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Purpose: To assess the tear levels of a set of apoptotic, matrix-degrading and antioxidant biomarkers, including Metalloproteinase 9 (MMP9), High Mobility Group Box 1 (HMGB1) and Superoxide Dismutase 3-Extracellular (SOD3)., Methods: Sandwich-ELISA commercial kits were used to test the expression of the three tear biomarkers in the lacrimal fluid of eligible participants. Linear logistic regression analysis was performed todetermine whether the set of tear biomarkers could be associated with clinically manifest keratoconus. ROC curve analysis using 10-fold cross-validation was performedto evaluate the prediction accuracy of the model., Results: Eighty-one participants aged 30-48 years old were enrolled in this study; 48 were patients with keratoconus and 33 were age-matched healthy subjects. The linear combination of the three tear biomarkers levels (AUC = 0.811; CI 95 %: 0.712-0.911) accurately indicated the existence of keratoconus; higher levels of MMP9 (Odd Ratio: 1.069; CI 95 %: 1.029-1.130) and HMGB1 (OR: 1.011; CI 95 %: 1.003-1.022) and lower levels of SOD3 (OR: 0.994; CI 95 %: 0.989-0.997) were significantly associated with a higher probability of keratoconus., Conclusion: Multivariable analysis of the set of tear levels of MMP9, HMGB1 and SOD3 biomarkers confirmed a chronic state of inflammation in the ocular surface of patients with keratoconus., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Childhood obesity represents a major public health issue worldwide. Evidence showed the need to implement prevention strategies mainly focused on lifestyle habits. Sleep hygiene is a variable of great interest and this review systematically examined the effects of sleep duration in increasing childhood obesity risk., Methods: A systematic literature review was conducted from December 2023 to February 2024. Study selection and data extraction procedures were performed in accordance with Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines and Statement, and risk of publication bias was assessed by the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies., Results: Original works in English were eligible for review and eleven studies that met the inclusion criteria were included. Studies collected were heterogeneous in terms of duration, sample characteristics, hours of sleep manipulation, anthropometric and hematological parameters collected, therefore it was not possible to perform a meta-analysis. A narrative synthesis of the reported evidence highlighted the impact of sleep duration above all on food intake, eating habits and hormone levels and consequently on the risk of childhood obesity development., Conclusion: This finding suggests the need to consider sleep hygiene as a modifiable lifestyle habit like diet and physical activity, in order to early prevent childhood obesity. Poor sleep hygiene can significantly contribute to weight gain and exacerbation of metabolic disorders linked to childhood obesity. Although more rigorous studies are needed, clinicians need to be aware of the role of sleep hygiene in reducing childhood obesity risk., 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 Porri, Luppino, Aversa, Corica, Valenzise, Messina, Pepe, Morabito, La Rosa, Lugarà, Abbate, Coco, Franchina, Lanzafame, Toscano, Li Pomi, Cavallaro and Wasniewska.)

Context: There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000., Objective: We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones., Methods: We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities., Results: The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started., Conclusion: In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: Evaluate the agreement between IOL Master 500 (Carl Zeiss Meditec AG, Germany ) and MYAH (Topcon EU, Visia Imaging, Japan) in measuring axial length, keratometry, and anterior corneal astigmatism., Setting: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Ophthalmology Clinic, University of Messina, Messina, Italy., Methods: In this prospective study, 40 eyes (right eye 25, left eye 15) of 40 patients were included. Axial length (AL), keratometry (K1, K2), and anterior corneal astigmatism (ACA) were measured. AL, mean K (Kavg) and magnitude of ACA were compared using Bland - Altman plot analysis, parametric and nonparametric statistical analysis. The difference vector and angle of error of the ACA measured by the two devices were evaluated by vector analysis using polar diagrams., Results: Mean and standard deviation with IOL Master and with MYAH device was for AL 24.25 ± 1.22 mm and 24.25 ± 1.22 mm (p = .99), for Kavg 42.75 ± 1.53 D and 42.85 ± 1.52 D (p = .78), for Magnitude of ACA 1.00 ± 0.58 D and 0.89 ± 0.56 D (p = .38) respectively. High correlations were found for AL (R² = 0.999), Kavg (R² = 0.996), and ACA Magnitude (R² = 0.889). Bland-Altman analysis of the two devices found high agreement and absence of proportional bias (MYAH-IOL MASTER) were found between the two assessments for AL (bias = -0.0005 mm, p = .93), Kavg (bias = 0.0955 D, p = .76) and ACA (bias = 0.11 D, p = .41). Limit of agreement (upper/lower LoA, 95%CI) were respectively +0.057/-0.058 mm for AL, + 0.29/-0.09 D for Kavg and +0.49/-0.27 D for ACA. No statistical difference was found between the x-component and y-component of the ACA vector (p > .01), the difference vector (IOL MASTER-MYAH) was +0.14 D axis 159 with an absolute mean angle of error of 7.2 ± 7.5 degree., Conclusions: The instruments appear to be interchangeable for measurements of AL, keratometry, and magnitude of ACA with high agreement between the two devices. Also, in the presence of low astigmatism, the two instruments give the same results in terms of ACA., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aimed to evaluate the safety and efficacy of povidone-iodine 0.6% (PVI) irrigation for preventing recurrence of stenosis after punctoplasty in patients with punctal and proximal canalicular stenosis treated using a venous catheter as a stent. Methods: Twenty patients were enrolled and divided into two groups. Group 1 received irrigation of 1 mL 0.6% PVI, while Group 2 received 1 mL of balanced salt solution (BSS). The patients underwent baseline, 15-, 30-, and 90-day assessments using the Ocular Surface Disease Index (OSDI) questionnaire, Symptoms Assessment in Dry Eye (SANDE), Schirmer I test, tear meniscus height (TMH), bulbar redness, meibography, and non-invasive breakup time (NIKBUT) through Keratograph 5M (Oculus, Germany). Results: At three months, both groups demonstrated statistically significant improvements in symptoms and ocular surface parameters. However, Group 1 showed statistically significant improvements in OSDI, SANDE scores, bulbar redness, and NIKBUT compared to Group 2. Additionally, no patients in Group 1 presented a recurrence of stenosis, while three patients in Group 2 demonstrated stenosis relapse at the end of the follow-up period. Conclusions: The application of a venous catheter and PVI 0.6% irrigations proved to be effective in treating proximal lacrimal duct stenosis, reducing the risk of recurrence and improving tear film stability, ocular discomfort symptoms, and ocular surface parameters., Competing Interests: The authors declare no conflicts of interest.

Objectives: The persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate., Methods: This is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan-Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence., Results: Overall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07-1.49, p = 0.006., Conclusion: Real-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate., 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.)

Purpose: To evaluate the prevalence, clinical ocular presentation and corneal healing in moderate and severe neurotrophic keratopathy (NK) caused by systemic diseases and treated with rh-NGF., Setting: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Ophthalmology Clinic, University of Messina, Italy., Design: Retrospective observational study of case series., Materials and Methods: In this retrospective observational study 11 patients (five female and six males) aged from 24 to 88 years (55.4 ± 21.3 years) with moderate and severe NK caused by systemic diseases were enrolled. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The underlying systemic causes of NK were determined., Results: The main cause of NK was post-neuroma surgery (36%), followed by diabetes (18%). The remaining causes were rheumatoid arthritis (9%), post-traumatic (9%), post-surgery (9%), atopia (9%), Graves' disease (9%). Seven eyes presented severe grade of NK with corneal ulcer and in four a moderate grade was registered. The rh-NGF (Cenegermin) was administered with a standard protocol one drop six times daily for 8 weeks. The complete healing of all corneal defects was registered at the end of the treatment., Conclusions: The post-neuroma surgery was the most common cause of NK and severe grade was clinically more represented. The rh-NGF proved effective to promote corneal recovery with all defects healed after the treatment., 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 © 2022 Meduri, Oliverio, Valastro, Azzaro, Camellin, Franchina, Inferrera, Roszkowska and Aragona.)

Purpose: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy., Methods: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice., Results: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns., Conclusion: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.

Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM-patients, suggesting their involvement in the pathogenesis of beta TM-osteoporosis.

Objective: Androgen-deprivation therapy (ADT) is the usual treatment for locally advanced or metastatic prostate cancer. Osteoporosis is a common complication of ADT. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate to prevent bone loss during androgen ablation., Methods: Sixty patients with prostate cancer and osteoporosis were enrolled and randomly assigned to 2 different treatment regimes: group A (30 patients) treated with maximum androgenic blockage (MAB), and group B (30 patients) treated with bicalutamide 150 mg. Each group was divided in 2 subgroups A1-A2 and B1-B2. All patients received calcium and cholecalciferol supplements (500 mg of elemental calcium and 400 IU cholecalciferol) daily. The A2 and B2 subgroups were also treated with neridronate (25 mg intramuscular monthly). Lumbar and femoral bone mineral density (BMD) was evaluated by dualenergy X-ray absorptiometry (DXA), both at baseline and after one year of treatment. Deoxypyridinoline (DPD) and bone-alkaline phosphatase (B-ALP) were determined at the beginning, midstudy and at the end., Results: Patients treated only with calcium and cholecalciferol (A1, B1 subgroups) showed a marked bone loss after 6, and 12 months, with increased levels of DPD and BALP, compared to baseline values. Patients treated with neridronate (A2 et B2 subgroups) showed unchanged levels of these markers. After one year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (A1 subgroup: -4.9% and -1.9% respectively). BMD did not change significantly at any site in patients treated also with neridronate (A2 subgroup: +1% and +0.8% respectively). Lumbar and total hip BMD did not change significantly (-1.5% and -1% respectively) in B1 subgroup. In B2 subgroup an important increase in lumbar spine and the total hip BMD was shown (+2.5% and 1.6% respectively). No relevant side effects were recorded during our study., Conclusion: In conclusion, neridronate is an effective and safe treatment in preventing bone loss in men receiving ADT for prostate cancer.