Bruins H.M.,Radboud University Nijmegen |
Veskimae E.,University of Tampere |
Hernandez V.,Hospital Universitario Fundacion Alcorcon |
Imamura M.,University of Aberdeen |
And 15 more authors.
European Urology | Year: 2014
Context Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).Objective To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. Evidence acquisition Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. Evidence synthesis Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear.Conclusions Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties.Patient summary The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed. © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Radonovich Jr. L.J.,National Center for Occupational Health and Infection Control |
Yanke R.,Malcom Randall Veterans Affairs Medical Center |
Cheng J.,Florida College |
Bender B.,Malcom Randall Veterans Affairs Medical Center
Journal of Occupational and Environmental Hygiene | Year: 2010
This study sought to determine the level of communication interference associated with commonly used disposable and reusable respirators and surgical masks worn by healthcare workers. Speech intelligibility was assessed using the modified rhyme test in an intensive care unit environment. Respirators decreased speech intelligibility by a range of 1% to 17%, although not all were statistically significant. Differences in speech intelligibility associated with surgical masks and disposable filtering facepiece respirators (without exhalation valves) were not statistically significant compared with controls. Wearing half-face elastomeric respirators with voice augmentation equipment was associated with higher speech intelligibility than models without this equipment (OR = 2.81). Hearing clarity while wearing a powered air-purifying respirator (PAPR) was 79% compared with 90% with no PAPR (OR = 0.40). While some respirators appear to have little or no effect on speech intelligibility, interference with speech intelligibility associated with certain types of respirators commonly worn by U.S. healthcare workers may be substantial.
Lomonaco R.,University of Florida |
Sunny N.E.,University of Florida |
Bril F.,University of Florida |
Cusi K.,University of Florida |
Cusi K.,Malcom Randall Veterans Affairs Medical Center
Drugs | Year: 2013
Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world. It is commonly associated with insulin resistance, obesity, dyslipidaemia, type 2 diabetes mellitus (T2DM) and cardiovascular disease. Nonalcoholic steatohepatitis (NASH) is characterized by steatosis with necroinflammation and eventual fibrosis, which can lead to end-stage liver disease and hepatocellular carcinoma. Its pathogenesis is complex, and involves a state of 'lipotoxicity' in which insulin resistance, with increased free fatty acid release from adipose tissue to the liver, play a key role in the onset of a 'lipotoxic liver disease' and its progression to NASH. The diagnosis of NASH is challenging, as most affected patients are symptom free and the role of routine screening is not clearly established. A complete medical history is important to rule out other causes of fatty liver disease (alcohol abuse, medications, other). Plasma aminotransferase levels and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for a definitive diagnosis. However, there is an active search for plasma biomarkers and imaging techniques that may non-invasively aid in the diagnosis. The treatment of NASH requires a multifaceted approach. The goal is to reverse obesity-associated lipotoxicity and insulin resistance via lifestyle intervention. Although there is no pharmacological agent approved for the treatment of NAFLD, vitamin E (in patients without T2DM) and the thiazolidinedione pioglitazone (in patients with and without T2DM) have shown the most consistent results in randomized controlled trials. This review concentrates on our current understanding of the disease, with a focus on the existing therapeutic approaches and potential future pharmacological developments for NAFLD and NASH. © 2013 Springer International Publishing Switzerland.
D'Silva K.A.,University of Toronto |
D'Silva K.A.,St Michaels Hospital |
Dahm P.,University of Florida |
Dahm P.,Malcom Randall Veterans Affairs Medical Center |
And 3 more authors.
JAMA - Journal of the American Medical Association | Year: 2014
IMPORTANCE: Early, accurate diagnosis of bladder outlet obstruction in men with lower urinary tract symptoms may reduce the need for invasive testing (ie, catheter placement, urodynamics), and prompt early treatment to provide symptomatic relief and avoid complications. OBJECTIVES: To systematically review the evidence on (1) the diagnostic accuracy of office-based tests for bladder outlet obstruction in men with lower urinary tract symptoms; and (2) the accuracy of the bladder scan as a measure of urine volume because management decisions rely on measuring postvoid bladder residual volumes. DATA SOURCES AND STUDY SELECTION: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (1950-March 2014), along with reference lists from retrieved articles were searched to identify studies of diagnostic test accuracy among males with lower urinary tract symptoms due to bladder outlet obstruction. MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1950-March 2014) were searched to identify studies of urine volumes measured with a bladder scanner vs those measured with bladder catheterization. Prospective studies were selected if they compared 1 or more office-based, noninvasive diagnostic test with the reference test or were invasive urodynamic studies, and if urine volumes were measured with a bladder scanner and bladder catheterization. DATA EXTRACTION AND SYNTHESIS: For the bladder outlet obstruction objective, 8628 unique citations were identified. Ten studies (1262 patients among 9 unique cohorts) met inclusion criteria. For the bladder scan objective, 2254 unique citations were identified. Twenty studies (n = 1397 patients) met inclusion criteria. MAIN OUTCOMES AND MEASURES: The first main outcome and measurewas the diagnostic accuracy of individual symptoms and questionnaires compared with the reference standard (urodynamic studies) for the diagnosis of bladder outlet obstruction in males with lower urinary tract symptoms. The second was the correlation between urine volumes measured with a bladder scanner and those measured with bladder catheterization. RESULTS: Among males with lower urinary tract symptoms, the likelihood ratios (LRs) of individual symptoms and questionnaires for diagnosing bladder outlet obstruction from the highest quality studies had 95% CIs that included 1.0, suggesting they are not significantly associated with one another. An International Prostate Symptom Score cutoff of 20 or greater increased the likelihood of bladder outlet obstruction (positive LR, 1.5; 95% CI, 1.1-2.0), whereas scores of less than 20 had an LR that included 1.0 in the 95% CI (negative LR, 0.82; 95% CI, 0.67-1.00). We found no data on the accuracy of physical examination findings to predict bladder outlet obstruction. Urine volumes measured by a bladder scanner correlated highly with urine volumes measured by bladder catheterization (summary correlation coefficient, 0.93; 95%CI, 0.91-0.95). CONCLUSIONS AND RELEVANCE In patients with lower urinary tract symptoms, the symptoms alone are not enough to adequately diagnose bladder outlet obstruction. A bladder scan for urine volume should be performed to assess patients with suspected large postvoid residual volumes. Copyright 2014 American Medical Association. All rights reserved.
Hwang M.,University of Florida |
Berceli S.A.,University of Florida |
Berceli S.A.,Malcom Randall Veterans Affairs Medical Center |
Garbey M.,University of Houston |
And 2 more authors.
Biomechanics and Modeling in Mechanobiology | Year: 2012
Although vein bypass grafting is one of the primary options for the treatment of arterial occlusive disease and provides satisfactory results at an early stage of the treatment, the patency is limited to a fewmonths in many patients. When the vein is implanted in the arterial system, it adapts to the high flow rate and high pressure of the arterial environment by changing the sizes of its layers, and this remodeling is believed to be a precursor of future graft failure. Hemodynamic forces, such as wall shear stress (WSS) and wall tension, have been recognized as major factors impacting vein graft remodeling. Although a wide range of experimental evidence relating hemodynamic forces to vein graft remodeling has been reported, a comprehensive mathematical model describing the relationship among WSS, wall tension, and the structural adaptation of each individual layer of the vein graft wall is lacking. The current manuscript presents a comprehensive and robust framework for treating the complex interaction between the WSS, wall tension, and the structural adaptation of each individual layer of the vein graft wall.We modeled the intimal and medial area and the radius of external elastic lamina, which in combination dictate luminal narrowing and the propensity for graft occlusion. Central to our model is a logistic relationship between independent and dependent variables to describe the initial increase and later decrease in the growth rate. The detailed understanding of the temporal changes in vein graft morphology that can be extracted from the current model is critical in identifying the dominant contributions to vein graft failure and the further development of strategies to improve their longevity. © Springer-Verlag 2011.
