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Background: Research has extensively documented inequalities in inpatient psychiatric care provided to people of minoritized ethnic groups. Nonetheless, the role of their previous engagement with community mental health care has been little studied., Aims: We aimed at exploring whether previous clinical care can influence key domains of subsequent psychiatric inpatient care for people of ethnic minorities., Methods: We identified patients with a first hospital admission between 2016 and 2022, from a representative, highly diverse, catchment area of Northern Italy, using electronic health data of the NOMIAC study. We aimed at testing the impact of clinical care prior to admission on indicators of poor inpatient care, as identified by a participatory expert panel, that is, compulsory admission, insufficient length of stay, administration of Long-Acting Antipsychotics (LAI) during the last 7 days before discharge. Multiple regression models, predicted and counterfactual proportions and path analyses from generalized structural equations modeling were used to explore the association between belonging to ethnic minorities and these indicators., Results: Among 1,524 participants, 18% were from minoritized ethnic groups. While these were more likely to experience an involuntary admission, regardless of previous care received, they were offered appropriate length of stay if had previous engagement with community mental health care. Both belonging to ethnic minorities and mental health care prior-to-admission were independently associated with early LAI administration., Conclusions: Several ethnic inequalities in inpatient care continue despite previous community mental health care provided. Future research should examine how these disparities translate into clinical outcomes. Nonetheless, there is the need to actively promote equity, improving the quality of inpatient care of minoritized ethnic groups.

Purpose: In the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses., Methods: We examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023. We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V 20Gy ), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose., Results: VMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V 20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected., Conclusions: In the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

In recent years, the restoration of p53 physiological functions has become an attractive therapeutic approach to develop novel and efficacious cancer therapies. Among other mechanisms, the oncosuppressor protein p53 is functionally regulated by MDM2 through its E3 ligase function. MDM2 promotes p53 ubiquitination and degradation following homodimerization or heterodimerization with MDM4. Recently, we discovered Pep3 (1, Pellegrino et al., 2015), a novel peptidic inhibitor of MDM2 dimerization able to restore p53 oncosuppressive functions both in vitro and in vivo. In this work, we were able to identify the key interactions between peptide 1 and MDM2 RING domain and to design peptide 2, a truncated version of 1 that is still able to bind MDM2. Integrating both computational and biophysical techniques, we show that peptide 2 maintains the conserved peptide 1-MDM2 interactions and is still able to bind to full-length MDM2., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Antonio Macchiarulo reports financial support was provided by Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi (C.I.N.M.P.I.S). Fabiola Moretti reports financial support was provided by the Italian Association for Cancer Research Grant (AIRC IG 21814). Andrea Temperini reports financial support was provided by Consorzio Interuniversitario Nazionale Metodologie e Processi Innovativi di Sintesi (C.I.N.M.P.I.S). Antonio Macchiarulo has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Fabiola Moretti has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Andrea Temperini has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Marco Ballarotto has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. Sonia Valentini has patent #IT102023000015816 pending to CNR, Via del Fosso di Fiorano 64, 00143 Roma. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The long-COVID syndrome is characterised by a plethora of symptoms. Given its social and economic impact, many studies have stressed the urgency of proposing innovative strategies other than hospital settings. In this double-blinded, randomised, case-control trial, we investigate the effects of sulphur thermal water inhalations, rich in H 2 S, compared to distilled water inhalations on symptoms, inflammatory markers and nasal microbiome in long-COVID patients., Methods: About 30 outpatients aged 18-75 with positive diagnosis for long-COVID were randomised in two groups undergoing 12 consecutive days of inhalations. The active group (STW) received sulphur thermal water inhalations whereas the placebo group received inhalations of sterile distilled non-pyrogenic water (SDW). Each participant was tested prior treatment at day 1 (T0), after the inhalations at day 14 (T1) and at 3 months follow-up (T2). At each time point, blood tests, nasal swabs for microbiome sampling, pulmonary functionality tests (PFTs) and pro-inflammatory marker measure were performed., Results: The scores obtained in the administered tests (6MWT, Borg score and SGRQ) at T0 showed a significant variation in the STW group, at T1 and T2. Serum cytokine levels and other inflammatory biomarkers reported a statistically significant decrease. Some specific parameters of PFTs showed ameliorations in the STW group only. Changes in the STW nasopharyngeal microbiota composition were noticed, especially from T0 to T2., Conclusions: Inhalations of sulphur thermal water exerted objective and subjective improvements on participants affected by long-COVID. Significant reduction of inflammatory markers, dyspnoea scores and quantitative and qualitative changes in the nasopharyngeal microbiome were also assessed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Digital mental health interventions (DMHIs) have surged in popularity over the last few years. However, adherence to self-guided interventions remains a major hurdle to overcome. The current study utilized a phased implementation design, incorporating diverse samples and contexts to delve into the engagement challenges faced by a recently launched online mental health platform in Brazil with self-evaluation forms. Employing an iterative mixed-methods approach, including focus groups, online surveys, and think-aloud protocols, the research aims to evaluate user satisfaction, identify barriers to adherence, and explore potential hybrid solutions. Engagement in the platform was evaluated by descriptive statistics of the number of instruments completed, and qualitative interviews that were interpreted thematically. In the fully self-guided mode, 2,145 individuals registered, but a substantial majority (88.9%) engaged with the platform for only 1 day, and merely 3.3% completed all activities. In another sample of 50 participants were given a choice between online-only or a hybrid experience with face-to-face meetings. 40% of individuals from the hybrid group completed all activities, compared to 8% in the online-only format. Time constraints emerged as a significant barrier to engagement, with suggested improvements including app development, periodic reminders, and meetings with healthcare professionals. While the study identified weaknesses in the number and length of instruments, personalized results stood out as a major strength. Overall, the findings indicate high satisfaction with the mental health platform but underscore the need for improvements, emphasizing the promise of personalized mental health information and acknowledging persistent barriers in a digital-only setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Moretti, Bortolini, Hartle, Moll, Mattos, Furtado, Fontenelle and Fischer.)

Underreporting is the main limitation of spontaneous reporting systems. This cohort-event monitoring study aims to examine the potential of short message service (SMS)-based surveillance compared to traditional surveillance systems. Using VigiVax software, parents of vaccinated children aged two years or younger, in the period March 2021-May 2022, received a single SMS inquiry about adverse events following immunization (AEFI). Responses were collected, validated by health operators and integrated with the information on electronic immunization registries. AEFI reports were automatically submitted to the Italian Pharmacovigilance system. Among 254,160 SMS messages sent, corresponding to 451,656 administered doses (AD), 71,643 responses were collected (28.2% response rate), and 21,231 of them (8.3%) reported AEFI. After a seriousness assessment based on clinical criteria, 50 reports (0.24%) were classified as serious. Among these, a causality assessment identified 31 reports at least potentially related to the vaccination (RR: 6.86/100,000 AD). Febrile seizures following MMRV (measles, mumps, rubella, varicella) vaccination accounted for 11 of these 31 cases, with an incidence of 32 per 100,000 AD. No fatal outcomes were reported. Our findings support the highly favorable risk profile of pediatric vaccinations and the possibility to improve spontaneous reporting through the integration of digital technologies.

Purpose: Posterior pelvic ring lesions are a common finding in patients with pelvic trauma, representing a challenging condition for trauma surgeons. Surgical options are different and there is not yet evidence about the best option. Aim of the study are: (i) to compare Lumbopelvic fixation (LPF) and ilio-sacral screw fixation (ISS) regarding clinical and radiological outcome in unstable posterior pelvic ring injuries, both as whole population and single similar fracture types according to Tile classification (C1vsC1, C2vsC2, C3vsC3); (ii) to analyze clinical outcomes and complications in lumbopelvic fixation group, comparing open and closed reduction technique., Methods: A retrospective multicenter study was performed. Data of the patients were collected. Inclusion criteria were: (i) unstable posterior ring lesions Tile C type, (ii) surgically treated either through ISS (Group A) or LPF (Group B), (iii) minimum follow-up 12 months. Radiological evaluation was made through plain radiographs in Antero-posterior (AP), inlet and outlet views. Last clinical evaluation at 12 months was assessed through Majeed Score, and quality of life (QoL) through SF-12., Results: Group A was represented by 76 patients, and Group B by 42. Group B had better result in Majeed score for non-workers (average 60.1 ± 21.6 vs 65.0 ± 15.6, p = 0.016*). Comparing only C3-type lesions, Group A showed a higher rate of implants breakage (p = 0.032*). Other differences had p > 0.05. Comparing patients underwent open (ORIF) or closed (CRIF) reduction in Group B, CRIF group had shorter hospitalization (47.2 vs 23.4 days, p = 0.020*), an earlier full weight-bearing recovery (4.1 vs 2.6 months, p = 0.035*) and a better Majeed score in workers patients (70.3 vs 82.8, p = 0.019*). Better results for CRIF group were also recorded in quality of life (QoL), both in mental (45.1 vs 55.2, p = 0.040*) and physical outcome (31.9 vs 50.7, p < 0.001*)., Conclusion: ISS and LPF represent both good choices in posterior pelvic ring lesions, however some significant differences were noted. LPF seems to be preferable if the patient did not work before the trauma, due to better clinical outcome. In Tile C3 lesions, LPF have lower breakage rates. If LPF is chosen, CRIF provides better clinical outcomes, QoL and lower hospitalization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Rationale & Objective: Body mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan., Study Design: A retrospective cohort study., Setting & Participants: 1,053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and at high risk of rapid disease progression., Predictor: Estimates of visceral adiposity extracted from coronal plane magnetic resonance imaging (MRI) scans using deep learning., Outcome: Annual change in total kidney volume (TKV) and effect of tolvaptan on kidney growth., Analytical Approach: Multinomial logistic regression and linear mixed models., Results: In fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of≥7% versus<5% (odds ratio [OR], 4.78 [95% CI, 3.03-7.47]). The association was stronger in women than men (interaction P<0.01). In linear mixed models with an outcome of percent change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (3-way interaction of treatment ∗ time ∗ visceral adiposity, P=0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual percent change in TKV for individuals with a normal BMI (DeLong's test z score: -2.03; P=0.04). Greater visceral adiposity was not associated with estimated glomerular filtration rate (eGFR) slope in the overall cohort; however, visceral adiposity was associated with more rapid decline in eGFR slope (below the median) in women (fully adjusted OR, 1.06 [95% CI, 1.01-1.11] per 10 unit increase in visceral adiposity) but not men (OR, 0.98 [95% CI, 0.95-1.02])., Limitations: Retrospective; rapid progressors; computational demand of deep learning., Conclusions: Visceral adiposity that can be quantified by MRI in the coronal plane using a deep learning segmentation model independently associates with more rapid kidney growth and improves classification of rapid progression in individuals with a normal BMI. Tolvaptan efficacy decreases with increasing visceral adiposity., Plain-Language Summary: We analyzed images from a previous study with the drug tolvaptan conducted in patients with autosomal dominant polycystic kidney disease (ADPKD) to measure the amount of fat tissue surrounding the kidneys (visceral fat). We had previously shown body mass index can predict kidney growth in this population; now we determined whether visceral fat was an important factor associated with kidney growth. Using a machine learning tool to automate measurement of fat in images, we observed that visceral fat was independently associated with kidney growth, that it was a better predictor of faster kidney growth in lean patients than body mass index, and that having more visceral fat made treatment of ADPKD with tolvaptan less effective., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Nursing homes (NHs) are crucial for de-hospitalization and addressing the needs of non-self-sufficient individuals with complex health issues. This study investigates the patient safety culture (PSC) in NHs within a northern Italian region, focusing on factor influencing overall safety perceptions and their contributions to subjective judgements of safety. A cross-sectional study was conducted on 25 NHs in the Autonomous Province of Trento. The Nursing Home Survey on Patient Safety Culture (NHSPSC) was utilized to assess PSC among NH staff. Multilevel linear regression and post hoc dominance analyses were conducted to investigate variabilities in PSC among staff and NHs and to assess the extent to which PSC dimensions explain overall perceptions of PS. Analysis of 1080 questionnaires (44% response rate) revealed heterogeneity in PSC across dimensions and NHs, with management support, organizational learning, and supervisor expectations significantly influencing overall safety perceptions. Despite some areas of concern, overall safety perceptions were satisfactory. However, the correlation between individual dimensions and overall ratings of safety was moderate, suggesting the need to enhance the maturity level of PSCs. Promoting a shift in PSC could enhance transparency, prioritize resident safety, empower nursing staff, and increase family satisfaction with care provided in NHs. The support provided by management to PSC appears essential to influence NH staff perceptions of PS.

Background: Identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. However, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. According to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). The primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using QuantiFERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated., Methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between October 2019 and August 2023., Results: We accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. All positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. Active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. During the 46 months of observation, no patients developed TB reactivation., Conclusions: Despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in Italy. This finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy., Competing Interests: Competing interests: The authors declare no conflict of Interest.

