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Background Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of “indirect” and “direct” cardiac and pulmonary lung ultrasound signs. Methods LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged > 65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns—each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5. Conclusions Lung ultrasound (LU), as a tool within the anesthesiologist’s armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.

Leksell Gamma Knife is a mini-invasive technique to obtain a complete destruction of cerebral lesions delivering a single high dose radiation beam. Positron Emission Tomography (PET) imaging is increasingly utilized for radiation treatment planning. Nevertheless, lesion volume delineation in PET datasets is challenging because of the low spatial resolution and high noise level of PET images. Nowadays, the biological target volume (BTV) is manually contoured on PET studies. This procedure is time expensive and operator-dependent. In this article, a fully automatic algorithm for the BTV delineation based on random walks (RW) on graphs is proposed. The results are compared with the outcomes of the original RW method, 40% thresholding method, region growing method, and fuzzy c-means clustering method. To validate the effectiveness of the proposed approach in a clinical environment, BTV segmentation on 18 patients with cerebral metastases is performed. Experimental results show that the segmentation algorithm is accurate and has real-time performance satisfying the physician requirements in a radiotherapy environment.

An algorithm for delineating complex head and neck cancers in positron emission tomography (PET) images is presented in this article. An enhanced random walk (RW) algorithm with automatic seed detection is proposed and used to make the segmentation process feasible in the event of inhomogeneous lesions with bifurcations. In addition, an adaptive probability threshold and a k-means based clustering technique have been integrated in the proposed enhanced RW algorithm. The new threshold is capable of following the intensity changes between adjacent slices along the whole cancer volume, leading to an operator-independent algorithm. Validation experiments were first conducted on phantom studies: High Dice similarity coefficients, high true positive volume fractions, and low Hausdorff distance confirm the accuracy of the proposed method. Subsequently, forty head and neck lesions were segmented in order to evaluate the clinical feasibility of the proposed approach against the most common segmentation algorithms. Experimental results show that the proposed algorithm is more accurate and robust than the most common algorithms in the literature. Finally, the proposed method also shows real-time performance, addressing the physician’s requirements in a radiotherapy environment.

The aim of this study is to combine Biological Target Volume (BTV) segmentation and Gross Target Volume (GTV) segmentation in stereotactic neurosurgery.Our goal is to enhance Clinical Target Volume (CTV) definition, including metabolic and morphologic information, for treatment planning and patient follow-up.We propose a fully automatic approach for multimodal PET and MR image segmentation. This method is based on the Random Walker (RW) and Fuzzy C-Means clustering (FCM) algorithms. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is presented, considering volume-based, overlap-based and spatial distance-based metrics. Statistics was also included to measure correlation. Finally, a five-point Likert scale was used to provide a qualitative evaluation about the clinical value of the proposed multimodal approach. Background and objectives: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation.Methods: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment, the feasibility and the clinical value of BTV integration in Gamma Knife treatment planning were considered. Therefore, a qualitative evaluation was carried out by three experienced clinicians.Results: The achieved experimental results showed that GTV and BTV segmentations are statistically correlated (Spearman's rank correlation coefficient: 0.898) but they have low similarity degree (average Dice Similarity Coefficient: 61.8714.64). Therefore, volume measurements as well as evaluation metrics values demonstrated that MRI and PET convey different but complementary imaging information. GTV and BTV could be combined to enhance treatment planning. In more than 50% of cases the CTV was strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI enhanced the CTV more accurately than BTV in 25% of cases.Conclusions: The proposed fully automatic multimodal PET/MRI segmentation method is a valid operator-independent methodology helping the clinicians to define a CTV that includes both metabolic and morphologic information. BTVMRI and GTV should be considered for a comprehensive treatment planning. Display Omitted

Purpose To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. Materials and methods MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. Results Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two ‘some concerns’ and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. Conclusions Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed., Highlights • As of June 2020 there is no high quality evidence regarding hydroxychloroquine (HCQ) as treatment or prophylaxis of COVID-19. • Treatment with HCQ may be associated with no reduction of in-hospital death compared to standard care. • High dosages, comorbidities and combinations with macrolides may increase the risk of death and cardiac adverse events. • Post-exposure prophylaxis with HCQ probably has no effect on preventing COVID-19-like symptoms. • HCQ should not be used outside high-quality RCTs in patients with COVID-19.

