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Background: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration: registered on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au), registration number ACTRN12615000707561. [ABSTRACT FROM AUTHOR]

Background: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. Aims: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. Methods: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). Results: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. Conclusions: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study assessed the effects of a new interface that combined CPAP 10 cm H2O by using a helmet with high-flow nasal cannula (HFNC) at varying flows in healthy volunteers. Outcome measures included pharyngeal pressures, diaphragm kinetics, breathing frequency, the temperature inside the helmet, and comfort. METHODS: After baseline assessment during spontaneous breathing, HFNC was applied at flows of 30, 40, and 50 L/min. Successively, the volunteers underwent helmet CPAP at 10 cm H2O and CPAP + HFNC at flows of 30, 40, and 50 L/min. We measured the variations of pharyngeal pressures at end-expiration and end-inspiration, referenced to spontaneous breathing for HFNC and to CPAP for CPAP + HFNC, diaphragm displacement and thickness at end-expiration and thickness at end-inspiration, breathing frequency, the temperature inside the helmet, the occurrence of the fog effect, and comfort. RESULTS: Variations of pharyngeal pressures at end-inspiration changes were small overall and clinically unimportant. With the mouth closed, at increasing HFNC flow, variations of pharyngeal pressures at endexpiration increased during both HFNC (from 2.8 up to 7.7) and, to a lesser extent, CPAP + HFNC (from 2.7 up to 3.8) (P < .001 for all comparisons). These variations were attenuated during open-mouth breathing. HFNC > 40 L/min and CPAP + HFNC ≥ 40 L/min compared with spontaneous breathing and CPAP, respectively, increased diaphragm displacement (P = .001), thickness at end-inspiration and thickness at end-expiration (P < .003 for both). At all flows, breathing frequency was slightly, although significantly, lower with CPAP + HFNC than with HFNC alone (P < .003). The temperature inside the helmet increased slightly and insignificantly at flows of ≤40 L/min with CPAP + HFNC compared with CPAP alone. The fog effect never occurred, whereas comfort was always rated as optimal, without differences between trials. CONCLUSIONS: CPAP + HFNC was well tolerated, with no adverse effects. Based on our findings, there was no need to vary the CPAP level when adding HFNC. At least in healthy subjects, CPAP + HFNC at 30 L/min seemed to be the best combination. [ABSTRACT FROM AUTHOR]

Background/Aim: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. Subjects and Methods: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. Results: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). Conclusions: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment. [ABSTRACT FROM AUTHOR]

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.