Reproductive toxicity assessment of cellulose nanofibers, citric acid, and branched polyethylenimine in sea urchins: Eco-design of nanostructured cellulose sponge framework (Part B).

In the framework of a safe-by-design approach, we previously assessed the eco-safety of nanostructured cellulose sponge (CNS) leachate on sea urchin reproduction. It impaired gamete quality, gamete fertilization competence, and embryo development possibly due to the leaching of chemical additives used during the CNS synthesis process. To extend this observation and identify the component(s) that contribute to CNS ecotoxicity, in the present study, we individually screened the cytotoxic effects on sea urchin Arbacia lixula and Paracentrotus lividus gametes and embryos of the three main constituents of CNS, namely cellulose nanofibers, citric acid, and branched polyethylenimine. The study aimed to minimize any potential safety risk of these components and to obtain an eco-safe CNS. Among the three CNS constituents, branched polyethylenimine resulted in the most toxic agent. Indeed, it affected the physiology and fertilization competence of male and female gametes as well as embryo development in both sea urchin species. These results are consistent with those previously reported for CNS leachate. Moreover, the characterisation of CNS leachate confirmed the presence of detectable branched polyethylenimine in the conditioned seawater even though in a very limited amount. Altogether, these data indicate that the presence of branched polyethylenimine is a cause-effect associated with a significant risk in CNS formulations due to its leaching upon contact with seawater. Nevertheless, the suggested safety protocol consisting of consecutive leaching treatments and conditioning of CNS in seawater can successfully ameliorate the CNS ecotoxicity while maintaining the efficacy of its sorbent properties supporting potential environmental applications.

Three-dimensional Versus Two-dimensional Laparoscopic Bariatric Surgery: A Systematic Review and Meta-analysis.

Three-dimensional (3D) laparoscopy has several advantages in gastrointestinal surgery. This systematic review determined whether similar benefits exist for bariatric surgical procedures by systematically searching the MEDLINE, Embase, and Scopus databases. Six studies including 629 patients who underwent 2D (386) and 3D (243) laparoscopic bariatric surgeries were selected. Operative time was significantly shorter in patients undergoing 3D laparoscopic gastric bypass (pooled standardized mean difference [SMD] 1.19, 95% confidence interval [CI] 2.22-0.15). Similarly, a shorter hospital stay was detected both during sleeve gastrectomy (SMD 0.42, 95% CI 0.70-0.13) and gastric bypass (SMD 0.39, 95% CI 0.64-0.14) with 3D laparoscopy. The study showed the potential benefit of 3D imaging in preventing intra- and postoperative complications. Despite the limited evidence, surgeons may benefit from 3D laparoscopy during bariatric surgery.

Photodynamic Therapy for the Treatment of Bowen's Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome.

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

Short-term effectiveness of guselkumab in psoriatic arthritis patients and suggestive features of axial involvement: results from a real-life multicentre cohort.

OBJECTIVE: To evaluate the short-term effectiveness of guselkumab in patients with psoriatic arthritis (PsA) and suggestive features of axial involvement in a prospective "real-life" multicentre cohort. METHODS: Between June 2022 and June 2023, PsA patients with axial involvement were evaluated if treated at least for 4 months with guselkumab. The effectiveness was evaluated by BASDAI, ASDAS, DAPSA, and achievement of BASDAI ≤ 4, also exploiting predictive factors. In a group of patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. RESULTS: Sixty-seven patients with PsA and suggestive features of axial involvement (age 53.4 ± 11.2 years, male sex 26.9%) were treated with guselkumab. After 4 months, a significant reduction of BASDAI, ASDAS, and DAPSA was observed. A ΔBASDAI of -2.11 ± 0.43 was estimated assessing the mean difference values before and after guselkumab administration and 52.2% of patients reached a BASDAI ≤ 4. In 27 patients, MRI findings on sacroiliac joints were assessed before and after guselkumab administration. A reduction of 0.80 or larger of the sacroiliac joint lesion score was observed in the majority of patients (70.3%) based on MRI improvements, paralleling with the clinical response.No life-threatening side effects were recorded; 17.9% of patients reported minor adverse events mainly injection site reactions. CONCLUSIONS: The short-term effectiveness of guselkumab in patients with PsA and suggestive features of axial involvement was shown. Although further studies are needed, our multicentre "real-life" study may suggest the clinical usability of guselkumab in this context.

Identification of an ultra-rare Alu insertion in the CFTR gene: Pitfalls and challenges in genetic test interpretation.

Cystic fibrosis (CF) is a life-limiting genetic disorder characterized by defective chloride ion transport due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Early detection through newborn screening programs significantly improves outcomes for individuals with CF by enabling timely intervention. Here, we report the identification of an Alu element insertion within the exon 15 of CFTR gene, initially overlooked in standard next-generation sequencing analyses. However, using traditional molecular techniques, based on polymerase chain reaction and Sanger sequencing, allowed the identification of the Alu element and the reporting of a correct diagnosis. Our analysis, based on bioinformatics tools and molecular techniques, revealed that the Alu element insertion severely affects the gene expression, splicing patterns, and structure of CFTR protein. In conclusion, this study emphasizes the importance of how the integration of human expertise and modern technologies represents a pivotal step forward in genomic medicine, ensuring the delivery of precision healthcare to individuals affected by genetic diseases.

Bimekizumab for the Treatment of Plaque Psoriasis With Involvement of Genitalia: A 16-Week Multicenter Real-World Experience - IL PSO (Italian Landscape Psoriasis).

INTRODUCTION: Genital involvement is observed in approximately 60% of patients with psoriasis, presenting clinicians with formidable challenges in treatment. While new biologic drugs have emerged as safe and effective options for managing psoriasis, their efficacy in challenging-to-treat areas remains inadequately explored. Intriguingly, studies have shown that interleukin (IL)-17 inhibitors exhibit effectiveness in addressing genital psoriasis. OBJECTIVES: We aimed to determine the effectiveness profile of bimekizumab in patients affected by moderate-to-severe plaque psoriasis with involvement of genitalia. METHODS: Bimekizumab, a dual inhibitor of both IL-17A and IL-17F, was the focus of our 16-week study, demonstrating highly favorable outcomes for patients with genital psoriasis. The effectiveness of bimekizumab was evaluated in terms of improvement in Static Physician's Global Assessment of Genitalia (sPGA-G) and Psoriasis Area and Severity Index. RESULTS: Sixty-five adult patients were enrolled. Remarkably, 98.4% of our participants achieved a clear sPGA-G score (s-PGA-g=0) within 16 weeks. Moreover, consistent improvements were observed in PASI scores, accompanied by a significant reduction in the mean Dermatology Life Quality Index (DLQI), signifying enhanced quality of life. Notably, none of the patients reported a severe impairment in their quality of life after 16 weeks of treatment. In our cohort of 65 patients, subgroup analyses unveiled that the effectiveness of bimekizumab remained unaffected by prior exposure to other biologics or by obesity. CONCLUSIONS: Our initial findings suggest that bimekizumab may serve as a valuable treatment option for genital psoriasis. Nevertheless, further research with larger sample sizes and longer-term follow-up is imperative to conclusively validate these results.

Comparative Study of Spheroids (3D) and Monolayer Cultures (2D) for the In Vitro Assessment of Cytotoxicity Induced by the Mycotoxins Sterigmatocystin, Ochratoxin A and Patulin.

Mycotoxins are secondary metabolites produced by filamentous fungi associated with a variety of acute and chronic foodborne diseases. Current toxicology studies mainly rely on monolayer cell cultures and animal models, which are undeniably affected by several limitations. To bridge the gap between the current in vitro toxicology approach and the in vivo predictability of the data, we here investigated the cytotoxic effects induced by the mycotoxins sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) on different 2D and 3D cell cultures. We focused on human tumours (neuroblastoma SH-SY5Y cells and epithelial breast cancer MDA-MB-213 cells) and healthy cells (bone marrow-derived mesenchymal stem cells, BM-MSC, and umbilical vein endothelial cells, HUVECs). The cytotoxicity of STE, OTA, and PAT was determined after 24, 48 and 72 h of exposure using an ATP assay in both culture models. Three-dimensional spheroids' morphology was also analysed using the MATLAB-based open source software AnaSP 1.4 version. Our results highlight how each cell line and different culture models showed specific sensitivities, reinforcing the importance of using more complex models for toxicology studies and a multiple cell line approach for an improved and more comprehensive risk assessment.

Systematic review and meta-analysis of postoperative outcomes after combined stoma reversal and incisional hernia repair versus stoma reversal alone.

BACKGROUND: The optimal management and timing of the abdominal wall reconstruction concomitantly performed with stoma closure are controversial. This study aims to compare short-term postoperative outcomes after concurrent stoma reversal (SR) with incisional hernia repair (IHR) and SR alone. METHODS: PubMed/MEDLINE, Scopus and Web of Science databases were consulted to identify comparative studies. Random and common-effect models were used for the pooled analysis of the proportions and means. RESULTS: Three studies met the inclusion criteria and a total of 504 patients who underwent simultaneous SR and IHR (N.=200) or SR alone (N.=304) were included in the meta-analysis. Postoperative morbidity increased after combined stoma and hernia surgery with a pooled OR for Surgical Site Occurrence (SSO) and severe postoperative complications (Clavien-Dindo ≥III) of 1.72 (95% CI 1.02-2.90) and 3.83 (95% CI 1.46-10.02), respectively. No significant difference was found between the two groups in terms of mortality (OR: 1.66; 95% CI 0.64-4.27), length of hospital stay (OR: 1.37; 95% CI 0.73-3.47). and readmission rate (OR: 1.17; 95% CI 0.67-2.06). CONCLUSIONS: There is limited evidence suggesting that synchronous repair of SR and IH appears to be associated with a higher risk of SSO and severe postoperative complications. Therefore, a stepwise approach may be considered the best strategy in this setting.

The prognostic contribution of CBL, NRAS, KRAS, RUNX1, and TP53 mutations to mutation-enhanced international prognostic score systems (MIPSS70/plus/plus v2.0) for primary myelofibrosis.

Contemporary risk models in primary myelofibrosis (PMF) include the mutation (MIPSS70) and mutation/karyotype enhanced (MIPSS70 plus/v2.0) international prognostic scoring systems. High molecular risk (HMR) mutations incorporated in one or both of these models include ASXL1, SRSF2, EZH2, IDH1/2, and U2AF1Q157; the current study examines additional prognostic contribution from more recently described HMR mutations, including CBL, NRAS, KRAS, RUNX1, and TP53. In a cohort of 363 informative cases (median age 58 years; 60% males), mutations included JAK2 61%, CALR 24%, MPL 6%, ASXL1 29%, SRSF2 10%, U2AF1Q157 5%, EZH2 10%, IDH1/2 4%, TP53 5%, CBL 5%, NRAS 7%, KRAS 4%, and RUNX1 4%. At a median follow-up of 4.6 years, 135 (37%) deaths and 42 (11.6%) leukemic transformations were recorded. Univariate analysis confirmed significant survival impact from the original MIPSS70/plus/v2.0 HMR mutations as well as CBL (HR 2.8; p < .001), NRAS (HR 2.4; p < .001), KRAS (HR 2.1; p = .01), and TP53 (HR 2.4; p = .004), but not RUNX1 mutations (HR 1.8; p = .08). Multivariate analysis (MVA) that included both the original and more recently described HMR mutations confirmed independent prognostic contribution from ASXL1 (HR 1.8; p = .007), SRSF2 (HR 4.3; p < .001), U2AF1Q157 (HR 2.9, p = .004), and EZH2 (HR 2.4; p < .001), but not from IDH1/2 (p = .3), TP53 (p = .2), CBL (p = .3), NRAS (p = .8) or KRAS (p = .2) mutations. The lack of additional prognostic value from CBL, NRAS, KRAS, RUNX1, and TP53 was further demonstrated in the setting of (i) MVA of mutations and karyotype, (ii) MVA of MIPSS70/plus/v2.0 composite scores and each one of the recently described HMR mutations, except TP53, and iii) modified MIPSS70/plus/plus v2.0 that included CBL, NRAS, KRAS, and TP53 as part of the HMR constituency, operationally referred to as "HMR+" category. Furthermore, "HMR+" enhancement of MIPSS70/plus/plus v2.0 did not result in improved model performance, as measured by C-statistics. We conclude that prognostic integrity of MIPSS70/plus/plus v2.0, as well as their genetic components, was sustained and their value not significantly upgraded by the inclusion of more recently described HMR mutations, including CBL, NRAS, KRAS, and RUNX1. Additional studies are needed to clarify the apparent additional prognostic value of TP53 mutation and its allelic state.

