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Ransom E.R.,University of Pennsylvania | Doghramji L.,University of Pennsylvania | Palmer J.N.,University of Pennsylvania | Chiu A.G.,University of Pennsylvania | And 2 more authors.
American Journal of Rhinology and Allergy | Year: 2012

Background: Minimally invasive surgery for neoplasms of the anterior skull base has revolutionized the treatment of these diseases. The relative effect of endoscopic procedures, however, has not been described in terms of disease-specific and global health-related quality of life (QoL). Methods: A single-center longitudinal study was performed of patients undergoing complete endoscopic resection of anterior skull base neoplasms. Patients presenting between October 2009 and September 2010 were enrolled. QoL assessments were based on the 22-question Sinonasal Outcomes Test (SNOT-22), Health Utilities Index Mark II (HUI-2), and Short-Form 12 (SF-12) and were completed preoperatively and at 3, 6, and 12 months postoperatively. Comparisons over time were made within subjects. Results: Fourteen patients were enrolled; 11 completed preoperative and postoperative assessments (79%). Our cohort consisted of five men and six women; mean age was 55 years. Six patients had malignant tumors; four required adjuvant therapy. SNOT-22 scores were stable or improved in 10 cases (91%), with a significant difference for the cohort (mean, -33 points; p < 0.01). Ten (91%) patients had stable or improved HUI-2 scores (mean utility change, +0.13). SF-12 scores were stable for both mental (p = 0.17) and physical (p = 0.26) components. Mean quality-adjusted life year gain over the study period was 0.07. Conclusion: Complete endoscopic resection of anterior skull base neoplasms is oncologically sound with anecdotal QoL improvements relative to open craniofacial resection. We show positive, quantifiable QoL results with validated global and disease-specific instruments. Additional work will help to improve outcomes in this population and will be used in formal cost-effectiveness analysis. Copyright © 2012, OceanSide Publications, Inc.


Berg K.A.,University of Texas Health Science Center at San Antonio | Patwardhan A.M.,Arizona Health science Center | Akopian A.N.,University of Texas Health Science Center at San Antonio
Pharmaceuticals | Year: 2012

Recent discoveries indicate that many G-protein coupled receptors (GPCRs) and channels involved in pain modulation are able to form receptor heteromers. Receptor and channel heteromers often display distinct signaling characteristics, pharmacological properties and physiological function in comparison to monomer/homomer receptor or ion channel counterparts. It may be possible to capitalize on such unique properties to augment therapeutic efficacy while minimizing side effects. For example, drugs specifically targeting heteromers may have greater tissue specificity and analgesic efficacy. This review will focus on current progress in our understanding of roles of heteromeric GPCRs and channels in pain pathways as well as strategies for controlling pain pathways via targeting heteromeric receptors and channels. This approach may be instrumental in the discovery of novel classes of drugs and expand our repertoire of targets for pain pharmacotherapy. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Kalish J.A.,Boston Medical Center | Farber A.,Boston Medical Center | Homa K.,Society for Vascular Surgery | Trinidad M.,Arizona Health Science Center | And 4 more authors.
Journal of Vascular Surgery | Year: 2014

Background: Surgical site infection (SSI) is a major source of morbidity after infrainguinal lower extremity bypass (LEB). This study examines processes of care associated with in-hospital SSI after LEB and identifies factors that could potentially be modified to improve outcomes. Methods: The Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) registry (2003 to 2012) was queried to identify in-hospital SSI after 7908 consecutive LEB procedures performed by 365 surgeons at 91 academic and community hospitals in 45 states. Variables associated with SSI were identified using multivariable logistic regression and hierarchical clustering. Expected and observed SSI rates were calculated for each hospital. Results: The overall in-hospital SSI rate after LEB was 4.8%. Univariate analysis showed that obesity, dialysis, tissue loss, preoperative ankle-brachial index <0.35, distal target, vein graft conduit, continuous incision for vein harvest, transfusion >2 units of packed red blood cells, procedure time >220 minutes, and estimated blood loss >100 mL were associated with higher SSI rates, whereas chlorhexidine (compared with iodine) skin preparation was protective. Multivariable analysis showed independent predictors of SSI included ankle-brachial index <0.35 (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.30, P < .04), transfusion >2 units (OR, 3.30; 95% CI, 2.17-5.02; P < .001), and procedure time >220 minutes (OR, 2.11; 95% CI, 1.05-4.23; P < .04). Chlorhexidine was protective against SSI (OR, 0.53; 95% CI, 0.35-0.79; P = .002). Stratified analyses based on the presence of tissue loss yielded similar results. Across VQI hospitals, observed SSI rates ranged from 0% to 30%, whereas expected SSI rates adjusted by the four independent predictors ranged from 0% to 7.2%. Conclusions: In-hospital SSI after LEB varies substantially across VQI hospitals. Three modifiable processes of care (transfusion rate, procedure time, and type of skin preparation) were identified and may be used by hospitals to reduce SSI rates. This study demonstrates the value of the SVS VQI detailed shared clinical registry to identify improvement opportunities directly pertinent to providers that are not available in typical administrative data sets. © 2014 by the Society for Vascular Surgery.


Kaleta E.J.,University of Arizona | Clark A.E.,University of Arizona | Johnson D.R.,University of Arizona | Gamage D.C.,University of Arizona | And 5 more authors.
Journal of Clinical Microbiology | Year: 2011

Sepsis is among the top 10 causes of mortality in the United States. Rapid administration of antibiotics is one of the most important contributors to patient survival, yet only a limited number of methods exist for rapid identification of microbes cultivated from bloodstream infections, which can lead to sepsis. While traditional single-target molecular methods have been shown to greatly improve survival for septic patients by enabling rapid deescalation of broad-spectrum antibiotics, multiplex methods offer even greater possibilities. A novel multiplex method, PCR coupled to electrospray ionization mass spectrometry (PCR/ESI-MS), was used to identify the genus and species of microorganisms found to cause human bloodstream infections. DNA was directly extracted from 234 BacT-Alert blood culture bottles, and results were compared to those obtained by clinical reference standard methods. The study results demonstrated 98.7% and 96.6% concordance at the genus and species levels, respectively. Mixtures of microbes were identified in 29 blood culture bottles, including mixed species of the same genus, as well as mixtures containing Gram-positive and Gram-negative organisms, exemplifying the PCR/ESI-MS capability to identify multiple organisms simultaneously without the need for cultivation. This study demonstrates high analytical accuracy in comparison to routine subculture of blood culture bottles and phenotypic identification of microbes. Without foreknowledge of the microorganisms potentially present, the PCR/ESI-MS methods can deliver accurate results in as little as 5 to 6 h after a positive alarm from the automated blood culture system; however, current batch mode testing limits the method's clinical utility at this time. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Dalsing M.C.,Indiana University | Makaroun M.S.,University of Pittsburgh | Harris L.M.,State University of New York at Buffalo | Mills J.L.,Arizona Health science Center | And 2 more authors.
Journal of Vascular Surgery | Year: 2012

Methods of learning may differ between generations and even the level of training or the training paradigm, or both. To optimize education, it is important to optimize training designs, and the perspective of those being trained can aid in this quest. The Association of Program Directors in Vascular Surgery leadership sent a survey to all vascular surgical trainees (integrated [0/5], independent current and new graduates [5 + 2]) addressing various aspects of the educational experience. Of 412 surveys sent, 163 (∼40%) responded: 46 integrated, 96 fellows, and 21 graduates. The survey was completed by 52% of the integrated residents, 59% of the independent residents, and 20% of the graduates. When choosing a program for training, the integrated residents are most concerned with program atmosphere and the independent residents with total clinical volume. Concerns after training were thoracic and thoracoabdominal aneurysm procedures and business aspects: 40% to 50% integrated, and 60% fellows/graduates. Integrated trainees found periprocedural discussion the best feedback (79%), with 9% favoring written test review. Surgical training and vascular laboratory and venous training were judged "just right" by 87% and ∼71%, whereas business aspects needed more emphasis (65%-70%). Regarding the 80-hour workweek, 82% felt it prevented fatigue, and 24% thought it was detrimental to patient care. Independent program trainees also found periprocedural discussion the best feedback (71%), with 12% favoring written test review. Surgical training and vascular laboratory/venous training were "just right" by 87% and 60% to 70%, respectively, whereas business aspects needed more emphasis (∼65%-70%). Regarding the 80-hour workweek, 62% felt it was detrimental to patient care, and 42% felt it prevented fatigue. A supportive environment and adequate clinical volume will attract trainees to a program. For "an urgent need to know," the integrated trainees are especially turning to online texts rather than traditional textbooks, which suggests an opportunity for a shift in educational focus. Point-of-care is the best time for education and feedback, suggesting a continued need for dedicated faculty. The business side of training is underserved and should be addressed. Copyright © 2012 Published by Elsevier Inc. on behalf of the Society for Vascular Surgery.


