Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a topology ensured the desired PI3Kδ selectivity. Achievement of low nanomolar cellular potencies through hinge binder group optimization, reduction of intrinsic permeability through head group optimization to extend lung retention, and screening of crystalline forms suitable for administration as dry powders culminated in the identification of compound .

Corrigendum: CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder.

[This corrects the article DOI: 10.3389/fphar.2024.

NUP98 fusion proteins and KMT2A-MENIN antagonize PRC1.1 to drive gene expression in AML.

Control of stem cell-associated genes by Trithorax group (TrxG) and Polycomb group (PcG) proteins is frequently misregulated in cancer. In leukemia, oncogenic fusion proteins hijack the TrxG homolog KMT2A and disrupt PcG activity to maintain pro-leukemogenic gene expression, though the mechanisms by which oncofusion proteins antagonize PcG proteins remain unclear. Here, we define the relationship between NUP98 oncofusion proteins and the non-canonical polycomb repressive complex 1.

The pediatric DAV-expert algorithm: A GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access device in children.

In pediatric patients, the choice of the venous access device currently relies upon the operator's experience and preference and on the local availability of specific resources and technologies. Though, considering the limited options for venous access in children if compared to adults, such clinical choice has a great critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems fully satisfactory and useful in clinical practice.

Growing teratoma syndrome in children and adolescents: Prevalence and surgical outcome.

Introduction: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome.

CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder.

Inhibition of p38 mitogen-activated protein kinase (MAPKs) is a potential therapeutic approach for the treatment of acute and chronic pulmonary inflammatory conditions. Here, we report the and characterization of the anti-inflammatory effects of CHF6297, a novel potent and selective p38α inhibitor designed for inhalation delivery as a dry powder formulation. CHF6297 has been proven to inhibit p38α enzymatic activity with sub-nanomolar potency (IC = 0.

Case report: A simple and reliable approach for progressive internal distraction of the sternum for Jeune syndrome (asphyxiating thoracic dystrophy): preliminary experience and literature review of surgical techniques.

Background: Described for the first time in 1954, Jeune syndrome (JS), often called asphyxiating thoracic dystrophy, is a congenital musculoskeletal disease characterized by short ribs, a narrow thorax, and small limbs. In this study, we analyzed and presented our preliminary experience with a device for progressive internal distraction of the sternum (PIDS) in patients with symptomatic JS. In addition, we reviewed the contemporary English literature on existing surgical techniques for treating children with congenital JS.

Recurrent thoracic air leak syndrome in patients affected by pulmonary graft-versus-host disease: Surgical strategies and outcome.

Background And Aims: Thoracic air leak syndrome (TALS) is a complication related to chronic pulmonary graft-versus-host disease (pGvHD) that affects approximately 0.83%-3.08% patients after allogenic hematopoietic stem cell transplant.

Preoperative Spinal Angiography for Thoracic Neuroblastoma: Impact of Identification of the Adamkiewicz Artery on Gross Total Resection and Neurological Sequelae.

Background: Patients with thoracic neuroblastoma (TNB) are at high risk of postoperative neurologic complications due to iatrogenic lesions of the artery of Adamkiewicz (AKA). The role of performing a preoperative spinal angiography (POSA) in these patients must be clarified. The present study sought to further understand the relationship between POSA and TNB, as well as the effects of identifying the AKA on surgical excision and neurological consequences.

Chemotherapy-induced cavitating Wilms' tumor pulmonary metastasis: Active disease or scarring? A case report and literature review.

The second most common abdominal tumor in children is Wilms' tumor, and the lung is where it most often metastasizes. The typical metastases are multiple, peripherally located, round, and variable-sized nodules. Atypical patterns are also possible and may create diagnostic challenges, especially in patients treated with chemotherapy.

Case report: Primary ovarian Burkitt's lymphoma: A puzzling scenario in pediatric population.

Burkitt's lymphoma (BL) is defined as a highly invasive B-cell lymphoma, usually characterized by an excellent prognosis, more than 90% of children and adolescents being cured with highly dose-intensive multiagent chemotherapy. Primary ovarian localization without involvement of other organs is a rare manifestation of BL, especially in pediatric population. Symptoms at diagnosis are similar to other ovarian lesions and differential diagnosis may be challenging for clinicians.

The Use of Cavitron Ultrasonic Surgical Aspirator for High-Risk Neuroblastoma with Image-Defined Risk Factors in Children.

