Research Spotlight

Posted April 15th 2016

Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis.

Michael Emmett, M.D.

Michael Emmett, M.D.

Hundemer, G. L., A. Z. Fenves, K. M. Phillips and M. Emmett (2016). “Sodium Thiosulfate and the Anion Gap in Patients Treated by Hemodialysis.” Am J Kidney Dis. Mar 15. [Epub ahead of print]

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Calciphylaxis is a syndrome of microvascular calcification and thrombosis leading to painful purpuric skin lesions that progress to necrotic ulcers. Calciphylaxis occurs primarily in patients with ESRD, for which its prevalence has been estimated at 1% annually, and carries a high mortality rate. Increasingly, sodium thiosulfate (STS) is used off-label for treating calciphylaxis. The STS mechanism of action in this condition is unknown. One postulated mechanism is by binding to calcium phosphate salts to form soluble calcium thiosulfate, though additional antioxidant, vasodilatory, and direct inhibitory actions on vascular calcification have been proposed. Dosing of STS, which contains 12.7 mEq/g of sodium and thiosulfate, is empirical and typically 12.5 or 25 g is given during the final 30 to 60 minutes of a hemodialysis (HD) session. A retrospective study showed that 73% of patients treated for calciphylaxis with STS had clinical improvement, with 26% having complete resolution of skin lesions . . . Using an electronic database, we identified all patients with a diagnosis of calciphylaxis who were treated with STS at Massachusetts General Hospital and Brigham and Women’s Hospital between January 2005 and December 2014. . . We found that HD patients treated with STS for calciphylaxis develop an elevated anion gap that is variable and often severe. In addition, we found a dose-response effect of STS on anion gap elevation. Future studies should address the exact mechanism of how STS improves calciphylaxis, which anion accumulates with STS treatment, why such high variability in anion gap effect exists, and clinical effects of the anion gap elevation. (Excerpts from text; no abstract.)


Posted April 15th 2016

Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis.

Xin J. Zhou M.D.

Xin J. Zhou, M.D.E

Wu, T., C. Xie, J. Han, Y. Ye, S. Singh, J. Zhou, Y. Li, H. Ding, Q. Z. Li, X. Zhou, C. Putterman, R. Saxena and C. Mohan (2016). “Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis.” PLoS One 11(3): e0151491.

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Kidney biopsy remains the mainstay of Lupus Nephritis (LN) diagnosis and prognostication. The objective of this study is to identify non-invasive biomarkers that closely parallel renal pathology in LN. Previous reports have demonstrated that serum Insulin-like growth factor binding protein 4 (IGFBP-4) was increased in diabetic nephropathy in both animal models and patients. We proceeded to assess if IGFBP4 could be associated with LN. We performed ELISA using the serum of 86 patients with LN. Normal healthy adults (N = 23) and patients with other glomerular diseases (N = 20) served as controls. Compared to the healthy controls or other glomerular disease controls, serum IGFBP-4 levels were significantly higher in the patients with LN. Serum IGFBP-4 did not correlate well with systemic lupus erythematosus disease activity index (SLEDAI), renal SLEDAI or proteinuria, but it did correlate with estimated glomerular filtration rate (R = 0.609, P < 0.0001). Interestingly, in 18 patients with proliferative LN whose blood samples were obtained at the time of renal biopsy, serum IGFBP-4 levels correlated strongly with the chronicity index of renal pathology (R = 0.713, P < 0.001). IGFBP-4 emerges a potential marker of lupus nephritis, reflective of renal pathology chronicity changes.


Posted April 15th 2016

Impact of Enhanced External Counterpulsation on Heart Failure Rehospitalization in Patients With Ischemic Cardiomyopathy.

Peter McCullough M.D.

Peter McCullough, M.D.

Tecson, K. M., M. A. Silver, S. D. Brune, C. Cauthen, M. D. Kwan, J. M. Schussler, A. Vasudevan, J. A. Watts and P. A. McCullough (2016). “Impact of Enhanced External Counterpulsation on Heart Failure Rehospitalization in Patients With Ischemic Cardiomyopathy.” Am J Cardiol 117(6): 901-905.

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Heart failure (HF) affects millions of Americans and causes financial burdens because of the need for rehospitalization. For this reason, health care systems and patients alike are seeking methods to decrease readmissions. We assessed the potential for reducing readmissions of patients with postacute care HF through an educational program combined with enhanced external counterpulsation (EECP). We examined 99 patients with HF who were referred to EECP centers and received heart failure education and EECP treatment within 90 days of hospital discharge from March 2013 to January 2015. We compared observed and predicted 90-day readmission rates and examined results of 6-minute walk tests, Duke Activity Status Index, New York Heart Association classification, and Canadian Cardiovascular Society classification before and after EECP. Patients were treated with EECP at a median augmentation pressure of 280 mm Hg (quartile 1 = 240, quartile 3 = 280), achieved as early as the first treatment. Augmentation ratios varied from 0.4 to 1.9, with a median of 1.0 (quartile 1 = 0.8, quartile 3 = 1.2). Only 6 patients (6.1%) had unplanned readmissions compared to the predicted 34%, p <0.0001. The average increase in distance walked was 52 m (18.4%), and the median increase in Duke Activity Status Index was 9.95 points (100%), p values <0.0001. New York Heart Association and Canadian Cardiovascular Society classes improved in 61% and 60% of the patients, respectively. In conclusion, patients with HF who received education and EECP within 90 days of discharge had significantly lower readmission rates than predicted, and improved functional status, walk distance, and symptoms.


Posted April 15th 2016

Initial Experience With Commercial Transcatheter Mitral Valve Repair in the United States.

Michael J. Mack M.D.

Michael J. Mack, M.D.

Sorajja, P., M. Mack, S. Vemulapalli, D. R. Holmes, Jr., A. Stebbins, S. Kar, D. S. Lim, V. Thourani, P. McCarthy, S. Kapadia, P. Grayburn, W. A. Pedersen and G. Ailawadi (2016). “Initial Experience With Commercial Transcatheter Mitral Valve Repair in the United States.” J Am Coll Cardiol 67(10): 1129-1140.

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BACKGROUND: Transcatheter mitral valve (MV) repair with the MitraClip received approval in 2013 for the treatment of prohibitive-risk patients with primary mitral regurgitation (MR). OBJECTIVES: The aim of this study was to report the initial U.S. commercial experience with transcatheter MV repair. METHODS: Data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with this percutaneous mitral valve repair device were analyzed. RESULTS: Of 564 patients (56% men, median age 83 years), severe symptoms were present in 473 (86.0%). The median Society of Thoracic Surgeons Predicted Risk of Mortality scores for MV repair and replacement were 7.9% (interquartile range: 4.7% to 12.2%) and 10.0% (interquartile range: 6.3% to 14.5%), respectively. Frailty was noted in 323 patients (57.3%). Transcatheter MV repair was performed for degenerative disease, present in 90.8% of patients. Overall, MR was reduced to grade


Posted April 15th 2016

Potential Indications for Tissue Engineering in Temporomandibular Joint Surgery.

Larry M. Wolford D.M.D.

Larry M. Wolford, D.M.D.

Salash, J. R., R. H. Hossameldin, A. J. Almarza, J. C. Chou, J. P. McCain, L. G. Mercuri, L. M. Wolford and M. S. Detamore (2016). “Potential Indications for Tissue Engineering in Temporomandibular Joint Surgery.” J Oral Maxillofac Surg 74(4): 705-711.

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PURPOSE: Musculoskeletal tissue engineering has advanced to the stage where it has the capability to engineer temporomandibular joint (TMJ) anatomic components. Unfortunately, there is a paucity of literature identifying specific indications for the use of TMJ tissue engineering solutions. The objective of this study was to establish an initial set of indications and contraindications for the use of engineered tissues for replacement of TMJ anatomic components. FINDINGS: There was consensus among the authors that the management of patients requiring TMJ reconstruction as the result of 1) irreparable condylar trauma, 2) developmental or acquired TMJ pathology in skeletally immature patients, 3) hyperplasia, and 4) documented metal hypersensitivities could be indications for bioengineered condyle and ramus TMJ components. There was consensus that Wilkes stage III internal derangement might be an indication for use of a bioengineered TMJ disc or possibly even a disc-like bioengineered “fossa liner.” However, there was some controversy as to whether TMJ arthritic disease (e.g., osteoarthritis) and reconstruction after failed alloplastic devices should be indications. Further research is required to determine whether tissue-engineered TMJ components could be a viable option for such cases. Contraindications for the use of bioengineered TMJ components could include patients with TMJ disorders and multiple failed surgeries, parafunctional oral habits, persistent TMJ infection, TMJ rheumatoid arthritis, and ankylosis unless the underlying pathology can be resolved. CONCLUSIONS: Biomedical engineers must appreciate the specific indications that might warrant TMJ bioengineered structures, so that they avoid developing technologies in search of problems that might not exist for patients and clinicians. Instead, they should focus on identifying and understanding the problems that need resolution and then tailor technologies to address those specific situations. The aforementioned indications and contraindications are designed to serve as a guide to the next generation of tissue engineers in their strategic development of technologies to address specific clinical issues.