Utilização do monitor de eventos externo (web-loop) na identificação de sintomas associados a arritmias cardíacas em uma população geral

ObjectiveTo correlate arrhythmic symptoms with the presence of significant arrhythmias through the external event monitoring (web-loop). MethodBetween January and December 2011, the web-loop was connected to 112 patients (46% of them were women, mean age 52±21 years old). Specific arrhythmic symptoms were defined as palpitations, pre-syncope and syncope observed during the monitoring. Supraventricular tachycardia, atrial flutter or fibrillation, ventricular tachycardia, pauses greater than 2 seconds or advanced atrioventricular block were classified as significant arrhythmia. The association between symptoms and significant arrhythmias were analyzed. ResultThe web-loop recorded arrhythmic symptoms in 74 (66%) patients. Of these, in only 14 (19%) patients the association between symptoms and significant cardiac arrhythmia was detected. Moreover, significant arrhythmia was found in 11 (9.8%) asymptomatic patients. There was no association between presence of major symptoms and significant cardiac arrhythmia (OR=0.57, CI95%: 0.21-1.57; p=0.23). ConclusionWe found no association between major symptoms and significant cardiac arrhythmia in patients submitted to event recorder monitoring. Event loop recorder was useful to elucidate cases of palpitations and syncope in symptomatic patients.ObjetivoCorrelacionar sintomas arrítmicos com a presença de arritmias significativas por meio do monitor de eventos externo (web-loop). MétodoEntre janeiro e dezembro de 2011, o web-loop foi instalado em 112 pacientes (46% mulheres, 52±21 anos). Sintomas específicos foram definidos como palpitação, pré-síncope e síncope, presentes durante a monitorização. Arritmia significativa foi definida como taquicardia paroxística supraventricular, flutter e fibrilação atrial, taquicardia ventricular, pausas superiores a 2 segundos ou bloqueio atrioventricular avançado. A associação entre presença de sintomas e arritmias significativas foi avaliada. ResultadoO monitor de eventos registrou sintomas específicos em 74 (66%) pacientes, entretanto a associação entre sintomas específicos e arritmia significativa foi observada em apenas 14 (19%) deles. Em 11 pacientes (9,8%), foi detectada arritmia significativa na ausência de sintomas. Não houve associação entre a presença de sintomas e a detecção de arritmia significativa (OR=0,57, IC95%: 0,21-1,57; p=0,23). ConclusãoEm pacientes monitorizados pelo web-loop, não houve associação entre a presença de sintomas específicos e a detecção de arritmias significativas. O monitor de eventos pode ter importância na elucidação de sintomas de palpitações e síncope dos pacientes.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Structure of Fat Jets at the Tevatron and Beyond

Boosted resonances is a highly probable and enthusiastic scenario in any process probing the electroweak scale. Such objects when decaying into jets can easily blend with the cornucopia of jets from hard relative light QCD states. We review jet observables and algorithms that can contribute to the identification of highly boosted heavy jets and the possible searches that can make use of such substructure information. We also review previous studies by CDF on boosted jets and its measurements on specific jet shapes.Comment: invited review for a special "Top and flavour physics in the LHC era" issue of The European Physical Journal C, we invite comments regarding contents of the review; v2 added references and institutional preprint number

Boletín NUESTRA AMÉRICA XXI - Desafíos y alternativas, num.40, Febrero 2020

Una excelente iniciativa del Grupo de Trabajo Crisis y economía mundial, coordinado por María Josefina Morales y Gabriela Roffinelli

Nutritional status and functional capacity of hospitalized elderly

Background: The nutritional status of the aging individual results from a complex interaction between personal and environmental factors. A disease influences and is influenced by the nutritional status and the functional capacity of the individual. We asses the relationship between nutritional status and indicators of functional capacity among recently hospitalized elderly in a general hospital.Methods: A cross-sectional study was done with 240 elderly (women, n = 127 and men, n = 113) hospitalized in a hospital that provides care for the public and private healthcare systems. The nutritional status was classified by the MNA (Mini Nutritional Assessment) into: malnourished, risk of malnutrition and without malnutrition (adequate). The functional autonomy indicators were obtained by the self-reported Instrumental Activity of Daily Living (IADL) and Activity of Daily Living (ADL) questionnaire. The chi-square test was used to compare the proportions and the level of significance was 5%.Results: Among the assessed elderly, 33.8% were classified as adequate regarding nutritional status; 37.1% were classified as being at risk of malnutrition and 29.1% were classified as malnourished. All the IADL and ADL variables assessed were significantly more deteriorated among the malnourished individuals. Among the ADL variables, eating partial (42.9%) or complete (12.9%) dependence was found in more than half of the malnourished elderly, in 13.4% of those at risk of malnutrition and in 2.5% of those without malnutrition.Conclusion: There is an interrelationship between the nutritional status of the elderly and reduced functional capacity

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes. Materials and methods: We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms. Results: Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers. Conclusions: Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe