Mammalian Meat Allergy and IgE to Alpha-Gal in Central Virginia: Findings From a COVID-19 Vaccine and Patient Cohort.

BACKGROUND: IgE to galactose-alpha-1,3-galactose (alpha-gal) is linked to tick bites and an important cause of anaphylaxis and urticarial reactions to mammalian meat. The alpha-gal syndrome (AGS) is recognized as being common in the southeastern United States. However, prevalence studies are lacking and open questions remain about risk factors and clinical presentation of alpha-gal sensitization. OBJECTIVE: Here we characterized the prevalence as well as the presentation and risk factors of AGS and alpha-gal IgE sensitization in adults in central Virginia recruited without regard to the history of allergic disease. METHODS: Adults in central Virginia, primarily University of Virginia Health employees, were recruited as part of a COVID-19 vaccine study. Subjects provided at least one blood sample and answered questionnaires about medical and dietary history. We used ImmunoCAP for IgE assays and assessed the ABO blood group by reverse typing using stored serum. We also investigated biobanked serum from COVID-19 patients. RESULTS: Median age of the 267 enrollees was 42 years, 76% were female, and 43 (16%) were sensitized to alpha-gal (cutoff of 0.1 IU/mL), of which mammalian meat allergy was reported by seven (2.6%). Sensitized subjects (1) were older, (2) had higher total IgE levels but a similar frequency of IgE to common respiratory allergens, and (3) were more likely to report tick bites than were nonsensitized subjects. Among those who were sensitized, alpha-gal IgE levels were higher among meat-allergic than nonallergic subjects (geometric mean, 9.0 vs 0.5 IU/mL; P < .001). Mammalian meat and dairy consumption was common in individuals with low-level sensitization. CONCLUSION: In central Virginia, AGS is a dominant cause of adult food allergy with a prevalence approaching or exceeding 2%.

Discharge within 1 day following elective single-level transforaminal lumbar interbody fusion: a propensityscore-matched analysis of predictors, complications, and readmission.

STUDY DESIGN: This was a retrospective case-control study using 8 years of data from a nationwide database of surgical outcomes in the United States. PURPOSE: This study aimed to improve our understanding of the risk factors associated with a length of stay (LOS) >1 day and aid in reducing postoperative hospitalization and complications. OVERVIEW OF LITERATURE: Despite the proven safety of transforaminal lumbar interbody fusion (TLIF), some patients face prolonged postoperative hospitalization. METHODS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program dataset from 2011 to 2018. The cohort was divided into patients with LOS up to 1 day (LOS ≤1 day), defined as same day or next-morning discharge, and patients with LOS >1 day (LOS >1 day). Univariable and multivariable regression analyses were performed to evaluate predictors of LOS >1 day. Propensity-score matching was performed to compare pre- and postdischarge complication rates. RESULTS: A total of 12,664 eligible patients with TLIF were identified, of which 14.8% had LOS ≤1 day and 85.2% had LOS >1 day. LOS >1 day was positively associated with female sex, Hispanic ethnicity, diagnosis of spondylolisthesis, American Society of Anesthesiologists classification 3, and operation length of >150 minutes. Patients with LOS >1 day were more likely to undergo intraoperative/postoperative blood transfusion (0.3% vs. 4.5%, p<0.001) and reoperation (0.1% vs. 0.6%, p=0.004). No significant differences in the rates of postdischarge complications were found between the matched groups. CONCLUSIONS: Patients with worsened preoperative status, preoperative diagnosis of spondylolisthesis, and prolonged operative time are more likely to require prolonged hospitalization and blood transfusions and undergo unplanned reoperation. To reduce the risk of prolonged hospitalization and associated complications, patients indicated for TLIF should be carefully selected.

St. Jude Survivorship Portal: Sharing and Analyzing Large Clinical and Genomic Datasets from Pediatric Cancer Survivors.

Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. More than 1,600 phenotypic variables and 400 million genetic variants from more than 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry. Significance: The St. Jude Survivorship Portal is the first data portal designed to share and explore clinical and genetic data from childhood cancer survivors. The portal provides both open- and controlled-access features and will fulfill a wide range of data sharing needs of the survivorship research community and beyond. See co-corresponding author Xin Zhou discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932617204/7d99fa4958.

Sleep bruxism: The past, the present, and the future-evolution of a concept.

