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Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme-which is entirely free-includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence., Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1-ABRAXAS1 interaction was assessed using a GFP-fragment reassembly-based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2., Results: Variant-carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0-155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6-40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2-2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03-61.6) emerged, warranting further evaluation. Likelihood-ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1-ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule-based model. Collectively, these findings allowed to classify the variant as pathogenic., Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Dravet syndrome, a developmental and epileptic encephalopathy, manifests with varying degrees of cognitive and communication impairment, postural and movement disorders (such as ataxia, coordination issues, and crouch gait) and behavioural challenges (including attention deficit/hyperactivity, oppositional/defiant behaviour, and autistic traits). Rehabilitation is a valuable tool for most patients, typically prescribed to address the most pressing issues. However, current practices often fall short in proactively preventing and treating known challenges associated with the syndrome, as indicated by the latest literature, at different life stages. Furthermore, there is a notable lack of evidence regarding treatment types and efficacy specific to people with Dravet Syndrome. Conducted in collaboration with one of the Italian Patient associations, this national survey provides a comprehensive view of the rehabilitation landscape in Dravet Syndrome, as perceived by caregivers. It outlines the types of treatments for 51 patients, based on age and relevant clinical features. The findings reveal a heterogenous rehabilitation approach, only partly tailored to the presence of specific comorbidities, and underline numerous unmet needs. Compared to the past there is indirect evidence that more patients are offered early rehabilitation. Nonetheless, while nowadays speech therapy and neuropsychomotor therapy are nearly universal for children up to the age of 10, some begin physiotherapy and psychotherapy thereafter, with a majority discontinuing treatments. Therefore, families of adolescent and adult patients often face a lack of comprehensive support, predominantly offered when epilepsy is more challenging to control affecting rehabilitation adherence and effectiveness. Finally, a negligible minority is offered treatments such as neurovisual training, augmentative and alternative communication, and occupational therapy. Many of these considerations could apply to other developmental and epileptic encephalopathy with lifelong disability. This survey calls for more data collection on this important topic for more efficient allocation of rehabilitation resources., 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 Inc. All rights reserved.)

Introduction: In the Emilia-Romagna region of Italy, a unique Hub and Spoke model was adopted to recognize BRCA-related breast cancer (BC) patients. Characteristics and outcomes of tumors identified by this model will be presented., Methods: This multicenter retrospective cohort study involved patients diagnosed with BRCA-related BC identified in the Emilia-Romagna region between January 2000 and December 2013. Seven provinces collected data on patient and tumor characteristics; clinical and gene testing information were also registered. Comparisons between BRCA1 and BRCA2 BC were performed. To balance different variants to identify significant predictors of survival, an inverse probability of treatment weighting (IPTW) analysis on Cox regression was conducted., Results: From 2000 to 2013, 284 BRCA-related BC were registered (171 BRCA1, 110 BRCA2, and 3 BRCA1 and BRCA2). BRCA1 were diagnosed at an earlier stage compared to BRCA2 (50.1 % vs 30 %, respectively, in stage I, P = 0.0015). BRCA2 patients underwent more up-front surgery (85 % vs. 74.9 %, P = 0.049) and less chemotherapy (69.1 % vs 88.9 %, P = 0.004) than BRCA1 patients. At 11.8 years median follow-up, BRCA1 patients developed more second contralateral BC (P = 0.09), while BRCA2 had more visceral relapses (P = 0.013). No differences in overall survival (OS) between BRCA1 and BRCA2 patients (P = 0.07) were found. An advantage in OS was independently seen for patients who underwent contralateral prophylactic mastectomy (P = 0.0001) and oophorectomy (P < 0.0001)., Conclusions: In conclusion, adopting a homogeneous regional framework provides important information about prevention and treatment strategies of BRCA-related BC and suggests using maximal surgery to improve OS., Competing Interests: Declaration of competing interest LC: speaker honoraria from Astra Zeneca, Pfizer, Novartis, Gilead, MSD; advisory role for Astra Zeneca, Pfizer, MSD, Amgen, Roche; GC, MV: no conflict of interest to disclose; AT: speaker honoraria from Lilly, Novartis, Pfizer, AstraZeneca, MSD, Seagen, Gilead, Daiichi Sankyo; EB: travel grants from Lilly, Novartis, Pfizer, MSD, AstraZeneca, Gilead, Daiichi Sankyo; FT: no conflict of interest to disclose; AM: Honoraria: Eli-Lilly, Pfizer, Macrogenics, Seagen, and Daiichi Sankyo; institutional research funding: Roche, Eli-Lilly; UDG: Advisory Board: MSD, Bristol Myers Squibb, Janssen, Astellas, Sanofi, Bayer, Pfizer, Ipsen, Novartis, and Pharmamar. Institutional Research grants: AstraZeneca, Sanofi, and Roche; GB, VA: no conflict of interest to disclose; CZ: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events by Roche, Eisai, Novartis, Astrazeneca, Pfizer, Pharmamar, Tesaro, Pierre Fabre, Ist. Gentili, Teva, Seagen, Eli Lilly, Celgene, MSD, GSK, Amgen, Daichii, Support for attending meetings and/or travel by Roche, Novartis, Pfizer, Pharmamar, Tesaro, Pierre Fabre, Ist. Gentili, Celgene, Participation on a Data Safety Monitoring Board or Advisory Board by Roche, Eisai, Novartis, Astrazeneca, Pfizer, Pharmamar, Amgen, Tesaro, QuintilesIms, Eli Lilly, Celgene, MSD, GSK, Daichii, Other financial or non-financial interests by Roche, Novartis, Astrazeneca, Pfizer, Amgen, Tesaro, QuintilesIms, MSD, GSK, Daichii. LC, MD: no conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before., Methods: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195)., Results: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported., Discussion: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time., (Copyright © 2023 by The American College of Gastroenterology.)

Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Screen time refers to the amount of time a child is exposed to a screen, that is, television, computer, smartphone, or any other digital medium. Prolonged screen time in the first years of life may affect a child's cognitive abilities, especially language acquisition. A systematic review was conducted, following the PRISMA-P guidelines, with the aim to explore the available literature relating to the impact of screen time on children's language development. This review identified 18 articles. The articles reviewed showed that prolonged screen time and exposure to screens in the first 2 years of life can negatively affect language development and communication skills, in terms of comprehension and vocabulary range. In addition, overexposure to screens in the early years can affect overall cognitive development, especially attention to environmental stimuli, social experiences, problem solving, and communication with others, e.g., the alternance of rhythms and roles in a conversation. In conclusion, our systematic review supports the idea that preschool screen time has negative effects on children's cognitive and language development. Television seems to be the medium most detrimental to children's skills, as it is used in a passive manner and is often characterised by language and content that do not suit the child's processing mode. Future studies should increasingly focus on the digital media that children possess at an early age, such as mobile phones and tablets, and on how children relate to the online world, such as social networks.

Introduction: Primary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes., Methods: We conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation., Results: Among the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04-3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75-3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50-4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients., Discussion: In conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease., Competing Interests: UG has received advisory board or consultancy fees from Merck Sharp & Dohme, Bristol Myers Squibb, Janssen, Astellas, Sanofi, Bayer, Pfizer, Ipsen, Novartis, and Pharmamar and institutional research grants from AstraZeneca, Sanofi, and Roche. AF has received personal honoraria for lectures from AstraZeneca, GSK-Tesaro, and Clovis and is on the advisory board of Janssen, AstraZeneca, and GSK-Tesaro. The remaining 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 Farolfi, Petracci, Gurioli, Tedaldi, Casanova, Arcangeli, Amadori, Rosati, Stefanetti, Burgio, Cursano, Lolli, Zampiga, Cangini, Schepisi and Giorgi.)

Introduction: Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems., Methods: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1., Results: In SLD, the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers., Conclusions: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration.

PVs and LPVs in BRCA1/2 genes are correlated to a high risk of developing breast cancer and/or ovarian cancer (Hereditary Breast and Ovarian Cancer syndrome, HBOC); additionally, in recent years, an increasing number of BRCA 1/2 variants have been identified and associated with pancreatic cancer. Epidemiologic studies have highlighted that inherited factors are involved in 10% to 20% of PCs, mainly through deleterious variants of BRCA2 . The frequency of BRCA1/2 germline alterations fluctuates quite a lot among different ethnic groups, and the estimated rate of PVs/LPVs variants in Italian HBOC families is not very accurate, according to different reports. The aim of our study is to describe the prevalence of a BRCA2 PV observed in a selected cohort of HBOC patients and their relatives, whose common origin is the eastern coast of Emilia Romagna, a region of Italy. This study provides insight into the frequency of the variant detected in this area and provides evidence of an increased risk of pancreatic and breast cancer, useful for genetic counseling and surveillance programs., Competing Interests: The authors declare no conflict of interest.

BRCA1 and BRCA2 are the most frequently mutated genes in ovarian cancer (OC) crucial both for the identification of cancer predisposition and therapeutic choices. However, germline variants in other genes could be involved in OC susceptibility. We characterized OC patients to detect mutations in genes other than BRCA1/2 that could be associated with a high risk of developing OC and permit patients to enter the most appropriate treatment and surveillance program. Next-generation sequencing analysis with a 94-gene panel was performed on germline DNA of 219 OC patients. We identified 34 pathogenic/likely pathogenic variants in BRCA1/2 and 38 in other 21 genes. The patients with pathogenic/likely pathogenic variants in the non-BRCA1/2 genes mainly developed OC alone compared to the other groups that also developed breast cancer or other tumors (p = 0.001). Clinical correlation analysis showed that the low-risk patients were significantly associated with platinum sensitivity (p < 0.001). Regarding PARP inhibitors (PARPi) response, the patients with pathogenic mutations in the non-BRCA1/2 genes had worse PFS and OS. Moreover, a statistically significantly worse PFS was found for every increase of one thousand platelets before PARPi treatment. To conclude, knowledge about molecular alterations in genes beyond BRCA1/2 in OC could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for OC patients.