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Background: Delirium is thought to be common across various settings of care; however, still little research has been conducted in rehabilitation. Aim: We investigated the prevalence of delirium, its features and motor subtypes in older patients admitted to rehabilitation facilities during the three editions of the “Delirium Day project”. Methods: We conducted a cross-sectional study in which 1237 older patients (age ≥ 65 years old) admitted to 50 Italian rehabilitation wards during the three editions of the “Delirium Day project” (2015 to 2017) were included. Delirium was evaluated through the 4AT and its motor subtype with the Delirium Motor Subtype Scale. Results: Delirium was detected in 226 patients (18%), and the most recurrent motor subtype was mixed (37%), followed by hypoactive (26%), hyperactive (21%) and non-motor one (16%). In a multivariate Poisson regression model with robust variance, factors associated with delirium were: disability in basic (PR 1.48, 95%CI: 1.17–1.9, p value 0.001) and instrumental activities of daily living (PR 1.58, 95%CI: 1.08–2.32, p value 0.018), dementia (PR 2.10, 95%CI: 1.62–2.73, p value < 0.0001), typical antipsychotics (PR 1.47, 95%CI: 1.10–1.95, p value 0.008), antidepressants other than selective serotonin reuptake inhibitors (PR 1.3, 95%CI: 1.02–1.66, p value 0.035), and physical restraints (PR 2.37, 95%CI: 1.68–3.36, p value < 0.0001). Conclusion: This multicenter study reports that 2 out 10 patients admitted to rehabilitations had delirium on the index day. Mixed delirium was the most prevalent subtype. Delirium was associated with unmodifiable (dementia, disability) and modifiable (physical restraints, medications) factors. Identification of these factors should prompt specific interventions aimed to prevent or mitigate delirium.

The present study aims to investigate cross-cultural differences and similarities in maternal and children's adjustment to COVID-19 restrictions in Spain and Italy, with reference to determinants of maternal stress. A total of 950 mothers (45.4% from Spain

BACKGROUND The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. METHODS SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective tial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d post-transplant; secondary end-points were severe complications. RESULTS The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% (P = 0.016) and 89.66% (P = 0.080) at 90 d and 86.21% (P = 0.041) and 86.2% (P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group (P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d (P = 0.017), (P = 0.015) in the simvastatin group. CONCLUSIONS Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.

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

Background Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. Methods Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. Results There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. Conclusion Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies.

The purpose was to investigate the effects of age on postural stability for children with autism spectrum disorder (ASD). Twenty-nine children with mild ASD were assigned into one of the three groups: 6–8 years (U8), 9–11 years (U11) and 12–14 years (U14). Participants stood barefoot with both feet on a force platform and maintained stationary for 15 seconds during eyes-open and eyes-closed conditions. Center of pressure data were collected and variables were calculated, including displacements, total distances, sway areas, and sample entropy. The variables were compared among the three groups using a mixed-model ANOVA. The age group effect was significant for mediolateral center of pressure displacement (p = 0.04) and sway distance (p = 0.02). Post-hoc comparisons revealed that U8 exhibited greater mediolateral displacement and total distance compared to U14, regardless of test conditions. The U14 group exhibited improved mediolateral postural stability compared to U8, whereas no differences were found between U8 and U11 or between U11 and U14. This may suggest that children with ASD could slowly develop postural stability but only demonstrate significant changes over a long period of time. Early intervention programs aimed to improve complexity of postural control could be beneficial.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

In this study, we investigated whether the difficulties in body motion (BM) perception may led to deficit in emotion recognition in Autism spectrum disorder (ASD). To this aim, individuals with high-functioning ASD were asked to recognise fearful, happy, and neutral BM depicted as static images or dynamic point-light and full-light displays. Results showed slower response times in participants with ASD only in recognising dynamic stimuli, but no group differences in accuracy. This suggests that i) a deficit in action chaining mechanism in ASD may prevent the recognition of dynamic BM automatically and rapidly, ii) individuals with ASD and high cognitive resources can develop alternative—but equally successful—strategies to recognise emotional body expressions. Implications for treatment are discussed

Parental rejection has been consistently empirically implicated in a wide array of developmental, behavioural and psychological problems worldwide. However, the interaction effect between parental rejection in childhood and the oxytocin receptor genotype on psychological adjustment has yet to be investigated. The present study aimed to investigate gene–environment interaction effects between parental rejection (maternal and paternal) and oxytocin receptor (OXTR) gene polymorphisms (rs53576 and rs2254298) on depressive symptoms in adults in different cultural contexts. Adults from Italy and Japan (N = 133, age = 18–27 years, females = 68) were preliminarily genotyped and then completed the Parental Acceptance-Rejection Questionnaire for mothers and fathers and the Beck Depression Inventory. Hierarchical multiple regression analysis showed that paternal rejection was related to self-reported depression and that the effect of parental rejection was moderated by OXTR gene polymorphisms and nationality. Among Italians, OXTR rs2254298 A-carriers showed resilience to negative early parental care, whereas among Japanese, OXTR rs53576 non-A-carriers showed resistance to negative early paternal care. These findings align with expected relations between perceived acceptance–rejection and an individual’s psychological adjustment, as proposed by interpersonal acceptance–rejection theory, and indicate the need for future studies adopting a multicultural and multilevel approach to better understand how the effects of parental rejection extend into adulthood.

Teriflunomide is a drug with immunosuppressive and selective immunomodulatory action, characterized by anti-inflammatory and antiproliferative properties. Several clinical studies have demonstrated the efficacy and safety of this drug in Multiple Sclerosis, estimating a significant improvement in cognitive performance.The aim of our study is to evaluate the effects of teriflunomide by analysing the correlation between brain atrophy and the general cognitive profile and evaluating long-term changes. The effect of teriflunomide was studied in 30 patients with multiple sclerosis and 30 control subjects. Patients underwent a full cognitive profile assessment using the Brief Repeatable Battery of Neuropsychological Tests and a neuroimaging examination with a 3.0 T working scanner.Our results suggested that treatment with teriflunomide could potentially not only slow down the accumulation of microstructural tissue damage in Grey Matter and With Matter, but also better preserve the cognitive profile, particularly by highlighting the benefits in the memory domain. Thanks to drug therapy, brain volume in our patients has remained constant, leading to improvements in memory, indicating teriflunomide as a neuroprotective potential and further strengthening the evidence of a link between loss of brain volume and cognitive impairment.

The few studies available on quality of attachment in school-age children with autism spectrum disorder (ASD) exclusively used questionnaires assessing explicit attachment representations. Thus, in the current study we assessed both explicit and implicit attachment representations in 23 children with ASD (without intellectual disability), 22 with learning disabilities and 27 with typical development aged from 7 to 13 years. A self-reported measure on the quality of attachment to parents and a semi-structured interview were administered to the children. In addition, a developmental assessment of the child including measures of intelligence and social-communication impairment was conducted. Despite the lack of group differences on explicit attachment representations, we found that children with ASD showed higher rates of at-risk self-protective strategies and psychological trauma compared to the TD group. Children with SLD also showed a high level of at-risk implicit attachment representations than TD, albeit to a lesser extent compared to children with ASD. These results may be related to several factors associated with ASD impairment and developmental pathways, such as the atypical learning process which occur at interpersonal level, the difficulties in social information processing and reflective functioning. Our findings suggested that children with ASD may experience difficulties in the construction of balanced implicit attachment representations. Thus, a more comprehensive assessment of attachment including both implicit and explicit representations is recommended.

Several studies reported the presence of a recently discovered polyomavirus (PyV), Lyon IARC PyV (LIPyV), in human and domestic animal specimens. LIPyV has some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV (MCPyV), respectively. In this study, we demonstrate that LIPyV early proteins immortalize human foreskin keratinocytes. LIPyV LT binds pRb, accordingly cell cycle checkpoints are altered in primary human fibroblasts and keratinocytes expressing LIPyV early genes. Mutation of the pRb binding site in LT strongly affected the ability of LIPyV ER to induced HFK immortalization. LIPyV LT also binds p53 and alters p53 functions activated by cellular stresses. Finally, LIPyV early proteins activate telomerase reverse transcriptase (hTERT) gene expression, via accumulation of the Sp1 transcription factor. Sp1 recruitment to the hTERT promoter is controlled by its phosphorylation, which is mediated by ERK1 and CDK2. Together, these data highlight the transforming properties of LIPyV in in vitro experimental models, supporting its possible oncogenic nature. IMPORTANCE Lyon IARC PyV is a recently discovered polyomavirus that shows some structural similarities to well-established animal and human oncogenic PyVs, such as raccoon PyV and Merkel cell PyV, respectively. Here, we show the capability of LIPyV to efficiently promote cellular transformation of primary human cells, suggesting a possible oncogenic role of this virus in domestic animals and/or humans. Our study identified a novel virus-mediated mechanism of activation of telomerase reverse transcriptase gene expression, via accumulation of the Sp1 transcription factor. In addition, because the persistence of infection is a key event in virus-mediated carcinogenesis, it will be important to determine whether LIPyV can deregulate immune-related pathways, similarly to the well-established oncogenic viruses.

The pulmonary artery catheter (PAC)-derived cardiac power index (CPI) has been found of prognostic value in cardiogenic shock (CS) patients. The original CPI equation included the right atrial pressure (RAP), accounting for heart filling pressure as a determinant of systolic myocardial work, but this term was subsequently omitted. We hypothesized that the original CPI formula (CPIA single-centre cohort of 80 consecutive Society for Cardiovascular Angiography and Interventions (SCAI) B-D CS patients with available PAC records was included. Overall in-hospital mortality was 21.3%. Results showed CPIIncorporating RAP in CPI calculation (CPI

Extracorporeal membrane oxygenation (ECMO) represents a therapeutic option for cardiopulmonary support in patients with high-risk pulmonary embolism (PE); however, no definite consensus exists on ECMO use in high-risk PE. Hence, we aim to provide insights into its real-world use pooling together all available published experiences. We performed a systematic review and pooled analysis of all published studies (up to April 17, 2020) investigating ECMO support in high-risk PE. All studies including at least four patients were collectively analyzed. Study outcomes were early all-cause death (primary endpoint) and relevant in-hospital adverse events. A total of 21 studies were included in the pooled analysis (n = 635 patients). In this population (mean age 47.8 ± 17.3 years, 44.5% females), ECMO was indicated for cardiac arrest in 62.3% and immediate ECMO support was pursued in 61.9% of patients. Adjunctive reperfusion therapies were implemented in 57.0% of patients. Pooled estimate rate of early all-cause mortality was 41.1% (95% CI 27.7%-54.5%). The most common in-hospital adverse event was major bleeding, with an estimated rate of 28.6% (95%CI 21.0%-36.3%). At meta-regression analyses, no significant impact of multiple covariates on the primary endpoint was found. In this systematic review of patients who received ECMO for high-risk PE, pooled all-cause mortality was 41.1%. Principal indication for ECMO was cardiac arrest, cannulation was chiefly performed at presentation, and major bleeding was the most common complication.