AtopyReg®, the Prospective Italian Patient Registry for Moderate-to-Severe Atopic Dermatitis in Adults: Baseline Demographics, Disease Characteristics, Comorbidities, and Treatment History.

BACKGROUND AND OBJECTIVE: AtopyReg® is a multicenter, prospective, observational, non-profit cohort study on moderate-to-severe atopic dermatitis in adults promoted in 2018 by the Italian Society of Dermatology and Venereology (SIDeMaST). We aimed to describe baseline demographics, disease characteristics, comorbidities, and therapeutic data of adult patients affected by moderate-to-severe atopic dermatitis. METHODS: Patients were selected based on the following inclusion criteria: age ≥ 18 years; Eczema Area and Severity Index score ≥ 16 or localization in visible or sensitive areas (face, neck, hands, or genitalia), or a Numeric Rating Scale itch score ≥ 7 or a Numeric Rating Scale sleep loss score ≥ 7, or a Dermatology Life Quality Index score ≥ 10. Demographic and clinical data at baseline were recorded and analyzed. RESULTS: A total of 1170 patients (male 51.1%; mean age: 44.7 years; range 18-90 years) were enrolled by 12 Italian Dermatology Units between January 2019 and November 2022. Skin lesions were eczematous in 83.2% of patients, the most involved site were the flexures (53.9%), face (50.9%), and neck (48.0%). Mean Eczema Area and Severity Index score was 22.3, mean Dermatology Life Quality Index value was 17.6, mean Patient Oriented Eczema Measure score was 13.1, and mean Numeric Rating Scale itch and sleep loss scores were 7.6 and 5.9, respectively. Previous systemic therapies were corticosteroids in 77.7% of patients, antihistamines in 50.3% of patients, and cyclosporine A in 42.6% of patients. CONCLUSIONS: This baseline data analysis deriving from AtopyReg® provides real-life evidence on patients with moderate-to-severe atopic dermatitis in Italy confirming the high burden of atopic dermatitis with a significant impact on patients' quality of life.

Availability of medical and endovascular therapies for venous thromboembolism: a global survey for World Thrombosis Day.

BACKGROUND: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE). OBJECTIVES: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation. METHODS: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories. RESULTS: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors. CONCLUSION: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally.

One-step NGS molecular analysis of the CFTR gene on newborn dried blood spots gives a higher diagnostic sensitivity in affected and carrier subjects: A pilot study.

BACKGROUND: Cystic fibrosis is the most common hereditary recessive disease with an incidence of about 1:2500/3000. It has long been known that the disease is caused by deleterious mutations in the CFTR gene. Conventionally, the disease is diagnosed in several phases. The analysis of all the possible disease-causing molecular alterations is time consuming and may not lead to a definitive diagnosis in several cases. Consequently, we propose, in this paper, a rapid sequencing method that, in a single procedural asset, reveals the presence of small mutations and also the copy number variants (CNVs) from the DNA extracted from the Guthrie Spot. MATERIALS AND METHODS: We first sequenced 30 blood spots, then we validated the method on 100 spots that underwent both traditional analyses and this complete NGS sequencing, and lastly, we tested the strategy on patients who normally do not reach the molecular sequencing step because of low level of Immune-Reactive Trypsinogen. RESULTS: Using this procedure, we identified 97 variants in the CFTR gene of our samples and 6 CNVs. Notably, the significant data were obtained in the group of patients with borderline or negative IRT who routinely would not undergo molecular testing. We also identified 6 carriers of "disease-causing" variants. CONCLUSION: This method is very robust. Indeed, there was a 100% concordance with Sanger sequencing validation, and 6 mutation carriers were identified who normally escaped molecular testing with actual conventional procedure. There were also 3 duplications of almost the entire gene in heterozygosity, which were not seen with traditional methods. Being quick and easy to perform, we suggest that complete sequencing of the CFTR gene, as in this study be considered for all newborns.

SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML.

KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. Silencing SET specifically abolished the clonogenic ability of KMT2A-R leukemic cells and the transcription of KMT2A targets genes HOXA9 and HOXA10. Subsequent mechanistic investigations showed that SET interacts with both KMT2A wild type and fusion proteins, and it is recruited to the HOXA10 promoter. Pharmacological inhibition of SET by FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest and increased sensitivity to chemotherapy in KMT2A-R-leukemic models. Phospho-proteomic analyses revealed that FTY720 reduced the activity of kinases regulated by PP2A, including ERK1, GSK3ß, AURB and PLK1 and led to suppression of MYC, supporting the hypothesis of a feedback loop among PP2A, AURB, PLK1, MYC, and SET. Our findings illustrate that SET is a novel player in KMT2A-R leukemia and they provide evidence that SET antagonism could serve as a novel strategy to treat this aggressive leukemia.

Brodalumab for severe hidradenitis suppurativa: a case of clinico-radiologic improvement and literature review.

Hidradenitis suppurativa (HS) is a chronic autoinflammatory follicular disease, affecting body areas that are rich in apocrine glands. Moderate-to-severe HS may severely impair patients' quality of life also because the available therapies are often unsatisfactory. Several lines of evidence suggest that inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-17 play a pivotal role in the physiopathology of HS. TNF-α inhibitors have long been used with benefit in moderate-severe forms of HS. However, several monoclonal antibodies against IL-17 isoforms are currently being investigated for HS. We report the case of a 50-year-old man with long-standing HS and concomitant palmo-plantar psoriasis treated with brodalumab after failure of various TNF-α inhibitors. The HS lesions and the patient's quality of life improved steadily over time until week-136. Interestingly, the clinical benefit was confirmed by radiological improvement with MRI evaluation. Our case report demonstrates the long-term efficacy and safety of brodalumab in HS encouraging the use of drugs to inhibit the T helper-type 17 immune axis, especially in cases of HS refractory to therapy with TNF-α inhibitors.

Ecological succession of blow flies (Diptera: Calliphoridae) in the decomposition of pig carcasses in Cerrado areas of Brazil.

This research aims to describe the process of ecological succession by associating the decomposition stages of pig carcasses with flies from the Calliphoridae family (Diptera). For this, 6 pig carcasses were exposed in Maranhão's Cerrado, utilizing metal cages with sawdust trays to catch immature specimens and "suspended traps" to capture adults. Adults of the Hemilucilia benoisti Séguy, and Hemilucilia townsendi Shannon species were only associated with the swelling stage. Chrysomya megacephala (Fabricius) was associated with 2 stages (black putrefaction and fermentation). The species Chloroprocta idioidea (Robineau-Desvoidy), Chrysomya albiceps (Wiedemann), Cochliomyia macellaria (Fabricius), and Lucilia eximia (Wiedemann) were associated with 4 of the 5 stages of decomposition, the latter being the only 1 associated with the initial stage. The larvae abandoned the carcasses to pupate from the second stage of decomposition, with L. eximia being the only 1 leaving the carcasses in the swelling stage, and C. albiceps the only 1 associated with both the fermentation and dry stages. Our findings indicate that calliphorid species can help forensic investigators estimine the post-mortem interval of cadavers in situations similar to those detailed in this study. Since there was a link between adult and immature species and certain stages, they can be used as indicators in future forensic investigations.

An Internship Approach to Strengthen the Pathway for Historically Underrepresented Groups in Health Sciences Research: The North Carolina Diversity and Inclusion Pathway Program.

BACKGROUND: To increase engagement of historically underrepresented groups in health sciences research, we created the North Carolina Diversity and Inclusion Pathway Program (NC-DIPP). This year-long, paid internship provides undergraduate and graduate students from 2 historically Black colleges and universities an opportunity to gain real-world experience under the mentorship of expert faculty. METHODS: To evaluate the early experiences with the NC-DIPP program, we conducted semi-structured interviews with interns and program leaders. Faculty mentors completed an online questionnaire to describe their experiences to date. A thematic approach was used to analyze the findings. RESULTS: In March-April 2023, 7 of 8 interns (88%), 6 of 11 mentors (54%), and 4 of 4 program leaders (100%) participated in various evaluation components. Overall, respondents agreed about the importance of programs like NC-DIPP, which further engage historically underrepresented groups in the health sciences. Interns had positive feedback about the internship, including real-world work experience, connections to experienced mentors, and early career planning. On a scale of 1 (poor) to 10 (excellent), interns rated their experience as a median of 8.3 (range: 4.5-10.0). Mentors had favorable but slightly lower scores (median: 7.0, range: 5.0-8.0). Areas for improvement were noted, including clearer expectations, improved logistical support, and central engagement of interns across projects. CONCLUSIONS: This early evaluation of NC-DIPP was generally favorable across all stakeholder groups. By providing a long-term experience in health science research, such programs can contribute to work experience, career planning, and professional networking.

Polysomnographic study in pediatric neurofibromatosis type 1.

Background: Neurofibromatosis type 1 (NF1) is a genetic disease that alters neurodevelopment. We aimed to analyze the sleep macrostructure of a sample of children affected by NF1 without neurocognitive co-morbidities and MRI reports of unidentified bright objects (UBOs). Methods: A 100 pre-pubertal children participated in the cross-sectional study: 50 subjects were children diagnosed with NF1 and 50 subjects were typically developing healthy children (TDC). All participants underwent polysomnographic evaluation through which conventional sleep parameters were collected: Total sleep time (TST), Sleep latency (SOL), first REM latency (FRL), number of stage shifts/h (SS/h), number of awakenings/h (AWN/h), wake after sleep onset (WASO%), sleep efficiency percentage (SE%), percentage of sleep time spent in sleep stages 1 (N1%) and 2 (N2%), slow-wave sleep (N3%), and REM sleep (REM%). Additionally, nocturnal respiratory events such as apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and periodic limb movement index (PLMI) were recorded. Results: Neurofibromatosis type 1 children showed a reduction in sleep duration parameters (TST; p < 0.001), sleep efficiency (SE%; p < 0.001), and stage N2% (p < 0.001). Moreover, the number of awakenings per hour (AWN/h), wake after sleep onset (WASO%), and respiratory events such as AHI, ODI, and PLMI resulted higher in NF1 vs. TDC children. Conclusion: The data showed that the sleep macrostructure differs between NF1 and TDC children. These findings suggest that the evaluation of sleep may provide useful support in corroborating the diagnosis and offers additional therapeutic management perspectives in NF1 and genetic neurodevelopmental disorders in general.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Background: Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years.Methods: All data were collected from 36 Italian dermatological or paediatric referral centres. Dupilumab was administered at label dosage with an induction dose of 300 mg on day 1 (D1), followed by 300 mg on D15 and 300 mg every 4 weeks (Q4W). Treatment effect was determined as overall disease severity, using EASI, P-NRS, S-NRS and c-DLQI at baseline, W16, W24, and W52. Ninety-six AD children diagnosed with moderate-to-severe AD and treated with dupilumab were enrolled.Results: Ninety-one (94.8%) patients completed the 52-week treatment period and were included in the study. A significant improvement in EASI score, P-NRS, S-NRS and c-DLQI was observed from baseline to weeks 16, 24 and 52.Conclusions: Our real-life data seem to confirm dupilumab effectiveness and safety in paediatric patients. Moreover, our experience highlighted that patients achieving clinical improvement at W16 preserved this condition over time.