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Gastric polyps represent an abnormal proliferation of the gastric mucosa. Chronic atrophic autoimmune gastritis (CAAG) targets parietal cells and results in hypo-achlorhydria and hypergastrinemia, which exerts a proliferative effect on the gastric mucosa. We investigate the incidence of gastric polyps in CAAG patients. This is a single-center retrospective study examining patients with confirmed CAAG from January 1990 until June 2022. Demographic, clinical, biochemical, and serological data were collected for each included patient. The histopathological characteristics of the detected polyps were recorded. A total of 176 CAAG patients were included. Eighty-nine (50.5%) had 163 incidental polyps. Seventy-six patients (85%) had 130 non-endocrine lesions, among which 118 (90.7%) were inflammatory, 6 (4.6%) adenomatous, and 4 (3%) fundic; 33 patients (37%) had gastric neuroendocrine neoplasms (gNENs), and 21 (23.6%) both; one had MALToma and one gastric adenocarcinoma. Higher circulating levels of gastrin and chromogranin A were observed among patients with polyps (median 668 vs 893 pg/ml p = 0.0237, 146 vs 207 ng/ml p = 0.0027, respectively). CAAG implies a high incidence of gNENs and exocrine lesions. Gastrin plays a possible trophic role on the mucosa. Further evidence is needed to validate its predictive role for increased polyp risk in CAAG. [ABSTRACT FROM AUTHOR]

CEUS is a safe and cost-effective imaging technique which allows a real-time evaluation of focal liver lesions (FLL). It has become a fundamental tool in HCC surveillance and diagnosis. Nevertheless, some concerns have risen in the past on its diagnostic accuracy, in particular in its ability to discriminate between HCC and small (<3 cm) Intraepatic cholangio-Carcinoma (ICC). Recent advances in AI-driven tools for medical imaging have demonstrated the potential of greatly improving accuracy. In ultrasonography, they have been proposed to perform diagnosis from CEUS images alone or in combination with Bi-modal ones: the former can provide information about the contrast pattern; the latter enhances structural characteristics.Two challenges arise in the use of machine learning in the analysis of liver ultrasound images. First, the lack of large public datasets, which makes it difficult to train deep learning models, capable of extracting powerful features, optimized for the task: Radiomics, represents an effective technique for extracting powerful quantitative features without the need of a training dataset. Second, the need for complete and standardized annotations, crucial for effective model training. To build an annotation software capable of selecting ROIs in CEUS imaging and of extracting Radiomics features from both CEUS and B-Mode views, with the intention to build an automated detection software protocol for FLL diagnosis. A stand-alone tool for annotating CEUS exams and extracting Radiomics features from the annotated ROIs is proposed. It inputs a CEUS exam stored in a WMV or a DICOM file, which includes both B-mode and CEUS views in split screen manner. It allows the radiologist to select the more suitable frame to be annotated within the exam. Two automatisms are introduced in the annotation procedure: first, the tool is capable of replicating in real-time the annotation performed by the annotator on one view, onto the other one. In addition, it is capable of automatically interpolating contour points of the lesion, in case the annotator will not perform a complete annotation. Once annotation is performed, both annotated CEUS and B-Mode views are prepared for labeling and feature extraction. Labeling concerns both the selection of the phase the frame belongs to, i.e., arterial, portal or late, and the type of annotated lesion. Feature extraction instead is performed through Radiomics: to this aim, the annotated views are automatically saved into two distinct NifTI files, from which histogram-based, shape-based and texture based Radiomics features are automatically extracted through PyRadiomics and saved into a specific folder for that exam. A total number of 102 features are automatically extracted and saved from each view. The proposed tool has been positively evaluated by radiologists from the University of Salerno, because of its ease of use and its ability to automatically reproduce on one view, the annotations manually made on the other one. In this work, a stand-alone tool for annotating multi-view liver ultrasound images is proposed. The next step is to use it to create a complete labeled dataset exploitable by AI methods from single or multi view liver lesion analysis. [ABSTRACT FROM AUTHOR]

Although the management of gynecological cancers recurrences may be challenging, due to the heterogeneity of recurrent disease, the aim of this work is to present a descriptive analysis of gynecological malignancies recurrences in our institution treated by robotic approach. We performed a retrospective review and analysis of data of patients who underwent robotic surgery for recurrent gynecological malignancies at Catholic University of the Sacred Hearth, Rome, from January 2013 to January 2024. A total of 54 patients underwent successful robotic cytoreductive surgery. The median age was 63 years; the median BMI was 33 kg/m2 and most of the patients (59 %) were obese. In 12 cases (22 %) the relapse presented was the second or third relapse. The most frequent patterns of recurrence were represented by lymph nodes (41 %), followed by peritoneal (26 %), pelvic (22 %) and parenchymal (11 %). In all patients complete cytoreduction was achieved. In 29 patients (54 %) the surgical field was previous treated. The median operative time and estimated blood loss were, respectively, 270 min and 100 ml. There were 2 intraoperative complications, managed endoscopically; 10 early postoperative complications, and 3 late postoperative complications. The 2-year progression-free-survival and overall survival were, respectively, 39.8 % and 72.3 %. Robotic approach in the treatment of recurrent gynecological cancers should be considered in selected patients with oligometastatic disease, in high-volume centers with expert surgeons, particularly in obese patients. • The oncological management of patients with relapsed gynecological cancer may be challenging, due to the heterogeneity of recurrent disease and clinical characteristics of patients. • Complete gross resection is associated by the best outcomes. • Patients' selection is crucial in the choice of a minimally invasive approach. • Robotic approach provides advantages in terms of 360° movements, tremor filtering, stable 3D-vision, and an ergonomic position of the surgeon. • Robotic approach should be considered in selected patients with oligometastatic disease, especially in obese patients. [ABSTRACT FROM AUTHOR]