The capacity of the Child Behavior Checklist 1½–5 (CBCL 1½–5) to identify children with autism spectrum disorder (ASD) at 18 months was tested on 37 children clinically referred for ASD and 46 children at elevated likelihood of developing ASD due to having an affected brother/sister. At 30 months the clinically referred children all received a confirmatory diagnosis, and 10 out of 46 siblings received a diagnosis of ASD. CBCL 1½-5 profiles were compared with a group of matched children with typical development (effect of cognitive level controlled for). The capacity of the CBCL 1½-5 DSM Oriented-Pervasive Developmental Problems scale to differentiate correctly between children diagnosed with ASD and children with typical development appeared dependent on group ascertainment methodology.

Severe coronary artery calcification increases percutaneous treatment complexity and the risk of intraprocedural complications, affecting acute and long-term outcomes. Current use of specialty balloons and atherectomy technologies is limited due to the higher risk of complications, degree of technical difficulty and operator experience. Intravascular lithotripsy (IVL) is a novel technology for severe calcified coronary artery disease that facilitates vessel preparation, enhancing vessel compliance. IVL system emits sonic waves that penetrate through vascular layers and disrupt both superficial and deep calcium, leaving the soft tissue unharmed. The purpose of the present review is to provide a summary of the evidence currently available on this therapy, including a practical description of the components and function of the shockwave coronary IVL system.

OBJECTIVES The unique factors associated with urinary tract infections (UTIs) in postmenopausal (PMP) women have been significantly less investigated as compared with premenopausal (PreMP) women. Our objective was to compare the prevalence of uropathogens and antibiotic resistance patterns between PreMP and PMP women with UTIs. METHODS This was a cross-sectional analysis of PreMP and PMP women treated for a UTI in a urogynecologic practice between November 2016 and November 2017. Diagnostic criteria for UTI included lower urinary tract symptoms and a positive urine culture. Our primary outcome was proportion of non-Escherichia coli UTIs between groups. RESULTS We had 370 women with mean (SD) age of 66.7 (12.8) years and body mass index of 29.1 (7.1) kg/m2. Most women were PMP (88.6%). Postmenopausal status did not increase the proportion of non-E. coli UTI (42.7% PMP vs 33.3% PreMP, P = 0.25) or decrease the proportion of pansensitive UTI (36.0% PMP vs 42.9% PreMP, P = 0.38).In multivariable analysis, women with a history of rUTI were at higher odds of having a non-E. coli UTI (adjusted odds ratio, 1.93; 95% confidence interval, 1.21-3.08; P = 0.01) and at lower odds of pansensitive urine culture (adjusted odds ratio, 0.37; 95% confidence interval, 0.22-0.63; P < 0.01) as compared with those without rUTI, when controlling for confounders. Postmenopausal women with a history of rUTI had the highest proportion of non-E. coli UTIs (51.1%, P < 0.01) and lowest proportion of pansensitive uropathogens (29.1%, P < 0.01) as compared with other PMP women and PreMP without a history of rUTI. CONCLUSIONS In a urogynecologic population, a history of rUTI, more than menopausal status, significantly impacted the prevalence of specific uropathogens and resistant organisms.

Background The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells. Methods Envisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed. Results We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway. Conclusion Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.

Percutaneous coronary intervention (PCI) for aorto-ostial chronic total coronary occlusion (CTO) can be a particularly challenging lesion subset. The aim of this study was to analyze the technical aspects and outcomes of aorto-ostial CTO PCI in a multicenter registry.Patients undergoing aorto-ostial CTO PCI at 4 centers between February 2013 and December 2018 were included. Success rates, as well as procedural aspects and outcomes, were analyzed.A total of 103 patients were included. Mean age was 64±10 years and the mean J-CTO score was 3.1±1.1. Thirty-one lesions (30.4%) were flush ostial CTOs. Technical and procedural success were achieved in 79 (76.7%) and 78 (75.7%) of the patients, respectively. The retrograde approach was the most frequent successful crossing technique (n=49; 62.0%), especially in flush vs nonflush aorto-ostial CTOs (82.6% vs 53.5%; P=.02). The only variable independently associated with technical failure was the absence of interventional collaterals (OR, 12.38; 95%CI, 4.02-38.15; P.001). Coronary perforation occurred in 4 patients (3.9%) requiring covered stent implantation (without subsequent cardiac tamponade) and 2 patients (1.9%) had a stroke (one of which was a transient ischemic attack). During a median follow-up of 31 months, 3 (2.9%) patients died from cardiovascular causes and 13 (12.6%) required repeat target vessel revascularization.Aorto-ostial occlusions represent a challenging subset for PCI. However, an acceptable success rate with favorable outcomes during follow-up can be achieved by experienced operators. The presence of interventional collaterals allowing the use of the retrograde approach is key for achieving procedural success.

