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Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p

Neuromodulation influences neuronal processing, conferring neuronal circuits the flexibility to integrate sensory inputs with behavioral states and the ability to adapt to a continuously changing environment. In this original research report, we broadly discuss the basis of neuromodulation that is known to regulate intrinsic firing activity, synaptic communication, and voltage-dependent channels in the olfactory bulb. Because the olfactory system is positioned to integrate sensory inputs with information regarding the internal chemical and behavioral state of an animal, how olfactory information is modulated provides flexibility in coding and behavioral output. Herein we discuss how neuronal microcircuits control complex dynamics of the olfactory networks by homing in on a special class of local interneurons as an example. While receptors for neuromodulation and metabolic peptides are widely expressed in the olfactory circuitry, centrifugal serotonergic and cholinergic inputs modulate glomerular activity and are involved in odor investigation and odor-dependent learning. Little is known about how metabolic peptides and neuromodulators control specific neuronal subpopulations. There is a microcircuit between mitral cells and interneurons that is comprised of deep-short-axon cells in the granule cell layer. These local interneurons express pre-pro-glucagon (PPG) and regulate mitral cell activity, but it is unknown what initiates this type of regulation. Our study investigates the means by which PPG neurons could be recruited by classical neuromodulators and hormonal peptides. We found that two gut hormones, leptin and cholecystokinin, differentially modulate PPG neurons. Cholecystokinin reduces or increases spike frequency, suggesting a heterogeneous signaling pathway in different PPG neurons, while leptin does not affect PPG neuronal firing. Acetylcholine modulates PPG neurons by increasing the spike frequency and eliciting bursts of action potentials, while serotonin does not affect PPG neuron excitability. The mechanisms behind this diverse modulation are not known, however, these results clearly indicate a complex interplay of metabolic signaling molecules and neuromodulators that may fine-tune neuronal microcircuits.

Non-achalasia oesophageal motility disorders (NAOMD) represent a heterogeneous group of rare diseases, including oesophagogastric junction outflow obstruction, distal oesophageal spasm, and hypercontractile oesophagus. Despite the differing aetiological, manometric and pathophysiological characteristics, these disorders are unified by similar clinical presentation, including dysphagia and chest pain. The management of these disorders remain a challenge for the clinician. Pharmacotherapy, botulinum toxin injection, endoscopic dilation, and laparoscopic Heller myotomy have been employed, with limited efficacy in the majority of patients. Currently, there are no controlled studies in literature that suggest which is the best management of these diseases. Since its introduction in clinical practice, PerOral Endoscopic Myotomy (POEM) has emerged as a very promising, minimally invasive and effective treatment for oesophageal achalasia. No longer after the first uses, POEM has been successfully used also for the management of selected patients with NAOMD, However, currently available data are limited by small study sample sizes and short-term follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Study Aims: Characterization of indeterminate biliary strictures (IDBS) still represents a major challenge. Digital single-operator cholangioscopy (DSOC) could potentially overcome limits of conventional biopsy and brush sampling. The aim of this study was to compare diagnostic accuracy of visual evaluation and DSOC-guided biopsies to conventional trans-papillary sampling techniques and to evaluate the inter-observer agreement (IOA) on visual diagnosis., Patients and Methods: All consecutive patients undergoing DSOC-guided biopsy after conventional sampling techniques for IDBS during a six-year period were retrospectively evaluated. Final diagnosis was based on histological evaluation of the surgical specimen if available or a clinical follow-up of at least 6 months. For IOA, 20-second DSOC clips were retrospectively reviewed by 6 experts and 6 trainees and classified according to the Monaco Classification., Results: Thirty-five patients underwent DSOC for IDBS in the study period; 14 patients (F = 9) with a median age of 64 years (range 53-76) met the study aim. After DSOC, strictures location was changed in three patients (additional yield of 21.4 %). Intraductal DSOC-guided biopsy were technically successful in all cases, with an adequacy of 92.8 %. No adverse events were recorded. Final diagnosis was benign disease in five cases and cholangiocarcinoma in the others. For IOA, 29 videos were evaluated with almost perfect agreement for final diagnosis (kappa 0.871; agreement 93.1, p <0.001), although overall accuracy of DSOC visual finding was 73.6 % and 64.4 % for experts and trainees, respectively., Conclusions: DSOC could improve diagnostic accuracy for IDBS, since it showed high sensitivity for visual finding and high specificity for DSOC guided-biopsy. Visual diagnosis seems reliable for diagnosis using the Monaco Classification., Competing Interests: Conflict of interest The Corresponding Author guarantees that he has obtained all potential Conflict of Interest from all authors: Ivo Boskoki: consultant for Apollo Endosurgery, Cook Medical, Boston Scientific, Endotools, Erbe, Nitinotes and Microtech; research grant recipient from Apollo Endosurgery. Guido Costamagna: consultant for Boston Scientific, Cook Medical and Olympus. Andrea Tringali: consultant for Boston Scientific and Olympus. Cristano Spada: consultant for Medtronic, AnX Robotics and Norgine; research grant recipient from AlfaSigma, Pentax, Olympus., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Pancreas divisum (PD) is a congenital variant of the pancreatic ductal system and a potential cause of acute recurrent pancreatitis (ARP). Endoscopic minor papilla sphincterotomy (MiES) is the most common procedure performed in the management of PD-related ARP. The aim of this study is to perform a meta-analysis estimating the efficacy and the safety of MiES in the management of patients with PD-related ARP., Methods: A research was performed in Pubmed, EMBASE and Web of science, the studies were reviewed and selected according to inclusion and exclusion criteria. Evaluation of Heterogeneity and publication bias was performed, and a random effect model was used to estimate the effect size of each study., Results: One hundred and thirteen articles were selected and reviewed, 13 met the inclusion criteria. All the studies were retrospective with a mean follow-up duration of 45.9 months. A total of 323 patients with PD-related ARP treated with MiES were included in the meta-analysis. The overall clinical success rate of MiES (defined as no further episodes of ARP, reduction of episodes of ARP, or improvement in quality of life) was of 77% (95%CI: 72%-81%; p  = 0.30). Evaluating only the studies with clinical success rate defined as "no further AP in the follow-up" the clinical success rate was of 69.8% (95%CI: 61.3%-77.2%; p  = 0.57), while evaluating the studies with other definitions (reduction of episodes of ARP or improvement in quality of life) the clinical success rate was of 81.2% (95%CI: 75.2%-86.1%; p  = 0.45). The common fixed effects model disclosed a 25.5% overall adverse events rate (95%CI: 19.3%-32.8%; p  = 0.42): acute pancreatitis in 14.3% (95%CI: 9.7%-20.6%; p  = 0.36), bleeding in 5.6% (95%CI: 2.9%-10.4%; p  = 0.98), and other adverse events in 5.6% (95%CI: 2.9%-10.4%; p  = 0.67)., Conclusion: MiES is an effective and relatively safe treatment in the management of PD-related ARP. The retrospective nature of the studies selected is the main limitations of this metanalysis. Prospective trials are needed to confirm these data.

Objectives: Worldwide, countries adopted different strategies in primary care (PC) to cope with the COVID-19 pandemic. This study aims to describe and evaluate the functions and activity load of a specific PC organizational model called "Special Continuity Care Units" (SCCU) in Florence, Italy, and to investigate the characteristics of the COVID-19 patients assisted by the service. Methods: The retrospective cross-sectional design used daily updated reports by SCCU team members to evaluate the activity load. The retrospective cohort study analyzed data of the demographics, clinical characteristics, and process outcomes of patients assisted during the second pandemic wave. Results: The analysis shows how the service activity load changed along with the epidemiological trend. Regarding people assisted by the SCCU, the median follow-up duration of symptoms was 6 days; male gender and being symptomatic were predictors of hospitalization. Conclusion: Some key characteristics can be described as indispensable in PC services facing health emergencies: model flexibility, the availability of resources, networking among services to enhance coordination and resource optimization, and close collaboration with general practitioners., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Milani, Buscemi, Velpini, Naldini, Cosma, Giannuzzi, Ionita, Monaci, Landi, Pontalti, Baggiani, Nerattini, Lorini and Bonaccorsi.)

