Search

Contains fulltext : 282593.pdf (Publisher’s version ) (Closed access) BACKGROUND: Despite application of the multimodal European Resuscitation Council and European Society of Intensive Care Medicine algorithm, neurological prognosis of patients who remain comatose after cardiac arrest remains uncertain in a large group of patients. In this study, we investigate the additional predictive value of visual and quantitative brain magnetic resonance imaging (MRI) to electroencephalography (EEG) for outcome estimation of comatose patients after cardiac arrest. METHODS: We performed a prospective multicenter cohort study in patients after cardiac arrest submitted in a comatose state to the intensive care unit of two Dutch hospitals. Continuous EEG was recorded during the first 3 days and MRI was performed at 3 ± 1 days after cardiac arrest. EEG at 24 h and ischemic damage in 21 predefined brain regions on diffusion weighted imaging and fluid-attenuated inversion recovery on a scale from 0 to 4 were related to outcome. Quantitative MRI analyses included mean apparent diffusion coefficient (ADC) and percentage of brain volume with ADC

Adrenal cortical carcinoma (ACC) is an uncommon neoplasm with variable prognosis. Several histologic criteria have been identified as predictors of malignancy in adrenal cortical tumors. The Weiss score is the system most widely employed for diagnostic purposes, but also possesses prognostic value. We aim to determine the relative impact of each Weiss parameter on ACC patient survival. A multicenter retrospective analysis was conducted on a series of 79 conventional ACCs surgically treated at the Florence and Utrecht centers of the European Network for the Study of Adrenal Tumors (ENSAT). Weiss classification was recapitulated using principal component analysis (PCA). The Kaplan–Meier and Cox multivariate regression analyses were applied in order to estimate the prognostic power of Weiss versus other clinical parameters. PCA reduced the nine Weiss parameters to the best fitting 4-component model, each parameter clustering with a single component. Necrosis and venous invasion clustered together with the highest scores, thus establishing the most relevant component (Component 1) to explain Weiss distribution variability. Only Component 1 significantly predicted overall survival (OS, log-rank = 0.008) and disease-free survival (DFS, log-rank p = 0.05, and HR = 12.2, 95% CI = 1.6–95.0, p = 0.017, respectively]. The presence of necrosis significantly shortened time to survival (TtS) and time to recurrence (TtR), 57.5 [31.5–103.5] vs 34 [12–78] months (p = 0.05) and 57.5 [31.5–103.5] vs 7 [1.0–31.5] months (p

Objective We sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) or reoperative surgical aortic valve replacement (redo-SAVR) in the Netherlands. Methods Patients who had undergone ViV-TAVI or redo-SAVR for a degenerated biological aortic valve prosthesis in the Netherlands between January 2014 and December 2018 were eligible for this retrospective study. Patients with a prior homograft, active endocarditis or mechanical aortic valve prosthesis were excluded. Patients were matched using the propensity score. The primary endpoint was a composite of 30-day all-cause mortality and in-hospital postoperative stroke. Secondary endpoints were all-cause mortality at different time points, in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year. Baseline characteristics and outcome data were collected from the Netherlands Heart Registration. Results From 16 cardiac centres, 653 patients were included in the study (374 ViV-TAVI and 279 redo-SAVR). European System for Cardiac Operative Risk Evaluation I (EuroSCORE I) was higher in ViV-TAVI patients (19.4, interquartile range (IQR) 13.3–27.9 vs 13.8, IQR 8.3–21.9, p Conclusion Patients with degenerated aortic bioprostheses treated with ViV-TAVI or redo-SAVR have similar mortality and morbidity.

Background Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5–26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines. Aim The aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs. Methods Clinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27. Results Nine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30–55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008). Conclusion Our data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.