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.

Skeletal maturity assessment may be performed using low-dose scoliosis radiographs (LDSS) with simultaneous imaging of the hand or proximal humerus. We sought to compare the practicality, reliability and validity of the Sanders skeletal maturity staging (SMSS), proximal humerus ossification system (PHOS) and the thumb ossification composite index (TOCI) as skeletal maturity assessment tools using LDSS.A survey including 85 LDSS and 42 hand radiographs was administered to four orthopedic clinicians. Each rater assessed the TOCI, SMSS and PHOS stage for each image. Standing LDSS with hands at the patient's side were used for TOCI, SMSS, and PHOS measurements. SMSS and TOCI measurements on dedicated hand radiographs were assessed as a comparison. Interobserver reliability was calculated for each scale using Fleiss' kappa. For SMSS and TOCI, intraobserver correlation between measurements on LDSS and measurements on hand radiographs were also assessed.472 TOCI measurements, 288 SMSS measurements, and 340 measurements were collected. Kappa interobserver reliability for TOCI was 0.79 (strong) using hand radiographs and 0.74 (strong) using LDSS. Kappa for SMSS was 0.66 (strong) using hand radiographs and 0.45 (moderate) using LDSS. Kappa for PHOS was 0.51 (moderate) using LDSS. Intraobserver agreement between LDSS and hand imaging averaged 0.78 (strong) for TOCI and 0.34 (weak) for SMSS.Skeletal maturity assessment with TOCI using LDSS demonstrates strong interobserver reliability when hands are placed at the patient's side and correlates well with assessment on hand radiographs. TOCI achieved better inter- and intraobserver reliability compared to SMSS and PHOS, likely because the thumb readily assumes a good position in standing scoliosis sterioradiographs.Diagnostic-Level III.

Objectives Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. Design This is a cross-sectional study nested in the 2017 Delirium Day project. Setting and Participants The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Methods Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. Results The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Conclusions and Implications Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.

Contrast-induced acute kidney injury (CI-AKI) consists in acute decline in renal function following iodinated contrast media exposure. It has a significant impact on long-term prognosis and mortality, development of chronic kidney disease and on the rate of hospitalization due to cardiovascular or renal events. Anamnestic and procedural aspects linked to higher risk of CI-AKI have been investigated and new devices have been designed in order to prevent it. This paper deals with CI-AKI in interventional cardiology, focusing on patients' risk stratification, contrast media agent selection and contrast media volume reduction strategies, in order to suggest a standardized algorithm.

The family and community nurse-led proactive management of COPD patients: experience of an Italian health district.Integrated care management for COPD may reduce healthcare utilisation, improving cost-efficiency.To assess the primary outcomes of a family and community nurse-led proactive management of COPD patients of an Italian health district.Target population comprised men and women60 years, resident in the municipalities of Collegno and Grugliasco (metropolitan area of Turin). Administrative databases (hospital discharge records, drug prescriptions, legal exemptions) were first used to identify patients with diagnosis of COPD; the cases were validated by the General Practitioners (GPs). The 335 patients were enrolled from July 1, 2015 to November 30, 2016. Family and community nurses were responsible for anamnesis, spirometry, assessment of adherence to therapy, counselling and healthy lifestyles education. GPs were responsible for the clinical staging and revision of therapy. Patients were followed-up to 12 months.Improvements were observed in smoking cessation (prevalence of smokers from 23.9% to 20%), BMI normalization (in 13.4% of patients out of standard), physical activity (from 32.5% to 64.5% of patients), and pneumococcal vaccinations (from 14.9% to 58%). The last two outcomes were statistically significant. Patients showed high levels of satisfaction; 12-months compliance was 62.1%.A family and community nurse-led proactive management of COPD patients in primary care is feasible and effective. Interventions should be structured, personalised and multi-component, oriented at motivating, engaging and supporting the patients. Positive results led to continue and extend the programme.

This study assesses the safety and efficacy of thin-strut stents in non-left main (non-LM) bifurcation coronary lesions.Thinner struts of recent drug-eluting stent (DES) devices are associated with improved outcomes, but data about their performance in challenging scenarios are scant.RAIN was a retrospective multicenter registry enrolling patients with coronary bifurcation lesions or left main (LM) disease treated with thin-strut DESs. Target-lesion revascularization (TLR) was the primary endpoint, while major adverse clinical event (MACE) rate, a composite of all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), TLR, and stent thrombosis (ST), and its single components were the secondary endpoints. Multivariable analysis was performed to identify predictors of TLR. Outcome incidences according to stenting strategy (provisional vs 2-stent technique), use of final kissing balloon (FKB), and intravascular ultrasound/optical coherence tomography optimization were further investigated in prespecified subanalyses.A total of 1803 patients (59% acute coronary syndrome, 41% stable coronary artery disease) with non-LM bifurcations were enrolled. After a median follow-up of 12 months, TLR incidence was 2.5% (2.2% for provisional stenting and 3.5% for 2-stent technique). MACE rate was 9.4% (all-cause death, 4.1%; MI, 3.2%; TVR, 3.7%; definite ST, 1.1%). After multivariable adjustment, postdilation (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.71; P.01) and provisional stenting (HR, 0.62; 95% CI, 0.55-0.89; P=.03) were associated with lower TLR rates. FKB was associated with a lower incidence of TLR in the 2-stent subgroup (P=.03). Intracoronary imaging had no significant impact on the primary endpoint.Thin-strut DES options represent an effective choice in bifurcation lesions. Postdilation and provisional stenting are associated with a reduced risk of TLR. FKB should be recommended in 2-stent techniques.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia., The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16. Here, we describe the characterization of the in vitro transforming properties of the entire beta-3 species, which includes three additional HPV types: HPV75, HPV76, and HPV115. HPV49, HPV75, and HPV76 E6 and E7 (E6/E7), but not HPV115 E6 and E7, efficiently inactivate the p53 and pRb pathways and immortalize or extend the life span of human foreskin keratinocytes (HFKs). As observed for HR HPV16, cell cycle deregulation mediated by beta-3 HPV E6/E7 expression leads to p16INK4a accumulation, whereas no p16INK4a was detected in beta-2 HPV38 E6/E7 HFKs. As shown for HPV49 E6, HPV75 and HPV76 E6s degrade p53 by an E6AP/proteasome-mediated mechanism. Comparative analysis of cellular gene expression patterns of HFKs containing E6 and E7 from HR HPV16, beta-3 HPV types, and beta-2 HPV38 further highlights the functional similarities of HR HPV16 and beta-3 HPV49, HPV75, and HPV76. The expression profiles of these four HPV HFKs show some similarities and diverge substantially from those of beta-3 HPV115 E6/E7 and beta-2 HPV38 E6/E7 HFKs. In summary, our data show that beta-3 HPV types share some mechanisms with HR HPV types and pave the way for additional studies aiming to evaluate their potential role in human pathologies. IMPORTANCE Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia.

Objectives To evaluate the safety and the feasibility of balloon aortic valvuloplasty (BAV) procedure made by trained operators in centers not performing transcatheter aortic valve implantation (TAVI). Background BAV is a valuable therapeutic tool for patients with symptomatic severe aortic valve stenosis (AS) at prohibitive risk for TAVI or surgery. Methods Consecutive high-risk AS patients underwent BAV in five non-TAVI centers, where BAV operators had completed a 6-month training period in high-volume TAVI centers (Group A). All clinical, echocardiographic, and procedural data were prospectively collected and compared with data of patients treated in TAVI center (Group B). Results Between June 2016 and June 2017, 55 patients (83.9 ± 7.0 years) were enrolled: 25 in Group A and 30 in Group B. After BAV, a substantial reduction of the peak-to-peak aortic valve gradient was obtained in both groups (-35.3 ± 15.2 vs -28.8 ± 13.9 mmHg, P =0.25). No major bleeding or vascular complications occurred. In-hospital death was observed in three patients of Group A and two patients of Group B (P =0.493). The mean follow-up time was 303 ± 188 days; no patients were lost. The 1-year survival free from overall death (Group A 75.8% vs Group B 68.8%; P =0.682) and heart failure rehospitalization (Group A 73.0% vs Group B 66.8%; P =0.687) was similar in the two groups. At multivariable analysis, low left ventricular (LV) ejection fraction (HR: 0.943; P = 0.011) and cardiogenic shock (HR: 5.128; P = 0.002) at admission were independent predictors of mortality. Conclusions BAV is a safe and effective procedure that can be performed by trained operators in centers not performing TAVI.

