Emergency Care EMTALA Alterations During the COVID-19 Pandemic in the United States.

The coronavirus 2019 pandemic has affected almost every aspect of health care delivery in the United States, and the emergency medicine system has been hit particularly hard while dealing with this public health crisis. In an unprecedented time in our history, medical systems and clinicians have been asked to be creative, flexible, and innovative, all while continuing to uphold the important standards in the US health care system. To continue providing quality services to patients during this extraordinary time, care providers, organizations, administrators, and insurers have needed to alter longstanding models and procedures to respond to the dynamics of a pandemic. The Emergency Medicine Treatment and Active Labor Act of 1986, or EMTALA, is 1 example of where these alterations have allowed health care facilities and clinicians to continue their work of caring for patients while protecting both the patients and the clinicians themselves from infectious exposures at the same time.

Clostridium difficile infection after antibiotic use.

Every day, patients are prescribed antibiotics to treat infections, and some of these patients will subsequently develop a superinfection with Clostridium difficile. Although the use of antibiotics is a necessary part of modern medical care, clinicians must be judicious with their use and choice of antibiotics to prevent consequences for patients whenever possible.

Using interpreters for Deaf patients and patients with limited English proficiency.

Communication breakdowns with patients who do not use English as their primary language can hurt the patient-provider relationship and leave patients at risk for health disparities and adverse reactions. An estimated 36 million patients in the United States identify as Deaf and more than 60 million patients prefer to speak a language other than English in primary communication. This article discusses the unique needs of patients who are Deaf or have limited English proficiency, and how to provide qualified interpreters to help improve patient communication and care.

Human umbilical cord blood cells restore vascular integrity in injured rat brain and modulate inflammation in vitro.

Aim: Traumatic brain injury is a complex condition consisting of a mechanical injury with neurovascular disruption and inflammation with limited clinical interventions available. A growing number of studies report systemic delivery of human umbilical cord blood (HUCB) as a therapy for neural injuries. Materials & methods: HUCB cells from five donors were tested to improve blood-brain barrier integrity in a traumatic brain injury rat model at a dose of 2.5 × 107 cells/kg at 24 or 72 h postinjury and for immunomodulatory activity in vitro. Results & Conclusion: We observed that cells delivered 72 h postinjury significantly restored blood-brain barrier integrity. HUCB cells reduced the amount of TNF-α and IFN-γ released by activated primary rat splenocytes, which correlated with the expression of COX2 and IDO1.

The Future State of Newborn Stem Cell Banking.

Newborn stem cell banking began with the establishment of cord blood banks more than 25 years ago. Over the course of nearly three decades, there has been considerable evolution in the clinical application of stem cells isolated from newborn tissues. The industry now finds itself at an inflection point as personalized medicine and regenerative medicine continue to advance. In this review, we summarize our perspective on newborn stem cell banking in the context of the future potential that stem cells from perinatal tissues are likely to play in nascent applications. Specifically, we describe the relevance of newborn stem cell banking and how the cells stored can be utilized as starting material for the next generation of advanced cellular therapies and personalized medicine.

Understanding osteosarcomas.

This article reviews the cause, clinical presentation, diagnostic methods, and management of osteosarcoma, the most common primary bone tumor and third most common cancer among children and adolescents. In the 1970s, the introduction of adjuvant chemotherapy following tumor resection improved overall 10-year survival from 30% to about 50% of patients. However, since that change in management strategy, the survival rate has since plateaued, with no improvement in overall 10-year survival since the 1990s. A better understanding of this disease is the first step to help improve these numbers.

Quantitative analysis of composite umbilical cord tissue health using a standardized explant approach and an assay of metabolic activity.

BACKGROUND: Umbilical cord (UC) tissue can be collected in a noninvasive procedure and is enriched in progenitor cells with potential therapeutic value. Mesenchymal stromal cells (MSCs) can be reliably harvested from fresh or cryopreserved UC tissue by explant outgrowth with no apparent impact on functionality. A number of stem cell banks offer cryopreservation of UC tissue, alongside cord blood, for future cell-based applications. In this setting, measuring and monitoring UC quality is critical. MATERIALS AND METHODS: UC explants were evaluated using a plating and scoring system accounting for cell attachment and proliferation. Explant scores for fresh and cryopreserved-then-thawed tissue from the same UC were compared. Metabolic activity of composite UC tissue was also assayed after exposure of the tissue to conditions anticipated to affect UC quality and compared with explant scores within the same UC. RESULTS: All fresh and cryopreserved tissues yielded MSC-like cells, and cryopreservation of the tissue did not prevent the ability to isolate MSCs by the explant method. Thawed UC tissue scores were 91% (±0.6%; P = 0.0009) that of the fresh, biologically identical tissue. Within the same UC, explant scores correlated well to both cell yield (R2 = 0.85) and tissue metabolic activity (R2 = 0.69). DISCUSSION: A uniform explant scoring assay can provide information about the quality of composite UC tissue. Such quantitative measurement is useful for analysis of tissue variability and process monitoring. Additionally, a metabolic assay of UC tissue health provides results that correlate well to explant scoring results.

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy.

Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 109 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR). Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Caring for patients who are deaf or hard of hearing.

Patients who are deaf and hard of hearing often find the American healthcare system to be inaccessible due to communication barriers. This article describes facilities' and providers' requirements under the Americans with Disabilities Act to provide qualified interpreters and other assistive devices to patients who are deaf or hard of hearing. Removing communication barriers can protect healthcare providers from potential legal action and lets them deliver consistent, quality healthcare to all patients.

The small GTPase Rheb affects central brain neuronal morphology and memory formation in Drosophila.