Aim of the study: The cavitron ultrasonic surgical aspirator (CUSA) has gained popularity in adult surgical oncology, but its application in children is limited to liver surgery and neurosurgical procedures. The complete resection of neuroblastoma with image-defined risk factors (IDRFs) is still considered one of the most difficult procedures to achieve in pediatric surgical oncology, with a high morbidity rate and potential risk of intraoperative mortality. The aim of our study is to describe the application of ultrasonic dissection in neuroblastoma with IDRFs.

Pigmented median raphe cyst of the scrotum. A rare pediatric case and review of the literature.

Aim: Median raphe cyst are uncommon malformations of male genitalia, in which are rarely described melanin pigments or melanocytes; less than ten cases have been reported in literature. The aim of our study is to describe a rare ormations, case of pigmented median raphe cyst of the scrotum, successfully treated in our hospital.

Case Experience: A 6-years-old boy underwent surgical removal of a melanocytic lesion of the ventral surface of the scrotum in Day Surgery regimen.

Intraoperative Neuromonitoring for Thyroid Surgery in Children and Adolescents: A Single Center Experience.

Intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) has been shown in adults to minimize nerve palsy after thyroid surgery, but only few studies on its efficacy in a pediatric population have been reported. We conducted a retrospective study on patients operated for thyroid lesions from 2016 to 2022. The analyzed population was divided in two groups: patients treated from 2016 to 2020, when the identification of the RLN was performed without IONM (Group A); and patients treated since 2021, when IONM was implemented in every surgical procedure on the thyroid (Group B).

Uterine leiomyoma in pediatric population: A case report and review of the literature.

Uterine leiomyomas are rare in the pediatric population with less than 20 cases in adolescences reported in the literature. Furthermore, these masses represent a common presentation of gynecologic tumors with increasing age. We report a case of a 14-year-old female who presented with abdominal pain and increasing abdominal girth.

Intraoperative Neuromonitoring for Pediatric Pelvic Tumors.

Background: Tumors of the pre-sacral and sacral spaces are a rare occurrence in children. Total tumor excision is required due to the significant risk of relapse in the event of partial surgery, but the surgical procedure may lead to postoperative problems such as urinary, sexual, and anorectal dysfunctions. Intraoperative neuromonitoring (IONM) has gained popularity in recent years as a strategy for preventing the onset of neurologic impairments by combining several neurophysiological techniques.

Percutaneous treatment of chest wall chondroid hamartomas: the experience of a single center.

Background: Thoracic mesenchymal hamartomas are rare benign lesions. Rarely symptomatic, they may compress pulmonary parenchyma, leading to respiratory distress. Although spontaneous regression has been documented, the more common outcome is progressive growth.

Phytotherapy as ancillary treatment after urinary stone lithotripsy in pediatric age.

Aim: Small stone fragments (NSRF) may be observed after mini-invasive lithotripsy. A 3-components herbal extract drug was tested in young patients presenting NSRF to assess efficacy, safety and tolerability.

Material And Methods: Patients aged 6-18 years, treated by endo-urological procedures in 5-year period, were randomly divided in 2 groups.

Case report: Bilateral pleural effusion secondary to late migration of a tunneled central venous catheter in a patient affected by high risk neuroblastoma.

The insertion of long-term central venous catheters is a standard of care for children affected by malignancies, although it can be associated with life-threatening complications. The present paper reports an unusual mechanical complication related to the use of a long term tunneled central venous catheter in a pediatric oncologic patient. An 18 months old child, diagnosed with stage M high-risk retroperitoneal neuroblastoma, underwent ultrasound-guided placement of a 6 Fr bilumen long-term tunneled central venous catheter in the right internal jugular vein prior to the beginning of induction chemotherapy.

Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases.

The identification of novel inhaled p38α/β mitogen-activated protein kinases (MAPK) (MAPK14/11) inhibitors suitable for the treatment of pulmonary inflammatory conditions has been described. A rational drug design approach started from the identification of a novel tetrahydronaphthalene series, characterized by nanomolar inhibition of p38α with selectivity over p38γ and p38δ isoforms. SAR optimization of is outlined, where improvements in potency against p38α and ligand-enzyme dissociation kinetics led to several compounds showing pronounced anti-inflammatory effects (inhibition of TNFα release).