Evidence of psychological distress in families during COVID-19 outbreak are arising. However, the perceived changes in psychological adjustment during home confinement with respect to the period before the pandemic have not been addressed yet. Moreover, little is known about the role of coparenting and specific COVID-19 contextual variables on parental stress and children's behavioral difficulties in the Italian context. Using a cross-sectional survey, we collected data on 841 Italian parents of children aged 3-11 years with typical development during the home confinement (20th April-18th May). We analyzed levels of parental stress, coparenting, and child externalizing behaviors before and during the home confinement. Additionally, hierarchical regressions were performed to investigate predictors of parental stress and child externalizing behaviors during the lockdown. Results showed that parental stress (especially in mothers) and child externalizing behaviors increased during the lockdown period. Coparenting was a strong predictor of parental stress, together with being a mother, younger child age, less time dedicated to the child, and scarce feasibility of remote working. Besides, child externalizing behaviors were predicted by male gender, less parental time dedicated to the child, higher parental stress, and child distance learning workload. Our findings indicate a negative impact of COVID-19 lockdown in both parents and children, suggesting that positive coparenting and time dedicated to children may help to reduce the detrimental effect of pandemic restrictions on family adjustment.Están surgiendo datos sobre el distrés psicológico en las familias durante el brote de la COVID-19. Sin embargo, aún no se han abordado los cambios percibidos en la adaptación psicológica durante el confinamiento. Este estudio tuvo como finalidad investigar los cambios en los niveles de estrés de los padres, las dificultades conductuales de los niños y la cocrianza antes y durante el confinamiento en el hogar. Además, analizamos los factores pronósticos de estrés por la crianza y las conductas de exteriorización de los niños durante el confinamiento. Utilizando una encuesta representativa, recogimos datos sobre 841 padres italianos durante el confinamiento en el hogar (desde el 20 de abril hasta el 18 de mayo). Analizamos los niveles de estrés de los padres, la cocrianza y las conductas de exteriorización de los niños antes y durante el confinamiento. Se realizaron regresiones jerárquicas para investigar los factores pronósticos de estrés de los padres y las conductas de exteriorización de los niños durante el confinamiento. El estrés de los padres (especialmente de las madres) y las conductas de exteriorización de los niños aumentaron durante el periodo de confinamiento. La cocrianza se mantuvo estable y fue un factor pronóstico fuerte del estrés de los padres, junto con ser madre, niños más pequeños, menos tiempo dedicado al niño y escasa viabilidad de trabajar virtualmente. Las conductas de exteriorización de los niños fueron pronosticadas por el género masculino, menos tiempo de los padres dedicado al niño, un mayor estrés de los padres y la cantidad de actividades de la enseñanza a distancia del niño. Nuestros resultados indican un efecto negativo del confinamiento por la COVID-19 tanto en los padres como en los niños e indican que la cocrianza positiva y el tiempo dedicado a los niños pueden contribuir a reducir el efecto perjudicial de las restricciones de la pandemia en la adaptación familiar.有证据表明，新冠肺炎疫情期间有家庭出现心理困扰。然而，封锁期间心理调整的变化尚未得到解决。本研究旨在调查父母压力水平的变化，儿童的行为困难，以及家庭被禁闭前和期间的亲子关系。此外，我们还考察了封闭期父母压力和儿童外化行为的预测因子。通过横断面调查，我们收集了841名意大利父母在家庭禁闭期间(4月20日- 5月18日)的数据。我们分析了在禁闭前和禁闭期间父母的压力水平，亲子关系和孩子的外化行为。父母压力(尤其是母亲)和儿童外化行为在封闭期有所增加。亲子关系保持稳定与否，可以预测父母压力，再加上身为母亲、孩子年龄更小、花在孩子身上的时间更少、远程工作的可能性更小。儿童外化行为的预测因素有: 男性、父母亲子时间较少、父母压力较大和儿童远程学习工作量较大。我们的研究结果表明，COVID-19封锁对父母和儿童都有负面影响，研究表明积极的父母教养方式和对儿童的投入时间可能有助于减少流行病期间的限制对家庭调整的不利影响。.

Contaminant concentrations in filter-feeding shellfish may indicate the health of coastal waters and consumption risks. Widespread expansion of the Pacific oyster (Crassostrea gigas) and its popularity as food make it a useful sentinel. We surveyed intertidal Pacific oysters in San Diego Bay, California for contaminants during summer 2018 and winter 2019. We compared contaminants in Pacific oyster to California mussel from California's State Mussel Watch Program (1993-2003) and human consumption thresholds. Contaminants such as neonicotinoid and chlorinated pesticides, selenium, and several metals were higher in Pacific oysters in summer, while PBDEs, benzylbutyl phthalate, and plastics were higher in winter. Contaminant levels were generally lower in Pacific oyster than mussel except for copper and zinc. Bay-wide PCB concentrations in oysters exceeded thresholds but individual samples (locations) also met or surpassed chlordane, PCB and PAH thresholds. Monitoring and risk assessments that consider species' biology, season, location, effects of multiple contaminants, and human consumption patterns will contribute to more effective consumption guidelines.

Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary approach. Both radiofrequency ablation (RFA) and radiation therapy (RT) were safe and effective in the management of painful metastases, even if they rely on totally different action mechanisms. A synergistic combination of RT and RFA seems to result in a better pain control. A systematic review was performed to describe the feasibility and effectiveness of the association between RFA and RT in the treatment of metastatic bone pain in oligo-metastatic patients, evaluating its role in alleviating bone pain, reducing the risk of fractures, and consequently ensuring a better quality of life.A systematic database search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review included studies that reported populations meeting the following inclusion criteria: (I) confirmed bone metastases in adult patients; (II) active bone metastases pain; (III) patients treated with combined RFA-RT; (IV) Original studies.Three papers that evaluated the combined treatment with doses ranging from moderately hypofractionated three-dimensional conformal RT (3D-CRT) and stereotactic body radiation therapy (SBRT) schedules were selected.The RFA-RT combined strategy appears to be promising in terms of efficiency and safety with adequate pain control and quality of life improvement. Positive effects on time to local failure and overall survival increase were also observed. Further prospective studies are needed to better delineate RFA-RT treatment benefits.

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Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. We are herein presenting and critically discussing the most representative evidence concerning immunotherapy in HER2+ BC cancer, both singularly and in combination with therapeutic agents acting throughout HER2-block, immune checkpoint inhibition and anti-cancer vaccines. The reader will be also provided with hints concerning potential future projection of the most promising immutherapeutic agents and approaches for the disease of interest.

The Absorb bioresorbable vascular scaffold (BVS) promised to avoid some of the disadvantages of its metal predecessors. Even though it has been taken off the market, limited data is available about its use in coronary chronic total occlusion (CTO) and its performance in overlap segments, which would be of special research interest due to its large thickness. This data is still pertinent since the platform of bioresorbable devices has not been abandoned, with several companies working on it. We aimed to compare healing and performance between overlap (OL) and non-overlap regions (NOL) of CTO lesions treated with BVS, using optical coherence tomography (OCT). Fourteen patients with overlapping BVS were included from the GHOST-CTO registry, resulting in 25 OL and 38 NOL regions. OCT based parameters were compared between OL and NOL groups at baseline (post-implantation) and 12-month follow-up. The mean age was 61.7 ± 7.2 years and 12 (86%) were males. Twelve (86%) patients underwent PCI for stable coronary artery disease and 2 (14%) had unstable angina. At 12-month follow-up, mean lumen area decreased in both NOL and OL regions, but the decrease was significantly larger in the OL region (NOL − 0.7 ± 1.33 vs. OL − 2.4 ± 1.54 mm2; p = 0.002). Mean scaffold area increased in both regions, but increased significantly more in NOL ( + 1.1 ± 1.54 vs. + 0.4 ± 1.16 mm2; p = 0.016). The percent of uncovered struts was lower in the OL group (5.0 ± 6.6% vs. 3.75 ± 8.7%, p = 0.043), whereas the percentage of malapposed struts was similar (0.3 ± 0.5% vs. 0.7 ± 2.3%, p = 0.441). Neointimal hyperplasia (NIH) was more pronounced in the OL region (0.13 ± 0.04 vs. 0.24 ± 0.10 mm2, p = 0.001). The OL and NOL segments showed comparable healing in terms of coverage and malapposition. However, NIH was more prominent in OL region. The long-term clinical implications of these findings needs further evaluation. The present study provides important insights for future development of BVS technology.

OBJECTIVE To determine the prevalence and predictors of nonattendance in an ACHD outpatient clinic, and to examine the relationship between nonattendance and emergency department (ED) visits, hospitalizations, and death. METHODS Patients ≥ 18 years who had scheduled appointments at an ACHD outpatient clinic between August 1, 2014 and December 31, 2014 were included. The primary outcome of interest was nonattendance of the first scheduled appointment of the study period, defined as "no-show" or "same-day cancellation." Secondary outcomes of interest were ED visits, hospitalizations, and death until December 2017. RESULTS Of 527 scheduled visits, 55 (10.4%) were nonattended. Demographic and socioeconomic characteristics such as race, income, and insurance type were associated with non-attendance (all P values

Background In the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, variable phenotypic expression may delay diagnosis. Panleukopenia, malignancy, and chronic lung disease all affect morbidity and mortality risks. Routinely used treatments include immunoglobulins, granulocyte-colony stimulating factor (G-CSF), and antibiotics; recent trials with a target C-X-C chemokine receptor type 4 (CXCR4) antagonist show promising results. Objective We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. Methods Data were collected from an international cohort of 18 patients with CXCR4 mutations. Results The clinical features manifested at 2.2 ± 2.6 years of age, whereas the disease diagnosis was delayed until 12.5 ± 10.4 years of age. Patients with WHIM commonly presented with a severe bacterial infection (78%). Pneumonia recurrence was observed in 61% of patients and was complicated with bronchiectasis in 27%. Skin warts were observed in 61% of patients at a mean age of 11 years, whereas human papilloma virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195 ± 102 cells/mm3 at onset), whereas lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, whereas G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. Conclusions The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. Patients with WHIM need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.

Preclinical rodent models of Parkinson's aim to recapitulate some of the hallmarks of the disease as it presents in humans, including the progressive neuronal loss of dopaminergic neurons in the midbrain as well as the development of a behavioral phenotype. AAV vector-based models of alpha-synuclein overexpression are a promising tool to achieve such animal models with high face and predictive validity.We have developed a preclinical rodent model of Parkinson's disease using an AAV-vector based overexpression of human alpha-synuclein. In the present work we characterize this model on a behavioral and histopathological level.We use a AAV9 vector for transgene delivery to overexpress human alpha-synuclein under a CBA promoter. We compare the behavioral and histopathological changes to a AAV vector control group where the transgene was omitted and to that of a 6-OHDA lesion control. We assessed the behavioral performance of these three groups on a series of tests (Cylinder, Stepping, Corridor) at baseline and up to 22 weeks post-injection at which point we performed electrochemical recordings of dopamine kinetics.The overexpression of human alpha-synuclein led to the progressive manifestation of behavioral deficits on all three behavioral tests. This was accompanied with impaired dopamine release and reuptake kinetics as demonstrated by electrochemical detection methods. Histopathological quantifications corroborated the findings that we induced a moderate cell loss with remaining cells displaying pathological markers which are abundant in the brains of human PD patients.In the present work we developed a characterized a rat model of PD that closely mimics human disease development and pathology. Such model will be of great use for investigation of disease mechanisms and early therapeutic interventions.

OBJECTIVE: To evaluate the prevalence, co-occurrence, sex differences and functional correlates of DSM-5 psychiatric disorders in 15-year-old adolescents born extremely preterm. METHOD: The Extremely Low Gestational Age Newborns (ELGAN) Study is a longitudinal study of children born < 28 weeks gestation. At age 15, six hundred and seventy adolescents completed the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), the Youth Self Report, a disability scale of participation in social roles and cognitive testing. Parents completed a family psychiatric history questionnaire. RESULTS: The most prevalent psychiatric disorders were anxiety, attention deficit hyperactivity disorder (ADHD) and major depression. More girls met criteria for anxiety than boys. Though 66% of participants did not meet criteria for a psychiatric disorder, 15% met criteria for one, 9% for two and 8% for ≥ 3 psychiatric disorders. Those with ≥ 2 psychiatric disorders were more likely to have repeated a grade, to have an individualized educational program (IEP) and to have a lower Non-Verbal IQ than those with no psychiatric disorders. Those with any psychiatric disorder were more likely to use psychotropic medications, to have greater cognitive and functional impairment, and to have mothers who were single, on public health insurance and had less than a high school education. Finally, a positive family psychiatric history was identified more frequently among adolescents with ≥ 3 psychiatric disorders. CONCLUSION: Among adolescents born extremely preterm anxiety, major depression and ADHD were the most prevalent psychiatric disorders at age 15. Adolescents with > 1 psychiatric disorder were at increased risk for multiple functional and participatory challenges.

Paget disease of the breast (PDB) is a rare form of cutaneous breast cancer. Up to date, no randomized studies evaluated the different management strategies. This systematic review investigates the role of radiotherapy and its best technical profile in the treatment of this disease, with great attention to doses and fractionation regimens.A systematic search was performed on PubMed, Embase and Scopus in order to detect case reports, case series and prospective as well as retrospective clinical studies describing histologically proven PDB and providing information about pertinent radiation treatments. Searching strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines.Inclusion criteria were met by six papers, dealing with radiation treatments performed postoperatively and in exclusive settings. No evaluations were performed on preoperative radiotherapy.Actually, the standard treatment of PDB reflects oncological principles of breast carcinoma therapy, including the role of breast-preserving surgery. The traditional radiotherapic dose is 50 Gy, with daily fractionation of 2 Gy. Adjuvant radiotherapy following breast preserving surgery represents the current standard of care; prospective studies could be of help in defining the role of exclusive radiotherapy, hypofractionated schemes and smaller target volumes.

International audience; Background: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed.Methods: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents.Results: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI.Conclusions: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Background The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. Methods and results All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 μm (n = 206) versus 81 μm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 μm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). Conclusion In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

To date, there is no severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-specific prognostic biomarker available. We assessed whether SARS-CoV-2 cycle threshold (Ct) value at diagnosis could predict novel CoronaVirus Disease 2019 (COVID-19) severity, clinical manifestations, and six-month sequelae. Hospitalized and outpatient cases were randomly sampled from the diagnoses of March 2020 and data collected at 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasopharyngeal swab at diagnosis as follows: Group A ≤20.0, 20.0&lt, group B ≤28.0, and Group C &gt, 28.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required, and survival. Two hundred patients were included, 27.5% in Groups A and B both, 45.0% in Group C, 90% of patients were symptomatic and 63.7% were hospitalized. The median time from COVID-19 onset to swab collection was five days. Lethality, disease severity, type, and number of signs and symptoms, as well as six-month sequelae distributed inversely among the groups with respect to SARS-CoV-2 Ct. After controlling for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p = 0.023), disease severity (p = 0.023), number of signs and symptoms (p &lt, 0.01), and presence of six-month sequelae (p &lt, 0.01). Early quantification of SARS-CoV-2 may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.

The administration of rescue medication at school concerns students for which it may be essential, on doctor's prescription, to take therapy during school hours. In this case, since the parents are absent, the first rescuer is necessarily the school staff, who should be properly trained because prolonged seizures can cause severe harm and even death.Every year, the Local Health Unit "TO3" in Northern Italy, provides training for school staff to administrate rescue medication at school. From December 2019 to February 2020, the same questionnaire was administered to school staff trained for seizures at the end of the course, while the staff trained for other diseases completed it before the course.About 60% of the sample (N = 123) had been trained in seizure management at least once in their lifetime. Median knowledge score in subjects with no seizures training was 7 (Q25/Q75: 5/8), while it was 9 (Q25/Q75: 6/10) in subjects with seizures training (p 0.001). The self-reported level of confidence in their skills to administer rescue medication was high in 10.2% of subjects not trained for seizures and in 62.9% of those trained (p 0.001).Results suggest that medical training for school staff increases knowledge scores and levels of self-confidence relating to the administration of rescue medication. Moreover, after the training, the school staff changed attitude toward seizures, no longer considering them a problem, and became more aware, less fearful, and more inclined to act in case of need, making school a better place for all students.

Introduction The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS. Methods All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes. Results Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6–59.9) in the VA-ECMO group and 58.3% (53.5–63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9–26.5) and 33.1% (25.9–41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0–22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039–3.159). Conclusion Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates.

Background although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. Objective to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients’ 30-day survival. Design observational study nested in the Delirium Day project, with 30-day follow-up. Setting acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. Subjects a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. Methods a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. Results overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45–1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41–1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27–2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33–2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28–2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. Conclusions in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.