In Veneto Region, HPV vaccine has been actively offered to 12 year-old females since 2008, and to 12 year-old males since 2015. The study aims to analyze the safety profile of HPV4v and HPV9v vaccines and perform a case-by-case review of conditions of interest. Spontaneous reports related to HPV uploaded to the database of the Regional Pharmacovigilance Center between 2008-2022 were included. HPV vaccine doses administered until April 2022 in the Veneto Region were considered to calculate the reporting rate (RR). Potential "safety concerns" examined as conditions of interest were included through Standardized MedDRA or preferred terms searching queries. The level of diagnostic certainty was evaluated as per the Brighton Collaboration case definition criteria. A total of 637 reports and 1316 Adverse Events Following Immunizations (AEFI) were retrieved: 469 for HPV4v (73.6 %) and 168 for HPV9v (26.4 %). Serious reports were 71 (11.1 %): 49 (10.4 %) for HPV4v and 22 (13.1 %) for HPV9v. The RR for serious events between 2008-2022 was 6.9/100,000 administered doses, with no differences by vaccine type. Females and adults showed higher overall RR compared to males and to children and adolescents (p < 0.001), this result was confirmed by stratifying analysis by vaccine type. One case of Guillain Barré syndrome, anaphylactic shock, thrombocytopenia, Henoch Schoenlein purpura and four generalized seizures were reviewed. Vaccinovigilance data from the Veneto Region reaffirm a good safety profile for HPV vaccination and found no vaccine-related unexpected events. Such a detailed analysis may assist healthcare providers to advocate properly for HPV vaccination., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Zinc tungstate is a semiconductor known for its favorable photocatalytic, photoluminescence, and scintillation properties, coupled with its relatively low cost, reduced toxicity, and high stability in biological and catalytic environments. In particular, zinc tungstate evinces scintillation properties, namely the ability to emit visible light upon absorption of energetic radiation such as x rays, which has led to applications not only as radiation detectors but also for biomedical applications involving the delivery of optical light to deep tissue, such as photodynamic therapy and optogenetics. Here, we report on the synthesis of zinc tungstate nanorods generated via an optimized but facile method, which allows for synthetic control over the aspect ratio of the as-synthesized anisotropic motifs via rational variation of the solution pH. We investigate the effect of aspect ratio on their resulting photoluminescent and radioluminescent properties. We further demonstrate the potential of these zinc tungstate nanorods for biomedical applications, such as photodynamic therapy for cancer treatment, by analyzing their toxicological profile within cell lines and neurons., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Cationic cyclometalated hafnocenes [Cp Pr Cp CH2CH2CH2 Hf][B(C 6 F 5 ) 4 ] ( 4 Pr ) and [Cp i Bu Cp CH2CH(Me)CH2 F 6 F 5 ) 4 ] ( 4a iBu and 4b iBu F Pr ) 2 HfMe][B(C 6 F 5 ) 4 ] ( 1 F Pr ) and [(Cp i Bu ) 2 HfMe][B(C 6 F 5 ) 4 ] ( 1 iBu ) complexes via C-H activation. 4a iBu , 4b iBu , and 4 Pr , mimicking a propagating M-polymeryl species (M = transition metal) with or without a β-methyl branch on the metalated chains, serve to investigate whether and how the nature of the last inserted olefin molecules changes the structure, stability, and reactivity of the corresponding heterobimetallic complexes, formed in the presence of aluminum- or zinc-alkyl chain transfer agents (CTAs), which are considered relevant intermediates in coordinative chain transfer polymerization (CCTP) and chain shuttling polymerization (CSP) technologies. NMR and DFT data indicate no major structural difference between the resulting heterobridged complexes, all characterized by the presence of multiple α-agostic interactions. On the contrary, thermodynamic and kinetic investigations, concerning the reversible formation and breaking of heterobimetallic adducts, demonstrate that isomer 4a iBu , in which the β-Me is oriented away from the reactive coordination site on Hf, but not 4b iBu , having the β-Me pointing in the opposite direction, is capable of reacting with CTAs. Quantification of kinetic rate constants highlights that the formation process is rate limiting and that the nature of the last inserted α-olefin unit modulates transalkylation kinetics. The reaction of 4a iBu , 4b iBu , and 4 Pr with diisobutylaluminum hydride (DiBAlH) allows the interception and characterization of new heterobinuclear and heterotrinuclear species, featuring both hydride and alkyl bridging moieties, which represent structural models of elusive intermediates in CCTP and CSP processes, capturing the instant when an alkyl chain has just transferred from a transition metal to a main group metal, while the two metals remain engaged in a single heterobimetallic intermediate.

Background: Internally displaced people (IDP) in Iraq are 1.2 million (as March 2023). Protracted refugee status endangers the mental health, especially of minorities who survived persecution and conflict, such as the Yazidis. This study aims to identify the mental health needs of Yazidi adolescents and young adults (AYA) in the IDP camp of Bajed Kandala (Iraqi Kurdistan)., Methods: A focus group discussion (FGD) study was conducted between April and August 2022. The FGDs involved AYAs, as well as the staff of the clinic of the Bajed Kandala camp. An inductive approach was adopted referring to the 'theme' as the unit of content analysis of the text. All FGDs were recorded and transcribed. The analysis was carried out independently by two researchers. The inter-rater agreement was assessed through the Cohen's k., Results: A total of 6 FGDs were conducted. The participants were 34 of whom 21 (61.8%) females with a median age of 18.5 years (IQR 17.0-21.0). A total of 156 themes were found as relevant to the objective of this study. Four main areas and twelve subareas of needs in mental health were identified. The interrater agreement over the main area and subareas was good (κ = 0.78 [0.95CI 0.69-0.88], κ = 0.82 [0.95CI 0.73-0.91], respectively). The four areas had a similar frequency: Activities (28.2%), Individual (27.6%), Social relationships (22.4%) and Places/setting (21.8%). The subareas 'community' and 'internal resources' were labelled as negative 85.7% and 61.9% of the time, respectively. These sub-areas referred to stigma and self-stigma towards mental health. The subarea 'female condition' was always considered as negative, as well as the subareas 'camp' and 'tent' referring to housing as an important social determinant of mental health., Conclusions: Community stigma and self-stigma are two still important factors preventing the achievement of mental well-being. Alongside these, a gender gap in mental health was identified in the FGDs. These factors should be taken into account in order to guide future mental health interventions in refugee camps., (© 2024. The Author(s).)

Coastal wetlands represent areas that can testify historical accumulation of litter. We analyzed the anthropogenic litter deposited on the channel bottom of a coastal wetland area that experienced water stress due to extreme summer dryness after about 20 years. We hypothesize that the litter accumulated in the different areas over the years reflects the different social user categories (i.e., fishermen, beach users, hunters) and exposure to meteo-marine events. Our findings highlight that historically accumulated litter is composed of plastics (78.8 %), clothes (8.9 %), and glass (4.9 %). Moreover, litter concentration averages 53.6 items/ha in the 8 sectors. The most found categories were common household items (25.4 %), diverse (professional and consumer) items (24.2 %), and food and beverages packaging (21.4 %). Finally, litter diversity indices and the Detrended Correspondence Analysis showed sector and litter type similarities. We reported for the first time the presence of litter accumulated for 20 years testifying non-more occurring recreational activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Uterine scarring is a risk factor for placenta accreta spectrum (PAS) disorder. We aimed to determine the factors related to PAS in women who had previously undergone a cesarean., Methods: We performed a case-control study where women who underwent postpartum hysterectomy for placenta accreta/percreta (cases) were matched to all women with a previous cesarean who delivered in the week before each case (controls). Maternal characteristics along with previous cesarean characteristics were compared between cases and controls. Univariate and multivariate logistic regression analyses were performed to determine risk factors related to PAS., Results: We compared 64 cases of PAS that required hysterectomy to 192 controls. The factors related to PAS were a history of uterine surgery (OR 27.4; 95% CI 5.1-146.5, P < 0.001) and the number of previous cesareans (2 cesareans: OR 7.2; 95% CI 3.4-15.4, P < 0.001; more than 2 cesareans: OR 7.9; 95% CI 2.9-21.5, P < 0.001). In women with a single previous cesarean without previous uterine surgery, an interdelivery interval of fewer than 18 months (OR 6.3; 95% CI 1.8-22.4, P = 0.004) and smoking (OR 5.8; 95% CI 1.2-27.8, P = 0.03) were related to PAS. The gestational age and the cervical dilatation at previous cesarean were not associated with PAS (all with P > 0.05). The lack of data regarding the closure of the uterus at previous cesareans prevents us from drawing solid conclusions., Conclusions: Previous uterine surgery, the number of previous cesareans, smoking, and an interdelivery interval of fewer than 18 months after cesarean are significant risk factors for PAS requiring postpartum hysterectomy., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3-147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored., Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022., Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V., Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

In patients with Acute Myeloid Leukemia (AML), the assessment of disease risk plays a central role in the era of personalized medicine. Indeed, integrating baseline clinical and biological features on a case-by-case basis is not only essential to select which treatment would likely result in a higher probability of achieving complete remission, but also to dynamically customize any subsequent therapeutic intervention. For young high-risk patients with low comorbidities burden and in good general conditions (also called "fit" patients), intensive chemotherapy followed by allogeneic stem cell transplantation still represents the backbone of any therapeutic program. However, with the approval of novel promising agents in both the induction/consolidation and the maintenance setting, the algorithms for the management of AML patients considered eligible for intensive chemotherapy are in constant evolution. In this view, we selected burning issues regarding the identification and management of high-risk AML, aiming to provide practical advice to facilitate their daily clinical management in patients considered eligible for intensive chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Palmieri, Billio, Ferrara, Galimberti, Lemoli, Todisco, Moretti and Venditti.)

Following the Russian-Ukrainian conflict, the well-being of millions of Ukrainians has been jeopardised. This study aims to translate and test the psychometric features of the Ukrainian version of the General Health Questionnaire 12 (GHQ-12). The study included Ukrainian refugees housed in Verona (Italy) between November/2022 and February/2023. The Ukrainian translation was obtained through a 'forward-backward' translation. Questionnaire was completed by 141 refugees (females: 78.7%). Median age was 36 years (IQR 23-43). Individuals with a score suggestive of psychological distress were 97 (68.8%). Cronbach's coefficient was 0.84 (0.95CI 0.80-0.88). According to confirmatory factor analysis, both single- (modelB1) and two-factor (model B2) structures with bimodal scoring method fitted the data satisfactorily. The two factors of model B2 had a 0.88 correlation. Pearson coefficient showed a positive significant correlation between the GHQ-12 and International Trauma Questionnaire scores (ρ = 0.53, 0.95CI 0.40-0.64, p < 0.001). The GHQ-12 Ukrainian translation showed good psychometric features being a reliable and valid instrument to assess Ukrainian refugees' general well-being., (© 2024. The Author(s).)

Objective: Evidence on the relationship between depression and clinical dimensions of schizophrenia remains limited. This cross-sectional study investigated the association between depression and Positive and Negative Syndrome Scale (PANSS) dimensions in people with schizophrenia spectrum disorders., Methods: Trained assessors administered the PANSS to measure symptoms of schizophrenia and the Calgary Depression Scale for Schizophrenia to measure depression. The association of depression with overall PANSS score and related dimensions was investigated in multiple logistic regression analyses., Results: We included 231 inpatients with schizophrenia spectrum disorders (mean age: 42.4 (SD: 12.9) years; men: 58.9%; mean overall PANSS score: 82.5 (SD: 20.1); drug-free or naïve: 39.3%), including 78 (33.8%) with clinically significant depressive symptoms. Depression was associated with higher overall (regression coefficient, SE: 0.029, 0.008; p < 0.001) and general psychopathology (regression coefficient, SE: 0.118, 0.023; p < 0.001) PANSS scores. We found an inverse relationship between depression and positive symptoms (regression coefficient, SE: -0.088, 0.028; p = 0.002). No association between depression and negative symptoms was found., Conclusion: Despite some limitations, our study shows that people affected by schizophrenia spectrum disorders with depression are likely to show more overall and general psychopathology symptoms but lower positive symptoms. Additional studies are needed to explore the generalizability of our findings., Competing Interests: FB has received consultant fees from Edra SpA and IQVIA Solutions Italy, and honoraria for editorial activities from Elsevier, IMR Press, and Med Reviews Ltd. The other authors report no conflicts of interest.

Background & Aims: In the classic form of α1-antitrypsin deficiency (ATD), the misfolded α1-antitrypsin Z (ATZ) variant accumulates in the endoplasmic reticulum (ER) of liver cells. A gain-of-function proteotoxic mechanism is responsible for chronic liver disease in a subgroup of homozygotes. Proteostatic response pathways, including conventional endoplasmic reticulum-associated degradation and autophagy, have been proposed as the mechanisms that allow cellular adaptation and presumably protection from the liver disease phenotype. Recent studies have concluded that a distinct lysosomal pathway called endoplasmic reticulum-to-lysosome completely supplants the role of the conventional macroautophagy pathway in degradation of ATZ. Here, we used several state-of-the-art approaches to characterize the proteostatic responses more fully in cellular systems that model ATD., Methods: We used clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genome editing coupled to a cell selection step by fluorescence-activated cell sorter to perform screening for proteostasis genes that regulate ATZ accumulation and combined that with selective genome editing in 2 other model systems., Results: Endoplasmic reticulum-associated degradation genes are key early regulators and multiple autophagy genes, from classic as well as from ER-to-lysosome and other newly described ER-phagy pathways, participate in degradation of ATZ in a manner that is temporally regulated and evolves as ATZ accumulation persists. Time-dependent changes in gene expression are accompanied by specific ultrastructural changes including dilation of the ER, formation of globular inclusions, budding of autophagic vesicles, and alterations in the overall shape and component parts of mitochondria., Conclusions: Macroautophagy is a critical component of the proteostasis response to cellular ATZ accumulation and it becomes more important over time as ATZ synthesis continues unabated. Multiple subtypes of macroautophagy and nonautophagic lysosomal degradative pathways are needed to respond to the high concentrations of misfolded protein that characterizes ATD and these pathways are attractive candidates for genetic variants that predispose to the hepatic phenotype., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Workplace violence (WPV) is a growing issue in health care with far-reaching consequences for health workers' physical and psychological well-being. While some medical specialities like emergency medicine have always been considered at higher risk for WPV, several studies have also reported its occurrence in radiology., Aims: This systematic review aimed to comprehensively synthesize the types of WPV in radiology, its psychological impact, and the underlying risk and protective factors., Methods: We searched five electronic databases (PubMed, Web of Science Core Collection, Scopus, PsycINFO and CINAHL) and additional literature, including grey literature, and established weekly search alerts. Two reviewers independently conducted all methodological steps, involving a third reviewer in case of disagreement., Results: Of the 12 205 retrieved records, 103 full-text articles were evaluated, and 15 studies were included. Across studies, verbal aggression, sexual harassment (mostly against women) and physical violence were experienced by up to 100%, 85% and 46% of health workers, respectively. Perpetrators were patients and patients' caregivers, followed by co-workers. Victims suffered from various psychological symptoms, such as anxiety (22%-54%), fear (6%-39%), depression (32%) and repeated disturbing memories (21%). Risk factors included female gender, understaffing, worker inexperience, poor communication and lengthy waiting times. Social support and security personnel presence were among the identified protective factors., Conclusions: Health workers are at high risk of experiencing WPV in the radiological setting, with a strong psychological impact. Radiological departments should create a safe healthcare environment that actively manages the identified risk factors and offers psychological support to affected workers., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Alterations of functional network connectivity have been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Recent studies also suggest that the temporal dynamics of functional connectivity (dFC) can be altered in these disorders. Here, we summarized the existing literature on dFC in SCZ and BD, and their association with psychopathological and cognitive features. We systematically searched PubMed, Web of Science, and Scopus for studies investigating dFC in SCZ and BD and identified 77 studies. Our findings support a general model of dysconnectivity of dFC in SCZ, whereas a heterogeneous picture arose in BD. Although dFC alterations are more severe and widespread in SCZ compared to BD, dysfunctions of a triple network system underlying goal-directed behavior and sensory-motor networks were present in both disorders. Furthermore, in SCZ, positive and negative symptoms were associated with abnormal dFC. Implications for understanding the pathophysiology of disorders, the role of neurotransmitters, and treatments on dFC are discussed. The lack of standards for dFC metrics, replication studies, and the use of small samples represent major limitations for the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Perturbation of angiogenesis is associated with a variety of diseases and pro- as well as antiangiogenic therapies are being actively explored. Additionally, unintended adverse drug effects on angiogenesis might lead to promotion of tumor progression and cardiovascular complications. Several tri-dimensional microfluidic vessel-on-chip systems have been described that allow a more accurate investigation of vascular physiology and pathology, compared to the two-dimensional static culture of endothelial cells. The OrganoPlate ® angiogenesis-on-chip system has been demonstrated to be amenable to high-throughput screening for the antiangiogenic properties of molecules. We set out to adapt this system for high-throughput screening of molecules with proangiogenic properties. Our technical advancement of the OrganoPlate ® angiogenesis-on-chip assay expands its applicability in the early screening of both anti- as well as proangiogenic properties of compounds for therapeutic modulation of angiogenesis as well as the identification of angiogenesis-associated drug-induced vascular toxicities.

Introduction: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes., Methods: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference., Results: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis., Discussion: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: to investigate vaccine uptake among pregnant women during the 2nd and 3rd trimester of pregnancy. To describe the factors influencing vaccine uptake during pregnancy, comparing sociodemographic and clinical characteristics of pregnant women who were vaccinated during the 2nd or 3rd trimester with those who were not vaccinated, despite having the indication for vaccination., Design: observational study with a cross-sectional approach and prevalence estimation in the population of women who gave birth in the study period, through record linkages between the ministry information flow Birth assistance certificate, the Regional vaccination register and the Italian flow for SARS-CoV-2 infections., Setting and Participants: the study included all the 4,772 pregnant women living in Trentino (north-east Italy), who were in the 2nd or 3rd trimester of pregnancy between the 5th May 2021 and the 28th February 2022 and who delivered in Trentino., Main Outcome Measures: vaccine uptake among pregnant women during the 2nd and 3rd trimester of pregnancy. Results: 33.3% of pregnant women got vaccinated with at least one dose of vaccine during the 2nd or 3rd trimester of pregnancy. Independent factors associated with vaccine uptake in the 2nd or 3rd trimester were the mother's citizenship, educational level, occupational status and age., Conclusions: the proportion of women who received at least one dose of COVID-19 vaccine during pregnancy was low. The results are important to start efficient actions to promote vaccination in pregnant women, particularly in the most vulnerable ones (unemployed, foreigners and with a low educational level), who appear to be less vaccinated frequently.

