This article describes the event detection system of the NEXT-White detector, a 5 kg high pressure xenon TPC with electroluminescent amplification, located in the Laboratorio Subterráneo de Canfranc ...(LSC), Spain. The detector is based on a plane of photomultipliers (PMTs) for energy measurements and a silicon photomultiplier (SiPM) tracking plane for offline topological event filtering. The event detection system, based on the SRS-ATCA data acquisition system developed in the framework of the CERN RD51 collaboration, has been designed to detect multiple events based on online PMT signal energy measurements and a coincidence-detection algorithm. Implemented on FPGA, the system has been successfully running and evolving during NEXT-White operation. The event detection system brings some relevant and new functionalities in the field. A distributed double event processor has been implemented to detect simultaneously two different types of events thus allowing simultaneous calibration and physics runs. This special feature provides constant monitoring of the detector conditions, being especially relevant to the lifetime and geometrical map computations which are needed to correct high-energy physics events. Other features, like primary scintillation event rejection, or a double buffer associated with the type of event being searched, help reduce the unnecessary data throughput thus minimizing dead time and improving trigger efficiency.
Esophageal perforation constitutes a surgical emergency. Despite its gravity, no single strategy has been described as sufficient to deal with most situations to date. The aim of this study was to ...assess the etiology, management, and outcome of esophageal perforation over a 28-year period, to characterize optimal treatment options in this severe disease. A retrospective clinical review of all patients treated for esophageal perforation at Ramón y Cajal Hospital between January 1987 and December 2015 was performed (n = 57). Iatrogenic injury was the most frequent cause of esophageal perforation (n = 32). Abdominal esophagus was the main location (23 patients; 40.4%). Eight patients (14%) were managed with antibiotics and parenteral nutrition. In seven patients (12.3%), an endoscopic stent was implanted. Surgical therapy was performed in 38 patients (66.7%). Morbidity and 90-day mortality rates were 61.4 and 28 per cent, respectively. Five patients were reoperated (8.8%). Median hospital stay was 23.5 days. The mortality rate was higher among patients with spontaneous and tumoral perforation (54.5 and 100%; P = 0.009), delayed diagnosis (>24 hours; P = 0.0001), and abdominal/thoracic location (37.5%; P = 0.05). No statistical differences were found between surgical and conservative/endoscopic management (31% vs 20%; P = 0.205) although hospital staying was longer in surgical group (36.30 days vs 15.63 days; P = 0.029). Esophageal perforation was associated with high morbidity and mortality rates. Global outcomes depend on etiology, site of perforation, and delay in diagnosis. An individualized approach for each patient should be chosen to prevent septic complications of this potentially fatal disease.
This article describes the event detection system of the NEXT-White detector, a 5 kg high pressure xenon TPC with electroluminescent amplification, located in the Laboratorio Subterráneo de Canfranc ...(LSC), Spain. The detector is based on a plane of photomultipliers (PMTs) for energy measurements and a silicon photomultiplier (SiPM) tracking plane for offline topological event filtering. The event detection system, based on the SRS-ATCA data acquisition system developed in the framework of the CERN RD51 collaboration, has been designed to detect multiple events based on online PMT signal energy measurements and a coincidence-detection algorithm. Implemented on FPGA, the system has been successfully running and evolving during NEXT-White operation. The event detection system brings some relevant and new functionalities in the field. A distributed double event processor has been implemented to detect simultaneously two different types of events thus allowing simultaneous calibration and physics runs. This special feature provides constant monitoring of the detector conditions, being especially relevant to the lifetime and geometrical map computations which are needed to correct high-energy physics events. Other features, like primary scintillation event rejection, or a double buffer associated with the type of event being searched, help reduce the unnecessary data throughput thus minimizing dead time and improving trigger efficiency.
Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical ...genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (
= 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.
Background: Assessing MRD has become a standard procedure in clinical trials to evaluate treatment efficacy. In accordance with its consistent prognostic value, the International Myeloma Working ...Group added MRD-negative criteria into response guidelines for its standardized use in clinical trials. That notwithstanding, the expectations for MRD as biomarker are to use it in routine clinical practice to help in treatment decisions, since in most clinical trials the therapeutic approach is defined upfront and does not vary according to patients' depth of response. However, the use of MRD in clinical practice is controversial and it remains unknown if tailoring treatment to achieve MRD-negativity is safe and improves patients' survival.