Although there is clear evidence that an Enhanced Recovery After Surgery (ERAS) program in colorectal surgery leads to significantly reduced morbidity rates and length of hospital stay (LOS), it is still unclear what modalities and levels of implementation of the program are necessary to achieve these results. The purpose of this study is to analyze the methods and results of the first year of structured implementation of a colorectal ERAS program in two surgical units of the Azienda Sanitaria Unica Regionale (ASUR) Marche in Italy. A two-center observational study on a prospectively maintained database was performed on 196 consecutive colorectal resections (excluding emergencies and American Society of Anesthesiologists class > III cases) over a 1-year period. More than 50 variables including adherence to the individual items of the ERAS program were considered. Primary outcomes were overall morbidity, major morbidity, mortality and anastomotic leakage rates; secondary outcomes were LOS, re-admission and re-operation. The results were evaluated by univariate and multivariate analyses through logistic regression. After a median follow-up of 39.5 days, we recorded complications in 72 patients (overall morbidity 36.7%), major complications in 14 patients (major morbidity 7.1%), 6 deaths (mortality 3.1%), anastomotic dehiscence in 9 cases (4.9%), mean overall LOS of 6.6 days, 10 readmissions (5.1%) and 13 reoperations (6.7%). The mean adherence rate to the items of the ERAS program was 85.4%, showing a significant dose–effect curve for overall and major morbidity rates, anastomotic leakage rates and LOS. The implementation methods of a colorectal ERAS program in this study led to a high adherence (> 80%) to the program items. High adherence had significant effects also on major morbidity and anastomotic leakage rates.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p

The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p

Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis. Improving our knowledge about ACC molecular features will result not only in a better diagnostic and prognostic accuracy, but also in the identification of more specific therapeutic targets for the development of more effective pharmacological anti-cancer approaches. In particular, the specific molecular alteration profiles identified in ACC may represent targetable events by the use of already developed or newly designed drugs enabling a better and more efficacious management of the ACC patient in the context of new frontiers of personalized precision medicine.

This paper examines the long-term placement trajectories of youth aged 10 to 17 years at initial investigation, with attention to the comparative trajectories of youth served for sexual abuse gender differences, and the mediating effects of behavioral difficulties experienced post investigation. This analysis draws administrative data on all youth served (N = 77,579) by child protection agencies in Quebec for the first time in the last 12 years. Hazard results suggest that youth served for CSA do not enter out-of-home care as quickly as other youth and once in out-of-home care, it takes longer for these youths to reunify with their families. Behavioral problems drive the increased risk of placement for all served youth but play a more influential role for youth served for CSA. Understanding the effects of CSA on youth placed in out-of-home care can help practitioners and program implementers offer more comprehensive and targeted services to improve reunification timelines, and possibly avoid out-of-home placement and placement instability.

L’ultimo decennio ha visto lo sviluppo esponenziale della genomica, ossia dell’insieme di tecniche di analisi molecolare dei campioni biologici. Tale approccio molecolare ha rivoluzionato la biologia e la genetica anche del carcinoma della corteccia surrenalica (ACC). L’applicazione di tali tecniche all’analisi di ampie casistiche di ACC ha portato all’identificazione di alterazioni nell’espressione genica, nello stato di metilazione, nella struttura cromosomica, dotate di valore prognostico e predittivo, permettendo di formulare una classificazione molecolare della malattia. Tale classificazione potrebbe rivestire un ruolo rilevante non solo per migliorare l’accuratezza della prognosi, ma soprattutto per identificare nuovi bersagli terapeutici utilizzabili per la cura di questo tumore, che ha ad oggi limitati e poco efficaci approcci terapeutici farmacologici.

Objectives To evaluate the procedural and clinical outcomes of a new primary percutaneous coronary intervention (PPCI) centre without surgical back-up (off-site PCI) and to investigate whether these results are comparable with a high volume on-site PCI centre in the Netherlands. Background Controversy remains about the safety and efficacy of PPCI in off-site PCI centres. Methods We retrospectively analysed clinical and procedural data as well as 6‑month follow-up of 226 patients diagnosed with ST-elevated myocardial infarction (STEMI) who underwent PPCI at VieCuri Medical Centre Venlo and 115 STEMI patients who underwent PPCI at Catharina Hospital Eindhoven. Results PPCI patients in VieCuri Medical Centre had similar procedural and clinical outcomes to those in Catharina Hospital. Overall there were no significant differences. The occurrence of procedural complications was low in both groups (8.4 % VieCuri vs. 12.3 % Catharina Hospital). In the VieCuri group there was one procedural-related death. No patients in either group needed emergency surgery. At 30 days, 17 (7.9 %) patients in the VieCuri group and 9 (8.1 %) in the Catharina Hospital group had a major adverse cardiac event. Conclusion Performing PPCI in an off-site PCI centre is safe and effective. The study results show that the procedural and clinical outcomes of an off-site PPCI centre are comparable with an on-site high-volume PPCI centre.