Objectives: Describe the current practice of Canadian obstetricians-gynaecologists in managing placenta accreta spectrum (PAS) disorders from suspicion of diagnosis to delivery planning and explore the impact of the latest national practice guidelines on this topic., Methods: We distributed a cross-sectional bilingual electronic survey to Canadian obstetricians-gynaecologists in March-April 2021. Demographic data and information on screening, diagnosis, and management were collected using a 39-item questionnaire. The survey was validated and pretested among a sample population. Descriptive statistics were used to present the results., Results: We received 142 responses. Almost 60% of respondents said they had read the latest Society of Obstetricians and Gynaecologists of Canada clinical practice guideline on PAS disorders, published in July 2019. Nearly 1 in 3 respondents changed their practice following this guideline. Respondents highlighted the importance of 4 key points: (1) limiting travel to thereby remain close to a regional care centre, (2) preoperative anemia optimization, (3) performance of cesarean-hysterectomy leaving the placenta in situ (83%), (4) access via midline laparotomy (65%). Most respondents recognized the importance of perioperative blood loss reduction strategies such as tranexamic acid and perioperative thromboprophylaxis via sequential compression devices and low-molecular-weight heparin until full mobilization., Conclusions: This study demonstrates the impact of the Society of Obstetricians and Gynaecologists of Canada's PAS clinical practice guideline on management choices made by Canadian clinicians. Our study highlights the value of a multidisciplinary approach to reducing maternal morbidity in individuals facing surgery for a PAS disorder and the importance of regionalized care that is resourced to provide maternal-fetal medicine and surgical expertise, transfusion medicine, and critical care support., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

In order to solubilize poorly soluble active pharmaceutical ingredients, various strategies have been implemented over the years, including the use of nanocarriers, such as cyclodextrins and liposomes. However, improving a drug's apparent solubility does not always translate to enhanced bioavailability. This work aimed to investigate to which extent complexation with cyclodextrins and incorporation into liposomes influence drug in vitro permeability and to find a mechanistic description of the permeation process. For this purpose, we investigated hydroxypropyl-β-cyclodextrin (HP-β-CD) and phosphatidylcholine liposomes formulations of three chemically diverse compounds (atenolol, ketoprofen and hydrocortisone). We studied drug diffusion of the formulations by UV-localized spectroscopy and advanced data fitting to extract parameters such as diffusivity and bound-/free drug fractions. We then correlated this information with in vitro drug permeability obtained with the novel PermeaPad Ⓡ barrier. The results showed that increased concentration of HP-β-CD leads to increased solubilization of the poorly soluble unionized ketoprofen, as well as hydrocortisone. However, this net increment of apparent solubility was not proportional to the increased flux measured. On the other hand, normalising the flux over the empirical free drug concentration, i.e., the free fraction, gave a meaningful absolute permeability coefficient. The results achieved for the liposomal formulation were consistent with the finding on cyclodextrins. In conclusion, we proved the adequacy and usefulness of our method for calculating free drug fractions in the examined enabling formulations, supporting the validity of the established drug diffusion/permeation theory that the unbounded drug fraction is the main driver for drug permeation across a membrane., Competing Interests: Declaration of Competing Interest Massimiliano Pio di Cagno, the corresponding and leading author of this article, is Scientific Consultant for Phabioc GmbH, the producer of the PermeaPad(Ⓡ)., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hypertension is an important morbidity factor. The prognostic consequences of the white-coat effect have been studied extensively. The repercussion on the circadian rhythm of urinary water and salt excretion in the same subgroup remain, conversely, among the open topics. Postulating an impaired diurnal sodium and volume excretion we decided to investigate both, in subjects with or without a white-coat effect, in the general population. A sample of 1023 subjects, has been considered. We collected 24-h urine samples, divided in day and night, and we measured the blood pressure with an Ambulatory Blood Pressure Monitoring (ABPM). ABPM values were then compared with physician collected in-office values to assign subjects to the group with or without the white-coat effect. Concerning the circadian pattern of urinary sodium excretion, we found no significant differences between the groups. There was instead in the white-coat effect group a higher night/day ratio of urinary water excretion. The white-coat effect, has been considered a potential hypertension precursor, and its consequent handling could be prospectively relevant in hypertension prevention. The absence of repercussions on the urinary circadian sodium excretion pattern and on the potentially related risk factors in subjects with a white coat effect is reassuring. The clinical significance of the impact on the night/day ratio of water excretion needs to be further investigated.

Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Nursing home (NH) residents are vulnerable subjects and highly susceptible to adverse events. Knowledge of patient safety culture (PSC) is essential for an organization to ensure patient safety. However, research on PSC in NHs, and its variability among staff, is still scarce. This study aimed to explore whether and how PSC differed among NH staff (Managers, Nurses, Direct Care Staff, Support Staff, Administrative Staff and Other Providers) in the Autonomous Province of Trento, Italy. This study employed a cross-sectional design and collected data from 1145 NH providers using the Nursing Home Survey on Patient Safety Culture (NHSPSC). Data were analyzed using linear mixed models, with each of the 12 NHSPSC domains as a response variable. The majority of the respondents (61.6%) were Direct Care Staff members. 'Feedback and Communication about Incidents' and 'Overall Perceptions of Resident Safety' were the domains with the highest proportions of positive answers (PPAs). For most staff categories, 'Staffing' was the domain with the lowest PPA. Support Staff showed significantly lower scores in the majority of domains (8/12). Shorter job tenure, fewer weekly working hours, working mostly during the day and working in highly specialized areas were associated with higher scores in several domains. Interventions to improve PSC must consider the differences between professional groups. Further research is needed to explore the relationship between job-related features and perceptions of patient safety among NH workers.

(1) Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway, leading to reduced or absent breathing during sleep. A nocturnal upper airway collapse is often multi-levelled. The aim of this communication is to describe a 3D multi-level surgery setting in OSA pathology, introducing new surgical approaches, such as 4K-3D endoscopic visualization for the tongue base approach with the aid of a coblator and exoscopic visualization in the palatal approach. (2) Methods: Seven patients affected by OSA underwent 3D Barbed Reposition Pharyngoplasty (BRP) surgery associated with transoral coblation tongue base reduction and nose surgery. (3) Results: No patients experienced intra-operative, post-operative or delayed complications. For OSA multi-level 3D surgery, it took less than 2 h: the median 3D system setting time was 12.5 ± 2.3 min; the overall procedure time was 59.3 ± 26 min. (4) Conclusions: The use of the 4K-3D endoscope and coblator for tongue base resectioning and of the 3D exoscope for lateral pharyngoplasty represents an excellent system in multi-level OSA related surgery that could reduce the time and the costs compared to those of robotic surgery.

Introduction: Migrant populations worldwide were disproportionately impacted by the COVID-19 pandemic. Although substantial resources have been invested in scaling COVID-19 vaccination campaigns, globally vaccine rate and uptake remained low among migrants from across many countries. This study aimed to explore the country of birth as a factor influencing access to the COVID-19 vaccine., Methods: This retrospective cohort study included adults vaccinated against SARS-CoV-2 receiving at least one dose in the Verona province between 27 December 2020 and 31 December 2021. Time-to-vaccination was estimated as the difference between the actual date of each person's first dose of COVID-19 vaccination and the date in which the local health authorities opened vaccination reservations for the corresponding age group. The birth country was classified based on both the World Health Organization regions and the World Bank country-level economic classification. Results were reported as the average marginal effect (AME) with corresponding 0.95 confidence intervals (CI)., Results: During the study period, 7,54,004 first doses were administered and 5,06,734 (F = 2,46,399, 48.6%) were included after applying the exclusion criteria, with a mean age of 51.2 years (SD 19.4). Migrants were 85,989 (17.0%, F = 40,277, 46.8%), with a mean age of 42.4 years (SD 13.3). The mean time-to-vaccination for the whole sample was 46.9 days (SD 45.9), 41.8 days (SD 43.5) in the Italian population, and 71.6 days (SD 49.1) in the migrant one (p < 0.001). The AME of the time-to-vaccination compared to the Italian population was higher by 27.6 [0.95 CI 25.4-29.8], 24.5 [0.95 CI 24.0-24.9], 30.5 [0.95 CI 30.1-31.0] and 7.3 [0.95 CI 6.2-8.3] days for migrants from low-, low-middle-, upper-middle- and high-income countries, respectively. Considering the WHO region, the AME of the time-to-vaccination compared to the Italian group was higher by 31.5 [0.95 CI 30.6-32.5], 31.1 [0.95 CI 30.6-31.5], and 29.2 [0.95 CI 28.5-29.9] days for migrants from African, European, and East-Mediterranean regions, respectively. Overall, time-to-vaccination decreased with increasing age (p < 0.001). Although both migrants and Italians mainly used hub centers (>90%), migrants also used pharmacies and local health units as alternative sites (2.9% and 1.5%, respectively), while Italians (3.3%) and migrants from the European region (4.2%) relied more on family doctors., Conclusion: The birth country of migrants influenced access to COVID-19 vaccine both in terms of time-to-vaccination and vaccination points used, especially for the LIC migrant group. Public health authorities should take socio-cultural and economic factors into consideration for tailored communication to people from migrant communities and for planning a mass vaccination campaign., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Benoni, Sartorello, Moretti, Marchiori, Accordini, Postiglione, Coffele and Tardivo.)

The brain-derived neurotrophic factor (BDNF) has received considerable attention as a potential biomarker of major depressive disorder (MDD) and antidepressant response. We conducted an overview of meta-analyses investigating the relationship of BDNF with MDD, related clinical features, and antidepressant treatment. Based on a systematic screening on main electronic databases, 11 systematic reviews with meta-analyses were included. Available evidence suggests that people with MDD have peripheral and central BDNF levels lower than non-depressed individuals. A negative correlation between blood BDNF and symptom severity emerged, while no association with suicidality was detected. Moreover, an increase in blood BDNF levels after antidepressant treatment, proportional to symptom improvement, was reported. BDNF levels seem to be increased in both treatment responders and remitters, remaining stable in non-responders. Conversely, no variations of BDNF concentrations after non-pharmacological interventions (electroconvulsive therapy, repetitive transcranial magnetic stimulation, and physical activity) were found. The findings of this overview appear consistent with the neurotrophic hypothesis of depression, suggesting that BDNF may play a role in both MDD pathophysiology and pharmacological treatment response., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Trans Oral Robotic Surgery (TORS) is a modality in the management of oropharyngeal squamous cell carcinoma(OPSCC). This study was conducted to show the rates of peri-operative complications after TORS for OPSCC in our experience. Single centre retrospective analysis of consecutive OPSCC treated with TORS. The surgical complication severity was recorded according to Clavien-Dindo criteria (CDC). Eighty-seven OPSCC were operated with TORS. According to CDC, grade I, grade II and IIIb were registered in 8%, 4.6% and 11.5% of cases, respectively. The postoperative pain, registered with visual-analogue scale (VAS) score, was 8 ± 1.2 for the secondary healing wounds and 6.2 ± 1.5 for the flap reconstructions ( p  < 0.01). The impact on swallowing function was not significant between secondary healing and flap reconstructions( p  = 0.96). Any major or life-threatening intraoperative complications have not been recorded. Only one patient had postoperative bleeding into the neck whilst 13.3% of patients had postoperative bleeding from the primary tumor. No total local or free flap failure were registered. The mean duration of tracheostomy use was 7.4 ± 2.6 days, and nasogastric tube 14.3 ± 6.9 days. Only one patient, who had also reconstruction with flap, experienced a postoperative severe dysphagia with severe aspiration, needing a permanent tracheostomy tube and percutaneous endoscopic gastrostomy feeding. TORS for OPSCC showed less morbidity, lower risk of severe complication and mortality. Thus, this treatment modality could be offered as first line treatment in selected cases., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Personalized Medicine is a novel medical practice that uses an individual's genetic profile to guide decisions made regarding the prevention, diagnosis, and treatment of disease. Knowledge of a patient's genetic profile is crucial to support doctors in selecting the proper therapy and administer it using the correct dose or regimen. Personalized Medicine is a great opportunity to turn the "one size fits all" approach to diagnostics, therapy, and prevention, into an individualized approach. In this paper we analyze the most recent achievements and regulatory challenges in Personalized Medicine and the role that research infrastructures can play in advancing its development.

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint.

Immunogenicity against intravitreally administered brolucizumab has been previously described and associated with cases of severe intraocular inflammation, including retinal vasculitis/retinal vascular occlusion (RV/RO). The presence of antidrug antibodies (ADAs) in these patients led to the initial hypothesis that immune complexes could be key mediators. Although the formation of ADAs and immune complexes may be a prerequisite, other factors likely contribute to some patients having RV/RO, whereas the vast majority do not. To identify and characterize the mechanistic drivers underlying the immunogenicity of brolucizumab and the consequence of subsequent ADA-induced immune complex formation, a translational approach was performed to bridge physicochemical characterization, structural modeling, sequence analysis, immunological assays, and a quantitative systems pharmacology model that mimics physiological conditions within the eye. This approach revealed that multiple factors contributed to the increased immunogenic potential of brolucizumab, including a linear epitope shared with bacteria, non-natural surfaces due to the single-chain variable fragment format, and non-native drug species that may form over prolonged time in the eye. Consideration of intraocular drug pharmacology and disease state in a quantitative systems pharmacology model suggested that immune complexes could form at immunologically relevant concentrations modulated by dose intensity. Assays using circulating immune cells from treated patients or treatment-naïve healthy volunteers revealed the capacity of immune complexes to trigger cellular responses such as enhanced antigen presentation, platelet aggregation, endothelial cell activation, and cytokine release. Together, these studies informed a mechanistic understanding of the clinically observed immunogenicity of brolucizumab and associated cases of RV/RO.

