Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

The ALTRO Chip: A 16-channel A/D Converter and Digital Processor for Gas Detectors

integrated circuit designed to be one of the building blocks of the readout electronics for gas detectors. Originally conceived and optimized for the time projection chamber (TPC) of the ALICE experiment at the CERN LHC, its architecture and programmability make it suitable for the readout of a wider class of detectors. In one single chip, the analog signals from 16 channels are digitised, processed, compressed, and stored in a multi-acquisition memory. The analog-to-digital converters embedded in the chip have a 10-bit dynamic range and a maximum sampling rate in the range of 20–. After digitization, a pipelined Data Processor is able to remove from the input signal a wide range of perturbations, related to the nonideal behavior of the detector, temperature variation of the electronics, environmental noise, etc. Moreover, the Data Processor is able to suppress the pulse tail within 1 s after the peak with 1 ‰ accuracy, thus narrowing the pulses to improve their identification. The signal is then compressed by removing all data below a programmable threshold, except for a specified number of pre- and post-samples around each peak. This produces nonzero data packets. Eventually, each data packet is marked with its time stamp and size – so that the original data can be reconstructed afterwards – and stored in the multi-acquisition memory that has a readout bandwidth of 300 Mbyte/s. This paper addresses the algorithms of the implemented digital functions and the performance of the ALTRO chip. Index Terms—Analog-digital conversion, CMOS mixed analogdigital integrated circuit, data processing, digital filter, gas detector