BACKGROUND: The concept of sleep bruxism (SB) has evolved exponentially over the past several decades. Many theories and hypotheses have been proposed as to the definition, pathophysiology, and management of SB, from the early 1960s through the present. The role of peripheral factors, such as dental occlusion, in the pathogenesis of SB has been discarded. TYPES OF STUDIES REVIEWED: The authors searched several electronic databases (ie, PubMed, Google Scholar, Web of Science, Embase, and Ovid MEDLINE) for studies on bruxism. The search was conducted from January 1961 through May 2023 and yielded 4,612 articles, of which 312 were selected for comprehensive review after eliminating duplicates and nonfocused articles. RESULTS: There has been an evident progressive shift from the role of peripheral factors, such as dental occlusion, to more central factors, such as the involvement of a central pattern generator as well as the autonomic nervous system, in the genesis of bruxing movements. There is continued robust interest in the dental community to elucidate the contributing factors involved in SB. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The neurophysiology of SB appears to be leaning more toward central rather than peripheral factors. There is increasing evidence of the role of the autonomic nervous system, genetics, and comorbidities in the genesis of SB. The scientific literature seems to refute the role of dental occlusion in the causation of bruxing movements. As per the literature, there has been a paradigm shift in the definition and genesis of SB and its possible dental implications and management, which also highlights the need for succinct scientific studies in this regard.

Blocking the Self-Destruct Program of Dopamine Neurons through Macrophage Migration Inhibitory Factor Nuclease Inhibition.

Parkinson's disease (PD) is a progressive neurodegenerative condition that pathognomonically involves the death of dopaminergic neurons in the substantia nigra pars compacta, resulting in a myriad of motor and non-motor symptoms. Given the insurmountable burden of this disease on the population and healthcare system, significant efforts have been put forth toward generating disease modifying therapies. This class of treatments characteristically alters disease course, as opposed to current strategies that focus on managing symptoms. Previous literature has implicated the cell death pathway known as parthanatos in PD progression. Inhibition of this pathway by targeting poly (ADP)-ribose polymerase 1 (PARP1) prevents neurodegeneration in a model of idiopathic PD. However, PARP1 has a vast repertoire of functions within the body, increasing the probability of side effects with the long-term treatment likely necessary for clinically significant neuroprotection. Recent work culminated in the development of a novel agent targeting the macrophage migration inhibitory factor (MIF) nuclease domain, also named parthanatos-associated apoptosis-inducing factor nuclease (PAAN). This nuclease activity specifically executes the terminal step in parthanatos. Parthanatos-associated apoptosis-inducing factor nuclease inhibitor-1 was neuroprotective in multiple preclinical mouse models of PD. This piece will focus on contextualizing this discovery, emphasizing its significance, and discussing its potential implications for parthanatos-directed treatment. © 2024 International Parkinson and Movement Disorder Society.

A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity.

Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated a comprehensive cell atlas of 55 neuroblastoma patient tumors, collected from two pediatric cancer institutions, spanning a range of clinical, genetic, and histologic features. Our atlas combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, and two spatial proteomic methods. Sc/snRNA-seq revealed three malignant cell states with features of sympathoadrenal lineage development. All of the neuroblastomas had malignant cells that resembled sympathoblasts and the more differentiated adrenergic cells. A subset of tumors had malignant cells in a mesenchymal cell state with molecular features of Schwann cell precursors. DNA methylation profiles defined four groupings of patients, which differ in the degree of malignant cell heterogeneity and clinical outcomes. Using spatial proteomics, we found that neuroblastomas are spatially compartmentalized, with malignant tumor cells sequestered away from immune cells. Finally, we identify spatially restricted signaling patterns in immune cells from spatial transcriptomics. To facilitate the visualization and analysis of our atlas as a resource for further research in neuroblastoma, single cell, and spatial-omics, all data are shared through the Human Tumor Atlas Network Data Commons at www.humantumoratlas.org.

A Real Headache: Intracranial Extension and Epidural Abscess As Complication of Chronic Mucocele.

Mucoceles are benign lesions of salivary glands typically originating from the paranasal sinuses. Intracranial extension and superinfection of these lesions are rare but serious complications of chronic mucoceles. Here, we discuss a patient with a known mucocele, initially lost to follow-up, who presented three years later with headache, purulent rhinorrhea, and intracranial extension of his mucocele with development of an epidural abscess. This case highlights the potential complications of chronic, large mucoceles and emphasizes the importance of thorough evaluation in patients with facial abscesses in the setting of known sinus pathology. Any mucocele with signs of superinfection such as purulent rhinorrhea, abscess near the sinuses, or refractory symptoms should warrant cranial imaging. Mucoceles with evidence of intracranial extension require neurosurgical and/or otolaryngologic evaluation for evacuation and debridement to avoid neurologic injury or devastating infection.