Prostate Cancer Unit Initiative in Europe: A position paper by the European School of Oncology.

The Prostate Cancer Programme of the European School of Oncology developed the concept of specialised interdisciplinary and multiprofessional prostate cancer care to be formalized in Prostate Cancer Units (PCU). After the publication in 2011 of the collaborative article "The Requirements of a Specialist Prostate Cancer Unit: A Discussion Paper from the European School of Oncology", in 2012 the PCU Initiative in Europe was launched. A multiprofessional Task Force of internationally recognized opinion leaders, among whom representatives of scientific societies, and patient advocates gathered to set standards for quality comprehensive prostate cancer care and designate care pathways in PCUs. The result was a consensus on 40 mandatory and recommended standards and items, covering several macro-areas, from general requirements to personnel to organization and case management. This position paper describes the relevant, feasible and applicable core criteria for defining PCUs in most European countries delivered by PCU Initiative in Europe Task Force.

Neuro-mechanical determinants of repeated treadmill sprints - Usefulness of an "hypoxic to normoxic recovery" approach.

To improve our understanding of the limiting factors during repeated sprinting, we manipulated hypoxia severity during an initial set and examined the effects on performance and associated neuro-mechanical alterations during a subsequent set performed in normoxia. On separate days, 13 active males performed eight 5-s sprints (recovery = 25 s) on an instrumented treadmill in either normoxia near sea-level (SL; FiO2 = 20.9%), moderate (MH; FiO2 = 16.8%) or severe normobaric hypoxia (SH; FiO2 = 13.3%) followed, 6 min later, by four 5-s sprints (recovery = 25 s) in normoxia. Throughout the first set, along with distance covered [larger sprint decrement score in SH (-8.2%) compared to SL (-5.3%) and MH (-7.2%); P < 0.05], changes in contact time, step frequency and root mean square activity (surface electromyography) of the quadriceps (Rectus femoris muscle) in SH exceeded those in SL and MH (P < 0.05). During first sprint of the subsequent normoxic set, the distance covered (99.6, 96.4, and 98.3% of sprint 1 in SL, MH, and SH, respectively), the main kinetic (mean vertical, horizontal, and resultant forces) and kinematic (contact time and step frequency) variables as well as surface electromyogram of quadriceps and plantar flexor muscles were fully recovered, with no significant difference between conditions. Despite differing hypoxic severity levels during sprints 1-8, performance and neuro-mechanical patterns did not differ during the four sprints of the second set performed in normoxia. In summary, under the circumstances of this study (participant background, exercise-to-rest ratio, hypoxia exposure), sprint mechanical performance and neural alterations were largely influenced by the hypoxia severity in an initial set of repeated sprints. However, hypoxia had no residual effect during a subsequent set performed in normoxia. Hence, the recovery of performance and associated neuro-mechanical alterations was complete after resting for 6 min near sea level, with a similar fatigue pattern across conditions during subsequent repeated sprints in normoxia.

The predictive value of preoperative B-type natriuretic peptide in children undergoing cardiac surgery

Introduction: B-type natriuretic peptide (BNP) is a biomarker of myocardial stress. In children, the value of preoperative BNP on postoperative outcome is unclear. The aim of this study was to determine the predictive value of preoperative NT-proBNP on postoperative outcome in children after congenital heart surgery. Results: Ninety-seven patients were included in the study with a median age of 3.3 years [0.7-5.2]. Preoperative median NT-proBNP was 412 pg/ml [164-1309]. NT-proBNP was above the P95 reference value for age in 56 patients (58%). Preoperative NT-proBNP was significantly higher in patients who had mechanical ventilation duration of more than 2 days (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) and who stayed more than 6 days in the pediatric intensive care unit (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). However, preoperative NT-proBNP was not significantly higher in patients with an increased inotropic score, a prolonged cardiopulmonary bypass time or an increased surgical risk category. Conclusions: An elevated preoperative NT-proBNP reflects hemodynamic status and cardiac dysfunction, and therefore is a valuable adjunct in predicting a complicated postoperative course. ___________________________________ Introduction: Le peptide natriurétique type B (BNP) est un marqueur reflétant le stress myocardique. Dans la population pédiatrique, la signification des valeurs préopératoire de BNP, en particulier sur l'évolution postopératoire, n'est pas clairement établie. Le but de l'étude est de déterminer la valeur prédictive de la partie NT sérique du BNP (NT-proBNP) sur l'évolution post opératoire d'enfants porteur d'une cardiopathie congénitale et ayant eu une chirurgie cardiaque. Résultats: Nonante-sept enfants ont été inclus dans l'étude, avec un âge médian de 3.3 ans [0.7-5.2]. La valeur médiane du NT-proBNP préopératoire était de 412 pg/ml [164-1309]. Le NT-proBNP préopératoire était supérieur au P95 des valeurs de référence pour l'âge chez 56 patients (58%). Le NT-proBNP préopératoire était significativement plus élevé chez les patients ayant eu plus de deux jours de ventilation mécanique dans la période postopératoire (1156 pg/ml [281-1951] vs. 267 pg/ml [136-790], p=0.003) et ayant été hospitalisés plus de 6 jours dans l'unité de soins intensifs pédiatrique (727 pg/ml [203-1951] vs. 256 pg/ml [136-790], p=0.007). Par contre, le NT-proBNP préopératoire n'était pas significativement plus élevé chez les patients ayant eu un score d'inotrope élevé pendant leur hospitalisation aux soins intensifs, un temps de circulation extracorporelle prolongé ou ayant subi une chirurgie avec un risque chirurgical élevé. Conclusions: Un NT-proBNP sérique élevé en préopératoire reflète l'importance du stress myocardique induit par l'hémodynamique et la dysfonction myocardique, il est un marqueur qui permet d'améliorer l'identification des patients à risque d'avoir une évolution post opératoire compliquée.

Toward on-the-fly quantum mechanical/molecular mechanical (QM/MM) docking: development and benchmark of a scoring function.

We address the challenges of treating polarization and covalent interactions in docking by developing a hybrid quantum mechanical/molecular mechanical (QM/MM) scoring function based on the semiempirical self-consistent charge density functional tight-binding (SCC-DFTB) method and the CHARMM force field. To benchmark this scoring function within the EADock DSS docking algorithm, we created a publicly available dataset of high-quality X-ray structures of zinc metalloproteins ( http://www.molecular-modelling.ch/resources.php ). For zinc-bound ligands (226 complexes), the QM/MM scoring yielded a substantially improved success rate compared to the classical scoring function (77.0% vs 61.5%), while, for allosteric ligands (55 complexes), the success rate remained constant (49.1%). The QM/MM scoring significantly improved the detection of correct zinc-binding geometries and improved the docking success rate by more than 20% for several important drug targets. The performance of both the classical and the QM/MM scoring functions compare favorably to the performance of AutoDock4, AutoDock4Zn, and AutoDock Vina.

Rectal enema is an alternative to full mechanical bowel preparation for primary rectal cancer surgery.

AIM: According to the French GRECCAR III randomized trial, full mechanical bowel preparation (MBP) for rectal surgery decreases the rate of postoperative morbidity, in particular postoperative infectious complications, but MBP is not well tolerated by the patient. The aim of the present study was to determine whether a preoperative rectal enema (RE) might be an alternative to MBP. METHODS: An analysis was performed of 96 matched cohort patients undergoing rectal resection with primary anastomosis and protective ileostomy at two different university teaching hospitals, whose rectal cancer management was comparable except for the choice of preoperative bowel preparation (MBP or RE). Prospective databases were retrospectively analysed. RESULTS: Patients were well matched for age, gender, body mass index and Charlson index. The surgical approach and cancer characteristics (level above anal verge, stage and use of neoadjuvant therapy) were comparable between the two groups. Anastomotic leakage occurred in 10% of patients having MBP and in 8% having RE (P = 1.00). Pelvic abscess formation (6% vs 2%, P = 0.63) and wound infection (8% vs 15%, P = 0.55) were also comparable. Extra-abdominal infection (13% vs 13%, P = 1.00) and non-infectious abdominal complications such as ileus and bleeding (27% and 31%, P = 0.83) were not significantly different. Overall morbidity was comparable in the two groups (50% vs 54%, P = 0.83). CONCLUSION: A simple RE before rectal surgery seems not to be associated with more postoperative infectious complications nor a higher overall morbidity than MBP.