Aim: Compare in clinical practice, outcome and tolerability of a treatment strategy tailored to achieve sustained undetectable MRD by NGF and imaging, as compared to conventional treatment approaches that are not modified according to patients' depth of response.
Methods: This study was conducted in a single Hospital and included a total of 66 patients with newly-diagnosed MM from July 2014 to May 2019. All patients younger than 76 were prospectively included, whereas patients with high frailty score, severe senile dementia, other neoplasms, or with significant comorbidities in whom the therapeutic objective was only palliative care were excluded. In accordance to the local ethical committee and the Helsinki Declaration, all patients gave informed consent prior entering the study and were given the choice between the MRD and image driven (MRD-driven) and the conventional treatment (CT) approach. In the former, persistent MRD after the first-line of therapy was considered as treatment failure and patients received subsequent lines until achieving undetectable MRD by NGF and imaging (treatment endpoint). In the CT approach, subsequent lines of therapy were given upon progressive disease. The most commonly used first, second, and third line therapies in the MRD-driven approach were VBMCP/VBAD, VCD, and lenalidomide combinations, whereas in the CT cohort these were VCD for first-line, and lenalidomide combinations in second and third lines. Maintenance therapy (Interferon α2b + Prednisone for a year) was administered in 61% of patients treated according to the MRD-driven approach, and in 12% (bortezomib until progression) in the CT cohort. MRD was assessed in patients achieving complete remission using EuroFlow NGF, with a limit of detection of 2x10-6. Undetectable MRD by imaging was defined by negative PET/CT and by negative MRI of the spine and pelvis.
Results: Of the 66 patients enrolled thus far, 49 were treated with the MRD-driven and 17 with the CT approach. There were no significant differences between groups regarding patients' age (median, 62 years), the Revised-ISS (37.5%, 53% and 37.5% with R-ISS-I, -II and -III) or the usage of HDT/ASCT (85% vs 76%; P>.05). Approximately 80% of patients treated with the MRD-driven approach achieved undetectable MRD at 30 months. The median time from start of treatment to undetectable MRD was 24 months, after a average of 2.2 lines of therapy. By contrast, only 1 (6%) patient treated with CT showed undetectable MRD after first line of therapy. With a median follow-up of 29 months, progression-free survival (PFS) rates at 30 months were 92% for patients treated with the MRD-driven vs 28% for the CT approach (hazard ratio 0.10 0.04-0.30; p<0.0001). Such impact in PFS was similarly observed in sub analyses of patients treated with or without maintenance. A trend for prolonged overall survival (OS) was observed (92% vs 81% at 30-months, respectively; p=0.12). Of note, PFS and OS rates for patients treated with the MRD-driven strategy and achieving undetectable MRD were of 100% at 30 months. No significant differences were observed regarding the number of patients with adverse events treated with the MRD-driven vs CT (47% vs 59%), the number of adverse events per patient (mean of 1.9 vs 2.4), or in the number of adverse events per year of exposure (annual incidence of 1.2 vs 2.1).
Conclusions: We show that as compared to pre-specified therapies that are not modified according to patients' depth of response, an MRD-driven treatment approach reduces by 90% the risk of progression or death without increasing toxicity. These results support the use of undetectable MRD by NGF and imaging as treatment endpoint in routine clinical practice.
Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau.
Aims
Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and ...outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs.
Methods and results
Clinical variables and outcomes after a median follow‐up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups.
Conclusion
LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted.
We sought to describe neonatal morbidities and therapeutic interventions in very low-birth-weight (VLBW) and extremely low-birth-weight (ELBW) infants cared for in Spanish hospitals. We preformed a ...prospective collection of data covering the perinatal period until discharge by the SEN1500 network. This network, set up by the Spanish Society of Neonatology, targets VLBW and ELBW infants (400 to 1500 g) admitted to neonatal units in Spanish hospitals. Data were recorded in electronic form and controlled for possible errors or inconsistencies before analysis. We report data for 8836 neonates admitted to 48 neonatal units from January 2002 to December 2005. Prenatal steroids were given to significantly more newborns in 2003 to 2005 (79.4%) than in 2002 (73.4%), although the remaining perinatal data examined failed to significantly vary. Delivery was by cesarean section in 69.8% of cases but significantly lower (35.9%) for infants under a postmenstrual age of 26 weeks. Hyaline membrane disease was diagnosed in 53.9% of the newborns and bronchopulmonary dysplasia (BPD) in 10.46%. Mechanical ventilation was employed in 69.1%, surfactant in 50.3%, and steroids for BPD in 5.3%. Intraventricular hemorrhage grades 3 to 4 (8.1%) and cystic leukomalacia (2.6%) were the most relevant brain ultrasonography findings. Rates of early- and late-onset septicemia were 5% and 29.4%, respectively. Further diagnoses were necrotizing enterocolitis (NEC; 6.9%) and persistent ductus arteriosus (PDA; 24.2%); 40.6% of the cases of NEC and 15.3% of those of PDA required surgery. In addition, 26.6% of the newborns required supplementary oxygen at 28 days of life. The number of newborns who had not recovered their birth weight at this age fell from 3.1% in 2002 to 1.5% in 2005. Rates of prenatal steroid use, cesarean delivery, and main morbidities were comparable to figures cited for other patient series, although our BPD rate was among the lowest reported and nosocomial sepsis rate among the highest.
The aim of this paper was to determine the prevalence of extracraneal carotid artery disease in patients with intermittent claudication, to describe classic cardiovascular risk factors in those with ...hemodynamically significant stenosis and to try to define subgroups at high risk, improving therefore the performance of non invasive testing.
A prospective descriptive study was conducted, with 146 patients reporting an intermittent claudication of the lower limbs and without a previous cerebrovascular event or carotid surgery. An ultrasonography examination was done. Risk factors were registed (smoking, dislipemia, arterial hypertension, diabetes mellitus), also ischemic cardiopathy and myocardial revascularization procedures. Univariate and multivariate analysis was made to define the variables associated with hemodynamically significant stenosis.
Prevalence of hemodynamically significant stenosis was 23.2%. Smoking, dislipemia, arterial hypertension and diabetes mellitus were not significantly associated with carotid stenosis; 24.2% of patients affected of ischemic cardiopathy present a severe stenosis, and myocardial revascularization was a risk factor for carotid stenosis.
Patients with claudication and ischemic miocardiopathy, especially when myocardial revascularization is needed, must be explored with carotid ultrasonography. In this patients, probably of hemodynamically significant carotid stenosis that requires treatment is more frequent.
The purpose of this study was to analyze the mortality and its prognostic factors in a Spanish cohort of very low birthweight (VLBW) infants during the period 2002 to 2005. Using the Spanish Society ...of Neonatology database (SEN 1500), 8942 infants with a birthweight < 1500 g were recruited. The overall mortality was 17.3%. However, this incidence underwent a significant decrease over the study period, from 19.4% in 2002 to 15.2% in 2005 ( P = 0.003). Mortality ranged from 12.4% in 25% of the participating neonatal units to 19.4% in a further 25%. Mortality was higher in outborn infants (25.8%) than in inborn infants (16.6%) ( P < 0.001). The mortality rates of these neonates are also presented by 100-g intervals (401 to 1500) and for the different hospitalization times: in the delivery room, within 24 hours and 28 days of birth, at 36 weeks of postmenstrual age, and on discharge. Of note was that mortality was greatest within 24 hours and 28 days of birth in each of the weight groups ( P < 0.001). In conclusion, in the cohort of infants < 1500 g examined, mortality in the period from 2002 to 2005 was still high, especially among newborns weighing < 1000 g. We did, however, observe a decreasing trend in mortality rates for the participating neonatal units over the 4 study years. Our findings highlight the need to promote intrauterine transport and improve neonatal transport as well as the management of these infants in the delivery room and within the first 28 days of life.
Se realiza un estudio comparativo en ratas singénicas de la cepa Wistar con objeto de valorar los efectos de preservación del injerto al utilizar el antagonista del factor de activación plaquetaria, ...WEB-2086. En la valoración ultraestructural se ha podido comprobar los efectos de esta sustancia al nivel de las células epiteliales de intestino trasplantado
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