Research Spotlight

Hanley, D., L. S. Prichep, N. Badjatia, J. Bazarian, R. P. Chiacchierini, K. C. Curley, J. S. Garrett, E. B. Jones, R. Naunheim, B. J. O’Neil, J. O’Neill, W. David and J. S. Huff (2017). “A brain electrical activity (eeg) based biomarker of functional impairment in traumatic head injury: A multisite validation trial.” J Neurotrauma: 2017 Jun [Epub ahead of print].

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The potential clinical utility of a novel quantitative EEG-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using EEG features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. 720 adult patients (18-85 years) evaluated within 72 hours of sustaining a closed head injury were enrolled at 11 US Emergency Departments. Glasgow Coma Scale was 15 in 97%. Standard clinical evaluations were conducted and 5-10 minutes of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that both the odds ratio of mild functionally impaired group compared to uninjured as well as the odds ratio of the moderate functionally impaired group compared to uninjured, were significantly different from the CT+ (structural injury visible on CT) TBI group (p=0.0009 and p=0.0026, respectively). However, no significance differences in odds (ratios compared to uninjured) of the mild and moderately functionally impaired groups were obtained. ANOVAs demonstrated significant differences in BFI among normal (16.8%), mTBI/concussed (61.3%), and CT+ (21.9%) patients (p<0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in the early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker available at the point of care, hand-held, non-invasive and rapid to obtain.

Blauvelt, A., K. Reich, S. Mehlis, F. Vanaclocha, H. Sofen, W. Abramovits, Y. Zhao, I. Gilloteau, E. Davenport, N. Williams, A. Guana and S. Tyring (2017). “Secukinumab demonstrates greater sustained improvements in daily activities and personal relationships than ustekinumab in patients with moderate-to-severe plaque psoriasis: 52-week results from the clear study.” J Eur Acad Dermatol Venereol: 2017 Jun [Epub ahead of print].

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BACKGROUND: Psoriasis can greatly impact patients’ lives by influencing clothing worn as well as by impairing sexual functioning. Secukinumab, a human monoclonal antibody selectively neutralizing interleukin-17A, has demonstrated good efficacy and safety in the treatment of moderate-to-severe psoriasis and psoriatic arthritis with a rapid onset of action and sustained response. OBJECTIVE: This analysis using the CLEAR study, a phase 3b double-blind study comparing the efficacy and safety of secukinumab versus ustekinumab in adults with moderate-to-severe plaque psoriasis, evaluated the treatment effects on patient’s daily activities and personal relationships. METHODS: Impact on daily activities (interference with home/shopping/garden, and influence on clothes worn) and impact on personal relationships (problems with partner/others, and sexual difficulties) as well as their corresponding subscales were selected from the Dermatology Life Quality Index scale and evaluated for patients treated with secukinumab vs. ustekinumab from the CLEAR study. Treatment differences in mean scores and proportions of responders (score = 0, indicating no impact) were evaluated through 52 weeks. Time to response was evaluated through week 16. RESULTS: Significant differences between secukinumab and ustekinumab were observed for daily activities and personal relationship at week 16 and sustained through Week 52 (Week 52 response rates for daily activities: 82.9% vs. 73.5%, including interference with home/shopping/garden: 88.5% vs. 78.2%, and influence on clothes worn: 85.6% vs. 74.4%; personal relationship: 86.1% vs. 73.7%, including problems with partner/others: 86.6% vs. 74.8%, and sexual difficulties: 88.5% vs. 74.3%; all P < 0.01). The median time to response was 4 weeks for secukinumab versus 8 weeks for ustekinumab for daily activities and personal relationships (both P < 0.05). CONCLUSION: Secukinumab treatment helps patients with moderate-to-severe plaque psoriasis have a more normal life faster when compared to ustekinumab, by providing greater and sustained improvement in clothing choice and sexual functioning.

Bloom, R. D., J. S. Bromberg, E. D. Poggio, S. Bunnapradist, A. J. Langone, P. Sood, A. J. Matas, S. Mehta, R. B. Mannon, A. Sharfuddin, B. Fischbach, M. Narayanan, S. C. Jordan, D. Cohen, M. R. Weir, D. Hiller, P. Prasad, R. N. Woodward, M. Grskovic, J. J. Sninsky, J. P. Yee and D. C. Brennan (2017). “Cell-free DNA and active rejection in kidney allografts.” J Am Soc Nephrol 28(7): 2221-2232.

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Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P<0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types >/=IB), 0.2% (T cell-mediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types >/=IB versus controls). Thus, dd-cfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels <1% reflect the absence of active rejection (T cell-mediated type >/=IB or ABMR) and levels >1% indicate a probability of active rejection.

Dunbar, K. B. and R. F. Souza (2017). “Beyond dysplasia grade: The role of biomarkers in stratifying risk.” Gastrointest Endosc Clin N Am 27(3): 447-459.

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Gastroenterology society guidelines recommend endoscopic surveillance as a means to detect early stage cancer in Barrett’s esophagus. However, the incidence of esophageal adenocarcinoma in Western countries continues to increase, suggesting that this strategy may be inadequate. Current surveillance methods rely on the endoscopist’s ability to identify suspicious areas of Barrett’s esophagus to biopsy, random biopsies, and on the histopathologic diagnosis of dysplasia. This review highlights the challenges of using dysplasia to stratify cancer risk and addresses the development and use of molecular biomarkers and in vivo molecular imaging to detect early neoplasia in Barrett’s esophagus.

Frieder, J., D. Kivelevitch and A. Menter (2017). “Calcipotriene betamethasone dipropionate aerosol foam in the treatment of plaque psoriasis: A review of the literature.” Ther Deliv: 2017 Jun [Epub ahead of print].

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Psoriasis is a common chronic immune-mediated skin disease which has a significant impact on patients’ quality of life, and is associated with numerous comorbidities (i.e., psoriatic arthritis, Crohn’s disease and cardiovascular disease). A greater understanding of its immunopathogenesis has guided the development of novel, more targeted therapies. Nonetheless, traditional treatment with topical agents, phototherapy and systemic medications is used in the management of the majority of psoriasis patients. Mainstay topical treatments include corticosteroids and vitamin D derivatives. Calcipotriene/betamethasone dipropionate aerosol foam is a novel single product combination, which seeks to provide superior therapeutic efficacy in addition to enhanced cosmetic properties. This article reviews the literature on the pharmacology and clinical data in terms of safety, efficacy and patient satisfaction of this topical medication.