Cross-cultural differences in men on active surveillance' anxiety: a longitudinal comparison between Italian and Dutch patients from the Prostate cancer Research International Active Surveillance study.

BACKGROUND: Men diagnosed with localized prostate cancer (PCa) on active surveillance (AS) have shown to cope with anxiety caused by living with an 'untreated cancer' and different factors can influence the tolerance level for anxiety in these patients. The present study analyzes Italian (Milan) and Dutch (Rotterdam) men prospectively included in the Prostate cancer International Active Surveillance (PRIAS) trial, aiming to explore whether socio-demographic factors (i.e. age, relationship status, education, nationality) may be relevant factors in conditioning the level of anxiety at AS entry and over time. METHODS: Italian and Dutch men participating in the IRB-approved PRIAS study, after signing an informed consent, filled in the Memorial Anxiety Scale for PCa (MAX-PC) at multiple time points after diagnosis. A linear mixed model was used to assess the relationship between the level of patient's anxiety and time spent on AS, country of origin, the interaction between country and time on AS, patients' relationship status and education, on PCa anxiety during AS. RESULTS: 823 MAX-PC questionnaires were available for Italian and 307 for Dutch men, respectively. Median age at diagnosis was 64 years (IQR 60-70 years) and did not differ between countries. On average, Dutch men had a higher total MAX-PC score than Italian men. However, the level of their anxiety decreased over time. Dutch men on average had a higher score on the PCa anxiety sub-domain, which did not decrease over time. Minimal differences were observed in the sub-domains PSA anxiety and fear of recurrence. CONCLUSION: Significant differences in PCa anxiety between the Italian and Dutch cohorts were observed, the latter group of men showing higher overall levels of anxiety. These differences were not related to the socio-demographic factors we studied. Although both PRIAS-centers are dedicated AS-centers, differences in PCa-care organization (e.g. having a multidisciplinary team) may have contributed to the observed different level of anxiety at the start and during AS. Trial registration This study is registered in the Dutch Trial Registry ( www.trialregister.nl ) under NL1622 (registration date 11-03-2009), 'PRIAS: Prostate cancer Research International: Active Surveillance-guideline and study for the expectant management of localized prostate cancer with curative intent'.

Potential of the Stromal Matricellular Protein Periostin as a Biomarker to Improve Risk Assessment in Prostate Cancer.

Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients.

How do prostate cancer patients navigate the active surveillance journey? A 3-year longitudinal study.

OBJECTIVE: To investigate whether prostate cancer (PCa) patients' coping strategies (i.e., fighting spirit, anxious preoccupation, fatalism, helplessness/hopelessness, and avoidance) significantly change during the first 3-year follow-up period of active surveillance (AS). MATERIALS AND METHODS: Altogether, 104 patients on AS completed the Mini-Mental Adjustment to Cancer (Mini-MAC) at baseline (T0), at 10 and 12 months after diagnostic biopsy (T1 and T2, respectively) and then at 24- (T3) and 36-month (T4) follow-up. Paired samples T test was used to detect statistically significant changes over time. Changes ≥ 1 point (or ≤ - 1) were hypothesized to be clinically relevant. RESULTS: During the first 3 years on AS, men experienced decreased anxiety, avoidance thoughts/behaviors, and fight-against-cancer attitudes, and these changes were found to be statistically significant. When considering clinically significant changes between inclusion in AS (T0) and 3-year follow-up (T4), avoidance decreased in 19% of patients. CONCLUSIONS: Most patients were observed to have adopted functional coping strategies at baseline, which were maintained through the first 3 years on AS. Overall, men on AS may perceive increasing control over their cancer and comfort with the AS protocol over time and experience slight decreases in anxious preoccupation, cancer-related avoidance thoughts and behaviors, and fight-against-cancer reactions. For those men who find it difficult to cope with AS, psychological monitoring and interventions could be helpful throughout the monitoring journey.

Plasma levels of extracellular vesicles and the risk of post-operative pulmonary embolism in patients with primary brain tumors: a prospective study.

