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To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up.Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models.Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008).Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

Left ventricular free-wall rupture (LVFWR) is an uncommon but serious mechanical complication of acute myocardial infarction (AMI). Surgical repair, though challenging, is the only definitive treatment. However, given the rarity of this condition, results following surgery are still not well established. The aim of this study was to review a multicenter experience with the surgical management of post-infarction LVFWR and analyze the associated early outcomes. Background: Left ventricular free-wall rupture (LVFWR) is an uncommon but serious mechanical complication of acute myocardial infarction. Surgical repair, though challenging, is the only definitive treatment. Given the rarity of this condition, however, results after surgery are still not well established. The aim of this study was to review a multicenter experience with the surgical management of post-infarction LVFWR and analyze the associated early outcomes. Methods: Using the CAUTION (Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort Study) database, we identified 140 patients who were surgically treated for post–acute myocardial infarction LVFWR in 15 different centers from 2001 to 2018. The main outcome measured was operative mortality. Multivariate analysis was carried out by constructing a logistic regression model to identify predictors of postoperative mortality. Results: The mean age of patients was 69.4 years. The oozing type of LVFWR was observed in 79 patients (56.4%), and the blowout type in 61 (43.6%). Sutured repair was used in the 61.4% of cases. The operative mortality rate was 36.4%. Low cardiac output syndrome was the main cause of perioperative death. Myocardial rerupture after surgery occurred in 10 patients (7.1%). Multivariable analysis revealed that preoperative left ventricular ejection fraction (P

The increased prevalence of obesity, metabolic syndrome and type 2 diabetes has prompted scientists to look for new active and safe molecules that may help the prevention of metabolic disorders: hyperglycemia, insulin-resistance and dyslipidemia. Berberine is an alkaloid compound derived from plants, and it is largely used in traditional Chinese medicine. The aim of this study is to investigate in SCOPUS and Web of Science (WOS) databases how the scientists focused on the use of berberine against metabolic disorders, in human subjects. We carried A bibliometric analysis of scientific literature and performed 2 searches: 1) “Berberine” AND “Diabetes” AND “Diabetes Type 2”, 2) “Berberine” AND “Metabolic Syndrome”, both in ARTICLE (Title/Abstract/Keyword) with a time limitation of 1st January, 2000 through 31st December, 2018, with the filter on “HUMAN” AND/OR “HUMANS”. The research sorted out 500 papers, finding about 300 (60 %) in the first search definition and 200 (40 %) in the second. The refined research sorted out 46 papers regarding the use of berberine in diabetes, and 40 articles on the use of the alkaloid compound in metabolic syndrome. For both topics, we found increasing interest between 2008 and 2009, with citation trends in a constant crescendo in the overall period studied. These findings underlined that berberine is a safe and interesting botanical compound, especially against chronic-metabolic disorder that affects billions of people globally, and emphasized that scientists are interested in searching for long-term therapies that show no major adverse effects.

Background: COVID-19 pandemic worsened vulnerability of patients with dementia (PWD). This new reality associated with government restriction and isolation worsened stress burden and psychological frailties in PWD caregivers. Objective: To give tele-psychological support to caregivers and evaluate the effect of this intervention by quantifying stress burden and quality of life during the first COVID-19 lockdown. Methods: 50 caregivers were divided into two groups: “Caregiver-focused group” (Cg) and “Patient-focused group” (Pg). Both groups received telephone contact every 2 weeks over a 28-week period, but the content of the call was different: in Cg, caregivers answered questions about the state of the PWD but also explored their own emotional state, stress burden, and quality of life. In Pg instead, telephone contacts were focused only on the PWD, and no evaluation regarding the caregiver mood or state of stress was made. Psychometric scales were administered to evaluate COVID-19 impact, stress burden, and quality of life. Results: Considering the time of intervention, from baseline (W0) to W28, Zarit Burden Interview and Quality of Life-caregiver questionnaires remained unchanged in Cg as compared with baseline (p > 0.05), whereas they worsened significantly in Pg (p

To assess factors associated with external limiting membrane (ELM)/ellipsoid zone (EZ) damage after pars plana vitrectomy (PPV) for epiretinal membrane and evaluate ELM/EZ damage impact on functional and anatomical outcomes.Patients who underwent PPV with epiretinal membrane ± inner limiting membrane peeling were retrospectively analyzed. Best-corrected visual acuity and central macular thickness were longitudinally collected based on the available follow-up. Demographic data, clinical data, and surgical details were included in logistic regression models having ELM/EZ damage as a binary outcome.Overall, 179 eyes (171 patients) were included; 93 had a 12-month follow-up. Thirty-four eyes (19%) had ELM/EZ damage after surgery; in nine eyes (5%), ELM/EZ damage persisted at 12 months. Phacoemulsification during PPV (odds ratio = 6.97; P = 0.007) and ELM/EZ damage before PPV (odds ratio = 6.91; P = 0.007) were risk factors for postoperative ELM/EZ disruption. Thicker outer nuclear layer (P = 0.002), thicker ectopic inner foveal layer (P0.001), and higher endoillumination power (P = 0.03) were associated with slower visual recovery. Inner limiting membrane peeling (P = 0.04) was associated with slower anatomical recovery.Cataract extraction and outer retinal damage before PPV are associated with higher risk of photoreceptor damage postoperatively. The rate of visual improvement varies as a function of retinal layers' distortion before surgery; additional retinal manipulation slows restoration of the macular anatomy.

Background & Aims The Pre-TACE-Predict model was devised to assess prognosis of patients treated with trans-arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). However, before entering clinical practice, a model should demonstrate that it performs a useful role. Methods We performed an independent external validation of the Pre-TACE model in a cohort that differs in setting and time period from the one that generated the original model. Data from 826 patients treated with TACE for naïve HCC (2008-2018) were used to assess calibration and discrimination of the Pre-TACE-Predict model. Results The four risk-categories identified by the Pre-TACE-Predict model had gradient monotonicity, with median survivals of 52.0, 36.2, 29.9, and 14.1 months respectively. However, predicted survivals systematically underestimated observed survivals (R2: 0.667). A recalibration was adopted maintaining fixed the prognostic index and modifying the baseline survival function. This resulted in an almost perfect calibration (R2: 0.995) in all the four risk categories. Cox regressions showed that aetiology and macrovascular invasion, included in the Pre-TACE-Predict model, had no prognostic impact in the present study population, and that coefficients for tumour size and multiplicity were overestimated. The c-index was similar to that of the m-HAP-III, but higher than those of HAP, m-HAP-II and the six-and-twelve models. Conclusions The recalibration of Pre-TACE-Predict model improved the estimation of survival probabilities of HCC patients treated with TACE. The highest discriminatory ability of the Pre-TACE-model in comparison to other available models, together with risk stratification and recalibration, makes it the best prognostic tool currently available for these patients.

