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Abstract Purpose Currently, no consistent guidelines for CT scans used within PET/CT examinations are available. This systematic review provides an up-to-date overview of studies to answer the following questions: What are the specific CT protocols used in PET/CT? What are the possible purposes of requiring a CT study within a PET/CT scan? Is the CT protocol obtained from a dosimetric optimisation study? Materials and method PubMed/MEDLINE, Cochrane Library, Embase and Scopus were systematically searched for relevant studies in accordance with the PRISMA statement. The literature search was conducted from January 2007 until June 2019. Data derived from studies were standardized in order to reduce possible biases, and they were divided into clinically homogeneous subgroups (adult, child or phantom). Subsequently, we divided the CT protocol intents into 3 types (anatomic localization only, attenuation correction only and diagnostic purpose). A narrative approach was used to summarise datasets and to investigate their heterogeneity (due to medical prescription methodology) and their combination in multiseries CT protocols. When weighted computed tomography dose index (CTDIw) was available, we calculated the volumetric computed tomography dose index (CTDIvol) using the pitch value to make the results uniform. Eventually, the correlation between protocol intents and CTDIvol values was obtained using a Kruskal–Wallis one-way ANOVA statistical test. Result Starting from a total of 1440 retrieved records, twenty-four studies were eligible for inclusion in addition to two large multicentric works that we used to compare the results. We analyzed 87 CT protocols. There was a considerable range of variation in the acquisition parameters: tube current–time product revealed to have the most variable range, which was 10–300 mAs for adults and 10–80 mAs for paediatric patients. Seventy percent of datasets presented scans acquired with tube current modulation, 9% used fixed tube current and in 21% of them, this information was not available. Dependence between mean CTDIvol values and protocol intent was statistically significant (p = 0.002). As expected, in diagnostic protocols, there was a statistically significant difference between CTDIvol values of with and without contrast acquisitions (11.68 mGy vs 7.99 mGy, p = 0.009). In 13 out of 87 studies, the optimisation aim was not reported; in 2 papers, a clinical protocol was used; and in 11 works, a dose optimisation protocol was applied. Conclusions According to this review, the dose optimisation in PET/CT exams depends heavily on the correct implementation of the CT protocol. In addition to this, considering the latest technology advances (i.e. iterative algorithms development), we suggest a periodic quality control audit to stay updated on new clinical utility modalities and to achieve a shared standardisation of clinical protocols. In conclusion, this study pointed out the necessity to better identify the specific CT protocol use within PET/CT scans, taking into account the continuous development of new technologies.

This systematic review aimed to update the perceived needs of individuals with breast cancer (BC). Databases were searched for studies reporting quantitative data collected through validated assessment tools. Needs of adults with BC were reported by survivorship phase. The post-diagnosis and the post-surgery phases revealed the most needs; health system and information needs represented the greatest concern, with average Supportive Care Needs Survey-Short Form (SCNS-SF34) scores ranging from 62.0 to 75.8 post-diagnosis and from 45.0 to 67.8 post-surgery. Needs then seemed to decrease or remain stable up to within one year from diagnosis, when needs in all domains increased again; health system and information needs remained a priority. Younger age, side effects, type of treatment, and advanced stage were associated with the occurrence of unmet needs. The needs of BC survivors vary over the course of their cancer experience. This knowledge can assist the planning of appropriate assessments., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To verify the effectiveness of experimental occupational therapy plus intensive standard rehabilitation compared to intensive standard rehabilitation alone on the reintegration to social activities of complex patients three months after hospital discharge., Materials and Methods: Patients with a score ≥ 9 on the Rehabilitation Complexity Scale at admission to an intensive rehabilitation ward were randomized to the control or experimental group. Both groups received intensive multidisciplinary rehabilitation aimed at recovering independence in the basic activities of daily life (ADL). The experimental group also received experimental occupational therapy services to address goals identified through the administration of the Canadian Occupational Performance Measure (COPM). Experimental occupational therapy began during the in-hospital phase and continued in the home-based setting. It consisted of teaching strategies, recommending aids, and providing personalized information regarding available community support., Results: Ninety-two individuals with a mean age of 65 years (female 44.6%) were enrolled. The experimental group significantly improved participation measured by the Reintegration to Normal Living Index (mean changes 8.61, 95% CI: 1-16.23, p  = 0.027). The performance and satisfaction scores of the COPM, both during hospitalization and after discharge, and independence in ADL also improved. No differences in mood disturbances were found., Conclusion: Early post-discharge occupational therapy integrated with multidisciplinary rehabilitation improves the social participation of complex patients. Future research should investigate the concrete feasibility of implementing this complex intervention cost-effectively and in different contexts., Trial Registration: ClinicalTrials.gov Identifier NCT03668938 (first posted date 13/09/2018).

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Aim: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM)., Methods: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM., Findings: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms., Interpretation: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paolo Giorgi Rossi reports financial support was provided by Italian Ministry of Health. Pierpaolo Pattacini reports was provided by Emilia-Romagna Regional Health Authority. Antonio Ponti reports financial support was provided by Piedmont Region (Department of Health). Antonio Ponti reports financial support was provided by foundation Edo Tempia (a non-profit organisation). Antonio Ponti reports equipment, drugs, or supplies was provided by Regional Consortium for Informative Systems (CSI). Antonio Ponti reports financial support was provided by University of Turin. Paola Mantellini reports financial support was provided by Tuscany Region. Pierpaolo Pattacini reports equipment, drugs, or supplies and travel were provided by GE Healthcare. Antonio Ponti reports equipment, drugs, or supplies was provided by im3D S.p.A Torino. Stephen Duffy has received indirect funding in the past from Hologic Inc. Valentina Iotti, Andrea Nitrosi reports travel was provided by GE Healthcare. Pierpaolo Pattacini, Valentina Iotti, Andrea Nitrosi, Francesco Sardanelli reports a relationship with GE Healthcare that includes: speaking and lecture fees. Valentina Iotti reports a relationship with Bayer that includes: speaking and lecture fees. Paolo Giorgi Rossi, Livia Giordano, Stephen Duffy, and Francesco Sardanelli are members of the European Commission Initiative on Breast Cancer working groups. They contributed to the development of new breast cancer screening recommendations and quality assurance scheme. Livia Giordano is past president of the Gruppo Italiano Screening Mammografico, the Italian scientific society on breast cancer screening. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Mindfulness-based therapies (MBTs) addressed to patients with cancer have been widely studied in the last two decades, and their efficacy has been systematically reviewed and meta-analysed. Although findings from literature highlight benefits of MBTs on several patients' health outcomes, these should be appraised taking into consideration the characteristics of the selected studies. In this systematic review, we summarised the current evidence of the efficacy of MBTs in improving the quality of life of both patients with cancer and their relatives, with a focus on the methodological quality, type of MBT evaluated and population involved in existing randomised controlled trials (RCTs)., Methods: We searched English language articles published until February 2021. Couples of authors independently applied inclusion criteria and extracted findings. Thirty RCTs were included., Results: Nearly half of the studies were performed in English-speaking countries outside of Europe, with females diagnosed with breast cancer. Most considered heterogeneous phases of illness; one study only was performed on relatives. In most cases, different measures were employed to evaluate the same outcome. The efficacy of MBTs has been demonstrated in 25 of the 30 included articles. The methodological quality of RCTs was acceptable., Conclusion: The heterogeneity of studies' characteristics makes findings on the efficacy of MBTs poorly informative with reference to different clinical and cancer-related psychological conditions. Studies on more homogeneous samples by cancer site and phase, as well as performed in different cultural contexts, could provide a basis for better evaluating and targeting MBTs' protocols for the specific needs of patients with cancer and their relatives., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

When conscious, about 50% to 60% of hospice patients report a "visitation" by someone who is not there while they dream or are awake: a phenomenon known as End-of-Life Dreams and Visions (ELDVs). Since the dying process is frequently complicated by delirium, ELDVs risk being misidentified as such by professionals and caregivers. To observe these phenomena from patients' perspectives, we conducted a systematic review to aggregate and synthesize the findings from the qualitative studies about ELDVs of patients assisted in hospices to indicate future directions for research and care. MEDLINE/PubMed, Embase, CINAHL, PsycINFO, Scopus, and Web of Science databases were searched, yielding 293 documents after duplicates were removed. Six qualitative articles reporting on five unique studies conducted in hospice settings were included in the meta-synthesis. We generated three main categories: i) typologies of ELDVs reported, ii) emotional consequences, and iii) intersubjective meaning-making. The ELDVs reported were experiences that remained intimate and unsocialized and thus preventing participants from defining a shared sense in their relationships. Training healthcare professionals to recognize ELDVs and take advantage of them in the care relationship is desirable. We also encourage the patient's family members to listen and understand ELDVs when they occur actively. For caregivers to know how to interpret these phenomena may provide them with additional strategies for supporting, reassuring, and strengthening their relationships with their loved ones. The review allowed us to inform healthcare professionals and caregivers about how to help patients share their emotional and identity-related experiences and meaning-making in end-of-life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The COVID-19 pandemic burdened health care systems worldwide. Health services were reorganized with the dual purpose of ensuring the most adequate continuity of care and, simultaneously, the safety of patients and health professionals. The provision of care to patients within cancer care pathways (cCPs) was not touched by such reorganization. We investigated whether the quality of care provided by a local comprehensive cancer center has been maintained using cCP indicators. A retrospective single-cancer center study was conducted on eleven cCPs from 2019 to 2021 by comparing three timeliness indicators, five care indicators and three outcome indicators yearly calculated on incident cases. Comparisons of indicators between 2019 and 2020, and 2019 and 2021, were performed to assess the performance of cCP function during the pandemic. Indicators displayed heterogeneous significant changes attributed to all cCPs over the study period, affecting eight (72%), seven (63%) and ten (91%) out of eleven cCPs in the comparison between 2019 and 2020, 2020 and 2021, and 2019 and 2021, respectively. The most relevant changes were attributed to a negative increase in time-to-treatment surgery-related indicators and to a positive increase in the number of cases discussed by cCP team members. No variations were found attributed to outcome indicators. Significant changes did not account for clinical relevance once discussed by cCP managers and team members. Our experience demonstrated that the CP model constitutes an appropriate tool for providing high levels of quality care, even in the most critical health situations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cigarini, Daolio, Caviola, Pellegri, Cavuto, Guberti, Mazzini and Cerullo.)

Background: Health information concerns both individuals' engagement and the way services and professionals provide information to facilitate consumers' health decision making. Citizens' and patients' participation in the management of their own health is related to the availability of tools making health information accessible, thus promoting empowerment and making care more inclusive and fairer. A novel instrument was developed (Evaluation Tool of Health Information for Consumers-ETHIC) for assessing the formal quality of health information materials written in Italian language. This study reports ETHIC's content and face validity., Methods: A convenience sample of 11 experts and 5 potential users was involved. The former were requested to evaluate relevance and exhaustiveness, the latter both readability and understandability of ETHIC. The Content Validity Index (CVI) was calculated for ETHIC's sections and items; experts and potential users' feedback were analyzed by the authors., Results: All sections and most items were evaluated as relevant. A new item was introduced. Potential users provided the researchers with comments that partly confirmed ETHIC's clarity and understandability., Conclusions: Our findings strongly support the relevance of ETHIC's sections and items. An updated version of the instrument matching exhaustivity, readability, and understandability criteria was obtained, which will be assessed for further steps of the validation process.

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia., Methods: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival., Results: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups., Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia., Competing Interests: Conflict of interest: The authors declare no competing interests., (Copyright ©The authors 2022.)

Oral mucositis is one of the worst effects of the conditioning regimens given to patients undergoing hematopoietic stem cell transplantation. It is characterized by dry mouth, erythema, mucosal soreness, ulcers, and pain, and it may impact patient outcomes. Bovine colostrum and Aloe vera contain a wide variety of biologically active compounds that promote mucosal healing. A non-randomized phase II study was designed to assess the safety and efficacy of a combined bovine colostrum and Aloe vera oral care protocol to prevent and to treat severe oral mucositis in transplant patients. Two commercially available products were given to patients in addition to the standard protocol: Remargin Colostrum OS® mouthwash and Remargin Colostrum Gastro-Gel® taken orally. Forty-six (78.0%) patients experienced oral mucositis, 40 (67.8%) developed mild-moderate forms, and 6 (10.2%) severe ones. Comparing the study group's outcomes with those of a homogeneous historical control group, severe oral mucositis decreased significantly (10.2% vs. 28.4%; P < 0.01), as did its duration (0.5 ± 1.9 vs. 1.5 ± 3.0 days; P < 0.01). Febrile neutropenia episodes (69.5% vs. 95.1%; P < 0.01) and duration (4.0 ± 4.7 vs. 6.2 ± 4.5 days; P < 0.01) also decreased. These findings show that the experimental protocol seems effective in preventing severe forms of oral mucositis. However, a randomized controlled trial is necessary to confirm this., (© 2022. The Author(s).)

Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate-high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

Background: Oral mucositis (OM) is one of the most debilitating effects of toxicity due to hematopoietic stem cell transplantation (HSCT) conditioning regimens. The aim of this secondary analysis of the data of a phase II study designed to assess the efficacy of a novel oral care protocol containing bovine colostrum and aloe vera to prevent oral mucositis was to compare outcomes reported by patients with those collected by healthcare professionals (HCPs)., Method: Data on oral mucositis severity, duration, time of onset and related pain were collected from patients using the Oral Mucositis Daily Questionnaire (OMDQ). HCPs assessed the same outcomes using the World Health Organization oral mucositis scale and pain numerical rating scale. Quality of life was assessed with the 3-level EuroQol-5 dimensions., Results: Fifty-nine autologous/allogeneic graft patients were recruited, 46 of whom (78.0%) experienced OM. Mean onset was 9.1 (SD ± 3.5) days after conditioning initiation, mean duration was 10.4 (SD ± 4.3) days, and the average maximum pain score was 3.7 (SD ± 2.7). Self-administration of the OMDQ detected oral symptoms at least 1 day sooner compared to objective assessments (p = 0.025). Significant differences were observed between the patient-reported and the HCP-assessment data on oral mucositis severity grading distribution (p < 0.0001) and highest pain score (p < 0.0001). Quality of life score variations were correlated with changes in oral mucositis severity during patients' hospital stay., Conclusions: Further studies are necessary to improve the understanding of these findings; a randomised controlled trial is being set up at our institution., (© 2022. The Author(s).)

Purpose: To describe the physical exercise (PE) habits, lifestyle, and motivation to change toward healthier behaviors in patients newly diagnosed with prostate cancer (PCa)., Methods: A cross-sectional study was conducted in an Italian hospital setting. Men newly diagnosed with PCa were consecutively invited to participate in a structured interview that was conducted either in person or by telephone., Results: The mean age of the 40 participants was 70.5 ± 6.6 (range 50-84). Most participants (65%) reported they were physically active, but more than half of the sample did not reach the recommended PE level. However, 40% of participants would be interested in participating in an exercise program. Only 10% of participants were current smokers, but 90% drank alcohol, and 62.5% were overweight/obese. Almost all participants were not willing to change their habits., Conclusions: A high proportion of Italian men are insufficiently active when diagnosed with PCa. Moreover, even when exposed to behavioral risk factors, they are not willing to change their lifestyle. Health-care professionals who deal with men newly diagnosed with PCa should take advantage of the teachable moment and apply strategies that support patients' motivation to exercise and adherence to healthier lifestyles., Trial Registration: The study was prospectively registered in ClinicalTrial.gov NCT03982095 on June 11, 2019., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: This living and systematic review aimed to provide an updated summary of the available evidence on pain undertreatment prevalence in patients with cancer; correlations with some potential determinants and confounders were also carried out., Materials and Methods: We updated a systematic review published on 2014, including observational and experimental studies reporting the use of the pain management index (PMI) in adults with cancer and pain, from 2014 to 2020. We conducted searches in PubMed/MEDLINE, Embase, and Google Scholar. We performed univariate and multivariable regression analyses to describe the relationship between PMI and a list of potential explanatory variables., Results: Twenty new papers were identified, yielding a total sample size of 66 studies. The proportion of patients classified as undertreated according to the year of study publication shows a higher decrease from 1994 to 2013 (-13% as relative change) than the most recent years 2014-2020 (-11%). The quality of the included studies has increased over the years (from 80% to 93%). At the multivariable analysis, a statistically significant relationship was confirmed between undertreatment and the year of the publication of the study and with a low-medium economic level of the countries, where the studies were conducted., Discussion: Despite the improvement when compared to the period 1994-2000, still about 40% of the cases identified received an analgesic treatment inadequate to the intensity of pain, according to the PMI. Despite its intrinsic limitations, PMI continues to be widely used, and it could allow a continuous monitoring of pain management across a different mix of studies and patients., (© 2022 World Institute of Pain.)

Introduction: Androgen deprivation therapy (ADT) and radiotherapy (RT) increase survival in selected patients with prostate cancer. Nevertheless, the side effects of these therapies are associated with an increased risk of accidental falls and fractures and a decreased quality of life. Preliminary evidence suggests that physical exercise can be a valid strategy to reduce the side effects of ADT and RT in men with prostate cancer. Despite this knowledge, most patients with prostate cancer are insufficiently active, and there is a lack of data on the safety and adherence to the recommended dose of physical exercise. This study protocol is designed to examine the feasibility and safety of a multicomponent experimental physical exercise intervention targeting psychophysical and cognitive functions and the quality of life in this population., Methods and Analysis: This is a pilot feasibility study. Twenty-five men currently treated with ADT and RT for prostate cancer will be invited to participate in a 20-week, multicomponent physical exercise intervention, including supervised and unsupervised exercise sessions and meeting the current recommendation for exercise in cancer. The primary outcomes are physical exercise feasibility (recruitment, adherence and drop-out rates) and safety (adverse events related and unrelated to the intervention). The secondary outcomes are muscle strength, balance, fatigue, symptoms of anxiety and depression, cognitive function, quality of life, and patient satisfaction. We will also record the number of accidental falls and fractures occurring during the intervention and at 1 year of follow-up., Ethics and Dissemination: The study has received ethics approval from The Area Vasta Nord Local Ethics Committee (Province of Reggio Emilia, 23 June 2020, Number 520/2020/SPER/IRCCSRE). Recruitment began in September 2020 and will be completed in September 2021. The results will be disseminated through scientific journals and conference presentations., Trial Registration Number: NCT04500080., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surgery for non-small cell lung cancer is proven to be the most effective treatment in early stages, although concerns exist on its negative impact on patients' overall fitness., Aim: To establish whether intensive pulmonary rehabilitation, preoperative and postoperative, improves exercise capacity in patients undergoing lung resection., Design: Single center, unblinded, designed for superiority, 1:1 randomized controlled trial with two parallel arms., Setting: S. Maria Nuova Hospital of Reggio Emilia (Reggio Emilia, Italy)., Population: Patients referred from local lung cancer multidisciplinary team for lung resection., Methods: Patients were randomized to either standard of care (SC) or SC + intensive perioperative pulmonary rehabilitation (SC+PR). The primary aim was to investigate the effectiveness of pulmonary rehabilitation in improving exercise capacity six months after surgery. Additionally, we wanted to investigate the same effect shortly after surgery (at one month), as well as the overall impact of rehabilitation on lung function, postoperative complications and length of stay, quality of life, mood disturbances and pain. Sample was sized based on the primary outcome assuming a minimal clinically significant difference of 25 meters in exercise tolerance, measured with 6 minutes walking test., Results: The exercise tolerance at 6 months after surgery was significantly higher in patients undertaking PR compared to SC (+48.9 meters vs. -7.5 meters respectively, difference: +56.4 meters, 95% CI: 29.6-83.0, P<0.001) and it showed significantly lower impairment at 1 month after surgery in the intervention group (-3.0 meters vs. -30.1 meters difference: +27.1 meters, 95% CI: 3.4-50.8, P=0.025). No other significant differences between groups were found., Conclusions: Comparison between groups showed that pulmonary rehabilitation, administered pre and postoperatively, significantly improved exercise capacity at 6 months in patients undergoing lung resection; it also significantly reduced the decrease in exercise tolerance observed 1 month after surgery., Clinical Rehabilitation Impact: The PUREAIR trial highlights the importance of combined preoperative and postoperative rehabilitation in reducing physical deconditioning in lung cancer patients undergoing surgery. Comprehensive pulmonary rehabilitation improves exercise capacity at 1 and 6 months after surgery. The PUREAIR trial results increase knowledge on comprehensive rehabilitation's outcomes in the first six months after surgery.

Objective: Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged., Design: Single-institution retrospective observational study., Methods: The clinical records of 786 patients treated at the Otolaryngology Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Patients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delayed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the primary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes., Results: Rates of transient HPT in group TT were higher than those observed in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transient HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and permanent HPT for group TT (P < 0.0001 and P = 0.0002, respectively)., Conclusions: This study suggests that the risk of transient postoperative HPT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid neoplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications.

Introduction: Hospitalisation represents a significant risk factor for the decline in the general conditions of the elderly. Loss of autonomy in elderly inpatients, together with immobilisation, has been defined as 'Hospital-Acquired Disability' and affects 65% of this class of patients. Less than half of them will regain independent mobilisation. Included among the negative effects are: falls, increased percentage of admission to nursing homes, longer hospital admissions, increased mortality and morbitity. Despite these facts, elderly patients remain in bed for 83-95% of their hospital stay; they rarely walk or are mobilised. Only on an international level has this issue been analysed OBJECTIVES: To analyse active mobilisation in inpatients., Methods: Prospective analytical and descriptive study performed from December 2018 - May 2019 in the Clinical Medicine department of the AUSL of Reggio Emilia. Descriptive analysis of the data has been performed., Results: A total of 1725 patients were screened for the study. After applying the inclusion criteria, 295 patients were enrolled in the study, 9 of which were then excluded for failure to be mobilised. 66.4% of these patients were mobilized the morning during hygiene-rounds. According to the nurse, they appeared in a stable state, alert and oriented (88.1%) and used a variety of aids (from 1 to 3) (57.3%). The frequency of mobilisations were: 44.4% once a day, 31.2% twice, 24.4% three times or more., Discussion: This study highlighted that mobilisation is strictly correlated to first assistance, frequently relying on health care assistants, and is mostly applied to oriented patients who only need one assistant. Further studies are required to investigate connections between patient's features and mobilisation.

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10 -11  M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6-19.0), P = 0.038 and 13.4 (25.4-2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10 -11  M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.

Background & Aims: Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy., Methods: Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up., Results: 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P < 0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P < 0.04). The self-assessment of appetite (P = 0.0152) and the FAACT score (P = 0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P = 0.03)., Conclusions: In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications., Competing Interests: Conflict of interest Authors do not declare any conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media. Citizens could access the survey in anonymity from 4 May until 15 June 2020. A total of 1826 adults completed the survey, with a worsening of physical activity (35.1%), diet (17.6%), alcohol drinking (12.5%), and cigarette smoking (7.7%) reported. In contrast, 33.5% reported an improvement in diet, 12.6% in alcohol drinking, 5.3% in physical activity and 4.1% in cigarette smoking. Female sex, young adult age, suspension of work activity, and symptoms of psychological distress were the factors associated with a greater likelihood of change, which was frequently for the worse. Lockdown had an impact on lifestyle, with some net beneficial effects on diet and mostly negative effects on physical activity. Public health measures should be implemented to avoid long-term negative effects of the lockdown, supporting individuals more prone to change for the worse.

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination ( p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17-18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26-4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10-11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03-1.7; p = 0.03, and HR = 1.30; CI = 1.04-1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Besutti, Massaro, Bonelli, Braglia, Casali, Versari, Ligabue, Pattacini, Cavuto, Merlo, Luminari, Merli, Vaccaro and Pellegrini.)

Background: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose)., Methods: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes., Results: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10-16 years). The cumulative risk of IBTR at 5-10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5-10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis)., Conclusion: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile., Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia., Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein., Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy., Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first., Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility., Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease., Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.

Background: The assessment of physical performance is a key element in the rehabilitation of individuals with disabilities, and understanding patients' perception of their abilities is of foremost importance for the success of the whole process. The Activities Scale for Kids performance (ASKp) is one of the few reliable and responsive outcome measures that allows children and adolescents to accurately report their physical functioning in typical activities for this age. The performance version of the ASKp has recently been translated and culturally adapted to the Italian context., Methods: This cross-sectional study was implemented to describe the ASKp score distribution in a population of Italian school aged individuals., Results: A population of 209 Italian children with a mean age of 10.96 years (SD 2.92, range 5-15) participated in this study during the academic year 2017/18. The ASKp score ranged from 52.58 to 100, with a mean value of 89.07 points (SD 10.57). Scores greater than 90 were attained for 57.4% of participants, confirming the ceiling effect of this assessment tool when administered in healthy children (95% CI: 50.4-64.2%). The ASKp was able to differentiate between different levels of physical performance according to different developmental ages (P<0.001), and it confirmed the ability to distinguish between children with typical development and those with disability (P<0.001)., Conclusions: The results of this study provide the first evidence of construct validity of the Italian version of the ASKp. These results will help clinicians to interpret ASKp scores of children with musculoskeletal limitations.

Background: Patients with advanced haematological malignancies suffer from a very high symptom burden and psychological, spiritual, social and physical symptoms comparable with patients with metastatic non-haematological malignancy. Referral to palliative care services for these patients remains limited or often confined to the last days of life. We developed a palliative care intervention (PCI) integrated with standard haematological care. The aim of the study was focussed on exploring the feasibility of the intervention by patients, professionals and caregivers and on assessing its preliminary efficacy., Methods/design: This is a mixed-methods phase 2 trial. The Specialist Palliative Care Team (SPCT) will follow each patient on a monthly basis in the outpatient clinic or will provide consultations during any hospital admission. SPCT and haematologists will discuss active patient issues to assure a team approach to the patient's care. This quantitative study is a monocentric parallel-group superiority trial with balanced randomisation comparing the experimental PCI plus haematological standard care versus haematological standard care alone. The primary endpoint will calculate on adherence to the planned PCI, measured as the percentage of patients randomised to the experimental arm who attend all the planned palliative care visits in the 24 weeks after randomisation. The qualitative study follows the methodological indications of concurrent nested design and was aimed at exploring the acceptability of the PCI from the point of view of patients, caregivers and physicians., Discussion: In this trial, we will test the feasibility of an integrated palliative care approach starting when the haematologist decides to propose the last active treatment to the patient, according to his/her clinical judgement. We decided to test this criterion because it is able to intercept a wide range of patients'needs. The feasibility of this approach requires that we enrol at least 60 patients and that more than 50% of them be followed by the palliative care team for at least 24 weeks. The trial will include integrated qualitative data analysis; to give essential information on feasibility and acceptability., Trial Registration: ClinicalTrials.gov: NCT03743480 (November 16, 2018).

Purpose: Currently, no consistent guidelines for CT scans used within PET/CT examinations are available. This systematic review provides an up-to-date overview of studies to answer the following questions: What are the specific CT protocols used in PET/CT? What are the possible purposes of requiring a CT study within a PET/CT scan? Is the CT protocol obtained from a dosimetric optimisation study?, Materials and Method: PubMed/MEDLINE, Cochrane Library, Embase and Scopus were systematically searched for relevant studies in accordance with the PRISMA statement. The literature search was conducted from January 2007 until June 2019. Data derived from studies were standardized in order to reduce possible biases, and they were divided into clinically homogeneous subgroups (adult, child or phantom). Subsequently, we divided the CT protocol intents into 3 types (anatomic localization only, attenuation correction only and diagnostic purpose). A narrative approach was used to summarise datasets and to investigate their heterogeneity (due to medical prescription methodology) and their combination in multiseries CT protocols. When weighted computed tomography dose index (CTDI w ) was available, we calculated the volumetric computed tomography dose index (CTDI vol ) using the pitch value to make the results uniform. Eventually, the correlation between protocol intents and CTDI vol values was obtained using a Kruskal-Wallis one-way ANOVA statistical test., Result: Starting from a total of 1440 retrieved records, twenty-four studies were eligible for inclusion in addition to two large multicentric works that we used to compare the results. We analyzed 87 CT protocols. There was a considerable range of variation in the acquisition parameters: tube current-time product revealed to have the most variable range, which was 10-300 mAs for adults and 10-80 mAs for paediatric patients. Seventy percent of datasets presented scans acquired with tube current modulation, 9% used fixed tube current and in 21% of them, this information was not available. Dependence between mean CTDI vol values and protocol intent was statistically significant (p = 0.002). As expected, in diagnostic protocols, there was a statistically significant difference between CTDI vol values of with and without contrast acquisitions (11.68 mGy vs 7.99 mGy, p = 0.009). In 13 out of 87 studies, the optimisation aim was not reported; in 2 papers, a clinical protocol was used; and in 11 works, a dose optimisation protocol was applied., Conclusions: According to this review, the dose optimisation in PET/CT exams depends heavily on the correct implementation of the CT protocol. In addition to this, considering the latest technology advances (i.e. iterative algorithms development), we suggest a periodic quality control audit to stay updated on new clinical utility modalities and to achieve a shared standardisation of clinical protocols. In conclusion, this study pointed out the necessity to better identify the specific CT protocol use within PET/CT scans, taking into account the continuous development of new technologies.

Background: Spirituality is particularly important for patients suffering from life-threatening illness. Despite research showing the benefits of spiritual assessment and care for terminally ill patients, their spiritual needs are rarely addressed in clinical practice. This study examined the factor structure and reliability of the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) in patients with advanced cancer. It also examined the clinical meaning and reference intervals of FACIT-Sp scores in cancer patients subgroups through a literature review., Methods: A forward-backward translation procedure was adopted to develop the Italian version of the FACIT-Sp, which was administered to 150 terminally ill cancer patients. Exploratory factor analysis was used for construct validity, while Cronbach's α was used to assess the reliability of the scale., Results: This study replicates previous findings indicating that the FACIT-Sp distinguish well between features of meaning, peace, and faith. In addition, the internal consistency of the FACIT-Sp was acceptable. The literature review also showed that terminal cancer patients have the lowest scores on the Faith and Meaning subscales, whereas cancer survivors have the highest scores on Faith., Conclusions: The Italian version of the FACIT-Sp has good construct validity and acceptable reliability. Therefore, it can be used as a tool to assess spiritual well-being in Italian terminally ill cancer patients. This study provides reference intervals of FACIT-Sp scores in newly diagnosed cancer patients, cancer survivors, and terminally ill cancer patients and further highlights the clinical meaning of such detailed assessment.

Patient-centered, interprofessional occupational therapy is feasible in complex patients in the early phase of rehabilitation, and it contributes to meet needs in the domains of self-care, productivity, and leisure, promoting social role. We planned this single-center single-blind two-arm parallel individual patient randomized controlled trial, to verify the superiority of interprofessional experimental occupational therapy (EOT) compared to standard rehabilitation (SR) in producing higher levels of patients' social participation assessed by the Reintegration to Normal Living Index. EOT is a patient-centered, hospital/home-based rehabilitation intervention based on the Canadian Model of Occupational Performance and Engagement. This appropriately powered study will provide evidence regarding the effectiveness of EOT on the recovery of social participation in the critical transition of complex patients from hospital to the home setting.

Background: Despite the great advances in the concept of palliative care (PC) and its benefits, its application seems to be delayed, leaving unfulfilled the many needs of patients and family members. One way to overcome this difficulty could be to develop a new training programme by palliative care specialists to improve PC primary skills in healthcare professionals. The aim of this study was to evaluate the training's impact on trainees within a hospital setting using Kirkpatrick's and Moore's models., Methods: We adopted a mixed-method evaluation with concurrent triangulation. The evaluation followed the first three steps of Kirkpatrick's and Moore's models and included a pre- and post-training evaluation through self-administered questionnaires and focus groups. We used the McNemar statistical test., Results: The results highlighted the significant amount of knowledge acquired by the hospital professionals after training, in terms of increasing their knowledge of palliative care and in terms of the change in meaning that they attributed to phenomena related to chronicity and incurability, which they encounter daily in their professional practice. In both quantitative and qualitative research, the results, in synthesis, highlight: (i) the development of a new concept of palliative care, centred on the response to the holistic needs of people; (ii) that palliative care can also be extended to non-oncological patients in advanced illness stages (our training was directed to Geriatrics and Nephrology/Dialysis professionals); (iii) the empowerment and the increase in self-esteem that healthcare professionals gained, from learning about the logistical and structural organization of palliative care, to activate and implement PC; (iv) the need to share personal aspects of their professional life (this result emerges only in qualitative research); (v) the appreciation of cooperation and the joining of multiple competences towards a synergistic approach and enhanced outcomes., Conclusion: It is necessary to further develop rigorous research on training evaluation, at the most complex orders of the Kirkpatrick and Moore models, to measure primary PC skills in health care professionals. This will develop the effectiveness of the integration of I- and II-level palliative care competencies in hospitals and improve outcomes of patients' and families' quality of life.

Aim: The aim of this study was to analyze the economic efficiency of second-line diagnostic investigations in patients with undetermined lung nodules., Participants and Methods: A retrospective review of all surgical cases included in the DANTE trial from 2001 to 2006 for lung cancer screening was performed. Overall, 217 patients and 261 lung nodules were analyzed. The cohort was divided into patients investigated with PET and/or computed tomography (CT)-guided biopsy (PET-CTB protocol; N=100), compared with those assessed with serial low-dose CT scans (standard protocol; N=161). Outpatient's and inpatient's costs were expressed in euros and derived from the Italian National Health Service. Ineffective costs were defined as the cost of procedures that lead to avoidable surgical intervention., Results: The diagnostic accuracy of the two protocols was 91% for the standard (sensitivity 100%, specificity 91%, positive predictive value 26%, and negative predictive value 100%) and 90% for the PET-CTB protocol (sensitivity 98%, specificity 81%, positive predictive value 85%, and negative predictive value 97%). Average costs for outpatient's diagnostics were 694 and 1.462 euros, respectively, for the standard and PET-CTB protocol. Average inpatient's costs for both protocols were 12.121 euros. The two protocols showed comparable effectiveness in terms of outpatient's costs (94 and 90%, respectively; P=0.252). Inpatient's costs were effective in 36% of cases monitored according to the standard protocol compared with 85% of patients investigated with PET-CTB protocol. Ineffective costs corresponded to 64 and 15%, respectively (P<0.0001)., Conclusion: Despite a higher average cost for outpatient's diagnostics, the implementation of PET imaging with or without CT-guided needle biopsy in the workup of suspicious lung nodules results in reduced unnecessary harm and costs related to inpatient's procedures.

Purpose: Noninvasive ventilation (NIV) may facilitate withdrawal of invasive mechanical ventilation (i-MV) and shorten intensive care unit (ICU) length of stay (LOS) in hypercapnic patients, while data are lacking on hypoxemic patients. We aim to determine whether NIV after early extubation reduces the duration of i-MV and ICU LOS in patients recovering from hypoxemic acute respiratory failure., Methods: Highly selected non-hypercapnic hypoxemic patients were randomly assigned to receive NIV after early or standard extubation. Co-primary end points were duration of i-MV and ICU LOS. Secondary end points were treatment failure, severe events (hemorrhagic, septic, cardiac, renal or neurologic episodes, pneumothorax or pulmonary embolism), ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT), tracheotomy, percent of patients receiving sedation after study enrollment, hospital LOS, and ICU and hospital mortality., Results: We enrolled 130 consecutive patients, 65 treatments and 65 controls. Duration of i-MV was shorter in the treatment group than for controls [4.0 (3.0-7.0) vs. 5.5 (4.0-9.0) days, respectively, p = 0.004], while ICU LOS was not significantly different [8.0 (6.0-12.0) vs. 9.0 (6.5-12.5) days, respectively (p = 0.259)]. Incidence of VAT or VAP (9% vs. 25%, p = 0.019), rate of patients requiring infusion of sedatives after enrollment (57% vs. 85%, p = 0.001), and hospital LOS, 20 (13-32) vs. 27(18-39) days (p = 0.043) were all significantly reduced in the treatment group compared with controls. There were no significant differences in ICU and hospital mortality or in the number of treatment failures, severe events, and tracheostomies., Conclusions: In highly selected hypoxemic patients, early extubation followed by immediate NIV application reduced the days spent on invasive ventilation without affecting ICU LOS.

Purpose To compare digital mammography (DM) plus digital breast tomosynthesis (DBT) versus DM alone for breast cancer screening in the Reggio Emilia Tomosynthesis trial, a two-arm test-and-treat randomized controlled trial. Materials and Methods For this trial, eligible women (45-70 years old) who previously participated in the Reggio Emilia screening program were invited for mammography. Consenting women were randomly assigned 1:1 to undergo DBT+DM or DM (both of which involved two projections and double reading). Women were treated according to the decision at DBT+DM. Sensitivity, recall rate, and positive predictive value (PPV) at baseline were determined; the ratios of these rates for DBT+DM relative to DM alone were determined. Results From March 2014 to March 2016, 9777 women were recruited to the DM+DBT arm of the study, and 9783 women were recruited to the DM arm (mean age, 56.2 vs 56.3 years). Recall was 3.5% in both arms; detection was 4.5 per 1000 (44 of 9783) and 8.6 per 1000 (83 of 9777), respectively (+89%; 95% confidence interval [CI]: 31, 72). PPV of the recall was 13.0% and 24.1%, respectively (P = .0002); 72 of 80 cancers found in the DBT+DM arm and with complete DBT imaging were positive at least at one DBT-alone reading. The greater detection rate for DM+DBT was stronger for ductal carcinoma in situ (+180%, 95% CI: 1, 665); it was notable for small and medium invasive cancers, but not for large ones (+94 [95% CI: 6, 254]; +122 [95% CI: 18, 316]; -12 [95% CI: -68, 141]; for invasive cancers < 10 mm, 10-19 mm, and ≥ 20 mm, respectively). Conclusion DBT+DM depicts 90% more cancers in a population previously screened with DM, with similar recall rates., (© RSNA, 2018 Online supplemental material is available for this article.)

Background: Brain tumors characterization by molecular imaging that allows the depiction of brain lesions metabolic pattern is crucial. Our study aimed to: 1) to evaluate the diagnostic performances of [18F]fluoroethylcholine positron emission tomography/computed tomography ([18F]FECH PET/CT), and 2) correlate PET imaging derived parameters of [18F]FECH to survival in brain tumors., Methods: From 2009 to 2012, we enrolled 30 patients who underwent [18F]FECH PET/CT. Final diagnosis was established by clinical and radiological follow-up., Results: Final diagnosis was consistent with tumor disease in 27/30 cases. In 3/30 cases tumor disease was ruled out. [18F]FECH PET/CT resulted true positive and negative in 21/30 and 9/30 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of [18F]FECH PET/CT were 78%, 100%, 100%, 33%, and 80%, respectively. Mean and maximum standardized uptake value (SUVmean and SUVmax) resulted statistically correlated to histology (P=0.0255 and P=0.0222, respectively). Using a SUVmax cut-off of 2.0 or 3.2, we distinguished between low- and high-grade gliomas with a good specificity (70% and 80%, respectively). SUVmax and histology resulted correlated to overall survival and disease related survival at multivariate analysis., Conclusions: Our results, worthy of further investigations, show high diagnostic performances of [18F]FECH PET/CT, and a correlation between PET imaging derived parameters and survival.

Background: There is evidence that early integration of palliative care improves quality of life, lowers spending and helps clarify preferences and goals for advanced cancer patients. Little is known about the feasibility and acceptability of early integration., Aim: Assessing feasibility of early integration of palliative care, and exploring concerns perceived and problems encountered by patients, relatives and oncologists., Design: A phase 2 mixed-methods study ( ClinicalTrials.Gov :NCT02078700)., Methods: Oncologists of two outpatient clinics offered a specialised palliative care intervention integrated with standard oncological care to all consecutive newly diagnosed metastatic respiratory/gastrointestinal cancer patients. We interviewed samples of patients, relatives and oncologists to explore strengths and weaknesses of the intervention., Results: The intervention was proposed to 44/54 eligible patients (81.5%), 40 (90.1%) accepted, 38 (95.0%) attended the first palliative care visit. The intervention was completed for 32 patients (80.0%). It did not start for three (7.5%) and was interrupted for three patients who refused (7.5%). The Palliative Care Unit performed 274 visits in 38 patients (median per patient 4.5), and 24 family meetings with relatives of 16 patients. All patients and most relatives referred to the usefulness of the intervention, specifically for symptoms management, information and support to strategies for coping. Oncologists highlighted their difficulties in informing patients on palliative intervention, sharing information and coordinating patient's care with the palliative care team., Conclusion: Early integration of palliative care in oncological setting seems feasible and well accepted by patients, relatives and, to a lesser extent, oncologists. Some difficulties emerged concerning patient information and inter-professional communication.

Background: Papillary Thyroid Carcinomas (PTCs) are generally indolent tumors. However, a small but significant percentage of PTCs behaves aggressively, progressing to a diffuse metastatic spreading and leading to patient's death. The lack of reliable markers for predicting the metastatic behavior of these tumors prevents a correct risk based stratification of the disease, thus contributing to the issue of patients' overtreatment. In this study we aimed at identifying genetic features associated with the development of distant metastasis in PTCs., Results: We showed that DM PTCs are characterized by a moderate degree of copy number alterations but display low level of microsatellite instability and a low mutational burden. We identified duplication of Chr1q, duplication of Chr5p harboring the TERT genomic locus and mutations of TERT promoter as distinctive features of DM PTCs. These three genetic variables defined a signature (THYT1) that was significantly associated with a metastatic behavior and a shortened survival. We analyzed the THYT1 signature in PTCs fine needle aspirate biopsies (FNAB) and we demonstrating the applicability of this signature as a molecular marker in the pre-operative diagnostic setting of PTCs., Materials and Methods: A consecutive series of 2,937 thyroid malignancies, diagnosed at the Arcispedale S. Maria Nuova - IRCCS, Italy between 1978 and 2015 were searched to retrieve those who developed distant metastasis (DM, n = 50). We performed a deep profiling to explore the genomic landscape of these tumors., Conclusions: Overall our data identify the first genetic signature that independently predicts metastasis and negative outcome of PTCs, and lay the basis for the possible application of the THYT1 as prognostic marker to improve risk-based stratification and management of PTC patients., Competing Interests: CONFLICTS OF INTEREST No conflicts of interest exists over this manuscript. Dr. Cavuto has a consulting role with Roche SPA, Italy about topics that do not concern thyroid cancer or any aspects addressed in this paper. The other authors have nothing to declare.

Objective: The risk-benefit ratio of central neck dissection (CND) in patients affected by papillary thyroid carcinoma (PTC) without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0) is currently debated. The aim of this study was to evaluate long-term outcome of CND on locoregional recurrence, distant metastasis, survival, and postoperative complications in a large series of patients with cN0-PTC., Study Design: Observational retrospective controlled study., Methods: Clinical records of patients (n=610) surgically treated for cN0-PTC at the Otolaryngology Unit of the Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy, from January 1984 to December 2008, were retrospectively reviewed. Study population was divided into three groups according to surgical treatment: Group A, total thyroidectomy (n=205); Group B, total thyroidectomy and elective ipsilateral CND (n=281); Group C, total thyroidectomy and bilateral CND (n=124)., Results: Of a total of 610 patients, 305 (50%) were classified as low-risk, 278 (45.57%) as intermediate-risk, and 27 (4.43%) as high-risk. Response to initial therapy was excellent in 567 patients (92.95%), acceptable in 21 (3.44%), and incomplete in 22 (3.61%), with no significant differences among groups. Locoregional recurrence was detected in 32 (5.2%) out of 610 patients. Distant metastasis was found in 15 patients (2.5%). Statistical analysis showed no significant differences in the rates of locoregional recurrence (p=0.890) or distant metastasis (p=0.538) among groups. Disease-specific mortality and overall survival did not significantly differ among groups (p=0.248 and 0.223, respectively). Rate of permanent hypoparathyroidism was significantly higher in Group C patients compared to those in Groups A and B., Conclusion: CND does not confer any clear advantage in the treatment of low-risk patients, regardless of surgical procedure. Instead, bilateral CND may be effective in limiting disease relapse and/or progression in patients at higher prognostic risk. Our data indicate that elective CND does not confer any clear advantage in terms of locoregional recurrence and long-term survival, as demonstrated by outcomes of the study Groups, regardless of their different prognostic risk. Elective CND allows a more accurate pathologic staging of central neck lymph nodes, despite its increasing the risk of permanent hypoparathyroidism. Intraoperative pathologic staging is a valuable tool to assess the risk of controlateral lymph node metastasis in the central neck compartment and to limit more aggressive surgery only to cases, otherwise understaged, with lymph node metastasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life., Methods: We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test., Discussion: Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice., Trial Registration: ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].