Reeder D.N.,Malcom Randall Veterans Affairs Medical Center |
Gillette M.A.,University of Florida |
Franck A.J.,Malcom Randall Veterans Affairs Medical Center |
Frohnapple D.J.,Medical Intensive Care Unit
Annals of Pharmacotherapy | Year: 2012
Background: Efficacy of ranolazine in the treatment of chronic stable angina (CSA) has been established; however, pivotal trials did not require the optimization of conventional antianginal drug therapy (CADT) prior to use in a veteran population. Objective: To determine whether ranolazine, when added to optimized doses of CADT, improves angina in a veteran population with CSA and refractory symptoms. Methods: In an observational retrospective study, 35 patients prescribed ranolazine and having a baseline Seattle Angina Questionnaire (SAQ) administered at a Veterans Affairs medical center in Gainesville, FL, were evaluated. Patients who were prescribed ranolazine by a provider from outside the institution and did not obtain a baseline SAQ were excluded. The primary outcome measure was the change in SAQ scores from baseline to 1 and 3 months after initiation of ranolazine treatment. Secondary measures included clinically significant QTc interval prolongation (>500 msec or an increase of at least 60 msec from baseline), adverse drug reactions, discontinuation rates, and drug-drug interactions. Results: The addition of ranolazine to optimized CADT was associated with improvement in all dimensions of the SAQ scores at 1 and 3 months compared to baseline scores (p < 0.001 for all dimensions). Mean changes in SAQ dimension scores at 1 and 3 months, respectively, were as follows: physical limitation, +9.86 and +11.94; angina stability, +39.29 and +32.69; angina frequency, +26.79 and +25.38; treatment satisfaction, +11.38 and +10.66; and disease perception, +16.85 and +18.59. Improvments in all dimensions, except treatment satisfaction, were clinically significant as defined by set criteria. Of the 7 patients whose ranolazine dosages were increased to 1000 mg twice daily, only 2 patients were able to maintain treatment at that dosage. Conclusions: Ranolazine added to optimized doses of CADT demonstrated an improvement in angina symptoms when given to a veteran population with persistent CSA.
Bril F.,University of Florida |
Lomonaco R.,University of Florida |
Cusi K.,University of Florida |
Cusi K.,Malcom Randall Veterans Affairs Medical Center
Clinical Lipidology | Year: 2012
Nonalcoholic fatty liver disease (NAFLD) is much more common than previously believed, affecting at least a third of the overall adults and two-thirds of obese subjects. The disease is strongly associated with the metabolic syndrome and Type 2 diabetes mellitus. Recent studies have shown that it may be also associated with cardiovascular disease. Among the many potential mechanisms for the association of NAFLD with cardiovascular disease, it is believed that abnormal lipoprotein metabolism plays a major role. Elevated plasma triglycerides, low HDL-cholesterol and increased apoB levels characterize dyslipidemia in NAFLD. Given the potential for dyslipidemia to increase cardiovascular disease in NAFLD, patients should be diagnosed early and treated aggressively. Paradoxically, most patients with NAFLD are denied lipid-lowering drugs as they frequently have elevated liver aminotransferases, and there is a perception of an increased risk of hepatotoxicity among clinicians treating these patients. We recommend starting low-dose statins with titration based on close monitoring, which overall appears to be safe, although there is a need for long-term studies. The available literature also suggests that fibrate therapy, with or without associated statin use, is, in general, well tolerated and safe. In summary, this review will address the clinical implications of dyslipidemia in NAFLD and the common dilemmas that healthcare providers face when lipid-lowering therapy is needed in these patients. © 2012 Future Medicine Ltd.
Khodayari N.,University of Florida |
Mohammed K.A.,University of Florida |
Mohammed K.A.,Malcom Randall Veterans Affairs Medical Center |
Goldberg E.P.,University of Florida |
Nasreen N.,University of Florida
Cancer Gene Therapy | Year: 2011
EphrinA1 binding with receptor EphA2 suppresses malignant mesothelioma (MM) growth. The mechanisms whereby EphrinA1 attenuates the MM cell (MMC) growth are not clear. In this study, we report that the activation of MMCs with EphrinA1 leads to an induction of let-7 microRNA (miRNA) expression, repression of RAS proto-oncogene and the attenuation of MM tumor growth. The expression of miRNAs was determined by reverse transcription-quantitative polymerase chain reaction and in situ hybridization. RAS expression was determined by q-PCR, western blotting and immunofluorescence. MMC proliferation and tumor growth were determined by WST-1 and Matrigel assay, respectively. EphrinA1 activation induced several fold increases in let-7a1, let-7a3, let-7f1 and let-7f2 miRNA expression in MMCs. In contrast, EphrinA1 activation significantly downregulated H-RAS, K-RAS and N-RAS expression and inhibited MMC proliferation and tumor growth. In MMCs transfected with 2′-O-methyl antisense oligonucleotides to let-7 miRNA, EphrinA1 activation failed to inhibit the proliferative response and tumor growth. In mismatch antisense oligonucleotide-treated MMCs, the proliferation and tumor growth were comparable to untreated proliferating cells. Furthermore, the transfection of MMCs with let-7a miRNA precursor inhibited RAS expression and attenuated MMC tumor growth. Our data revealed that EphrinA1 signaling induces let-7 miRNA expression and attenuates MM tumor growth by targeting RAS proto-oncogene in MMCs. © 2011 Nature America, Inc. All rights reserved.