Introduction: Progastrin-releasing peptide (proGRP), a precursor of GRP, has been recently reported as a putative circulating biomarker for differential diagnosis between non–small cell lung cancer (NSCLC) and SCLC. We evaluated the diagnostic effectiveness of proGRP to differentiate patients with NSCLC and SCLC and the usefulness of combined measurement of proGRP and neuron-specific enolase (NSE) for diagnosing SCLC. Methods: Serum proGRP, NSE, cytokeratin 19 fragment 21-1 (CYFRA 21.1), squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) were prospectively collected and measured in patients with a new diagnosis of lung cancer. Serum proGRP was also measured in healthy subjects. The serum proGRP, NSE, CYFRA 21.1 and CEA concentrations were determined by an electrochemiluminescence immunoassay and the serum SCC Ag concentration was determined by an automated immunofluorescence assay. Differences between proGRP and NSE in patients with SCLC and NSCLC were evaluated and compared using Mann-Whitney test. Results: A total of 77 patients affected by SCLC (n = 17) and NSCLC (n = 60) were enrolled in the present study. Moreover, 50 cases of healthy subjects were analyzed for proGRP. SCLC patients showed a significantly higher proGRP (1,484 pg/mL; range 168-3,777) levels compared to NSCLC patients (45 pg/mL; range 31.7-60.6), p

Background Neonatal infectious spondylodiscitis is a rare bony infection with atypical clinical presentation and non-specific systemic symptoms. Diagnosis and treatment are often delayed resulting in vertebral destruction and severe complications. We retrospectively reviewed the case of an infant with infectious spondylodiscitis resulting in T12 body destruction and marked angular kyphosis. Case-report A 4-week-old infant developed an infectious spondylodiscitis resulting in destruction of the T12 vertebral body and involvement of disc between T12 and L1. At 6 months of age, X-ray showed a marked thoracolumbar angular kyphosis above 50 Cobb degrees. Therefore, the patient underwent single time surgery with double anterior and posterior approach. At 9 years follow up, clinical and radiological findings show a stable correction with good aesthetic appearance. Conclusion Neonatal spondylodiscitis could lead to marked kyphosis similar to the congenital one. Since treatment with casts and tutors is often inefficacious, prompt surgery should be considered. The double anterior and posterior approach is the best option in this condition.

Purpose: Cycloidal computed tomography is a novel imaging concept which combines a highly structured x-ray beam, offset lateral under-sampling, and mathematical data recovery to obtain high-resolution images efficiently and flexibly, even with relatively large source focal spots and detector pixels. The method reduces scanning time and, potentially, delivered dose compared to other sampling schemes. This study aims to present and discuss several implementation strategies for cycloidal computed tomography (CT) in order to increase its ease of use and facilitate uptake within the imaging community. Methods: The different implementation strategies presented are step-and-shoot, continuous unidirectional, continuous back-and-forth, and continuous pixel-wise scanning. In step-and-shoot scans the sample remains stationary while frames are acquired, whereas in all other cases the sample moves through the scanner continuously. The difference between the continuous approaches is the trajectory by which the sample moves within the field of view. Results: All four implementation strategies are compatible with a standard table-top x-ray setup. With the experimental setup applied here, step-and-shoot acquisitions yield the best spatial resolution (around 30µm), but are the most time-consuming (1.4h). Continuous unidirectional and back-and-forth images have resolution between 30 and 40µm, and are faster (35min). Continuous pixel-wise images are equally time-efficient, although technical challenges caused a small loss in image quality with a resolution of about 50µm. Conclusion: The authors show that cycloidal CT can be implemented in a variety of ways with high quality results. They believe this posits cycloidal CT as a powerful imaging alternative to more time-consuming and less flexible methods in the field.

Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.

Knee valgus is one of the most frequent paediatric orthopaedic problems based on the evaluation by the paediatricians. Most cases are physiological variants that resolve spontaneously with growth, however pathological cases require surgical treatment. Therefore, the paediatrician must know how to distinguish between the two entities from the beginning, sending the child to the specialist when necessary, thus respecting the correct timing for treatment. The most frequent condition is idiopathic knee valgus, which occurs when the physiological variant persists after the age of 8 without spontaneous resolution. Children who always need specialist evaluation are those who on physical examination show a tibiofemoral angle greater than 15° with an intermalleolar distance of about 10 cm that persists beyond 10 years of age. The gold standard treatment in these children is growth-guided hemiepiphysiodesis, namely a simple and minimally invasive procedure that reshapes the altered angle of the knees through the application of the 8-plate. The correction is based on the presence of residual growth of the physical cartilages, therefore it should not be performed too late, but not before 10 years of age.

Background and purpose The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive appropriate treatment (e.g. thrombolysis). Methods We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords “insular stroke” and “insular infarction”, to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. Results We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. Conclusions The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations.

Objectives This study investigated whether pulmonary artery (PA) 18F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures. Background 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH). Methods In a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, 18F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE). Results Thirty-three subjects demonstrated clear 18F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA 18F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA 18F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P Conclusions We demonstrate that 18F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.

The ongoing COVID-19 pandemic highlighted a significant interplay between cardiovascular disease (CVD), COVID-19 related inflammatory status, and depression. Cardiovascular (CV) injury is responsible for a substantial percentage of COVID-19 deaths while COVID-19 social restrictions emerged as a non-negligible risk factor for CVD as well as a variety of mental health issues, and in particular, depression. Inflammation seems to be a shared condition between these two disorders. Gender represents a potential modifying factor both in CVD and depression, as well as in COVID-19 short- and long-term outcomes, particularly in cases involving long-term COVID complications. Results from emerging studies indicate that COVID-19 pandemic affected male and female populations in different ways. Women seem to experience less severe short-term complications but suffer worse long-term COVID complications, including depression, reduced physical activity, and deteriorating lifestyle habits, all of which may impact CV risk. Here, we summarize the current state of knowledge about the interplay between COVID-19, depression, and CV risk in women.

