Charlie Norwood VA Medical Center

About: Charlie Norwood VA Medical Center is a healthcare organization based out in Augusta, Georgia, United States. It is known for research contribution in the topics: Autophagy & Kidney. The organization has 349 authors who have published 490 publications receiving 16360 citations. The organization is also known as: Augusta VA Medical Center.

Glycoconjugate Antigens in Neural Stem Cells

Abstract: The nervous tissue is composed of neurons, which transmit impulses, and glia (i.e., astrocytes and oligodendrocytes), which provide support and protection for the neurons. The central nervous system (CNS), including the brain and the spinal cord, is generated from progenitor cells that are recognized as neural stem cells (NSCs). NSCs are undifferentiated neural cells characterized by high proliferative potential and the capacity for self-renewal with retention of multipotency to differentiate into neurons and glia. Throughout neural development, NSCs undergo cellular differentiation and proliferation, and dynamic changes are observed in the composition of carbohydrate-rich molecules, including glycolipids, glycoproteins, and proteoglycans, that are expressed primarily on the outer surface of plasma membranes. The structural diversity of the carbohydrate moieties renders them ideally suited as stage-specific biomarkers for various cell types. More importantly, these molecules are increasingly recognized to play crucial functional roles in cell proliferation, differentiation, interaction, migration, and signal transduction. This chapter provides an introduction to some of the major carbohydrate-rich molecules [stage-specific embryonic antigen-1 (SSEA)-1; human natural killer-1 (HNK-1) antigen; and the ganglioside, GD3] in NSCs and presents current approaches to elucidate their functions in NSCs.

Does Bernard-Soulier syndrome protect against thrombotic thrombocytopenic purpura?

Abstract: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy which is either congenital (Upshaw-Schulman syndrome) due to genetic mutations causing deficient function of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), or acquired due to antibodies against ADAMTS-13.1–4 TTP is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia (detected by identifying significant numbers of schistocytes on a peripheral blood smear) and is associated with mental status changes, renal failure, and fever. Plasma transfusion is first-line therapy for patients with congenital TTP, while plasma exchange (PLEX) is first-line treatment for acquired TTP patients. PLEX has increased the survival rate among patients with acquired TTP to >80%. The pathophysiology of TTP has been attributed to an increase in ultra-large von Willebrand factor (UL-vWF) multimers, which are produced by endothelial cells and stored in Weibel-Palade bodies. UL-vWF multimers are released by endothelial cells and are normally cleaved by ADAMTS-13. In TTP patients, UL-vWF multimers either remain adherent to endothelial cells or circulate in the blood. The UL-vWF multimers are highly adhesive to platelets through binding of the A1 domain of vWF to platelet glycoprotein (GP)Ib receptors. The attachment of ADAMTS-13 to platelets leads to microthrombosis, leading to ischemia and formation of schistocytes. The importance of platelet GPIb binding to the A1 domain of UL-vWF multimers has been shown through the evaluation of candidate anti-vWF therapies. Aptamer ARC1779, humanized mAb GBR600, and the anti-vWF humanized single-variable-domain immunoglobulin (Nanobody) caplacizumab are three candidate therapies being tested for TTP.5–7 These compounds bind to the A1 domain of vWF, which prevents attachment to GPIb on platelets.5–7 Caplacizumab is the most successful of these drugs. In a recent phase 2 TITAN study, caplacizumab was shown to induce faster resolution of acquired TTP in the acute setting, compared to a placebo. The pathophysiology of Bernard-Soulier syndrome (BSS) and TTP both involve platelet GPIb. BSS is usually an inherited autosomal recessive (rarely autosomal dominant) condition characterized by prolonged bleeding time and macrothrombocytopenia.8–10 BSS is often associated with epistaxis, gingival and cutaneous bleeding, and hemorrhage following trauma. BSS is caused by mutations in the GPIbIX-V complex, which is encoded by four genes (GP1BA, GP1BB, GP9, and GP5). The mutations are most common in GP9, but may also occur in GP1BA or GP1BB, but have not been reported in GP5. This is because GP5 expression is not needed for expression of the other subunits of the GPIb-IX-V complex. These mutations almost always result in either very low or undetectable levels of GPIb-IX-V. An exception is the Bolzano variant of BSS, caused by an A156V mutation in GP1BA, in which platelets express GPIb-IX-V in normal levels, but are unable to bind vWF. An examination of how TTP would be affected by BSS has not been performed. This can be attributed to the extreme unlikeliness of a single patient having two exceptionally rare medical conditions. The incidence of BSS is estimated to be 1 in a million persons. The incidence of TTP is estimated to be 3.7 in a million persons in the USA. Thus, only 3.7 in a trillion persons are estimated to have both medical conditions. In other words, only one person in 270 billion persons would have both conditions. To put this in perspective, the US Census Bureau (www.census.gov/popclock) estimates that the current global population is approximately 7.4 billion persons. Furthermore, the Population Reference Bureau (www.prb.org) estimated in 2011 that approximately 108 billion persons have ever lived. This number is still less than the 270 billion persons which would be needed to have one person with both BSS and TTP. Therefore, it is extremely unlikely that a person has ever had both conditions. Although patients with BSS could have a congenital or acquired deficiency of ADAMTS-13, they should be protected against the clinical severity of TTP. Patients with BSS have platelets that should not be able to strongly bind to ULvWF multimers due to the lack of functional platelet GPIb. To further explore this topic, PubMed searches were performed for “Bernard-Soulier” AND “TTP”. Two search results were identified. However, neither article described a patient with both conditions, nor discussed the relationship between TTP and BSS. In the unlikely event that a patient

