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Cortez K.J.,Veteran Affairs Medical Center | Kottilil S.,U.S. National Institutes of Health
Therapeutic Advances in Chronic Disease | Year: 2015

Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. © The Author(s), 2014.

Alix J.J.P.,University of Leicester | Alix J.J.P.,University of Sheffield | Zammit C.,University of Malta | Riddle A.,Oregon Health And Science University | And 4 more authors.
Annals of Neurology | Year: 2012

Objective: Developing central white matter is subject to ischemic-type injury during the period that precedes myelination. At this stage in maturation, central axons initiate a program of radial expansion and ion channel redistribution. Here we test the hypothesis that during radial expansion axons display heightened ischemic sensitivity, when clusters of Ca2+ channels decorate future node of Ranvier sites. Methods: Functionality and morphology of central axons and glia were examined during and after a period of modeled ischemia. Pathological changes in axons undergoing radial expansion were probed using electrophysiological, quantitative ultrastructural, and morphometric analysis in neonatal rodent optic nerve and periventricular white matter axons studied under modeled ischemia in vitro or after hypoxia-ischemia in vivo. Results: Acute ischemic injury of central axons undergoing initial radial expansion was mediated by Ca2+ influx through Ca2+ channels expressed in axolemma clusters. This form of injury operated only in this axon population, which was more sensitive to injury than neighboring myelinated axons, smaller axons yet to initiate radial expansion, astrocytes, or oligodendroglia. A pharmacological strategy designed to protect both small and large diameter premyelinated axons proved 100% protective against acute ischemia studied under modeled ischemia in vitro or after hypoxia-ischemia in vivo. Interpretation: Recent clinical data highlight the importance of axon pathology in developing white matter injury. The elevated susceptibility of early maturing axons to ischemic injury described here may significantly contribute to selective white matter pathology and places these axons alongside preoligodendrocytes as a potential primary target of both injury and therapeutics. Copyright © 2012 American Neurological Association.

Florek A.G.,Northwestern University | Dellavalle R.P.,Veteran Affairs Medical Center
Journal of Medical Case Reports | Year: 2016

A case report is a detailed narrative that usually illustrates a diagnostic or therapeutic problem experienced by one or several patients. Case reports commonly serve as the first line of evidence for new interventions or they function as alarms that an issue exists with an already established therapy. Case reports are of minor importance in evidence-based medicine; however, they make meaningful contributions to both the knowledge and education of medical students, residents, and fellows. Case reports are written with the goal of sharing information for medical, scientific, or educational purposes. They often serve as medical or even undergraduate students' first experience with medical writing and they provide a solid foundation for manuscript preparation and publication. In the last few decades, there has been an exponential increase in medical student research, specifically in the number of manuscripts published by medical students. It is important to foster this academic spirit among students by encouraging them to become involved in research. This editorial will focus on the value and educational benefits of writing case reports for medical students, university students, residents, and fellows. © 2016 Florek and Dellavalle.

A 57-year-old Caucasian man with a history of Child's class A hepatitis C, cirrhosis and progressive multifocal hepatocellular carcinoma was treated with sorafenib but progressed after 7 months of stable disease. At progression he was given salvage chemotherapy consisting of 5-fluorouracil and leucovorin and went into complete radiographic remission after 12 cycles of treatment. He did develop a portal vein thrombosis but nevertheless his hepatic lesions continued to resolve. Throughout his therapy α-fetoprotein (AFP) levels decreased only minimally. He did not seek retreatment after 14 cycles of chemotherapy and presented 3 months later with relapsed disease on CT scans with markedly elevated AFP levels. He received one more chemotherapy cycle but was unable to tolerate further treatment, succumbing to his disease 3 months thereafter, and a total of 29 months after he was deemed a sorafenib failure. Copyright 2013 BMJ Publishing Group. All rights reserved.

Kallini J.R.,Eisenhower Medical Center | Kallini J.R.,Baylor College of Medicine | Hamed N.,Alexandria University | Khachemoune A.,New York University | Khachemoune A.,Veteran Affairs Medical Center
International Journal of Dermatology | Year: 2015

Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer. It originates from epidermal keratinocytes or adnexal structures (such as eccrine glands or pilosebaceous units). We describe the salient features of cutaneous SCC. We also review novel classification schemes proposed during the last decade which attempt to stratify SCC lesions based on prognosis. Biopsy leads to definitive diagnosis. Treatment includes surgical excision; Mohs micrographic surgery produces excellent cure rates and spares the maximal amount of tissue. Other modalities include electrodessication and curettage, cryosurgery, radiotherapy, topical medications, photodynamic therapy, and systemic therapy. Management and follow-up depend on the risk stratification of individual lesions. © 2014 The International Society of Dermatology.

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