Lean Manufacturing tools were originally developed to improve manufacturing production systems and enhance productivity and quality in organizations. For this reason, they are used more frequently in manufacturing than in service companies. The Ergo-Lean approach applies Lean Manufacturing to the field of Occupational Safety and Health, focusing on reducing activities that do not add value and on reducing the associated muscular-skeletal disorders. The purpose of this study is to integrate Lean Manufacturing tools in risk management to help control work-related accidents. Based on work accident data at a service company, the causes of the accidents were analyzed and the main Lean Manufacturing tools were reviewed and integrated, in order to develop a new methodology for the implementation of these tools to help prevent work-related accidents and diseases and to develop a culture of self-care. [ABSTRACT FROM AUTHOR]

Background and Aim: Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS.Methods and Results: Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (Conclusions: Among elderly patients with ACS, BMI did not condition the survival or the risk of major cardiovascular and bleeding complications. The results were consistent across several patient risk categories. [ABSTRACT FROM AUTHOR]

Medium-vessel occlusions (MeVO) are emerging as a new target for endovascular treatment (EVT). Primary MeVO occur de novo, while secondary MeVO arise from large vessel occlusion (LVO) through clot migration or fragmentation - spontaneously, following intravenous thrombolysis or EVT. We aimed to evaluate efficacy and safety of EVT in primary and EVT-induced secondary MeVO. Retrospective single-center study on consecutive EVT-treated acute ischemic stroke, from 2019-to-2021. We considered: (1) exclusive-LVO, patients with LVO and – in case of residual distal occlusion – no rescue endovascular procedure; (2) primary MeVO: initial A2, A3, M2 non-dominant, M3, P2, P3 occlusions; (3) EVT-induced secondary MeVO, presenting LVO with subsequent (treated) EVT-induced MeVO. We compared (univariable/multivariable logistic regression) EVT efficacy (eTICI≥2b, 3-month modified Rankin Scale [mRS] 0-2) and safety (EVT-complications [vessel dissection, perforation, persistent-SAH], symptomatic ICH) in all MeVO versus exclusive-LVO, primary MeVO versus exclusive-LVO, EVT-induced secondary MeVO versus exclusive-LVO and EVT-induced secondary MeVO versus primary MeVO. We included 335 patients: 221 (66.0 %) exclusive-LVO and 114 (34.0 %) MeVO (55 [48.2 %] primary, 59 [51.8 %] secondary). Compared to exclusive-LVO, primary MeVO had higher rates of EVT complications (aOR 3.77 [95%CI 1.58-9.00],p=0.003), lower rates of eTICI≥2b (aOR 0.32 [95%CI 0.12-0.88],p=0.027) and mRS 0-2 (aOR 0.28 [95%CI 0.13-0.63],p=0.002). EVT-induced secondary MeVO had no major differences in efficacy and safety outcomes compared to exclusive-LVO, but a better mRS 0-2 (aOR 8.00 [95%CI 2.12-30.17],p=0.002) compared to primary MeVO. Primary and EVT-induced secondary MeVO showed different safety/efficacy EVT-related profiles. Dedicated randomized data are needed to identify the best acute reperfusion strategy in the two categories. [ABSTRACT FROM AUTHOR]

Study Objective: To assess the feasibility and efficacy of minimally invasive pelvic exenteration (MIPE) in a multi-institutional Italian case series of women with gynecologic cancer and a review of the literature.Design: Retrospective cohort study (Canadian Task Force classification II-2).Setting: Three Italian university/teaching hospitals: "Agostino Gemelli" Foundation University Hospital in Rome, "ARNAS Civico Di Cristina Benfratelli" Hospital in Palermo, and "Maggiore della Carità" Hospital in Novara.Patients: We reviewed all consecutive cases with gynecologic malignancies in this multi-institutional setting recorded between March 2014 and June 2017. Women with primary or central recurrent/persistent gynecologic cancer considered suitable for exenterative surgery after multidisciplinary tumor board discussion were included. Clinicopathological, perioperative, and survival data were retrieved from the institutional electronic database (STAR center).Interventions: All patients underwent total or anterior MIPE with a laparoscopic or robotic approach.Measurements and Main Results: Twenty-three patients underwent MIPE during the study period, including 12 (52.1%) by a laparoscopic approach and 11 (47.9%) by a robotic approach. All but 1 woman underwent MIPE for recurrent disease. The overall median operative time was 540 minutes (range, 310-720 minutes) with laparoscopy, slightly longer than with the robotic approach (p = .04). Median estimated blood loss was 400 mL (range, 200-600 mL). R0 resection was achieved in 17 of 23 patients (73.9%). There were no perioperative deaths. Early major postoperative complications occurred in 2 patients (8.7%). The median duration of hospitalization was 10 days (range, 6-33 days). With a median follow-up of 15 months, 11 patients (47.8%) developed recurrence. The median disease-free survival was 11 months (range, 5-18 months). To date, 155 MIPEs for gynecologic cancers have been reported in the literature. Among these, 12.6% had major postoperative complications, and overall postoperative mortality was 0.6%.Conclusion: MIPE is a feasible procedure with low rate of intraoperative and postoperative complications. Careful patient selection is crucial to balance perioperative risks and potential survival benefits and to achieve complete tumor resection. [ABSTRACT FROM AUTHOR]

Abstract Background to assess the feasibility of minimally invasive surgery in the management of lymph-nodal recurrences of gynecological cancers, in terms of surgical and oncological outcomes. Methods we retrospectively collected patients with isolated lymph-nodal recurrent disease of gynecological malignancies who underwent to minimally invasive lymphadenectomy at Catholic University of the Sacred Hearth in Rome (Italy), from January 2013 to November 2017. Results Forty patients were considered eligible (31 LPS, 9 Robot); 24 (60.0%) with an ovarian cancer, 8 (20.0%) with a cervical cancer and 8 (20.0%) with an endometrial cancer recurrence. The most frequent site of lymph-nodal recurrence was represented by the aortic region (47.5%), while 18 patients (45.0%) experiencing pelvic lymph-nodal recurrence, 2 (5.0%) both pelvic and aortic relapse, and only 1 (2.5%) had an hepato-celiac lymph node recurrence. No patient required a laparotomic conversion. Median operative time was 220 min, median EBL was 80 mL, and median post-operative hospital stay was 2 days. There were 2 (5.0%) intra-operative and 4 (10.0%) post-operative complications, of which 2 were grade 3. The median follow-up was 22.5 months, and during this time 15 patients showed another relapse with a median time to progression of 12 months. Seven women died because of the disease. The 2-year post-relapse disease-free survival (PR-DFS) was 54.7%, and the 2-year post-relapse overall survival (PR-OS) was 79.3%. Conclusions In our experience minimally invasive surgery is a valid therapeutic approach in very select patients with localized lymph-nodal recurrence of gynecological cancers, with benefits about peri and post-operative morbidities and without compromising their oncological outcome. [ABSTRACT FROM AUTHOR]

Background This study aims at evaluating the feasibility, surgical outcome and oncological results observed after robotic radical hysterectomy (RH) compared to laparoscopy for patients with early stage cervical cancer (ECC) patients. Methods Between January 2010 and October 2016, 210 patients underwent RH for treatment of ECC: 70 underwent robotic approach (Cases), and 140 underwent laparoscopic approach (Controls). Results There was no statistically significant difference between the two approaches with regard to clinical patient characteristics and in terms of extent of RH and rate of pelvic and aortic lymphadenectomy. Operative time was significantly longer in the robotic versus laparoscopic group (median = 243 min, range 90–612 versus median = 210 min, range 80–660; p value = 0.008). Conversion to laparotomy was necessary in 4 patients (1.9%) in the whole series. No difference was found in terms of intraoperative and postoperative complications between the two groups. Overall, during the observation period, 34 (16.2%) patients experienced any grade postoperative complications, and 21 (10.0%) had >G2 complications. The 3-yr DFS was 88.0% versus 84.0% in robotic and laparoscopic group, respectively (p value = 0.866). Central and/or lateral pelvic disease represented the most common site of relapse. The 3-yr OS was 90.8% in patients underwent robotic RH versus 94.0% in patients underwent laparoscopic RH (p value = 0.924). Conclusions The present study shows the equivalence of robotic and laparoscopic approaches to radical surgery of ECC patients, in terms of perioperative and postoperative outcomes with equivalent survival figures, and thus the choice of approach can be tailored to the choice of patient and surgeon. [ABSTRACT FROM AUTHOR]

Software documentation is a basic component of the software development process and it is very important in all the phases of a software system life cycle. It is plays a very important role from the point of view of both the software engineer and user. Software documentation usually includes textual documentation required by the Software engineering standards, API documentation, Wiki pages and source code comments. Surveys and studies indicate that the documentation is not always available and, if available, only partially addresses the developers’ needs, as it is often wrong, incomplete, out-of-date and ambiguous. In the context of ERP – Enterprise Resource Planning, the relevance of the software documentation is even more important due to the complexity of such a kind of software systems and the strategic role they have within operative organizations. This paper focuses on the quality assessment of the documentation of ERP open source systems with the aim of understanding if they include high quality documentation for adequately support anyone want to adopt them and/or executing maintenance activities. Specifically, a quality model is defined and its application to three Open source software system is performed. [ABSTRACT FROM AUTHOR]