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH 4 ), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs)., Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I 2 statistic., Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I 2  = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I 2  = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH 4 ., Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Adverse events (AEs) are a leading cause of patient morbidity and mortality, greatly impacting healthcare providers' well-being (second victim (SV) phenomenon). Since it is not accurately captured by existing psychometric instruments, we developed a clinimetric instrument for assessing SVs' emotional distress before and after an AE., Methods: Content validity and clinical utility of the WITHSTAND-PSY Questionnaire (WS-PSY-Q) were examined using cognitive interviews. Rasch analysis (n = 284) was applied for clinimetric assessment (i.e., construct, concurrent, and clinical validity, internal consistency), considering two crucial psychological facets of the SV phenomenon (1st: emotional impact of the AE, 2nd: current emotional state)., Results: The Rasch partial credit model was used. The 1st facet demonstrated overall acceptable clinimetric properties with the subscale anxiety meeting clinimetric threshold values (e.g., all items with ordered thresholds, Loevinger's coefficient h ≥ 0.40; Person Separation Reliability Index (PSI) = 0.7). The 2nd facet showed overall better clinimetric properties for both subscales (e.g., h ≥ 0.40, PSI = 0.82 and 0.79, respectively; receiver operating characteristic area of 0.80 and 0.86, respectively). For both datasets, item fit statistics, except those for item 19, were within the critical range (z-score &lt; ±2.5), and meaningful differential functioning analysis was observed for only 4 (out of 24) items. Local dependency was not observed, except for two item couples in the depression subscales., Conclusions: The WS-PSY-Q is the first clinimetric tool assessing SVs' emotional distress. It should be regarded as part of the armamentarium used by clinicians to assess in-depth healthcare providers' psychological reactions in the aftermath of an AE to mitigate burnout and allostatic overload., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objective: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder., Method: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence., Results: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p  < 0.001) and unemployed (odds ratio = 1.45; p  = 0.045), and less likely to be married (odds ratio = 0.62; p  = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p  < 0.001); more mood episodes (standardized mean difference = 0.35; p  = 0.007), particularly depressive (standardized mean difference = 0.30; p  = 0.011) and mixed (standardized mean difference = 0.30; p  = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p  = 0.024) and attempted suicides (odds ratio = 1.83; p  < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p  = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p  = 0.019), panic disorder (odds ratio = 1.89; p  < 0.001), social phobia (odds ratio = 1.61; p  = 0.017), eating disorders (odds ratio = 1.91; p  = 0.007), antisocial personality disorder (odds ratio = 3.59; p  = 0.004) and substance (odds ratio = 2.29; p  < 0.001) or alcohol (odds ratio = 2.28; p  < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate)., Conclusion: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age., (Copyright © 2022 Massachusetts Medical Society.)

We have synthesized several morphologies and crystal structures of MgWO 4 using a one-pot hydrothermal method, producing not only monoclinic stars and large nanoparticles but also triclinic wool balls and sub-10 nm nanoparticles. Herein we describe the importance of reaction parameters in demonstrating morphology control of as-prepared MgWO 4 . Moreover, we correlate structure and composition with the resulting photoluminescence and radioluminescence properties. Specifically, triclinic-phase samples yielded a photoluminescence emission of 421 nm, whereas monoclinic-phase materials gave rise to an emission maximum of 515 nm. The corresponding radioluminescence data were characterized by a broad emission peak, located at 500 nm for all samples. Annealing the wool balls and sub-10 nm particles to transform the crystal structure from a triclinic to a monoclinic phase yielded a radioluminescence (RL) emission signal that was two orders of magnitude greater than that of their unannealed counterparts. Finally, to confirm the practical utility of these materials for biomedical applications, a series of sub-10 nm particles, including as-prepared and annealed samples, were functionalized with biocompatible PEG molecules, and subsequently were found to be readily taken up by various cell lines as well as primary cultured hippocampal neurons with low levels of toxicity, thereby highlighting for the first time the potential of this particular class of metal oxides as viable and readily generated platforms for a range of biomedical applications., (© 2022 The Authors.)

We examined neonatal outcomes in pregnancies complicated by placental abruption (PA) and acute chorioamnionitis (CA). Exposure was acute CA; primary outcome - fetal death; secondary outcomes - adverse Apgar score, neonatal intensive care unit (NICU) admission, and cardiac depression. 267 placentas - 18.4% exhibited acute CA. PA pregnancies with CA - 29% experienced fetal death. Funisitis, acute CA and adverse neonatal outcomes are dependent. Without accounting for funisitis, aforementioned findings hold, though effect sizes are smaller. PA, acute CA with funisitis could affect fetal death and NICU admission. Acute CA and PA alone could impact fetal death and adverse Apgar scores., Competing Interests: Declaration of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost-effectiveness of a new children's treatment has several non-trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Discordant birth weight in twins is linked to poor outcomes and predicting this discrepancy may lead to enhanced screening and surveillance. Our purpose was to quantify the relationship between intertwin nuchal translucency (NT) and crown-rump length (CRL) discordance with birth weight discrepancies ≥ 20%., Methods: We conducted a retrospective cohort study of 887 live twin births delivering at a Canadian tertiary care center over a 7-year period who opted for integrated prenatal screening. Categorical data are presented as numbers and percentages, and continuous data are expressed as means and standard deviations. Chi-square tests, Fisher's Exact tests, or T -test were performed as appropriate. We then used published data and receiver operating curves to determine the optimal thresholds for predicting birth weight discordance based on first trimester intertwin NT differences. These values were used in multivariate logistic regression models accounting for known confounders., Results: Roughly 16% of twin pairs exhibited ≥ 20% difference in birth weight. Twin pairs with a CRL discordance greater than 10% have nearly a 4 times greater likelihood of having a birth weight discordance greater than 20% (OR 3.71, CI 2.24-6.14) while controlling for chorionicity, maternal age, gestational age at delivery, maternal body mass index (BMI), and parity. In these models, intertwin NT discordance ≥ 20% (OR 1.16, CI 0.77-1.77) and NT discordance ≥ 14% (OR 1.08, CI 0.73-1.60) were not statistically significant predictors of twin birth weight differences. However, when evaluating the effect of the larger intertwin NT value corresponding to the 95 th percentile, an NT difference ≥ 0.9 mm was predictive of birth weight discordance ≥ 20% (OR 2.53, CI 1.21-5.29)., Conclusion: Although intertwin CRL and NT discordance measured via ultrasound between 11-14 weeks gestation are related to birth weight discordance, there is uncertainty as to whether twin birth weight differences are related to adverse pregnancy outcomes in this population., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Zachary Michael Ferraro et al.)