Mutations in either of two tumor suppressor genes, TSC1 or TSC2, cause tuberous sclerosis complex (TSC), a syndrome resulting in benign hamartomatous tumors and neurological disorders. Cellular growth defects and neuronal disorganization associated with TSC are believed to be due to upregulated TOR signaling. We overexpressed Rheb, an upstream regulator of TOR, in two different subsets of D. melanogaster central brain neurons in order to upregulate the Tsc-Rheb-TOR pathway. Overexpression of Rheb in either the mushroom bodies or the insulin producing cells resulted in enlarged axon projections and cell bodies, which continued to increase in size with prolonged Rheb expression as the animals aged. Additionally, Rheb overexpression in the mushroom bodies resulted in deficiencies in 3 hr but not immediate appetitive memory. Thus, Rheb overexpression in the central brain neurons of flies causes not only morphological phenotypes, but behavioral and aging phenotypes that may mirror symptoms of TSC.

Pay-per-view in interlibrary loan: a case study.

QUESTION: Can purchasing articles from publishers be a cost-effective method of interlibrary loan (ILL) for libraries owing significant copyright royalties? SETTING: The University of Nebraska Medical Center's McGoogan Library of Medicine provides the case study. METHOD: Completed ILL requests that required copyright payment were identified for the first quarter of 2009. The cost of purchasing these articles from publishers was obtained from the publishers' websites and compared to the full ILL cost. A pilot period of purchasing articles from the publisher was then conducted. RESULTS: The first-quarter sample data showed that approximately $500.00 could have been saved if the articles were purchased from the publisher. The pilot period and continued purchasing practice have resulted in significant savings for the library. CONCLUSION: Purchasing articles directly from the publisher is a cost-effective method for libraries burdened with high copyright royalty payments.

Fine-tuning of secondary arbor development: the effects of the ecdysone receptor on the adult neuronal lineages of the Drosophila thoracic CNS.

The adult central nervous system (CNS) of Drosophila is largely composed of relatively homogenous neuronal classes born during larval life. These adult-specific neuron lineages send out initial projections and then arrest development until metamorphosis, when intense sprouting occurs to establish the massive synaptic connections necessary for the behavior and function of the adult fly. In this study, we identified and characterized specific lineages in the adult CNS and described their secondary branch patterns. Because prior studies show that the outgrowth of incumbent remodeling neurons in the CNS is highly dependent on the ecdysone pathway, we investigated the role of ecdysone in the development of the adult-specific neuronal lineages using a dominant-negative construct of the ecdysone receptor (EcR-DN). When EcR-DN was expressed in clones of the adult-specific lineages, neuroblasts persisted longer, but we saw no alteration in the initial projections of the lineages. Defects were observed in secondary arbors of adult neurons, including clumping and cohesion of fine branches, misrouting, smaller arbors and some defasciculation. The defects varied across the multiple neuron lineages in both appearance and severity. These results indicate that the ecdysone receptor complex influences the fine-tuning of connectivity between neuronal circuits, in conjunction with other factors driving outgrowth and synaptic partnering.

Use of time-lapse imaging and dominant negative receptors to dissect the steroid receptor control of neuronal remodeling in Drosophila.

During metamorphosis, the reorganization of the nervous system of Drosophila melanogaster proceeds in part through remodeling of larval neurons. In this study, we used in-vitro imaging techniques and immunocytochemistry to track the remodeling of the thoracic ventral neurosecretory cells. Axons of these neurons prune their larval arbors early in metamorphosis and a larger, more extensive adult arbor is established via branch outgrowth. Expression of EcR dominant negative constructs and an EcR inverted repeat construct resulted in pruning defects of larval axon arbors and a lack of filopodia during pruning, but showed variable effects on outgrowth depending on the construct expressed. Cells expressing either UAS-EcR-B1(W650A) or UAS-EcR-A(W650A) lacked filopodia during the outgrowth period and formed a poorly branched, larval-like arbor in the adult. Cells expressing UAS-EcR-B1(F645A), UAS-EcR-B2(W650A) or UAS-IR-EcR (core) showed moderate filopodial activity and normal, albeit reduced, adult-like branching during outgrowth. These results are consistent with the role of activation versus derepression via EcR for successive phases of neuronal remodeling and suggest that functional ecdysone receptor is necessary for some, but not all, remodeling events.

rHuKGF ameliorates symptoms in DSS and CD4(+)CD45RB(Hi) T cell transfer mouse models of inflammatory bowel disease.

There is an acute need for effective therapy for inflammatory bowel disease (IBD), particularly at the level of repair of the damaged epithelium. We evaluated the efficacy of recombinant human keratinocyte growth factor (rHuKGF) in both the dextran sodium sulfate (DSS) and the CD4(+)CD45RB(Hi) T cell transfer models of IBD. Disease was induced either by the ad libitum administration to normal mice of 4% DSS in the drinking water or by the injection of 4 x 10(5) CD4(+)CD45RB(Hi) T cells into immunodeficient scid/scid mice. rHuKGF was administered by subcutaneous injection at doses of 1.0 or 3.0 mg/kg in both preventative and therapeutic regimens during both studies. rHuKGF significantly improved survival and body weight loss in the DSS model in both preventative and therapeutic dosing regimens. It also improved diarrhea, hematochezia, and hematological parameters, as well as large intestine histopathology. In the T cell transfer model, rHuKGF improved body weight loss, diarrhea, and levels of serum amyloid A, as well as large intestine histopathology. In both models of IBD, the colonic levels of intestinal trefoil factor (ITF) were elevated by the disease state and further elevated by treatment with rHuKGF. These data suggest that rHuKGF may prove useful in the clinical management of IBD and its effects are likely mediated by its ability to locally increase the levels of ITF.