Research Spotlight

Garrett, G. L., P. D. Blanc, J. Boscardin, A. A. Lloyd, R. L. Ahmed, T. Anthony, K. Bibee, A. Breithaupt, J. Cannon, A. Chen, J. Y. Cheng, Z. Chiesa-Fuxench, O. R. Colegio, C. Curiel-Lewandrowski, C. A. Del Guzzo, M. Disse, M. Dowd, R. Eilers, Jr., A. E. Ortiz, C. Morris, S. K. Golden, M. S. Graves, J. R. Griffin, R. S. Hopkins, C. C. Huang, G. H. Bae, A. Jambusaria, T. A. Jennings, S. I. Jiang, P. S. Karia, S. Khetarpal, C. Kim, G. Klintmalm, K. Konicke, S. A. Koyfman, C. Lam, P. Lee, J. J. Leitenberger, T. Loh, S. Lowenstein, R. Madankumar, J. F. Moreau, R. I. Nijhawan, S. Ochoa, E. B. Olasz, E. Otchere, C. Otley, J. Oulton, P. H. Patel, V. A. Patel, A. V. Prabhu, M. Pugliano-Mauro, C. D. Schmults, S. Schram, A. F. Shih, T. Shin, S. Soon, T. Soriano, D. Srivastava, J. A. Stein, K. Sternhell-Blackwell, S. Taylor, A. Vidimos, P. Wu, N. Zajdel, D. Zelac and S. T. Arron (2017). “Incidence of and risk factors for skin cancer in organ transplant recipients in the united states.” JAMA Dermatol: 2017 Jan [Epub ahead of print].

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Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants: This multicenter retrospective cohort study examined 10649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results: Overall, 10649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59923 years of follow-up. The incidence rates for posttransplant skin cancer was 1408 per 100000 person-years. Specific subtype rates for SCC, MM, and MCC were 1328, 122, and 4 per 100000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

Harrison, J. K., G. C. Hughes, M. J. Reardon, R. Stoler, P. Grayburn, R. Hebeler, D. Liu, Y. Chang and J. J. Popma (2017). “Balloon post-dilation following implantation of a self-expanding transcatheter aortic valve bioprosthesis.” JACC Cardiovasc Interv 10(2): 168-175.

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OBJECTIVES: This study sought to explore the impact of balloon post-dilation (BPD) on outcomes in the CoreValve US Clinical Trials. BACKGROUND: BPD following transcatheter aortic valve replacement (TAVR) has been used in selected cases to optimize hemodynamic results. METHODS: Procedural details of 3,532 patients were examined to determine whether BPD was performed after self-expanding TAVR. “Best practice” guidelines recommended BPD for treatment of suboptimal intraprocedural valve function, primarily manifested by moderate or severe residual aortic regurgitation (AR). RESULTS: Procedural BPD was performed in 782 patients (22%) patients. The most common (58.1%) indication was greater than or equal to moderate AR following valve deployment. Greater baseline aortic valve gradients (p < 0.001), higher grades of baseline AR (p < 0.001), larger annular diameters (p < 0.001), and lower device to annular ratios (p < 0.001) were more common in patients who underwent BPD. BPD was performed less often with the 26-mm valve (17.9%) compared to the 31 mm (38.1%) (p < 0.05). BPD reduced moderate or severe AR by 75.6% from 58.1% to 14.2%. Thirty-day and 1-year clinical events were similar in the 2 groups, although acute kidney injury was more common in patients undergoing BPD (p = 0.026). In-hospital major adverse cardiovascular and cerebrovascular event rates were 9.3% in the BPD group versus 7.5% for others (p = NS). There was no increase in neurological events. CONCLUSIONS: BPD of the self-expanding bioprosthesis was performed in 22% of patients in the CoreValve US Clinical Trials most commonly to reduce the degree of residual AR. BPD was effective in acutely improving valve performance without an associated increase in neurologic events.

Keller, D. S., D. Kroll, H. T. Papaconstantinou and C. N. Ellis (2017). “Development and validation of a methodology to reduce mortality using the veterans administration surgical quality improvement program risk calculator.” J Am Coll Surg: 2017 Jan [Epub ahead of print].

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BACKGROUND: To identify patients with a high risk of 30 day mortality after elective surgery that may benefit from referral for tertiary care, an institution-specific process using the Veterans Administration Surgical Quality Improvement Program (VASQIP) Risk Calculator was developed. The goal was to develop and validate the methodology. Our hypothesis was the process could optimize referrals and reduce mortality. STUDY DESIGN: A VASQIP risk score was calculated for all patients undergoing elective non-cardiac surgery at a single Veteran’s Administration (VA) facility. After statistical analysis, a VASQIP risk score of 3.3% predicted mortality was selected as the institutional threshold for referral to a tertiary-care center. The model predicted 16 percent of patients would require referral and 30 day mortality would be reduced by 73 percent at the referring institution. The main outcome measures were the actual versus predicted referrals and mortality rates at the referring and receiving facilities. RESULTS: The validation included 565 patients; 90 (16 percent) had VASQIP risk scores greater than 3.3 percent and were identified for referral; 60 consented. In these patients, there were 16 (27 percent) predicted mortalities, but only 4 actual deaths (p=0.007) at the receiving institution. Where referral was not indicated, the model predicted 4 mortalities (1%), but no actual deaths (p=0.1241). CONCLUSIONS: These data validate this methodology to identify patients for referral to a higher level of care, reducing mortality at the referring institutions and significantly improving patient outcomes. This methodology can help guide decisions on referrals and optimize patient care. Further application and studies are warranted.

Kieliszak, C. R., J. R. Griffin, T. H. Pollinger and J. M. Junkins-Hopkins (2017). “Pseudo-bullous dermatosis induced by topical anesthetic agent-clues to this localized toxic reaction.” Am J Dermatopathol 39(2): e19-e22.

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Eutectic mixture of 2.5% lidocaine and 2.5% prilocaine (EMLA AstraZeneca, DE) is a widely used topical anesthetic cream for preprocedural cutaneous analgesia. In addition to potential clinical cutaneous and systemic adverse effects, EMLA may also induce microscopic changes detectable by light and electron microscopy leading to difficulty in accurate diagnosis. We report the case of a biopsy demonstrating EMLA-induced histopathologic changes. The biopsy was taken from the back of a 5-month-old infant and submitted to rule out psoriasis. Hematoxylin and eosin (H&E) staining of the biopsy demonstrated spongiosis and a noninflammatory subepidermal bulla, raising the histopathologic possibility of epidermolysis bullosa. Further investigation confirmed that EMLA was applied under occlusion before biopsy. A second biopsy without topical anesthetic did not demonstrate a bulla and supported the clinical diagnosis of psoriasiform dermatitis. Our case highlights the importance of awareness of EMLA-induced histopathologic changes to avoid potential misdiagnosis. The histopathologic findings of this case in conjunction with other previously reported cases of EMLA-induced bullae were analyzed. Vacuolization of the basal and suprabasilar layer, pallor and swelling of upper layer epidermal keratinocytes, a pauci-inflammatory cleavage beneath or within the basal layer, basophilic granular karyorrhectic debris in the subepidermal cleft, and congestion of papillary dermal vessels characterized the biopsy findings of this localized adverse reaction.

Kumar, R. G., S. B. Juengst, Z. Wang, K. Dams-O’Connor, S. S. Dikmen, T. M. O’Neil-Pirozzi, M. N. Dahdah, F. M. Hammond, E. R. Felix, P. M. Arenth and A. K. Wagner (2017). “Epidemiology of comorbid conditions among adults 50 years and older with traumatic brain injury.” J Head Trauma Rehabil: 2017 Jan [Epub ahead of print].

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OBJECTIVES: Aging individuals with traumatic brain injury (TBI) experience multiple comorbidities that can affect recovery from injury. The objective of this study was to describe the most commonly co-occurring comorbid conditions among adults 50 years and older with TBI. SETTING: Level I Trauma centers. PARTICIPANTS: Adults 50 years and older with moderate/severe TBI enrolled in the TBI-Model Systems (TBI-MS) from 2007 to 2014 (n = 2134). DESIGN: A TBI-MS prospective cohort study. MAIN MEASURES: International Classification of Disease-9th Revision codes collapsed into 45 comorbidity categories. Comorbidity prevalence estimates and trend analyses were conducted by age strata (50-54, 55-64, 65-74, 75-84, >/=85 years). A dimension reduction method, Treelet Transform, classified clusters of comorbidities that tended to co-occur. RESULTS: The 3 most commonly occurring comorbid categories were hypertensive disease (52.6/100 persons), other diseases of the respiratory system (51.8/100 persons), and fluid component imbalances (43.7/100 persons). Treelet Transform classified 3 clusters of comorbid codes, broadly classified as (1) acute medical diseases/infections, (2) chronic conditions, and (3) substance abuse disorders. CONCLUSION: This study provides valuable insight into comorbid conditions that co-occur among adults 50 years and older with TBI and provides a foundation for future studies to explore how specific comorbidities affect TBI recovery.