Aconitine intoxication by ingestion of Aconitum roots can lead to ventricular tachycardia and cardiac arrest and provides an example of the potential effect of self‐medication. Educational campaigns should be implemented to contain acute intoxications caused by herbal‐derived products.

68Ga-DOTATOC represents a useful tool in tumor contouring for radiosurgery planning. We present a case series of patients affected by meningiomas on who we performed 68Ga-DOTATOC positron emission tomography (PET)/CT pre-operatively, a subgroup of which also underwent a post-operative 68Ga-DOTATOC PET/CT to evaluate the standardized uptake value (SUV) modification after Gamma Knife ICON treatment in single or hypofractionated fractions. Twenty patients were enrolled/included in this study: ten females and ten males. The median age was 52 years (range 33–80). The median tumor diameter was 3.68 cm (range 0.12–22.26 cm), and the median pre-radiotherapy maximum SUV value was 11 (range 2.3–92). The average of the relative percentage changes between SUVs at baseline and follow up was −6%, ranging from −41% to 56%. The SUV was reduced in seven out of 12 patients (58%), stable in two out of 12 (17%), and increased in three out of 12 (25%), suggesting a biological response of the tumor to the Gamma Knife treatment in most of the cases. 68Ga-DOTATOC-PET represents a valuable tool in assessing the meningioma diagnosis for primary radiosurgery, it is also promising for follow-up assessment.

Background: Italy was the first Western country to be heavily affected by COVID-19. Healthcare workers (HCWs) were exposed to a high risk of occupational infection, partially due to insufficient personal protective equipment (PPE) supplies. This study aimed to describe the practices, availability, training, confidence in PPE use and the adverse effects due to extended PPE use, as reported by HCWs in Italy. We also aimed to provide a comparison between Italian data and those from other countries. Methods: This study was a secondary analysis of a previously published international study, the PPE-SAFE Survey, conducted in April 2020. Data were analysed from the original study database. Results: We analysed the responses from 380 healthcare workers based in Italy, out of the 2711 respondents to the international survey. Among the Italian respondents, FFP2 and FFP3 respirators or equivalent were the most used masks for routine tasks (respectively 188/380, 50%; and 163/380, 43%). The median time of wearing PPE without taking a break was 5 h [interquartile range (IQR) 4–6], with statistically significant difference from other countries [median 4 h (IQR 2–5) p Conclusion: Most of the surveyed Italian HCWs reported working at above usual capacity, long shifts with PPE without breaks and routine use in intensive care unit of aerosol protection (e.g. FFP2/FFP3), hazmat suits and face shields/visors. The correct adherence to safety procedures (e.g. donning/doffing in pairs, performing fit test) has substantial scope for improvement in the future.

Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a &beta, lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) aimed to evaluate the effectiveness of C/T combination therapy compared to C/T monotherapy for the treatment of severe infections and to describe the prevalence of microorganisms in the included studies. We retrieved literature from PubMed, EMBASE, and CENTRAL, until 26 November 2020. Eligible studies were both randomised trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was all-cause mortality, secondary outcomes were (i) clinical improvement and (ii) microbiological cure. Eight nonrandomised studies were included in the qualitative synthesis: Seven retrospective cohort studies and one case-control study. The meta-analysis of the four studies evaluating all-cause mortality (in total 148 patients: 87 patients treated with C/T alone and 61 patients treated with C/T combination therapy) showed a significant reduction of mortality in patients receiving C/T combination therapy, OR: 0.31, 95% CI: 0.10&ndash, 0.97, p = 0.045. Conversely, the meta-analysis of the studies evaluating clinical improvement and microbiological cure showed no differences in C/T combination therapy compared to C/T monotherapy. The most consistent data come from the analysis of the clinical improvement, n = 391 patients, OR: 0.97, 95% CI: 0.54&ndash, 1.74, p = 0.909. In 238 of the 391 patients included (60.8%), C/T was used for the treatment of infections caused by Pseudomonas aeruginosa.

Background The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear. Methods We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay. Results Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69–1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709–1.352) as compared to crystalloid. Conclusion Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis.

Background Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. Methods MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. Results We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. Conclusions There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.

BackgroundPositron Emission Tomography (PET) is increasingly utilized in radiomics studies for treatment evaluation purposes. Nevertheless, lesion volume identification in PET images is a critical and still challenging step in the process of radiomics, due to the low spatial resolution and high noise level of PET images. Currently, the biological target volume (BTV) is manually contoured by nuclear physicians, with a time expensive and operator-dependent procedure.This study aims to obtain BTVs from cerebral metastases in patients who underwent L-[11C]methionine (11C-MET) PET, using a fully automatic procedure and to use these BTVs to extract radiomics features to stratify between patients who respond to treatment or not. For these purposes, 31 brain metastases, for predictive evaluation, and 25 ones, for follow-up evaluation after treatment, were delineated using the proposed method. Successively, 11C-MET PET studies and related volumetric segmentations were used to extract 108 features to investigate the potential application of radiomics analysis in patients with brain metastases. A novel statistical system has been implemented for feature reduction and selection, while discriminant analysis was used as a method for feature classification.ResultsFor predictive evaluation, 3 features (asphericity, low-intensity run emphasis, and complexity) were able to discriminate between responder and non-responder patients, after feature reduction and selection. Best performance in patient discrimination was obtained using the combination of the three selected features (sensitivity 81.23%, specificity 73.97%, and accuracy 78.27%) compared to the use of all features. Secondly, for follow-up evaluation, 8 features (SUVmean, SULpeak, SUVmin, SULpeakprod-surface-area, SUVmeanprod-sphericity, surface mean SUV 3, SULpeakprod-sphericity, and second angular moment) were selected with optimal performance in discriminant analysis classification (sensitivity 86.28%, specificity 87.75%, and accuracy 86.57%) outperforming the use of all features.ConclusionsThe proposed system is able i) to extract 108 features for each automatically segmented lesion and ii) to select a sub-panel of 11C-MET PET features (3 and 8 in the case of predictive and follow-up evaluation), with valuable association with patient outcome. We believe that our model can be useful to improve treatment response and prognosis evaluation, potentially allowing the personalization of cancer treatment plans.

Prone positioning is feasible in pregnancy and may have contributed to the positive outcome in this case. Doctors should not be reluctant to move a patient to a prone position just because they are pregnant.

Background The efficacy and safety of high flow nasal therapy (HFNT) in patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to evaluate the short-term effect of HFNT versus NIV in patients with mild-to-moderate AECOPD, with the hypothesis that HFNT is non-inferior to NIV on CO2 clearance after 2 h of treatment. Methods We performed a multicenter, non-inferiority randomized trial comparing HFNT and noninvasive ventilation (NIV) in nine centers in Italy. Patients were eligible if presented with mild-to-moderate AECOPD (arterial pH 7.25–7.35, PaCO2 ≥ 55 mmHg before ventilator support). Primary endpoint was the mean difference of PaCO2 from baseline to 2 h (non-inferiority margin 10 mmHg) in the per-protocol analysis. Main secondary endpoints were non-inferiority of HFNT to NIV in reducing PaCO2 at 6 h in the per-protocol and intention-to-treat analysis and rate of treatment changes. Results Seventy-nine patients were analyzed (80 patients randomized). Mean differences for PaCO2 reduction from baseline to 2 h were − 6.8 mmHg (± 8.7) in the HFNT and − 9.5 mmHg (± 8.5) in the NIV group (p = 0.404). By 6 h, 32% of patients (13 out of 40) in the HFNT group switched to NIV and one to invasive ventilation. HFNT was statistically non-inferior to NIV since the 95% confidence interval (CI) upper boundary of absolute difference in mean PaCO2 reduction did not reach the non-inferiority margin of 10 mmHg (absolute difference 2.7 mmHg; 1-sided 95% CI 6.1; p = 0.0003). Both treatments had a significant effect on PaCO2 reductions over time, and trends were similar between groups. Similar results were found in both per-protocol at 6 h and intention-to-treat analysis. Conclusions HFNT was statistically non-inferior to NIV as initial ventilatory support in decreasing PaCO2 after 2 h of treatment in patients with mild-to-moderate AECOPD, considering a non-inferiority margin of 10 mmHg. However, 32% of patients receiving HFNT required NIV by 6 h. Further trials with superiority design should evaluate efficacy toward stronger patient-related outcomes and safety of HFNT in AECOPD. Trial registration: The study was prospectively registered on December 12, 2017, in ClinicalTrials.gov (NCT03370666).

Objective: Positron Emission Tomography (PET) with F-18-Fluoro-deoxy-glucose (FDG) emerged as a prognostic tool to predict treatment outcome in Hodgkin Lymphoma (HL). Moreover, a FDG-PET adapted strategy is currently assessed in clinical trial to minimize the toxic effect while maintaining the efficacy of treatment in HL. Purpose was to analyze the quantitative parameters to support the prognostic role of FDG-PET today based on the semi-quantitative Deauville 5-point Scale (D5-PS). Methods: This retrospective study included 53 patients diagnosed with advanced-stage HL between 2009 and 2014, enrolled in the PET response-adapted clinical trial HD 0607. FDG-PET was performed at baseline (PET0) and after two cycles of chemotherapy (PET2). Analysis was based on two main approaches: on the single lesion presenting the higher FDG uptake and on the five hottest lesions. Different metabolic parameters were analyzed. Patients were classified into responders and nonresponders. Optimal cut-offs were derived from Receiver Operating Characteristic (ROC) curves. Results were correlated with Progression Free Survival (PFS) using Kaplan-Meier. Results: A 71% threshold in SUVmax reduction (?SUVmax) was found to be the best cutoff quantitative parameter able to identify responders vs. non-responders, also with a multivariate analysis, joining clinical data with SUVmax. After a mean follow-up of 34.2 months (95% CI, 26.2 to 39.1), the median PFS for non-responders was 8 months vs. not reached for responders. These results were superimposable to that obtained by an independent group of reviewers using the D5-PS. Conclusion: Semi-quantitative analysis by ?SUVmax outperforms qualitative assessment by D5-PS in predicting treatment outcome in ABVD-treated advanced-stage HL.

We performed a bench (BS) and human (HS) study to test the hypothesis that estimation of tidal volume (VT) during noninvasive helmet pressure support ventilation (nHPSV) would be possible using a turbine driven ventilator (TDV) coupled with an intentional leak single-limb vented circuit. During the BS a mannequin was connected to a lung simulator (LS) and at different conditions of respiratory mechanics, positive end expiratory pressure (PEEP) levels and leaks (30, 50 and 80 L/min). All differences were within the 95% limits of agreement (LoA) in all conditions in the Bland-Altman plot. The overall bias (difference between VT measured by TDV and LS) was 35 ml (95% LoA 10 to 57 ml), 15 ml (95% LoA −40 to 70 ml), 141 ml (95% LoA 109 to 173 ml) in the normal, restrictive and obstructive conditions. The bias at different leaks flow in normal condition was 29 ml (95% LoA 19 to 38 ml). In the HS four healthy volunteers using nHPSV had a pneumotachograph (P) inserted through a mouthpiece to measure subject’s VT.The bias showed a scarce clinical relevance. In conclusions, VT estimation seems to be feasible and accurate in all conditions but the obstructive one. Additional leaks seem not to affect VT reliability.

