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    Predictors of Clinical Success of Cardioneuroablation in Patients With Syncope: Results of a Multicenter Study.

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    20.500.12530/87854Cardioneuroablation (CNA) is a promising treatment for syncope. This study sought to analyze the success and risk of CNA, and to describe predictive factors of CNA success in patients with syncope. Seventy-seven consecutive patients with syncope treated with CNA in 22 hospitals and at least 6 months of follow-up were included. Patients with reflex cardioinhibitory, mixed syncope, functional sinus node dysfunction (SND), or functional atrioventricular block were included. The primary endpoint was the recurrence of syncope after the CNA. Mean age was 49.3 ± 13.4 years and 54.5% were women. Five (6.5%) patients presented complications. Three patients presented SND, 1 required a pacemaker. During a median follow-up of 12 months (Q1-Q3: 8-20 months), 26 (33.8%) patients had recurrence of syncope. Women had a significantly higher risk of recurrence compared with men (HR: 3.3; 95% CI: 1.2-8.8; P = 0.016). Patients >50 years of age had a significantly lower risk of recurrence compared with younger patients (HR: 0.3; 95% CI: 0.1-0.9; P = 0.032). The risk of recurrence in mixed syncope was significantly higher than in cardioinhibitory syncope (HR: 4.4; 95% CI: 1.1-17.5; P = 0.033). Syncope recurrence was significantly less frequent in patients treated with general anesthesia or deep sedation compared with conscious sedation (HR: 0.2; 95% CI: 0.1-0.6; P = 0.002). Finally, the number of radiofrequency applications (≤30 or >30) had a significant association with CNA success (HR: 0.4; 95% CI: 0.2-0.9; P = 0.042). These results were adjusted for confounding factors. In this multicenter study, the effectiveness of CNA was less than previously reported. We found a 3.9% risk of SND. Male sex, age >50 years, cardioinhibitory syncope, general anesthesia or deep sedation, and >30 radiofrequency applications could predict success of CNA for syncope

    COVID-19 Outcomes in Patients with Hematologic Malignancies in the Era of COVID-19 Vaccination and the Omicron Variant.

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    20.500.12530/87908A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64-2.87), with >1 comorbidity (2.44, 1.85-3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19-2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2-0.37) or BA.4/BA.5 (0.13, 0.08-0.19) periods and among patients vaccinated with one or two (0.51, 0.34-0.75) or three or four (0.22, 0.16-0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03-3.25) and Omicron (3.19, 95% CI 1.59-6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients

    The Hypoxic Burden, Clinical Implication of a New Biomarker in the Cardiovascular Management of Sleep Apnea Patients: A Systematic Review.

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    20.500.12530/87854Obstructive sleep apnea (OSA) is a highly prevalent sleep-disordered breathing. It is associated with adverse co-morbidities, being the most scientific evidence of cardiovascular (CV) disease. Currently, OSA is measured through the apnea-hypopnea index (AHI), the total number of respiratory events per hour of sleep. However, different studies have questioned its utility in OSA management, highlighting the need to search for new parameters that better reflect the heterogeneity of the disease. Hypoxic burden (HB) has emerged as a novel biomarker that informs about the frequency, duration and depth of the desaturation related to the respiratory events. We conducted a systematic review in order to find publications about the heterogeneity of OSA measured by HB and its associations with future disease. Systematic review was conducted using PubMed and Web of Science. The terms "sleep apne" and "hypoxic burden" were used to look for publications from the date of inception to August 15, 2023. Inclusion criteria: articles in English published in peer-reviewed journals. Exclusion criteria: (1) not available publications; (2) duplicated articles; (3) letters, editorials, and congress communications; (4) articles not including information about HB as a specific biomarker of OSA. 33 studies were included. The results were classified in 2 main sections: (1) HB implication in the CV sphere: HB showed to be a better predictor of CV risk in OSA patients than traditional measures such as AHI with possible clinical management implication in OSA. (2) HB response to OSA treatment: pharmacological and nonpharmacological treatments have demonstrated to be effective in improving hypoxia measured through the HB. HB could be a better and more effective parameter than traditional measurements in terms of diagnosis, risk prediction and therapeutic decisions in patients with OSA. This measure could be incorporated in sleep units and could play a role in OSA management, driving the clinic to a more personalized medicine

    Early inflammation as a footprint of increased mortality risk in infants living with HIV from three African countries.

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    In this work our aim was to identify early biomarkers in plasma samples associated with mortality in children with perinatal HIV treated early in life, to potentially inform early intervention targeting this vulnerable group. 20/215 children (9.3%) with perinatal HIV, enrolled within 3 months of age died prematurely within the first year of the study, despite early ART initiation. Using a propensity score, we selected 40 alive study participants having similar clinical and virological records compared to the deceased group. 13 HIV unexposed (HU) healthy children were additionally used as controls. Baseline plasma samples were analyzed using a targeted proteomic approach, and to assess pathogen-associated and damage-associated molecular patterns (PAMPs, DAMPs) levels. Data from deceased participants were compared to both control groups, with multivariate logistic regression models used to evaluate the association between mortality and plasma proteins. We developed a machine learning model to predict mortality risk, finding that IL-6 and CXCL11 not only were higher in deceased children than Matched-children with HIV (p

    Cephalic Duodenopancreatectomy In The Neonatal Period: A Case Report And Review Of The Literature

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    20.500.12530/87858Background:Pancreatic masses in the neonatal period are a rare pathology. Resection of the head of the pancreas is an exceptional surgical challenge due to the need to perform millimetric anastomosis, therefore, subsequent complications are frequent. Methods:Case report and review of published articles on cephalic duodenopancreatectomies (CDP) in patients less than 28 days-old. Case report:An 11-days-old female newborn, 3030g, consulted for apnea and cyanosis. Magnetic resonance imaging showed a cystic mass in the right hypochondrium measuring 6.2x5.9x6.4mm with suspicion of malignancy. At 22 days of life a laparotomy was performed finding a mass in the head of the pancreas firmly adhered to the extrahepatic biliary tract and duodenum. A CDP and reconstruction by gastroduodenostomy, hepatico-duodenostomy (Kasai-like) and dunking pancreato-gastrostomy were performed. The pathological anatomy described a serous cystadenoma. With 6 years of follow-up, she has presented a single episode of cholangitis, with no signs of endocrine or exocrine insufficiency. Results (Table 1): 6 patients with CDP less than 28 days have been described. The surgical technique presented many variations. Five patients presented complications, the most frequent being exocrine insufficiency. Conclusion: CDP in the neonatal period is an exceptional procedure, with only 5 other cases described in the literature. We present CDP on the largest mass described so far, with no signs of pancreatic insufficiency in a long-term follow-up

    Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

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    20.500.12530/87854Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non-small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC

    Therapeutic targeting of TGF-β in lung cancer.

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    Transforming growth factor-β (TGF-β) plays a complex role in lung cancer pathophysiology, initially acting as a tumor suppressor by inhibiting early-stage tumor growth. However, its role evolves in the advanced stages of the disease, where it contributes to tumor progression not by directly promoting cell proliferation but by enhancing epithelial-mesenchymal transition (EMT) and creating a conducive tumor microenvironment. While EMT is typically associated with enhanced migratory and invasive capabilities rather than proliferation per se, TGF-β's influence on this process facilitates the complex dynamics of tumor metastasis. Additionally, TGF-β impacts the tumor microenvironment by interacting with immune cells, a process influenced by genetic and epigenetic changes within tumor cells. This interaction highlights its role in immune evasion and chemoresistance, further complicating lung cancer therapy. This review provides a critical overview of recent findings on TGF-β's involvement in lung cancer, its contribution to chemoresistance, and its modulation of the immune response. Despite the considerable challenges encountered in clinical trials and the development of new treatments targeting the TGF-β pathway, this review highlights the necessity for continued, in-depth investigation into the roles of TGF-β. A deeper comprehension of these roles may lead to novel, targeted therapies for lung cancer. Despite the intricate behavior of TGF-β signaling in tumors and previous challenges, further research could yield innovative treatment strategies

    Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

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    20.500.12530/87909A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS

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