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Purpose: To present the state-of-art of radiomics in the context of pancreatic neuroendocrine tumors (PanNETs), with a focus on the methodological and technical approaches used, to support the search of guidelines for optimal applications. Furthermore, an up-to-date overview of the current clinical applications of radiomics in the field of PanNETs is provided. Methods: Original articles were searched on PubMed and Science Direct with specific keywords. Evaluations of the selected studies have been focused mainly on (i) the general radiomic workflow and the assessment of radiomic features robustness/reproducibility, as well as on the major clinical applications and investigations accomplished so far with radiomics in the field of PanNETs: (ii) grade prediction, (iii) differential diagnosis from other neoplasms, (iv) assessment of tumor behavior and aggressiveness, and (v) treatment response prediction. Results: Thirty-one articles involving PanNETs radiomic-related objectives were selected. In regard to the grade differentiation task, yielded AUCs are currently in the range of 0.7–0.9. For differential diagnosis, the majority of studies are still focused on the preliminary identification of discriminative radiomic features. Limited information is known on the prediction of tumors aggressiveness and of treatment response. Conclusions: Radiomics is recently expanding in the setting of PanNETs. From the analysis of the published data, it is emerging how, prior to clinical application, further validations are necessary and methodological implementations require optimization. Nevertheless, this new discipline might have the potential in assisting the current urgent need of improving the management strategies in PanNETs patients.

BACKGROUND Migrants from Africa are vulnerable to viral infections during their journey. METHODS Migrants who arrived in western Sicily were offered early screening for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. A questionnaire was administered to evaluate risk factors, and antiviral therapy was offered to subjects with active infection. A multiple regression analysis and adjusted odds ratio were obtained to evaluate risk factors. RESULTS Overall, 2,639 of 2,751 (95.9%) migrants who arrived between 2015 and 2017 accepted screening and 1,911 (72.4%) completed the questionnaire. HBsAg was positive in 257 (9.7%) migrants, 24 (0.9%) were anti-HCV positive and 57 (2.2%) had HIV infection. The prevalence of HBV infection was higher in women (aOR 2.47,95%CI 1.90-3.20),p = 0.003) and in people who endured physical and/or sexual violence (aOR 2.24,95%CI 1.87-3.55,p

Aim To explore the potentiality of radiomics analysis, performed on 68Ga-DOTATOC and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) images, in predicting tumour aggressiveness and outcome in patients candidate to surgery for pancreatic neuroendocrine neoplasms (PanNENs). Patients and methods Retrospective study including 61 patients who underwent 68Ga-DOTATOC and 18F-FDG PET/CT before surgery for PanNEN. Semiquantitative variables [SUVmax and somatostatin receptor density (SRD) for 68Ga-DOTATOC PET; SUVmax and MTV for 18F-FDG PET] and texture features [intensity variability, size zone variability (SZV), zone percentage, entropy; homogeneity, dissimilarity and coefficient of variation (Co-V)] have been analysed to evaluate their possible role in predicting tumour characteristics. Principal component analysis (PCA) was firstly performed and then multiple regression analyses were performed by using the extracted principal components. Results Regarding 68Ga-DOTATOC PET, SZV, entropy, intensity variability and SRD were predictive for tumour dimension. Regarding 18F-FDG PET, intensity variability, SZV, homogeneity, SUVmax and MTV were predictive for tumour dimension. Four principal components were extracted from PCA: PC1 correlated with all 18F-FDG variables, while PC2, PC3 and PC4 with 68Ga-DOTATOC variables. PC1 was the only significantly predicting angioinvasion (P = 0.0222); PC4 was the only one significantly predicting lymph nodal involvement (P = 0.0151). All principal components except PC4 significantly predicted tumour dimension (P

Epidemiology; Health services; Viral hepatitis Epidemiologia; Serveis de salut; Hepatitis viral Epidemiología; Servicios de salud; Hepatitis viral Chronic hepatitis B virus (HBV) infection is a major public health threat for migrant populations in Spain and efforts to scale up testing are needed to reach the WHO elimination targets. The Hepatitis B Virus Community Screening and Vaccination in Africans (HBV-COMSAVA) study aims to use point-of-care testing and simplified diagnostic tools to identify, link to care, or vaccinate African migrants in Barcelona during the COVID-19 pandemic. From 21/11/20 to 03/07/2021, 314 study participants were offered HBV screening in a community clinic. Rapid tests for HBsAg screening were used and blood samples were collected with plasma separation cards. Patients received results and were offered: linkage to specialist care; post-test counselling; or HBV vaccination in situ. Sociodemographic and clinical history were collected and descriptive statistics were utilized. 274 patients were included and 210 (76.6%) returned to receive results. The HBsAg prevalence was 9.9% and 33.2% of people had evidence of past resolved infection. Overall, 133 required vaccination, followed by post-test counselling (n = 114), and linkage to a specialist (n = 27). Despite the COVID-19 pandemic, by employing a community-based model of care utilizing novel simplified diagnostic tools, HBV-COMSAVA demonstrated that it was possible to diagnose, link to care, and vaccinate African migrants in community-based settings. This study was carried out by ISGlobal with competitive funding through the Gilead Sciences global HBV-CARE program (IN-ES-988–5799).

We present the current clinical applications of radiomics in the context of prostate cancer (PCa) management. Several online databases for original articles using a combination of the following keywords: “(radiomic or radiomics) AND (prostate cancer or prostate tumour or prostate tumor or prostate neoplasia)” have been searched. The selected papers have been pooled as focus on (i) PCa detection, (ii) assessing the clinical significance of PCa, (iii) biochemical recurrence prediction, (iv) radiation-therapy outcome prediction and treatment efficacy monitoring, (v) metastases detection, (vi) metastases prediction, (vii) prediction of extra-prostatic extension. Seventy-six studies were included for qualitative analyses. Classifiers powered with radiomic features were able to discriminate between healthy tissue and PCa and between low- and high-risk PCa. However, before radiomics can be proposed for clinical use its methods have to be standardized, and these first encouraging results need to be robustly replicated in large and independent cohorts.

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

Purpose\ud To assess the value of 18F-Fluorodeoxyglucose (18F-FDG) PET Radiomic Features (RF) in predicting Distant Relapse Free Survival (DRFS) in patients with Locally Advanced Pancreatic Cancer (LAPC) treated with radio-chemotherapy.\ud \ud Materials & methods\ud One-hundred-ninety-eight RFs were extracted using IBSI (Image Biomarker Standardization Initiative) consistent software from pre-radiotherapy images of 176 LAPC patients treated with moderate hypo-fractionation (44.25 Gy, 2.95 Gy/fr). Tumors were segmented by applying a previously validated semi-automatic method. One-hundred-twenty-six RFs were excluded due to poor reproducibility and/or repeatability and/or inter-scanner variability. The original cohort was randomly split into a training (n = 116) and a validation (n = 60) group. Multi-variable Cox regression was applied to the training group, including only independent RFs in the model. The resulting radiomic index was tested in the validation cohort. The impact of selected clinical variables was also investigated.\ud \ud Results\ud The resulting Cox model included two first order RFs: Center of Mass Shift (COMshift) and 10th Intensity percentile (P10) (p = 0.0005, HR = 2.72, 95%CI = 1.54–4.80), showing worse outcomes for patients with lower COMshift and higher P10. Once stratified by quartile values (highest quartile vs the remaining), the index properly stratified patients according to their DRFS (p = 0.0024, log-rank test). Performances were confirmed in the validation cohort (p = 0.03, HR = 2.53, 95%CI = 0.96–6.65). The addition of clinical factors did not significantly improve the models’ performance.\ud \ud Conclusions\ud A radiomic-based index including only two robust PET-RFs predicted DRFS of LAPC patients after radio-chemotherapy. The current results could find relevant applications in the treatment personalization of LAPC. A multi-institution independent validation has been planned.

Background Containment policies and other restrictions introduced by the Spanish government in response to the COVID-19 pandemic present challenges for marginalised populations, such as people who use drugs. Harm reduction centres are often linked to social services, mental health services, and infectious disease testing, in addition to tools and services that help to reduce the harms associated with injecting drugs. This study aimed to explore the impact of the pandemic on these services in four autonomous communities in Spain. Methods This is a cross-sectional study that employed a seven-section structured survey administered electronically to 20 centres in July 2020. Data from the most heavily affected months (March–June) in 2020 were compared to data from the same period in 2019. Averages were calculated with their ranges, rates, and absolute numbers. Results All 11 responding centres reported having had to adapt or modify their services during the Spanish state of alarm (14 March–21 June 2020). One centre reported complete closure for 2 months and four reported increases in their operating hours. The average number of service users across all centres decreased by 22% in comparison to the same period in the previous year and the average needle distribution decreased by 40% in comparison to 2019. Most centres reported a decrease in infectious disease testing rates (hepatitis B and C viruses, human immunodeficiency virus, and tuberculosis) for March, April, and May in 2020 compared to the previous year. Reported deaths as a result of overdose did not increase during the state of alarm, but 2/11 (18%) centres reported an increase in overdose deaths immediately after finalisation of the state of alarm. Conclusion Overall, Spanish harm reduction centres were able to continue operating and offering services by adjusting operating hours. The number of overall service users and needles distributed fell during the Spanish state of alarm lockdown period, suggesting that fewer clients accessed harm reduction services during this time, putting them at greater risk of reusing or sharing injecting equipment, overdosing, acquiring infectious diseases with decreased access to testing or discontinuing ongoing treatment such as methadone maintenance therapy, hepatitis C treatment, or antiretroviral therapy.

ObjectiveTo investigate the predictive value of the Diverticular Inflammation and Complication Assessment (DICA) classification and to develop and validate a combined endoscopic-clinical score predicting clinical outcomes of diverticulosis, named Combined Overview on Diverticular Assessment (CODA).DesignA multicentre, prospective, international cohort study.Setting43 gastroenterology and endoscopy centres located in Europe and South America.Participants2215 patients (2198 completing the study) at the first diagnosis of diverticulosis/diverticular disease were enrolled. Patients were scored according to DICA classifications.InterventionsA 3-year follow-up was performed.Main outcome measuresTo predict the acute diverticulitis and the surgery according to DICA classification. Survival methods for censored observation were used to develop and validate a novel combined endoscopic-clinical score for predicting diverticulitis and surgery (CODA score).ResultsThe 3-year cumulative probability of diverticulitis and surgery was of 3.3% (95% CI 2.5% to 4.5%) in DICA 1, 11.6% (95% CI 9.2% to 14.5%) in DICA 2 and 22.0% (95% CI 17.2% to 28.0%) in DICA 3 (p10% and >2.5% in CODA C, respectively. The CODA score showed optimal discrimination capacity in predicting the risk of surgery in the development (c-statistic: 0.829; 95% CI 0.811 to 0.846) and validation cohort (c-statistic: 0.943; 95% CI 0.905 to 0.981).ConclusionsDICA classification has a significant role in predicting the risk of diverticulitis and surgery in patients with diverticulosis, which is significantly enhanced by the CODA score.Trial registration numberNCT02758860.

Purpose: To present the progresses of hybrid 18F-FDG PET/MR imagingin the staging/restaging setting of endometrial cancer (EC), with particular focus on performance evaluations and biomarker analyses. Methods: Original articles were searched on PubMed, EMBASE and Web of Science, until March 2021. Reports were screened to select studies using simultaneous PET/MR acquisition, discarding those using sequential protocols. Studies including heterogeneous and/or homogeneous cohorts of pelvic tumor patients were considered, while works for which the exact number of EC patients was not reported have been discarded. Evaluations of selected articles were focused on (i) performance evaluation, (ii) biomarker analysis. The quality of papers was assessed by QUADAS-2. Results: Eleven articles involving 18F-FDGPET/MRI EC-related objectives were selected. The quality of papers was generally high. Compared to other imaging techniques, PET/MRI seems to show a higher diagnostic accuracy in detecting soft tissue invasion and abdominopelvic metastases from primary EC. Among different PET- and MRI-derived biomarkers, SUV-to-ADC ratio seems to be the most informative index in differentiating EC aggressiveness. Moreover, PET/MRI provided the chance to differentiate post-therapeutic changes from local relapse, and to detect small, morphologically unsuspicious lymph node metastases in patients with recurrent EC, with better performances compared to other imaging modalities. Conclusions: Preliminary results demonstrated how 18F-FDG PET/MRI could be a valid imaging technique in patients with EC, both in staging and restaging, also considering the limited radiation exposure. From the limited availability of the existing literature, it is clear that further prospective trials on larger and homogeneous cohorts are needed.

Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

Background Infliximab and adalimumab are widely used for the treatment of Crohn's disease and ulcerative colitis. Aim To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn's disease and ulcerative colitis patients reflecting real-life clinical practice. Methods Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn's disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36-72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36-84). Results In Crohn's disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P 10 were predictors of failure in Crohn's disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P Conclusion Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.

Hepatology; Public health; Virology Hepatología; Salud pública; Virología Hepatologia; Salut pública; Virologia Introduction The hepatitis C virus (HCV) is a highly infectious and deadly disease, affecting some 58 million people worldwide. Of the 1.13 million people living in the Balearic Islands, Spain, about 1350 individuals have untreated HCV. Of these, about 1120 (83%) are estimated to be people who use drugs (PWUD), who are one of the key at-risk groups for HCV infection globally. Carrying out micro-elimination approaches focused on this population is crucial to achieve the WHO goal of eliminating HCV by 2030. Thus, the primary objective of this study is to validate a model of care that simplifies the screening and linkage to HCV care pathways for PWUD on the Balearic Islands. Methods and analysis This intervention study will be implemented across 17 sites, in 4 different settings: addiction service centres (n=12), non-governmental organisation centres (n=3), a mobile methadone unit and a prison, with an estimated 3725 participants. Together with the healthcare staff at each centre, the intervention protocols will be adapted, focusing on four phases: recruitment and testing; linkage to care; treatment for those who test positive; and monitoring of sustained virological response 12 weeks after treatment and reinfection. The primary outcomes will be the number of tested and treated individuals and the secondary outcomes will include individuals lost at each step in the cascade of care. Descriptive analysis and multivariable logistic regression of the data will be undertaken. Ethics and dissemination The Hospital Clínic Barcelona, Spain, Ethics Committee approved this study on 18 February 2021 (HCB/2020/2018). Findings will be disseminated through peer-reviewed publications, conference presentations and social media. The results of this study could provide a model for targeting PWUD for HCV testing and treatment in the rest of Spain and in other settings, helping to achieve the WHO HCV elimination goal. This project is supported by Gilead Sciences, through the competitive research call HCV STAT.

Purpose: High-grade gliomas are aggressive primitive brain tumors presenting aberrant vasculature, regional necrosis, and areas of hypoxia. Tumor hypoxia is associated withresistance to conventional treatment and worse prognosis. [18F]-fluoromisonidazole (18F-FMISO) is the most extensively investigated radiotracer for the evaluation of hypoxia. However, the use of 18F-FMISO in clinical practice has been hampered mainly due to the slow clearance of the unbound tracer from normoxic tissue and its low tumor-to-background ratio (TBR).The research community has therefore investigated other radiotracers to overcome the drawbacks of 18F-FMISO. This mini-review aims to present an update on the most relevant PET studies published in the last 15years evaluating the utility of radiotracers for hypoxia imaging other than 18F-FMISO in high-grade glioma (HGG) patients. Methods: A comprehensive computer literature search of studies was carried out in PubMed/MEDLINE database to identify the most relevant studies published in the last 15years which investigated the utility of hypoxia PET tracers other than 18F-FMISO in the assessment of tumor hypoxia in patients with HGG. Results: 18F-flouroazomycin arabinoside (18F-FAZA) has been proposed as a valid alternative to 18F-FMISO for the assessment of hypoxia, due to its improved biodistribution and enhanced tumor-to-background ratio. Also 1-(2-[18F]fluoro-1[hydroxymethyl]ethoxy)methyl-2-nitroimidazole(18F-FRP170) seems a valuable hypoxia tracer in patients with brain tumor. The value of copper-diacetyl-bis(N4-methylthiosemicarbazone)(Cu-ATSM) seems controversial. Few evidences still exist regarding the utility of 18F-2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (18F-EF5). Conclusion: Hypoxia PET imaging has the potential to provide useful information for the clinicians and to guide hypoxia tailored treatments. According to the present literature, the most promising hypoxic tracer seems to be 18F-FAZA, but well-designed and wide trials to validate hypoxia radiotracers and evaluate their clinical utility in daily practice are still lacking.

Purpose: PET with radiolabeled somatostatin receptors (SSTR) analogues, such as 68Ga-DOTATOC, is commonly used in all stages of gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Magnetic resonance Imaging (MRI) has excellent soft-tissue contrast and it is mainly applied in this oncological setting for assessing liver disease. Simultaneous PET/MRI scanners allow the combined acquisition of PET and MRI data with improved patient comfort and reduced radiation dose. The aim of the present pictorial essay is to highlight the assets and limits of fully hybrid PET/MRI in the field of GEP-NETs, presenting significant clinical cases performed in our Centre. Technique and findings: PET/MRI protocol: simultaneous PET/MRI acquisition started approximately 60min after 68Ga-DOTATOC tracer injection; MR localizer was performed to define the number of table positions (PET-FOV) for PET/MRI whole-body acquisition. A dedicated MRI protocol was performed on the abdomen, following the whole-body PET/MRI scan. Conclusion: 68Ga-DOTATOC PET/MRI combines the high sensitivity and specificity of 68Ga-DOTATOC PET tracer and MR high-quality imaging, especially for the liver. The clinical setting of GEP-NETs represents an interesting setting of application of this imaging technique, although the pros and cons should be taken into account until further methodological improvements will occur, especially for the characterization of lung findings.

Purpose: In patients with neuroendocrine neoplasm (NEN), the diagnostic role of positron-emission tomography (PET) using somatostatin receptor-targeted tracers, such as 68Ga-DOTATOC and 68Ga-DOTATATE in combination with 18F-FDG to assess glucose metabolism, is still a matter of debate. This systematic review aims to examine all published data on the role ofcombined 68Ga DOTA-peptides and 18F-FDG PET in the diagnosis and management of patients with NEN. Methods: A systematic search of studies assessing the use of dual-tracer PET in patients with NEN has been carried out on PubMed, Web of Science and Scopus databases. PRISMA guidelines have been used to screen the suitable studies. Results: Overall, 13 articles (658 patients in total) were considered for the analysis. All but three studies included patients with NEN of different primary sites of origin and different histologic grades. Seven studies included patients at initial diagnosis, whereas the remaining six considered patients at first diagnosis and at restaging after therapy. The median sensitivity of 68Ga DOTA-peptide PET (68Ga-DOTATOC, 68Ga-DOTATATE and 68Ga-DOTANOC) and 18F-FDG PET was 93% (range 82–100%) and 58% (range 37–75%), respectively. The median sensitivity of combined examinations was 94% (range 92–100%). Conclusions: There is still very limited evidence supporting the role of a routine use of combined 68Ga DOTA-peptide and 18F-FDG PETs in the diagnostic work-up of NEN.

Purpose Several factors have been identified that predict positive fluorine-18-fluoromethylcholine (18F-FCH) PET/CT result in patients with prostate cancer undergoing PET/CT for biochemical failure. Among these factors, prostate-specific antigen (PSA) is the single factor most consistently associated with the prediction of positive 18F-FCH PET/CT. In this study, we wished to confirm this finding and expand it in a large series of patients. Patients and methods We retrospectively analyzed 192 patients with prostate cancer who were recruited from the Nuclear Medicine Department of the Sant'Andrea Hospital of La Spezia, Italy, from March 2013 to March 2018 and who underwent 18F-FCH PET/CT owing to biochemical failure after radical prostatectomy. Results Median trigger PSA was 2.57 ng/ml. The overall positive detection rate of 18F-FCH PET/CT was 60.9%. The percent of positive scans was 30.5% for PSA less than 1 ng/ml, 59.4% (38/64) for PSA between 1 and 5 ng/ml, and 88.4% for PSA greater than 5 ng/ml (P

Purpose of Review Lowering the impact of forest utilisation on the forest environment is a part of the improvement in sustainable forest management. As part of forest utilisation, timber harvesting can also cause environmental implications. The main impact of forest operations is on the soil, on regeneration and on the residual stand. The aim of the present review was to identify the state of the art in forest utilisation, identifying how and how much forest operations affect forest soil, regeneration and the remaining stand. Particular attention was paid to the level of impact and potential to limit this. Recent Findings There are a large number of publications tackling forest harvesting, but most of them do not give a comprehensive framework and they mainly focus on one or very few aspects of forest damage. In order to improve general knowledge of the impact of forest operations, it was proposed that the scope of recent findings should be examined and a compilation of the available results from different regions should be presented in one paper. Summary It was found that the least impactful machine-based forest operations were harvester–forwarder technologies, while a larger scale of damage could be expected from ground-based extraction systems (skidders) and cable yarders. Animal power, if applicable, tended to be very neutral to the forest environment. A decrease in damage is possible by optimising skid trail and strip road planning, careful completion of forest operations and training for operators. The existence of legal documents controlling post-harvesting stand damage are rare and have been implemented in only two countries; there is no post-harvesting control on soil damage and natural regeneration.

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke., We are grateful for the technical assistance received from the Pre-clinical imaging Platform at Vall d’Hebron Institut de Recerca, the Servei RMN at Universitat Autònoma de Barcelona, and the Unitat de Microscopia Òptica Avançada, Facultat de Medicina at the Universitat de Barcelona. This work has been supported under the Euronanomed MAGGBRIS collaborative project by grants from the Spanish Ministry of Science and Innovation (PCIN-2017-090 grant), the Instituto de Salud Carlos III (AC17/00004 with FEDER funds), the Slovak Research and Development Agency under the Contract No.APVV-19-0324 and the Italian Ministry of Health (Ricerca Corrente year 2017 funds); by the Expression of Interest (EoI) for Collaborative Projects on Regenerative Medicine 2019 P-CMR[C]); programs 2017-SGR-1427 and 2017-SGR-765 from the Generalitat de Catalunya; RETICS-INVICTUS PLUS from ISCIII (RD16/0019/0021 with FEDER funds); the ‘Severo Ochoa’ Program for Centers of Excellence in R&D (SEV-2015-0496) and the RYC-2017- 22412 and PID2019-107989RB-I00. A.G has been supported by fellowships from ISCIII (FI17/00073 and MV18/00006), A.R by a visiting-scientist fellowship from ISCIII (BA17/00052) and Y. Z has been supported by the China Scholarship Council (CSC).

Simple Summary Pancreatic cancer (PC) has a severe prognosis and even after radical surgery, relapse rate is very high (70–80%). The impact of PET/CT in PC clinical management has been increasingly investigated in the last decades. As regards localized and potentially resectable disease, the role of PET/CT is still controversial and international guidelines do not recommend its routine use. Despite this, PET may play a role in assessing PC stage and grade and potential resectability after neoadjuvant treatment. Aim of this review is to discuss the current use for staging and disease response assessment and future developments of PET/CT in resectable PC. Abstract Pancreatic Cancer (PC) has a poor prognosis, with a 5-year survival rate of only 9%. Even after radical surgical procedures, PC patients have poor survival rates, with a high chance of relapse (70–80%). Imaging is involved in all aspects of the clinical management of PC, including detection and characterization of primary tumors and their resectability, assessment of vascular, perineural and lymphatic invasion and detection of distant metastases. The role of Positron Emission Tomography/Computed Tomography (PET/CT) in detecting PC is still controversial, with the international guidelines not recommending its routine use. However, in resectable PC, PET/CT may play a role in assessing PC stage and grade and potential resectability after neoadjuvant treatment. Quantitative image analysis (radiomics) and new PET/CT radiotracers account for future developments in metabolic imaging and may further improve the relevance of this technique in several aspects of PC. In the present review, the current state of the art and future directions of PET/CT in resectable PC are presented.

ObjectiveThis study describes the prevalence of vaccine hesitancy associated with the Catalan systematic childhood vaccination calendar and some related psychosocial determinants among paediatric primary care nurses in Barcelona (Spain).MethodsCross-sectional descriptive study. In 2017 we invited the paediatric nurses (N = 165) working in Barcelona public primary health centres with paediatric departments (N = 41) to participate. They answered a questionnaire with sociodemographic and behavioural variables: severity and perceived probability of contracting the diseases of the vaccines in the vaccination schedule; safety and protection offered by each vaccine; and beliefs, social norms, and knowledge about vaccines. Outcome variable was vaccine hesitancy, dichotomized into not hesitant (nurses who would vaccinate their own offspring), and hesitant (including those who would not vaccinate them, those who had doubts and those who would delay the administration of one or more vaccines). We performed bivariate analysis and adjusted logistic regression models.Results83% of paediatric nurses (N = 137) agreed to participate. 67.9% had the intention to vaccinate their children of all the vaccines in the systematic schedule. 32.1% of nurses experienced vaccine hesitancy, especially about the HPV (21.9%) and varicella (17.5%) vaccines. The multivariate analysis suggests associations between hesitancy and low perception of the severity of whooping cough (aOR: 3.88; 95%CI:1.32–11.4), low perception of safety of the HPV vaccine (aOR:8.5;95%CI:1.24–57.8), the belief that vaccines are administered too early (aOR:6.09;95%CI:1.98–18.8), and not having children (aOR:4.05;95%CI:1.22–13.3).ConclusionsAlthough most paediatric nurses had the intention to vaccinate their own children, almost one-third reported some kind of vaccine hesitancy, mainly related to doubts about HPV and varicella vaccines, as well as some misconceptions. These factors should be addressed to enhance nurses’ fundamental role in promoting vaccination to families.

Purpose: The aim of the present systematic review was to provide an overview on the different positron emission tomography (PET) hypoxia radiotracers in the clinical setting of lung cancer. Methods: We performed a comprehensive literature review on the role of PET hypoxia imaging in lung cancer using the electronic databases PubMed and Scopus to select English written language articles on humans from January 2007 to February 2017. The following keywords have been used: “hypoxia” or “hypoxic” and “PET” and “lung cancer”. Reviews, clinical reports, and editorial articles were excluded. Results: Originally, we considered 76 manuscripts, coming to a selection of 37 original articles. In particular, the selected original articles included the following PET radiotracer categories: nitroimidazole compounds, glucose analogue and bis(thiosemicarbazone) complexes. PET radiotracers, particularly nitroimidazole compounds, are the most suitable method to directly identify the presence of hypoxia in lung cancer. Conclusions: Based on the literature review, the definition of the role of clinical application of PET hypoxia radiotracers has been provided reporting that in vivo hypoxia imaging is needed for effective treatment selection, individual treatment planning, and treatment monitoring in oncology.

Objective: Several studies have reported about the performance of C-choline-PET/computed tomography (CT) (choline) in patients with biochemical recurrent (BCR) prostate cancer, but there is a lack of information regarding negative choline in the same clinical setting. Our aim was to retrospectively analyse negative choline in a cohort of BCR-patients with high prostate-specific antigen (PSA). Methods and results: We retrospectively analysed all choline-scans performed at two high-volume imaging centres between 2005 and 2018, selecting those of interest according to the following inclusion criteria: (1) proven prostate cancer treated either with radical prostatectomy or primary external beam radiation therapy (EBRT), (2) BCR after radical prostatectomy or EBRT, (3) PSA serum values >20 ng/mL at the time of scan and (4) scan reported as negative for active disease. Overall, among 5792 scans performed for BCR-prostate cancer, 14 matched the inclusion criteria and were classified as follows: 5/14(36%) inaccurate reports, 3/14(21%) questionable underestimation of positive findings, originally described as unclear, 6/14(43%) negatives. Choline showed a high detection rate in BCR-prostate cancer patients with PSA >20 ng/mL. Conclusions: Although negative reports can be found in this clinical setting, in our review various disease-relevant findings were identified in more than half of the cases originally reported as negative warranting a double reading in such cases to avoid false-negative reports.

Purpose: To define an imaging risk profile in a population of patients affected by Pancreatic neuroendocrine neoplasms (PanNENs) candidates to surgery, by assessing the predictive role of 68Ga-DOTATOC and 18F-FDG PET/CT and PET/MR derived parameters in risk stratification, particularly regarding histological features of aggressive behaviour. Patients and methods: Retrospective study including 83 patients (53 males, 30 females; median age: 60 years, interquartile range 52–66.5), who underwent to 68Ga-DOTATOC (PET/CT: n = 77; PET/MR: n = 6) and, 68/83 patients, also to 18F-FDG PET (PET/CT: n = 65; PET/MR: n = 3) before surgery for PanNEN between 2011 and 2019, with available histological and follow-up data. The PET scans were interpreted with both qualitative (positive vs. negative) and semiquantitative measurements as follows: maximum and mean standardized uptake value (SUVmax and SUVmean) for both 18F-FDG and 68Ga-DOTATOC scans, metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG scans and somatostatin receptor density (SRD) and total lesion somatostatin receptor density (TLSRD) for 68Ga-DOTATOC PET. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of several PET parameters in predicting tumour stage or characteristic. For each PET parameter, the optimal cut-off was derived. Logistic regression analysis was used to assess if the PET parameters, categorized with the optimal cut-off values, were able to predict significantly the corresponding tumour stage or characteristic. Results: Overall, 29 (35%) patients had G1, 49 (59%) a G2 and five (6%) had a G3 PanNEN. The median Ki-67 index was 4% (interquartile range: 1–8%). SRD and TLSRD significantly discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as well as 18F-FDG MTV and TLG. 68Ga-DOTATOC SUVmax was able to significantly predict the presence of distant metastases with a threshold of 51.27 (sensitivity and specificity of 85.7 and 68.1%, respectively). 18F-FDG MTV and TLG were predictors of angioinvasion. The cut-off threshold for MTV was 7.98 (sensitivity and specificity of 69.7 and 82.4%, respectively) (p = 0.0004) whereas the cut-off for TLG was 32.4 (sensitivity and specificity of 69.7% and 82.4%, respectively) (p = 0.0004). Conclusion: Dual tracer 68Ga-DOTATOC and 18F-FDG PET scans provide relevant information regarding tumour behaviour and aggressiveness, implementing the diagnostic preoperative work-up.

BACKGROUND To investigate the correlation between 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET data and hypoxia immunohistochemical markers in patients with high-grade glioma (HGG). PATIENTS AND METHODS Prospective study including 20 patients with brain MRI suggestive for HGG and undergoing 18F-FAZA PET/CT before treatment for hypoxia assessment. For each 18F-FAZA PET scan SUVmax, SUVmean and 18F-FAZA tumour volume (FTV) at 40, 50 and 60% threshold of SUVmax were calculated; hypoxic volume was estimated by applying different thresholds (1.2, 1.3 and 1.4) to tumour/blood ratio. Seventeen patients were analysed. The immunohistochemical analysis assessed the following parameters: hypoxia-inducible factor 1α, carbonic anhydrase IX (CA-IX), glucose transporter-1, tumour vascularity and Ki-67. RESULTS 18F-FAZA PET showed a single lesion in 15/17 patients and multiple lesions in 2/17 patients. Twelve/17 patients had grade IV glioma and 5/17 with grade III glioma. Bioptic and surgical samples have been analysed separately. In the surgical subgroup (n = 7) a positive correlation was observed between CA-IX and SUVmax (P = 0.0002), SUVmean40 (P = 0.0058), SUVmean50 (P = 0.009), SUVmean60 (P = 0.0153), FTV-40-50-60 (P = 0.0424) and hypoxic volume1.2-1.3-1.4 (P = 0.0058). In the bioptic group (n = 10) tumour vascularisation was inversely correlated with SUVmax (P = 0.0094), SUVmean40 (P = 0.0107), SUVmean50 (P = 0.0094) and SUVmean60 (P = 0.0154). CONCLUSIONS The correlation of 18F-FAZA PET parameters with CD31 and CA-IX represents a reliable method for assessing tumour hypoxia in HGG. The inverse correlation between tumour vascularisation, SUVmax and SUVmean suggest that highly vascularized tumours might present more oxygen supply than hypoxia.

Background: The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer. Methods: A proof-of-concept phase 2 study including 20 kidney cancer patients (ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient’s history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen. Results: Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7–15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study. Conclusions: 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

Background and Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Background The aim of the present study is to explore the correlation between PET and MRI parameters of primary tumour and clinicopathological features and to determine their synergic predictive role in patients with endometrial cancer candidate to surgery. Methods Retrospective study including 27 patients with endometrial cancer and preoperative 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI scan. The following parameters, calculated on the primary tumour, were used for analysis: maximum standardized uptake value (SUVmax), SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) for PET scans; mean apparent diffusion coefficient (ADCmean) and volume index for MRI scans. FIGO stage, grade, histotype, lymphovascular space invasion (LVSI) and myometrial invasion were the considered clinicopathological features. Results MRI volume index was a good predictor for deep myometrial invasion [area under the curve (AUC) = 0.85; P = 0.003] and for LVSI (AUC = 0.74; P = 0.039). A cutoff value of 9.555 for MRI volume index was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%); a cutoff of 12.165 was predictive for LVSI (sensitivity = 69.2%; specificity = 83.3%). A TLG cutoff value of 26.03 was predictive for deep myometrial invasion (sensitivity = 84.6%; specificity = 76.9%). A high-direct correlation was found with MRI volume index (rho = 0.722; P < 0.001); low-direct correlation with SUVmax (rho = 0.484; P = 0.012), SUVmean (rho = 0.47; P = 0.015) and TLG (rho = 0.482; P = 0.013) were identified. The SUVmax/ADCmean ratio showed a low-direct correlation with percentage of myometrial invasion (rho = 0.467; P = 0.016). Conclusion Volume index, TLG and SUVmax/ADCmean ratio are associated with deep myometrial invasion. As myometrial invasion is the index used to predict lymph node involvement in endometrial cancer, the synergic use of these imaging parameters may be suggested to predict lymphnodal metastases.

Purpose: The main drawback of 11C-choline PET/CT for restaging prostate cancer (PCa) patients with biochemical failure is the relatively low positive detection rate for prostate specific antigen (PSA) < 1 ng/ml. This study assessed whether 11C-choline PET/CT predicts survival in PCa patients with PSA < 1 ng/ml. Methods: This retrospective study included 210 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004 to July 31, 2007 due to biochemical failure. PCa-specific survival was estimated using Kaplan–Meier curves. Cox regression analysis was used to evaluate the association between clinicopathologic variables and PCa-specific survival. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. Results: Median follow-up after radical prostatectomy was 6.9 years (95% confidence interval, CI, 2.0–14.5 years). 11C-choline PET/CT was positive in 20.5% of patients. Median PCa-specific survival was 13.4 years (95% CI, 9.9–16.8 years) in patients with positive 11C-choline PET/CT, and it was not achieved in patients with negative 11C-choline PET/CT (log-rank, chi-square = 15.0, P < 0.001). Ten-year survival probabilities for patients with negative 11C-choline PET/CT and for patients with positive 11C-choline PET/CT were 86.0% (95% CI: 80.7%–91.3%) and 63.6% (95% CI: 54.5–72.7%). At multivariate analysis, only 11C-choline PET/CT significantly predicted PCa-specific survival (hazard ratio = 2.54, 95% CI, 1.05–6.13, P = 0.038). Patients with pathological 11C-choline uptake in the prostatic bed or in pelvic lymph nodes had longer PCa-specific survival in comparison to patients with pathological tracer uptake in the skeleton (log-rank: chi-square = 27.4, P < 0.001). Conclusion: Despite the relatively low positive detection rate for PSA < 1 ng/ml, positive 11C-choline PET/CT predicts PCa-specific survival in this low PSA range. As long as more sensitive radiotracers, such as 68Ga-PSMA-11, do not become more widely available, these results might support a broader use of radiolabeled choline in restaging PCa for PSA < 1 ng/ml.

Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis. The wall of inflamed arteries contains an abundant infiltrate of lymphocytes and macrophages and undergoes substantial remodeling, with hyperplasia of the intimal layer, luminal occlusion and potentially aneurysm formation and

Purpose: The value of FDG PET-derived parameters in predicting overall survival (OS), local relapse-free survival (LRFS) and distant relapse-free survival (DRFS) in treated patients with malignant pleural mesothelioma (MPM) was evaluated. Methods: This retrospective evaluation included 55 MPM patients treated between March 2006 and February 2015 with FDG PET/CT-guided salvage helical tomotherapy (HTT) after previous surgery plus chemotherapy. Univariate Cox regression analysis was performed to assess the impact of the following FDG PET-derived parameters: biological target volume (BTV), mean and maximum standardized uptake values (SUVmean/max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), measured using different uptake thresholds (40%, 50% and 60%). Logistic regression was then performed to identify the best FDG PET-derived parameters for selecting patients with poorer survival. Results: The median OS was 9.1months (range 0.0 – 69.6months) after the end of HTT; 54/55 patients were dead at the last follow-up. BTV and TLG40, TLG50 and TLG60 were the most significant predictors of OS (p< 0.005). The median OS was 4.8months in patients with MTV60 >5cm3 and TLG40 >334.4, compared with 13.8months and 16.1months in patients with smaller values, respectively. The median LRFS and DRFS were 6.2months (range 1.2 – 39.4months) and 6.5months (0.0 – 66.4months), respectively. TLG40, TLG50 and TLG60 were significantly correlated with LRFS (p< 0.015). Median DRFS was 6.4months in patients with MTV40 >39.6cm3 and 6.2months in patients with TLG40 >334.4, compared with 17months and 18.8months in patients with smaller values. BTV, TLG40 and MTV40 were also found to be good predictors in patients with poor OS/LRFS/DRFS (median survival times less than the median values). Conclusion: FDG PET-derived parameters effectively discriminated patients with a poor prognosis and may be helpful in the selection of MPM patients for salvage HTT.

Tree climbing techniques for arboriculture are becoming more and more popular, but like any work activity, there are risks for the operator. The PPE (personal protective equipment) and protective systems studied here include semi-static ropes and friction hitches. The work rope/friction hitch system is a combination that many operators rely on, but unlike current mechanical rope clamps and descenders, they do not have European certifications. For this reason, tensile tests were carried out using a traction bench on rope/knot systems. Two rope models and two types of knots were used to stress the systems and materials as much as possible, so as to observe the resulting ratios. A total of 36 tests were carried out in which measurements were taken, including applied load in traction, knot creep, and rope diameter changes. Several results were obtained, including a maximum load of 18.7 kN, a maximum slip of 9.6 cm and a maximum diameter variation of 3 mm. This work represents a preliminary investigation for verifying the relationship between work ropes and friction knots. Relationships among the variables were observed, differences emerged mainly as a function of the type of knot used rather than the type of rope used. The data obtained is also important for applications towards improving preventative safety measures.

Background and Aim: Although rifaximin and mesalazine seem to be effective in treating the majority of people suffering from diverticular disease (DD), some patients still experience symptoms following those treatments. The aim of this study was to assess the efficacy of budesonide MMXTM in managing symptoms and raised fecal calprotectin (FC) in patients with endoscopic diagnosis of DD and not responding to standard treatments. Methods: We performed a post-hoc analysis of the patients enrolled in the DICA prospective study. All patients were at the first diagnosis of DD, scored according to DICA classification. We assessed abdominal pain, meteorism, constipation and diarrhea (scored from 0 to 10) and FC expression at baseline and after six months. Patients were treated with budesonide MMXTM for 4 weeks (9 mg/day for 2 weeks, followed by 9 mg every other day for further 2 weeks), followed by mesalazine 2.4 grams/day for further 5 months. Results: We studied 24 patients (18 females and 6 males, median age 64, inter quartile range (IQR): 57.5- 73.5), previously treated with mesalazine and/or rifaximin (equally subdivided between DICA 2 and DICA 3). At 6-month follow-up, a significant reduction of all symptoms assessed was observed (abdominal pain and meteorism: p

Background Italian data currently available in managing ulcerative colitis (UC) and Crohn's disease (CD) patients with vedolizumab (VDZ) are coming just from secondary and tertiary centers. The present study aimed to assess the real-life efficacy and safety of VDZ to achieve remission in inflammatory bowel diseases (IBD) outpatients in primary gastroenterology centers. Methods Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), and steroid discontinuation. Results One hundred and thirty-six pts. were enrolled (91 UC and 45 CD pts). During an 18-month median follow-up, clinical remission was present in 63 (46.3%) pts.: in particular, it occurred in 48 (52.7%) patients in UC group and in 15 (33.3%) patients in CD group (p = 0.003). more in UC group. Fecal calprotectin ≥400 μg/g and presence of comorbidities were factors significantly related to the failure of remission in UC and CD, respectively. Ten (7.3%) cases of adverse events were recorded (2 required suspension of treatment). Clinical response was present in 105 (72.2%) pts.: 71 (78.0%) in UC and 34 (75.5%) in CD group. MH occurred in 47 (62.7%) UC and in 9 (50.0%) CD patients. Steroids discontinuation occurred in 92 (67.6%) pts.; 61 (67.0%) UC and 31 (68.9%) CD pts. Conclusion VDZ is effective and safe in IBD outpatients, especially in UC patients.

