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Short K.D.,Mayo Medical School | Rajkumar S.V.,Mayo Medical School | Larson D.,Mayo Medical School | Buadi F.,Mayo Medical School | And 7 more authors.
Leukemia | Year: 2011

We studied 174 consecutive patients with relapsed refractory multiple myeloma (MM) enrolled on a phase II clinical trial of pomalidomide plus low-dose dexamethasone at Mayo Clinic. Extramedullary disease (EMD) was present at the time of trial entry in 7.5% (13 of 174 patients). The rate of EMD in the first 3 years following diagnosis of MM was 3%. The response of EMD to pomalidomide plus low-dose dexamethasone included two complete and two partial responses among the 13 patients (response rate, 31%). Overall survival measured from trial entry was significantly shorter for patients with treatment-emergent EMD compared with those who did not have EMD, (median 16 months versus not reached, P0.002). © 2011 Macmillan Publishers Limited All rights reserved.

Shahid M.W.,Mayo Clinic in Florida | Buchner A.M.,University of Pennsylvania | Raimondo M.,Mayo Clinic in Florida | Woodward T.A.,Mayo Clinic in Florida | And 2 more authors.
Endoscopy | Year: 2012

Background and study aims: Probe-based confocal laser endomicroscopy (pCLE) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures. Most studies have evaluated offline interpretation of pCLE images. In clinical practice, real-time interpretation is necessary to assist decision-making during the procedure. The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies. Patients and methods: pCLE was performed in patients undergoing screening and surveillance colonoscopy. Once a polyp had been identified, one endoscopist analyzed pCLE images during the procedure and made a provisional "real-timeo" diagnosis. Saved video recordings were de-identified, randomized, and reviewed "offlineo" 1 month later by the same endoscopist, who was blinded to the original diagnoses. Results: Images from a total of 154 polyps were recorded (80 neoplastic, 74 non-neoplastic). The overall accuracy of real-time pCLE diagnosis (accuracy 79 %, sensitivity 81 %, specificity 76 %) and offline pCLE diagnosis (83 %, 88 %, and 77 %, respectively) for all 154 polyps were similar. Among polyps < 10 mm in size, the accuracy of real-time interpretation was significantly lower (accuracy 78 %, sensitivity 71 %, specificity 83 %) than that of offline pCLE interpretation (81 %, 86 %, 78 %, respectively). For polyps 10 mm, the accuracy of pCLE diagnosis in real-time was better (accuracy 85 %, sensitivity 90 %, specificity 75 %) than offline pCLE diagnosis (81 %, 97 %, and 50 %, respectively). Conclusions: These results suggest that real-time and offline interpretations of pCLE images are moderately accurate. Real-time interpretation is slightly less accurate than offline diagnosis, but overall both are comparable. Additionally, there was contrasting accuracy between the two methods for small and large polyps. © Georg Thieme Verlag KG Stuttgart New York.

News Article | February 19, 2017
Site: www.eurekalert.org

JACKSONVILLE, Fla. -- Consider it one physician's giant leap for mankind. Today, the latest rocket launch from NASA's Kennedy Space Center in Cape Canaveral, Florida, included a payload of several samples of donated adult stem cells from a research laboratory at Mayo Clinic's Florida campus. The launch by SpaceX, an American aerospace manufacturer and space transport services company, is part of NASA's commercial resupply missions to the International Space Station. The biological cells come from the laboratory of Abba Zubair, M.D., Ph.D., who says he has eagerly awaited the launch following several delays over the past couple of years. Dr. Zubair, who specializes in cellular treatments for disease and regenerative medicine, hopes to find out how the stem cells hold up in space. He says he's eager to know whether these special cells, which are derived from the body's bone marrow, can be more quickly mass-produced in microgravity and used to treat strokes. Microgravity is the condition in which people or objects appear to be weightless. The effects of microgravity can be seen when astronauts and objects float in space. Microgravity refers to the condition where gravity seems to be very small. "At Mayo Clinic, research drives everything we do for patients," says Gianrico Farrugia, M.D., vice president, Mayo Clinic, and CEO of Mayo Clinic in Florida. "This space cargo carries important material for research that could hold the key for developing future treatments for stroke -- a debilitating health issue. Research such as this accelerates scientific discoveries into breakthrough therapies and critical advances in patient care." Dr. Zubair says he has dreamed of this moment all his life, with a passion for space that goes back to his childhood in the northern city of Kano, Nigeria. There, he says he came across a book about the first moon launch and became instantly enthralled. In high school, he recruited other physics students to build a model rocket prototype using corrugated metal and rudimentary materials from the local blacksmith. When it came time to apply for college, however, the school adviser steered him from becoming an astronaut. "He said it may be a long time before Nigeria sends rockets and astronauts into space, so I should consider something more practical," Dr. Zubair recalls. With the goal of being useful to patients and helping cure disease, he headed to medical school in Nigeria. His training took him to the University of Sheffield, in Sheffield, England; the University of Pennsylvania in Philadelphia; and Harvard University in Cambridge, Massachusetts, as he specialized in bone marrow transplants and stem cell research. He came to Mayo Clinic's Florida campus to treat cancer patients and others whose conditions could be helped by regenerative medicine -- all the while running a research lab that studies adult stem cells. Dr. Zubair came across a request for research proposals that involved medicine and outer space four years ago. His mother had died of stroke in 1997, and he had been thinking about stem cells as a treatment for stroke-related brain injury. Collaborating with Mayo Clinic neurologists James Meschia, M.D., and William D. Freeman, M.D., he studied mouse models of stroke. "Stem cells are known to reduce inflammation," he explains. "We've shown that an infusion of stem cells at the site of stroke improves the inflammation and also secretes factors for the regeneration of neurons and blood vessels." One big problem is that it may take as many as 200 million cells to treat a human being, and developing vast numbers of stem cells on Earth can take weeks. "It's further complicated, because some patients are unable to donate cells for themselves, and, sometimes, there aren't enough donors who are a good match, as sometimes occurs for minorities," he says. Studies in simulators on Earth have shown that adult stem cells -- the undifferentiated cells that exist in the body to replace damaged or dying cells -- reproduce quickly and reliably in microgravity. While it's not known why microgravity works better than a petri dish, some researchers speculate the conditions may be similar to the floating environment of developing cells in the body. With funding from the Center for the Advancement of Science in Space, a nonprofit organization, Dr. Zubair hopes to find that, in space, stem cells can be reproduced safely in large quantities, providing new opportunities for patients. He'll gather real-time information about the cells as astronauts conduct experiments measuring molecular changes. "We'll be looking to see if there are genes activated in microgravity and analyzing the stages of the cell cycle," he says. "We may discover proteins or compounds that are produced that we can synthesize on Earth to encourage stem cell growth without having to go to microgravity." Over the last three years of planning, he says he's been tickled to learn about the challenges of space-based research, such as the need for techniques to handle fluids that don't mix in microgravity. Most importantly, experiments will continue after the expanded stem cells return to Earth. "We'll study them to make sure they're normal, functional and safe for patients with stroke," he says. "My work in regenerative medicine has always been intentionally translational -- not just to study what the cells do and what can be done with them but to make a difference for patients. That's what makes our project unique." For the launch, Mayo Clinic is collaborating with the Center for Applied Space Technology (CAST) in Cape Canaveral, and BioServe Space Technologies in Boulder, Colorado. CAST supported Dr. Zubair's research by providing strategic mission planning, proposal development, spaceflight technical support and served as an interface between the research team and various space activities and agencies. BioServe provided space flight hardware, on orbit research protocol and scheduling interface.

Smith C.D.,Mayo Clinic in Florida | Spackman T.,Mayo Clinic in Florida | Brommer K.,Nursing Administration | Stewart M.W.,Mayo Clinic in Florida | And 3 more authors.
Journal of the American College of Surgeons | Year: 2013

Background: Variability in flow of patients through operating rooms has a dramatic impact on a hospital's performance and finances. Natural variation (uncontrollable) and artificial variation (controllable) differ and require different resources and management. The aim of this study was to use variability methodology for a hospital's surgical services to improve operational performance. Study Design: Over a 3-month period, all operations at a referral center were classified as either scheduled (artificial variation) or unscheduled (natural variation). Data regarding patient flow were collected for all cases. From these data, mathematical models determined explicit resources to be allocated for scheduled and unscheduled cases, with isolation of the 2 flow streams. Services were allocated block time based on 80% prime time use, and scheduled cases were capped at 5:00 PM. Guidelines for operating room access were implemented to smooth the daily schedule and minimize artificial variation on the day of surgery. After implementation of this redesign, 12 months of data were compared with the previous 12-month period. Metrics analyzed included prime time use, overtime minutes, access for urgent or emergent cases, the number of room changes to the elective schedule on the day of surgery, and variation of daily schedules. Results: Surgical volume and surgical minutes increased by 4% and 5%, respectively. Prime time use increased by 5%. Overtime staffing decreased by 27%. Day-to-day variability decreased by 20%. The number of elective schedule same day changes decreased by 70%. Staff turnover rate decreased by 41%. Net operating income and margin improved by 38% and 28%, respectively. Conclusions: Variability management results in improvement in operating room operational and financial performance. This optimization may have a significant impact on a hospital's ability to adapt to health care reform. © 2013 by the American College of Surgeons.

Thompson K.M.,Mayo Clinic Florida | Oldenburg W.A.,Mayo Clinic Florida | Deschamps C.,Mayo Medical School | Rupp W.C.,Mayo Clinic in Florida | Smith C.D.,Mayo Clinic Florida
Annals of Surgery | Year: 2011

Objectives: It is estimated that healthcare associated infections (HAI) account for 1.7 million infections and 99,000 associated deaths each year, with annual direct medical costs of up to $45 billion. Surgical Site Infections (SSI) account for 17% of HAIs, an estimated annual cost of $3.5 to 10 billion for our country alone. This project was designed to pursue elimination of SSIs and document results. Methods: Starting in 2009 a program to eliminate SSIs was undertaken at a nationally recognized academic health center. Interventions already outlined by CMS and IHI were utilized, along with additional interventions based on literature showing relationships with SSI reduction and best practices. Rapid deployment of multiple interventions (SSI Bundle) was undertaken. Tactics included standardized order sets, a centralized preoperative evaluation (POE) clinic, high compliance with intraoperative interventions, and widespread monthly reporting of compliance and results. Data from 2008 to 2010 were collected and analyzed. Results: Between May 1, 2008 and June 30, 2010, all patients with Class I and Class II wounds were tracked for SSIs. Baseline data (May-June 2008) was obtained showing a Class I surgical site infection rate of 1.78%, Class II of 2.82% (total surgical volume: 4160 cases). As of the second quarter 2010, those rates have dropped to 0.51% and 1.44%, respectively (P < 0.001 and P = 0.013; total surgical cases: 2826). This represents a 57% decrease in the SSI rate with an estimated institution specific cost savings of nearly $1 million during the study period. Conclusion: Committed leadership, aggressive assurance of high compliance with multiple known interventions (SSI Bundle), transparency to achieve high levels of staff engagement, and centralization of critical surgical activities result in significant declines in SSIs with resulting substantial cost savings. © 2011 by Lippincott Williams & Wilkins.

Nguyen J.H.,Mayo Clinic in Florida
Neurochemistry International | Year: 2010

Vasogenic mechanism of brain edema in acute liver failure (ALF) remains poorly understood. Recent work demonstrates that matrix metalloproteinase-9 (MMP-9) contributes to the development of brain edema in experimental ALF (J Hepatol 44:1105, 2006). Importantly, MMP-9 blockage with specific monoclonal antibodies and/or synthetic inhibitor, the edema is attenuated. Specifically, utrastructural evaluations demonstrate intact blood-brain barrier and its tight junction. These results suggest that subtle alterations in BBB are likely to involve in the brain edema associated with ALF. © 2009 Elsevier Ltd. All rights reserved.

Bosch W.,Mayo Clinic in Florida | Heckman M.G.,Mayo Clinic in Florida | Pungpapong S.,Mayo Clinic in Florida | Diehl N.N.,Mayo Clinic in Florida | And 2 more authors.
Transplantation | Year: 2012

Background. Cytomegalovirus (CMV) has been inconsistently associated with recurrent hepatitis C virus (HCV) after liver transplant (LT). Methods. A retrospective study of 347, donor or recipient CMV seropositive, first LT recipients transplanted for HCV was performed to evaluate the associations of CMV infection and disease occurring within 1-year of LT with the primary endpoints of allograft inflammation grade ≥2 and fibrosis stage ≥2. Associations were evaluated using multivariable Cox regression models. Results. CMV infection and disease occurred in 111 (32%) and 24 (7%) patients, respectively. Hepatic allograft inflammation grade ≥2 and fibrosis stage ≥2 occurred in 221 (64%) and 140 (40%) patients, respectively. CMV infection was associated with increased risk of fibrosis stage ≥2 (relative risk [RR], 1.52; P=0.033). CMV disease was associated with increased risk of inflammation grade ≥2 (RR, 3.40; P<0.001), and although not significant, with fibrosis stage ≥2 (RR, 2.03; P=0.052). These associations did not differ significantly according to recipient CMV seropositivity. Conclusions. Our results support an association between CMV infection and disease with recurrence of HCV after LT. Investigation of prevention of CMV infection and disease as a strategy to mitigate recurrent HCV in LT recipients is warranted. © 2012 by Lippincott Williams & Wilkins.

Liesegang T.J.,Mayo Clinic in Florida
American Journal of Ophthalmology | Year: 2013

Purpose: To provide a current overview of the movement for open access to the peer review literature. Design: Perspective. Methods: Literature review of recent advances in the open access movement with a personal viewpoint of the nuances of the movement. Results: The open access movement is complex, with many different constituents. The idealists for the open access movement are seeking open access to the literature but also to the data that constitute the research within the manuscript. The business model of the traditional subscription journal is being scrutinized in relation to the surge in the number of open access journals. Within this environment authors should beware predatory practices. More government and funding agencies are mandating open access to their funded research. This open access movement will continue to be disruptive until a business model ensures continuity of the scientific record. A flood of open access articles that might enrich, but also might pollute or confuse, the medical literature has altered the filtering mechanism provided by the traditional peer review system. At some point there may be a shake-out, with some literature being lost in cyberspace. Conclusions: The open access movement is maturing and must be embraced in some format. The challenge is to establish a sustainable financial business model that will permit the use of digital technology but yet not endanger the decades-old traditional publication model and peer review system. Authors seem to be slower in adopting open access than the idealists in the movement. © 2013 by Elsevier Inc. All rights reserved.

Ogawa E.,Kyoto University | Hori T.,Mayo Clinic in Florida | Doi H.,Kyoto University | Segawa H.,Kyoto University | Uemoto S.,Kyoto University
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2012

Background Candidates for orthotopic liver transplantation (OLT) often have porto-pulmonary hypertension (PPHTN) with pulmonary arterial hypertension (PAH). Poor outcomes of PPHTN contraindicate OLT. There are no guidelines for living-donor liver transplantation (LDLT) in PPHTN patients. Methods We present our experiences of LDLT in six patients with moderate or severe PPHTN, along with our institutional guidelines. Three had liver cirrhosis and three were non-cirrhotic. Catheterization studies were undertaken before, during and after LDLT, and the mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance and total peripheral resistance (TPR) were monitored. Results The results showed significant differences in CO and TPR between cirrhotic and non-cirrhotic patients before, during and after LDLT. Cirrhotic patients showed systemic hyperdynamic state. Two cirrhotic patients showed poor responses to pre-transplant treatment, and continued to have increased PAH and poor clinical courses after LDLT. LDLT has an advantage of flexible timing of LT. Currently in our institution, PPHTN patients with mPAP<40 mmHg are registered for LDLT after treatment and catheterization. However, LDLT is performed when mPAP is ≤35 mmHg, leading to improved outcomes. Conclusion PPHTN patients with well-controlled PAH, or secondary PAH resulting from porto-systemic shunts, may be appropriate candidates for LDLT after careful considerations. © Japanese Society of Hepato-Biliary- Pancreatic Surgery and Springer 2011.

Gonwa T.A.,Mayo Clinic in Florida | Gonwa T.A.,Mayo Clinic Transplant Center | Wadei H.M.,Mayo Clinic in Florida
Blood Purification | Year: 2012

Development of renal failure requiring renal replacement therapy (RRT) in the cirrhotic patient is a devastating complication. Survival without RRT is less than 10% on average at 6 months. However, it is now appreciated that all renal failure in this group of patients is not due solely to hepatorenal syndrome, and the cause of the renal failure affects the prognosis. This paper reviews the prognosis depending on cause and points out the difficulty in making the correct diagnosis. Provision of RRT is difficult in this group of patients due to hypotension and coagulopathy which is highly prevalent. Survival with RRT is still poor with only 30-60% of patients surviving to liver transplant. Provision of RRT should be offered as a bridge to patients awaiting liver transplant or those undergoing liver transplant evaluation. Provision of long-term RRT is usually not indicated in other cirrhotic patients who develop a need for RRT except as a trial to see if renal function will return. The decision between intermittent hemodialysis or continuous renal replacement therapy (CRRT) is usually based on the clinical characteristics of the patient. Neither has been demonstrated to be superior to the other, although CRRT may be better tolerated in the unstable patient. CRRT is clearly indicated in cases of fulminant hepatic failure as it does not raise intracranial pressure. Provision of intraoperative CRRT during liver transplant may be indicated to help control volume and electrolytes in those patients presenting for liver transplant with renal failure. Newer extracorporeal support systems, such as extracorporeal albumin dialysis (MARS) and fractional plasma separation and adsorption with hemodialysis (Prometheus), have recently been developed to provide both renal and liver support in this group of patients. These are still considered experimental, although the MARS system has been utilized to treat patients with hepatorenal syndrome, and is available outside the United States. © 2012 S. Karger AG, Basel.

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