MRI Investigation of the Differential Impact of Left Ventricular Ejection Fraction After Myocardial Infarction in Elderly vs. Nonelderly Patients to Predict Readmission for Heart Failure

Acute heart failure; Acute myocardial infarction; ElderlyInsuficiència cardíaca aguda; Infart agut de miocardi; Gent granInsuficiencia cardíaca aguda; Infarto agudo de miocardio; AncianoBackground Patients with ST-segment elevation myocardial infarction (STEMI), especially elderly individuals, have an increased risk of readmission for acute heart failure (AHF). Purpose To study the impact of left ventricular ejection fraction (LVEF) by MRI to predict AHF in elderly (>70 years) and nonelderly patients after STEMI. Study Type Prospective. Population Multicenter registry of 759 reperfused STEMI patients (23.3% elderly). Field Strength/Sequence 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. Assessment One-week MRI-derived LVEF (%) was quantified. Sequential MRI data were recorded in 579 patients. Patients were categorized according to their MRI-derived LVEF as preserved (p-LVEF, ≥50%), mildly reduced (mr-LVEF, 41%–49%), or reduced (r-LVEF, ≤40%). Median follow-up was 5 [2.33–7.54] years. Statistical Tests Univariable (Student's t, Mann–Whitney U, chi-square, and Fisher's exact tests) and multivariable (Cox proportional hazard regression) comparisons and continuous-time multistate Markov model to analyze transitions between LVEF categories and to AHF. Hazard ratios (HR) with 95% confidence intervals (CIs) were computed. P < 0.05 was considered statistically significant. Results Over the follow-up period, 79 (10.4%) patients presented AHF. MRI-LVEF was the most robust predictor in nonelderly (HR 0.94 [0.91–0.98]) and elderly patients (HR 0.94 [0.91–0.97]). Elderly patients had an increased AHF risk across the LVEF spectrum. An excess of risk (compared to p-LVEF) was noted in patients with r-LVEF both in nonelderly (HR 11.25 [5.67–22.32]) and elderly patients (HR 7.55 [3.29–17.34]). However, the mr-LVEF category was associated with increased AHF risk only in elderly patients (HR 3.66 [1.54–8.68]). Less transitions to higher LVEF states (n = 19, 30.2% vs. n = 98, 53%) and more transitions to AHF state (n = 34, 53.9% vs. n = 45, 24.3%) were observed in elderly than nonelderly patients. Data Conclusion MRI-derived p-LVEF confers a favorable prognosis and r-LVEF identifies individuals at the highest risk of AHF in both elderly and nonelderly patients. Nevertheless, an excess of risk was also found in the mr-LVEF category in the elderly group. Evidence Level 2. Technical Efficacy Stage 2.Grant sponsor: This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637, PI15/00531, and CIBERCV16/11/00486, CIBERCV16/11/00420, CIBERCV16/11/00479, and CM21/00175 to V.M.-G.), Fundació La Marató TV3 (grant 20153030-31-32), La Caixa Banking Foundation (HR17-00527) and by Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). J.G. acknowledges financial support from the “Agencia Estatal de Investigación” (grant FJC2020-043981-I/AEI/10.13039/501100011033)

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement : The REAC-TAVI Trial

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066

Effective Lagrangian approach to neutrinoless double beta decay and neutrino masses

Neutrinoless double beta ($0\nu\beta\beta$) decay can in general produce electrons of either chirality, in contrast with the minimal Standard Model (SM) extension with only the addition of the Weinberg operator, which predicts two left-handed electrons in the final state. We classify the lepton number violating (LNV) effective operators with two leptons of either chirality but no quarks, ordered according to the magnitude of their contribution to \znbb decay. We point out that, for each of the three chirality assignments, $e_Le_L, e_Le_R$ and $e_Re_R$, there is only one LNV operator of the corresponding type to lowest order, and these have dimensions 5, 7 and 9, respectively. Neutrino masses are always induced by these extra operators but can be delayed to one or two loops, depending on the number of RH leptons entering in the operator. Then, the comparison of the $0\nu\beta\beta$ decay rate and neutrino masses should indicate the effective scenario at work, which confronted with the LHC searches should also eventually decide on the specific model elected by nature. We also list the SM additions generating these operators upon integration of the heavy modes, and discuss simple realistic examples of renormalizable theories for each case.Comment: Accepted for publication. Few misprints corrected and new references adde

Use of water-Cherenkov detectors to detect Gamma-Ray-Bursts at the Large Aperture GRB Observatory (LAGO)

The Large Aperture GRB Observatory (LAGO) project aims at the detection of high energy photons from Gamma Ray Bursts (GRB) using the single particle technique in ground-based water-Cherenkov detectors (WCD). To reach a reasonable sensitivity, high altitude mountain sites have been selected in Mexico (Sierra Negra, 4550 m a.s.l.), Bolivia (Chacaltaya, 5300 m a.s.l.) and Venezuela (Me´ rida, 4765 m a.s.l.). We report on detector calibration and operation at high altitude, search for bursts in 4 months of preliminary data, as well as search for signal at ground level when satellites report a burst.Fil: Allard, D.. Université Paris Diderot - Paris 7; FranciaFil: Allekotte, Ingomar. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, C.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Asorey, Hernán Gonzalo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Barros, H.. Universidad Simon Bolivar; VenezuelaFil: Bertou, Xavier Pierre Louis. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Burgoa, O.. Instituto de Investigaciones Fisicas; BoliviaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Martinez, O.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Miranda Loza, P.. Instituto de Investigaciones Fısicas; BoliviaFil: Murrieta, T.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Perez, G.. Facultad de Ciencias Fısico-Matematicas; MéxicoFil: Rivera, H.. Instituto de Investigaciones Fısicas; BoliviaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Saavedra, O.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Salazar, H.. Facultad de Ciencias Fısico-Matematicas ; MéxicoFil: Tello, J. C.. Universidad Simon Bolıvar; VenezuelaFil: Ticona Peralda, R.. Instituto de Investigaciones Fısicas; BoliviaFil: Velarde, A.. Instituto de Investigaciones Fısicas; BoliviaFil: Villaseñor, L.. Universidad de Michoacan; MéxicoFil: Areso, Omar Antonio. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Arnaldi, Luis Horacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Dasso, Sergio Ricardo. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Gonzalez, M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Gulisano, Adriana Maria. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Martin, R.. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; ArgentinaFil: Masías Meza, Jimmy Joel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Sidelnik, Iván Pedro. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Alvarez, W.. Universidad de San Carlos; GuatemalaFil: The LAGO Collaboration

Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m−2 of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1–3, 8–10, 15–17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1–9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44–72) and median duration of PSA response was 8.0 months (95% CI: 6.9–9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel