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A resonant-cavity antenna is implemented assembling on an open-ended rectangular waveguide a wideband electromagnetic band gap (EBG), designed as a multilayer. Two different implementations of the multilayer are proposed, labeled as Cases A and B. As to Case A, a high-permittivity layer is embedded between two slabs of low permittivity, whereas a single layer of low permittivity, surrounded by two high-permittivity slabs, is employed in Case B. Successful performances of the broadband behavior are also dependent on the side length of the EBG, that is truncated to small footprints, with an effect of high sidelobe level (SLL). Therefore, grid layouts with nonuniform air holes are proposed for in-plane realization of the dielectric slabs. Their effect in the EBG superstrate is a nonuniform spatial reflectivity, that reduces the SLL keeping a good wideband response. In the EBG manufacturing, both numerically controlled machining techniques and 3-D printing have been employed. 3-D printing has been used for the low permittivity layers, realized in the polylactic acid (PLA) filament, allowing more flexibility in the fabrication of the grid slabs to custom layouts. Results of two antenna prototypes assembling the EBGs, with the parameters of Cases-A and -B and grid layout, to the waveguide source are reported.

The aims of this work are focused on the evaluation of the solid rocket motor residual thrust and on the impact of thermal protection properties on such thrust. Indeed, tail-off thrust of solid rocket motors upper stages can last tens of seconds after motor burn-out, affecting the performance of the rocket on sequencing of stage separation. Hence, the knowledge of the tail-off thrust profile is fundamental to properly design wait times and separation systems total impulse of a multi-stage launcher. Therefore, although it has been shown in the past that pyrolysis gases responsible for the residual thrust are mostly produced by alumina molten slag deposited next to the nozzle nose within the combustion chamber, this study is aimed at suggesting that the portion of the nozzle within the combustion chamber can act as the main radiative heat source leading to thermal protection material ablation, and then to residual thrust production. An analysis of an actual solid rocket motor has been performed in the direction of proving the effectiveness of the overall procedure. Then a sensitivity analysis with respect to the quantities identifying the thermal protection properties has been computed in order to evaluate the impact of such variations on the residual thrust profile.

Study Design: Retrospective study. Objective: Following SARS-CoV-2 pandemic break-out a lockdown period for the population and a reorganization of the Health System were needed. Hub-function Centers for time-dependent diseases were identified and Niguarda Hospital (Milan) was selected as main Regional Trauma Center. The purpose of our study is to report the experience of Niguarda Maxillofacial Trauma Team during this period, pointing out epidemiological changes in the presentation of trauma in comparison to the previous 3 years. Methods: Two hundred and sixteen patients were admitted to the Emergency Department from 8th March 2020 to 8th May 2020. One hundred and eighty-one had a diagnosis of Major Trauma and 36 had also facial fractures; 35 patients had isolated facial fractures. Data were compared to the activity during the same period in 2017-2019 and statistical analysis was carried out concerning demographic and clinical characteristics, trauma dynamics and positivity to COVID-19. Results: Cumulative curves of patients admitted because of Major Trauma describe a superimposable linear trend in years 2017-2019, while 2020 shows an increase from April 16th. Average age and number of more severe patients were higher than previous years. Epidemiological changes concerned road accidents, accidents involving pedestrians and cyclists, interpersonal violence, suicide attempts and domestic accidents. The incidence of facial fractures was confirmed through years and, according to its measured severity, 75% of patients required management. COVID-19 positivity without systemic symptoms didn’t influence the type of treatment. Conclusion: The COVID-19 lockdown offers a unique opportunity to study the reversal epidemiological effects on trauma.

Rationale and objectives Myxofibrosarcoma (MFS) is a common soft tissue sarcoma in the elderly patients with both clinical and magnetic resonance imaging (MRI) peculiar features: very high recurrence rate, relatively low risk of distant metastases. On MRI it shows an infiltrative pattern (“tail sign”) and high myxoid matrix content with water-like appearance on fluid-sensitive sequences. Due to these unusual characteristics, we propose a specific MRI grading system to stratify the risk of local recurrence (LR) and offer other prognostic information. Materials and methods: Two expert radiologists retrospectively and blindly reviewed preoperative MRI of 150 patients affected by MFS of the extremities treated at a single Institution. Myxoid matrix component and contrast enhancement of the tumor were evaluated and graded with a semiquantitative method. The presence of an infiltrative pattern, the depth of the tumor (deep and/or superficial) and tumor sizes were also recorded. MRI features were analyzed separately and correlated to LR risk, sarcoma specific survival and distant metastases rate. Then, according to the statistical significance of the correlation between MRI features and prognosis a 3-grade scoring system was proposed and evaluated to assess the risk of LR. Results: Mean age was 66.1 ± 14.4 years; mean follow-up was 16 ± 28.3 months. The MRI features most associated with higher risk of LR resulted to be: lesion sizes (both volume and maximum diameter with a cut-off of 20 cm – p = 0.01), the “tail sign” (p = 0.045), and high myxoid matrix content with MRI water-like appearance (p = 0.0493). Ninety-four patients (94 of 150- 62.7%) were grade 1, 33 (22.0%) grade 2, and 23 (15.3%) grade 3. Interobserver agreement was substantial with K= 0.779 (95%CI 0.685–0.874). Higher grades of MRI grading system proposed were significantly associated with an increased LR risk, hazard ratio = 2.031 (95%CI 1.366–3.019; p Conclusion: This is the largest series evaluating MRI features as prognostic factors for MFS. The MRI grading system proposed is significantly able to stratify the risk of LR in MFS of the extremities. The system is applicable to all the standard MRI studies protocols, might help in surgical planning, and may offer prognostic information.

Aims: To investigate the occurrence of myopathy with oral glucose-lowering drugs (OGLDs) and statins, with a focus on dipeptidyl peptidase-4 inhibitors (DPP4-is). Methods: The FDA adverse event reporting system (FAERS) was queried (2004–2016) to compare the proportion of adverse events with OGLDs, alone and in combination with statins, using the reporting odds ratio (ROR) with relevant 95% confidence interval (95%Cl), adjusted for sex, age and concomitant presence of other OGLDs/lipid-lowering drugs. Drug–drug interaction is claimed whenever the frequency of an event is enhanced by combination treatment. Consistency/robustness of findings was tested by applying additive/multiplicative models and accounting for competition bias (i.e., adverse events previously known to be associated with OGLDs were removed). Results: Over a 13-year period, we retrieved 142,888 cases of myopathy. The use of DPP4-is alone was not associated with higher reporting of myopathy (no. of cases = 4898; adjusted ROR = 1.00; 95%CI = 0.96–1.04), with the notable exclusion of vildagliptin (262; 1.64; 1.42–1.88). No increased occurrence emerged when used in combination with statins, with consistent findings from additive/multiplicative models for all DPP4-is. Likewise, no increased reporting was found for other OGLDs (28,964; 0.64; 0.62–0.67); data on the interaction with statins were consistent/robust across analyses only for sulfonylureas (the interaction is likely and biologically plausible) and sodium glucose cotransporter-2 inhibitors. Conclusions: Real-world FAERS data do not raise concern for muscular toxicity with DPP4-is in combination with statins, making a drug interaction very unlikely.

The aim of this study was to assess the risk of hospitalization associated with the concomitant prescription of 10 highly prevalent drug-drug interactions (DDIs) among all individuals aged ≥65 residing in Bologna's area, Italy. We used incidence density sampling, and the effect of current (last month) and past (≥30 days before) exposure to DDI was investigated through conditional multivariable logistic regression analysis. Two DDIs were associated with increased hospitalization due to DDI related conditions: ACE-inhibitors/ diuretics plus glucocorticoids (current DDI: OR 2.36, 95% CI 1.94-2.87; past DDI: OR 1.36, 95% CI 1.12-1.65) and antidiabetic therapy plus current use of fluoroquinolones (OR 4.43, 95% CI 1.61-11.2). Non-Steroidal Anti-inflammatory Drugs (NSAIDs) increased the risk of re-bleeding in patients taking Selective Serotonin Reuptake Inhibitors (OR 5.56, 95% CI 1.24-24.9), while no significant effect was found in those without a history of bleeding episodes. Concomitant prescription of NSAIDs and ACE-inhibitors/diuretics in patients with a history of high-risk conditions was infrequent. Within the pattern of drug prescriptions in the older population of Bologna's area, we distinguished DDIs with actual clinical consequences from others that might be considered generally safe. Observed prescribing habits of clinicians reflect awareness of potential interactions in patients at risk.

Objective: To evaluate patency of circummaxillary sutures in children with Apert, Crouzon, and Pfeiffer Syndromes and to compare it to a nonsyndromic matched control group. Design: Case–control study. Setting: Tertiary care public hospital. Materials and Methods: Thirty-eight computed tomography (CT) scans of patients affected by syndromic craniofacial synostosis (13 patients with Apert syndrome, 20 patients with Crouzon syndrome, and 5 patients with Pfeiffer syndrome), average age 5 ± 2.8 years, range 1.9 to 12 years, were compared to age- and sex-matched control CTs of 38 nonsyndromic children. Computed tomography scans of the study group had to be performed prior to any midfacial surgery. Main Outcome Measures: Midpalatal suture, zygomaticomaxillary sutures, and pterigomaxillary sutures were evaluated and scored. Results: The syndromic group showed a significant earlier ossification of all sutures compared to the nonsyndromic group. Significant differences were already present in early childhood and continued through adolescence. Conclusions: Based on the differences in terms of maxillary sutural ossification identified, midfacial hypoplasia does not seem to be only secondary to premature cranial base ossification, but also to primary synostosis of facial sutures, thus providing new insights into the pathogenesis of midface deficiency in children with craniofacial-synostosis. Care should be taken when planning any maxillary orthopedics, such as expansion or maxillary protraction, given the high frequency of early fusion of circummaxillary sutures.

Background: Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized. Objective: The aim of this study was to characterize the spectrum, frequency, and clinical features of ICI-related adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS). Patients and methods: AEs from FAERS (up to June 2018) recording ICIs (ipilimumab, nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab) as suspect were extracted. Comprehensive disproportionality analyses were performed through the reporting odds ratio (ROR) with 95% confidence interval (95% CI), using other oncological drugs as comparison. An overview of systematic reviews (OoSRs) was also undertaken to identify irAEs with consistent positive associations. Results: ICIs were recorded in 47,266 reports, submitted mainly by consumers receiving monotherapy with anti-PD1/PDL1 drugs. Three areas of toxicity emerged from both disproportionality analysis and the OoSRs (32 studies): endocrine (N = 2863; ROR = 6.91; 95% CI 6.60–7.23), hepatobiliary (2632; 1.33; 1.28–1.39), and respiratory disorders (7240; 1.04; 1.01–1.06). Different reporting patterns emerged for anti-CTLA4 drugs (e.g., hypophysitis, adrenal insufficiency, hypopituitarism, and prescribed overdose) and anti-PD1/PDL1 agents(e.g., pneumonitis, cholangitis, vanishing bile duct syndrome, tumor pseudoprogression, and inappropriate schedule of drug administration). No increased reporting emerged when comparing combination with monotherapy regimens, but multiple hepatobiliary/endocrine/respiratory irAEs were recorded. Conclusions: This parallel approach through contemporary post-marketing analysis and OoSRs confirmed that ICIs are associated with a multitude of irAEs, with different reporting patterns between anti-CTLA4 and anti-PD1/PDL1 medications. Close clinical monitoring is warranted to early diagnose and timely manage irAEs, especially respiratory, endocrine, and hepatic toxicities, which warrant further characterization; patient- and drug-related risk factors should be assessed through analytical pharmaco-epidemiological studies and prospective multicenter registries.

Given its approval for the treatment of cytokine release syndrome, tocilizumab is under investigation in severe coronavirus disease-2019. To characterize serious adverse events (AEs) with tocilizumab, we queried the worldwide FDA Adverse Event Reporting System and performed disproportionality analysis, selecting only designated medical events (DMEs) where tocilizumab was reported as suspect, with a focus on hepatic reactions. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL 95% CI) > 1. A total of 2,433 reports of DMEs were recorded with tocilizumab, mainly in rheumatic diseases. Statistically significant RORs emerged for 13 DMEs, with drug-induced liver injury (n = 91; LL 95% CI 3.07), pancreatitis (151; 1.41), and pulmonary fibrosis (222; 7.21) as unpredictable AEs. A total of 174 cases of liver-related DMEs were retrieved (proportion of deaths = 18.4%), with median onset of 27.5 days. These serious unpredictable reactions occurring in chronic real-world tocilizumab use may support patient care and monitoring of ongoing clinical trials.

The remarkable scientific progress in the treatment of patients with heart failure (HF) and reduced ejection fraction (HFrEF) has more than halved the risk of sudden cardiac death (SCD) in this setting. However, SCD remains one of the major causes of death in this patient population. Beyond the acknowledged role of beta blockers and inhibitors of the renin-angiotensin-aldosterone system (RAAS), a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNI), proved to reduce the overall cardiovascular mortality and, more specifically, the risk of SCD in HFrEF patients. The mechanism by which ARNI may reduce the mortality connected with harmful ventricular arrhythmias is not utterly clear. A variety of direct and indirect mechanisms have been suggested, but a favorable left ventricular reverse remodeling seems to play a key role in this setting. Furthermore, the well-known protective effect of implantable cardioverter-defibrillator (ICD) has been debated in HFrEF patients with non-ischemic cardiomyopathy (NICM) arguing against the role of primary prevention ICD in this setting, particularly when ARNI therapy is considered. The purpose of this review was to provide insights into the SCD mechanisms involved in HFrEF patients together with the current role of electrical therapies and new drug agents in this setting. [Figure not available: see fulltext.].

Patient safety is a great concern of healthcare institutions and the correct reporting and management of adverse events is a key element for supporting safety improvement efforts. Patient falls are the most frequent adverse event in hospitals and often cause serious patient outcomes. In this work, we describe the experience of the Local Healthcare Authority of Romagna, Italy that, within the framework of a quality and safety improvement programme, designed, developed and implemented a desktop application for monitoring inpatient falls. A multidisciplinary team created a software tool based on R, an open source software for statistical computing that, appropriately combined with the existing hospital information system, is used to obtain Shewhart u-control charts for monitoring the monthly fall rates. The tool had been implemented in twenty nine hospital units. The results indicate that the proposed application gave a valuable contribution in the safety improvement activities. Its usefulness extended beyond the “safety problem” as it also enabled hospital managers to identify a number of critical issues in data collection. As a result, where necessary, improvement actions had been implemented. Furthermore, the use of open source software led to a considerable cost reduction and facilitated customization of the software tool.

Background Regulatory agencies warned against fluoroquinolones for the management of minor infections because of the risk of emerging adverse events (collagen-associated adverse events, neuropsychiatric toxicity and long-term disability). We aimed to assess quality and credibility of evidence as well as causality regarding these putative associations. Methods MEDLINE, Scopus, Web of Science and PROSPERO were searched, from inception to August 2019, for systematic reviews with meta-analyses investigating emerging adverse events. Two investigators extracted data to grade quality (through validated AMSTAR-2 tool), rank credibility of the evidence (convincing, highly suggestive, suggestive, weak) through adapted criteria including E-value calculation, and assess causality (Hill's criteria). Results Seven systematic reviews of observational studies providing 16 risk estimates [seven, five and four, respectively, for aortic aneurysm/dissection (AAD), retinal detachment (RD) and any tendon disorders (ATD)] met inclusion criteria. No systematic reviews with meta-analysis investigating the risk of neuropsychiatric toxicity or long-term disability were found. The associations between fluoroquinolones and AAD/ATD showed highly suggestive credibility and were supported by strong evidence of causality (double increased risk, especially within first 2 months of treatment). Conflicting data concerning the emergence of RD were retrieved, resulting in weak evidence of causality. Quality of the evidence ranged from high to low for AAD, from moderate to critically low for RD, and it was moderate for ATD. Conclusion Our analysis supports credible, plausible and highly suggestive associations with AAD (rare occurrence but strong causality) and ATD. Limitations of both umbrella reviews and observational evidence should be considered.

ObjectiveTo describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls.MethodsConsecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups.ResultsA total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006).ConclusionWe found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

Purpose Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion. Methods Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose–volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0 × 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio Results A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5–55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS. Conclusion Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

BACKGROUND In multiethnic societies, it has frequently and repeatedly been shown that some minority groups have higher rates of traditional coronary artery disease (CAD) risk factors, different rates of treatment with revascularization procedures, and excess morbidity and mortality from CAD when compared with the white population. In the last two decades, Italy is becoming a diverse society with more than five millions of inhabitants from minority ethnic groups: for this reason, we decided to investigate whether ethnic differences in our metropolitan area are similar compared with the experience of Western countries. METHODS AND RESULTS We performed a retrospective cohort study of 1285 patients with acute coronary syndromes (ACS) hospitalized at Intensive Cardiac Care Unit (ICCU), Heart Center of ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy between 2014 and the end of 2019. Six percent of these patients were South-Asian, North-African, and South-American. Despite the younger age of nonwhite patients, their comorbid conditions and traditional cardiovascular risk factors showed peculiar differences. We did not observe any difference in terms of the number of coronary arteries involved at the enrollment, patients candidate to coronary artery bypass graft and either intra-hospital or at follow-up mortality. Nevertheless, the rate of re-infarction at follow-up was significantly higher in the nonwhite group. CONCLUSION We believe that a better knowledge and understanding of epidemiological changes in Italian society could improve our clinical practice, in particular, in order to better customize treatments and therapies.

In solid rocket motors, propellant debondings are very dangerous since they could cause an increment of the burning surface area and anticipate the exposure of case-insulating thermal protection material. Therefore, when a debonding internal zone is discovered, it is of primary importance to guarantee that the solid rocket motor is still able to accomplish the mission within its operational requirements. From a numerical point of view, debondings cannot be evaluated in an analytical, closed form due to their variety of shapes. The present study is aimed at assessing the impact of debondings through the adoption of advanced computer graphic techniques like the offsetting of the solid rocket motor burning surface discretized as a dynamic three-dimensional triangular mesh. Mesh handling algorithms are discussed in detail. Numerical results are obtained through an in-house simulation software which has been developed based on the aforementioned methods.

Collaborative projects imply a wide variety of skills, ranging from technical abilities to teamwork and problem-solving attitudes. Innovative teaching programmes focused on the use and promotion of open-source geospatial tools represent a key element in developing such transversal abilities. OpenStreetMap (OSM) brings into play open and collaborative dynamics that build a critical ecosystem where single contributions are part of collective intelligence. This initiative led to the foundation of structured contributors groups such as PoliMappers, the first European YouthMappers chapter based in Politecnico di Milano (Italy). Pursuing the objective to build a responsible student-led community of Free and Open Source Software users, in 2021 PoliMappers organised the course entitled “Collaborative and Humanitarian Mapping”. The programme is structured into 7 meetings and aims to introduce university students to the OSM environment with a focus on the potential of open data and related geospatial tools, especially in the humanitarian field. It has seen the participation of the World Food Programme, Open Knowledge Foundation, TECHO Colombia, IMM Design Lab, Map for Future, UN Mappers, Spazio Vita Niguarda Onlus, Ledha Milano, AUS Niguarda Onlus and Humanitarian OpenStreetMap Team. Enrolled attendants’ contributions have been assessed with tools for quality review and statistics. Also, Q&As and suggestions to the attendants have been collected to detect common issues. The paper presents the course, from the design to the assessment of the students’ activities, and the lessons learned in this experience in such a way to provide some guidance to those who want to organize similar initiatives.

Introduction The objective of this study was to evaluate short and long-term results of the application of the alternate rapid maxillary expansion/constriction (Alt-RAMEC) technique in patients with skeletal Class III malocclusion. Methods Forty-two white patients were consecutively treated with the Alt-RAMEC technique. The average age of the patients was 12.7 ± 1.6 years (range, 9.4-15.9 years) before protraction. The average age at long-term follow-up was 19.4 ± 2.8 years (range, 17.2-26.9 years). A sample of nontreated patients with Class III malocclusion from the archives of orthognatic surgery in our hospital was used as a control group. The initial records were matched for sex, the severity of Class III malocclusion, and age (mean, 12.1 ± 1.4 years; range, 9.7-14.1 years) with the old records available in the archive. The control sample had records presurgery (mean, 19.8 ± 2.2 years; range, 16.6-21.6 years). Results The sagittal advancement of A-point, after the application of the technique, was 5.43 ± 2.71 mm. Some mandibular dentoalveolar adaptation was noted. The position of the maxilla was stable in the long term. In contrast, the control group showed limited growth at the maxillary level during the long-term follow-up period. Conclusions Our results showed that the Alt-RAMEC technique, performed at the correct time, with a double-hinged expander, followed by Class III spring or elastic traction, 24 h/d, allows for satisfactory maxillary protraction, with stable long-term results. The comparison with a sample of matched nontreated patients with Class III malocclusion allowed to suggest the positive effect of the treatment on the maxillary position vs the natural evolution of the Class III skeletal discrepancy.

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory arteriopathy, considered a rare cause of coronary artery disease. Although familial cases have been described, no specific gene association has been detected so far. When the coronary vessels are involved, the main clinical scenarios are stable angina, acute coronary syndromes, left ventricular dysfunction, and sudden death. Specific clinical and angiographic findings may suggest this as the underlying disease, but certain diagnosis histological. The involvement of the lower and upper limbs is unusual; however, it may have decisive clinical implications for the most appropriate revascularization method and the selection of the arterial graft to be used.

A woman's first childbirth represents a moment of elevated maternal emotional vulnerability. Indeed, there is a prevalence of anxiety and depression symptomatology in primiparas during the postpartum period that negatively influences the well-being of the woman, of her newborn, and of the quality of their attachment bond. Much attention has been paid to the possible risk factors involved in the onset of mood disturbance in the postpartum. However, knowledge is still limited regarding the role played by the specific clinical aspects linked to labor. Therefore, the aim of the present study was to explore whether spontaneous or elective induction labor is linked to the level of postnatal depression and anxiety three months after birth. One hundred and sixty-one women (Mage = 31.63; SD = 4.88) were recruited, using the following inclusion criteria: native Italian women; age > 18 years; physically and psychologically healthy nulliparous with singleton no-risk pregnancy; no previous abortion or interruption of pregnancy; no previous psychopathological diagnoses. Exclusion criteria: twin pregnancy, fetal pathologies, and planned elective cesarean. Data was collected at two different times: T1 (day of childbirth) clinical data of labor (spontaneous or induced) from hospital records; T2 (three months after birth) level of mother's depression and anxiety. In order to explore if the level of depression and anxiety three months after childbirth differ in women according to the type of labor, spontaneous or induced, two univariate analyses of variance (ANOVA) were conducted. Results showed that women who had a spontaneous labor reported lower levels of anxiety and depression than women who had an induced labor. Our results highlight the significant implications that the mode of labor has on the emotional well-being of mothers, underlining the need to support women throughout all their transition to motherhood, including the childbirth experience.

Purpose Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. Methods The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). Results The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%,p < 0.001) and NS prostatectomy (58.4% vs. 52.9%,p = 0.04), but received LND less frequently (47.7% vs. 76.7%,p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS >= (4 + 3) and positive cancer cores >= 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. Conclusions PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Summary Background & aims Alpha-lipoic acid (ALA)-containing dietary supplements are widely used in clinical practice, although their safety assessment is under-investigated. We characterize the safety profile of ALA-containing products by analysing spontaneous reports of suspected adverse reactions (ARs). Methods Suspected ARs to ALA-containing products were extracted from the Italian Phytovigilance System (IPS), and scrutinized in terms of seriousness and causality (through WHO UMC system), with a specific focus on important (IMEs) and designated medical events (DMEs). To characterize the reporting profile from an international perspective, the WHO-VigiBase was also queried. Results From March 2002 to February 2020, out of 2147 total reports, 116 reports concerning 212 ARs to ALA-containing products were collected. Women were involved in 68.1% of cases. Skin (44.9%) and gastrointestinal disorders (10.8%) were the most frequently represented ARs. Causality assessment resulted as definite (15), probable (35), possible (24), unlikely (5), and unclassifiable (37). In 70% of cases, events occurred within 30 days of ALA use. Forty-five reports were serious (38.8%), being insulin autoimmune syndrome the most frequently reported (N = 10). IMEs were recorded in 20 cases, including four DMEs (3 angioedema and one anaphylactic shock). Similar distribution emerged from the 5641 reports in the WHO-VigiBase. Conclusions The remarkable reporting of unpredictable skin, immune and hepatic ARs, coupled with seriousness, strong causality and early onset, calls for a) careful risk-benefit assessment of ALA-containing products by regulators; b) awareness and monitoring by clinicians and c) continuous vigilance of their safety profile through valuable spontaneous reporting systems such as IPS.

Aims The aim of this study was to characterise clinical priority of adverse events with sacubitril/valsartan for targeting preventive measures. Methods We used the US Food and Drug Administration adverse event reporting system (worldwide pharmacovigilance database) to compare adverse events recording sacubitril/valsartan as suspect with other cardiovascular drugs. Disproportionality analyses were performed by calculating the reporting odds ratios, deemed significant when the lower limit of the 95% confidence interval was greater than 1. Clinical priority was assigned to adverse events with significant disproportionality by scoring (range 0–10 points) five features (number of events, magnitude of the lower limit of the 95% confidence interval, mortality frequency, important/designated medical event, biological plausibility). Results Sacubitril/valsartan was recorded in 20,021 reports, with 178 adverse events associated with significant disproportionality: 71.9%, 25.9% and 2.2% were classified as weak, moderate and strong clinical priorities, respectively. Increased reporting emerged for several cardiovascular adverse events, including ‘renal failure’ (N = 388; lower limit of the 95% confidence interval 2.26), ‘hyperkalaemia’ (314; 2.42) and ‘angioedema’ (309; 1.56). Sudden cardiac death (priority score 9 points) was the only designated medical event with strong clinical priority. Notably, sudden cardiac death occurred early after sacubitril/valsartan administration (average onset 124 days), with concomitant drugs known for pro-arrhythmic potential (e.g. amiodarone, escitalopram, mirtazapine, loop diuretics) in 26.2% of records. Conclusion The increased cardiovascular reporting of sacubitril/valsartan in the real world was largely predictable from pre-approval evidence, underlying disease and likely patients’ comorbidities. The unexpected reporting of sudden cardiac death occurred well before the complete development of positive electrical remodelling induced by sacubitril/valsartan, and calls for stringent clinical monitoring (to reduce the pro-arrhythmic burden related to co-medications), and further investigation on appropriate combination with other preventive measures.

A oftalmologia veterinária abrange o diagnóstico das alterações oculares, perioculares e retrobulbares primárias, e também suas manifestações sistêmicas e secundárias, o que se torna possível a partir da avaliação completa do bulbo ocular, órbita e anexos por meio do exame oftálmico completo e de exames complementares. Dentre os exames de imagens que auxiliam no diagnóstico das afecções oculares, a ultrassonografia está entre os exames de imagem mais utilizados na rotina veterinária, auxiliando na observação de anormalidades retrobulbares e na avaliação das estruturas bulbares na presença de opacificação de meios transparentes, por exemplo. Além da ultrassonografia, existem outras modalidades de exames, dentre eles a tomografia computadorizada, ressonância magnética, angiografia, microscopia especular, tomografia de coerência óptica (OCT) e angiografia por tomografia de coerência óptica (OCT-A). Em virtude dos avanços tecnológicos na obtenção de imagens, a avaliação globo ocular e das estruturas orbitárias pode ser realizada com maior precisão, o que favorece o diagnóstico e a escolha terapêutica adequada. Objetiva-se com esta revisão enumerar os exames disponíveis, suas principais indicações, bem como sua aplicabilidade e estudos em animais domésticos.

This article examines Natalia Oreiro, a film and television star who has contributed to representations of on-screen queer subjectivities in Latin America. I examine her film Miss Tacuarembó (Sastre 2010) as a musical that resignifies heteronormative notions of gender commonly found in popular family film genres. I consider the film’s layered intertexts such as choreography, pop songs, and telenovelas, as well as the role of Oreiro in resignifying those intertextual codes as signs of queerness. This article thus reveals the ways in which intertexts disrupt this formulaic family and young adult film.

Background Atopic dermatitis (AD) is a multifactorial long-standing inflammatory skin disease with a high incidence worldwide in both adults and children. According to the recognized correlation between skin and intestine-the so-called "gut-skin axis"-gut unbalances can affect skin by inducing systemic inflammation and triggering dermatological diseases such as AD. Objectives To evaluate the efficacy of a food supplement containing selected strains of probiotics in ameliorating AD symptoms and skin conditions in adult volunteers. Materials & methods Eighty adult subjects showing mild-to-severe AD, skin dryness, desquamation, erythema and itching were enrolled in a randomized controlled trial to receive, for 56 days, a placebo or a mixture of lactobacilli (L. plantarum PBS067, L. reuteri PBS072 and L. rhamnosus LRH020). The latter was chosen according to the patients' production of post-biotic metabolites and B-group vitamins, anti-inflammatory and anti-oxidant capacity and anti-microbial activity. Clinical and instrumental dermatological evaluation was performed at T0d, T28d and T56d, and then at T84d (after a one-month wash-out). Inflammatory cytokine levels from skin tape stripping, sampled close to AD lesions at T0d and T56d, were also measured. Results Subjects receiving the probiotic mixture showed an improvement in skin smoothness, skin moisturization, self-perception, and a decrease in SCORAD index as well as in the levels of inflammatory markers associated with AD at T28d, with a positive trend up to T56d which was maintained at T84d. Conclusions Administration of selected probiotic strains resulted in a fast and sustained improvement in AD-related symptoms and skin conditions.

Made available in DSpace on 2021-06-26T04:48:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Research question: Does the association of basal FSH and anti-Mullerian hormone (AMH) concentrations with post-IVF/intracytoplasmic sperm injection (ICSI) live birth change with maternal age? Design: A total of 2003 IVF/ICSI patients were stratified according to basal FSH/AMH in concordant favourable (CF; AMH >1 ng/ml and FSH 10 IU/l), discordant with favourable AMH (DFA) and discordant with favourable FSH (DFF) groups, as well as according to age in pre-advanced maternal age (pre-AMA; = 35, 37, 40). IVF/ICSI outcomes were compared among CF, CU, DFA and DFF groups, and the association of basal FSH and AMH concentrations with live birth was tested by univariate and multivariate analysis in total, pre-AMA and AMA groups, separately. Results: Different outcome patterns were observed in discordant AMH/FSH groups from different age categories; favourable basal FSH concentrations were associated with higher delivery rates in pre-AMA patients, but with lower delivery rates in AMA groups. Within pre-AMA patients, DFF patients presented higher delivery rates but lower oocyte yield compared with DFA patients. In the univariate analysis, favourable AMH (P < 0.02) and oocyte yield (P < 0.002) were positively associated with live birth in all AMA groups. The multivariate analysis revealed that favourable basal FSH, but not AMH or oocyte yield, is associated with live birth in pre-AMA patients independently of other variables (P = 0.012). Conclusions: The relationship of basal FSH and AMH with IVF/ICSI success changes with maternal age; basal FSH better reflects clinical outcomes probably determined by oocyte quality in pre-AMA patients, while AMH better suits AMA patients. Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil Reprod Med Ctr, Biogenesi, Monza, Italy ASST Monza, Dept Med Phys, Monza, Italy Clin Eugin, Modena, Italy Univ Modena & Reggio Emilia, Dept Med & Surg Sci Mother Children & Adults, Modena, Italy Sao Paulo State Univ, Inst Biosci, Dept Struct & Funct Biol, Botucatu, SP, Brazil

Aims This report describes the findings of the 2018 Italian Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC). Methods The Italian Catheter Ablation Registry systematically collects data on the ablation procedures performed in Italy. Data collection was retrospective. A standardized questionnaire was completed by participating centres. Results We collected data on 15 714 catheter ablation procedures performed in Italy during 2018 in 94 electrophysiology centres. In most centres (75/94, 80%), a single electrophysiology laboratory was available, and a hybrid electrophysiology laboratory was available in 15% (14/94) of centres. In most (93%) centres, at least two electrophysiologists were involved in the catheter ablation procedures. In only 13 out of 94 (14%) electrophysiology laboratories, an anaesthesiologist assists every electrophysiology procedure; in most cases (74/94, 79%), an on-demand anaesthesiology service was available. On-site cardiothoracic surgery was reported in 43 out of 94 (46%) centres.Nonfluoroscopic navigation systems were available in most centres (88/94, 93%). Intracardiac echocardiography was used in 59 out of 94 (63%) electrophysiology laboratories. Atrial fibrillation (31%) was the most frequently treated ablation target, followed by atrioventricular nodal re-entrant tachycardia (20%) and cavo-tricuspid isthmus (15%). In 61.7% of all procedures, a 3D mapping system was used. In about one-third of procedures, a near-zero approach was performed. Conclusion In most Italian electrophysiology centres, a single electrophysiology laboratory was available and at least two electrophysiologists were involved in the ablation procedures. An increasing number of procedures were performed by means of a nonfluoroscopic mapping system with a near-zero approach.

Background: Cyclin-dependent kinase (CDK)-4/6 inhibitors have been associated with dermatologic reactions, especially alopecia, in pivotal trials. Objective: We aimed to comprehensively describe skin toxicities with CDK4/6 inhibitors reported in the real world through the US FDA Adverse Event Reporting System (FAERS). Methods: Cutaneous adverse events (AEs) were characterized in terms of spectrum and clinical features, including seriousness (with fatality proportion), latency, and discontinuation. Disproportionality analyses were performed through the reporting odds ratio (ROR) and 95% confidence interval (CI) by comparing CDK4/6 inhibitors with other anticancer drugs used in breast cancer. Results: As of December 2020, a total of 7986 cutaneous events were reported with CDK4/6 inhibitors (15% of total AEs with CDK4/6 inhibitors), mainly by consumers (39.6%), with 43.5% classified as serious and 25% requiring discontinuation. In 49% of the cases, five or more noncutaneous events were co-reported. The most frequently reported cutaneous events were alopecia (N = 3528), rash (N = 1493), and pruritus (N = 1211): rashes were recorded in the first month (median onset 28 days), whereas alopecia and nail alterations were recorded after a median of 67 and 112 days, respectively. Several cutaneous AEs were associated with increased reporting, including vitiligo (N = 6; ROR 8.88; 95% CI 2.95–22.46) and bullous dermatitis with ribociclib (N = 7; ROR 2.90; 95% CI 1.13–6.27); erythema multiforme with abemaciclib (N = 9; ROR 5.80; 95% CI 2.57–11.48); onychoclasis (N = 142, ROR 2.27; 95% CI 1.83–2.79) and trichorrhexis (N = 22; ROR 3.27; 95% CI 1.78–5.93) with palbociclib. Conclusions: Although causality cannot be demonstrated, a diverse reporting pattern of cutaneous AEs emerged from FAERS, including dermal/epidermal conditions, hair/nail disorders, and serious bullous conditions, with variable onsets and a remarkable proportion ofdiscontinuations. The potential differential reporting among CDK4/6 inhibitors deserves further investigation.

Report of currently available medical strategies for treatment of childhood chronic uveitis in the biologic era. The management of non-infectious chronic uveitis in children is based on immunomodulatory treatment. In case of failure to conventional disease-modifying anti-rheumatic drugs (cDMARDs) and/or frequent flares, tumor necrosis factor-alpha (TNF-α) blocking agents represent the first biologic choice. Adalimumab is the TNF-α inhibitor more frequently adopted. Two multicenter, double blind, randomized, placebo-controlled trials stated its efficacy and safety in this clinical setting. For refractory disease not responsive to TNF-α inhibitors, emerging biologic therapies have been reported. Most of the current literature refers to expert opinion and remains non-standardized. However, retrospective studies and short case series report tocilizumab, abatacept, and rituximab as promising biologic alternatives in patients with refractory, sight-threatening uveitis even in children. The role of anti-TNF-α inhibitor in chronic uveitis therapy met unanimous level of agreement. Rescue therapy approach still remains controversial. Randomized controlled trials and large series with long-term follow-up are mandatory to assess efficacy and cost effectiveness in this challenging disease. ClinicalTrials.gov ID: NCT01279954. ClinicalTrials.gov ID: NCT04088409

The impact of sudden cardiac death (SCD) in heart failure (HF) patients is important and prevention of SCD is a reasonable and clinically justified endpoint if associated with a reduction in all-cause mortality. According to literature, in HF with reduced ejection fraction, only three classes of agents were found effective in reducing SCD and all-cause mortality: beta-blockers, mineralcorticoid receptor antagonists and, more recently, angiotensin-receptor neprilysin-inhibitors. In the PARADIGM trial that tested sacubitril/valsartan vs. enalapril, the 20% relative risk reduction in cardiovascular deaths obtained with sacubitril/valsartan was attributable to reductions in the incidence of both SCD and death due to HF worsening and this effect can be added to the known positive effect of implantable cardioverter-defibrillators in appropriately selected patients. In order to maximize the implementation of all the available treatments, patients with HF should be included in virtuous networks with a dialogue between all the physician involved, with commitment by all these physicians for appropriate decision-making on application of pharmacological and device treatments according to available evidence, as well as commitment for drug titration before and after device implant, taking advantage from remote monitoring, and with the safety of back up device therapy when indicated. There are potential synergistic effects of drug therapy, with all the therapies acting on neuro-hormonal and sympathetic activation, but specifically with sacubitril/valsartan, and device therapy, in particular cardiac resynchronization therapy, with added incremental benefits on positive cardiac remodelling, prevention of HF progression, and prevention of ventricular tachyarrhythmias.

An accessory pathway (AP) can be apparent during sinus rhythm if it depolarizes part of the ventricles ahead of the normal wave front from the conduction system. An AP can generate an anatomic circuit able to sustain a macroreentrant atrioventricular reentrant tachycardia. This arrhythmia can engage the normal conducting system in an antegrade direction or retrogradely, generating, respectively, a narrow or a wide complex tachycardia. The combined use of a standard electrocardiogram and an esophageal recording-pacing can be particularly useful in the first approach to patients with Wolff-Parkinson-White syndrome, further stratifying patients requiring electrophysiology study and transcatheter ablation.

Over the last decades, the approach to the Wolff-Parkinson-White syndrome, as well as its treatment, has substantially changed, leading to improvement in the prognosis and quality of life of these patients. From the first diagnostic electrophysiologic studies to the most recent evaluations, important data on pathophysiologic and clinical aspects have been gathered, and this learning journey is still not concluded. This body of knowledge is a fundamental part of any cardiologists' armamentarium despite the fact that this syndrome is rarely observed in adult patients.

Aims Limited data are available on the pathophysiological role of the right ventricle (RV) in patients with acute heart failure with preserved ejection fraction (AHF-PEF) and its impact on the main clinical manifestation such as pulmonary oedema or peripheral congestion. Mainly through right-to-left stroke volume mismatch and ventricular-arterial decoupling, right chambers size and function may play a key role leading to fluid overload or maldistributed phenotypes. Methods and results In this monocenter, prospective, observational study 80 consecutive patients with AHF-PEF were enrolled. A complete echocardiographic examination was performed within 6 hours from emergency department admission; multiparametric RV function was carefully evaluated in the very acute phase. Focusing on hypertensive pulmonary oedema (H-AHF) and decompensated AHF without pulmonary oedema (D-AHF) phenotypes, the study aims to analyze the echocardiographic peculiarities of these clinical entities in the early phase of admission and its modification at discharge (D-AHF n = 58, H-AHF n = 22). Baseline clinical characteristics were comparable in both groups, except for coronary artery disease more prevalent in H-AHF and atrial fibrillation more prevalent in D-AHF. D-AHF patients showed dilated and dysfunctional right chambers compared to H-AHF. Regarding systolic function, normal values of fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) were registered in H-AHF at admission and at discharge. D-AHF showed greater systolic pulmonary artery pressure (sPAP) and lower TAPSE/sPAP ratio. Left ventricular dimensions and function were comparable in both groups. Conversely, E/e’ ratio was significantly higher in H-AHF at admission. Data are summarized in the tables and figures below. Conclusion D-AHF and H-AHF represent different phenotypes of AHF-PEF. Right heart structure and function and ventricular-arterial coupling could play a crucial role in their pathophysiology. Non dilated RV with preserved systolic function seems to be crucial to develop pulmonary oedema without signs of peripheral congestion. Further investigations are needed to corroborate the hypothesis of interventricular stroke volume mismatch in the complex AHF-PEF clinical scenario.

Ventricular preexcitation is a depolarization of the ventricles that occurs before the conventional sequence, and the electrocardiogram is the specific test for diagnosis. A Kent bundle is the paradigm of ventricular preexcitation, and it is associated with short PR, wide QRS and delta wave. This finding is not always very evident, as it can have different degrees of pre-eccitazione; therefore great diagnostic care must be taken in this field. If not properly identified, the pattern of ventricular preexcitation may lead to an incorrect diagnosis. The methodology of precision electrocardiology is able to confront all these aspects.

BACKGROUND TNF-α is an important mediator in the pathogenesis of psoriasis and polymorphisms influence its transcription and could be implicated in psoriasis risk and modify certain aspects of disease, such as age at onset of psoriasis vulgaris and disease severity. Six TNF-α single nucleotide polymorphisms (SNPs) in promoter region has been identified and studied but with discordant results. The aim of this study was to evaluate whether the polymorphisms in TNF-α (-238 (rs361525), -308 (rs1800629), -857 (rs1799724), -1031 (rs1799964)) are associated with gravity, prurity, early onset or response to drug therapy in psoriasis in Caucasian Italian patients. METHODS 58 psoriasis patients from Turin PSOCARE, 23 with psoriasis vulgaris and 35 with psoriatic arthritis were studied. Ready to used master mix for allelic discrimination of rs1800629, rs361525 and rs1799964 respectively. RESULTS Our data showed a significant association between the -857(G) variant and both VAS-itch (p=0,03) and VAS-pain index (p=0,006), OR=0,2 (0,04-0,98) and OR=0,12 (0,02-0,59). No significant association between the genotypes or alleles of TNF-α SNPs as been observed with other clinic-pathologic parameters or etanercept response. CONCLUSIONS Our data suggest that -857 CC genotype could be involved in pain and itch severity in psoriasis patients.

Background To investigate the adverse event (AE) profile of tedizolid and linezolid in post-marketing surveillance. Research design and methods We queried the worldwide FDA Adverse Event Reporting System and selected all records where tedizolid and linezolid were reported as suspect by removing potential duplicates. Disproportionality analysis was performed investigating designated medical events (DMEs) and specific AEs of clinical interest reported with tedizolid. The reporting odds ratios (RORs) were calculated, deemed significant by a lower limit of the 95% confidence interval (LL95%CI)>1, using linezolid as comparator. Case-by-case assessment of AEs reported in at least three cases with tedizolid was performed. Results Overall, 271 and 11,259 reports mentioning respectively tedizolid and linezolid were recorded, of which respectively 59 and 4,473 patients with DMEs or selected AEs were found. No difference emerged for the selected AEs except for increased reporting of hepatic failure (N=3; LL95%CI=1.06) with tedizolid considering reports collected after 2014. Extensive off-label use in terms of therapeutic indications (83.6%) and treatment duration was reported with tedizolid. Conclusions Similar AE reporting between the two oxazolidinones was found. Considering limitations of pharmacovigilance, this hypothesis of comparable safety profile should be tested prospectively through dedicated real-world studies.

Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Background: Possible relationship between drug exposure and multiple sclerosis (MS) development is insufficiently investigated, and further challenged by the incomplete understanding of MS etiopathogenesis. The study aims to investigate whether drug exposure could contribute to MS, by analyzing worldwide spontaneous reporting archives of adverse drug reaction (ADRs). Research design and methods: We retrieved information from the US Food and Drug Administration Adverse Event Reporting System (FAERS) over a 13-year period. Reporting odds ratio (ROR) for MS was calculated for each single substance. Disproportionality signals were considered when at least 10 cases were retrieved with a lower limit of the 95% confidence interval (CI) >1. Results: After a customized data-mining process, 3,226 reports of MS were retrieved. ‘Antineoplastic and immunomodulating drugs’ (33% of total reports) were the most frequently reported, with 10 disproportionality signals, including etanercept (445 cases; ROR: 2.48; 95% Cl: 2.24–2.74), adalimumab (329; 2.05; 1.83–2.30), and infliximab (119; 2.25; 1.87–2.70). We also observed signals for drugs acting on hormone balance, bone density, and central nervous system. Conclusion: Our findings suggest that immunomodulatory drugs increase the risk of MS and point out that some other drug classes should be further investigated for this risk.

Direct oral anticoagulants are now recommended by major guidelines as first-choice agents for both stroke prevention in non-valvular atrial fibrillation and treatment/prevention of venous thromboembolism in non-cancer patients. Although there are no published head-to-head trials comparing different direct oral anticoagulants, a growing body of evidence from indirect comparisons and observational studies is suggesting that each direct oral anticoagulant may have a specific risk profile. This review aims to (1) synthesize and critically assess the latest evidence in comparative effectiveness and safety research in the aforementioned consolidated therapeutic uses, by performing an overview of systematic reviews and (2) highlight current challenges, namely underexplored areas, where research should be directed, also considering ongoing unpublished studies. The evidence gathered so far on the risk-benefit profile of direct oral anticoagulants is appraised in the light of existing guidelines to discuss whether further implementation should be proposed.

The aim of this survey was to assess the management and organization of cardiac implantable electronic device (CIED) replacement in Italy.A questionnaire consisting of 24 questions on organizational aspects and on the peri-procedural management of anticoagulant therapies and antibiotic prophylaxis was sent via the Internet to 154 Italian arrhythmia centers.A total of 103 out of 154 centers completed the questionnaire (67% response rate). In 43% of the centers, the procedures were performed under day-case admission, in 40% under ordinary admission, and in 17% under either day-case or ordinary admission. The most frequent reason (66%) for choosing ordinary admission rather than day-case admission was to obtain full reimbursement. Although warfarin therapy was continued in 73% of the centers, nonvitamin K oral anticoagulants were discontinued, without bridging, 24 h or less prior to replacement procedures in 88%. Prophylactic antibiotic therapy was systematically administered in all centers; in 97%, the first antibiotic dose was administered 1-2 h prior to procedures. Local antibacterial envelopes were also used in 43% of the centers in patients with a higher risk of device infection.This survey provides a representative picture of how CIED replacements are organized and managed in current Italian clinical practice. The choice of the type of hospitalization (short versus ordinary) was more often motivated by economic reasons (reimbursement of the procedure) than by clinical and organizational factors. Peri-procedural management of anticoagulation and prophylactic antibiotic therapy was consistent with current scientific evidence.

This letter shows that the position of a source inside an electromagnetic bandgap material determines how the emission is shaped and focused. Two degenerate electromagnetic configurations, allowed by a square lattice at a given frequency, can be selectively excited by placing the feeding point in specific locations within the building block of the periodic structure. In this way, the radiated energy can be directed toward defined focusing directions, without need to change the lattice and its dispersion diagram. A practical application, where embedded emitters selectively drive single lattice modes, is presented, showing that such a mechanism may open the way to important uses in the microwave domain, e.g., for cell splitting, smart antennas, and multiple-input-multiple-output technology, as well as in terahertz communications and optical applications.

Background: Data from recently published trials have provided practice-changing recommendations for the surgical approach to the axilla in breast cancer. Patients with T1-2 lesions, treated with breast conservation, who have not received neoadjuvant chemotherapy and have 1-2 positive sentinel nodes (Z0011-criteria) may avoid axillary lymph node dissection (ALND). We aim to describe the dissemination of this practice in Europe over an extended period of time. Methods: Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified cases fulfilling Z0011-criteria from 2005 to 2016 from 34 European breast centers and report trends in ALND. Data derived from Germany, Italy, Belgium, Switzerland, Austria, and Netherlands. Results: 6671 patients fulfilled Z0011-criteria. Rates of ALND showed a statistically significant decrease from 2010 (89%) to 2011 (73%), reaching 46% in 2016 (p < 0.001). After multivariable analysis, factors associated with higher probability of ALND were earlier year of surgery, younger age, increasing tumor size and grade, and being operated in Italy (p < 0.001). The minimum and maximal rates of ALND in the most recent two-year period (2015-2016) were 0% and 83% in two centers located in different countries (p < 0.001). Conclusion: Our study demonstrates, a decrease in rates of ALND that started after year 2010 through the end of the study period. Wide differences were observed among centers and countries indicating the need to spread unified clinical guidelines in Europe to allow for homogeneous evidence-based practice patterns. (C) 2019 Elsevier Ltd. All rights reserved.

Objective: The aim of this study was to review the existence and types of correlations between body composition densitometric parameters and laboratory values associated to cardiometabolic risk. Methods: We retrospectively analyzed data from 316 individuals in the weight range from normality to super-obesity, submitted to total body dual-energy x-ray absorptiometry (DXA) scans and routine biochemistry at S.Orsola-Malpighi Hospital from June 2010 to March 2014. The study included 182 women, 45.8 ± 13.4 y of age, with a body mass index (BMI) of 31.5 (± 11) kg/m2 (group F) and 134 men, 45.4 ± 13.6 y of age, with a BMI of 27.6 (± 7.8) kg/m2 (group M). All patients underwent whole-body scan (Lunar iDXA, GE Healthcare, Madison, WI, USA) and laboratory analysis (blood fasting glucose, total cholesterol, high-density lipoprotein cholesterol, tricylglycerides [TGs], aspartate aminotransferase, and alanine aminotransferase). Correlation between laboratory values and total body and regional fat mass (including visceral adipose tissue [VAT] and subcutaneous adipose tissue in the android region), and lean mass parameters were analyzed with linear and stepwise regressions analysis (significance limit, P < 0.05). Receiver operating characteristic curves were performed to assess the accuracy of the best-fit DXA parameter (VAT) to identify at least one laboratory risk factor. Results: In both groups, BMI and densitometric parameters showed a linear correlation with fasting blood glucose and TG levels and an inverse correlation with high-density lipoprotein cholesterol (P < 0.05), whereas no correlation was observed with total cholesterol levels. The only densitometric parameter retained in the final model of stepwise multiple regression was VAT for fasting blood glucose (group F: β = 0.4627, P < 0.0001; group M: β = 0.6221, P < 0.0001) and TG levels (group F: β = 0.4931, P < 0.0001; group M: β = 0.1990, P < 0.0261) independently of BMI. The optimal cutoff points of VAT to identify the presence of at least one laboratory risk factor were >1395 g and >1479 cm3 for men and >1281 g and >1357 cm3 for women. Conclusions: DXA analysis of VAT is associated with selected laboratory parameters used for the evaluation of cardiometabolic risk and could be per se a helpful parameter in the assessment of clinical risk.

Background and objectives: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined. Methods: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies. Results: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001). Conclusions: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC.

PURPOSE We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer. METHODS Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed. RESULTS Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175). CONCLUSION Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

O mundo está a viver uma situação de pandemia por causa do vírus SARS-CoV-2. Comparamos níveis de estresse peritraumático durante a pandemia Covid-19 (EPC) entre Brasil e Portugal, países latinos com longa história conjunta. Os resultados apontaram níveis elevados de EPC para os brasileiros com 19% (nível grave), e 64% de EPC de leve a grave, contra 5.3% e 38% dos portugueses. Os brasileiros demonstraram maior gravidade em 20 (de 24) itens de EPC. O índice global (IEPC) foi mais elevado nos brasileiros. Essas diferenças são explicadas como consequência das diferentes decisões políticas de saúde seguidas nos dois países.

Dysregulation of the human's energy balance, mediated by non-performing endocrine organs (liver, skeletal muscle and adipose tissue, above all), can be related to human metabolic disorders characterized by an impaired body composition (BC), such as obesity and sarcopenia. While it is possible to monitor the BC and its variations at different levels, the tissue-organ composition studies have been proven to provide the most clinically applicable information. Ultrasonography (US), a fast, non-invasive, low-cost and widely available technique, holds great potential in the study of BC, as it can directly measure muscles, organs, visceral and subcutaneous fat tissue in different sections of the abdomen and body, overcoming some limits of anthropometric evaluation and other imaging techniques. Purpose of this review article is to explore the technical aspects and the applied methods of US examination to assess the potential clinical role of this technique in the context of BC characterization, investigating four pivotal topics [abdominal fat compartments, subcutaneous adipose tissue (SAT), skeletal muscle, liver].

Graphical abstract, Highlights • The origins and courses of the coronary arteries can be detected on TTE. • Three “echo-signs” can detect an anomalous origin of the circumflex coronary artery. • A significant stenosis in the anomalous left circumflex artery can be detected on TTE.

Aims An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve. Methods and results We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001). Conclusion The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks., Graphical Abstract Graphical Abstract