Background Procalcitonin (PCT) is a biomarker used to assess systemic inflammation, infection, and sepsis and to optimize antimicrobial therapies. Its role in the in the differential diagnosis between candidemia and bacteremia is unclear. The aim of this systematic review was to summarize the current evidence about PCT values for differentiating candidemia from bacteremia. Methods PubMed and EMBASE were searched for studies reporting data on the diagnostic performance of serum PCT levels in intensive care unit (ICU) or non-ICU adult patients with candidemia, in comparison to patients with bacteremia. Results We included 16 studies for a total of 45.079 patients and 785 cases of candidemia. Most studies claimed to report data relating to the use of PCT values for differentiating between candidemia and bacteremia in septic patients in the intensive care unit. However, the studies identified were all retrospective, except for one secondary analysis of a prospective dataset, and clinically very heterogeneous and involved different assessment methods. Most studies did show lower PCT values in patients with candidemia compared to bacteremia. However, the evidence supporting this observation is of low quality and the difference seems insufficiently discriminative to guide therapeutic decisions. None of the studies retrieved actually studied guidance of antifungal treatment by PCT. PCT may improve diagnostic performance regarding candidemia when combined with other biomarkers of infection (e.g., beta-d-glucan) but more data is needed. Conclusions PCT should not be used as a standalone tool for the differential diagnosis between candidemia and bacteremia due to limited supporting evidence. Electronic supplementary material The online version of this article (10.1186/s13054-019-2481-y) contains supplementary material, which is available to authorized users.

Background Acute respiratory distress syndrome (ARDS) survivors are affected with long-term physical/mental impairments, with improvements limited mostly to the first year after intensive care (ICU) discharge. Furthermore, caregivers of ICU patients exhibit psychological problems after family-member recovery. We evaluated the long-term physical and mental recovery of ARDS survivors treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO), and the long-term psychological impact on their caregivers. Methods Single-center prospective evaluation of a retrospective cohort of 75 ARDS patients treated with VV-ECMO during a seven-year period (25.10.2009-11.08.2016). Primary outcomes were the 36-Item Short-Form Health-Survey (SF-36, patients only), and risks of depression, anxiety or post-traumatic stress disorder (PTSD), both for patients and their caregivers. We investigated correlations between outcomes and population characteristics. Results Of 50 ICU-survivors, seven died later and five were not contactable. Among 38 living patients, 33 participated (87%, 31 with their caregiver) with 2.7 years of median follow-up. Physical and mental SF-36 component scores were 42 (inter-quartile range, IQR:22) and 52 (IQR:18.5), respectively. The worst domains of the SF-36 were physical-role limitations (25, IQR:100) and general-health perception (56, IQR:42.5). Psychological tests highlighted high risk of depression (39-42%, patients; 39-52%, caregivers), anxiety (42%, patients; 39%, caregivers), and PTSD (47%, patients; 61%, caregivers). Patient depression or anxiety scores were correlated to age and to the outcome reported by caregivers. Conclusions At almost three-year follow-up, ARDS survivors treated with VV-ECMO showed reduced health-related quality-of-life and high risk of psychological impairment, in particular PTSD. Caregivers of this population were at high psychological risk as well.

// Alessandra Romano 1 , Nunziatina Laura Parrinello 1 , Calogero Vetro 1 , Daniele Tibullo 1 , Cesarina Giallongo 1 , Piera La Cava 1 , Annalisa Chiarenza 1 , Giovanna Motta 1 , Anastasia L. Caruso 1 , Loredana Villari 2 , Claudio Tripodo 3 , Sebastiano Cosentino 4 , Massimo Ippolito 4 , Ugo Consoli 5 , Andrea Gallamini 6 , Stefano Pileri 7 , Francesco Di Raimondo 1 1 Division of Hematology, AOU “Policlinico - Vittorio Emanuele”, University of Catania, Catania, Italy 2 Division of Pathology, AOU “Policlinico - Vittorio Emanuele”, Catania, Italy 3 Tumor Immunology Unit, Department of Health Science, University of Palermo, Palermo, Italy 4 Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy 5 Division of Hematology, ARNAS Garibaldi, Catania, Italy 6 Research, Innovation and Statistics Department. A. Lacassagne Cancer Centre, Nice, France 7 Unita di Diagnosi Emolinfopatologica, IEO, Milano, Italy Correspondence to: Alessandra Romano, email: sandrina.romano@gmail.com Francesco Di Raimondo, email: diraimon@unict.it Keywords: Arginase-1, Hodgkin lymphoma, PET-2 Received: June 30, 2016 Accepted: September 05, 2016 Published: September 14, 2016 ABSTRACT Purpose: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. Experimental design: First, N-HL function was evaluated in vitro , showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training ( N = 40) and validation ( N = 78) sets. Results: s-Arg-1 was higher in patients with advanced stage ( p = 0.045), B-symptoms ( p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2. Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012). Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% ( p = 0.0004). Conclusions: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.