Objective: Peroral endoscopic myotomy (POEM) has become standard treatment for achalasia with comparable efficacy to surgery. In most of published series, the length of myotomy is 12-13 cm. Shorter cuts could have the advantage of shorter procedure time and possibly reduced gastro-oesophageal reflux disease (GORD) rate., Design: This single-centre, patient-blinded, randomised, non-inferiority clinical trial included 200 patients, who were randomly allocated, to receive either a long-POEM (13 cm; 101 patients) or a short-POEM (8 cm; 99 patients). Primary outcome was defined as an Eckardt symptom score of ≤3 at 24 months after the procedure; a non-inferiority design was chosen with an accepted success range of 6% between the two treatments. Secondary outcomes included operating time, complication rate, postoperative manometry, GORD rate and quality of life., Results: In the intention-to-treat analysis, clinical success rates were 89.1% in the long-POEM and 98.0% in the short-POEM group, resulting in an absolute between-group difference of -8.9% (90% CI -14.5 to -3.3).Procedure time was significantly reduced in the short-POEM as compared with the long-POEM group (40 vs 50 min, p<0.0001). Severe adverse events occurred in one patient in both groups.No differences were observed in postoperative GORD: acid exposure >6% on pH monitoring study at 6 months was seen in 34.3% (long-POEM) vs 31.1% (short-POEM), while endoscopic oesophagitis was diagnosed in 37.6% vs 51.5% at 6 months and in 21% vs 24.5% at 24 months. Regular proton pump inhibitor use was not different either (36.8% vs 37.5%)., Conclusions: Our study demonstrates non-inferiority of a shorter cut length of POEM as compared with the standard treatment, which saved some procedural time. GORD rate was not reduced by reducing cutting length., Trial Registration Number: NCT03450928., Competing Interests: Competing interests: PF, FBdA, RL, FM, AT and VP have no conflict of interest or financial ties to disclose. GC is a member of the advisory board of Cook Medical, Olympus and Johnson & Johnson. He received a Research Grant from Boston Scientific and Apollo Endosurgery. IB is a consultant for Apollo Endosurgery, Cook Medical and Boston Scientific. He received a Research Grant from Apollo Endosurgery. He is a member of the scientific board of EndoTools., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.

More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient's outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0-1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35-2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients' COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19.

Background: SARS-CoV-2 is a single-stranded RNA virus, known to be the causative agent of COVID-19. As the resulting disease shows a very heterogeneous range of clinical manifestations, the identification of early biomarkers allowing patients stratification according to the expected disease severity is still an unmet clinical need., Methods: In this observational prospective cohort study, 137 consecutive patients, testing positive for SARS-CoV-2 infection by nasopharyngeal swab RT-PCR or antigenic test, were enrolled to evaluate their plasma viral load at the time of hospitalization., Results: Even if all of them had a molecular diagnosis of COVID-19, only 29 patients showed a detectable plasma SARS-CoV-2 RNAemia. Such viremic patients also showed other clinical and laboratory finding alterations (increased troponin I, IL-6, RDW-CV, and creatinine levels along with decreased platelet count and glomerular filtration rate). A plasma detectable RNA viral load predicted in hospital death or ICU admission with an odds ratio of 3.53 (CI: 1.44-8.64, P=0.0058), while the lack of a detectable viral load was associated with a faster recovery, with an odds ratio of 4.06 (CI: 1.72-9.59, P=0.0014). These findings were confirmed in multivariate models including age, sex and baseline National Early Warning Score 2 and arterial oxygen tension over inspired oxygen fraction ratio., Conclusions: Our data thus suggest that plasma viral RNA load at the time of hospital admission could represent a useful independent biomarker allowing early patients' stratification according to the expected disease evolution, and driving clinical decisions tailored on the specific needs of the individual patient.

SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07-7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19-7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation., Competing Interests: The authors declare no conflict of interest.

Reliable biomarkers allowing early patients' stratification for the risk of adverse outcomes in COVID-19 are lacking. Gas6, together with its tyrosine kinase receptors named TAM, is involved in the regulation of immune homeostasis, fibrosis, and thrombosis. Our aim was to evaluate whether Gas6, sAxl, and sMerTK could represent early predictors of disease evolution either towards a negative (death or need of ICU admission) or a positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. To this purpose, between January and May 2021 (corresponding to third pandemic wave in Italy), 139 consecutive SARS-CoV-2 positive patients were enrolled in a prospective observational study. Plasma levels of these molecules were measured by ELISA at the time of hospitalization and after 7 and 14 days. We observed that higher plasma Gas6 concentrations at hospital admission were associated with a worsening in clinical conditions while lower sMerTK concentrations at baseline and after 7 days of hospitalization were associated with a more favorable outcome. At multivariate analysis, after correction for demographic and COVID-19 severity variables (NEWS2 and PiO 2 /FiO 2 ), only Gas6 measured at baseline predicted an adverse prognosis with an odds ratio of 1.03 (C.I. 1.01-10.5). At ROC curve analysis, baseline Gas6 levels higher than 58.0 ng/ml predicted a severe disease evolution with 53.3% sensitivity and 77.6% specificity (area under the curve 0.653, p = 0.01, likelihood ratio of 2.38, IQR: 1.46-3.87). Taken together, these results support the hypothesis that a dysregulation in the Gas6/TAM axis could play a relevant role in modulating the course of COVID-19 and suggest that plasma Gas6 may represent a promising prognostic laboratory parameter for this condition., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Stelvio Tonello et al.)

Background: SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients' stratification according to disease severity. In this observational prospective cohort study, patients' immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome., Methods: Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay., Results: According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP - 10 > 4271 pg/mL and CRP > 2.3 mg/dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001, respectively)., Conclusions: According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Manuela Rizzi et al.)

Background: The Coronavirus disease (COVID-19) outbreak is putting the European National Health Systems under pressure. Interestingly, Emergency Department (ED) referrals for other reasons than COVID-19 seem to have declined steeply. In the present paper, we aimed to verify how the COVID-19 outbreak changed ED referral pattern., Methods: We retrospectively reviewed the clinical records of patients referred to the ED of a University Hospital in Northern Italy from 1 March to 13 April 2020. We compared the following data with those belonging to the same period in 2019: number of EDs accesses, rate of hospital admission, frequencies of the most common causes of ED referral, priority codes of access., Results: The number of ED referrals during the COVID-19 outbreak was markedly reduced when compared to the same period in 2019 (3059 vs. 5691; -46.3%). Conversely, the rate of hospital admission raised from 16.9% to 35.4% (P<0.0001), with a shift toward higher priority codes of ED admission. In 2020, we observed both a reduction of the number of patients referred for both traumatic (513, 16.8% vs. 1544, 27.1%; χ 2 =118.7, P<0.0001) and non-traumatic (4147 vs. 2546) conditions. Among the latter, suspected COVID-19 accounted for 1101 (43.2%) accesses., Conclusions: The COVID-19 pandemic completely changed the pattern of ED referral in Italy, with a marked reduction of the accesses to the hospitals. This could be related to a limited exposure to traumas and to a common fear of being infected during EDs in-stay. This may limit the misuse of EDs for non-urgent conditions but may also delay proper referrals for urgent conditions.

Background and study aims  The aim of this study was to assess long-term clinical outcomes beyond 6 years in patients who underwent per-oral endoscopic myotomy (POEM) for the treatment of achalasia. Patients and methods  Patients with achalasia who underwent POEM between 2010 and 2012 and had follow-up of at least 6 years were retrospectively identified at eight tertiary care centers. The primary outcome evaluated was clinical success defined by an Eckardt symptom score (ESS) ≤ 3 for the duration of the follow-up period. The clinical success cohort was compared to failure (ESS > 3 at any time during follow-up) in order to identify characteristics associated with symptom relapse. The incidence of patient-reported gastroesophageal reflux (GER) was also evaluated. Results  Seventy-three patients with 6-year follow-up data were identified. Sustained clinical remission was noted in 89 % (65/73) at 6-years. Mean ESS decreased from 7.1 ± 2.3 pre-procedure to 1.1 ± 1.1 at 6 years ( P  < 0.001). Symptomatic reflux was reported by 27 of 72 patients (37.5 %). Type I achalasia (OR 10.8, P  = 0.04) was found to be associated with clinical failure on logistic regression analysis. Conclusions  In patients with achalasia, POEM provides high initial clinical success with excellent long-term outcomes. There are high rates of patient-reported gastroesophageal reflux post-procedure which persist at long-term follow-up., Competing Interests: Competing interests Dr. N. Thosani is a consultant for Boston Scientific, Medtronic, Endogastric Solutions, and Pentax of America; a speaker for Abbvie, and receives royalties from UpToDate. Dr. M.A. Khashab is a consultant for Boston Scientific, Medtronic and Olympus. Dr. Alessandro Repici MD -Boston consulting fee, speaker fee, research grant. Fujifilm advisory board speaker fee. ERBE advisory board consulting fee. EndoKey advisory board. EndoStart advisory board. Medtronic research grant, consulting fee, advisory board. Dr. Sachin Wani is a Consultant for Boston Scientific, Medtronic, Cernostics and Interpace. Supported by the University of Colorado Department of Medicine Outstanding Early Scholars Program. All remaining authors declare they have nothing to disclose., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: to evaluate the contribution of edema associated with histological features to the prediction of breast cancer (BC) prognosis using T2-weighted MRI radiomics., Methods: 160 patients who underwent staging 3T-MRI from January 2015 to January 2019, with 164 histologically proven invasive BC lesions, were retrospectively reviewed. Patient data (age, menopausal status, family history, hormone therapy), tumor MRI-features (location, margins, enhancement) and histological features (histological type, grading, ER, PgR, HER2, Ki-67 index) were collected. Of the 160 MRI exams, 120 were considered eligible, corresponding to 127 lesions. T2-MRI were used to identify edema, which was classified in four groups: peritumoral, pre-pectoral, subcutaneous, or diffuse. A semi-automatic segmentation of the edema was performed for each lesion, using 3D Slicer open-source software. Main radiomics features were extracted and selected using a wrapper selection method. A Random Forest type classifier was trained to measure the performance of predicting histological factors using semantic features (patient data and MRI features) alone and semantic features associated with edema radiomics features., Results: edema was absent in 37 lesions and present in 127 (62 peritumoral, 26 pre-pectoral, 16 subcutaneous, 23 diffuse). The AUC-classifier obtained by associating edema radiomics with semantic features was always higher compared to the AUC-classifier obtained from semantic features alone, for all five histological classes prediction (0.645 vs. 0.520 for histological type, 0.789 vs. 0.590 for grading, 0.487 vs. 0.466 for ER, 0.659 vs. 0.546 for PgR, and 0.62 vs. 0.573 for Ki67)., Conclusions: radiomic features extracted from tumor edema contribute significantly to predicting tumor histology, increasing the accuracy obtained from the combination of patient clinical characteristics and breast imaging data.

Red blood cell distribution width (RDW) has been studied as a prognostic biomarker for different chronic inflammatory diseases. In this paper we aim to evaluate its potential role in the prediction of early relapse in patients affected by polymyalgia rheumatica (PMR). We revised retrospectively clinical records of patients who received a diagnosis of PMR, according to 2012 ACR/EULAR classification criteria, for whom baseline clinical and laboratory data were available. The baseline RDW variation coefficient was correlated to the risk of relapse, in the first 6 months of the disease. We identified 44 patients [females 15 (34.0%)/males 29 (66.0%); median age 80 (72-83)], 9 of whom had an early relapse. These patients showed a larger median RDW than patients who did not relapse [13.7 (13.5-14.9)% vs 13.5 (12.7-14.2)%; p=0.04). The two groups were comparable for all the other clinical and laboratory parameters considered. Interestingly, patients in the higher half of the RDW distribution showed a shorter relapse-free survival (p<0.03). In a stepwise logistic regression, RDW (p=0.01) predicted the risk of relapse at 6 months, while age, gender, CRP, ESR, Hb, MCV and prednisone dose did not fit the model. Our results show that RDW is an independent biomarker of early relapse, making this parameter a potentially promising predictive marker in PMR.

Objectives: To create a review of the existing literature on the radiomic approach in predicting the lymph node status of the axilla in breast cancer (BC)., Materials and Methods: Two reviewers conducted the literature search on MEDLINE databases independently. Ten articles on the prediction of sentinel lymph node metastasis in breast cancer with a radiomic approach were selected. The study characteristics and results were reported. The quality of the methodology was evaluated according to the Radiomics Quality Score (RQS)., Results: All studies were retrospective in design and published between 2017 and 2020. The majority of studies used DCE-MRI sequences and two investigated only pre-contrast images. The sample size was lower than 200 patients for 7 studies. The pre-processing used software, feature extraction and selection methods and classifier development are heterogeneous and a standardization of results is not yet possible. The average RQS score was 11.1 (maximum possible value = 36). The criteria with the lowest scores were the type of study, validation, comparison with a gold standard, potential clinical utility, cost-effective analysis and open science data., Conclusion: The field of radiomics is a diagnostic approach of relative recent development. The results in predicting axillary lymph node status are encouraging, but there are still weaknesses in the quality of studies that may limit the reproducibility of the results.

Introduction: The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions., Materials and Methods: In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded., Results: At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006), and platelet count ( χ 2 5.39; p = 0.02), along with age ( χ 2 87.6; p < 0.001) and gender ( χ 2 17.3; p < 0.001), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality (OR) = 3.40 (2.40-4.82), while the OR for a RDW > 13.7% was 4.09 (2.87-5.83); a platelet count > 166,000/ μ L was, conversely, protective (OR: 0.45 (0.32-0.63))., Conclusion: Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2021 Mattia Bellan et al.)

Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract's cancer and has still today a poor prognosis. Endoscopy plays a crucial role in malignant HBO from the diagnosis to the palliation. This technique allows the collection of cytological or histological samples, direct visualization of the suspect malignant tissue, and an echoendoscopic evaluation of the primary tumor and its locoregional staging. Because obstructive jaundice is the most common clinical presentation of malignant HBO, endoscopic biliary drainage, when indicated, is the preferred treatment over the percutaneous approach. Several endoscopic techniques are today available for both the diagnosis and the treatment of biliary obstruction. The choice among them can differ for each clinical scenario. In fact, a personalized endoscopic approach is mandatory in order to perform the proper procedure in the singular patient.

Competing Interests: Dr. G. Costamagna is a member of the advisory board of Cook Medical, Olympus Co. and Johnson & Johnson. He received a Research Grant from Boston Scientific Inc. and Apollo Endosurgery Inc.Dr. I. Boskoski is a consultant for Apollo Endosurgery, Cook Medical and Boston Scientific. He received a Research Grant from Apollo Endosurgery. He is a member of the scientific board of EndoTools.

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO 2 /FiO 2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk.

Background: The premalignant nature of ampullary adenomas justifies their radical excision., Aims: Aim of this study is to evaluate the long-term results of endoscopic snare papillectomy in a consecutive series of patients with ampullary adenomas., Methods: Patients who underwent endoscopic snare papillectomy between October 1999 and October 2017 were identified from an electronic database. Endoscopic snare papillectomy was performed en bloc, when possible; a pancreatic stent or a nasopancreatic drainage were inserted. Endoscopic follow-up was scheduled after 3, 6 and 12 months for the first year, then yearly., Results: Endoscopic snare papillectomy was performed in 135 patients (70 M, mean age 60.5 years) by en bloc (83%) or piecemeal (17%) resection. Delayed bleeding occurred in 16 patients (11.8%), infected retroperitoneal collections in 6 patients (4.4%), pancreatitis in 4 patients (3%). One patient died (0.7%). Follow-up was available in 103/114 (90.3%) patients. In case of residual (24.3%) and recurrent (23.3%), adenomas endoscopic retreatment was successful in 42/49 cases (85.7%). After a mean follow-up of 40 months, 93.2% (96/103) of the patients were disease free CONCLUSION: Endoscopic snare papillectomy of ampullary adenomas is effective with favorable long-term outcomes. Compliance to the scheduled follow-up is important for the early detection and re-treatment of recurrences., Competing Interests: Conflicts of interest Dr. Tringali is a consultant for Boston Scientific. Dr. Boškoski is a research grant holder from Apollo Endosurgery and a consultant for Apollo Endosurgery, Cook Medical, and Boston Scientific. Professor Costamagna is a consultant for Olympus, Cook Medical, and Boston Scientific. The remaining authors disclose no competing interests., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

On 31 December 2019, the WHO China Country Office was informed of cases of pneumonia of unknown etiology detected in Wuhan (Hubei Province of China). In January 2020, a new coronavirus named SARS-CoV2 was isolated and, since that time, SARS-CoV2 related disease (COVID-19) rapidly spread all over the world becoming pandemic in March 2020. The COVID-19 outbreak dramatically affected the public-health and the health-care facilities organization. Bilio-pancreatic endoscopy is considered a high-risk procedure for cross-contamination and, even though it is not directly involved in COVID-19 diagnosis and management, its reorganization is crucial to guarantee high standards of care minimizing the risk of SARS-CoV2 transmission among patients and health-care providers. Bilio-pancreatic endoscopic procedures often require a short physical distance between the endoscopist and the patient for a long period of time, a frequent exchange of devices, the involvement of a large number of personnel, the use of complex endoscopes difficult to reprocess. On this basis, endoscopic units should take precautions with adjusted management of bilio-pancreatic endoscopy. The aim of this article is to discuss the approach to bilio-pancreatic endoscopy in the COVID-19 era with focus on diagnostic algorithms, indications, management of the endoscopic room, proper use of Personal Protective Equipment and correct reprocessing of instrumentation., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Background and study aims  Per-oral endoscopic myotomy (POEM) is associated with a short-term clinical response of 82 % to 100 % in treatment of patients with achalasia. Data are limited on the long-term durability of the clinical response in these patients. The aim of this study was to determine the long-term outcomes of patients undergoing POEM for management of achalasia. Methods  This was a retrospective multicenter cohort study of consecutive patients who underwent POEM for management of achalasia. Patients had a minimum of 4 years follow-up. Clinical response was defined by an Eckardt score ≤ 3. Results  A total of 146 patients were included from 11 academic medical centers. Mean (± SD) age was 49.8 (± 16) years and 79 (54 %) were female. The most common type of achalasia was type II, seen in 70 (47.9 %) patients, followed by type I seen in 41 (28.1 %) patients. Prior treatments included: pneumatic dilation in 29 (19.9 %), botulinum toxin injection in 13 (8.9 %) and Heller myotomy in seven patients (4.8 %). Eight adverse events occurred (6 mucosotomies, 2 pneumothorax) in eight patients (5.5 %). Median follow-up duration was 55 months (IQR 49.9-60.6). Clinical response was observed in 139 (95.2 %) patients at follow-up of ≥ 48 months. Symptomatic reflux after POEM was seen in 45 (32.1 %) patients, while 35.3 % of patients were using daily PPI at 48 months post POEM. Reflux esophagitis was noted in 16.8 % of patients who underwent endoscopy. Conclusion  POEM is a durable and safe procedure with an acceptably low adverse event rate and an excellent long-term clinical response., Competing Interests: Competing interests Vivek Kumbhari is a consultant for Boston Scientific, Apollo Endosurgery, Medtronic, ReShape Medical. Mouen A. Khashab is a consultant and advisory board for Boston Scientific and consultant for Olympus.

Background and Aims: Right aberrant hepatic ducts are an anatomic variant with clinical relevance because of the risk of injury during cholecystectomy. Treatment options for aberrant hepatic duct injuries are not standardized. This study aims to analyze the long-term results of endoscopic treatment of aberrant hepatic duct lesions., Methods: Patients who underwent ERCP for aberrant hepatic duct lesions were retrospectively identified. Demographic data, type of aberrant duct lesion according to the Strasberg classification, type of treatment (number of plastic stents inserted, treatment duration, and number of ERCPs), and adverse events were recorded. Follow-up was obtained by telephone contact or medical examinations., Results: Between January 1996 and March 2019, 32 patients (78% women, mean age 51.7 years) with aberrant hepatic duct injuries underwent ERCP at our Endoscopy Unit. Six patients had Strasberg type B lesions, 11 patients had type C, and 8 patients had type E5, and 7 patients had a stenosis of the aberrant duct. A mean of 3.7 biliary plastic stents per patient were used; mean treatment duration was 6.3 months. All patients with isolated aberrant duct stenosis and 1 of 6 patients (17%) with type B Strasberg lesions achieved patency. Ten of 11 patients (91%) with type C Strasberg lesions achieved duct recanalization. After a mean follow-up of 109.3 ± 61.2 months, 29 of 32 patients (91%) were asymptomatic; 1 underwent surgery for recurrent cholangitis, 1 received a new endoscopic procedure because of cholangitis, and 1 reported episodic biliary colic without an increase in liver function test values and was successfully managed with a low-fat diet., Conclusions: An endoscopic approach to aberrant hepatic duct lesions after cholecystectomy can be considered an effective first-line therapy., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: POEM has recently had a widespread diffusion, aiming at being the treatment of choice for esophageal achalasia. The results of ongoing RCTs against laparoscopic myotomy are not available, yet. We, therefore, designed this propensity score (PS) case-control study with the aim of evaluating how POEM compares to the long-standing laparoscopic Heller myotomy + Dor fundoplication (LHD) and verifying if it may really replace the latter as the first-line treatment for achalasia., Methods: Two groups of consecutive patients undergoing treatment for primary achalasia from January 2014 to November 2017 were recruited in two high-volume centers, one with extensive experience with POEM and one with LHD. Patients with previous endoscopic treatment were included, whereas patients with previous LHD or POEM were excluded. A total of 140 patients in both centers were thus matched. LHD and POEM were performed following established techniques. The patients were followed with clinical (Eckardt score), endoscopic, and pH-manometry evaluations., Results: The procedure was successfully completed in all the patients. POEM required a shorter operation time and postoperative stay compared to LHD (p < 0.001). No mortality was recorded in either group. Seven complications were recorded in the POEM group (five mucosal perforations) and 3 in the LHD group (3 mucosal perforations)(p = 0.33). Two patients in the POEM group and one in the LHD were lost to follow-up. One patient in both groups died during the follow-up for unrelated causes. At a median follow-up of 24 months [15-30] for POEM and 31 months [15-41] for LHD (p < 0.05), 99.3% of the POEM patients and 97.7% of the LHD patients showed an Eckardt score ≤ 3 (p < 0.12). Four years after the treatment, the probability to have symptoms adequately controlled was > 90% for both groups (p = 0.2, Log-rank test). HR-Manometry showed a similar reduction in the LES pressure and 4sIRP; 24-h pH-monitoring showed however an abnormal exposure to acid in 38.4% of POEM patients, as compared to 17.1% of LHD patients (p < 0.01) and esophagitis was found in 37.4% of the POEM and 15.2% of LHD patients (p < 0.05)., Conclusion: POEM provides the same midterm results as LHD. This study confirms, however, a higher incidence of postoperative GERD with the former, even if its real significance needs to be further evaluated.

Background and Aims: Endoscopic therapy of benign biliary strictures with multiple plastic stent (MPS) placement has shown satisfactory results. However, the literature describes various benign biliary stricture etiologies. The aim of this study was to evaluate long-term MPS results in patients with postcholecystectomy biliary strictures (PCBSs)., Methods: PCBS patients without complete bile duct transection were included. ERCP consisted of placing an increasing plastic stent number over time, exchanged at regular intervals (3-4 months), until complete morphologic stricture disappearance. After stent removal, patient follow-up comprised liver function tests and clinical assessment., Results: One hundred fifty-four patients (43.5% men; mean age, 53 years) were enrolled; in 43% of the cases, PCBSs were involved or were close to the main hepatic confluence. PCBS resolution rate was 96.7% (n = 149). A mean maximum number of 4.3 ± 1.6 stents were placed side-by-side; a mean of 4.2 ± 1.5 ERCPs per patient was needed to obtain PCBS resolution during a mean treatment period of 11.8 ± 6.4 months. Unscheduled stent exchange because of cholangitis, jaundice, or pain occurred in 7.4% of cases. Procedure-related mortality was absent. Follow-up data were available in 85.2% of cases. After a mean follow-up of 11.1 ± 4.9 years, stricture recurrence rate was 9.4% (n = 12). Subsequent to retreatment, 83.3% of patients (n = 10) were asymptomatic after a mean time of 9 years, whereas 2 patients underwent hepaticojejunostomy because of failed retreatment. Statistical analysis revealed no risk factors for PCBS recurrence after MPS., Conclusions: Endoscopic therapy of PCBSs with MPSs is safe and effective at long-term follow-up. PCBSs involving or close to the main hepatic confluence were successfully treated with MPSs. PCBS recurrence rate is low and can be successful endoscopically retreated without precluding possible surgical treatment., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)