Leukocytoclastic Vasculitis in a 66-Year-Old Woman After Fusion of the Second Right Metatarsocuneiform Joint Using Titanium Plate and Screws: A Case Report

Metallic orthopaedic implants are known to instigate cutaneous reactions; however, the mechanism by which this occurs is not fully understood. Contact dermatitis after implantation of stainless steel fracture plates was first described in 1966, and similar reactions to various implants have been documented subsequently. Leukocytoclastic vasculitis (LCV) is an inflammatory condition of small dermal blood vessels resulting from neutrophil invasion, degranulation, and cell death caused by a type III hypersensitivity reaction. No studies have reported use of titanium orthopaedic implants resulting in LCV. We describe a 66-year-old woman who developed LCV after the fusion of her second right metatarsocuneiform joint with a titanium plate and screws. At 4 months after removal of the titanium plate and screws, the LCV symptoms had resolved without further intervention. Although this rash might be a rare complication associated with orthopaedic implants, it is an important differential diagnosis for orthopaedic surgeons to consider when assessing and treating postoperative rashes

Geriatric Hip Fracture Quality Initiative

Introduction: Multiple studies demonstrate increased morbidity, mortality, and loss of independence after hip fractures in geriatric patients. The 1-year mortality rate after a hip fracture has been estimated at anywhere from 14% to 58%. Hip fractures are one of the most common injuries evaluated by the UNM Orthopedic department. Geriatric hip fracture protocols have shown improved outcomes at many other centers with regard to improved functionality and decreased morbidity. The goal of this initiative is to improve outcomes with regard to length of hospital stay, functionality after surgery, and as a result, decreased morbidity and mortality. Materials/methods: All deaths in the orthopedic department were reviewed and analyzed from June 2009 to July 2019. Deaths were identified from morbidity and mortality submissions and NSQIP data. The geriatric hip fracture protocol was developed and implemented in Fall 2019, with non-critical care patients being primarily admitted to orthopedics, with hospitalist co-management. Specific post-operative and pain order sets were developed for efficiency and improved standard of care. Results: Early results of the newly developed geriatric hip fracture protocol demonstrate decreased length of stay in the hospital and earlier time to surgical intervention. It is too early to determine if morbidity and mortality has seen any decrease, however this can be anticipated with earlier time to surgery and decreased time in the hospital. Conclusions: We identified a need and successfully developed an initiative to improve care for geriatric patients with hip fractures. Implementation of this protocol decreased length of hospital stay as well as time to surgery. The analysis of the effect of this protocol on overall morbidity and mortality is ongoing

The Transcriptome of Human Epicardial, Mediastinal and Subcutaneous Adipose Tissues in Men with Coronary Artery Disease

The biological functions of epicardial adipose tissue (EAT) remain largely unknown. However, the proximity of EAT to the coronary arteries suggests a role in the pathogenesis of coronary artery disease (CAD). The objectives of this study were to identify genes differentially regulated among three adipose tissues, namely EAT, mediastinal (MAT) and subcutaneous (SAT) and to study their possible relationships with the development of cardiovascular diseases.Samples were collected from subjects undergoing coronary artery bypass grafting surgeries. Gene expression was evaluated in the three adipose depots of six men using the Illumina® HumanWG-6 v3.0 expression BeadChips. Twenty-three and 73 genes were differentially up-regulated in EAT compared to MAT and SAT, respectively. Ninety-four genes were down-regulated in EAT compared to SAT. However, none were significantly down-regulated in EAT compared to MAT. More specifically, the expression of the adenosine A1 receptor (ADORA1), involved in myocardial ischemia, was significantly up-regulated in EAT. Levels of the prostaglandin D2 synthase (PTGDS) gene, recently associated with the progression of atherosclerosis, were significantly different in the three pairwise comparisons (EAT>MAT>SAT). The results of ADORA1 and PTGDS were confirmed by quantitative real-time PCR in 25 independent subjects.Overall, the transcriptional profiles of EAT and MAT were similar compared to the SAT. Despite this similarity, two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in EAT. These results provide insights about the biology of EAT and its potential implication in CAD

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Circadian clock and vascular disease.

Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprachiasmatic nucleus (SCN), the clock in each tissue or cell is designated as a peripheral clock. It is now accepted that peripheral clocks have their own roles specific to each peripheral organ by regulating the expression of clock-controlled genes (CCGs), although the oscillation mechanisms of the peripheral clock are similar to that of the SCN. However, little was known about how the peripheral clock in the vasculature contributes to the process of cardiovascular disorders. The biological clock allows each organ or cell to anticipate and prepare for changes in external stimuli. Recent evidence obtained using genetically engineered mice with disrupted circadian rhythm showed a novel function of the internal clock in the pathogenesis of endothelial dysfunction, hypertension and hemostasis. Loss of synchronization between the central and peripheral clock also contributes to the pathogenesis of cardiovascular diseases, as restoration of clock homeostasis could prevent disease progression. Identification of CCGs in each organ, as well as discovery of tools to manipulate the phase of each biological clock, will be of great help in establishing a novel chronotherapeutic approach to the prevention and treatment of cardiovascular disorders

Associations of statin use with motor performance and myalgia may be modified by 25-hydroxyvitamin D: findings from a British birth cohort

The objective was to examine whether: (1) statin use was associated with muscle related outcomes at age 60–64, (2) these associations were modifed by 25-hydroxyvitamin D (25(OH)D) status and explained by infammation, body-size or lifestyle in a British birth cohort. Markers of myalgia (intrusive body pain) and myopathy (self-reported and performance-based measures) were examined in 734 men and 822 women (MRC National Survey of Health and Development). Statin use was associated with intrusive body pain, difculty climbing stairs and slower chair rise speed. Some associations were modifed by 25(OH)D e.g. the association with intrusive body pain was evident in the insufcient (13–20ng/l) and defcient(20ng/l (OR=0.8,95% CI 0.5–1.4) (p=0.003 for interaction). Associations were maintained in fully adjusted models of intrusive body pain and difculty climbing stairs, but for chair rise speed they were fully accounted for by infammation, body-size and lifestyle. In a nationally representative British population in early old age, statin use was associated with lower limb muscle-related outcomes, and some were only apparent in those with 25(OH)D status below 20ng/l. Given 25(OH)D is modifable in clinical practice, future studies should consider the links between 25(OH)D status and muscle related outcomes