Research Spotlight

Posted February 19th 2016

The spectrum of nephrocutaneous diseases and associations: Genetic causes of nephrocutaneous disease.

Alan M. Menter M.D.

Alan M. Menter, M.D.

Wofford, J., A. Z. Fenves, J. M. Jackson, A. B. Kimball and A. Menter (2016). “The spectrum of nephrocutaneous diseases and associations: Genetic causes of nephrocutaneous disease.” J Am Acad Dermatol 74(2): 231-244.

Full text of this article.

There are a significant number of diseases and treatment considerations of considerable importance relating to the skin and renal systems. This emphasizes the need for dermatologists in practice or in clinical training to be aware of these associations. Part I of this 2-part continuing medical education article reviews the genetic syndromes with both renal and cutaneous involvement that are most important for the dermatologist to be able to identify, manage, and appropriately refer to nephrology colleagues. Part II reviews the inflammatory syndromes with relevant renal manifestations and therapeutic agents commonly used by dermatologists that have drug-induced effects on or require close consideration of renal function. In addition, we will likewise review therapeutic agents commonly used by nephrologists that have drug-induced effects on the skin that dermatologists are likely to encounter in clinical practice. In both parts of this continuing medical education article, we discuss diagnosis, management, and appropriate referral to our nephrology colleagues in the context of each nephrocutaneous association. There are a significant number of dermatoses associated with renal abnormalities and disease, emphasizing the need for dermatologists to be keenly aware of their presence in order to avoid overlooking important skin conditions with potentially devastating renal complications. This review discusses important nephrocutaneous disease associations with recommendations for the appropriate urgency of referral to nephrology colleagues for diagnosis, surveillance, and early management of potential renal sequelae.

Posted February 19th 2016

Subspecialization within pediatric surgical groups in North America.

Dr. Li Ern Chen M.D.

Dr. Li Ern Chen, M.D.

Langer, J. C., J. S. Gordon and L. E. Chen (2016). “Subspecialization within pediatric surgical groups in North America.” J Pediatr Surg 51(1): 143-148.

Full text of this article.

PURPOSE: The purpose of this study was to assess the current status of subspecialization in North American pediatric surgical practices and to evaluate factors associated with subspecialization. METHODS: A survey was sent to each pediatric surgical practice in the United States and Canada. For each of 44 operation types, ranging in complexity and volume, the respondents chose one of the following responses: 1. everyone does the operation; 2. group policy – only some surgeons do the operation; 3. group policy – anyone can do it but mentorship required; 4. only some do it due to referral patterns; 5. no one in the group does it. Association of various factors with degree of subspecialization was analyzed using nonparametric statistics with p<0.05 considered significant. RESULTS: Response rate was 70%. There was significant variability in subspecialization among groups. Factors found to be significantly associated with increased subspecialization included free-standing children's hospitals, pediatric surgery training programs, higher number of surgeons, higher case volume, and greater volume of tertiary/quaternary cases. CONCLUSIONS: There is wide variation in the degree of subspecialization among North American pediatric surgery practices. These data will help to inform ongoing debate around strategies that may be useful in optimizing pediatric surgical care and patient outcomes in the future.

Posted February 19th 2016

Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database.

Mitchell J. Magee M.D.

Mitchell J. Magee, M.D.

Jacobs, J. P., D. M. Shahian, X. He, S. M. O’Brien, V. Badhwar, J. C. Cleveland, Jr., A. P. Furnary, M. J. Magee, P. A. Kurlansky, J. S. Rankin, K. F. Welke, G. Filardo, R. S. Dokholyan, E. D. Peterson, J. M. Brennan, J. M. Han, D. McDonald, D. Schmitz, F. H. Edwards, R. L. Prager and F. L. Grover (2016). “Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database.” Ann Thorac Surg 101(1): 33-41.

Full text of this article.

BACKGROUND: The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) has been successfully linked to the Centers for Medicare and Medicaid (CMS) Medicare database, thereby facilitating comparative effectiveness research and providing information about long-term follow-up and cost. The present study uses this link to determine contemporary completeness, penetration, and representativeness of the STS ACSD. METHODS: Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft (CABG) surgery hospitalizations discharged between 2000 and 2012, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. RESULTS: Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% in 2000 to 90% in 2012. In 2012, 973 of 1,081 CMS CABG sites (90%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% in 2000 to 94% in 2012. In 2012, 71,634 of 76,072 CMS CABG hospitalizations (94%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2012. In 2012, 69,213 of 70,932 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. CONCLUSIONS: Linkage of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data facilitates studying long-term outcomes and costs of cardiothoracic surgery.

Posted February 19th 2016

Transient Ischemic Attack Caused by Contrast Echocardiography in a Patient with Platypnea-Orthodeoxia.

Paul A. Grayburn M.D.E

Paul A. Grayburn, M.D.

Main, M. L., S. B. Feinstein, L. M. Feinstein, P. A. Grayburn and S. R. Wilson (2016). “Transient Ischemic Attack Caused by Contrast Echocardiography in a Patient with Platypnea-Orthodeoxia.” Echocardiography 33(1): 165-166.

Full text of this article.

We read with interest the recent report by Loncar et al. The authors report a case of transient right hemiparesis temporally associated with the intravenous injection of agitated saline microbubbles. The study reportedly revealed “massive passage” of the agitated saline into the left heart in the setting of a large atrial septal aneurysm and two separate atrial septal defects. As the authors note, agitated saline studies have been associated with transient ischemic attacks (TIA), although this is the first report in a patient with platypnea-orthodeoxia. Although the authors reach a broad conclusion regarding risk associated with “contrast echocardiography” in general, they fail to distinguish the known differences between ultrasound contrast agents (UCAs) comprised of agitated saline microbubbles, used in their study, and UCAs that are commercially prepared and FDA-approved. Agitated saline studies utilize significant quantities (~10 mL) of large, unstable, air-filled microbubbles that have no shell and typically are injected with concomitant provocative maneuvers such as Valsalva or cough, aimed at actively potentiating atrial septal passage. In contrast, commercially prepared UCAs consist of very small microspheres (3–4 µm mean diameter) with a narrow size distribution and an encapsulating, biocompatible shell. Commercial UCAs have been approved by regulatory agencies worldwide and act as true intravascular flow tracers. The authors note that commercially available UCAs are contraindicated in patients with right to left shunts, based on theoretical concern for similar neurologic events following administration of these agents. However, the FDA has been asked to rescind the contraindication because it is not based on sound scientific data. In fact, there have been no published reports of ischemic neurologic events attributed to injection of commercial UCAs despite use in millions of patients worldwide, and empiric and experimental observations directly refute the contention that there is any neurologic risk with commercial UCAs. In a recent single-center study of 39 020 patients who were administered commercial UCAs, no TIAs or strokes were found in a subset of 418 patients with known PFOs. Additionally, large registries have reported no neurologic safety signals, despite the fact that based on population statistics, up to ~25% of these patients likely had PFOs. Further, as we have previously noted, FDA guidance regarding UCAs in patients with PFOs is contradicted by FDA’s own labeling for macroaggregated albumin (MAA), which is routinely used in ventilation–perfusion scans of the lungs. MAA has a particle size of 10–90 µm and is potentially capable of occluding arterioles, yet carries only a “warning” for use in patients with PFOs. Recent data indicate that judicious use of commercial UCAs in critically ill patients with baseline technically difficult echocardiograms is associated with lower mortality,[6] perhaps due to earlier and more accurate diagnosis. Withholding UCAs based on discredited theoretical risks is not evidence-based medicine or patient-centered care. The authors should use more specificity when describing “contrast echocardiography” to avoid confusion between agitated saline studies and commercially prepared UCAs that have decidedly different physio-chemical attributes and safety profiles.

Posted February 19th 2016

Interferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: Real-world experience from the hepatitis C therapeutic registry and research network.

Jacqueline O'Leary M.D.

Jacqueline O’Leary, M.D.

Brown, R. S., Jr., J. G. O’Leary, K. R. Reddy, A. Kuo, G. J. Morelli, J. R. Burton, Jr., R. T. Stravitz, C. Durand, A. M. Di Bisceglie, P. Kwo, C. T. Frenette, T. G. Stewart, D. R. Nelson, M. W. Fried and N. A. Terrault (2016). “Interferon-free therapy for genotype 1 hepatitis C in liver transplant recipients: Real-world experience from the hepatitis C therapeutic registry and research network.” Liver Transpl 22(1): 24-33.

Full text of this article.

Recurrent infection with the hepatitis C virus (HCV) after liver transplantation (LT) is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon (IFN)-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to IFN-free direct-acting antiviral (DAA) regimens. This article describes the experience with DAAs in the treatment of posttransplant genotype (GT) 1 HCV from a consortium of community and academic centers (Hepatitis C Therapeutic Registry and Research Network [HCV-TARGET]). Twenty-one of the 54 centers contributing to the HCV-TARGET consortium participated in this study. Enrollment criteria included positive posttransplant HCV RNA before treatment, HCV GT 1, and documentation of use of a simeprevir (SMV)/sofosbuvir (SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment. A total of 162 patients enrolled in HCV-TARGET started treatment with SMV+SOF with or without ribavirin (RBV) following LT. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with SOF and SMV alone (n = 119; 79%) or with RBV (n = 32; 21%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SMV with or without RBV, 133/151 (88%) achieved sustained virological response at 12 weeks after therapy and 11 relapsed (7%). One patient had virological breakthrough (n = 1), and 6 patients were lost to posttreatment follow-up. Serious adverse events occurred in 11.9%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multiorgan failure. One experienced LT rejection. IFN-free DAA treatment represents a major improvement over prior IFN-based therapy. Broader application of these and other emerging DAA regimens in the treatment of posttransplant hepatitis C is warranted. Liver Transpl 22:24-33, 2016.