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Introduction The association between the level of physical activity and quality of cardio-pulmonary resuscitation (CPR) performed by laypeople is unclear. The aim of this study was to evaluate the associations between physical activity level and laypeople performance during an eight-minute scenario of CPR. Materials and methods This study was a secondary analysis of the MANI-CPR Trial. The entire cohort of participants was grouped based on the level of physical activity assessed using the International Physical Activity Questionnaire (IPAQ) into a “low-moderate” level group and a “high” level group. Descriptive statistics were used for unadjusted analysis and multivariate logistic and linear regression models were also performed. Results A total of 492 participants who reached the score of “Advanced CPR performer” at the 1-min final test monitored by Laerdal Resusci Anne QCPR were included in this analysis; 224 with a low-moderate level and 268 with a high level of physical activity. A statistically significant difference was found for the outcome of percentage of compressions with adequate depth (low-moderate group: 87.8% [41·4%-99·3%], high group: 97% [63·2%–100%]; P = 0·003). No associations remained significant after controlling for biometric characteristics of the participants, compression protocols and sex. Conclusion Adequate quality CPR may not need high baseline level of physical activity to be performed by a lay rescuer.

Introduction: Optimizing maintenance of weight loss for people with obesity following intragastric balloon (IGB) therapy hinges on the degree to which health care providers can recognize both the impact of emotional problems and mood difficulties on their capacity to self-manage, and requirements for additional support. However, there is limited research on the psychological correlates of IGB therapy. This systematic review, for the first time, attempts to identify and synthesize the empirical evidence for the reciprocal influence between psychological variables and IGB outcomes. Methods: A literature search was performed in the PubMed, SCOPUS, MEDLINE, and Google Scholar databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed using rigorous inclusion criteria and screening by at least 2 reviewers. The selected articles were assessed for quality using the Strengthening the Reporting of Observational Studies Epidemiology (STROBE) checklist. Data were extracted to address the review aims and presented as a narrative synthesis. The review protocol was preregistered (Prospero CRD42019121291). Results: A total of 16,179 titles, 14,369 abstracts, and 51 full-text articles were screened, of which 16 studies were included. Findings suggest that female gender, older age, basic educational level, and single/divorced civil status, together with lower levels of depression, binge eating, higher perceived quality of life, and motivation to change were predictors of enhanced IGB treatment outcomes. Dissatisfaction with treatment was higher in those with impaired obesity-related social-life difficulties. The IGB treatment was effective in reducing weight and improving depression, anxiety, eating disorder symptoms, and the overall life quality of patients with obesity – mainly within 6 months from the device positioning and in conjunction with conventional therapies. Discussion/Conclusion: In line with the available literature on obesity and bariatric surgery interventions, poor mental health appears to be an important barrier for successful weight loss among patients with obesity undergoing IGB treatment. In order to improve the efficacy and effectiveness of the IGB therapy, more comprehensive and standardized studies are needed to provide insight into the psychological mechanisms maintaining weight management issues.

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sjögren’s syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies., Currò et al. investigate the prevalence of RFC1 expansions in a cohort of patients with chronic idiopathic axonal polyneuropathy. RFC1 expansions were found in 34% of patients with sensory neuropathy, but in none with sensory-motor neuropathy. Clinical features and diagnostic clues that should lead to suspicion of RFC1 neuropathy are discussed.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare tumours of gastrointestinal tract, extremely rare in anal canal. We report a case of misdiagnosed MiNEN in a 38-year-old woman initially conservatively treated for a supposed anal fistula. In a second proctological evaluation, biopsy of the anal neoformation was performed and the histological specimen diagnosed a MiNEN. The complete staging showed a disseminate disease and the patient started a chemotherapy schedule. After 6 months, stable disease was revealed at the last imaging performed and radical surgery was offered to the patient that is actually on oncological follow-up without recurrence at 1 year.

Background Scaphoid proximal pole fractures with avascular necrosis represent a complex surgical problem. Many reconstruction techniques are based on osteosynthesis with a vascularized or nonvascularized bone graft. These procedures do not allow early mobilization and therefore sometimes lead to unsatisfying functional results. In some cases, it is possible to perform a scaphoid hemiarthroplasty using a pyrocarbon implant (adaptive proximal scaphoid implant [APSI]) in place of the necrotic proximal pole, allowing an early mobilization and delaying palliative treatments such as 4-corner arthrodesis or proximal row carpectomy. Methods In this study, we reviewed all patients who had undergone a scaphoid hemiarthroplasty using APSI in our institutions from 1999 to 2017; the F.U. was performed through radiographic, clinical, and subjective (Disabilities of the Arm, Shoulder, and Hand) analysis. Results The performances of scaphoid proximal pole implants are encouraging; radiographic, clinical, and subjective outcomes were good, and the functional recovery proved to be fast and reliable over time. Conclusions This study reports our experience in the use of APSI implants, which proved to be a good alternative to traditional techniques for treating avascular necrosis of the proximal pole, still allowing further surgical steps in case of clinical worsening over time (wrist osteoarthritis). These patients are usually young and present high functional demands. Our experience is promising, but we believe that further evaluation over time will be needed.

Objective Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p, Synopsis The prevalence of patients with early-stage endometrial cancer (EC) has been lower during coronavirus disease 2019 (COVID-19) pandemic than before its onset. Further evidence is needed to assess the impact of COVID-19 pandemic on survival outcomes of EC patients.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control). Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65–0.80 and 0.61–0.75, respectively, p Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.

The goal of this paper is to advance the understanding of the impact of hard switching on the dynamic performance of GaN-based HEMTs. To this aim, we developed a fast (10 V/ns) on-wafer system for testing devices in hard switching. The system has been used to study the reliability of several WG = 2 mm p-type GaN HEMTs with different LGD or buffer properties. First, we show that by optimizing the drain node capacitance, we can speed-up the hard-switching transition to a few ns, even on-wafer level. Second, repeating the experiment by using multiple frequencies, from 1 kHz to 100 kHz, we demonstrate that, in real-world applications, cumulative turn-on stress has a much stronger effect on RON compared to off-state stress. Third, by comparing the results on identical devices having shorter LGD, we pinpoint hot electrons as the main mechanism in the device degradation, ruling out the contribution of self-heating. Finally, by comparing three wafers with different processing conditions (different passivation, different buffer) we suggest that trapping phenomena related to hot electrons happen in ns time scale and that the properties of the buffer can significantly impact the dynamic performance of the devices in hard switching.

Background: Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection caused by John Cunningham virus (JCV) reactivation, potentially associated with natalizumab (NTZ) treatment for Multiple Sclerosis (MS). The anti-JCV antibodies titre (JCV index) increases during NTZ treatment; however, the effects of other disease-modifying therapies (DMTs) on the JCV index have not been fully explored. Objective: The aim of the study was to evaluate changes in the JCV index during treatment with several DMTs. Methods: This longitudinal study evaluated the JCV index before starting DMT (T0) and during treatment with DMT (T1). Results: A total of 260 participants (65.4 % females, mean age 43 ± 11.3 ) were enrolled: 68 (26.2 %) treated with fingolimod (FTY), 65 (25 %) rituximab or ocrelizumab (RTX/OCR), 37 (14.2 %) dimethyl-fumarate (DMF), 29 (11.2 %) cladribine (CLD), 23 (8.8 %) teriflunomide (TFM), 20 (7.7 %) interferon or glatiramer acetate (IFN/GA), and 18 (6.9 %) alemtuzumab (ALM). At T1, the percentage of patients with JCV index 1.51 was found to be significantly reduced in the RTX/OCR group (51.6 % versus 37.5 %, p = 0.04). In the FTY group, a significant reduction in the percentage of patients with JCV index Conclusion: DMTs with a T and/or B depleting mechanism of action induced a significant reduction in the JCV index. These results may suggest new possible sequencing strategies potentially maximizing disease control while reducing the PML risk.

The ongoing trend from mass-produced to mass-customized products with batch sizes as small as a single unit has highlighted the need for highly adaptable robotic systems with lower downtime for maintenance. To address these demands, this article proposes the development of a novel reconfigurable collaborative robot (cobot), which has the potential to open up many new scenarios within the rapidly emerging flexible manufacturing environments. As the technological contribution, we present a complete hard- and software architecture for a quickly reconfigurable EtherCAT-based robot. This novel approach allows to automatically reconstruct the topology of different robot structures, composed of a set of body modules, each of which represents an EtherCAT slave. As the theoretical contribution, we propose a method to obtain in an automatic way the kinematic and dynamic model of the robot and store it in universal robot description format (URDF) as soon as the physical robot is assembled or reconfigured. The method also automatically reshapes a generic optimization-based controller to be instantly used after reconfiguration. While this article focuses on reconfigurable manipulators, the proposed concept can support arbitrary serial kinematic tree-like configurations. We demonstrate the contributions with examples of the following: how the topology of the robot is reconstructed and the URDF model is generated, and a Cartesian task application for a cobot built with the basic modules, demonstrating the quick reconfigurabilty of the system from a 4-degrees-of-freedom (DOF) robot to a 5-DOF robot, in order to satisfy new workspace requirements.

To investigate the correlation between choroidal vascularity index and the enlargement of geographic atrophy (GA) lesion secondary to age-related macular degeneration during the 2-year follow-up.In this longitudinal observational study, 26 eyes (26 patients, mean age 75.7 ± 8.8 years) affected by GA were included. Choroidal vascularity index was calculated in the subfoveal 3000-µm area. The main outcome measure included correlation analysis between baseline choroidal vascularity index and the rate of GA enlargement.During the 2-year follow-up, the mean GA area increased from 6.99 ± 5.28 mm2 to 10.69 ± 6.61 mm2(P0.001), accounting for a growth rate of 0.35 ± 0.20 and 0.31 ± 0.17 mm/year after the square root transformation in the first and second year of follow-up, respectively. Stromal choroidal area significantly decreased during the 2-year follow-up (P = 0.002). Interestingly, there was a significant correlation between the baseline choroidal vascularity index and the rate of GA enlargement (r=-0.432, P = 0.027) and between stromal choroidal area and the rate of GA enlargement (r = 0.422, P = 0.032). No other significant relationship was disclosed among choroidal parameters with the rate of GA enlargement.Choroidal vascularity index impairment is strictly related to the rate of GA enlargement during the 1-year and 2-year follow-up in patients affected by GA. For this reason, choroidal vascularity index could be considered a predictor of GA progression in the clinical setting, and it could be considered as a new potential biomarker in the efficacy evaluation of new GA interventions.

Background/aim: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. Materials and methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

The rise of data platforms has enabled the collection and processing of huge volumes of data, but has opened to the risk of losing their control. Collecting proper metadata about raw data and transformations can significantly reduce this risk. In this paper we propose MOSES, a technology-agnostic, extensible, and customizable framework for metadata handling in big data platforms. The framework hinges on a metadata repository that stores information about the objects in the big data platform and the processes that transform them. MOSES provides a wide range of functionalities to different types of users of the platform. Differently from previous high-level proposals, MOSES is fully implemented and it was not conceived for a specific technology. Besides discussing the rationale and the features of MOSES, in this paper we describe its implementation and we test it on a real case study. The ultimate goal is to take a significant step forward towards proving that metadata handling in big data platforms is feasible and beneficial.

BACKGROUND The radial artery is recommended by international guidelines as the default vascular access in patients with acute coronary syndromes (ACS) managed invasively. However, crossover from radial to femoral access is required in 4-10% of cases and has been associated with worse outcomes. No standardised algorithm exists to predict the risk of radial crossover. AIMS We sought to derive and externally validate a risk score to predict radial crossover in patients with ACS managed invasively. METHODS The derivation cohort consisted of 4,197 patients with ACS undergoing invasive management via the randomly allocated radial access from the MATRIX trial. Using logistic regression, we selected predictors of radial crossover and developed a numerical risk score. External validation was accomplished among 3,451 and 491 ACS patients managed invasively and randomised to radial access from the RIVAL and RIFLE-STEACS trials, respectively. RESULTS The MATRIX score (age, height, smoking, renal failure, prior coronary artery bypass grafting, ST-segment elevation myocardial infarction, Killip class, radial expertise) showed a c-index for radial crossover of 0.71 (95% CI: 0.67-0.75) in the derivation cohort. Discrimination ability was modest in the RIVAL (c-index: 0.64; 95% CI: 0.59-0.67) and RIFLE-STEACS (c-index: 0.66; 95% CI: 0.57-0.75) cohorts. A cut-off of ≥41 points was selected to identify patients at high risk of radial crossover. CONCLUSIONS The MATRIX score is a simple eight-item risk score which provides a standardised tool for the prediction of radial crossover among patients with ACS managed invasively. This tool can assist operators in anticipating and better addressing difficulties related to transradial procedures, potentially improving outcomes.

The Internet of Vehicles aims to fundamentally improve transportation by connecting vehicles, drivers, passengers, and service providers together. Several new services such as parking space identification, platooning and intersection control—to name just a few—are expected to improve traffic congestion, reduce pollution, and improve the efficiency, safety and logistics of transportation. Proposed end-user services, however, make extensive use of private information with little consideration for the impact on users and third parties (those individuals whose information is indirectly involved). This article provides the first comprehensive overview of privacy and trust issues in the Internet of Vehicles at the service level. Various concerns over privacy are formalised into four basic categories: privacy of personal information, trust, consent to provide information, and multi-party privacy. To help analyse services and to facilitate future research, the main relevant end-user services are taxonomised according to voluntary and involuntary information they require and produce. Finally, this work identifies several open research problems and highlights general approaches to address them. These especially relate to measuring the trade-off between privacy and service functionality, automated consent negotiation, trust towards the IoV and its individual services, and identifying and resolving multi-party privacy conflicts.

Interventional cardiologists are significantly exposed to X- rays and no dose of radiation may be considered well tolerated or harmless. Leaded aprons protect the trunk and the thyroid gland, leaded glasses protect the eyes. The operator's legs, arms, neck and head are, instead, not fully protected. In fact, the operator's brain remains the closest part to the primary X-ray beam and scatter in most interventional procedures and specifically the physician's front head is the most exposed region during device implantation performed at the patient's side. After the initial description of cases of brain and neck tumours, additional reports on head and neck malignancies have been published. Although a direct link between operator radiation exposure and brain cancer has not been established, these reports have heightened awareness of a potential association. The use of lead-based cranial dedicated shields may help reduce operator exposure but upward scattered radiation, weight and poor tolerability have raised concerns and hindered widespread acceptance. The purpose of this review is to describe current knowledge on occupational X-ray exposure of interventional cardiologists, with a special focus on the potential risks for the head and neck and efficacy of available protection devices.

Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.

PurposeThis paper analyses the impact of digitalization in the marketing of geographic indication (GI) products. Specifically, the objective is to provide a systemic and comprehensive view of marketing issues and challenges arising from evolving digitalization in the agriculture sector.Design/methodology/approachThe authors employed an explorative cognitive mapping technique on a sample of key informants among Italian companies and a consortium of registered food, spirits and wine products.FindingsThis study describes the key concepts dominant in the discourse of informants concerning digitalization and its influence on the GI market. Three clusters and two loops were also identified to explain the relationship among key concepts, which stress changes regarding the relationship with the consumer, product experience and innovation, and the integration between physical and virtual space.Research limitations/implicationsThis is the first attempt to apply cognitive maps to GIs. However, the study does have limitations: it was conducted on a small number of producers and was restricted to only Italy. Another limitation is that interviews were conducted during the COVID-19 pandemic.Practical implicationsThe results suggest important practical implications that stress the need for learning and increased digital competences for the efficient embedding of digital technologies in all business areas, increase product value and innovation, and the need for governance in support of digital transformation.Originality/valueThis work creates the new and valuable literature on food marketing and, specifically, on a changing market environment resulting from digitalization, by providing a holistic overview of digitalization in reference to the marketing of GIs.

To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years.Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered.A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small ( 10 mL) (74%), medium (49%), or large ( 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment.Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN.• Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Aims Carpal tunnel (CT) syndrome is a recognized red‐flag of cardiac amyloidosis (CA) and increased cardiovascular (CV) morbidity. We designed this study to characterize the CV profile of patients with CT syndrome at the time of first surgery and to identify high‐risk presentations. Methods and results We retrospectively reviewed 643 patients who underwent CT surgery between 2007 and 2019. Of them, 130 patients (77 years, 45% male patients, left ventricular ejection fraction 62%) with available CV characterization within ±12 months from CT surgery were included. Abnormal loading conditions causing cardiac left ventricular hypertrophy (LVH) were investigated to distinguish explained LVH (Ex‐LVH) from unexplained LVH (Un‐LVH). LVH was found in 66 (51%) patients, 33% of them presented Un‐LVH. Compared with the others, Un‐LVH patients were older (77 and 75 vs. 70 years in Un‐LVH, Ex‐LVH, and non‐LVH, respectively; P = 0.002), had higher rates of electrocardiogram‐echo discrepancy (70%, 14.3%, and 1.6%, respectively; P

The deployment of bioenergy has turned into a severe issue associated with energy security and greenhouse gas reduction. The development of technologies in the renewable energy market depends on the profitability of their investment. However, the Net Present Value of new technologies’ investment is affected by technical and economic uncertainties. Hence, the probability assessment of a positive Net Present Value and identifying critical economic and technical parameters can inform investors and decision-makers about any investment risks. This study evaluates the overall uncertainty in the Net Present Value of investment in cogeneration plants composed of a gasifier fed with biomass and a bottoming Internal Combustion Engine fed by the gasification product gas. Monte Carlo simulation assesses the probability of a positive Net Present Value for three sizes of cogeneration plants. Regarding sizes, the chance of generating a positive Net Present Value ranges from 66% to 90%, while the larger plants have a higher chance. The sensitivity analysis findings show that above all, biomass cost and then the sale price of electricity and the quantity of gasification product gas are the most dominant parameters. Using an internally produced biomass waste resource and possible achievement of green energy certificates on energy produced would make the initiative successful.

Context Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction. Objective Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed. Methods In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action. Results From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported. Conclusions Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency.

The CC5 and CXC3 chemokines (CK) pathways are involved in the pathogenesis and outcome of several disease states, including chronic hepatitis C (CHC). The kinetics of Regulated upon Activation Normal T cell Expressed and Secreted (RANTES) (CCL5) and IP-10 (CXCL10) during direct-acting antivirals (DAA) treatment was retrospectively analyzed in 18 liver transplant recipients (LT-R) compared with 20 patients with CHC and 49 healthy controls (HC). CK levels were determined at baseline, week 4, end of treatment, 24 weeks post-treatment (sustained virological response [SVR]), and later-on during follow-up (FU), 12 and 24 months post-DAA. At baseline, median RANTES levels were higher in HC than in both LT-R (

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Nowadays, buildings are responsible for large consumption of energy in our cities. Moreover, buildings can be seen as the smallest entity of urban energy systems. On these premises, in this article, we present a flexible and distributed cosimulation platform that exploits a multimodeling approach to simulate and evaluate energy performance in smart buildings. The developed platform exploits the Mosaik cosimulation framework and implements the functional mock-up interface standard in order to couple and synchronize heterogeneous simulators and models. The platform combines in a shared simulation environment: 1) the thermal performance of the building simulated with EnergyPlus; 2) a heat pump integrated with a proportional–integral–derivative control strategy modeled in Modelica to satisfy the heating demand of the building; 3) an electrical energy storage system modeled in MATLAB Simulink; and 4) different Python models used to simulate household occupancy, electrical loads, photovoltaic production, and smart meters, respectively. The platform guarantees a plug-and-play integration of models and simulators, in which one or more models can be easily replaced without affecting the whole simulation engine. Finally, we present a demonstration example to test the functionalities, capability, and usability of the developed platform and discuss future developments of our framework.

This chapter presents a novel distributed software infrastructure to enable energy management and simulation of novel control strategies in smart cities. In this context, the following heterogeneous information, describing the different entities in a city, needs to be taken into account to form a unified district information model: internet-of-things (IoT) devices, building information model, system information model, and georeferenced information system. IoT devices are crucial to monitor in (near-) real-time both building energy trends and environmental data. Thus, the proposed solution fulfills the integration and interoperability of such data sources providing also a correlation among them. Such correlation is the key feature to unlock management and simulation of novel energy policies aimed at optimizing the energy usage accounting also for its impact on building comfort. The platform has been deployed in a real-world district and a novel control policy for the heating distribution network has been developed and tested. Finally, experimental results are presented and discussed.

© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80-0.89) and 0.90 (0.86-0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75-0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model's ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions., This study was supported in the Netherlands by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813,733050103 and 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), the European Joint Programme—Neurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); V.V. and S.K. have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 666992 (EuroPOND). E.B. was supported by the Hartstichting (PPP Allowance, 2018B011); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1); J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); I.J.S. is supported by the Alzheimer’s Association; J.B.R. is supported by the Wellcome Trust (103838); in Spain by the Fundació Marató de TV3 (20143810 to R.S.V.); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198) and by grant 779357 ‘Solve-RD’ from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529–2014-7504, Swedish Research Council (VR) 2015–02926, Swedish Research Council (VR) 2018–02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla Tjänarinnor, Karolinska Institutet Doctoral Funding and StratNeuro. H.Z. is a Wallenberg Scholar.

Objective To compare vascular complications in patients undergoing percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) using ultrasound guidance (USG) versus fluoroscopy guidance (FSG) for femoral access. Background In patients undergoing PCI, using the arterial femoral access increases the risk of vascular complications compared using the radial access. USG reduces time to access, number of attempts, and vascular complications compared with FSG, but the efficacy of USG has never been tested in the setting of CTO-PCI. Methods A total of 197 patients undergoing CTO-PCI using at least a femoral vascular access from November 2015 to September 2020 were screened. The primary outcome was a composite of local hematoma, pseudoaneurysm , retroperitoneal hemorrhage , arteriovenous fistula or hemoglobin drop ≥3 g/dL during hospitalization. The independent association between USG and the primary outcome of interest was explored. Results The primary outcome occurred in 17.3% of patients. Patients in the USG group had a significantly lower incidence of vascular complications compared with patients in the FSG group (8.5% vs. 21.0%, p = 0.039), driven by a reduction of localized hematomas (3.4% vs 13.0%, p = 0.042). After adjustment for type of CTO approach and heparin dose, USG was significantly associated with a reduced relative risk of the composite primary outcome (adjusted odds ratio 0.16, 95% confidence interval 0.05 to 0.51; p = 0.002). Conclusion USG in CTO-PCI is associated with a decreased risk of vascular complications, primarily driven by a reduction in local hematomas, especially in complex CTO-PCI where the larger use of heparin increases the risk of vascular complications.

Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.

BACKGROUND A number of patient-reported outcome measure (PROMs) instruments are used to assess shoulder pain, function, and postoperative satisfaction. Computer adaptive tests (CAT) have been developed in an effort to tailor question delivery, decrease time to completion and floor/ceiling effects, and increase compliance. Previous investigations have demonstrated excellent correlation between Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity CAT (UE-CAT) and American Shoulder and Elbow Surgeons (ASES) instruments, indicating that the PROMIS UE-CAT may be an acceptable alternative to the ASES. Prior to widespread adoption, however, rigorous psychometric validation must be performed. Thus, the purpose of this study was to evaluate the psychometric properties of PROMIS UE-CAT relative to the ASES score in patients undergoing primary rotator cuff repair (RCR). METHODS A retrospective study of an institutional RCR registry was performed from July 2018 through March 2019. Preoperative PROMIS UE-CAT and ASES scores were collected. Floor and ceiling effects were determined, and convergent validity was established through Pearson correlations. Rasch partial credit modeling was used for psychometric analysis of the validity of PROMIS UE-CAT and ASES question items, a previously established methodology for assessing shoulder PROMs. Person-item maps were generated to characterize the distribution of question responses along the latent dimension of shoulder disability. RESULTS Responses from 107 patients (107 shoulders) were included. PROMIS UE-CAT had a strong correlation to ASES (r=0.684; P

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe. Objective: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice. Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or 90% or Results: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors. Conclusion: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

To report outcomes of a multi-staged approach for endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) by fenestrated/branched endografting (F/B-EVAR).Between 2010 and 2020 (June), patients undergoing F/B-EVAR for TAAAs were collected. Data of cases managed by a multi-staged approach, to reduce the incidence of spinal cord ischemia (SCI), were retrospectively analyzed and reported in a cohort study. Thirty-day mortality and SCI were assessed as study's outcomes.One hundred and thirty-seven patients underwent TAAAs repair by F/B-EVAR. A multi-staged approach was applied in 73(53%) cases, more frequently for Crawford's extent I-III (60/78) compared with IV (13/59) (P0.0001). A complete TAAAs exclusion was achieved in 2, 3 or 4 steps in 64(88%), 8(11%) and 1(1%) cases, respectively, within the same hospitalization in 68(93%) cases. The mean time between first and last step was 16 ± 8days, with a mean hospital stay of 21 ± 12days. In 3(4%) cases the complete TAAA repair was not achieved due to inter-steps mortality (2) or permanent paraplegia (1). There were no cases of aortic rupture or target visceral vessels occlusions between the different steps. Seven (10%) patients suffered postoperative SCI with 2(4%) cases of permanent paraplegia. In 5/7 cases SCI occurred after the first stage; in 3/5 cases TAAAs exclusion was successfully completed with total SCI recovery. The 30-day mortality was 4% (3/73).A multi-staged endovascular repair with F/B-EVAR can be safely performed for TAAAs repair. The majority of cases can be treated within a single, long hospitalization. The cost/effectiveness of the prolonged in-hospital time should be evaluated.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

Objectives: Contrast induced nephropathy occurs in up to 7.5% of cases in endovascular aortic repair (EVAR). Carbon Dioxide (CO2) has been proposed as an alternative agent to iodinated contrast medium (ICM); however, specific protocols are not universally adopted, and the visualization of the renal arteries may be suboptimal in some cases. The aim of this study was to analyze our CO2-EVAR experience with automatic injections, in order to identify the anatomical characteristics associated with the best visualization of all the aortic vessels, with particular attention to the lowest renal artery (LoRA). Methods: From 2016 to 2019, all EVAR performed with either CO2 or ICM were analyzed and compared. CO2-EVAR was performed using an automated injector (600 mmHg pressure; 100 cc volume); a small amount of ICM was injected in case of difficulty in LoRA visualization or doubts at the completion angiogram. Clinical and CT-Scan preoperative characteristics were considered. The study endpoints were technical success, amount of ICM and radiation dose, postoperative renal function and possible CO2-related adverse events. Statistical analysis was by Fisher's exact, t-Student, Mann-Whitney tests and ROC curve. Results: In the considered period, 321 EVAR procedures, 72 (22.4%) with CO2 and 249 (77.6%) with ICM, were performed. The two groups were similar for clinical characteristics and preoperative renal function. ICM was injected in a significantly lower amount in the CO2-EVAR group (52.8 ± 6.1 vs. 88.1 ± 9.2 cc, p ± 377394.6 mGy/cm2 CO2-EVAR vs. 332301.8 ± 230139.3 mGy/cm2 ICM-EVAR, p=0.001). Postoperative eGFR decreased significantly less in the CO2-EVAR (2.3 ± 1.1 ml/min) compared with the ICM-EVAR group (10.6 ± 5.3 ml/min), p 24.5 mm was predictive of LoRA visualization (72.1% sensitivity, 73.8% specificity). Three CO2-EVAR cases had intraoperative transient hypotension with no consequences. Sixteen/72 (22.2%) CO2-EVAR procedures were performed using 0 cc of ICM. Conclusions: CO2-EVAR by automated injections is safe and requires a lower amount of ICM if compared with ICM-EVAR, with a consequent significant benefit on postoperative renal function. If specific anatomical situations are present, ICM may be completely unnecessary. The radiation dose is however significantly higher, therefore procedural protocols need further refinements.

Background: Direct locoregional treatments were recently proposed for the local control of cervical and distant metastasis of thyroid cancer, but data on their use as part of a multimodality approach for primary thyroid tumors are poor. In this feasibility study, laser ablation (LTA) was successfully used for the initial debulking of unresectable radioiodine-refractory thyroid cancer in sequential therapy with Tyrosine-Kinase Inhibitors (TKI). Case Presentation: A 69-year-old woman underwent partial resection of papillary thyroid cancer with extensive tracheal infiltration. Post-treatment whole-body scan (131I, 8140 MBq) showed the absence of cervical thyroid uptake. The patient experienced a rapid increase in her cervical mass associated with dysphonia, dyspnea, and dysphagia. Due to a concomitant severe hypertensive state and cardiac failure, the patient was treated with LTA after a multidisciplinary consultation. After local anesthesia, two 300 nm optic fibers were inserted into the lesion through 21G spinal needles. Two illuminations with 4-watt output power and 3600 Joules energy delivery were performed with a diode-laser source. LTA resulted in rapid cancer debulking, and mass volume decreased from 23.9 to 7.5 mL resulting in significant improvement of pressure symptoms. Three months later, the patient was started on lenvatinib due to the initial regrowth of the tumor mass. The cervical tumor burden was controlled by TKI for 20 months when a rapid disease progression occurred, and the patient died. Discussion: Locally advanced, unresectable, and radioiodine-refractory thyroid tumors can be managed with a novel multimodality approach. The initial debulking with LTA of the locally aggressive disease results in rapid control of the tumor burden threatening patients’ life and is effectively followed by long-term control with TKI treatment. Conclusion: Based on this experience, sequential multimodality treatment with an initial locally directed laser ablation procedure followed by TKI therapy may be considered as a salvage option in patients with unresectable and rapidly progressive RR thyroid tumors.

To date, there are no standardized systemic treatment options for patients with metastatic pituitary carcinoma progressed to chemo and radiation therapy. Immune-checkpoint inhibitors (ICIs) have been successfully assessed in other solid malignancies and could be a concrete hope for these patients. We performed a critical review of the literature aimed to evaluate studies assessing ICIs in pituitary malignancies. We also conducted research about published translational data assessing immune-contexture in these malignancies. Some preliminary reports reported a successful administration of pembrolizumab or the combination between nivolumab and ipilimumab in patients with metastatic ACTH-secreting pituitary carcinomas. Translational data suggest that adenomas secreting growth hormone and ACTH have a suppressed immune-microenvironment, which could be more likely to benefit from ICIs. Immune-checkpoint inhibitors can be an effective treatment in patients with pituitary carcinoma and maybe also recurrent adenoma. Tumors secreting growth hormone and ACTH are more likely to benefit from ICIs due to a different immune-microenvironment.

In a context of high demand for hospital services among older people, we aimed to assess the rate and determinants of inappropriate hospitalizations of older patients, and to what extent they were associated with inappropriate hospital stay. This prospective observational multicentre study evaluated a random sample of consecutive patients aged ≥ 70 years accessing the Emergency Department (ED) of two Italian tertiary hospitals. A standardized comprehensive geriatric assessment was carried out in each patient, including the Blaylock Risk Assessment Screen Scale (BRASS) for identification of patients at risk of difficult discharge. Inappropriate hospitalization was defined by the ED physician when patients did not necessitate hospital-provided procedures but was due to social reasons or lack of an alternative care-setting. Among 1877 patients (median age 80.7 years, 50.1% male), with a high prevalence of functional dependence and social isolation (around 30% and 25%, respectively), 767 (40.9%) were hospitalized. Incidence of inappropriate hospitalization was 14.6% (95% CI 12.1%-17.1%) and was associated with moderate-high risk of difficult discharge at BRASS (OR = 1.98, 95% CI 1.16-3.39, p = 0.013) and the presence of dementia with behavioural disorders (OR = 1.79, 95% CI 1.10-2.91, p = 0.020). Compared with patients appropriately admitted, inappropriate hospitalizations had shorter length of hospital stay but accounted for 1059/9154 days of stay (11.6%). Inappropriate hospitalizations occurred in less than 15% of cases, mainly accounted for by patients no longer manageable at home, but contributed to the greatest proportion of inappropriate hospital stay. These findings highlight the need of implementing appropriate home-care services and ensuring rapid access to suitable care-facilities for community-dwelling frail older patients.

Background Nursing home (NH) residents have been dramatically affected by COVID-19, with extremely high rates of hospitalization and mortality. Aims To describe the features and impact of an assistance model involving an intermediate care mobile medical specialist team (GIROT, Gruppo Intervento Rapido Ospedale Territorio) aimed at delivering “hospital-at-nursing home” care to NH residents with COVID-19 in Florence, Italy. Methods The GIROT activity was set-up during the first wave of the pandemic (W1, March–April 2020) and became a structured healthcare model during the second (W2, October 2020–January 2021). The activity involved (1) infection transmission control among NHs residents and staff, (2) comprehensive geriatric assessment including prognostication and geriatric syndromes management, (3) on-site diagnostic assessment and protocol-based treatment of COVID-19, (4) supply of nursing personnel to understaffed NHs. To estimate the impact of the GIROT intervention, we reported hospitalization and infection lethality rates recorded in SARS-CoV-2-positive NH residents during W1 and W2. Results The GIROT activity involved 21 NHs (1159 residents) and 43 NHs (2448 residents) during W1 and W2, respectively. The percentage of infected residents was higher in W2 than in W1 (64.5% vs. 38.8%), while both hospitalization and lethality rates significantly decreased in W2 compared to W1 (10.1% vs 58.2% and 23.4% vs 31.1%, respectively). Discussion Potentiating on-site care in the NHs paralleled a decrease of hospital admissions with no increase of lethality. Conclusions An innovative “hospital-at-nursing home” patient-centred care model based on comprehensive geriatric assessment may provide a valuable contribution in fighting COVID-19 in NH residents.

Background For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. Methods We included all children aged Results Incidence of children commencing KRT Conclusions We found a stable incidence and increasing prevalence of European children on KRT 2007–2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

A 57-year-old man with severe aortic valve stenosis at high surgical risk underwent transcatheter valve replacement with a 29-mm Edwards Sapien-3 valve (Edwards Lifesciences). The valve was successfully implanted using the right femoral access, but at the end of the deployment the balloon ruptured (Videos 1 and 2) and could not be retrieved from the e-Sheath. The Commander delivery system was then readvanced in the aorta over the wire (Video 3), which was snared and externalized using a 25-mm AndraSnare (Andramed GmbH) inserted through the left femoral artery using a 25-cm-long 22-F Cook sheath (Cook Medical) (Figure 1). Then, the Commander was pushed over the wire, across the aortic bifurcation, making the ruptured balloon get into the Cook sheath (Figure 2). The Commander was then truncated (Figure 3), and the ruptured balloon proximal part attached to the pusher/balloon catheter unit was retrieved through the eSheath (Figure 4). Then, the ruptured balloon distal part attached to the inner balloon shaft was pushed forward such that it could be externalized through the left femoral sheath, cut (Figure 5), and finally pulled back with the wire through the eSheath (Figure 6).

Introduction The aim of our study is to describe the management of a maternity ward in a referral center during the COVID-19 pandemic and 2020 lockdown. Methods This is a retrospective single-center study. We analyzed the records of all women consecutively admitted to our delivery ward during lockdown and compared them with those of women admitted in the same period in 2019. Results The number of patients (1260) admitted to our department in 2020 was similar (1215) to that in 2019. Among patients admitted during lockdown, 50 presented with a Sars-CoV-2 infection (3.9%). In 2020, the number of antenatal check-ups was lower than in 2019 [7.9 (1.5) vs 8.2 (1.3), p

PurposeThis paper aims to highlight the importance of (public) value(s) and publicness in accounting and accountability research. It pinpoints a range of issues that scholars need to contemplate when reconsidering publicness in accounting research and practice.Design/methodology/approachThe paper adopts an interdisciplinary literature review associated with a conceptual discussion of the actual and future challenges of public service accounting and accountability in considering public value(s).FindingsThe paper illustrates the centrality of (public) value(s) at the individual, organizational and societal levels in shaping and being shaped by calculative practices, and shows that looking at the interconnections between values and accounting is a fruitful research avenue. Moreover, it highlights the power of embracing interdisciplinary approaches to illuminate these interconnections and relate them to complex and current phenomena.Originality/valueThe paper’s originality lies in the reconsideration of (public) value(s) for public service accounting scholars, providing a critical reflection and setting new research avenues.

Pathogenesis of endometriosis is still unclear and a role of both innate and adaptive immune system has been postulated. Some recent findings have revealed an increased risk to have concomitant autoimmune disease in women with endometriosis, but no study so far has investigated whether this association could affect endometriosis severity and stage. We retrospectively reviewed medical patients’ notes of women with a confirmed diagnosis of endometriosis who referred to our endometriosis outpatient clinic between January 2015 and December 2019. Cases (endometriosis and an autoimmune disease) were matched in a 1:3 ratio by age and study period with controls (endometriosis without history of autoimmunity). At univariate logistic analysis, concomitant autoimmunity (OR 2.63, 95% CI 1.64–4.21, p .002) emerged as factors significantly associated with the likelihood of stage IV endometriosis. In the multivariate logistic regression model, concomitant autoimmunity remained a significant predictor of stage IV endometriosis (OR 2.54, 95% CI 1.57–4.10, p = 0.004), whereas the association between the number of laparoscopic procedures performed and stage IV endometriosis was found to be of borderline-significance (OR 2.70, 95% 1.37–5.30, p = 0.050). Our findings suggest that endometriosis is more severe in patients who are also affected by autoimmune disturbances after controlling for relevant confounders.

Glioblastoma (GBM) is the most common primary tumor of the central nervous system. Arising from neuroepithelial glial cells, GBM is characterized by invasive behavior, extensive angiogenesis, and genetic heterogeneity that contributes to poor prognosis and treatment failure. Currently, there are several molecular biomarkers available to aid in diagnosis, prognosis, and predicting treatment outcomes; however, all require the biopsy of tumor tissue. Nevertheless, a tissue sample from a single location has its own limitations, including the risk related to the procedure and the difficulty of obtaining longitudinal samples to monitor treatment response and to fully capture the intratumoral heterogeneity of GBM. To date, there are no biomarkers in blood or cerebrospinal fluid for detection, follow-up, or prognostication of GBM. Liquid biopsy offers an attractive and minimally invasive solution to support different stages of GBM management, assess the molecular biology of the tumor, identify early recurrence and longitudinal genomic evolution, predict both prognosis and potential resistance to chemotherapy or radiotherapy, and allow patient selection for targeted therapies. The aim of this review is to describe the current knowledge regarding the application of liquid biopsy in glioblastoma, highlighting both benefits and obstacles to translation into clinical care.Implications for PracticeTo translate liquid biopsy into clinical practice, further prospective studies are required with larger cohorts to increase specificity and sensitivity. With the ever-growing interest in RNA nanotechnology, microRNAs may have a therapeutic role in brain tumors.

Objective: Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion: In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence: III

Purpose Constant and frequent technological changes within organizations call for further scholarly attention, as behavioural intentions need to be coupled also with future learning intentions to predict the present and prospective individual adaptations and performance. This study, grounded on the technology acceptance model, aims to examine the association between training opportunities and behavioural and future learning intentions also taking into account the role of task–technology fit as a moderator. Design/methodology/approach A survey was carried out within a single organization in the water processing sector on a sample of 200 workers who recently experienced a technological change through the adoption of System Application and Product in data processing. A moderated–mediation model was estimated through regression analyses with bootstrapping. Findings The results were consistent with study hypotheses. In particular, task–technology fit amplified the positive association between perceived ease of use and training opportunities as well as the indirect effect of this latter on both behavioural and future learning intentions through perceived ease of use and perceived usefulness. In sum, the hypothesized moderated–mediation model was confirmed. Originality/value Three novelty factors of this study can be stressed: it is among the few studies carried out on Italian workers in the realm of technology adoption, it expanded the technology acceptance model by including traditional behavioural intentions and future learning intentions as outcome variables and it integrated the task–technology fit perspective within the technology acceptance model.

© 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Background Patients in heart transplantation (HTx) waiting list for advanced heart failure (HF) are susceptible to acute deterioration refractory to standard HF medical therapies. Limited data are available on long‐term in‐hospital continuous intravenous (IV) inotropic therapy as bridge to definite therapies. Methods and results We reviewed medical records of all heart transplant recipients treated in the pre‐HTx phase with in‐hospital continuous IV inotropes at our institution between 2012 and 2018. We analysed data before the beginning of continuous IV therapy and at the moment of HTx. We report data of 24 patients (mean age of 43.5 ± 15.7 years) treated with IV inotropes as bridge to HTx (median follow‐up of 28 months after HTx). The main length of IV inotropic therapy was 84 ± 66 days (min 22; max 264 days). At the beginning, the most frequently used inotrope was dopamine (median dosage of 3 mcg/kg/min, interquartile range 2.5–3.75), alone (n = 11, 46%) or in combination with other inotropes (n = 13, 54%). In 18 patients, the class of inotropes was changed during the hospitalization. We registered a progressive improvement of perfusion markers and neuro‐hormonal activation. Conclusion In‐hospital continuous parenteral inotropic therapy may serve as a temporary pharmacological bridge to HTx in patients with advanced HF that are actively listed to HTx with good reply in terms of prognosis and perfusion markers.

Objectives To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II–III serous borderline ovarian tumors (BOTs). Methods A multi-institutional retrospective study was conducted within the MITO Group. Results A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91–179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5–57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6–167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. Conclusions Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.