• State and trait anxiety are highly prevalent in people with multiple sclerosis (PwMS). • State anxiety is more frequent among subjects with a recent MS diagnosis. • PwMS and clinically relevant state anxiety more often display MRI disease activity. • Trait anxiety is more prevalent among female PwMS with higher severity of fatigue. • Both state and trait anxiety are associated with higher depression severity. Anxiety represents one of the most prevalent psychiatric symptoms in multiple sclerosis (MS), impacting the overall disease burden and quality of life. This psychopathological feature can be expressed as state (S-ANX) and trait (T-ANX) anxiety, but few studies specifically evaluated these two components in MS. The present study was aimed at investigating the prevalence and specific correlates of S-ANX and T-ANX in a cohort of people with MS (PwMS). 88 in- and out-patients with MS were consecutively recruited. S-ANX and T-ANX were evaluated with the two subscales of the State and Trait Anxiety Inventory. Bivariate analyses were performed to compare PwMS who displayed clinically significant S-ANX and T-ANX and those who did not. Two logistic regression models were run in order to identify variables significantly associated with S-ANX and T-ANX. S-ANX and T-ANX presented a prevalence of 42% and 45.5%, respectively. S-ANX was more frequent in subjects hospitalized due to recent MS onset. PwMS and S-ANX more frequently had a recent relapse, as well as evidence of disease activity on brain magnetic resonance imaging. Subjects with T-ANX were more often females and displayed higher severity of fatigue. Depressive features at the Beck Depression Inventory were more severe in both S-ANX and T-ANX subjects. PwMS with S-ANX reported a higher prevalence of T-ANX and vice versa. At the logistic regressions, depression severity displayed a significant association with S-ANX and T-ANX. We also detected positive associations between S-ANX and inpatient status, as well as between T-ANX and female sex. Both S-ANX and T-ANX are highly prevalent features in PwMS. These two components of anxiety should be adequately identified and discriminated in the clinical practice. The higher severity of depression in PwMS with clinically significant anxiety should not be neglected. [ABSTRACT FROM AUTHOR]

Objective: To develop an in vivo model for rapid assessment of cartilage aggrecan degradation and its pharmacological modulation.Design: Tumor necrosis factor-alpha (TNFalpha) was injected intra-articularly (IA) in rat knees and aggrecan degradation was monitored at various times following challenge. Articular cartilage was assessed for aggrecan content by Safranin O staining and by immunohistochemistry for the NITEGE epitope. Synovial fluids (SFs) were analyzed for sulfated glycosaminoglycans (GAGs) using the dimethylmethylene blue dye assay and for aggrecan fragments generated by specific cleavage at aggrecanase-sensitive sites by Western blot analysis with neoepitope antibodies. Indomethacin, dexamethasone, and an aggrecanase inhibitor were evaluated for their ability to modulate TNFalpha-induced proteoglycan degradation in vivo.Results: (1) IA injection of TNFalpha in the knee joint of rats resulted in transient aggrecan degradation and release of aggrecanase-generated aggrecan fragments from the articular cartilage into the SF; (2) a correlation was observed between histologically assessed depletion of aggrecan from the articular cartilage and the appearance of specific neoepitopes in the SF; (3) aggrecan degradation was inhibited by an aggrecanase inhibitor as well as by dexamethasone, but not by the non-steroidal anti-inflammatory drug (NSAID), indomethacin.Conclusion: TNFalpha injection in the knee joints of rats results in rapid transient cartilage proteoglycan degradation, mediated by cleavage at the aggrecanase sites. Biomarker read-out of specific neoepitopes in the SF enables the use of this mechanism-based model for rapid evaluation of aggrecanase-mediated aggrecan degradation in vivo. [ABSTRACT FROM AUTHOR]

Background: Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding.Study Design: The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score).Conclusion: The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503). [ABSTRACT FROM AUTHOR]

The search for flexibility in the new product development (NPD) entails an increasing need for integration of services and products (servitization). Hence, companies aim at maximizing the customer perceived value, which may demand new capabilities development, besides marketing, engineering and manufacturing. This paper suggests that the ‘customer service’ functional area has a central role in this context, since it deals with customers’ problems in a front-end position, and its knowledge can help other functional areas to develop required capabilities for servitization. Moreover, the level of knowledge transfer (KT) among different functional areas is also proposed as an essential activity to improve the servitization process. Thus, the aim of this paper is to investigate the moderator role of both the customer service area and the KT activities in the impact of the NPD related functional areas on servitization performance. For this purpose, the paper presents a cross-industry survey with 83 Brazilian companies, analyzed by means of an Ordinary Least Square (OLS) regression. Results show that the last border to transcend the servitization barriers in NPD is the integration of the customer service area to the other main functional areas of NPD. Moreover, our findings indicate which areas are the most critical ones in order to address an intensive KT activity to enhance the servitization performance. [ABSTRACT FROM AUTHOR]

