive value of ELR on the progression of language development and socio-communicative outcomes to guide clinicians in addressing parents’ concerns at the time of diagnosis. Methods We used socio-communicative, language, and cognitive data of 2,047 autism spectrum participants from the Simons Simplex Collection, aged 4–18 years (mean = 9 years; SD = 3.6). Cox proportional hazard and logistic regression models were used to evaluate the effect of ELR on language milestones and the probability of using complex and flexible language, as defined by the choice of ADOS module at enrollment. Linear models were then used to evaluate the relationship of ELR and non-verbal IQ with socio-communicative and language levels. Results ELR is associated with earlier language milestones but delayed attainment of fluent, complex, and flexible language. However, this language outcome can be expected for almost all autistic children without intellectual disability at 18 years of age. It is mostly influenced by non-verbal IQ, not ELR. The language and socio-communicative level of participants with flexible language, as measured by the Vineland and ADOS socio-communicative subscales, was not affected by ELR. Limitations This study is based on a relatively coarse measure of ultimate language level and relies on retrospective reporting of early language milestones and ELR. It does not prospectively document the age at which language catches up, the relationship between ELR and other behavioral areas of regression, nor the effects of intervention. Conclusions For autistic individuals with ELR and a normal level of non-verbal intelligence, language development follows a “bayonet shape” trajectory: early first words followed by regression, a plateau with limited progress, and then language catch up.

BACKGROUND Left atrial wall thickness (LAWT) has been related to pulmonary vein (PV) reconnections after atrial fibrillation (AF) ablation. The aim was to integrate 3D-LAWT maps in the navigation system and analyze the relationship with local reconnection sites during AF-redo procedures. METHODS Consecutive patients referred for AF-redo ablation were included. Procedure was performed using a single catheter technique. LAWT maps obtained from multidetector computerized tomography (MDCT) were imported into the navigation system. LAWT of the circumferential PV line, the reconnected segment and the reconnected point, were analyzed. RESULTS Sixty patients [44 (73%) male, age 61 ± 10 years] were included. All reconnected veins were isolated using a single catheter technique with 55 min (IQR 47-67) procedure time and 75 s (IQR 50-120) fluoroscopy time. Mean LAWT of the circumferential PV line was 1.46 ± 0.22 mm. The reconnected segment was thicker than the rest of segments of the circumferential PV line (2.05 + 0.86 vs. 1.47 + 0.76, p

Background Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti-PP1Pk or anti-P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti-P and a history of recurrent miscarriages. Case report This P2 k (GLOB:-1; P1PK:-1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non-reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti-P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti-P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. Discussion and review of the literature The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1 k (GLOB:-1; P1PK:1,3), P2 k (GLOB:-1; P1PK:-1,3), or Tj(a-)/p (GLOB:-1; P1PK:-1,-3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. Conclusion Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti-PP1Pk or anti-P fetomaternal incompatibilities.

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections.(1-3) However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.

While over a hundred genes are significantly associated with autism, little is known about the prevalence of variants affecting them in the general population. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Using data from more than 13,000 autistic individuals and 210,000 undiagnosed individuals, we provide a gene-level map of the odds ratio for autism associated to rare loss-of-function (LoF) variants in 185 genes robustly associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the phenotype of undiagnosed individuals heterozygous for such variants and show that they exhibit a decrease in fluid intelligence, qualification level and income, and an increase in material deprivation. These effects were larger for LoFs in autism-associated genes than in other LoF-intolerant genes and appeared largely independent of sex and polygenic scores for autism. Using brain imaging data from 21,049 UK-Biobank individuals, we provide evidence for smaller cortical surface area and volume among carriers of LoFs in genes with high odds ratios for autism. Our gene-level map is a key resource to distinguish genes with high and low odds ratio for autism, and highlights the importance of including quantitative data on both diagnosed and undiagnosed individuals to better delineate the effect of genetic variants beyond the categorical diagnosis. Data are available at https://genetrek.pasteur.fr/.

