Research Spotlight

Smith, J. S., C. I. Shaffrey, E. Klineberg, V. Lafage, F. Schwab, R. Lafage, H. J. Kim, R. Hostin, G. M. Mundis, Jr., M. Gupta, B. Liabaud, J. K. Scheer, B. G. Diebo, T. S. Protopsaltis, M. P. Kelly, V. Deviren, R. Hart, D. Burton, S. Bess and C. P. Ames (2017). “Complication rates associated with 3-column osteotomy in 82 adult spinal deformity patients: Retrospective review of a prospectively collected multicenter consecutive series with 2-year follow-up.” J Neurosurg Spine 27(4): 444-457.

Full text of this article.

OBJECTIVE Although 3-column osteotomy (3CO) can provide powerful alignment correction in adult spinal deformity (ASD), these procedures are complex and associated with high complication rates. The authors’ objective was to assess complications associated with ASD surgery that included 3CO based on a prospectively collected multicenter database. METHODS This study is a retrospective review of a prospectively collected multicenter consecutive case registry. ASD patients treated with 3CO and eligible for 2-year follow-up were identified from a prospectively collected multicenter ASD database. Early ( 6 weeks after surgery) complications were collected using standardized forms and on-site coordinators. RESULTS Of 106 ASD patients treated with 3CO, 82 (77%; 68 treated with pedicle subtraction osteotomy [PSO] and 14 treated with vertebral column resection [VCR]) had 2-year follow-up (76% women, mean age 60.7 years, previous spine fusion in 80%). The mean number of posterior fusion levels was 12.9, and 17% also had an anterior fusion. A total of 76 early (44 minor, 32 major) and 66 delayed (13 minor, 53 major) complications were reported, with 41 patients (50.0%) and 45 patients (54.9%) affected, respectively. Overall, 64 patients (78.0%) had at least 1 complication, and 50 (61.0%) had at least 1 major complication. The most common complications were rod breakage (31.7%), dural tear (20.7%), radiculopathy (9.8%), motor deficit (9.8%), proximal junctional kyphosis (PJK, 9.8%), pleural effusion (8.5%), and deep wound infection (7.3%). Compared with patients who did not experience early or delayed complications, those who had these complications did not differ significantly with regard to age, sex, body mass index, Charlson Comorbidity Index, American Society of Anesthesiologists score, smoking status, history of previous spine surgery or spine fusion, or whether the 3CO performed was a PSO or VCR (p >/= 0.06). Twenty-seven (33%) patients had 1-11 reoperations (total of 44 reoperations). The most common indications for reoperation were rod breakage (n = 14), deep wound infection (n = 15), and PJK (n = 6). The 24 patients who did not achieve 2-year follow-up had a mean of 0.85 years of follow-up, and the types of early and delayed complications encountered in these 24 patients were comparable to those encountered in the patients that achieved 2-year follow-up. CONCLUSIONS Among 82 ASD patients treated with 3CO, 64 (78.0%) had at least 1 early or delayed complication (57 minor, 85 major). The most common complications were instrumentation failure, dural tear, new neurological deficit, PJK, pleural effusion, and deep wound infection. None of the assessed demographic or surgical parameters were significantly associated with the occurrence of complications. These data may prove useful for surgical planning, patient counseling, and efforts to improve the safety and cost-effectiveness of these procedures.

Calkins, H., G. Hindricks, R. Cappato, Y. H. Kim, E. B. Saad, L. Aguinaga, J. G. Akar, V. Badhwar, J. Brugada, J. Camm, P. S. Chen, S. A. Chen, M. K. Chung, J. C. Nielsen, A. B. Curtis, D. Wyn Davies, J. D. Day, A. d’Avila, N. de Groot, L. Di Biase, M. Duytschaever, J. R. Edgerton, K. A. Ellenbogen, P. T. Ellinor, S. Ernst, G. Fenelon, E. P. Gerstenfeld, D. E. Haines, M. Haissaguerre, R. H. Helm, E. Hylek, W. M. Jackman, J. Jalife, J. M. Kalman, J. Kautzner, H. Kottkamp, K. H. Kuck, K. Kumagai, R. Lee, T. Lewalter, B. D. Lindsay, L. Macle, M. Mansour, F. E. Marchlinski, G. F. Michaud, H. Nakagawa, A. Natale, S. Nattel, K. Okumura, D. Packer, E. Pokushalov, M. R. Reynolds, P. Sanders, M. Scanavacca, R. Schilling, C. Tondo, H. M. Tsao, A. Verma, D. J. Wilber and T. Yamane (2017). “2017 hrs/ehra/ecas/aphrs/solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary.” J Interv Card Electrophysiol: 2017 Sep [Epub ahead of print].

Full text of this article.

During the past three decades, catheter and surgical ablation of atrial fibrillation (AF) have evolved from investigational procedures to their current role as effective treatment options for patients with AF. Surgical ablation of AF, using either standard, minimally invasive, or hybrid techniques, is available in most major hospitals throughout the world. Catheter ablation of AF is even more widely available, and is now the most commonly performed catheter ablation procedure.

Cheng, L., Z. Zhang, G. Li, F. Li, L. Wang, L. Zhang, S. M. Zurawski, G. Zurawski, Y. Levy and L. Su (2017). “Human innate responses and adjuvant activity of tlr ligands in vivo in mice reconstituted with a human immune system.” Vaccine: 2017 Sep [Epub ahead of print].

Full text of this article.

TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-alpha production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-alpha than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4+ T cell response, while only R848 and Poly I:C induced CD8+ cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans.

Sannino, A., R. C. Stoler, R. F. Hebeler, Jr., M. Szerlip, M. J. Mack and P. A. Grayburn (2017). “Clinical relevance of baseline tcp in transcatheter aortic valve replacement.” J Invasive Cardiol 29(10): 353-358.

Full text of this article.

AIMS: To investigate the influence of baseline thrombocytopenia (TCP) on short-term and long-term outcomes after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 732 consecutive patients with severe, symptomatic aortic stenosis undergoing TAVR from January 2012 to December 2015 were included. Primary outcomes of interest were the relationship of baseline TCP with 30-day and 1-year all-cause mortality. Secondary outcomes of interest were procedural complications and in-hospital mortality in the same subgroups. The prevalence of TCP (defined as platelet count <150 x 109/L) at baseline was 21.9%, of whom 4.0% had moderate/severe TCP (defined as platelet count <100 x 109/L). Compared to no or mild TCP, moderate/severe TCP at baseline was associated with a significantly higher 30-day mortality (23.3% vs 2.3% and 3.1%, respectively; P<.001) and 1-year mortality (40.0% vs 8.3% and 13.4%, respectively; P<.001). In Cox regression analysis, moderate/severe baseline TCP was an independent predictor of 30-day and 1-year mortality (hazard ratio [HR], 13.18; 95% confidence interval [CI], 4.49-38.64; P<.001 and HR, 5.90; 95% CI, 2.68-13.02; P<.001, respectively). CONCLUSIONS: In conclusion, baseline TCP is a strong predictor of mortality in TAVR patients, possibly identifying a specific subgroup of frail patients; therefore, it should be taken into account when addressing TAVR risk.

Roostaeyan, O., D. Kivelevitch and A. Menter (2017). “A review article on brodalumab in the treatment of moderate-to-severe plaque psoriasis.” Immunotherapy 9(12): 963-978.

Full text of this article.

Psoriasis is a chronic immune-mediated skin disorder affecting approximately 2-3% of the worldwide population. Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-17, a pro-inflammatory cytokine, plays a pivotal role in psoriasis. Therapeutic agents targeting this cytokine have shown clinical effectiveness in the treatment of moderate-to-severe plaque psoriasis. Brodalumab, a human antibody against IL-17 receptor A, has been approved by the US FDA in February 2017, by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 and by the EMA in July 2017 for the treatment of moderate-to-severe psoriasis. This article reviews the published data relating to brodalumab for the treatment of moderate-to-severe plaque psoriasis.