The field of workplace communication has grown in the past 20 years to encompass the negotiation of identities and the role of power in collaboration. Nonetheless, identity struggles at work remain an underexplored phenomenon, particularly for emerging or marginalised professional groups such as tertiary language and learning advisors (TLAs) in higher education. In this article, we explore how challenges encountered in collaboration between TLAs and content specialist academics (CSs) in an Australian tertiary setting can impact the negotiation of professional identities as well as the success of the work. We draw on transcripts of meeting talk from two novice TLAs as they negotiate collaborative work with one CS in a postgraduate subject, and we use critical discourse analysis to demonstrate how power discursively manifests in the meetings. The study sheds new light on the complexities of collaborative work, manifested through interactions, in hierarchical professional environments.

Background Yolk sac tumor (YST) is a malignant entity that often occurs in girls less than 3 years of age and is the most frequent type of primary extragonadal germ cell tumor. Case We describe the case of an 11-month-old girl who was referred to our center for vaginal bleeding with evidence of a uterine mass on ultrasonography. Preoperative investigations confirmed YST of the uterine cervix without metastasis. After 4 cycles of systemic chemotherapy, the patient was treated with laparoscopic trachelectomy (fertility-sparing surgery) without perioperative complications. Summary and Conclusion After 12 months of follow-up, no residual mass was seen. The laparoscopic technique for trachelectomy for uterine cervix YST seems to be feasible and safe in children under 1 year of age.

Purpose: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). Materials and methods: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020–December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. Results: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1–18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6–96.9), a specificity of 95.6% (95% CI: 90.6–98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3–92.3), a negative PV of 97.1% (95% CI: 74.6–96.9) and an accuracy of 94.2% (95% CI: 89.6–97.2) in predicting PMD/PNX (AUC:0.924). Conclusions: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

COVID-19 is a viral respiratory illness caused by the SARS-CoV-2 infection. In addition to lung disease, clinical complications of COVID-19 include myocardial damage and ischemia-related vascular disease. Severe manifestations and poor prognosis in these patients are associated with a hypercoagulable state predisposing to thrombotic-related complications and eventually death. However, these clinical features can also occur in other forms of pneumonia, such as community-acquired pneumonia (CAP), which, is also complicated by vascular diseases and characterized by platelet activation. Platelets play a pivotal role in these settings as bacteria and viruses may induce activation via Toll-like receptors (TLRs) in CAP patients and different and multiple pathways, including ACE2-AngII axis and/or TLRs, in COVID-19 patients. Despite evidence confirming the implication of platelet activation in both settings, their contribution to the thrombotic process is still under investigation. Thus, in this review, we (1) compare the thrombotic features of SARS-CoV-2 infection and CAP, (2) analyze the putative mechanisms accounting for venous and arterial thrombosis in SARS-CoV-2 infection, and (3) discuss the potential anticoagulant armamentarium to counteract thrombosis.

Purpose: To develop anautomated treatment planning approach for whole breast irradiation with simultaneous integrated boost using an automated hybrid VMAT class solution (HVMAT). Materials and methods: Twenty-five consecutive patients with left breast cancer received 50 Gy (2 Gy/fraction) to the whole breast and an additional simultaneous 10 Gy (2.4 Gy/fraction) to the tumor cavity. Ipsilateral lung, heart, and contralateral breast were contoured as main organs-at-risk. HVMAT plans were inversely optimized by combining two open fields with aVMAT semi-arc beam. Open fields were setup to include the whole breast with a2 cm flash region and to carry 80% of beams weight. HVMAT plans were compared with three tangential techniques: conventional wedged-field tangential plans (SWF), field-in-field forward planned tangential plans (FiF), and hybrid-IMRT plans (HMRT). Dosimetric differences among the plans were evaluated using Kruskal–Wallis one-way analysis of variance. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 15002D-array. Results: No significant differences were found among the four techniques for both targets coverage. HVMAT plans showed consistently better PTVs dose contrast, conformity, and homogeneity (p < 0.001 for all metrics) and statistically significant reduction of high-dose breast irradiation. V55 and V60 decreased by 30.4, 26.1, and 20.8% (p < 0.05) and 12.3, 9.9, and 6.0% (p < 0.05) for SWF, FIF, and HMRT, respectively. Pretreatment dose verification reported agamma pass-rate greater than the acceptance threshold of 95% for all HVMAT plans. In addition, HVMAT reduced the time for full planning optimization to about 20 min. Conclusions: HVMAT plans resulted in superior target dose conformity and homogeneity compared to other tangential techniques. Due to fast planning time HVMAT can be applied for all patients, minimizing the impact on human or departmental resources.

BACKGROUND Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1-positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort. METHODS This was a retrospective study enrolling HIV-1-infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses. RESULTS Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45-58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression

Background Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme that modulates the S-thiolation status of intracellular factors involved in cancer cell survival or in the inflammatory response. Studies focusing on chronic obstructive pulmonary disease (COPD) have demonstrated that GSTO1-1 is detectable in alveolar macrophages, airway epithelium and in the extracellular compartment, where its functions have not been completely understood. Moreover GSTO1-1 polymorphisms have been associated with an increased risk to develop COPD. Against this background, the aim of this study was to evaluate GSTO1-1 levels and its polymorphisms in cystic fibrosis (CF) patients. Methods Clinical samples from a previous study published by our groups were analyzed for GSTO1-1 levels and polymorphisms. For comparison, a model of lung inflammation in CFTR-knock out mice was also used. Results Our data document that soluble GSTO1-1 can be found in the airways of CF patients and correlates with inflammatory parameters such as neutrophilic elastase and the chemokine IL-8. A negative correlation was found between GSTO1-1 levels and the spirometric parameter FEV1 and the FEV1/FVC ratio. Additionally, the A140D polymorphism of GSTO1-1 was associated with lower levels of the antiinflammatory mediators PGE2 and 15(S)-HETE, and with lower values of the FEV1/FVC ratio in CF subjects with the homozygous CFTR ΔF508 mutation. Conclusions Our data suggest that extracellular GSTO1-1 and its polymorphysms could have a biological and clinical significance in CF. Pathophysiological functions of GSTOs are far from being completely understood, and more studies are required to understand the role(s) of extracellular GSTO1-1 in inflamed tissues.

Background food production represents one of the highest impacting activities on our planet, significantly contributing to climate change. Agriculture is one of the most important drivers of these changes since farming, forestry, and livestock, emit approximately one third of the global total CO2. Moreover, the modern agriculture systems mainly focus on starchy vegetables leading to energy dense and nutrient poor dietary patterns related to chronic diseases, such as NCDs. Elderly are the most vulnerable population portion that experiences even more than others the impact of unhealthy dietary patterns. Therefore, a transition to healthier and more sustainable solutions must be adopted to reach the SDGs promoted by the Agenda 2030, positively impacting the environment and human health. The role of pulses in this context is discussed. Scope and approach authors focus on the role of Leguminosae considering their potential impact both on health in the ageing population as well as on agri-food chains sustainability. Key findings and conclusions there is an increasing awareness on how legumes represent an important source of bioactive compounds (i.e., phenolics, saponins and peptides) with a wide range of healthy activities, all of which share antioxidant properties, essential to prevent or delay oxidative stress and disease in elderly population. With an ever-ageing population at the global level, healthy ageing is an emerging public health priority for securing citizens’ quality of life and minimizing healthcare associated costs.

Anna Vittoria Mattioli,1 Francesca Coppi,2 Antonio Manenti,1 Alberto Farinetti3 1Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy; 2Cardiology Division, Policlinico di Modena, Modena, Italy; 3Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, ItalyCorrespondence: Anna Vittoria MattioliSurgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine University of Modena and Reggio Emilia, Via del pozzo, 71, Modena, 41100, ItalyEmail annavittoria.mattioli@unimore.itAbstract: The cardiovascular risk assessment must be carried out during all the different phases of life because the cardiovascular risk and the related prevention actions are dynamic and constantly evolving. As patients age, they change their exposure to various risk factors and accumulate comorbidities by changing their subjective cardiovascular risk, so it is necessary to undertake personalized early and preventive diagnostic actions. The main approach to asymptomatic vascular disease is based on primary prevention with the adoption of a healthy lifestyle. Indeed, lifestyle influences most of the traditional risk factors. In recent years, important differences between the sexes regarding cardiovascular risk factors have emerged and in particular, risk factors specific for female sex have been identified. Women are more likely to be categorized into lower risk categories for cardiovascular disease and, as a result, receive less lifestyle counseling than men, as well as less intensive prevention. This narrative review aims to analyze CVD risk prevention in asymptomatic atherosclerosis with a look at new emerging factors. In the end, we quickly analyzed the effects of the recent pandemic on lifestyle and cardiovascular risk and the potential negative effects in the long term.Keywords: prevention, risk factors, women, lifestyle, microbiota, pandemic

The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7days and treated with GLP-1R agonists. Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Cells exposed to high glucose showed lower NF-κB and SOD2 methylation levels, increased NF-κB and reduced SOD2 expression compared to normal glucose cells. Co-treatment with GLP-1 agonists prevented methylation and genes expression changes induced by high glucose. Both high glucose and incretins exposure increased DNA methyltransferases and demethylases levels. In diabetics, incretin treatment resulted a significant predictor of NF-κB DNA methylation, independently of age, sex, body mass index (BMI), glucose and plasma lipid levels. NF-κB DNA methylation inversely correlated with IMT after adjusting for multiple covariates. Our results firstly provide new evidences of an additional mechanism by which incretin drugs could prevent vascular diabetic complications.

Numerous nutritional approaches aimed at reducing body weight have been devel- oped as a strategy to reduce obesity. Most of these interventions rely on reducing caloric intake or limiting calories access to a few hours per day. In this work, we analyzed the effects of the extended (24 hours/day) or restricted (1 hour/day) access to a cafeteria-style (CAF) diet, on rat body weight and hepatic lipid metabolism, with respect to control rats (CTR) fed with a standard chow diet. The body weight gain of restricted-fed rats was not different from CTR, despite the slightly higher total caloric intake, but resulted significantly lower than extended-fed rats, which showed a CAF diet-induced obesity and a dramatically higher total caloric intake. However, both CAF-fed groups of rats showed, compared to CTR, unhealthy serum and hepatic parameters such as higher serum glucose level, lower HDL values, and increased hepatic triacylglycerol and cholesterol amount. The hepatic expression and activity of key enzymes of fatty acid synthesis, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), was similarly reduced in both CAF-fed groups of rats with respect to CTR. Anyway, while in extended-fed rats this reduction was associ- ated to a long-term mechanism involving sterol regulatory element-binding protein-1 (SREBP-1), in restricted-fed animals a short-term mechanism based on PKA and AMPK activation occurred in the liver. Furthermore, hepatic fatty acid oxidation (FAO) and oxidative stress resulted significantly increased in extended, but not in restricted-fed rats, as compared to CTR. Overall, these results demonstrate that al- though limiting the total caloric intake might successfully fight obesity development, the nutritional content of the diet is the major determinant for the health status.

Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p=0.42), between low- and high-penetrance mutations (p=0.62), and according to different dosages (p=0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.

Introduction: To investigate choroidal thickness changes related to the clinical activity of inflammatory choroidal neovascularization in punctate inner choroidopathy/multifocal choroiditis as compared to myopic choroidal neovascularization. Materials and methods: Consecutive inflammatory choroidal neovascularization secondary to punctate inner choroidopathy/multifocal choroiditis, and myopic choroidal neovascularization were retrospectively reviewed. By means of enhanced-depth imaging optical coherence tomography, choroidal thickness was assessed at the same location before choroidal neovascularization development, at choroidal neovascularization onset (baseline), and after treatment. Results: Eleven eyes with inflammatory choroidal neovascularization and 11 eyes with myopic choroidal neovascularization were analyzed. Choroidal thickness beneath inflammatory choroidal neovascularization significantly increased at baseline and decreased after therapy (“Sponge sign”), reaching preclinical values. In particular, mean choroidal thickness under inflammatory choroidal neovascularization was 145 ± 85 µm at the preclinical stage, increased to 210 ± 103 µm at baseline (p = 0.006), and decreased to 136 ± 87 µm after treatment (p = 0.017). Conversely, no significant choroidal thickness changes were disclosed in myopic choroidal neovascularization eyes, under any location. Conclusion: Optical coherence tomography–based choroidal thickness evaluation may represent an additional useful tool to monitor inflammatory choroidal neovascularization activity. Moreover, choroidal thickness under choroidal neovascularizations could be used to discriminate the origin of choroidal neovascular membrane, either inflammatory or myopic, in doubtful cases and guide the therapeutic management.

BackgroundThis study aimed to assess the prevalence and causes of vision loss in sub-Saharan Africa (SSA) in 2015, compared with prior years, and to estimate expected values for 2020.MethodsA systematic review and meta-analysis assessed the prevalence of blindness (presenting distance visual acuity In SSA, age-standardised prevalence of blindness, MSVI and MVI in 2015 were 1.03% (80% uncertainty interval (UI) 0.39–1.81), 3.64% (80% UI 1.71–5.94) and 2.94% (80% UI 1.05–5.34), respectively, for male and 1.08% (80% UI 0.40–1.93), 3.84% (80% UI 1.72–6.37) and 3.06% (80% UI 1.07–5.61) for females, constituting a significant decrease since 2010 for both genders. There were an estimated 4.28 million blind individuals and 17.36 million individuals with MSVI; 101.08 million individuals were estimated to have near vision loss due to presbyopia. Cataract was the most common cause of blindness (40.1%), whereas undercorrected refractive error (URE) (48.5%) was the most common cause of MSVI. Sub-Saharan West Africa had the highest proportion of blindness compared with the other SSA subregions.ConclusionsCataract and URE, two of the major causes of blindness and vision impairment, are reversible with treatment and thus promising targets to alleviate vision impairment in SSA.

Inherited retinal dystrophies (IRD) are a heterogeneous group of rare chronic disorders caused by genetically determined degeneration of photoreceptors and retinal pigment epithelium cells. Ultra-widefield (UWF) imaging is a useful diagnostic tool for evaluating retinal integrity in IRD, including Stargardt disease, retinitis pigmentosa, cone dystrophies, and Best vitelliform dystrophy. Color or pseudocolor and fundus autofluorescence images obtained with UWF provide previously unavailable information on the retinal periphery, which correlates well with visual field measurement or electroretinogram. Despite unavoidable artifacts of the UWF device, the feasibility of investigations in infants and in patients with poor fixation makes UWF imaging a precious resource in the diagnostic armamentarium for IRD.

Head and neck carcinoma (HNC) are diseases arising from several tracts of the aerodigestive ways. Most HNC are squamous cell carcinoma (SCCHN). Immunotherapy is a treatment strategy aimed to reinforce the immune system. Several types of immunotherapy are available in the clinical scenario. Checkpoint inhibitors were developed later in SCCHN; nivolumab and pembrolizumab have reached the clinical approval, having both drugs demonstrated to significantly improve the overall survival, if compared with the standard of treatment (according to the results of the CheckMate 141 and KEYNOTE-040 trials). Nevertheless, immunotherapy may fail because of the genetics of SCCHN. In fact, two genetically different types of SCCHN have been discovered, one virus-related (HPV) and the other mutagens-related. They seem to show in clinical trials very different responses to immunotherapy. Given the existence of a number of factors predictive of response to immunotherapy in SCCHN, a future clinical approach may be to characterize the genetic and immunologic feature of SCCHN and to perform a well-tailored immunotherapy. This review will summarize the main immunotherapy strategies available in SCCHN, discussing their real efficacy, highlighting also the ways to improve them.

OBJECTIVES Papillary muscle rupture (PMR) is a rare but potentially fatal complication of acute myocardial infarction. The aim of this study was to analyse the patient characteristics and early outcomes of the surgical management of post-infarction PMR from an international multicentre registry. METHODS Patients underwent surgery for post-infarction PMR between 2001 through 2019 were retrieved from database of the CAUTION study. The primary end point was in-hospital mortality. RESULTS A total of 214 patients were included with a mean age of 66.9 (standard deviation: 10.5) years. The posteromedial papillary muscle was the most frequent rupture location (71.9%); the rupture was complete in 67.3% of patients. Mitral valve replacement was performed in 82.7% of cases. One hundred twenty-two patients (57%) had concomitant coronary artery bypass grafting. In-hospital mortality was 24.8%. Temporal trends revealed no apparent improvement in in-hospital mortality during the study period. Multivariable analysis showed that preoperative chronic kidney disfunction [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.07–6.45, P = 0.036], cardiac arrest (OR: 3.99, 95% CI: 1.02–15.61, P = 0.046) and cardiopulmonary bypass duration (OR: 1.01, 95% CI: 1.00–1.02, P = 0.04) were independently associated with an increased risk of in-hospital death, whereas concomitant coronary artery bypass grafting was identified as an independent predictor of early survival (OR: 0.38, 95% CI: 0.16–0.92, P = 0.031). CONCLUSIONS Surgical treatment for post-infarction PMR carries a high in-hospital mortality rate, which did not improve during the study period. Because concomitant coronary artery bypass grafting confers a survival benefit, this additional procedure should be performed, whenever possible, in an attempt to improve the outcome. Clinical trial registration clinicaltrials.gov: NCT03848429.

Purpose: The role of immunotherapy in hormone receptor (HR)-positive, HER2-negative breast cancer is underexplored. Patients and Methods: The neoadjuvant phase II GIADA trial (NCT04659551, EUDRACT 2016-004665-10) enrolled stage II–IIIA premenopausal patients with Luminal B (LumB)-like breast cancer (HR-positive/HER2-negative, Ki67 ≥ 20%, and/or histologic grade 3). Patients received: three 21-day cycles of epirubicin/cyclophosphamide followed by eight 14-day cycles of nivolumab, triptorelin started concomitantly to chemotherapy, and exemestane started concomitantly to nivolumab. Primary endpoint was pathologic complete response (pCR; ypT0/is, ypN0). Results: A pCR was achieved by 7/43 patients [16.3%; 95% confidence interval (CI), 7.4–34.9]; the rate of residual cancer burden class 0–I was 25.6%. pCR rate was significantly higher for patients with PAM50 Basal breast cancer (4/8, 50%) as compared with other subtypes (LumA 9.1%; LumB 8.3%; P = 0.017). Tumor-infiltrating lymphocytes (TIL), immune-related gene-expression signatures, and specific immune cell subpopulations by multiplex immunofluorescence were significantly associated with pCR. A combined score of Basal subtype and TILs had an AUC of 0.95 (95% CI, 0.89–1.00) for pCR prediction. According to multiplex immunofluorescence, a switch to a more immune-activated tumor microenvironment occurred following exposure to anthracyclines. Most common grade ≥3 treatment-related adverse events (AE) during nivolumab were γ-glutamyltransferase (16.7%), alanine aminotransferase (16.7%), and aspartate aminotransferase (9.5%) increase. Most common immune-related AEs were endocrinopathies (all grades 1–2; including adrenal insufficiency, n = 1). Conclusions: Luminal B-like breast cancers with a Basal molecular subtype and/or a state of immune activation may respond to sequential anthracyclines and anti–PD-1. Our data generate hypotheses that, if validated, could guide immunotherapy development in this context.

Cardio-cerebrovascular (CCV) disease contributes significantly to the global burden of disease, with dramatic consequences in terms of mortality and general health. Mitigate CCV risk factors is the key to reduce individual and population risk of CCV events. Evidence-based medicine and epidemiological investigations of risk factors are essential to optimize actions. To contribute to the knowledge of the burden of risk factors in determining CCV events in the individual patient and in the community. Clinical data and risk factors were collected through a longitudinal survey (1999) as part of a larger epidemiology and cardiovascular prevention project, namely the “VIP (Valle dell'Irno Prevention) Project”. We assessed the incidence of major cardiovascular events (MACE) and for each risk factor we calculated: prevalence, absolute risk, odds ratio (OR), additional risk (AR) = risk of exposed to the risk factor − risk of non-exposed, population attributable risk (PAR) = additional risk * prevalence, population attributable risk fraction (PAF) = PAR/total incidence of the disease. Comparing the MACE group with the non-MACE group, a statistically significant difference was found for the following: glomerular filtration rate (GFR), glucose and systolic blood pressure (SBP), BMI, diastolic blood pressure (DBP), cholesterol, triglycerides, creatinine and uric acid. GFR, glucose and SBP showed the highest OR. Age, creatinine, glycemia, SBP and uric acid were independent predictor of MACE. When calculating the PAF, the CCV risk factors with the greatest impact on MACE were: SBP (29.6%), triglyceridemia (19.4%) and metabolic syndrome (18.3%). The burden of risk factors on MACE changes substantially according to whether it is calculated in the single patient or in the population. It is crucial for physicians to take these differences into account when applying their own intervention to reduce CCV events.

Purpose The purpose of this paper is to understand how firms may be segmented with respect to their attitudes towards the use of mobile instant messaging (MIM) apps (e.g. WhatsApp, Messenger, WeChat, etc). in their marketing practices to identify the main approaches to the use of MIM in business. Moreover, this paper identifies the key factors which can motivate or hinder the adoption of these digital platforms. Design/methodology/approach Firms are segmented on the basis of their attitudes (perceived usefulness and perceived effectiveness of performance) towards the use of MIM apps in the business. Categories for size, age of the firm and the organization’s predisposition towards MIMs are explored using data from 311 firms and latent class analysis. Threats, triggers and their real usage are also identified to describe the different approaches towards the application of MIM apps in marketing practices. Findings Four clusters are identified – lukewarm, cold, believer and unaffected – along with significant covariates such as the importance of conversation with the client, the use of MIMs in the business, the threats and triggers that can foresee adherence. The results help to understand how to approach the client using social messenger applications. MIM apps can be used for strategic marketing and not only for operative marketing. Originality/value This paper offers a more nuanced understanding of how firms engage through MIM apps by focusing on the firms’ attitudes towards MIM apps. It extends the knowledge on the firms’ reactions to these disruptive technologies and profiles the firms according to their social innovation attitudes, something that has not yet been investigated in the extant marketing literature.

The opening of international markets following World War II highlighted the differences between territories at regional and national level in terms of the attractiveness of economic activities, investment and human resources. In this context, an important aspect concerned the entrepreneurial process: businesses and entrepreneurs have played a leading role in the activation of the paths of economic growth on the product value, employment and international competitiveness. From this perspective, the study of entrepreneurial dynamics - who the entrepreneurs are, their formation, the path followed for the creation of the enterprise, socio-economic and institutional context in which they acted - becomes crucial to understand the influence of economic and social conditions in the countries of origin as well as the employment and market opportunities, infrastructures and attractiveness of the destination countries. From this point of view, the entrepreneurial path is linked to the migration process and requires a study to highlight the relationship between these two phenomena and their impacts on the development and territorial competitiveness. Starting from the analysis of the literature and researches available at national and international level, in this paper we present the first results of a quantitative and qualitative research at the Archives of the American Chamber of Commerce in Italy, as well as in other American economic institutions. The study aims to highlight the scale of the phenomenon in the Italian-Americans economic relations after World War II, the characteristics of firms with immigrant entrepreneurs, as well as the relationship between immigrant entrepreneurship and entrepreneur training. Even though the two authors share the article’s setting, please note that introduction and paragraph 1 are by Vittoria Ferrandino and paragraphs 2, 3 and 4 are by Valentina Sgro. Both of the authors wrote the conclusions.

Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures.We retrospectively analyzed data of 1115 patients with seizure onset18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model.Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p0.001).In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events.

Aortic stenosis (AS) is defined as severe in the presence of: mean gradient ≥40 mmHg, peak aortic velocity ≥4 m/s, and aortic valve area (AVA) ≤1 cm2 (or an indexed AVA ≤0.6 cm2/m2). However, up to 40% of patients have a discrepancy between gradient and AVA, i.e. AVA ≤1 cm2 (indicating severe AS) and a moderate gradient: >20 and

Purpose To describe a clinical picture resembling classic multiple evanescent white dot syndrome (MEWDS) potentially triggered by previous or concurrent, apparently unrelated, ocular events and to provide a literature review of similar presentations. Design Retrospective chart series and literature review. Participants Consecutive patients diagnosed with MEWDS at the Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and the IRCCS San Raffaele Scientific Institute, Milan, Italy, between July 2019 and June 2020. Methods Charts of patients were reviewed. Ophthalmic history, best-corrected visual acuity, spectral-domain OCT results, OCT angiography results, fundus autofluorescence results, ultra-widefield fluorescein angiography results, and indocyanine green angiography results were collected. A PubMed-based search was carried out for similar presentations using the terms MEWDS and white spot syndromes. Main Outcome Measures An ocular history positive for previous or concurrent ocular events in patients with MEWDS was sought in our cohort and the existing literature. Results Five eyes of 4 patients (2 females; age range, 16–81 years) were included. The first eye had a history of bilateral Best vitelliform dystrophy and unilateral choroidal neovascularization. The second eye had angioid streaks complicated by choroidal neovascularization and underwent prior thermal laser photocoagulation. The third eye had a history of high myopia and a scleral buckle procedure for retinal detachment. The fourth patient had bilateral idiopathic retinochoroiditis. We identified 16 case reports from 5 previous publications that support a MEWDS-like reaction to previous ocular insults. Conclusions We suggest a MEWDS-like reaction may be elicited by ocular events in a subset of susceptible patients. We hypothesize that damage to the outer retina may play a role in triggering the local inflammatory response.

Patients with advanced heart failure suffer from severe and persistent symptoms, often not responding disease-modifying drugs, a marked limitation of functional capacity and poor quality of life that can ameliorate with inotropic drugs therapy. In small studies, pulsed infusions of classical inotropes (ie, dobutamine and milrinone) are associated with improvement in hemodynamic parameters and quality of life in patients with advanced heart failure. However, because of the adverse effects of these drugs, serious safety issues have been raised. Levosimendan is a calcium-sensitizing inodilators with a triple mechanism of action, whose infusion results in hemodynamic, neurohormonal, and inflammatory cytokine improvements in patients with chronic advanced HF. In addition, levosimendan has important pleiotropic effects, including protection of myocardial, renal, and liver cells from ischemia-reperfusion injury, and anti-inflammatory and antioxidant effects; these properties possibly make levosimendan an "organ protective" inodilator. In clinical trials and real-world evidence, infusion of levosimendan at fixed intervals is safe and effective in patients with advanced HF, alleviating clinical symptoms, reducing hospitalizations, and improving the quality of life. Therefore, the use of repeated doses of levosimendan could represent the therapy of choice as a bridge to transplant/left ventricular assist device implantation or as palliative therapy in patients with advanced heart failure.

Background Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies. Study design A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at “Scuola Medica Salernitana”, Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls. Results Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease. Conclusions Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.

Visual Abstract, Highlights • Because autophagy and Nox2 activation were identified as possible mechanisms for preservation of vessel integrity, they could be useful biomarkers to predict risk of aneurysm rupture by detecting the presence of a subclinical aneurysm or monitoring their growth. • Biomarkers such as molecules involved in autophagic machinery or Nox2 activation may help to explain pathological processes involved in TAA development and expansion, thereby opening up novel potential therapeutic strategies, such as the use of natural activators of autophagy or molecules that inhibit Nox2 activation, in the setting of aneurysmatic pathology. • Formation of aortic aneurysmal disease is multifactorial. Among the mechanisms involved, there is endothelial damage, oxidative stress, as well as an autophagy process, that seem to play a key role in TAA. Therefore, to identify the molecular mechanisms of these processes in TAA patients could lay the groundwork for defining strategies for preventing and slowing the progression of TAA., Summary Thoracic aortic aneurysms (TAA) pathogenesis and progression include many mechanisms. The authors investigated the role of autophagy, oxidative stress, and endothelial dysfunction in 36 TAA patients and 23 control patients. Univariable and multivariable analyses were performed. TAA patients displayed higher oxidative stress and endothelial dysfunction then control patients. Autophagy in the TAA group was reduced. The association of oxidative stress and autophagy with aortic disease supports the role of these processes in TAA. The authors demonstrate a putative role of Nox2 and autophagy dysregulation in human TAA. These findings could pinpoint novel treatment targets to prevent or limit TAA progression.

Acute infections may be complicated by thrombosis occurring in the venous and arterial circulation. This may be observed in patients with community-acquired pneumonia (CAP) and also in patients with coronavirus 2019 (COVID-19), that is a pandemic characterized by severe acute respiratory syndrome (SARS-CoV-2) needing mechanical ventilation and intensive care unit treatment. However, the type and rate of thrombosis can vary according to the cause of pneumonia as is more frequently complicated by arterial thrombosis in CAP, while an equal incidence of venous and arterial thrombosis occurs in SARS-CoV-2. The mechanisms of disease are overall platelet-related in CAP while activation of both platelets and clotting system is implicated in the pathogenesis of thrombosis in SARS-CoV-2; this finding could imply a different therapeutic approach of the two settings. Thrombosis may also occur in subjects vaccinated against SARS-CoV-2 even if its incidence is not so high (1/100 000); this rare effect occurs more prevalently in young women, is independent from known risk factors of thrombosis, is caused by antibodies against platelet PF4 and is counteracted by treatment with immunoglobulin and glucocorticoids.

The arteriovenous fistula (AVF) has long been considered the optimal vascular access. However, the evolving characteristics of the ageing dialysis population limit the creation of an AVF in all patients. Thus, more patients start hemodialysis (HD) with a central venous catheter (CVC) rather than an AVF, and the supremacy of the AVF has recently been questioned. The aim of this study was to analyze the incidence and rate of access complications in 100 patients between 2010 and 2015. A total of 63 patients started HD with an AVF, while 37 began HD with a CVC. We found no differences in patient survival according to the vascular access in use at the beginning of dialysis, but patients were more likely to die while undergoing dialysis by means of a CVC than an AVF. Patients started on dialysis with a CVC had more cardiovascular disease, while patients who began dialysis with an AVF presented more hypertension. Fistulas presented a longer survival time despite more hospital admissions, but CVCs bore a higher risk of infections. Our results suggest that starting dialysis with a CVC does not confer a greater risk of death.

Objective To validate the Italian version of the Myasthenia Gravis Impairment Index (MGII). Introduction MGII is a recent promising measure developed for MG patient evaluation. It includes a clinical severity evaluation and a patient-reported questionnaire. It has been developed in English and has demonstrated feasibility, reliability, and construct validity. Recently, its Dutch translation has been validated. Methods MGII was translated to Italian with a multi-step forward process. We assessed correlations with the following scores: Istituto Nazionale Carlo Besta score for Myasthenia Gravis (INCB-MG), the MG Activities of Daily Living (MG-ADL), the Myasthenia Gravis Composite (MGC), the Quality of Life 15 for Myasthenia Gravis (QOL15-MG), and the Myasthenia Gravis Disability (MGDIS). We also assessed differences in MGII scores by disease severity with the ANOVA Kruskal–Wallis test. Results One hundred forty-one patients were enrolled. The mean MGII total score was 13.3 ± 11.9 (range 0–49), with a mean ocular subscore of 3.7 ± 4.7 and a mean MGII generalized subscore of 9.6 ± 9.0. As expected, the MGII had a good correlation with the other severity scores. The MGII had a lower floor effect (3.5%) than the other measures. Twenty-five patients were assessed in follow-up; as expected, the MGII change scores had moderate correlations with change in other MG severity measures and lower correlations with quality of life measures. Conclusions The MGII score was cross-culturally validated in an Italian cohort of MG patients. We confirmed its lower floor effect and the correlations with other MG measures including INCB-MG that was not evaluated in previous studies.

Over the past decade, the fields of civil engineering, i.e., structural engineering, have increasingly used the building information modelling (BIM) approach in both professional practice and as the focus of research. However, the field of structural engineering, which can be seen as a sub-discipline of civil engineering, misses, as far as the authors are aware, a real state-of-the-art on the use of BIM in this regard. The aim of this paper, therefore, is to start bridging that gap. In particular, the authors have conducted a traditional literature review on the utilisation of BIM in structural engineering, enabling them to perform a detailed content analysis of publications. The qualitative investigation of the literature that the authors have conducted has highlighted six main BIM uses in structural engineering: (1) structural analyses; (2) production of shop drawings; (3) optimized structural design, early identification of constructability issues, and a comparison of different structural solutions; (4) seismic risk assessments; (5) existing-condition modelling and retrofitting of structures; and (6) structural health monitoring. Each of these is discussed in relation to their reference workflows; use of information models; information exchanges; and main limitations. In the conclusions, the authors identify current gaps in knowledge, as well as likely developments and improvements in the utilization of BIM in structural engineering. The authors also outline the possible significance of this work more broadly.

Long-term outcomes are poorly understood, and data in patients undergoing transvenous lead extraction (TLE) are lacking.The purpose of this study was to evaluate factors influencing survival in patients undergoing TLE depending on extraction indication.Clinical data from consecutive patients undergoing TLE in the reference center between 2000 and 2019 were prospectively collected. The total cohort was divided into groups depending on whether there was an infective or noninfective indication for TLE. We evaluated the association of demographic, clinical, and device-related and procedure-related factors on mortality.A total of 1151 patients were included. Mean follow-up was 66 months, and mortality was 34.2% (n = 392). Of these patients, 632 (54.9%) and 519 (45.1%) were for infective and noninfective indications, respectively. A higher proportion in the infection group died (38.6% vs 28.5%; P.001). In the total cohort, multivariable analysis demonstrated increased mortality risk with age75 years (hazard ratio [HR] 2.98; 95% confidence interval [CI] 2.35-3.78; P.001), estimated glomerular filtration rate60 mL/min/1.73 mLong-term mortality for patients undergoing TLE remains high. Consensus guidelines recommend evaluating risk for major complications when determining whether to proceed with TLE. This study suggests also assessing longer-term outcomes when considering TLE in those with a high risk of medium- and long-term mortality, particularly for noninfective indications.

Pleuropulmonary blastoma (PPB) is a rare but aggressive pediatric tumor originates from either lung or pleura. It was recently linked to the DICER I mutation as a part of predisposition syndrome for different type of tumor. It is characterized histologically by a primitive, variably mixed blastomatous and sarcomatous tissue. PPB is classified into four subtypes: cystic (type I and type Ir); cystic and solid (type II); solid (type III). PPB has no characteristic imaging findings. Integrated imaging can help to make a differential diagnosis and to recognize the subtypes in order to set up therapy. An early recognition and differentiation from congenital airway malformations and other benign cysts are very important. The treatment consists in a multimodal therapy including surgery and chemoterapy. We report a case of 3 years old female admitted at our hospital with fever, non productive cough and dyspnea, who was diagnosed with type II PPB.

Frame of the research: A managerial perspective of public engagement can help universities to strengthen the communication of university identity from a social, scientific, or accessibility point of view. Purpose of the paper: The goal of this paper is to investigate the concept of the online university public engagement from a managerial standpoint by examining those Italian universities that have engaged in Third Mission activities thanks also to recent ministerial decrees issued on the subject. Methodology: A content analysis of the main official websites of 50 Italian universities was performed. An exploratory factorial analysis made it possible to identify the main approaches to online public engagement. Findings: There are 4 main dimensions of online public engagement that have been communicated on Italian websites (social, cultural, research and widening engagement), each referring to a specific target. A so-called “Cultural engagement” approach emerges which underlines the role of the university as a pole of cultural and artistic attraction. Research limits: The research explores public engagement only in the Italian context. Although the article investigates more than 50% of the Italian universities, it does not allow the extension of the results to the reference population. Practical implications: Research results contribute to the understanding of online public engagement and map the current uses of stakeholder engagement activities in the university context to date. Originality of the paper: The research enriches the knowledge of the online public engagement construct thanks to the identification of a new dimension “Cultural engagement”, that had not yet emerged in international contexts.