Background We aimed to report clinical characteristics and outcomes of patients with and without SARS-CoV-2 infection referred for acute coronary syndrome (ACS) during the peak of the pandemic in France. Methods We included all consecutive patients referred for ST-elevation myocardial infarction (STEMI) or NSTEMI during the first 3 weeks of April 2020 in 5 university hospitals (Paris, south and north of France), all performing primary percutaneous coronary intervention (PCI). Results The study included 237 patients (67±14, 69% of male), 116 (49%) with STEMI and 121 (51%) with NSTEMI. The prevalence of SARS-CoV-2 associated ACS was 11% (n=26) and 11 patients had severe hypoxemia on presentation (mechanical ventilation or nasal oxygen >6L/min). Patients were comparable regarding medical history and risk factors, except a higher prevalence of diabetes mellitus in SARS-CoV-2 patients (53.8% vs 25.6%, p=0.003). In SARS-CoV-2 patients, cardiac arrest on admission was more frequent (26.9% vs. 6.6%, p, In this registry we included patients presenting with ACS during the first pic of the SARS-CoV-2 epidemic in France. ACS in SARS-CoV-2 patients presented with high percentage of cardiac arrest on admission, high incidence of no-reflow and high in-hospital mortality. Further studies are needed in order to elucidate the mechanisms and the optimal management of coronary thrombosis in SARS-CoV- 2 patients.

Short RP interval atrioventricular re-entrant tachycardias do not typically present as an incessant form. We present 2 cases of incessant atrioventricular re-entrant tachycardias leading to tachycardia-induced cardiomyopathy with severe heart failure presentation in middle-aged adults. Both underwent accessory pathway ablation and recovered normal left ventricle function before hospital discharge. (Level of Difficulty: Intermediate.), Graphical abstract

Performing large-scale plasma proteome profiling is challenging due to limitations imposed by lengthy preparation and instrument time. We present a fully automated multiplexed proteome profiling platform (AutoMP3) using the Hamilton Vantage liquid handling robot capable of preparing hundreds to thousands of samples. To maximize protein depth in single-shot runs, we combined 16-plex Tandem Mass Tags (TMTpro) with high-field asymmetric waveform ion mobility spectrometry (FAIMS Pro) and real-time search (RTS). We quantified over 40 proteins/min/sample, doubling the previously published rates. We applied AutoMP3 to investigate the naked mole-rat plasma proteome both as a function of the circadian cycle and in response to ultraviolet (UV) treatment. In keeping with the lack of synchronized circadian rhythms in naked mole-rats, we find few circadian patterns in plasma proteins over the course of 48 h. Furthermore, we quantify many disparate changes between mice and naked mole-rats at both 48 h and one week after UV exposure. These species differences in plasma protein temporal responses could contribute to the pronounced cancer resistance observed in naked mole-rats. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD022891.

We report on the combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS), and the latest-generation Orbitrap Eclipse Tribrid mass spectrometer for greatly improved single-cell proteome profiling. FAIMS effectively filtered out singly charged ions for more effective MS analysis of multiply charged peptides, resulting in an average of 1056 protein groups identified from single HeLa cells without MS1-level feature matching. This is 2.3 times more identifications than without FAIMS and a far greater level of proteome coverage for single mammalian cells than has been previously reported for a label-free study. Differential analysis of single microdissected motor neurons and interneurons from human spinal tissue indicated a similar level of proteome coverage, and the two subpopulations of cells were readily differentiated based on single-cell label-free quantification., The combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS) and latest-generation mass spectrometry instrumentation provides dramatically improved single-cell proteome profiling.

Resume Contexte Les referentiels des societes savantes de medecine et des colleges des enseignants des specialites medicales sont utilises comme des references officielles pour les examens facultaires et les epreuves nationales. L’oncologie est une discipline transdisciplinaire, pratiquee et enseignees par les oncologues mais egalement des specialistes d’organe. Ce travail avait pour objectif d’identifier les discordances entre les chapitres traitant du cancer dans les referentiels des colleges d’enseignants en medecine et d’en evaluer l’impact chez les etudiants. Materiel et methodes Les discordances entre les chapitres traitant du cancer dans les referentiels des colleges d’enseignants en medecine ont ete recensees par des etudiants, volontaires, en sixieme annee a la faculte de medecine Sorbonne universite. Il leur etait egalement demande d’evaluer, de maniere individuelle, l’impact de ces discordances sur leur apprentissage. Resultats En mars 2017, les 17 items de cancerologie du programme officiel du deuxieme cycle des etudes medicales etaient traites dans 14 referentiels de colleges d’enseignants en medecine (deux a quatre referentiels par localisation tumorale). Soixante-dix-huit des 390 etudiants de sixieme annee se sont portes volontaires et ont travaille en binomes. Chaque localisation etait analysee par trois binomes (un a deux cancers par binome). Cent cinquante-quatre discordances ont ete relevees (quatre a dix-huit par cancer). L’ensemble des etudiants declarait que l’existence de ces discordances etait source de doute et d’anxiete. Quatre-vingt-cinq pour cent d’entre eux consideraient qu’une harmonisation des referentiels devrait etre recherchee dans l’ensemble des domaines du programme des etudes medicales. Conclusions Les discordances entre referentiels des colleges d’enseignants sont frequentes, generant une anxiete chez les etudiants avec un impact ressenti sur leur apprentissage.

Background Many cancer survivors receive primary care in community health centers (CHCs). Cancer history is an important factor to consider in the provision of primary care, yet little is known about the completeness or accuracy of cancer history data contained in CHC electronic health records (EHRs). Methods We probabilistically linked EHR data from more than1.5 million adult CHC patients to state cancer registries in California, Oregon, and Washington and estimated measures of agreement (eg, kappa, sensitivity, specificity). We compared demographic and clinical characteristics of cancer patients as estimated by each data source, evaluating distributional differences with absolute standardized mean differences. Results A total 74 707 cancer patients were identified between the 2 sources (EHR only, n = 22 730; registry only, n = 23 616; both, n = 28 361). Nearly one-half of cancer patients identified in registries were missing cancer documentation in the EHR. Overall agreement of cancer ascertainment in the EHR vs cancer registries (gold standard) was moderate (kappa = 0.535). Cancer site–specific agreement ranged from substantial (eg, prostate and female breast; kappa > 0.60) to fair (melanoma and cervix; kappa < 0.40). Comparing population characteristics of cancer patients as ascertained from each data source, groups were similar for sex, age, and federal poverty level, but EHR-recorded cases showed greater medical complexity than those ascertained from cancer registries. Conclusions Agreement between EHR and cancer registry data was moderate and varied by cancer site. These findings suggest the need for strategies to improve capture of cancer history information in CHC EHRs to ensure adequate delivery of care and optimal health outcomes for cancer survivors.

Resume La bronchiolite est la premiere cause d’infection respiratoire chez le nourrisson. Des complications peuvent etre associees, notamment hydroelectrolytiques a type d’hyponatremie, definie par un seuil plasmatique

The aims of this study were to characterize the incidence and outcomes of severe toxicities following the administration of high-dose methotrexate (HD-MTX; ≥1 g/m2). Among the 468 patients included...

International audience; This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.

We retrospectively examined the results of a new chemo-free approach combining blinatumomab with ponatinib (blina/pona) in 26 relapsed/refractory Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) patients. All but one achieved complete morphologic remission, and 23 achieved a complete molecular response. With a median follow-up of 34.4 months, the median overall (OS) and event-free (EFS) survivals were 20 and 15.3 months, respectively. After blina/pona, 8 patients underwent an allotransplant (allo), while among the 18 non-transplanted cases, 15 received ponatinib in maintenance. Fifteen relapse/progressions occurred with a significant difference between allo and non allo cases (12.5% vs 82.3%

International audience; Introduction Cardio-pulmonary exercise test (CPET) is becoming a key examination to assess physical capacity and disease severity in paediatric cardiology. The VE/VCO2 slope has been increasingly used as a surrogate marker for morbidity and mortality in adult heart failure, pulmonary arterial hypertension and for adult patients with CHD. Nevertheless, the use of the VE/VCO2 slope in children remains limited in the absence of reference values and clearly identified clinical determinants. This study aimed to compare the VE/VCO2 slope in a paediatric cohort with CHD to that of age- and gender-adjustedhealthy controls. We also intended to identify the clinical and CPET variables associated with VE/VCO2 slope in this population. Methods This cross-sectional study was carried out between November 2010 and September 2015 in two tertiary care paediatric cardiology reference centres. Results A total of 700 children were enrolled (399 CHD and 301 healthy controls). The mean VE/VCO2 slope was significantly higher in CHD than in healthy subjects (31.6±4.8 vs. 29.3±4.8; P

For many years, adjuvant chemoradiotherapy remained essential in the therapeutic management of gastric and pancreatic adenocarcinomas. For these tumours, surgical excision, the only hope of offering the patient prolonged survival, is only possible in 20% of cases. The median survival of operated patients is only 12 to 20 months due to the frequency of locoregional and/or metastatic recurrences. For stomach cancers, adjuvant chemoradiotherapy is justified by the results of the phase III trial Intergroup 0116 published by MacDonald et al. The gain in survival was at the cost of significant toxicity. This treatment was supplanted in the early 2000s by perioperative chemotherapy. Currently, neoadjuvant chemoradiotherapy clinical studies are ongoing with the aim of improving treatments observance and tolerance. For pancreatic cancers, the role of adjuvant chemoradiotherapy has long been discussed because of trials with contradictory results. Neoadjuvant radiotherapy has many advantages in terms of efficacy and tolerance. It increases the chances of subsequent complete tumour resection. Several prospective trials are currently ongoing to clarify its place in the therapeutic arsenal.

Resumen Introduccion Las herramientas para analizar la casuistica en consultas externas son escasas e insatisfactorias. El objetivo de este trabajo de la Sociedad Castellano Manchega de Endocrinologia, Nutricion y Diabetes (SCAMEND) fue el desarrollo de una herramienta que permita analizar la casuistica de las consultas externas de Endocrinologia y Nutricion teniendo en cuenta la complejidad de la patologia atendida. Material y metodos Se definio el Indice SCAMEND de Complejidad en Consultas Externas de Endocrinologia y Nutricion (ISCCE-EyN) mediante metodo Delphi con dos rondas entre especialistas en Endocrinologia y Nutricion, comparando la complejidad de cada patologia con la de una revision de hipotiroidismo primario. Resultados Las primeras visitas fueron consideradas mas complejas que las visitas sucesivas. La patologia tiroidea no neoplasica y el sobrepeso/obesidad sin complicaciones fueron consideradas las patologias menos complejas, mientras que las metabolopatias, los sindromes de neoplasias endocrinas multiples y el carcinoma suprarrenal fueron consideradas las mas complejas. El grado de consenso fue elevado en la mayoria de las patologias analizadas. Conclusiones Presentamos una herramienta que permite analizar la casuistica de las consultas externas de Endocrinologia y Nutricion teniendo en cuenta la complejidad inherente a la patologia del paciente atendido. Esta herramienta puede servir para realizar comparaciones entre centros, para asignar mejores recursos dentro de un determinado servicio o para la autoevaluacion.

In recent years, magnetic resonance imaging (MRI) has become one of the standard imaging tools to define the macroscopic gross tumor volume in locally advanced cervical cancer patients based on T2-weighted sequence. Recent data suggest that functional MRI could be used to potentially improve the delineation of target volumes based on physiologic features, defining radioresistant subvolumes that may require higher doses to achieve local cure. Functional imaging can be used to predict tumor biology and outcome, as well as for assessment of tumor response during radiotherapy. The concept of adaptive radiotherapy relies on the possibility of monitoring variations in target volumes structures to guide treatment-plan modification during radiotherapy, taking into account not only internal movements but also tumor response. With integrated MRI in radiotherapy linear accelerators, motion monitoring during treatment delivery has become available. MRI can be also used to accurately evaluate cervical tumor residual volume after chemoradiotherapy, and therefore allowing a personalized treatment planning for brachytherapy boost, based on tumor radiosensitivity. In this review, we discuss how MRI tumor response assessment could be included into clinical practice during radiation therapy in locally advanced cervical cancer patients.

Resumen A pesar de que es conocido que la presencia cronica de microorganismos en las vias aereas de pacientes con enfermedad pulmonar obstructiva cronica (EPOC) en fase de estabilidad conlleva una evolucion desfavorable, ninguna guia de manejo de la enfermedad establece pautas sobre como diagnosticar y tratar este tipo de casos. Con la intencion de orientar a los profesionales, desde la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) se ha elaborado un documento que pretende aportar respuestas clinicas sobre el manejo de pacientes con EPOC en los que se aislan microorganismos de forma puntual o persistente. Dado que la heterogeneidad de las evidencias cientificas disponibles no permite crear una Guia de Practica Clinica, se ha elaborado un documento basado en la literatura cientifica existente y/o en la propia experiencia clinica que aborda tanto la definicion de las diferentes situaciones clinicas como su diagnostico y manejo. El texto ha sido consensuado entre un amplio numero de neumologos con gran experiencia clinica y cientifica en este ambito. Este documento cuenta con el aval del Comite Cientifico de SEPAR.

Shoot branching mechanisms where branches arise in association with leaves – referred to as lateral or axillary branching – evolved by convergence in the sporophyte of vascular plants and the gametophyte of bryophytes, and accompanied independent events of plant architectural diversification1. Previously, we showed that three hormonal cues, including auxin, have been recruited independently to co-ordinate branch patterning in flowering plant leafy shoots and moss gametophores (Coudert, Palubicki et al., 2015)2–4. Moreover, auxin-mediated apical dominance, which relies on local auxin production, has been proposed as a unifying molecular regulatory mechanism of branch development across land plants5. Whilst our previous work in the moss Physcomitrium patens has gathered indirect evidence supporting the notion that auxin synthesized in gametophore apices regulates branch formation at a distance2, direct genetic evidence for a role of auxin biosynthesis in gametophore branching control is still lacking. Here, we show that gametophore apex decapitation promotes branch emergence through massive and rapid transcriptional reprogramming of auxin-responsive genes and altering auxin biosynthesis gene activity. Specifically, we identify a subset of P. patens TRYPTOPHAN AMINO-TRANSFERASE (TAR) and YUCCA FLAVIN MONOOXYGENASE-LIKE (YUC) auxin biosynthesis genes expressed in apical and basal regions of the gametophore, and show that they are essential for branch initiation and outgrowth control. Our results demonstrate that local auxin biosynthesis coordinates branch patterning in moss and thus constitutes a shared and ancient feature of shoot architecture control in land plants.

International audience; Rationale Stimulant use, including cocaine, often occurs in a social context whose influence is important to understand todecrease intake and reduce associated harms. Although the importance of social influence in the context of drug addictionis known, there is a need for studies assessing its neurobiological substrate and for translational research.Objectives Here, we explored the influence of peer presence and familiarity on cocaine intake and its neurobiological basis.Given the regulatory role of the subthalamic nucleus (STN) on cocaine intake and emotions, we investigated its role on suchinfluence of social context on cocaine intake.Methods We first compared cocaine consumption in various conditions (with no peer present or with peers with differentcharacteristics: abstinent peer or drug-taking peer, familiar or not, cocaine-naive or not, dominant or subordinate) in rats(n = 90). Then, with a translational approach, we assessed the influence of the social context (alone, in the group, in a dyadwith familiar or non-familiar peers) on drug intake in human drug users (n = 77).Results The drug consumption was reduced when a peer was present, abstinent, or drug-taking as well, and further dimin-ished when the peer was non-familiar. The presence of a non-familiar and drug-naive peer represents key conditions todiminish cocaine intake. The STN lesion by itself reduced cocaine intake to the level reached in presence of a non-familiarnaive peer and affected social cognition, positioning the STN as one neurobiological substrate of social influence on drugintake. Then, the human study confirmed the beneficial effect of social presence, especially of non-familiar peers.Conclusion Our results indirectly support the use of social interventions and harm reduction strategies and position the STNas a key cerebral structure to mediate these effects.; The presence of a non-familiar and possibly drug-naive peer is the most efficient condition to diminish stimulant intake. Our results indirectly support the use of harm reduction strategies, in particular supervised consumption rooms for stimulant users.

Objective: Some attempts have previously been made to stratify patients with CIS for the purpose of risk-adapted clinical management and clinical trial design. In particular, two classification systems have been proposed: clinical classification, comprising primary (P-CIS), concomitant (C-CIS), and secondary (S-CIS) disease, and pathological classification, comprising P-CIS, cTa-CIS, and cT1-CIS. The aim of the present study was to assess the impact of both classifications on BCG response, recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). Patients and Methods: We performed a retrospective analysis of 386 patients with bladder CIS, with or without associated cTa/cT1 disease, treated with BCG instillations between 2008 and 2015. Patients were stratified according to the two classification systems. Cox multivariate regression models were used to assess the impact of these subtypes on BCG response, RFS, PFS, OS, and CSS. We also performed a cumulative meta-analysis according to PRISMA guidelines. Results: The median follow-up was 70.5 months. According to the clinical classification, 34 (8.8%) patients had P-CIS, 81 (21%) S-CIS, and 271 (70.2%) C-CIS. The pathological classification showed 34 (8.8%) patients to have P-CIS, 190 (49.2%) cTa-CIS, and 162 (42%) cT1-CIS. In the overall cohort, BCG response was reported in 296 (76.7%); 159 (41.2%) had recurrence, 55 (14.2%) had progression, and 67 (17.4%) underwent radical cystectomy. Death from any cause was recorded in 135 (35%) and death from urothelial carcinoma in 38 (9.9%). Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for BCG response, RFS, PFS, OS, or CSS after adjusting for confounders. In the pooled meta-analysis, two studies and the present series were included for evidence synthesis, recruiting a total of 941 patients. We found no statistically significant difference across the groups for both classifications with respect to BCG response, RFS, PFS, and CSS. Conclusions: Currently, the supporting evidence for an impact of clinical classification and pathological classification on oncological outcomes of CIS of the bladder is insufficient to justify their use to guide clinical management or follow-up. (C) 2021 Published by Elsevier Inc.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: There has been resurgence in the use of bismuth quadruple therapy (proton pump inhibitor, bismuth, tetracycline and metronidazole) for treating Helicobacter pylori infection thanks to a three-in-one single-capsule formulation. Objective: To evaluate the effectiveness and safety of the single-capsule bismuth quadruple therapy. Methods: Data were collected in a multicentre, prospective registry of the clinical practice of gastroenterologists on the management of H. pylori infection, where patients were registered at the Asociación Española de Gastroenterologia REDCap database on an electronic case report form until January 2020. Effectiveness by modified intention-to-treat and per-protocol as well as multivariable analysis were performed. Independent factors evaluated were: age, gender, indication, compliance, proton pump inhibitor dose and treatment line. Results: Finally, 2100 patients were prescribed single-capsule bismuth quadruple therapy following the technical sheet (i.e., three capsules every 6 h for 10 days). The majority of these patients were naive (64%), with an average age of 50 years, 64% women and 16% with peptic ulcer. An overall modified intention-to-treat effectiveness of 92% was achieved. Eradication was over 90% in first-line treatment (95% modified intention-to-treat, n = 1166), and this was maintained as a rescue therapy, both in second (89% modified intention-to-treat, n = 375) and subsequent lines of therapy (third to sixth line: 92% modified intention-to-treat, n = 236). Compliance was the factor most closely associated with treatment effectiveness. Adverse events were generally mild to moderate, and 3% of patients reported a severe adverse event, leading to discontinuation of treatment in 1.7% of cases. Conclusions: Single-capsule bismuth quadruple therapy achieved H. pylori eradication in approximately 90% of patients in real-world clinical practice, both as a first-line and rescue treatment, with good compliance and a favourable safety profile, The author(s) would like to thank the Spanish Association of Gastroenterology (AEG) for providing the electronic case report form service free of charge. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was promoted and funded by the European Helicobacterand Microbiota Study Group, and received support from the Spanish Association of Gastroenterology (AEG) and the Centro de Investigación Biomedica en Red de Enfermedades Hepaticas y Digestivas

It is challenging to estimate the phenotypic impact of the structural genome changes known as copy-number variations (CNVs), since there are many unique CNVs which are nonrecurrent, and most are too rare to be studied individually. In recent work, we found that CNV-aggregated genomic annotations, that is, specifically the intolerance to mutation as measured by the pLI score (probability of being loss-of-function intolerant), can be strong predictors of intellectual quotient (IQ) loss. However, this aggregation method only estimates the individual CNV effects indirectly. Here, we propose the use of hierarchical Bayesian models to directly estimate individual effects of rare CNVs on measures of intelligence. Annotation information on the impact of major mutations in genomic regions is extracted from genomic databases and used to define prior information for the approach we call HBIQ. We applied HBIQ to the analysis of CNV deletions and duplications from three datasets and identified several genomic regions containing CNVs demonstrating significant deleterious effects on IQ, some of which validate previously known associations. We also show that several CNVs were identified as deleterious by HBIQ even if they have a zero pLI score, and the converse is also true. Furthermore, we show that our new model yields higher out-of-sample concordance (78%) for predicting the consequences of carrying known recurrent CNVs compared with our previous approach.

Background The question of an optimal strategy and outcomes in COVID-19 tracheostomy has not been answered yet. The critical focus in our case study is to evaluate the outcomes of tracheostomy on intubated COVID-19 patients. Methods A multicentric prospective observational study of 1890 COVID-19 patients undergoing tracheostomy across 120 hospitals was conducted over 7 weeks in Spain (March 28 to May 15, 2020). Data were collected with an innovative approach: instant messaging via WhatsApp. Outcome measurements: complications, achieved weaning and decannulation and survival. Results We performed 1,461 surgical (81.3%) and 429 percutaneous tracheostomies. Median timing of tracheostomy was 12 days (4–42 days) since orotracheal intubation. A close follow-up of 1616/1890 (85.5%) patients at the cut-off time of 1-month follow-up showed that in 842 (52.1%) patients, weaning was achieved, while 391 (24.2%) were still under mechanical ventilation and 383 (23.7%) patients had died from COVID-19. Decannulation among those in whom weaning was successful (n = 842) was achieved in 683 (81%) patients. Conclusion To the best of our knowledge, this is the largest cohort of COVID-19 patients undergoing tracheostomy. The critical focus is the unprecedented amount of tracheostomies: 1890 in 7 weeks. Weaning could be achieved in over half of the patients with follow-up. Almost one out of four tracheotomized patients died from COVID-19.

Background Purple tulip extract is a rich source of flavonoids which are powerful antioxidants and can hence be considered as an ideal candidate for use in skin care products. Objectives We aimed to evaluate the effects of purple tulip extract on skin quality and to determine its molecular modes of interaction. Methods A pangenomic study on human skin fibroblasts was carried out to analyse multiple changes in gene expression. Ex vivo studies of human skin explants exposed to ultraviolet (UV) irradiation or H2 O2 were performed to assess modulations of protein expression. Finally, a clinical assay was carried out to evaluate the efficacy of purple tulip extract on skin appearance and condition of aged women. Results Genetic modulation analyses led us to infer the induction of many biological functions including cell differentiation, proliferation, migration, inflammatory responses, and matrix remodelling. The ex vivo studies revealed an enhancement of the collagen network and increased expression of glycosaminoglycans (GAG), fibronectin and collagen VI. Finally, the clinical study highlighted the potential anti-ageing properties of the purple tulip extract which decreased the relaxation of the oval face and improved skin elasticity after 28 days of treatment. Significant reductions of the length and depth of the nasolabial wrinkles were also observed. Conclusion Our genomics data on the effect of purple tulip extract on the ex vivo UV challenged skin, showed that genes responsible for, amongst others, the upkeep of the skin, such as collagen induction, immune cell proliferation and epidermal repair, were all upregulated. More importantly, the clinical study corroborated these data by the visible and measurable effects of the topical purple tulip extract on the aged skin of 22 women, further demonstrating the beneficial impact of the extract on aged skin.

Objective: To evaluate the prevalence of ADHD in a group of parents of children with ADHD compared with the general population. To compare academic level, unemployment aid rate and marital separati...

The OPAL study is a French multicenter observational retrospective analysis of adults with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia treated in a real-life setting by ponatinib. Twenty-nine patients were included since 2012. Median age was 55 years. The initial dose of ponatinib, combined to chemotherapy in half of the patients, was 45 mg/day in most instances. The remission rate was 90% and seven patients received allogeneic stem cell transplantation. Median disease-free and overall survival were only 3.5 and 9.9 months respectively. The outcome of patients with

International audience; Pesticides are now recognised to interact with drug transporters, but only few data are available on this issue for carbamate pesticides, a widely-used class of agrochemicals, to which humans are highly exposed. The present study was therefore designed to determine whether four representative carbamate pesticides, i.e., the insecticides aminocarb and carbofuran, the herbicide chlorpropham and the fungicide propamocarb, may impair activities of main drug transporters implicated in pharmacokinetics.The interactions of carbamates with solute carrier and ATP-binding cassette transporters were investigated using cultured transporter-overexpressing cells, reference substrates and spectrofluorimetry-, liquid chomatography/tandem mass spectrometry- or radioactivity-based methods.Aminocarb and carbofuran exerted no or minimal effects on transporter activities, whereas chlorpropham inhibited BCRP and OAT3 activities and propamocarb decreased those of OCT1 and OCT2, but cis-stimulated that of MATE2-K. Such alterations of transporters however required chlorpropham/propamocarb concentrations in the 5-50 µM range, likely not relevant to environmental exposure. Trans-stimulation assays and propamocarb accumulation experiments additionally suggested that propamocarb is not a substrate for OCT1, OCT2 and MATE2-K.These data indicate that some carbamate pesticides can interact in vitro with some drug transporters, but only when used at concentrations higher than those expected to occur in environmentally-exposed humans.