Hamartoma of mature cardiac myocytes presenting as a polypoid epicardial tumor in the interatrial groove and with gene fusions by copy number anomalies of chromosome 7.

Hamartoma of mature cardiac myocytes (HMCM) is an extremely rare cardiac tumor characterized by benign growth of differentiated mature striated cardiac myocytes, and usually involves the ventricular myocardium. We describe the case of a 15-year-old female who presented with a short history of atrial fibrillation and a polypoid epicardial tumor that was attached to the interatrial groove by a short pedicle. The resected specimen showed features consistent with HMCM.

Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects.

Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs.

Management of High-Risk Neuroblastoma with Soft-Tissue-Only Disease in the Era of Anti-GD2 Immunotherapy.

Neuroblastoma presents with two patterns of disease: locoregional or systemic. The poor prognostic risk factors of locoregional neuroblastoma (LR-NB) include age, or amplification, 11q, histology, diploidy with or mutations, and aberrations. Anti-GD2 immunotherapy has significantly improved the outcome of high-risk (HR) NB and is mostly effective against osteomedullary minimal residual disease (MRD), but less so against soft tissue disease.

StarD7 deficiency switches on glycolysis and promotes mitophagy flux in C2C12 myoblasts.

StarD7 is a member of the START protein family required for phosphatidylcholine delivery to the mitochondria, thus key to maintain mitochondrial structure. Its deficiency has been associated with an impairment of cellular processes, such as proliferation and migration, and it has also been reported that it is needed in myogenic differentiation. Here, we show that StarD7 deficiency in C2C12 muscle cells results in the accumulation of abnormal mitochondria, a reduced number of mitochondria per cell area and increased glycolysis.

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes.

Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment.

Mechanisms of Modulation of Mitochondrial Architecture.

Mitochondrial network architecture plays a critical role in cellular physiology. Indeed, alterations in the shape of mitochondria upon exposure to cellular stress can cause the dysfunction of these organelles. In this scenario, mitochondrial dynamics proteins and the phospholipid composition of the mitochondrial membrane are key for fine-tuning the modulation of mitochondrial architecture.

Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms.

This study investigated the effect of nicotinamide (NAM) supplementation on the development of brain inflammation and microglial activation in a mouse model of type 1 diabetes mellitus. C57BL/6J male mice, which were made diabetic with five consecutive, low-dose (55 mg/kg i.p.

Risk factors for major complications after surgical treatment of primary ileocecal Crohn's disease. A multicentric Latin American experience.

Introduction: Complications after ileocecal resection for Crohn's disease (CD) are frequent. The aim of this study was to analyze risk factors for postoperative complications after these procedures.

Materials And Methods: We conducted a retrospective analysis of patients treated surgically for Crohn's disease limited to the ileocecal region during an 8-year period at 10 medical centers specialized in inflammatory bowel disease (IBD) in Latin America.

Novel infusion strategy reduces severe adverse events caused by the anti-GD2 monoclonal antibody naxitamab.

Introduction: Anti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) are associated with Grade ≥3 (≥G3) adverse events (AEs) such as severe pain, hypotension, and bronchospasm. We developed a novel method of administering the GD2-binding mAb naxitamab, termed "Step-Up" infusion (STU), to reduce the risk of AEs of severe pain, hypotension, and bronchospasm.

Methods: Forty-two patients with GD2-positive tumors received naxitamab under "compassionate use" protocols and administered either the standard infusion regimen (SIR) or the STU regimen.

Naxitamab Combined with Granulocyte-Macrophage Colony-Stimulating Factor as Consolidation for High-Risk Neuroblastoma Patients in First Complete Remission under Compassionate Use-Updated Outcome Report.

Naxitamab is an anti-GD2 antibody approved for the treatment of relapsed/refractory HR-NB. We report the survival, safety, and relapse pattern of a unique set of HR-NB patients consolidated with naxitamab after having achieved first CR. Eighty-two patients were treated with 5 cycles of GM-CSF for 5 days at 250 μg/m/day (-4 to 0), followed by GM-CSF for 5 days at 500 μg/m/day (1-5) and naxitamab at 3 mg/kg/day (1, 3, 5), on an outpatient basis.

FTY720-P, a Biased S1PR Ligand, Increases Mitochondrial Function through STAT3 Activation in Cardiac Cells.

FTY720 is an FDA-approved sphingosine derivative drug for the treatment of multiple sclerosis. This compound blocks lymphocyte egress from lymphoid organs and autoimmunity through sphingosine 1-phosphate (S1P) receptor blockage. Drug repurposing of FTY720 has revealed improvements in glucose metabolism and metabolic diseases.

Acute myocarditis with transient myocardial thickening in two oncologic patients treated with anti-GD2 immunotherapy.

Immunotherapy has considerably improved clinical outcomes in different types of cancers but has also been associated with the development of myocarditis, especially with that mediated by immune checkpoint inhibitors. To the best of our knowledge, these are the first cases of myocarditis after anti-GD2 immunotherapy reported to date. We present two cases of paediatric patients who, after anti-GD2 infusion, presented severe myocarditis with myocardial hypertrophy detected on echocardiography and confirmed with cardiac magnetic resonance imaging.

Nek4 regulates mitochondrial respiration and morphology.

Nek4 is a serine/threonine kinase which has been implicated in primary cilia stabilization, DNA damage response, autophagy and epithelial-to-mesenchymal transition. The role of Nek4 in cancer cell survival and chemotherapy resistance has also been shown. However, the precise mechanisms by which Nek4 operates remain to be elucidated.

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission.

Background: Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF).

Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma.

Background: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs).

GRP94 Is Involved in the Lipid Phenotype of Brain Metastatic Cells.

Metabolic adaptation may happen in response to the pressure exerted by the microenvironment and is a key step in survival of metastatic cells. Brain metastasis occurs as a consequence of the systemic dissemination of tumor cells, a fact that correlates with poor prognosis and high morbidity due to the difficulty in identifying biomarkers that allow a more targeted therapy. Previously, we performed transcriptomic analysis of human breast cancer patient samples and evaluated the differential expression of genes in brain metastasis (BrM) compared to lung, bone and liver metastasis.

Patient-Specific iPSC-Derived Astrocytes Contribute to Non-Cell-Autonomous Neurodegeneration in Parkinson's Disease.

Parkinson's disease (PD) is associated with the degeneration of ventral midbrain dopaminergic neurons (vmDAns) and the accumulation of toxic α-synuclein. A non-cell-autonomous contribution, in particular of astrocytes, during PD pathogenesis has been suggested by observational studies, but remains to be experimentally tested. Here, we generated induced pluripotent stem cell-derived astrocytes and neurons from familial mutant LRRK2 G2019S PD patients and healthy individuals.

Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency.

Opa1 participates in inner mitochondrial membrane fusion and cristae morphogenesis. Here, we show that muscle-specific Opa1 ablation causes reduced muscle fiber size, dysfunctional mitochondria, enhanced Fgf21, and muscle inflammation characterized by NF-κB activation, and enhanced expression of pro-inflammatory genes. Chronic sodium salicylate treatment ameliorated muscle alterations and reduced the muscle expression of Fgf21.

Induction of oxidative metabolism by the p38α/MK2 pathway.

Adequate responses to environmental stresses are essential for cell survival. The regulation of cellular energetics that involves mitochondrial energy production and oxidative stress is central in the process of stress adaptation and response. The p38α signalling pathway plays a key role in the response to stress stimuli by orchestrating multiple cellular processes.

Natal foraging philopatry in eastern Pacific hawksbill turtles.

The complex processes involved with animal migration have long been a subject of biological interest, and broad-scale movement patterns of many marine turtle populations still remain unresolved. While it is widely accepted that once marine turtles reach sexual maturity they home to natal areas for nesting or reproduction, the role of philopatry to natal areas during other life stages has received less scrutiny, despite widespread evidence across the taxa. Here we report on genetic research that indicates that juvenile hawksbill turtles () in the eastern Pacific Ocean use foraging grounds in the region of their natal beaches, a pattern we term natal foraging philopatry.

[Sacral neuromodulation. Long-term results].

Sacral neuromodulation involves electrical stimulation of af­ferent nerve roots to restore the balance between inhibitory and excitatory reflexes who improve the functional activity of the pelvic floor. With benefits in patients with fecal inconti­nence, constipation and chronic anorectal pain. Objective.