Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.
Astrocytoma ; genetics ; metabolism ; pathology ; Cell Adhesion Molecules ; genetics ; metabolism ; Cell Line, Tumor ; Central Nervous System Neoplasms ; genetics ; metabolism ; pathology ; CpG Islands ; genetics ; DNA Methylation ; Down-Regulation ; Gene Deletion ; Glioblastoma ; genetics ; metabolism ; pathology ; Humans ; Oligodendroglioma ; genetics ; metabolism ; pathology ; Promoter Regions, Genetic ; genetics ; Survival Rate

Background: Predicting the need for post-traumatic reconstruction of lower extremity injuries remains a challenge. Due to the larger volume of cases in adults than in children, the majority of the medical literature has focused on adult lower extremity reconstruction. This study evaluates predictive risk factors associated with the need for free flap reconstruction in pediatric patients following lower extremity trauma. Methods: An IRB-approved retrospective chart analysis over a 5-year period (January 1, 2012 to December 31, 2017) was performed, including all pediatric patients (<18 years old) diagnosed with one or more lower extremity wounds. Patient demographics, trauma information, and operative information were reviewed. The statistical analysis consisted of univariate and multivariate regression models to identify predictor variables associated with free flap reconstruction. Results: In total, 1,821 patients were identified who fit our search criteria, of whom 41 patients (2.25%) required free flap reconstruction, 65 patients (3.57%) required local flap reconstruction, and 19 patients (1.04%) required skin graft reconstruction. We determined that older age (odds ratio [OR], 1.134; P =0.002), all-terrain vehicle accidents (OR, 6.698; P<0.001), and trauma team activation (OR, 2.443; P=0.034) were associated with the need for free flap reconstruction following lower extremity trauma in our pediatric population. Conclusions Our study demonstrates a higher likelihood of free flap reconstruction in older pediatric patients, those involved in all-terrain vehicle accidents, and cases involving activation of the trauma team. This information can be implemented to help develop an early risk calculator that defines the need for complex lower extremity reconstruction in the pediatric population.

Background: Total shoulder arthroplasty (TSA) with a nonspherical humeral head component and inlay glenoid is a successful bone-preserving treatment for glenohumeral arthritis. This study aimed to describe the 90-day complication profile of TSA with this prosthesis and compare major and minor complication and readmission rates between inpatient- and outpatient-procedure patients. Methods: A retrospective review was performed of a consecutive cohort of patients undergoing TSA with a nonspherical humeral head and inlay glenoid in the inpatient and outpatient settings by a single surgeon between 2017 and 2022. Age, sex, body mass index, American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and 90-day complication and readmission rates were compared between inpatient and outpatient groups. Results: One hundred eighteen TSAs in 111 patients were identified. Mean age was 64.9 years (range, 39–90) and 65% of patients were male. Ninety-four (80%) and 24 (20%) patients underwent outpatient and inpatient procedures, respectively. Four complications (3.4%) were recorded: axillary nerve stretch injury, isolated ipsilateral arm deep venous thrombosis (DVT), ipsilateral arm DVT with pulmonary embolism requiring readmission, and gastrointestinal bleed requiring readmission. There were no reoperations or other complications. Outpatients were younger with lower ASA and CCI scores than inpatients; however, there was no difference in complications (1/24 vs. 3/94, P=1.00) or readmissions (1/24 vs. 1/94, P=0.37) between these two groups. Conclusions TSA with a nonspherical humeral head and inlay glenoid can be performed safely in both inpatient and outpatient settings. Rates of early complications and readmissions were low with no difference according to surgical setting.Level of evidence: IV.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide