Necrotizing Fasciitis: A Review of Management Guidelines in a Large Obstetrics and Gynecology Teaching Hospital

Necrotizing fasciitis is a severe, life-threatening soft tissue infection that results in rapid and progressive destruction of the superficial fascia and subcutaneous tissue. Because of its varied clinical presentation and bacteriological make-up, it has been labelled with many other names such as acute streptococcal gangrene, gangrenous erysipelas, necrotizing erysipelas, hospital gangrene, and acute dermal gangrene. Although described by Hippocrates and Galen, it has received increasing attention in obstetrical and gynecological literature only within the last 20 years. This review includes two recent cases successfully managed at Parkland Memorial Hospital, Dallas, Texas. The first patient was a 50 year old, morbidly obese, diabetic woman who presented with a small, painful lesion on the vulva. After failing triple antibiotic therapy with ampicillin, clindamycin, and gentamicin, the diagnosis of necrotizing fasciitis of the vulva was made, and she was taken to the operating room for extensive excision. She was discharged home on hospital day 29. The second patient was a 65 year old, obese, diabetic woman with risk factors for atherosclerosis who had a wound separation after an abdominal hysterectomy. Two days later a loss of resistance to probing was noted in the subcutaneous tissue. Necrotizing fasciitis was suspected, and she was taken to the operating room for resection. The patient was discharged home on hospital day 27. The mortality rate after diagnosis of necrotizing fasciitis has been reported to be 30% to 60%. We review the literature and outline the guidelines used in a large Ob/Gyn teaching hospital to minimize the adverse outcome. Lectures on soft-tissue infections are included on a regular basis. The high-risk factors of age over 50, diabetes, and atherosclerosis are emphasized. The need for early diagnosis and surgical treatment within 48 hours is stressed, and any suspicious lesions or wound complications are reported to experienced senior house officers and staff. We use two recent cases to highlight the diagnostic clues and management strategies for this often fatal polymicrobial infection

A Seat at the Table: Minority Representation and County Governing Boards

This study focuses on minority representation on county governing boards to determine the extent of minority representation, and then to provide explanation for the exiting patterns in its representation. The dependent variable used in this paper is a count variable employing a Zero-Inflated Negative Binomial model. The results indicate that minority populations, counties located in the South, partisan elections, the size of county governing boards and urban counties have positive effects on increased minority representation, while at-large voting districts have a negative effect. Furthermore, it advances the need for greater research on county governing boards, county governments in general and a new agenda for the future study of minority representation on local governing bodies

Hard and soft news: A review of concepts, operationalizations and key findings

Over 30 years, a large body of research on what is often called ‘hard’ and ‘soft news’ has accumulated in communication studies. However, there is no consensus about what hard and soft news exactly is, or how it should be defined or measured. Moreover, the concept has not been clearly differentiated from or systematically related to concepts addressing very similar phenomena – tabloidization and ‘infotainment’. Consequently, the results of various studies are hard to compare and different scientific discourses on related issues remain unconnected. Against this backdrop, this article offers a conceptual analysis of the concept based on studies in English and other languages. We identify key dimensions of the concept and make suggestions for a standardized definition and multi-dimensional measurement of harder and softer news. In doing so, we propose to distinguish thematic, focus and style features as basic dimensions that – in their combination – make up harder and softer types of news

Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics

The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF) is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2). In this study, we evaluate the use of CT-322, a novel biologic (Adnectin). This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2.</p> <p>Methods</p> <p>The efficacy of CT-322 was evaluated <it>in vivo </it>using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically) for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL), microvessel density (MECA-32), and VEGF-activated blood vessels (Gv39M).</p> <p>Results</p> <p>Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors. Finally, CT-322, in combination with gemcitabine was safe and effective at controlling the growth of syngeneic pancreatic tumors in immunocompetent mice.</p> <p>Conclusion</p> <p>We conclude that CT-322 is an effective anti-VEGFR2 agent and that further investigation of CT-322 for the treatment of pancreatic cancer is warranted.</p

GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for <it>in vivo </it>efficacy in the MMTV-PyMT transgenic model of breast cancer.</p> <p>Results</p> <p>The derivative GU81 has increased <it>in vitro </it>efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.</p> <p>Conclusion</p> <p>This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.</p

Revenue optimization for the Ocean Grazer wave energy converter through storage utilization

Increased penetration of renewable energy generation motivates a change of paradigm in the way power systems are structured and operated, as advocated by the smart grid concept. Accordingly, in this paper we investigate the lossless storage capabilities of the Ocean Grazer wave energy converter (WEC), which could facilitate the aforementioned paradigm shift. This specific WEC exhibits both adaptability with respect to the incoming waves and significant lossless storage capabilities. We propose a model predictive control (MPC) strategy based on a lumped dynamical model in order to mitigate power imbalances in the power grid and maximize the revenue of the WEC. Furthermore, we illustrate that the proposed strategy exploits the WEC energy storage capabilities and we show the economic benefits it brings. Lastly, the proposed strategy is compared with a heuristic approach and a setting without storage