Janvier A.L.,Johns Hopkins Bayview Medical Center | Hamdan H.,Arizona Health science Center | Malas M.,Johns Hopkins Bayview Medical Center
Clinical Nephrology | Year: 2010

A 53-year-old man developed a deep venous thrombus (DVT) and pulmonary embolism (PE) shortly after an open Rouxen-Y gastric bypass was performed. He later suffered a life-threatening gastrointestinal bleed while on anticoagulation for the DVT. Thus, anticoagulation was held and an inferior vena cava (IVC) filter (G2, Bard Inc., Tempe, AZ, USA) was placed for PE prophylaxis. About 10 days after filter placement, he presented with severe low back pain and syncope. He also presented with hypotension and anuria unresponsive to intravenous fluids. A STAT non-contrast CT scan of the abdomen revealed that his IVC filter had migrated from an infrarenal to a suprarenal position. Given the high clinical suspicion for renal vein thrombosis, an attempt at IVC filter retrieval was made. The filter could not be retrieved because it was embedded in a large IVC thrombus that extended from the hepatic veins down to the common iliac veins. The patient received nearly 4 days of tPA that was administered at the site of the thrombus with a long thrombolytic catheter (UNIFUSE, Angiodynamics, Queensbury, NY, USA). While his creatinine peaked at 7.6 on hospital Day 4, he eventually began to produce urine and his creatinine had declined to his baseline of 1.0 on follow-up 1 month later. About 18 months after admission, his creatinine had further declined to 0.8. We report the first published case of acute renal failure due to bilateral renal vein thrombosis in the setting of IVC filter migration and thrombosis. This report highlights an important, but rare complication of IVC filter placement as well as the non-operative management of acute bilateral renal vein thrombosis. ©2010 Dustri-Verlag Dr. K. Feistle.


Boitano S.,Arizona Health science Center | Flynn A.N.,Arizona Health science Center | Sherwood C.L.,Arizona Health science Center | Schulz S.M.,Arizona Health science Center | And 3 more authors.
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2011

Allergens are diverse proteins from mammals, birds, arthropods, plants, and fungi. Allergens associated with asthma (asthmagens) share a common protease activity that may directly impact respiratory epithelial biology and lead to symptoms of asthma. Alternaria alternata is a strong asthmagen in semiarid regions. We examined the impact of proteases from A. alternata on lung inflammation in vivo and on cleaving protease-activated receptor-2 (PAR2) in vitro. A. alternata filtrate applied to the airway in nonsensitized Balb/c mice induced a protease-dependent lung inflammation. Moreover, A. alternata filtrate applied to human bronchial epithelial cells (16HBE14o-) induced changes in intracellular Ca2+ concentration ([Ca2+]i), consistent with PAR2 activation. These effects were blocked by heat inactivation or by serine protease inhibition of A. alternata filtrates, and mimicked by PAR2 specific ligands SLIGRL-NH2 or 2-furoyl-LIGRLO-NH2, but not the PAR1-specific ligand TFLLR-NH2. De-sensitization of PAR2 in 16HBE14o- cells with 2-furoyl-LIGRLO-NH2 or trypsin prevented A. aternata-induced [Ca2+]i changes while desensitization of PAR1, PAR3, and PAR4 with thrombin had no effect on A. aternata-induced Ca2+ responses. Furthermore, the Ca2+ response to A. alternata filtrates was dependent on PAR2 expression in stably transfected HeLa cell models. These data demonstrate that A. alternata proteases act through PAR2 to induce rapid increases in human airway epithelial [Ca2+]i in vitro and cell recruitment in vivo. These responses are likely critical early steps in the development of allergic asthma. © 2011 the American Physiological Society.


Veeramah K.R.,University of Arizona | O'Brien J.E.,University of Michigan | Meisler M.H.,University of Michigan | Cheng X.,Yale University | And 11 more authors.
American Journal of Human Genetics | Year: 2012

Individuals with severe, sporadic disorders of infantile onset represent an important class of disease for which discovery of the underlying genetic architecture is not amenable to traditional genetic analysis. Full-genome sequencing of affected individuals and their parents provides a powerful alternative strategy for gene discovery. We performed whole-genome sequencing (WGS) on a family quartet containing an affected proband and her unaffected parents and sibling. The 15-year-old female proband had a severe epileptic encephalopathy consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy. We discovered a de novo heterozygous missense mutation (c.5302A>G [p.Asn1768Asp]) in the voltage-gated sodium-channel gene SCN8A in the proband. This mutation alters an evolutionarily conserved residue in Nav1.6, one of the most abundant sodium channels in the brain. Analysis of the biophysical properties of the mutant channel demonstrated a dramatic increase in persistent sodium current, incomplete channel inactivation, and a depolarizing shift in the voltage dependence of steady-state fast inactivation. Current-clamp analysis in hippocampal neurons transfected with p.Asn1768Asp channels revealed increased spontaneous firing, paroxysmal-depolarizing-shift-like complexes, and an increased firing frequency, consistent with a dominant gain-of-function phenotype in the heterozygous proband. This work identifies SCN8A as the fifth sodium-channel gene to be mutated in epilepsy and demonstrates the value of WGS for the identification of pathogenic mutations causing severe, sporadic neurological disorders. © 2012 The American Society of Human Genetics.


Riojas M.,University of Arizona | Feng C.,University of Arizona | Hamilton A.,University of Arizona | Hamilton A.,Arizona Health science Center | And 2 more authors.
Applied Soft Computing Journal | Year: 2011

Effective training is the key to minimizing the dangers of minimally invasive surgery (MIS). At present, the assessment of laparoscopic skills relies on the expertise of senior surgeons. The judgment is typically based on and expressed in ordinal variables that can take values such as low, medium, high or other comparable terms. This limited assessment, along with the lack of expert surgeons' metacognitive awareness of how the judgment process takes place, results in imprecise rules for the evaluation of laparoscopic surgical skills. In this work, we present the knowledge elicitation process to model the performance metrics and the rules involved in the assessment of minimally invasive surgical skills. We have implemented a scoring system for the evaluation of laparoscopic skills based on five performance metrics capable of distinguishing between four proficiency levels while providing a quantitative score. Our assessment model is based on fuzzy logic, so that it is easier to mimic the judgment that is already performed by experienced surgeons. The presented framework was empirically validated using the performance data of 38 subjects belonging to five groups: non-medical students, medical students with no previous laparoscopic training, medical students with some training, residents, and expert surgeons. © 2011 Elsevier B.V.


Boyle P.K.,Arizona Health science Center | Badal J.J.,Arizona Health science Center | Boeve J.W.,Arizona Health science Center
Local and Regional Anesthesia | Year: 2011

Although regional anesthesia offers advantages for intraoperative and postoperative pain relief, it is not possible without complications. A case of a significant burn injury after splint placement is described after a peripheral nerve block was performed for postoperative pain management. It is our hope that this case alerts physicians and others involved in the management of postoperative patients to the challenges of managing a blocked extremity after thermal cast placement and offers solutions that can be standardized. © 2011 Boyle et al, publisher and licensee Dove Medical Press Ltd.

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