Objective There is increasing burnout incidence among medical disciplines, and physicians working in emergency settings seem at higher risk. Cardiac anesthesiology is a stressful anesthesiology subspecialty dealing with high-risk patients. The authors hypothesized a high risk of burnout in cardiac anesthesiologists. Design National survey conducted on burnout. Setting Italian cardiac centers. Participants Cardiac anesthesiologists. Interventions The authors administered via email an anonymous questionnaire divided into 3 parts. The first 2 parts evaluated workload and private life. The third part consisted of the Maslach Burnout Inventory test with its 3 constituents: high emotional exhaustion, high depersonalization, and low personal accomplishment. Measurements and Main Results The authors measured the prevalence and risk of burnout through the Maslach Burnout Inventory questionnaire and analyzed factors influencing burnout. Among 670 contacts from 71 centers, 382 cardiac anesthesiologists completed the survey (57%). The authors found the following mean Maslach Burnout Inventory values: 14.5 ± 9.7 (emotional exhaustion), 9.1 ± 7.1 (depersonalization), and 33.7 ± 8.9 (personal accomplishment). A rate of 34%, 54%, and 66% of respondents scored in “high” or “moderate-high” risk of burnout (emotional exhaustion, depersonalization, and personal accomplishment, respectively). The authors found that, if offered to change subspecialty, 76% of respondents would prefer to remain in cardiac anesthesiology. This preference and parenthood were the only 2 investigated factors with a protective effect against all components of burnout. Significantly lower burnout scores were found in more experienced anesthesiologists. Conclusion A relatively high incidence of burnout was found in cardiac anesthesiologists, especially regarding high depersonalization and low personal accomplishment. Nonetheless, most of the respondents would choose to remain in cardiac anesthesiology.

Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool. Conclusions: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions. Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool. Conclusions: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions.

MR Imaging is being increasingly used in radiation treatment planning as well as for staging and assessing tumor response. Leksell Gamma Knife (R) is a device for stereotactic neuro-radiosurgery to deal with inaccessible or insufficiently treated lesions with traditional surgery or radiotherapy. The target to be treated with radiation beams is currently contoured through slice-by-slice manual segmentation on MR images. This procedure is time consuming and operator-dependent. Segmentation result repeatability may be ensured only by using automatic/semi-automatic methods with the clinicians supporting the planning phase. In this paper a semi-automatic segmentation method, based on an unsupervised Fuzzy C-Means clustering technique, is proposed. The presented approach allows for the target segmentation and its volume calculation. Segmentation tests on 5 MRI series were performed, using both area-based and distance-based metrics. The following average values have been obtained: DS = 95.10, JC = 90.82, TPF = 95.86, FNF = 2.18, MAD = 0.302, MAXD = 1.260, H = 1.636.

The aim of the present study was to evaluate the changes in cervical cancer glucose metabolism for different levels of cellular differentiation. The metabolic activity was measured by standardized uptake value (SUV), SUV normalized to lean body mass, metabolic tumor volume and total lesion glycolysis using fluorine-18 fluorodeoxyglucose positron emission tomography (PET). A correlation study of these values could be used to facilitate therapeutic choice and to improve clinical practice and outcome. This study considered 32 patients with diagnosed cervical cancers, at different International Federation of Gynecology and Obstetrics stages. Glucose metabolism was assessed by PET examination, and histological specimens were examined to determine their initial grade of differentiation. A correlation study of these values was evaluated. Histological examination showed that all cases were of squamous cell carcinoma. Regarding the differentiation of the tumor, 19 well- to moderately-differentiated tumors and 13 poorly-differentiated tumors were determined. Negative findings for correlations between metabolic parameters and initial grade of histological differentiation were found, and considering that histological grade has been shown to have no consistent prognostic value in cervical cancer treatment, PET imaging could play a significant role in cervical cancer prognosis.