Enterprise Open Source Software is continuously gaining acceptance in business organizations. This is essentially due to the understanding of the potential benefits deriving from the adoption of OSS project solution. Indeed, Open Source Software solutions offer great opportunities for cost reduction and quality improvement, especially for small and medium enterprises that typically have to address major difficulties due to the limited resources. In this direction it is relevant understand and gain knowledge regarding the evolution of such software over systems the time. This paper report results of an empirical study aimed at analyzing the evolution of most relevant ERP open source system during their lifetime. [ABSTRACT FROM AUTHOR]

Numerical models are instrumental to more effective flood forecasting and managementservices though they suffer from numerous uncertaintysources. An effective model calibration is hence essential. In this research work,a methodology of optimal sampling design has been investigated and developed forwater drainage networks. Optimal hydrometer sensors locationsalong the Amato River (South Italy)have been defined by optimizing a two-objective function that maximizes the calibrated model accuracy and minimizesthe total metering cost. This problem has been solved by using an enumerative search solution, run on the ENEA/CRESCO HPC infrastructure, evaluating the exact Pareto-front byefficient computational time. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has heavily impacted social, economic and health systems worldwide. Necessary confinement measures have, in turn, contributed to the occurrence of several stress-related conditions and deterioration of pre-existing mental conditions, including insomnia. The present study sought to investigate the occurrence and severity of insomnia during the COVID-19 lockdown among psychiatric patients and in the general population in the largest Italian sample examined to date. Potential factors associated with a risk of developing insomnia in the global sample were examined as well. A sample of 20,720 people (5.5% of them being psychiatric patients) was assessed through an online survey conducted during lockdown between March and May 2020. To investigate the occurrence and severity of sleep related issues, the Insomnia Severity Index (ISI) was used. In order to evaluate factors associated with the severity of insomnia in the global sample, multivariate linear regression models were performed. During the lockdown, patients with pre-existing mental disorders reported a mean higher score on the ISI scale (p < 0.001) compared to the general population. According to the multivariate regression models, the first three weeks of lockdown were significantly associated with a higher risk of insomnia, but the risk disappeared in the fourth week. Other associated factors included: the presence of a pre-existing mental disorder, ages 24 to 64 years old, and/or being female (p < 0.001). Although containment measures represent essential public health strategies to avoid the spread of the COVID-19 pandemic, sleep was one of the aspects affected during the early stages of the lockdown in both people with pre-existing mental disorders and general population. As an integral part of COVID-19 intervention, it is useful to raise awareness about these issues and to adopt both preventive and therapeutic interventions. • Insomnia represents a relevant issue during the COVID-19 pandemic. • Higher levels of sleep deterioration were reported in psychiatric patients. • Initial exposure weeks to the lockdown were significantly associated with risk of insomnia, although this risk was found to be less relevant at the end of the containment measures. • Being psychiatric patients and female gender were related with risk of insomnia. • It may be useful to adopt both preventive and therapeutic interventions in anticipation of future pandemics. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer screening may reduce disease-related mortality by early-stage detection of cancers. Aims To study the effect of a single immunochemical faecal occult blood test (i-FOBt) screening round on reduction in colorectal cancer-related-mortality among average risk subjects. Methods Comparison of 5-year mortality rates in 3 cohorts from a Northern Italian province: (1) colorectal cancers detected at the 1st biennial round of a mass-screening programme targeting 50–69 years old subjects, (2) non-screening cancers symptomatically diagnosed during the same time period, and (3) cancers detected in the pre-screening biennium. Multivariate analyses were performed with the Cox regression model including tumour node metastasis (TNM) stage at diagnosis, anatomical distribution of cancers, age at diagnosis, gender and patient group. Kaplan–Meyer survival estimates and log-rank test for equality of survivor functions were calculated. Results Stage distribution significantly differed between screening and non-screening colorectal cancers: 73% of screen-detected colorectal cancers were stages I and II versus 43% and 40% of non-screening and pre-screening colorectal cancers. Cumulative 5-year mortality rate was significantly lower in screening compared to non-screening or pre-screening colorectal cancers patients (19% versus 37% and 41%, p < 0.001). Conclusions Colorectal cancers were detected at earlier stages in i-FOBT-positive subjects in comparison with non-screening patients; colorectal cancers found at screening had a significantly improved 5-year survival. [ABSTRACT FROM AUTHOR]

This paper aims to identify bundles of Healthcare 4.0 (H4.0) digital applications and measure the impacts of their adoption on patient-centered performance. We conducted an empirical-exploratory study based on a survey with 119 middle/senior managers from different hospitals. Multivariate data techniques were applied to identify the H4.0 bundles, create combined adoption measures and analyze associations between H4.0 adoption and performance. Configuration theory provided the theoretical underpinnings to explain the relationships among the investigated elements. Four bundles of H4.0 digital applications were proposed: Smart Healthcare Supply Chain, Smart Patient Diagnosis, Smart Patient Treatment, and Smart Patient Follow-up. We found that high H4.0 adoption scores in hospitals positively impact patient-centered performance, measured through five indicators (patient readmission rate, mortality rate, length-of-stay, satisfaction, and safety). As the utilized measures for H4.0 digital applications were initially raised from academic works and validated based on practitioners' perceptions, the establishment of bundles brings a more practical oriented framework with a strong theoretical background, which is still scarce in the literature. Instead of addressing a wide range of concerns related to H4.0, the proposed bundles focus on the most popular and relevant aspects in a hospital with a significant impact on patients' interests. • Identification of bundles of Healthcare 4.0 (H4.0) and their association with patient-centered performance • Survey with 119 middle and senior managers from different hospitals • Four constructs of H4.0 digital applications were validated • These bundles positively affect patient-centered performance in hospitals [ABSTRACT FROM AUTHOR]

Abstract: Background: Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFVs) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries. Methods: We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery. Results: The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate. Conclusion: The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFVs. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU. [Copyright &y& Elsevier]

Abstract: The alignment degree existing between a business process and the supporting software systems strongly affects the performance of the business process execution. Methodologies and tools are needed for detecting the alignment level and either keeping a business process aligned with the supporting software systems even when they evolve or increasing its level by identifying convenient software changes. This paper improves an approach previously proposed for managing alignment. In particular, a new set of metrics have been introduced in the existing approach for business goals and dynamic behavior to evaluate the alignment. The application of the new approach is explored through a case study. [Copyright &y& Elsevier]

In the last years, the alignment issue was addressed in several researches and numerous methods, techniques and tools were proposed. Indeed, the business and IT performance are tightly coupled, and enterprises cannot be competitive if their business and IT strategies are not aligned. This paper proposes a literature review useful for evaluating different alignment approaches, with the aim of discovering similarity, maturity, capability to measure, model, asses and evolve the alignment level existing among business and technological assets of an enterprise. The proposed framework is applied to analyse the alignment research published in the Information & Management journal and the Journal of Strategic Information Systems, that are the ones that more published on this topic. The achieved evaluation results are presented. [ABSTRACT FROM AUTHOR]

Summary: In this study, we investigated the prognostic value of metastasis tumor antigen 1 expression in 81 untreated patients with ovarian cancer. The expression of metastasis tumor antigen 1 was evaluated by immunohistochemistry, and staining was analyzed in relation to clinicopathologic variables, disease-free survival, and overall survival. High expression of metastasis tumor antigen 1 was found to be associated with advanced stage (I/II versus III/IV, P = .02) and with worse response to first-line treatment (P = .03). Cases with high metastasis tumor antigen 1 expression showed a lower disease-free survival compared with cases with low expression (P = .02). In multivariate analysis of disease-free survival, metastasis tumor antigen 1 overexpression retained an independent negative prognostic role (P = .04), when considered together with histotype, stage of disease, residual tumor at surgery, and chemosensitivity. The evaluation of the prognostic relevance of metastasis tumor antigen 1 in late-stage disease showed that overexpression was a prognostic factor for poor disease-free survival and overall survival in this subset of patients, in both univariate and multivariate models. These findings indicate that metastasis tumor antigen 1 overexpression can be used as a predictor of clinical outcome in patients with ovarian cancer and therefore may represent a new prognostic marker. [Copyright &y& Elsevier]

Summary: Objective: To characterize pain-related behavior during the course of knee osteoarthritis (OA) induced by destabilization of the medial meniscus (DMM) in wild type (WT) and in ADAMTS-5 null mice. Methods: DMM surgery was performed in the right knee of CD-1 mice. At regular intervals up to 8 weeks after surgery, mice were assessed for the following parameters: mechanical allodynia (via withdrawal thresholds to von Frey filaments applied to the plantar surface of both hind paws or to the tail), thermal hyperalgesia, locomotor activity and gait analysis. In addition, mechanical allodynia was tested in C57BL/6 WT or ADAMTS-5 null mice following DMM surgery. Results: In CD-1 mice, a robust and progressive decrease in withdrawal threshold was observed in both hind paws after DMM but not sham surgery. Allodynia was apparent as early as 14 days postoperatively. Both sexes developed OA changes after surgery with concurrent mechanical allodynia. No other pain-related behavioral changes were detected up to 8 weeks post-surgery. In C57BL/6 mice, a genetic background in which only males develop OA changes after DMM, males but not females developed allodynia in the ipsilateral hind paw. In contrast, C57BL/6 ADAMTS-5 null mice did not develop OA changes or mechanical allodynia up to 8 weeks post-surgery. Conclusion: Joint pathology following DMM surgery in mice is associated with progressive mechanical allodynia. ADAMTS-5 null mice are resistant to DMM-induced OA-like lesions and to the associated mechanical allodynia. [Copyright &y& Elsevier]

Summary: Objective: To develop an in vivo model for rapid assessment of cartilage aggrecan degradation and its pharmacological modulation. Design: Tumor necrosis factor-α (TNFα) was injected intra-articularly (IA) in rat knees and aggrecan degradation was monitored at various times following challenge. Articular cartilage was assessed for aggrecan content by Safranin O staining and by immunohistochemistry for the NITEGE epitope. Synovial fluids (SFs) were analyzed for sulfated glycosaminoglycans (GAGs) using the dimethylmethylene blue dye assay and for aggrecan fragments generated by specific cleavage at aggrecanase-sensitive sites by Western blot analysis with neoepitope antibodies. Indomethacin, dexamethasone, and an aggrecanase inhibitor were evaluated for their ability to modulate TNFα-induced proteoglycan degradation in vivo. Results: (1) IA injection of TNFα in the knee joint of rats resulted in transient aggrecan degradation and release of aggrecanase-generated aggrecan fragments from the articular cartilage into the SF; (2) a correlation was observed between histologically assessed depletion of aggrecan from the articular cartilage and the appearance of specific neoepitopes in the SF; (3) aggrecan degradation was inhibited by an aggrecanase inhibitor as well as by dexamethasone, but not by the non-steroidal anti-inflammatory drug (NSAID), indomethacin. Conclusion: TNFα injection in the knee joints of rats results in rapid transient cartilage proteoglycan degradation, mediated by cleavage at the aggrecanase sites. Biomarker read-out of specific neoepitopes in the SF enables the use of this mechanism-based model for rapid evaluation of aggrecanase-mediated aggrecan degradation in vivo. [Copyright &y& Elsevier]

[Display omitted] Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, −8 and −13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37 – 39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC 50 of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design. [ABSTRACT FROM AUTHOR]

• Main teaching practices and information and communication technologies (ICTs) used to teach operations management (OM) in emerging economies during COVID-19. • Effect of contextual characteristics on the adoption level of those teaching practices and ICTs. • Relationship between the adoption of ICTs and OM teaching practices during COVID-19. • OM lecturers and professors located in emerging economies that have been teaching during COVID-19 outbreak were surveyed. • ICTs positively relate with OM teaching practices in emerging economies, although in a much less extent than expected. The objective of this article is three-fold. First, it aims at identifying the main teaching practices and information and communication technologies (ICTs) used to teach Operations Management (OM) in emerging economies during COVID-19 outbreak. Second, it investigates the effect of contextual characteristics on the adoption level of those teaching practices and ICTs. Third, this study examines the relationship between the adoption of ICTs and OM teaching practices during COVID-19 outbreak. Expectedly, schools around the world have pivoted to online learning and digital classrooms. Thus, OM lecturers and professors located in emerging economies that have been teaching during COVID-19 outbreak were surveyed. The collected data was analyzed through multivariate techniques. Findings indicate that lecturers and professors have been remarkably adopting specific teaching practices and ICTs to teach OM. Nevertheless, when considering the contextual characteristics of the universities, departments, and lecturers/professors, the adoption level of those practices and ICTs may significantly vary, especially depending on subject type and teaching experience. Moreover, we empirically verified that ICTs positively relate with OM teaching practices in emerging economies, although in a much less extent than expected. This research provides OM instructors guidelines to better plan their courses and subjects in face of extreme disruptive moments, such as the one caused by the COVID-19. Understanding how the concurrent utilization of ICTs and teaching practices helps OM programs to continue developing their activities is particularly important for universities located in emerging economies, since they are more likely to struggle with resources scarcity and more financially humble students. [ABSTRACT FROM AUTHOR]

• Influence of contingencies on the healthcare 4.0 (H4.0) adoption and barriers. • 159 managers from 16 hospitals located in Brazil, India, Mexico and Argentina. • Contingencies' effect is more prominent on H4.0 technologies adoption than barriers. • Hospitals' managers can anticipate issues inherent to emerging economies. Studies on the influence of contingency factors on the introduction of novel digital technologies into high-complexity systems, such as hospitals, are still incipient. As the introduction of Healthcare 4.0 (H4.0) usually implies in high capital expenditures and requires a more skilled labor force, such understanding gains relevance when considering hospitals in emerging economies, more likely to be resource-constrained. This study examines the effect of five contingency factors on the adoption of H4.0 technologies and associated barriers to H4.0 adoption in emerging economies; they are: hospital's ownership and age, number of employees, number of inpatient beds, and functionality (teaching hospital or not). The analysis is based on a transnational survey with 159 middle and senior managers from 16 hospitals, located in Brazil, India, Mexico and Argentina. Results indicate that contingencies do affect both H4.0 technologies adoption and associated barriers although not homogeneously in terms of effect, being more prominent on technologies' adoption than on barriers to H4.0 implementation. Our study sheds light on these relationships, providing hospitals' managers a means to anticipate potential issues and handle eventual difficulties inherent to the context in which they are inserted. [ABSTRACT FROM AUTHOR]

• Long-term remission of Multiple Sclerosis-related trigeminal neuralgia is uncommon. • Patients with higher disability undergo surgery earlier and more frequently. • Higher disability is associated less frequently with long-term to pain remission. The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common. [ABSTRACT FROM AUTHOR]

Abstract: We detected a novel CLN1 mutation (c.125-15t>g) in two Italian siblings. The clinical phenotype is that of a variant late-infantile neuronal ceroid lipofuscinosis and consisted of early-onset visual loss, psychomotor deterioration, and seizures. Ultrastructurally, granular osmiophilic deposits were found in skin biopsy of both patients. The novel mutation occurs in the acceptor sequences for splicing and leads to skipping of multiple exons. This predicts a protein lacking part or all of the active site of the enzyme and the palmitate-binding pocket. Consequently, biochemical activity of the palmitoyl protein thioesterase-1 enzyme was drastically reduced. The new mutation was not identified in a large set of ethnically matched control chromosomes. Our findings support the notion that CLN1 patients are not rare in Southern Europe and facilitate DNA-based mutation and carrier testing in this family. [Copyright &y& Elsevier]

Background: Minimally invasive hysterectomy may require the use of morcellation to remove the uterus. In the presence of unexpected sarcoma, morcellation risks disseminating malignant cells and worsening survival outcomes. As a consequence, in 2014 the US Food and Drug Administration issued a black box warning against the use of power morcellator for the treatment of uterine fibroids. However, the proportion of unexpected sarcoma at the time of hysterectomy for presumed benign indication remains unclear.Objective: The objective of the study was to estimate the incidence of sarcoma among women undergoing hysterectomy for benign indication in Olmsted County, MN, between 1999 and 2013.Study Design: We conducted a population-based study including all hysterectomies performed for benign indication in Olmsted County women between Jan. 1, 1999, and Dec. 31, 2013. Cases were identified using the medical records-linkage system of the Rochester Epidemiology Project, and data were abstracted by a gynecologist who reviewed the complete medical records of each woman who underwent hysterectomy. An expert pathologist reviewed the pathologic slides of each sarcoma to ensure the accuracy of the diagnosis. Incidences of sarcoma (overall and by type of sarcoma) were estimated both overall and stratified by menopausal status, indication for surgery, and uterine weight as a rate per 100 persons.Results: A total of 4232 hysterectomies were performed during the study period. Among them, we identified 16 sarcomas, of which 11 (69%) were suspected preoperatively and 5 (31%) were unexpected. Of the total number of hysterectomies, 3759 (88.8%) were performed for benign indication. Among those, the incidence of unexpected sarcoma was 0.13% (5 per 3759 [95% confidence interval, 0.04-0.31%]). Uterine fibroids comprised 27.3% of all hysterectomies for benign indication (n = 1025) and was the indication most commonly associated with diagnosis of unexpected sarcoma. The incidence of unexpected sarcoma among surgeries for uterine fibroids was 0.35% (3 of 851) for premenopausal women and 0.57% (1 of 174) for peri/postmenopausal, and all 4 unexpected sarcomas were leiomyosarcoma. The incidence of unexpected sarcoma progressively increased with higher uterine weight with an incidence of 0.03% (1 of 2993) among women with a uterine weight <250 g vs 15.4% (2 of 13) with a uterine weight ≥2000 g.Conclusion: Unexpected uterine sarcoma was low in all women undergoing hysterectomy for benign indication (0.13% or 1 in 752 surgeries) while it was increased in women with uterine fibroids (0.39% or 1 in 256 surgeries). Peri/postmenopausal women, women with large uteri, and age ≥45 years were risk factors for sarcoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to analyze in a large series of unresectable advanced ovarian cancer (AOC) patients the prognostic role of pathological response to neoadjuvant chemotherapy (NACT). STUDY DESIGN: We retrospectively evaluated 322 unresectable AOC patients treated with NACT followed by interval debulking surgery (IDS). Pathological response was classified as follows: complete (cPR) in the absence of residual disease, microscopic (microPR) in the presence of microscopic tumor foci (maximum diameter <=3 mm), and macroscopic (macroPR) when macroscopic residual disease was detected. RESULTS: cPR was observed in 21 (6.5%), microPR in 104 (32.3%), and macroPR in 197 (61.2%) patients. No differences were observed in the distribution of baseline clinicopathological characteristics between the groups. Median progression-free survival was 36 months in cPR, 16 in microPR, and 13 in macroPR (P = .001). Median overall survival was 72 months in cPR, 38 in microPR, and 29 in macroPR (P = .018). The survival differences between microPR and macroPR patients were not confirmed when the analysis included only cases resected to no gross residual disease at IDS. cPR retained the independent prognostic role in the multivariate analysis. International Federation of Gynecology and Obstetrics stage IV was the only negative independent predictor of cPR ([chi](2) = 5.362, P = .021). CONCLUSION: cPR is an uncommon event in AOC patients receiving NACT and is associated with a longer progression-free survival and overall survival compared with women showing no cPR, even in patients receiving IDS with no gross residual disease. The proposed classification of pathological response may serve in the next future as an easily assessable and highly valuable prognostic tool in this clinical setting. [ABSTRACT FROM AUTHOR]