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Balanitis xerotica obliterans (BXO) is a chronic inflammatory skin disorder, considered the male genital variant of lichen sclerosus. Anti-inflammatory drugs are commonly used in BXO. We evaluated the effects of an innovative formulation of ozonated olive oil with vitamin E acetate (OZOILE®) on the inflammatory status and tissue remodeling in male children with BXO. The mRNA transcripts of proteins involved either in inflammation or in dynamics of tissue regeneration were analyzed by quantitative real-time PCR, in foreskins affected by BXO removed from patients untreated or treated with OZOILE® cream for 7 days before circumcision. We found a significant reduction in mRNA levels of IL-1β, TNF-α, INF–γ, transglutaminase 2 and NOS2 in foreskins treated with OZOILE® in comparison to untreated ones (p < 0.001). No significant differences were observed in NF-κB activation in the specimens obtained from treated and untreated patients. Hence, OZOILE® treatment up-regulated hypoxia-inducible factor (HIF)-1alpha, vascular endothelial growth factor (VEGF) and E-cadherin gene expression (p < 0.001). The treatment with OZOILE® showed effective results in children affected by BXO by reducing the inflammatory process and stimulating mechanisms for tissue regeneration of the foreskin. A randomized clinical trial on a large number of children affected by BXO might be useful to verify the efficacy of topical treatment with OZOILE®.

Dear Editor, I would like to express my sincere appreciation for the publication and detailed discussion of therapies for dermatological and inflammatory conditions, as exemplified in the recent article “Onychocryptosis: a retrospective study of clinical aspects, inflammation treatment, and pain management using Ozoile as a hydrogel and cream formulation” by Vincenzo Francavilla et al. This insightful study has provided a comprehensive overview of the management of onychocryptosis, a common and often distressing condition, and has highlighted the innovative use of OZOILE® in a clinical setting.1 [...]

Background/Objectives: Acute scrotal pain in children and adolescents requires prompt evaluation to differentiate testicular torsion from other scrotal pathologies. Testicular torsion, a surgical emergency, can lead to irreversible testicular damage if not managed rapidly. This study aims to assess the clinical signs, diagnostic tools, and outcomes related to testicular torsion in patients presenting with acute scrotal pain. Methods: A retrospective analysis was conducted on 111 patients diagnosed with acute scrotal conditions. Clinical signs, presentation times, ultrasound findings, and treatment outcomes (surgical intervention, orchiectomy, or medical management) were evaluated. The statistical analysis was performed with a p-value < 0.05 being considered significant. Correlations between clinical signs, diagnostic imaging, and treatment modalities were assessed. Results: The most prevalent clinical signs were scrotal swelling (92.2%), pain on palpation (93.5%), and scrotal hyperemia (84.4%). Testicular torsion was strongly associated with the absence of the cremasteric reflex (p < 0.0001) and testicular retraction (p < 0.0001). Ultrasound findings, including absent blood flow and testicular heterogeneity, were highly predictive of surgical intervention (p < 0.01). Patients presenting within 8 h of symptom onset had higher success rates of detorsion and testicular preservation. Conclusions: Timely and accurate clinical assessment, including the identification of key signs such as the absence of the cremasteric reflex and testicular retraction, is critical for differentiating testicular torsion from other conditions. Ultrasound findings are pivotal in guiding treatment decisions in cases of clinical uncertainty. Early intervention significantly improves testicular viability and outcomes, underscoring the importance of rapid diagnosis and management.

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.

Background: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was to define the LS immunohistochemical profile of foreskin in children, focusing on tissue immune response and cell proliferation. Methods: Thirty specimens of foreskins removed from pediatric patients during circumcision were included: six from ritual operation (A), twelve from phimosis (B), and twelve from phimosis with LS (C). Formalin-fixed paraffin-embedded sections were stained for histomorphology and immunohistochemistry. A quantitative evaluation for CD8, CD57, p53, and Ki-67 and a statistical analysis were performed. Results: As compared to groups A and B, the samples from group C patients showed an acanthotic epidermis, a dermal band of lymphoid infiltrate with a significant enhancement of CD8+ CD57+ lymphocytes, and a keratinocytic hyperplasia with an overexpression of Ki67+ and p53+ cells. Conclusions: Immunohistological findings confirmed an immune reaction and proliferative behavior in juvenile LS of foreskin. We believe that radical circumcision should be the first treatment of choice in pediatric patients with clinical suspicious of LS for the potential risk of transformation to SCC in adulthood.

Stem cell factor receptor (c-kit) plays a crucial role in regulating proliferation and survival of germ cells. The aim of this study was to find the correlation between the number of c-kit positive germ cells, testicular asymmetry and histological grade in varicocele affected testis samples of adolescents. Twenty testicular biopsy samples of adolescents affected by varicocele and eight normal control testes were included. The relationship between percentage of testicular asymmetry, number of tubular c-kit positive germ cells and severity of spermatogenic failure was assessed. The mean (SD; median) histological grade for spermatogenic failure in controls was 1.37(0.52; 1), while in the varicocele group, it was 2.70(1.08; 3) (P = .0052). Mean(SD; median) number c-kit positive germ cells in the control group were 20.1(2.52; 20), while in the varicocele group it was 12.35(7.16; 12.5) (P = .0059). Spearman test documented a significant positive correlation between percentage of hypotrophy and histological grade of spermatogenic failure (r = 0.5544 , 95% CI: 0.1345 to 0.8055, P = .0112) but a negative correlation with the number of c-kit positive cells (r = - 0.5871, 95% CI: - 0.8219 to -0.1817, P = .0065). Moreover, a significant negative correlation was found between grade of histological changes and number of c-kit positive germ cells (P < .0001). A significant correlation between hypotrophy, histological lesions and c-kit positive germ cells exists in varicocele testes. This finding suggests a possible role for c-kit in the pathogenesis of germ cell impairment in varicocele. Histological changes and lack of c-kit germ cells were also noted in testes not displaying hypotrophy. We believe that reliable markers should be found as better predictors of testicular function in adolescent with varicocele.

Aim To systematically review literature and to assess the status of the ERAS protocol in pediatric populations undergoing gastrointestinal surgery. Methods Literature research was carried out for papers comparing ERAS and traditional protocol in children undergoing gastrointestinal surgery. Data on complications, hospital readmission, length of hospital stay, intraoperative fluid volume, post-operative opioid usage, time to defecation, regular diet, intravenous fluid stop, and costs were collected and analyzed. Analyses were performed using OR and CI 95%. A p value <0.05 was considered significant. Results A total of 8 papers met the inclusion criteria, with 943 included patients. There was no significant difference in complication occurrence and 30-day readmission. Differently, length of stay, intraoperative fluid volume, post-operative opioid use, time to first defecation, time to regular diet, time to intravenous fluid stop, and costs were significantly lower in the ERAS groups. Conclusions ERAS protocol is safe and feasible for children undergoing gastrointestinal surgery. Without any significant complications and hospital readmission, it decreases length of stay, ameliorates the recovery of gastrointestinal function, and reduces the needs of perioperative infusion, post-operative opioid administration, and costs.