Estimation of a recurrent event gap time distribution: an application to morbidity outcomes following lower extremity fracture in Veterans with spinal cord injury

Abstract: Recurrent event data is frequently encountered in biomedical research. Estimators describing the time to the next event occurrence could be useful information in healthcare settings to deliver targeted, preemptive, patient-specific care. Distribution estimation of recurrence times is varied based on both the underlying assumptions of the estimator (e.g., dependence vs. independence of recurrence times within individual) and estimator construct. In an example among Veterans with spinal cord injury, distributional changes in recurrence times of health complications subsequent lower extremity (LE) fracture are explored. Veterans with LE fracture (cases) were matched to Veterans without LE fracture (controls) on demographic (age, race), level of injury (paraplegia vs. tetraplegia), extent of injury, Veterans Affairs connected service status, and comorbidities using Mahalanobis metric matching. Stratified distributional estimates of recurrence times between successive morbidity outcomes are compared between Veterans with/without LE fracture using three estimators: independent identically distributed product limit estimator, Wang–Chang product limit estimator, and a gamma frailty maximum likelihood estimator. It can be seen that the estimator selection can provide a very different showcasing of a recurrence time distribution. There is a change in the time-to-recurrence of recurrent urinary tract infections and pressure ulcers for fracture cases directly following LE fracture, however testing if this difference is statistically significant remains unclear. Causal inference of gap time analyses in observational data with recurrent events is considered and a call for methods in this area is much warranted.

Reduction of Central-Line–Associated Bloodstream Infections in a Spinal Cord Injury Unit

Abstract: Background: Central-line–associated bloodstream infections (CLABSIs) are a complication of indwelling central venous catheters, which increase morbidity, mortality, and cost to patients. Objective: Due to increased rates in a spinal cord injury unit (SCIU), a performance improvement project was started to reduce CLABSI in the patient population. Methods: To reduce the incidence of CLABSI, a prevention bundle was adopted, and a peer-surveillance tool was developed to monitor compliance with the bundle. Staff were trained to monitor their peers and submit weekly surveillance. Audits were conducted by the clinical nurse leader with accuracy feedback. Bundle peer-surveillance was implemented in February of 2018 with data being fed back to leadership, peer monitors, and stakeholders. Gaps in compliance were addressed with peer-to-peer education, changes in documentation requirements, and meetings to improve communication and reduce line days. In addition, the use of an antiseptic-impregnated disc for vascular accesses was implemented for dressing changes. Further quality improvement cycles during the first 2 quarters of fiscal year 2019 included service-wide education reinforcement, identification in variance of practice, and reporting to staff and stakeholders. Results: CLABSI bundle compliance increased from 67% to 98% between February and October 2018. The weekly audit reporting accuracy improved from 33% to 100% during the same period. Bundle compliance was sustained through the fourth quarter of 2019 at 98%, and audit accuracy was 99%. The initial CLABSI rates the quarter prior to the intervention were 6.10 infections per 1,000 line days for 1 of the 3 SCIUs and 2.68 infections per 1,000 line days for the service overall. After the action plan was initiated, no CLABSIs occurred for the next 3 quarters in all SCIUs despite unchanged use of central lines (5,726 line days in 2018). The improvement was sustained, and the line days decreased slightly for 2019, with a fiscal year rate of 0.61 per 1,000 line days (ie, 3 CLABSIs in 4,927 central-line days). Conclusions: The incidence of CLABSI in the SCIU was reduced by an intensive surveillance intervention to perform accurate peer monitoring of bundle compliance with weekly feedback, communication, and education strategies, improvement of the documentation, and the use of antiseptic-impregnated discs for dressings. Despite the complexity of the patient population requiring long-term central lines, the CLABSI rate was greatly impacted by evidence-based interventions coupled with reinforcement of adherence to the bundle. Funding: None Disclosures: None