Burr Hole Hemispherotomy-Modification of Trans-Sylvian Peri-Insular Technique: 2-Dimensional Operative Video.

Trans-sylvian peri-insular hemispherotomy represents a functional hemispherectomy with minimal brain removal used for treatment of refractory hemispheric epilepsy.1 Exposure for this procedure is achieved by craniotomy. Refinement in the hemispherotomy technique, including trends toward minimizing cortical resection, has contributed to a substantial drop in complication rates.

Peripheral Nervous System (PNS) Myelin Diseases.

This is a review of inherited and acquired causes of human demyelinating neuropathies and a subset of disorders that affect axon-Schwann cell interactions. Nearly all inherited demyelinating neuropathies are caused by mutations in genes that are expressed by myelinating Schwann cells, affecting diverse functions in a cell-autonomous manner. The most common acquired demyelinating neuropathies are Guillain-Barré syndrome and chronic, inflammatory demyelinating polyneuropathy, both of which are immune-mediated.

Which OCT Measure of the Optic Nerve Head Improves Fastest? Towards Optimizing Early Detection of Resolving Papilledema in Children.

Purpose: Optical coherence tomography (OCT) has been used to monitor papilledema. This study aims to determine which OCT-derived measures of the optic nerve head (ONH) detect resolving papilledema in children faster than standard OCT measures.

Methods: Children (≤18 years of age) with papilledema who completed optic nerve SD-OCT pretreatment and had evidence of treatment response on one or more follow-up OCTs within 4 months were included.

Recurrent missense variant identified in two unrelated families with MPZL2-related hearing loss, expanding the variant spectrum associated with DFNB111.

MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss.

Predicting pediatric emergence delirium using data-driven machine learning applied to electronic health record dataset at a quaternary care pediatric hospital.

Objectives: Pediatric emergence delirium is an undesirable outcome that is understudied. Development of a predictive model is an initial step toward reducing its occurrence. This study aimed to apply machine learning (ML) methods to a large clinical dataset to develop a predictive model for pediatric emergence delirium.

The importance of REM sleep fragmentation in the effects of stress on sleep: Perspectives from preclinical studies.

Psychological stress poses a risk for sleep disturbances. Importantly, trauma-exposed individuals who develop posttraumatic stress disorder (PTSD) frequently report insomnia and recurrent nightmares. Clinical studies have provided insight into the mechanisms of these sleep disturbances.

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.

Loss of Baz1b in mice causes perinatal lethality, growth failure, and variable multi-system outcomes.

BAZ1B is one of 25-27 coding genes deleted in canonical Williams syndrome, a multi-system disorder causing slow growth, vascular stenosis, and gastrointestinal complaints, including constipation. BAZ1B is involved in (among other processes) chromatin organization, DNA damage repair, and mitosis, suggesting reduced BAZ1B may contribute to Williams syndrome symptoms. In mice, loss of Baz1b causes early neonatal death.

Next-generation of melanoma researchers: Trainee perspectives from around the world.

The Society for Melanoma Research (SMR) was created 20 years ago and has unequivocally contributed to the vast progress of the field, particularly for the treatment of melanoma patients with metastatic disease by facilitating synergistic collaborations between clinicians, researchers at the bench, and industry. In commemoration of the 20th anniversary of the first SMR International Congress (held in 2003 in Philadelphia), we look to the future by highlighting the perspectives of the next generation of rising stars, medical, and graduate students across six continents.

AAV-Mediated Targeting of the Activin A-ACVR1 Signaling in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive disabling heterotopic ossification (HO) at extra-skeletal sites. Here, we developed adeno-associated virus (AAV)-based gene therapy that suppresses trauma-induced HO in FOP mice harboring a heterozygous allele of human () while limiting the expression in non-skeletal organs such as the brain, heart, lung, liver, and kidney. AAV gene therapy carrying the combination of codon-optimized human ACVR1 (ACVR1) and artificial miRNAs targeting Activin A and its receptor ACVR1 ablated the aberrant activation of BMP-Smad1/5 signaling and the osteogenic differentiation of skeletal progenitors.

Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

Purpose: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy.

Experimental Design: We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients.

Multi-disciplinary Insights from the First European Forum on Visceral Myopathy 2022 Meeting.