Primary brain tumors are associated with an increased risk of pulmonary embolism (PE), particularly in the early post-operative period. The pathophysiological mechanisms of PE are poorly understood. This study aims to describe prospectively extracellular vesicles (EVs) levels and investigate whether or not their variations allow to identify patients at increased risk of post-operative PE. Consecutive meningioma or glioma patients candidate to tumor resection were included in the study if a pulmonary perfusion scan (Q-scan) performed before surgery ruled out PE. EVs derived from platelets (CD41+) or endothelial cells (CD144+), tissue factor-bearing EVs (CD142+) and their procoagulant subtype (annexin V+) were analyzed by flow cytometry before surgery (T0), within 24 h (T1), two (T2) and seven days (T7) after surgery. Q-scan was repeated at T2. Ninety-three patients with meningioma, 59 with glioma and 76 healthy controls were included in the study. CD142+ and annexin V+/CD142+ EVs were increased at T0 in meningioma and glioma patients compared to healthy controls. Twenty-nine meningioma (32%) and 16 glioma patients (27%) developed PE at T2. EVs levels were similar in meningioma patients with or without PE, whereas annexin V+ and annexin V+/CD142+ EVs were significantly higher at T1 and T2 in glioma patients with PE than in those without. Procoagulant EVs, particularly annexin V+/CD142+, increase after surgery and are more prevalent in glioma patients who developed PE after surgery than in those who did not.

Making Active Surveillance a path towards health promotion: A qualitative study on prostate cancer patients' perceptions of health promotion during Active Surveillance.

OBJECTIVE: Health promotion is a key aspect for health outcomes of prostate cancer (PCa) patients. However, it has been poorly explored among patients following monitoring programmes, for example Active Surveillance (AS). This study aimed to explore PCa patients' perceptions of health promotion during AS. METHODS: An explorative qualitative research design was adopted. Four focus groups were used to collected data from 24 men enrolled in the Prostate Cancer Research International: AS (PRIAS) protocol. A thematic analysis with an inductive approach was performed. RESULTS: Participants described promoting health during AS as challenged by mental, age-related, informational and organisational issues. It was reported as an effort to stay in the present with a positive outlook, despite the worries for the future ("the mental theme"). It was perceived as impacted by being older and having to manage physical and mental struggles related to age ("the life-course theme"). It depended, in their accounts, on obtaining reliable information and personalised education ("the educational theme"). Finally, it was related on taking responsibility on the care process ("the organisational theme"). CONCLUSION: This study suggested ways of promoting health during AS that can help healthcare professionals and organisations building a "health-promoting AS," able to improve overall health outcomes.

Stability of Multi-Parametric Prostate MRI Radiomic Features to Variations in Segmentation.

Stability analysis remains a fundamental step in developing a successful imaging biomarker to personalize oncological strategies. This study proposes an in silico contour generation method for simulating segmentation variations to identify stable radiomic features. Ground-truth annotation provided for the whole prostate gland on the multi-parametric MRI sequences (T2w, ADC, and SUB-DCE) were perturbed to mimic segmentation differences observed among human annotators. In total, we generated 15 synthetic contours for a given image-segmentation pair. One thousand two hundred twenty-four unfiltered/filtered radiomic features were extracted applying Pyradiomics, followed by stability assessment using ICC(1,1). Stable features identified in the internal population were then compared with an external population to discover and report robust features. Finally, we also investigated the impact of a wide range of filtering strategies on the stability of features. The percentage of unfiltered (filtered) features that remained robust subjected to segmentation variations were T2w-36% (81%), ADC-36% (94%), and SUB-43% (93%). Our findings suggest that segmentation variations can significantly impact radiomic feature stability but can be mitigated by including pre-filtering strategies as part of the feature extraction pipeline.

Induced myocardial ischemia in candidates to liver transplantation without evidence of heart disease.

BACKGROUND: Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease. METHODS: LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography. CCTA was performed in patients ≥50 years with two or more CV risk factors (e.g. diabetes, CAD family history, dyslipidaemia). Coronary angiography (CAG) was scheduled when stress echocardiography and/or CCTA were positive. Sensibility, specificity, positive and negative predictive values of stress echocardiography and CCTA were assessed by numbers of coronary revascularization (true positives) and lack of acute coronary events over a mean follow-up of 3 years (true negatives). RESULTS: Stress echocardiography was performed in 273 patients, CCTA in 34 and CAG in 41. Eight patients had critical coronary lesions, and 19 not-critical lesions. Sensitivity, specificity, positive and negative predictive values were 50.0%, 90.2%, 13.3% and 98.4% for stress echocardiography and 100%, 76.7%, 36.4% and 100% for CCTA. Among 163 patients who underwent LT (57.6%), 16 died and 5 had major adverse CV events over a mean follow-up of 3 years. CONCLUSIONS: A very low prevalence of CAD in a selected population of ESLD at intermediate to high CV risk was found. A screening based on stress echocardiography and CCTA resulted in low incidence of post-LT acute coronary events in ELSD patients. CAD has no impact on mid-term survival.

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort.

Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG ≥ 3, pT ≥ 3, pN > 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores < 3, PSA < 10 ng/mL, PSA density [PSAD] < 0.15 ng/mL/cm3) and low-risk (LR: GG1, cT1-2, PSA ≤ 10 ng/mL) patients undergoing subsequent RP. The Kaplan−Meier method and log−rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p < 0.001) and earlier (median time: 40.3 vs. 62.6 months; p < 0.001) in LR patients, and consisted of pT ≥ 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p < 0.001), but not of GG ≥ 3 or node involvement. Age (OR 1.05, p < 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.

Prediction of Grade Reclassification of Prostate Cancer Patients on Active Surveillance through the Combination of a Three-miRNA Signature and Selected Clinical Variables.

Active surveillance (AS) has evolved as a strategy alternative to radical treatments for very low risk and low-risk prostate cancer (PCa). However, current criteria for selecting AS patients are still suboptimal. Here, we performed an unprecedented analysis of the circulating miRNome to investigate whether specific miRNAs associated with disease reclassification can provide risk refinement to standard clinicopathological features for improving patient selection. The global miRNA expression profiles were assessed in plasma samples prospectively collected at baseline from 386 patients on AS included in three independent mono-institutional cohorts (training, testing and validation sets). A three-miRNA signature (miR-511-5p, miR-598-3p and miR-199a-5p) was found to predict reclassification in all patient cohorts (training set: AUC 0.74, 95% CI 0.60-0.87, testing set: AUC 0.65, 95% CI 0.51-0.80, validation set: AUC 0.68, 95% CI 0.56-0.80). Importantly, the addition of the three-miRNA signature improved the performance of the clinical model including clinicopathological variables only (AUC 0.70, 95% CI 0.61-0.78 vs. 0.76, 95% CI 0.68-0.84). Overall, we trained, tested and validated a three-miRNA signature which, combined with selected clinicopathological variables, may represent a promising biomarker to improve on currently available clinicopathological risk stratification tools for a better selection of truly indolent PCa patients suitable for AS.

Supporting Patients With Untreated Prostate Cancer on Active Surveillance: What Causes an Increase in Anxiety During the First 10 Months?

BACKGROUND: The psychological burden possibly deriving from not immediately undergoing radical treatment for prostate cancer (PCa) could be a potential disadvantage of active surveillance (AS), especially in the eve of some relevant clinical exams [i.e., re-biopsy, prostate-specific antigen (PSA) test, and medical examination]. Even if it is known from the literature that the majority of PCa men in AS do not report heightened anxiety, there is a minority of patients who show clinically significant levels of anxiety after diagnosis. The present study aimed to investigate if demographic, clinical, and psychological variables at the entrance in AS (T0) were associated with the risk of developing clinically significant PCa-related anxiety 2 months before the first re-biopsy (T1) and to offer psychological support to improve quality of life (QoL). MATERIALS AND METHODS: A total of 236 patients participated in the PCa Research International: AS (PRIAS) protocol and in PRIAS-QoL study. Demographic/clinical features, health-related QoL domains, coping with cancer, PCa-related anxiety [Memorial Anxiety Scale for PCa (MAX-PC)], personality traits, and decision-making-related factors were assessed at T0. MAX-PC was also administered at T1. PCa-related anxiety at T1 was considered to be of clinical significance if the MAX-PC score was ≥1.5. Multivariable logistic regression coupled to bootstrap was used to detect factors associated with high levels of anxiety. RESULTS: The median age was 64.4 years. Fifty-six patients (24%) reported MAX-PC total score above the cutoff. Three factors were associated with a high level of PCa anxiety at T1: anxious preoccupation [odds ratio (OR) = 4.36], extraversion (OR = 1.9), and prostate-related symptoms (median OR = 0.46). Physical well-being was associated with a low PCa anxiety subscale (median OR = 0.15); neuroticism and functional well-being were associated with PSA anxiety (median OR = 7.05 and 0.73, respectively). Neuroticism and helplessness/hopelessness were associated with fear of progression (median OR = 18.1 and 5.8, respectively). CONCLUSION: Only a partial portion of the sample experienced significant levels of anxiety after 10 months. Psychological assessment should be routinely conducted to detect risk factors (i.e., anxious preoccupation, extraversion) for increased anxiety, offering tailored psychological interventions aimed at promoting interpersonal awareness and emotional well-being.

Prevalence of endotoxemia after surgery and its association with ICU length of stay.

INTRODUCTION: The aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay. METHODS: 102 patients admitted to a university ICU after surgery were recruited. Within four hours of admission, functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity (EA)). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P < 0.05 as significant. Data are expressed as mean +/- SD. RESULTS: EA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61 +/- 17 years) and APACHE II score 8.3 +/- 3.7 (P = 0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093 +/- 4605 cells/mm3 (P = 0.385), heart rate 76 +/- 16 bpm (P = 0.898), mean arterial pressure 88.8 +/- 13.6 mmHg (P = 0.576), lactate 1.18 +/- 0.77 mmol/L (P = 0.370), PaO2/FiO2 383 +/- 109 mmHg (P = 0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9 +/- 3.0 days in the low EA group, 1.8 +/- 1.4 days in intermediate and 5.2 +/- 7.8 days in high group (P = 0.038). CONCLUSIONS: 17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.

Intraoperative hypotension is not associated with postoperative cognitive dysfunction in elderly patients undergoing general anesthesia for surgery: results of a randomized controlled pilot trial.

STUDY OBJECTIVE: To assess the effect of different intraoperative blood pressure targets on the development of POCD and test the feasibility of a larger trial. DESIGN: Randomized controlled pilot trial. SETTING: Perioperative care in a tertiary care teaching hospital with outpatient follow-up. PATIENTS: One hundred one patients aged ≥75 years with ASA physical status <4, undergoing elective, non-cardiac surgery under general anesthesia and 33 age-matched healthy controls. INTERVENTIONS: Randomization to a personalized intraoperative blood pressure target, mean arterial pressure (MAP) ≥ 90% of preoperative values (Target group), or to a more liberal intraoperative blood pressure management (No-Target group). Strategies to reach intraoperative blood pressure target were at discretion of anesthesiologists. MEASUREMENTS: An experienced neuropsychologist performed a validated battery of neurocognitive tests preoperatively and 3 months after surgery. Incidence of POCD at three months and postoperative delirium were assessed. Intraoperative time spent with MAP ≥ 90% of preoperative values, recruitment and drop-out rate at 3 months were feasibility outcomes. MAIN RESULTS: The Target group spent a higher percentage of intraoperative time with MAP ≥90% of preoperative values (65 ±â€¯25% vs. 49 ±â€¯28%, p < 0.01). Incidence of POCD (11% vs. 7%, relative risk 1.52; 95% CI, 0.41 to 6.3; p = 0.56) and delirium (6% vs. 14%, relative risk, 0.44; 95% CI, 0.12 to 1.60; p = 0.21) did not differ between groups. No correlation was found between intraoperative hypotension and postoperative cognitive performance (p = 0.75) or delirium (p = 0.19). Recruitment rate was of 6 patients/month (95% confidential interval (CI), 5 to 7) and drop-out rate at 3 months was 24% (95% CI, 14 to 33%). CONCLUSIONS: Intraoperative hypotension did not correlate with postoperative cognitive dysfunction or delirium occurrence in elderly patients undergoing general anesthesia for non-cardiac surgery. A multicenter randomized controlled trial is needed in order to confirm the effect of intraoperative blood pressure on the development of POCD. TRIAL REGISTRATION NUMBER: NCT02428062www.clinicaltrials.gov.