PubMed | Medical University of South Carolina, University of Florida and Malcom Randall Veterans Affairs Medical Center
Type: Journal Article | Journal: PloS one | Year: 2017
Methicillin Resistant Staphylococcus aureus (MRSA) cause pneumonia and empyema thoraces. TLR9 activation provides protection against bacterial infections and Heme oxygenase-1 (HO-1) is known to enhance host innate immunity against bacterial infections. However, it is still unclear whether HO-1 regulates TLR-9 expression in the pleura and modulates the host innate defenses during MRSA empyema. In order to determine if HO-1 regulates host innate immune functions via modulating TLR expression, in MRSA empyema, HO-1+/+ and HO-1-/- mouse pleural mesothelial cells (PMCs) were infected with MRSA (1:10, MOI) in the presence or absence of Cobalt Protoporphyrin (CoPP) and Zinc Protoporphyrin (ZnPP) or CORM-2 (a Carbon monoxide donor) and the expression of mTLR9 and mBD14 was assessed by RT-PCR. In vivo, HO-1+/+ and HO-1-/- mice were inoculated with MRSA (5x106 CFU) intra-pleurally and host bacterial load was measured by CFU, and TLR9 expression in the pleura was determined by histochemical-immunostaining. We noticed MRSA inducing differential expression of TLR9 in HO-1+/+ and HO-1 -/- PMCs. In MRSA infected HO-1+/+ PMCs, TLR1, TLR4, and TLR9 expression was several fold higher than MRSA infected HO-1-/- PMCs. Particularly TLR9 expression was very low in MRSA infected HO-1-/- PMCs both in vivo and in vitro. Bacterial clearance was significantly higher in HO-1+/+ PMCs than compared to HO-1-/- PMCs in vitro, and blocking TLR9 activation diminished MRSA clearance significantly. In addition, HO-1-/- mice were unable to clear the MRSA bacterial load in vivo. MRSA induced TLR9 and mBD14 expression was significantly high in HO-1+/+ PMCs and it was dependent on HO-1 activity. Our findings suggest that HO-1 by modulating TLR9 expression in PMCs promotes pleural innate immunity in MRSA empyema.
Pandey A.K.,Florida College |
Pandey A.K.,Malcom Randall Veterans Affairs Medical Center |
Heilman K.M.,Florida College |
Heilman K.M.,Malcom Randall Veterans Affairs Medical Center
Cognitive and Behavioral Neurology | Year: 2014
Conduction aphasia, most often caused by damage to the inferior parietal lobe and arcuate fasciculus, is usually characterized by mildly dysfluent speech with frequent phonemic paraphasic errors, impaired repetition, and impaired word finding and naming, but with relatively spared comprehension. We report an 86-year-old right-handed man with conduction aphasia caused by an infarction that damaged his right temporoparietal region. On testing with the Western Aphasia Battery, however, he named objects almost perfectly. To test his naming ability further, we showed him half the items in the Boston Naming Test; we described or defined the other half of the items, but did not show them to the patient. He performed excellently when naming the objects that he could see, but he had difficulty naming the objects that were only described or defined. These observations suggest that visual word naming may be mediated by a network that is somewhat independent of the networks that mediate spontaneous word finding and word finding based on verbal descriptions or definitions. © 2014 by Lippincott Williams & Wilkins.