Visceral myopathy is a rare, life-threatening disease linked to identified genetic mutations in 60% of cases. Mostly due to the dearth of knowledge regarding its pathogenesis, effective treatments are lacking. The disease is most commonly diagnosed in children with recurrent or persistent disabling episodes of functional intestinal obstruction, which can be life threatening, often requiring long-term parenteral or specialized enteral nutritional support.

Assessment of proxy-reported responses as predictors of motor and sensory peripheral neuropathy in children with B-lymphoblastic leukemia.

Chemotherapy-induced peripheral neuropathy (CIPN), a common condition in children with acute lymphoblastic leukemia, can be challenging to diagnose. Using data from Children's Oncology Group AALL0932 physical function study, we sought to determine if parent/guardian proxy-reported responses from the Pediatric Outcomes Data Collection Instrument could identify children with motor or sensory CIPN diagnosed by physical/occupational therapists (PT/OT). Four variables moderately discriminated between children with and without motor CIPN (c-index 0.

Generation of CHOPi012-A iPSC line from a patient with visceral myopathy-related chronic intestinal pseudo-obstruction.

Visceral myopathies are debilitating conditions characterized by dysfunction of smooth muscle in visceral organs (bowel, bladder, and uterus). Individuals affected by visceral myopathy experience feeding difficulties, growth failure, life-threatening abdominal distension, and may depend on intravenous nutrition for survival. Unfortunately, our limited understanding of the pathophysiology of visceral myopathies means that current therapies remain supportive, with no mechanism-based treatments.

Prognostic significance of ETP phenotype and minimal residual disease in T-ALL: a Children's Oncology Group study.

The early thymic precursor (ETP) immunophenotype was previously reported to confer poor outcome in T-cell acute lymphoblastic leukemia (T-ALL). Between 2009 and 2014, 1256 newly diagnosed children and young adults enrolled in Children's Oncology Group (COG) AALL0434 were assessed for ETP status and minimal residual disease (MRD) using flow cytometry at a central reference laboratory. The subject phenotypes were categorized as ETP (n = 145; 11.

Urinary Biomarkers of Kidney Tubule Health and Mortality in Persons with CKD and Diabetes Mellitus.

Key Points: Among adults with diabetes and CKD, biomarkers of kidney tubule health were associated with a greater risk of death, independent of eGFR, albuminuria, and additional risk factors. Higher urine levels of YKL-40 and KIM-1 were associated with a greater risk of death. For cause-specific death, UMOD was independently and inversely associated with the risk of cardiovascular death.

Comprehensive Gene Panel Testing for Hearing Loss in Children: Understanding Factors Influencing Diagnostic Yield.

Objective: To evaluate factors influencing the diagnostic yield of comprehensive gene panel testing (CGPT) for hearing loss (HL) in children and to understand the characteristics of undiagnosed probands.

Study Design: This was a retrospective cohort study of 474 probands with childhood-onset HL who underwent CGPT between 2016 and 2020 at a single center. Main outcomes and measures included the association between clinical variables and diagnostic yield and the genetic and clinical characteristics of undiagnosed probands.

Recent Advancements in the Diagnosis and Treatment of Congenital Hand Differences.

Congenital hand and upper limb differences include a wide spectrum of structural abnormalities that affect functional, appearance, and psychosocial domains of affected children. Ongoing advances in the understanding and treatment of these differences continue to shape management. Over the past 10 years, new developments have been made in areas of molecular genetics, noninvasive treatments, surgical techniques, and outcome measures in several commonly seen congenital hand differences.

Goals of Care Among Parents of Children Receiving Palliative Care.

Importance: While knowing the goals of care (GOCs) for children receiving pediatric palliative care (PPC) are crucial for guiding the care they receive, how parents prioritize these goals and how their priorities may change over time is not known.

Objective: To determine parental prioritization of GOCs and patterns of change over time for parents of children receiving palliative care.

Design, Setting, And Participants: A Pediatric Palliative Care Research Network's Shared Data and Research cohort study with data collected at 0, 2, 6, 12, 18, and 24 months in hospital, outpatient, or home settings from April 10, 2017, to February 15, 2022, at 7 PPC programs based at children's hospitals across the US.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

Background And Objectives: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

Methods: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort.