Research Spotlight

Posted October 15th 2016

Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia.

Marvin J. Stone M.D.

Marvin J. Stone M.D.

Castillo, J. J., R. Garcia-Sanz, E. Hatjiharissi, R. A. Kyle, X. Leleu, M. McMaster, G. Merlini, M. C. Minnema, E. Morra, R. G. Owen, S. Poulain, M. J. Stone, C. Tam, M. Varettoni, M. A. Dimopoulos, S. P. Treon and E. Kastritis (2016). “Recommendations for the diagnosis and initial evaluation of patients with waldenstrom macroglobulinaemia: A task force from the 8th international workshop on waldenstrom macroglobulinaemia.” Br J Haematol 175(1): 77-86.

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The diagnosis of Waldenstrom macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM.


Posted October 15th 2016

Predictors of Rehospitalization Among Adults With Congenital Heart Disease Are Lesion Specific.

Ari M. Cedars M.D.

Ari M. Cedars M.D.

Cedars, A. M., S. Burns, E. L. Novak and A. P. Amin (2016). “Predictors of rehospitalization among adults with congenital heart disease are lesion specific.” Circ Cardiovasc Qual Outcomes 9(5): 566-575.

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BACKGROUND: Readmission is responsible for a large proportion of inpatient care costs in adult congenital heart disease. There are, however, few data available to identify at-risk patients or to suggest strategies for intervention to prevent rehospitalization. METHODS AND RESULTS: We conducted an analysis of admissions in patients over the age of 18 years with a 3-digit International Classification of Diseases-Ninth Revision code of 745 to 747 from the State Inpatient Databases of Arkansas (2008-2010), California (2003-2012), Florida (2005-2012), Hawaii (2006-2010), Nebraska (2003-2011), and New York (2005-2012). We investigated index admission diagnoses most commonly associated with 1-year readmission and the most common reasons for readmission. We then selected variables we thought would be associated with increased rates of 1-year readmission and constructed multivariable regression models grouping patients by congenital lesion, to examine the relative contribution of the specified variables to readmission risk for each lesion. A total of 64 420 patients were included in the final analysis. Thirty-nine percent of patients experienced a readmission within 12 months of an index admission. Compared with those who did not experience a readmission, those who did were more likely to have had a primary diagnosis of congestive heart failure at the time of index admission, and the most common diagnoses at the time of readmission were congestive heart failure and arrhythmia. There is lesion-specific heterogeneity in risk factors for readmission. CONCLUSIONS: Patients with adult congenital heart disease have high rates of readmission, predominantly for congestive heart failure and arrhythmia. Predictors of readmission are lesion specific, and future strategies aimed at decreasing readmission rate will likely need to be individualized.


Posted October 15th 2016

Emerging Trends in the Etiology, Prevention, and Treatment of Gastrointestinal Anastomotic Leakage.

James W. Fleshman M.D.

James W. Fleshman M.D.

Chadi, S. A., A. Fingerhut, M. Berho, S. R. DeMeester, J. W. Fleshman, N. H. Hyman, D. A. Margolin, J. E. Martz, E. C. McLemore, D. Molena, M. I. Newman, J. F. Rafferty, B. Safar, A. J. Senagore, O. Zmora and S. D. Wexner (2016). “Emerging trends in the etiology, prevention, and treatment of gastrointestinal anastomotic leakage.” J Gastrointest Surg: 2016 Sep [Epub ahead of print].

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Anastomotic leaks represent one of the most alarming complications following any gastrointestinal anastomosis due to the substantial effects on post-operative morbidity and mortality of the patient with long-lasting effects on the functional and oncologic outcomes. There is a lack of consensus related to the definition of an anastomotic leak, with a variety of options for prevention and management. A number of patient-related and technical risk factors have been found to be associated with the development of an anastomotic leak and have inspired the development of various preventative measures and technologies. The International Multispecialty Anastomotic Leak Global Improvement Exchange group was convened to establish a consensus on the definition of an anastomotic leak as well as to discuss the various diagnostic, preventative, and management measures currently available.


Posted October 15th 2016

A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

Lynn D. Canavan, M.D.

Lynn D. Canavan, M.D.

Cox, C. E., S. Russell, V. Prowler, E. Carter, A. Beard, A. Mehindru, P. Blumencranz, K. Allen, M. Portillo, P. Whitworth, K. Funk, J. Barone, D. Norton, J. Schroeder, A. Police, E. Lin, F. Combs, F. Schnabel, H. Toth, J. Lee, B. Anglin, M. Nguyen, L. Canavan, A. Laidley, M. J. Warden, R. Prati, J. King and S. C. Shivers (2016). “A prospective, single arm, multi-site, clinical evaluation of a nonradioactive surgical guidance technology for the location of nonpalpable breast lesions during excision.” Ann Surg Oncol 23(10): 3168-3174.

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OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT((R)) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT((R)) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT((R)) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT((R)) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT((R)) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.


Posted October 15th 2016

Amikacin Optimal Exposure Targets in the Hollow-Fiber System Model of Tuberculosis.

Tawanda Gumbo M.D.

Tawanda Gumbo M.D.

Srivastava, S., C. Modongo, C. W. Siyambalapitiyage Dona, J. G. Pasipanodya, D. Deshpande and T. Gumbo (2016). “Amikacin optimal exposure targets in the hollow-fiber system model of tuberculosis.” Antimicrob Agents Chemother 60(10): 5922-5927.

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Aminoglycosides such as amikacin are currently used for the treatment of multidrug-resistant tuberculosis (MDR-TB). However, formal pharmacokinetic/pharmacodynamic (PK/PD) studies to identify amikacin exposures and dosing schedules that optimize Mycobacterium tuberculosis killing have not been performed. It is believed that aminoglycosides do not work well under acidic conditions, which, if true, would mean poor sterilizing activity against semidormant bacilli at low pH. We performed time-kill studies to compare the bactericidal effect of amikacin in log-phase-growth bacilli with the sterilizing effect in semidormant bacilli at pH 5.8 in broth. In log-phase M. tuberculosis at normal pH versus semidormant M. tuberculosis at pH 5.8, the maximal kill (Emax) estimate and 95% confidence interval (CI) were 5.39 (95% CI, 4.91 to 5.63) versus 4.88 (CI, 4.46 to 5.22) log10 CFU/ml, while the concentration mediating 50% of Emax (EC50) was 1.0 (CI, 0. 0.86 to 1.12) versus 0.60 (CI, 0.50 to 0.66) times the MIC, respectively. Thus, the optimal exposures and kill rates identified for log-phase M. tuberculosis will be optimal even for semidormant bacilli. Next, we performed exposure-response and dose-scheduling studies in the hollow-fiber system model of tuberculosis using log-phase M. tuberculosis We recapitulated the amikacin concentration-time profiles observed in lungs of patients treated over 28 days. The PK/PD index linked to M. tuberculosis kill was the peak concentration (Cmax)-to-MIC ratio (r(2) > 0.99), closely followed by the area under the concentration-time curve from 0 to 24 h (AUC0-24)-to-MIC ratio (r(2) = 0.98). The EC90 was a Cmax/MIC ratio of 10.13 (95% CI, 7.73 to 12.48). The EC90 is the dosing target for intermittent therapy that optimizes cure in TB programs for MDR-TB patients.