AIM: This study explores clinical outcome in cytochrome P450 2C19 (CYP2C19)-related poor metaboliser patients treated with either clopidogrel or prasugrel after percutaneous coronary intervention (PCI) and investigates whether this could be cost-effective.METHODS AND RESULTS: This single-centre, observational study included 3260 patients scheduled for elective PCI between October 2010 and June 2013 and followed for adverse cardiovascular events until October 2014. Post PCI, CYP2C19 poor metaboliser patients were treated with clopidogrel or prasugrel, in addition to aspirin. In total, 32 poor metabolisers were treated with clopidogrel and 41 with prasugrel. The number of adverse cardiovascular events, defined as death from cardiovascular cause, myocardial infarction, stent thrombosis, every second visit to the catheterisation room for re-PCI in the same artery, or stroke, within 1.5 years of PCI, was significantly higher in the CYP2C19 poor metaboliser group treated with clopidogrel (n = 10, 31 %) compared with the poor metaboliser group treated with prasugrel (n = 2, 5 %) (p = 0.003). Costs per gained quality-adjusted life years (QALY) were estimated, showing that genotype-guided post-PCI treatment with prasugrel could be cost-effective with less than € 10,000 per gained QALY.CONCLUSION: This study provides evidence that for CYP2C19-related poor metabolisers prasugrel may be more effective than clopidogrel to prevent major adverse cardiovascular events after PCI and this approach could be cost-effective.

Reliability of water distribution networks (WDNs) has received much attention in recent years due to progressive aging of infrastructures and climate change. Several reliability indicators, focusing on hydraulic aspects rather than water quality, have been proposed in literature. Reliability is generally assessed resorting to well established methods coupling hydraulic simulations and stochastic techniques that describe the WDNs hydraulic performance and component availability respectively. Two main algorithms are employed to simulate WDNs: the demand driven approach (DDA) that disregards the physical relationship between actual water demand and nodal pressure, and the pressure driven approach (PDA) that explicitly incorporates it. In this paper, we show how the choice of hydraulic solver may affect reliability indicators. We modify existing quantitative indicators at nodal and network level, and define novel indicators to consider water quality aspects. These indicators are evaluated for three example WDNs; discrepancies between results obtained with the two approaches depend on network size, feeding scheme and skeletonization. Results suggest to use with caution the DDA for reliability assessment at both local and global level.

Background Large-diameter head metal-on-metal (MoM) bearings in total hip arthroplasty (THA) are associated with increased whole blood levels of chromium (Cr) and cobalt (Co), adverse reactions to metal debris (ARMD) and poor survival rates. The prevalence of high metals concentrations, ARMD and the risk of revision surgery may vary significantly among different prostheses and long-term studies are few. This single-center study reports the long-term results of the 38-mm MoM bearing system. Materials and methods Between 2003 and 2009, 80 patients received primary cementless THA using the large head metal-on-metal articulating surface M2A-38 cup (Biomet, Inc., Warsaw, IN, USA) at a single institution. Forty-five patients (53 hips) were retrospectively reviewed for a mean follow-up of 127 months. Results Two cups were revised. The cumulative implant survival rate was 98% at 10 years and 74% at 13 years. In the whole sample, the median Co and Cr concentrations were 4.8 µg/L (IQR 1.2–4.9 µg/L) and 2.5 µg/L (IQR 0.6–3.0 µg/L), respectively. The incidence of Co or Cr levels > 7 μg/L was 15.5% and the incidence of ARMD was 3.8%. Co and Cr levels showed no correlation with cup inclination, Harris Hip Score, or total Hip Disability and Osteoarthritis Outcome score. Conclusions Our results confirm that the problems of release of metal ions with the possible increase of metal circulating levels and of adverse reactions may also occur in the long term with this brand of MoM large head, and that a structured follow-up program is mandatory. Levels of evidence Level 4.