Differential Binding of NLRP3 to non-oxidized and Ox-mtDNA mediates NLRP3 Inflammasome Activation.

The NLRP3 inflammasome is a key mediator of the innate immune response to sterile tissue injury and is involved in many chronic and acute diseases. Physically and chemically diverse agents activate the NLRP3 inflammasome. Here, we show that NLRP3 binds non-oxidized and Ox-mtDNA differentially, with a half maximum inhibitory concentration (IC) for non-oxidized and Ox-mtDNA of 4 nM and 247.

Late Infection After Spinal Fusion for Adolescent Idiopathic Scoliosis: Implant Exchange Versus Removal.

Background: Late infection after posterior spinal arthrodesis for adolescent idiopathic scoliosis (AIS) is the leading cause of late revision. While implant removal and antibiotic therapy are usually curative, patients may experience deformity progression. The goal of this study was to compare outcomes after implant exchange (IE) or removal (IR) to treat late-onset (≥1 y postoperative) deep surgical site infection (SSI) after spinal arthrodesis in patients with AIS.

Pharmacogenetics of childhood uncontrolled asthma.

Introduction: Asthma is a heterogeneous, multifactorial disease with multiple genetic and environmental risk factors playing a role in pathogenesis and therapeutic response. Understanding of pharmacogenetics can help with matching individualized treatments to specific genotypes of asthma to improve therapeutic outcomes especially in uncontrolled or severe asthma.

Areas Covered: In this review, we outline novel information about biology, pathways, and mechanisms related to interindividual variability in drug response (corticosteroids, bronchodilators, leukotriene modifiers, and biologics) for childhood asthma.

Surgery for Otitis Media with Effusion: A Survey of Otolaryngologists Who Treat Children in Brazil.

 Myringotomy and ear tube placement (MTP) is the surgical treatment for otitis media with effusion (OME), and it is the most common surgery performed in children. Several guidelines have been developed to assist in the care of patients who become candidates for MTP.  To evaluate the practice of Brazilian otorhinolarynogologists when performing MTP according to the years of clinical experience.

Successful treatment of 5-fluorouracil toxicosis with hemodialysis.

Objective: To describe the successful treatment of lethal dose 5-fluorouracil (5-FU) toxicosis using hemodialysis.

Case Summary: A 4-month-old intact female Golden Retriever was presented to the emergency department after ingesting 20 g of 5% 5-FU cream. The puppy developed refractory seizures and became comatose with uncontrolled tonic-clonic convulsions.

Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age.

Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over 350 dogs.

Background: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages.

Hypothesis/objectives: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection.

Animals: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test.

Leveraging Electronic Health Records for Guideline-Based Asthma Documentation.

Background: Asthma is the most common pediatric chronic disease; thus, clinical guidelines have been developed for its assessment and management, which rely on systematic symptom documentation. Electronic health records (EHR) have the potential to record clinical data systematically; however, variability in documentation persists.

Objective: To identify if the use of a structured asthma template is associated with increased guideline-based asthma documentation and clinical outcomes when compared with the use of nonstructured ones.

Assessing proximity effect of high-acuity pediatric emergency departments on the pediatric readiness scores in neighboring general emergency departments.

Study Objectives: The objective of this study was to determine if there is a proximity effect of high-acuity, pediatric-capable emergency departments (EDs) on the weighted pediatric readiness score of neighboring general EDs and whether this effect is attributable to specific components of the National Pediatric Readiness Guidelines.

Methods: Pediatric readiness was assessed using the weighted pediatric readiness score of EDs based on the 2013 National Pediatric Readiness Project assessment. High-acuity, pediatric-capable EDs were defined as those with a separate pediatric ED and inpatient pediatric services, including the following: pediatric ICU, pediatric ward, and neonatal ICU.

Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling.

Mitochondrial DNA (mtDNA) escaping stressed mitochondria provokes inflammation via cGAS-STING pathway activation and, when oxidized (Ox-mtDNA), it binds cytosolic NLRP3, thereby triggering inflammasome activation. However, it is unknown how and in which form Ox-mtDNA exits stressed mitochondria in non-apoptotic macrophages. We found that diverse NLRP3 inflammasome activators rapidly stimulated uniporter-mediated calcium uptake to open mitochondrial permeability transition pores (mPTP) and trigger VDAC oligomerization.

Malnutrition from anorexia nervosa triggers severe complications of hereditary spherocytosis in an adolescent girl: A case report.

Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS who developed unexpected and life-threatening complications of her inherited hemolytic anemia as a consequence of anorexia nervosa and severe malnutrition.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here.

Inter-Rater Reliability and Agreement Among Mass-Casualty Incident Algorithms Using a Pediatric Trauma Dataset: A Pilot Study.

Introduction: Many triage algorithms exist for use in mass-casualty incidents (MCIs) involving pediatric patients. Most of these algorithms have not been validated for reliability across users.

Study Objective: Investigators sought to compare inter-rater reliability (IRR) and agreement among five MCI algorithms used in the pediatric population.

Mutational analysis using next generation sequencing in pediatric thyroid cancer reveals BRAF and fusion oncogenes are common.

Background: We previously described mutation rates of BRAF, RAS, RET-PTC and PAX8-PPARγ in pediatric subjects with well-differentiated thyroid cancer (WDTC). We expanded the cohort adding next-generation sequencing (NGS) and assessed genotype-phenotype correlations.

Methods: Single-center retrospective cohort examining thyroidectomy tissue blocks from consecutive pediatric WDTC patients between 2001 and 2015.

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study.

Background: Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China.

Methods: A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study.

Prevalence of positive urine culture in the presence of inactive urine sediment in 1049 urine samples from dogs.

Background: Urinalysis (UA) is often used to screen for bacterial cystitis, regardless of sediment results, and followed up by quantitative urine culture (UC) for definitive diagnosis.

Objectives: Determine prevalence of positive UCs in dogs with inactive urine sediments on routine UA.

Animals: A total of 1049 urine samples with inactive urine sediments and UCs collected from dogs presented to a veterinary specialty hospital between January 2018 and February 2020.

Total Isolated Monocular Vision Loss in a Patient Who Suffered Closed Head Injury.

Background: Head injuries are an important cause of morbidity and mortality in children and young adults. There are multiple sight-threatening complications of head injury, even in closed head injury without visible violation of the globe or orbits. One such entity is traumatic optic neuropathy.

Comparison of prehospital professional accuracy, speed, and interrater reliability of six pediatric triage algorithms.

Objectives: We evaluated prehospital professionals' accuracy, speed, interrater reliability, and impression in a pediatric disaster scenario both without a tool ("No Algorithm"-NA) and with 1 of 5 algorithms: CareFlight (CF), Simple Triage and Rapid Treatment (START) and JumpSTART (J-START), Pediatric Triage Tape (PTT), Sort, Assess, Life-saving interventions, Treatment/Transport (SALT), and Sacco Triage Method (STM).

Methods: Prehospital professionals received disaster lectures, focusing on 1 triage algorithm. Then they completed a timed tabletop disaster exercise with 25 pediatric victims to measure speed.

Multicenter, randomized, double-blinded, placebo-controlled study of rabacfosadine in dogs with lymphoma.

Background: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs.

Hypothesis/objectives: To determine the efficacy and safety of RAB in dogs with lymphoma.

Animals: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019.

Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review.

Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of side effects, a high rate of paradoxical responses, and frequent treatment resistance.

Comparison of Outcome Tools Used to Test Mass-Casualty Algorithms in the Pediatric Population.

Introduction: Mass-casualty incident (MCI) algorithms are used to sort large numbers of patients rapidly into four basic categories based on severity. To date, there is no consensus on the best method to test the accuracy of an MCI algorithm in the pediatric population, nor on the agreement between different tools designed for this purpose.

Study Objective: This study is to compare agreement between the Criteria Outcomes Tool (COT) to previously published outcomes tools in assessing the triage category applied to a simulated set of pediatric MCI patients.