In the literature, there is a large evidence against the use of drains in laparoscopic cholecystectomy (LC) in elective surgery. However, evidence is lacking in the setting of acute cholecystitis (AC). The present meta-analysis was performed to assess the role of drains to reduce complications and improve recovery in LC for AC. An electronic search of the MEDLINE, Science Citation Index Expanded, SpringerLink, Scopus, and Cochrane Library database from January 1990 to July 2018 was performed to identify randomized clinical trials (RCTs) that compare prophylactic drainage with no drainage in LC for AC. Odds ratio (OR) with confidence interval (CI) for qualitative variables and mean difference (MD) with CI for continuous variables were calculated. Three RCTs were included in the meta-analysis, involving 382 patients randomized to drain (188) versus no drain (194). Morbidity was similar in both the study groups (OR 1.23; 95% CI 0.55–2.76; p = 0.61) as well as wound infection rate (OR 1.98; 95% CI 0.53–7.40; p = 0.31) and abdominal abscess rate (OR 0.62; 95% CI 0.08–4.71; p = 0.31). Abdominal pain 24 h after surgery was less severe in the no drain group (MD 0.80; 95% CI 0.46–1.14; p

Background The purpose of this study was to assess the efficacy and safety of biosimilar infliximab (IFX) CT-P13 in treating outpatients with inflammatory bowel disease (IBD) in Italian primary gastroenterology centers. Methods Consecutive IBD outpatients who completed the induction treatment were evaluated retrospectively. Clinical activity was scored according to the Mayo score for ulcerative colitis (UC) and to the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD). The primary endpoint was the achievement of clinical remission (Mayo score ≤2 in UC and HBI ≤5 in CD). Secondary endpoints were clinical response to treatment, achievement of mucosal healing, and safety. Results One hundred forty-one patients (96 UC and 45 CD) were enrolled. Previous treatment with anti-tumor necrosis factor (TNF)α had been provided to 26% of UC patients and 28.9% of CD patients. Remission was achieved in 57.3% UC patients and in 75.6% CD patients during a median (interquartile range) follow up of 24 (6-24) months. Clinical response and mucosal healing were achieved in 87.5% and 75.0% of UC patients and in 84.4% and 84.2% of CD patients, respectively. By both univariate and multivariate analysis, age >40 years, presence of comorbidities, and naivety to anti-TNFα were significantly related to remission. Only one (0.7%) adverse event was reported in the CD group. Surgery was performed in 2.1% of UC patients and 6.7% of CD patients. Switching from IFX originator to biosimilar did not influence the maintenance of the clinical remission. Conclusion This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD, in both naive patients and those switching from IFX originator.

Although rifaximin is currently advised in managing symptomatic uncomplicated diverticular disease (SUDD) of the colon, no long-term data are available. This retrospective study assessed the outcome of a large cohort of patients with SUDD, treated with rifaximin, during an 8-year follow-up. The study group (group A) included 346 patients with SUDD (median age 64 years, IQR 58–69, 62.4% females), treated with rifaximin 800 mg/d for 7 days every month. The control group (group B) included 470 patients with SUDD (median age 65 years, IQR 59–74 years, 60.8% females), taking any other treatment on demand. Two symptoms (left lower abdominal pain and bloating) were assessed by a visual analog scale (VAS), graded from 0=no symptom to 10=the most severe symptom. Daily bowel movements were also reported. Median (IQR) VAS score for pain was 6 (5–7) in group A and 6 (6–7) in group B at baseline (p=0.109); at 8-year follow-up it was 3 (3–4) and 6 (5–7), respectively (p

Purpose. Assessment of deep myometrial invasion (MI) and lymphovascular space invasion (LVSI) is of utmost importance in preoperative staging of endometrial cancer (EC). Imaging parameters derived respectively from MRI and PET have shown good predictive value. Aim of the present study is to assess the diagnostic performance of hybrid 18F-FDG PET/MRI in EC staging, with particular focus on MI and LVSI detection.Methods. Prospective monocentric study including 35 patients with biopsy-proven EC undergoing preoperative 18F-FDG PET/MRI for staging purpose. Histological examination was the reference standard. PET (SUVmax, SUVmean40, MTV40, TLG40) and MRI (volume index-VI, total tumor volume-TTV, tumor volume ratio-TVR, ADCmean, ADCmin) parameters were calculated on the primary tumor, and their role in predicting histological findings (grade, high- vs. low-risk groups, LVSI, MI, p53 hyper-expression) was assessed through a ROC analysis.Results. 18F-FDG-PET/MRI identified the primary tumor in all patients. In the LVSI detection, PET/MRI demonstrated high accuracy, specificity and negative predictive value (sensitivity=0.8571, specificity=0.9286, accuracy=0.9143, NPV=0.9630, PPV=0.7500). Assessment of MI using PET/MRI correctly staged 27 patients, showing a good positive predictive value (77.1%; sensitivity= 0.7273, specificity=0.8462, accuracy=0.7714, PPV=0.8889, NPV=0.647). VI, TTV, and TVR significantly predicted risk groups (p=0.0059, 0.0235, 0.0181, respectively). VI, TTV, TVR, MTV40 and TLG40 significantly predicted LVSI (p=0.0023, 0.0068, 0.0068, 0.0027, 0.0139, respectively). Imaging was not able to predict grading, MI nor p53 hyper-expression.Conclusion. 18F-FDG-PET/MRI has good accuracy in preoperative staging of EC; PET and MRI parameters have synergic role in preoperatively predicting LVSI, with MRI parameters being also predictive for EC risk groups.

Purpose: The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in PCa staging. Methods: Fifteen patients with biopsy-proven PCa underwent both 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI within one month. TNM classification based on image findings was performed and semi-quantitative PET and quantitative MRI parameters were collected for each scan. Finally, DICE score between regions of interest manually segmented on the primary tumor on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. Results: All imaging modalities detected the primary PCa in 15 patients, with slight differences regarding the multifocality of intra-prostatic findings. Two patients presented seminal vesicles involvement on MRI, one of these was also detected by 68Ga-PSMA, with no uptake on 68Ga-DOTA-RM2 images. Regarding extra prostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in 6, 2 and 4 patients at lymph-nodal level, respectively, and at bone level in 2, 0 and 1 patients, respectively, with 68Ga-PSMA PET detecting more lesions compared to 68Ga-DOTA-RM2 PET. The different findings detected by 68Ga-PSMA PET and 68Ga-DOTA-RM2 PET might reflect the complementary role of these radiotracers, as they detected different foci of intraprostatic disease, seminal vesicle invasion, lymph nodal and bone involvement. Conclusion: These preliminary results suggest a synergic role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and mpMRI in PCa characterization during the staging phase. (EudraCT: 2018-001034-18)

The aim of this review is to report on the value of 11C-choline PET imaging as a diagnostic procedure for metastasis-directed therapies. Furthermore, the role of 11C-choline PET/CT as a diagnostic tool for monitoring castration-resistant prostate cancer patients treated with systematic therapy is assessed. Finally, the role of 11C-choline PET/CT in the prediction of survival in both castration-resistant prostate cancer patients and hormone-naïve patients is investigated.

Aim The real prevalence of symptomatic uncomplicated diverticular disease (SUDD) is still unknown. The aim of this study was to assess the prevalence of SUDD, post-diverticulitis SUDD (PD-SUDD) and irritable bowel syndrome (IBS)-like symptoms in a real-life population. Methods A cohort of patients, submitted to colonoscopy from 1st January 2012 to 30th April 2018 was revised. Results A cohort of 5451 patients with diverticulosis was identified during the study period. Abdominal pain was recorded in 1141 patients (20.93%), diarrhea in 288 (5.28%) and constipation in 536 (9.83%) patients. SUDD was recorded in 371 patients (6.81% of the patients having diverticulosis and 32.51% of the patients experiencing abdominal pain), PD-SUDD was recorded in 103 patients (1.89% of the patients having diverticulosis and 9.03% of the patients experiencing abdominal pain) and IBS-like was recorded in 348 patients (6.38% of the patients having diverticulosis and 30.5% of the patients experiencing abdominal pain). Three hundred and nineteen patients were not part of any of the previous categories (5.85% of the patients having diverticulosis and 27.96% of the patients experiencing abdominal pain). SUDD and PD-SUDD were more frequent in older ages (>60 years), while IBS-like symptoms were more frequent in younger. Nonspecific abdominal pain was equally distributed in through the ages. Conclusion The prevalence of SUDD seems to be lower than expected, and most of patients with diverticulosis and abdominal symptoms may suffer from IBS-like or other causes.

Basic and translational research on lung biology and pathology can greatly benefit from the development of 3D in vitro models with physiological relevance. Lung organoids and lungs-on-chip allow the creation of different kinds of in vitro microenvironments, that can be useful for the elucidation of novel pathogenetic pathways, for example concerning tissue fibrosis in chronic diseases. Moreover, they represent important translational models for the identification of novel therapeutic targets, and for preliminary testing of new drugs. In this chapter, we provide a selected overview of recent studies on innovative 3D in vitro models that have enhanced our knowledge on chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), particularly concerning oxidative stress and pro-fibrotic pathogenetic mechanisms. Despite several limitations, these complex models must be considered as complementary in all respects to in vivo studies on animal models and clinical research.

ObjectivesWith the goal of facilitating the use of HIV-TRePS to optimize therapy in settings with limited healthcare resources, we aimed to develop computational models to predict treatment responses accurately in the absence of commonly used baseline data.MethodsTwelve sets of random forest models were trained using very large, global datasets to predict either the probability of virological response (classifier models) or the absolute change in viral load in response to a new regimen (absolute models) following virological failure. Two ‘standard’ models were developed with all baseline variables present and 10 others developed without HIV genotype, time on therapy, CD4 count or any combination of the above.ResultsThe standard classifier models achieved an AUC of 0.89 in cross-validation and independent testing. Models with missing variables achieved AUC values of 0.78–0.90. The standard absolute models made predictions that correlated significantly with observed changes in viral load with a mean absolute error of 0.65 log10 copies HIV RNA/mL in cross-validation and 0.69 log10 copies HIV RNA/mL in independent testing. Models with missing variables achieved values of 0.65–0.75 log10 copies HIV RNA/mL. All models identified alternative regimens that were predicted to be effective for the vast majority of cases where the new regimen prescribed in the clinic failed. All models were significantly better predictors of treatment response than genotyping with rules-based interpretation.ConclusionsThese latest models that predict treatment responses accurately, even when a number of baseline variables are not available, are a major advance with greatly enhanced potential benefit, particularly in resource-limited settings. The only obstacle to realizing this potential is the willingness of healthcare professions to use the system.

PURPOSE: Oligorecurrent prostate cancer with exclusive nodal involvement represents a common state of disease, amenable to local therapy. New radio-labeled tracers have enriched the possibility of cancer detection and treatment. In this review, we aim to illustrate the main nuclear medicine diagnostic options and the role of radiotherapy in this setting of patients.METHODS: We performed a PubMed search referring to the PRISMA guidelines to analyze the performance of PSMA- and choline-PET in detecting oligorecurrence limited to lymph nodes, and to review the main studies supporting either ablative stereotactic body radiotherapy or regional lymph node irradiation in this clinical setting.RESULTS: PSMA-PET has shown higher efficacy in the diagnosis of nodal lesions if compared with choline-PET. More specifically, for PSA ≤ 2 ng/ml, the median detection rate of choline-PET ranges from 19.5 to 44.5%, whereas PSMA ranges from 51.5 to 74%. SBRT achieves high local control rates positively affecting progression-free survival (PFS), with androgen deprivation therapy (ADT)-free survival ranging from 25 to 44 months and with low toxicity rates (0-15%). Prophylactic nodal irradiation shows 3-year PFS rates ranging from 62 to 75%, but with a potential higher risk of toxicity. However, the chosen treatment option needs to be tailored on the single patient.CONCLUSIONS: Newer PET/CT radio-labeled tracers have increased disease detection in oligorecurrent prostate cancer patients. Growing evidence of their impact on metastasis-directed therapy encourages the use of the most advanced radiotherapy techniques in the clinical management of such patients.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

Background Radiomic features are increasingly utilized to evaluate tumor heterogeneity in PET imaging but to date its role has not been investigated for Cho-PET in prostate cancer. The potential application of radiomics features analysis using a machine-learning radiomics algorithm was evaluated to select 18F-Cho PET/CT imaging features to predict disease progression in PCa. Methods We retrospectively analyzed high-risk PCa patients who underwent restaging 18F-Cho PET/CT from November 2013 to May 2018. 18F-Cho PET/CT studies and related structures containing volumetric segmentations were imported in the "CGITA" toolbox to extract imaging features from each lesion. A Machine-learning model has been adapted using NCA for feature selection, while DA was used as a method for feature classification and performance analysis. Results 106 imaging features were extracted for 46 lesions for a total of 4876 features analyzed. No significant differences between the training and validating sets in terms of age, sex, PSA values, lesion location and size (p > 0.05) were demonstrated by the machine-learning model. Thirteen features were able to discriminate FU disease status after NCA selection. Best performance in DA classification was obtained using the combination of the 13 selected features (sensitivity 74%, specificity 58% and accuracy 66%) compared to the use of all features (sensitivity 40%, specificity 52%, and accuracy 51%). Per-site performance of the 13 selected features in DA classification were as follow: T= sensitivity 63%, specificity 83%, accuracy 71%; N= sensitivity 87%, specificity 91% of and accuracy 90%; bone-M= sensitivity 33%, specificity 77% and accuracy 66%. Conclusions An artificial intelligence model demonstrated to be feasible and able to select a panel of 18F-Cho PET/CT features with valuable association with PCa patients' outcome.

In the present case, we report the first experience of a patient with high-grade glioma who underwent dual F-FAZA PET/CT imaging for intratumoral hypoxia assessment, before treatment, and for therapy monitoring in the suspicious of recurrence, as part of a clinical research protocol. In addition, despite the diagnosis of glioblastoma, the patient at 3 years from diagnosis was alive and underwent C-methionine simultaneous PET/MRI for disease monitoring after treatment, showing stability of disease. The multitracer capability of PET in assessing different and complementary metabolic features along with the use of a last-generation scanner as PET/MRI in brain oncology are here enlighten.

The presence of hypoxia is a typical feature of solid tumors and has been identified in many neoplasms, favouring the survival of malignant cells in a hostile environment and the expression of an aggressive phenotype. Malignant brain tumors have large proportions of hypoxic tissue, thus contributing to resistance to radiation and chemotherapy. Positron emission tomography (PET) is an attractive technique to gain a non-invasive assessment of tumor hypoxia within the whole tumor, with 18F-fluoromisonidazole (18F-FMISO) and 18F-flouroazomycin arabinoside (18F-FAZA) being the most promising radiotracers. In this short review, we aim to discuss the available clinical studies focused on the use of 18F-FAZA PET/computed tomography in patients affected by high-grade glioma.