Banerjee A.,St John Hospital And Medical Center |
Guttridge D.C.,Ohio State University
Current Opinion in Supportive and Palliative Care | Year: 2012
Purpose of review The balance between the rates of protein synthesis and protein degradation governs the maintenance of muscle mass in the body. The main purpose of this review is to highlight the latest understanding of the various pathways that maintain this balance between muscle atrophy and hypertrophy. Recent findings The maintenance of muscle mass is an interplay between anabolic and catabolic pathways that are interconnected at several junctures. The insulin-like growth factor 1/IRS1/PI3K/Akt pathway along with the ubiquitin-proteasome pathway, lysosomal/autophagy pathway and myostatin pathway maintain this homeostasis with the aid of various transcriptional and genetic factors, many of which continue to be discovered and studied in an ongoing fashion. Summary We tried to present, in this short review, a holistic view of the various players, old and new, responsible for the maintenance of this delicate equilibrium between muscle gain and loss. The development of novel therapeutics aimed at the activation or suppression of these described mediators may help the field of medicine in the management of a myriad of clinical conditions, thereby improving mobility and quality of life of affected patients. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.
Pigott J.P.,Jobst Vascular Institute |
Raja M.L.,El Paso Cardiology Associates |
Davis T.,St John Hospital And Medical Center
Journal of Vascular Surgery | Year: 2012
Objective: Percutaneous techniques for crossing femoropopliteal chronic total occlusions (CTOs) offer an alternative to bypass surgery in patients deemed to be at increased risk due to advanced age or comorbidities. Recent reports document good success rates in catheters designed to reconstitute peripherally occluded arteries following failed guidewire passage. The Wildcat catheter (Avinger, Redwood City, Calif) is a novel device with a rotating distal tip and deployable wedges fashioned for channeling a passage through arterial occlusions. This report describes the results of a prospective, multicenter, nonrandomized trial evaluating the safety and efficacy of the Wildcat device when crossing de novo or restenotic femoropopliteal CTOs. Methods: Between August 2010 and April 2011, patients with peripheral arterial disease due to a femoropopliteal CTO >1 cm and ≤35 cm were evaluated for study enrollment at 15 U.S. sites. During treatment, the physician initially attempted to cross the CTO using conventional guidewires per protocol; if the guidewire successfully crossed, the patient was considered a screen failure and the Wildcat was not deployed. At 30 days, patients were reevaluated. The primary efficacy end point was successful crossing of the Wildcat into the distal true lumen as confirmed by angiography. Primary safety end points included no in-hospital or 30-day major adverse events, no clinically significant perforation or embolization, and no grade C or greater dissection. Additional data collected included lesion length, degree of calcification, and location. Results: Eighty-eight patients were enrolled in the trial. Of these, the Wildcat device was used in 84 patients (95%) per protocol. Successful CTO crossing was reported and confirmed by independent review in 89% (75/84) of cases with 5% (4/84) major adverse events as defined in the protocol (predominantly perforations sealed with balloon inflation). There were no clinically relevant events associated with any of the perforations. The mean CTO length was 174 ± 96 mm (range, 15-350 mm). Approximately 57% (n = 48) of all lesions were categorized as containing at least moderate calcification. Eighty-nine percent (n = 75) of vessels recanalized were superficial femoral arteries. Conclusions: In this multicenter study, the Wildcat catheter demonstrated an 89% crossing success rate with little associated morbidity. The Wildcat catheter is a viable device for crossing moderately calcified femoropopliteal CTOs. © 2012 Society for Vascular Surgery.
Bagdasarian N.,St John Hospital And Medical Center |
Bagdasarian N.,Wayne State University |
Rao K.,University of Michigan |
Malani P.N.,University of Michigan
JAMA - Journal of the American Medical Association | Year: 2015
IMPORTANCE Since 2000, the incidence and severity of Clostridium difficile infection (CDI) have increased. OBJECTIVE To review current evidence regarding best practices for the diagnosis and treatment of CDI in adults (age≥18 years). EVIDENCE REVIEW Ovid MEDLINE and Cochrane databases were searched using keywords relevant to the diagnosis and treatment of CDI in adults. Articles published between January 1978 and October 31, 2014, were selected for inclusion based on targeted keyword searches, manual review of bibliographies, and whether the article was a guideline, systematic review, or meta-analysis published within the past 10 years. Of 4682 articles initially identified, 196 were selected for full review. Of these, the most pertinent 116 articles were included. Clinical trials, large observational studies, and more recently published articles were prioritized in the selection process. FINDINGS Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C difficile. Diagnostic approaches are complex due to the availability of multiple testing strategies. Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single-step PCR on liquid stool samples have the best test performance characteristics (for multistep: sensitivity was 0.68-1.00 and specificity was 0.92-1.00; and for single step: sensitivity was 0.86-0.92 and specificity was 0.94-0.97). Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3%formetronidazole vs 78.5%for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94%for recurrent CDI). CONCLUSIONS AND RELEVANCE Diagnostic testing for CDI should be performed only in symptomatic patients. Treatment strategies should be based on disease severity, history of prior CDI, and the individual patient's risk of recurrence. Vancomycin is the treatment of choice for severe or complicated CDI, with or without adjunctive therapies. Metronidazole is appropriate for mild disease. Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence. Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.
Conant M.M.,Rush University Medical Center |
Erdman S.M.,Purdue University |
Osterholzer D.,St John Hospital And Medical Center
Journal of Antimicrobial Chemotherapy | Year: 2014
Objectives: The use of outpatient parenteral antimicrobial therapy (OPAT) has been increasing worldwide due to its evident clinical utility; however, there is also concern about overuse and increased risk to patients in terms of antibiotic toxicity and intravenous line-associated complications. At our university-affiliated county teaching hospital with mandatory Infectious Diseases (ID) approval for all OPAT courses, we looked at clinical outcomes and cost savings of patients denied OPAT. Methods: Electronic medical records of patients denied OPAT were retrospectively reviewed. Demographic, medical, infection-specific and drug-specific data were collected for each patient, including the regimen ultimately recommended by ID in lieu of OPAT. Patients were determined to have clinical cure, probable cure or treatment failure based on resolution or recurrence of infection for up to 1 year after OPAT denial. The amount of money saved in direct OPAT costs in these patients was calculated. Results: Fifty-six patients were denied OPAT during the study period and were discharged with either oral or no additional antibiotics. Clinical curewas documented in 42 patients (75%), probable cure in 7 patients (12.5%) and treatment failure in 7 patients (12.5%). Of the seven treatment failures, only one patient (1.8%) was deemed to be a true failure after thorough chart review. Overall, the estimated OPAT-specific cost saving was $215424 or $3847 per patient. Conclusions: Mandatory ID approval of all OPAT courses can decrease healthcare costs while maintaining good clinical outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Bone H.,St John Hospital And Medical Center
Endocrinology and Metabolism Clinics of North America | Year: 2012
Future directions in osteoporosis treatment will include development of medications with increasingly precise mechanistic targets, including the RANK-ligand pathway, cathepsin K inhibition, and Wnt signaling manipulation. More gains are likely with anabolics and newer antiresorptives that cause little or no suppression of formation. Optimal treatment of osteoporosis may require coordination of anabolic and antiresorptive treatment, following stimulation of bone formation with consolidation and long-term maintenance. Some well-established drugs may be useful in such regimens. We can also anticipate emphasis on cost containment using currently available drugs, especially as they become generic. Effective implementation and treatment continuity will be important themes. © 2012.