Could a careful clinical examination distinguish physiologic phimosis from balanitis xerotica obliterans in children?

The diagnosis of balanitis xerotica obliterans (BXO) in children may be challenging, since clinical examination only could lead to an underestimation of its incidence. The aim of this retrospective and single-centre study is to assess the diagnostic performance of clinical examination, together with clinical history, in identifying BXO. Ninety-seven children underwent circumcision for phimosis from 2015 to 2019. Histology was routinely performed. Cohen\u2019s kappa coefficient, sensitivity, specificity, predictive values, likelihood ratios and accuracy of macroscopic appearance of the foreskin, steroid administration and past medical history were estimated. Forty-eight patients (50%) were affected by BXO; 31 of them (69%) presented with suggestive clinical signs. A strictured or whitish urethral meatus was detected during surgery in nine cases (19%); this was associated to allergic or immune diseases (p = 0.046). Foreskin appearance alone mildly correlated with histology (k = 0.494; p < 0.001) and it showed a diagnostic accuracy of 75%. The specificity and positive predictive value of abnormal macroscopic findings at examination, together with a positive clinical history for other allergic or immune diseases, and/or for balanitis, were 100% and the positive likelihood ratio was greater than 10. Conversely, sensitivity decreased to 4.5% (95% CI 0\u201311%). Conclusion: Foreskin appearance together with clinical history could predict BXO with certainty. However, since the absence of a positive medical history could not exclude the diagnosis, foreskin histology is still highly recommended

Pediatric Surgery and Anesthesia in Low-Middle Income Countries: Current Situation and Ethical Challenges

Low-middle income countries (LMICs) are currently experiencing an important population growth, leading to a substantial raise in the number of children living in those areas. As a consequence, the existing gap between the need for surgical and anesthetic care and the available therapeutic options will increase. To overcome this, an improvement in the available expertise, infrastructures, and supplies will be mandatory. The implementation of educational and training programs for local healthcare providers should be a top priority. Alongside, the population's awareness on the necessity to seek for medical care should be deployed, together with an eased access to health facilities. Based on the existing literature and our 20-years' experience in humanitarian missions, our article aims to investigate the status of pediatric surgery in LMICs, and the role of western aids in the implementation of this ever-increasing field of expertise

Prevalence of Gastroesophageal Reflux Disease in Congenital Diaphragmatic Hernia Survivors From Infancy to Adulthood

Background: Gastroesophageal reflux disease (GERD) is a common comorbidity associated with congenital diaphragmatic hernia (CDH), with reported cases of Barrett's esophagus (BE) and esophageal adenocarcinoma before the age of 25. The prevalence and natural course of GERD in CDH survivors remain uncertain due to variations in diagnostic methods. We aimed to analyse the GERD prevalence from infancy through young adulthood. Methods: We retrospectively analyzed pH-impedance measurements and endoscopic findings in 96 CDH survivors evaluated as routine care using well established clinical protocols. GERD was defined as an abnormal acid exposure time for pH-MII measurements and as presence of reflux esophagitis or BE at upper endoscopy. Clinical data including symptoms at time of follow-up and use of antireflux medication were collected. Results: GERD prevalence remained consistently low (≤10%) across all age groups, yet many patients experienced GER symptoms. Histological abnormalities were observed in 80% of adolescents and young adults, including microscopic esophagitis in 50%. BE was diagnosed in 7% before the age of 18, all had GER symptoms. CDH severity, anatomy at the time of CDH correction, alcohol usage, and smoking did not emerge as significant risk factors for GERD. Conclusions: Given the low GERD prevalence in CDH survivors, a symptom-driven approach to diagnosis and follow-up is warranted. We advise long-term follow-up for all adult patients due to the early onset of BE and the limited evidence available. The longitudinal course and impact of GERD on other long-term CDH-related comorbidities should be explored in larger cohorts.</p

Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups

IntroductionMetabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.MethodsWe performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides.ResultsPancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival.DiscussionPJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Innovative Techniques Associated with Traditional Abdominal Surgery in Complex Pediatric Cases: A Tertiary Center Experience

Pediatric abdominal surgery is constantly evolving, alongside the advent of new surgical technologies. A combined use of new tools and traditional surgical approaches can be useful in the management of complex cases, allowing less invasive procedures and sometimes even avoiding multiple interventions. This combination of techniques has implications even from the anesthetic point of view, especially in post-operative pain control. Thereby, tertiary level centres, including highly-specialized professionals and advanced equipment, can maximize the effectiveness of treatments to improve the final outcomes. Our paper aims to present some possible combinations of techniques recently used at our institution to provide a one-session, minimally invasive treatment within different areas of abdominal surgery

Surgical Approaches to Neuroblastoma: Review of the Operative Techniques

Neuroblastoma (NB) is the most commonly occurring soft-tissue malignancy of childhood. Surgery plays an important role in multidisciplinary treatment and its principal aim is a local control of the disease, respecting the integrity of the surrounding structures. There is no unanimous consensus on the best surgical technique, and the operative approach largely depends on the anatomical location and the extension of the mass. To have a complete overview of the different type of treatment, we made a review of the literature from the last twenty years of all the surgical approaches applied for NBs resection, accordingly to the anatomical site