Core Biopsies from Prostate Cancer Patients in Active Surveillance Protocols Harbor PTEN and MYC Alterations.

BACKGROUND: Genomic characterization of prostate cancer (PCa) biopsies may improve criteria for the selection of patients suitable for active surveillance (AS). OBJECTIVE: To identify somatic genomic aberrations associated with adverse outcome as AS protocol exclusion indicators. DESIGN, SETTING AND PARTICIPANTS: Whole-exome sequencing profiles were generated for Gleason score (GS)=3+3 biopsies obtained from 54 PCa patients enrolled in two AS protocols. Patients were selected as representative of a nonindolent population, consisting of 27 patients who dropped out from AS due to upgrading (ie, finding of GS>3+3 at a follow-up biopsy) within 2 yr, and a potentially indolent population, consisting of 27 patients in AS for ≥4 yr without any evidence of reclassification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape of core biopsies was analyzed using an integrated computational pipeline and correlated with patient reclassification due to upgrading. RESULTS AND LIMITATIONS: Of all the GS=3+3 biopsies of the study cohort, 34% showed clear evidence of somatic copy number aberrations along the genome. Of these, 39% came from the potentially indolent and 61% from the nonindolent population. Single-nucleotide variants demonstrated low allelic fractions and included a common F133C mutation in the SPOP gene. The minimally altered genomic landscape of the study cohort presented a distinct set of monoallelic deletions, including on 8p, 13q, 16q, and 21q, and rare amplifications of 8q, which were observed in both AS patient populations. Concerning lesions typically associated with adverse outcome, PTEN deletions and MYC amplification, though observed in a small number of cases, were detected exclusively or preferentially, respectively, in nonindolent patients. Such molecular findings were confirmed by immunohistochemistry on the same tissue blocks. The small sample size and the retrospective nature of the analysis represent the main study limitations. CONCLUSIONS: Genomic features enriched in aggressive tumors can be detected in GS=3+3 core biopsies of AS patients. PATIENT SUMMARY: PTEN and MYC alterations at the time of diagnosis would deserve investigation in larger cohorts of AS patients to assess their potential as biomarkers for a more precise/earlier identification of patients at risk of reclassification.

Participation in clinical trials as viewed by the patient: understanding cultural and emotional aspects which influence choice.

BACKGROUND: Patients invited to take part in a clinical trial may evoke an archetype on which they may base their decision of adherence to participation, instead of on the study itself. METHODS: A 17-item, multiple choice questionnaire was developed, tested and then administered to 102 Italian-speaking patients with advanced lung or breast cancers who had never been exposed to participation in a trial. RESULTS: The questionnaire was answered by all patients. Eighty-five percent were positive about trial participation. Demographic factors did not influence patients' willingness to participate. Trust in the investigator (76%) or in the institute (64%) and hope of receiving a new chance for cure (78%) were cited as reasons to accept participation. A minority was concerned by potential conflicts of interest (31%) or the thought of being 'guinea pigs' (36%), and feared that doctors were interested in advancing their own research, even though there were more efficient drugs available (28%). Fifty percent feared receiving a little-known medicine, and 76% considered that a thorough explanation of toxicity/safety of the proposed treatment helped them decide. CONCLUSION: Several prejudices, fears and some hopes have been captured by the questionnaire. Understanding such specifics will improve patient information leading patients to a more conscious motivation in deciding whether to participate in a clinical trial.

Italian cultural adaptation of the Memorial Anxiety for Prostate Cancer scale for the population of men on active surveillance.

PURPOSE: The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) is a self-report questionnaire that was developed in English to assess prostate cancer (PCa)-related anxiety. The aim of this study was to perform a cultural adaptation for the tool to be used in a population of Italian men on active surveillance (AS). METHODS: A total of 222 patients with localized PCa who were recruited for the Prostate Cancer Research International: Active Surveillance (PRIAS) protocol completed the MAX-PC. Psychometric analysis was performed to assess reliability indexes. A Spearman rank correlation was used to test the association between MAX-PC scales and other questionnaires and was used for longitudinal analysis. RESULTS: Cronbach coefficients and item to total correlation demonstrated good internal consistency. Some items related to the repetition of the PSA test showed a large floor effect and thus were poorly effective in measuring anxiety for PSA testing in patients on AS. Confirmatory factor analysis partly failed to reproduce the structure of the original version. A modified version of MAX-PC, excluding the items with a large floor effect, was thus considered for AS patients. Factor analysis on this version demonstrated considerable consistency with the presence of 3 subscales: anxiety related to PCa, anxiety related to PSA testing, and anxiety related to the fear of tumor progression. Longitudinal analysis showed an acceptable validity over time. The MAX-PC was correlated with the anxious preoccupation subscale of the Mini-Mental Adjustment to Cancer scale. CONCLUSIONS: A slightly modified version of the MAX-PC was developed for use in Italian men on AS. This instrument appears to be a valid and reliable tool that measures anxiety in men with PCa who are enrolled in AS programs.

Bedside selection of positive end-expiratory pressure by electrical impedance tomography in hypoxemic patients: a feasibility study.

BACKGROUND: Positive end-expiratory pressure (PEEP) is a key element of mechanical ventilation. It should optimize recruitment, without causing excessive overdistension, but controversy exists on the best method to set it. The purpose of the study was to test the feasibility of setting PEEP with electrical impedance tomography in order to prevent lung de-recruitment following a recruitment maneuver. We enrolled 16 patients undergoing mechanical ventilation with PaO2/FiO2 <300 mmHg. In all patients, under constant tidal volume (6-8 ml/kg) PEEP was set based on the PEEP/FiO2 table proposed by the ARDS network (PEEPARDSnet). We performed a recruitment maneuver and monitored the end-expiratory lung impedance (EELI) over 10 min. If the EELI signal decreased during this period, the recruitment maneuver was repeated and PEEP increased by 2 cmH2O. This procedure was repeated until the EELI maintained a stability over time (PEEPEIT). RESULTS: The procedure was feasible in 87% patients. PEEPEIT was higher than PEEPARDSnet (13 ± 3 vs. 9 ± 2 cmH2O, p < 0.001). PaO2/FiO2 improved during PEEPEIT and driving pressure decreased. Recruited volume correlated with the decrease in driving pressure but not with oxygenation improvement. Finally, regional alveolar hyperdistention and collapse was reduced in dependent lung layers and increased in non-dependent lung layers. CONCLUSIONS: In hypoxemic patients, a PEEP selection strategy aimed at stabilizing alveolar recruitment guided by EIT at the bedside was feasible and safe. This strategy led, in comparison with the ARDSnet table, to higher PEEP, improved oxygenation and reduced driving pressure, allowing to estimate the relative weight of overdistension and recruitment.

Eleven-year management of prostate cancer patients on active surveillance: what have we learned?

PURPOSE: To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification. METHODS: In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0.2 ng/mL/cm3 (PRIAS). Switching to active treatment was advised for a worsening of GPS, increased positive cores, or PSA doubling time <3 years. Active treatment-free survival (ATFS) was assessed using the Kaplan-Meier method. Factors associated with ATFS were evaluated with a multivariate Cox proportional hazards model. RESULTS: A total of 818 patients were included: 200 in SAINT, 530 in PRIAS, and 88 in personalized AS monitoring. Active treatment-free survival was 50% after a median follow-up of 60 months. A total of 404/818 patients (49.4%) discontinued AS: 274 for biopsy-related reclassification, 121/404 (30%) for off-protocol reasons, 9/404 (2.2%) because of anxiety. Biopsy reclassification was associated with PSA density (hazard ratio [HR] 1.8), maximum percentage of core involvement (HR 1.5), positive cores at diagnostic biopsy (HR 1.6), older age (HR 1.5), and prostate volume (HR 0.6) (all p<0.01). Patients from SAINT were significantly more likely to discontinue AS than were the patients from PRIAS (HR 1.65, p<0.0001). CONCLUSIONS: Five years after diagnosis, 50% of patients with early PCa were spared from active treatment. Wide inclusion criteria are associated with lower ATFS. However, at preliminary analysis, this does not seem to affect the probability of unfavorable pathology.

Real-time urinary electrolyte monitoring after furosemide administration in surgical ICU patients with normal renal function.

BACKGROUND: Although the loop-diuretic furosemide is widely employed in critically ill patients with known long-term effects on plasma electrolytes, accurate data describing its acute effects on renal electrolyte handling and the generation of plasma electrolyte alterations are lacking. We hypothesized that the long-term effects of furosemide on plasma electrolytes and acid-base depend on its immediate effects on electrolyte excretion rate and patient clinical baseline characteristics. By monitoring urinary electrolytes quasi-continuously, we aimed to verify this hypothesis in a cohort of surgical ICU patients with normal renal function. METHODS: We retrospectively enrolled 39 consecutive patients admitted to a postoperative ICU after major surgery, and receiving single low-dose intravenous administration of furosemide. Urinary output, pH, sodium [Na(+)], potassium [K(+)], chloride [Cl(-)] and ammonium [NH4 (+)] concentrations were measured every 10 min for three to 8 h. Urinary anion gap (AG), electrolyte excretion rate, fractional excretion (Fe) and time constant of urinary [Na(+)] variation (τNa(+)) were calculated. RESULTS: Ten minutes after furosemide administration (12 ± 5 mg), urinary [Na(+)] and [Cl(-)], and their excretion rates, increased to similar levels (P < 0.001). After the first hour, urinary [Cl(-)] decreased less rapidly than [Na(+)], leading to a reduction in urinary AG and pH and an increment in urinary [NH4 (+)] (P < 0.001). Median urinary [Cl(-)] over the first 3-h period was higher than baseline urinary and plasmatic [Cl(-)] (P < 0.001). During the first 2 h, difference between FeCl(-) and FeNa(+) increased (P < 0.05). Baseline higher values of central venous pressure and FeNa(+) were associated with greater increases in FeNa(+) after furosemide (P = 0.03 and P = 0.007), whereas higher values of mean arterial and central venous pressures were associated with a longer τNa(+) (P < 0.05). In patients receiving multiple administrations (n = 11), arterial pH, base excess and strong ion difference increased, due to a decrease in plasmatic [Cl(-)]. CONCLUSIONS: Low-dose furosemide administration immediately modifies urinary electrolyte excretion rates, likely in relation to the ongoing proximal tubular activity, unveiled by its inhibitory action on Henle's loop. Such effects, when cumulative, found the bases for the long-term alterations observed. Real-time urinary electrolyte monitoring may help in tailoring patient diuretic and hemodynamic therapies.

Lifestyle interventions to improve the quality of life of men with prostate cancer: A systematic review of randomized controlled trials.

Improving quality of life is a key issue for patients with prostate cancer (PCa). Lifestyle interventions could positively impact the quality of life of patients. However, there is no clear-cut understanding of the role of diet, exercise and risky behaviour reduction in improving the quality of life of men with PCa. The aim of this review was to systematically summarize randomized controlled trials on lifestyle in PCa patients with quality of life as main outcome. 17 trials were included. Most of them referred to exercise interventions (71%) and involved men undergoing androgen deprivation therapy (47%). Exercise studies yielded the greater amount of positive results on quality of life outcomes (67%), followed by dietary interventions (50%) and combined lifestyle interventions (33%). In particular, supervised exercise programs with resistance training sessions were the ones producing greater convincing evidence for benefits on quality of life. Further studies with high methodological quality providing adequate information to develop evidence-based, personalized lifestyle interventions that can effectively ameliorate PCa-related quality of life are needed.