Research Spotlight

Wang, X., Tong, J., Han, X., Qi, X., Zhang, J., Wu, E. and Huang, J.H. (2020). “Acute effects of human protein S administration after traumatic brain injury in mice.” Neural Regen Res 15(11): 2073-2081.

Full text of this article.

Despite years of effort, no effective acute phase treatment has been discovered for traumatic brain injury. One impediment to successful drug development is entangled secondary injury pathways. Here we show that protein S, a natural multifunctional protein that regulates coagulation, inflammation, and apoptosis, is able to reduce the extent of multiple secondary injuries in traumatic brain injury, and therefore improve prognosis. Mice subjected to controlled cortical impact were treated acutely (10-15 minutes post-injury) with a single dose of either protein S (1 mg/kg) or vehicle phosphate buffered saline via intravenous injection. At 24 hours post-injury, compared to the non-treated group, the protein S treated group showed substantial improvement of edema and fine motor coordination, as well as mitigation of progressive tissue loss. Immunohistochemistry and western blot targeting caspase-3, B-cell lymphoma 2 (Bcl-2) along with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that apoptosis was suppressed in treated animals. Immunohistochemistry targeting CD11b showed limited leukocyte infiltration in the protein S-treated group. Moreover, protein S treatment increased the ipsilesional expression of aquaporin-4, which may be the underlying mechanism of its function in reducing edema. These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis. Animal Use Protocols (AUPs) were approved by the University Committee on Animal Resources (UCAR) of University of Rochester Medical Center (approval No. UCAR-2008-102R) on November 12, 2013.

Soto, J.M., Feng, D., Sun, H., Zhang, Y., Lyon, K.A., Liang, B., Reed, L.K. and Huang, J.H. (2020). “Novel Decompressive Hemicraniectomy Technique for Traumatic Brain Injury: Technical Note.” World Neurosurg Oct 17;146:15-19. [Epub ahead of print]. 15-19.

Full text of this article.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality across all age groups. Decompressive hemicraniectomy is the treatment for TBI-related refractory intracranial hypertension. The traditional technique for this procedure can result in wound complications due to injury of the scalp flap’s vascular supply, namely the superficial temporal and postauricular arteries. METHODS: In this technical note we describe our experience using a novel technique that preserves both vascular territories by placing the inferior aspect of the incision posterior to the ear as opposed to anterior to it. This modification has the potential to reduce wound healing complications, especially in those at higher risk, while also reducing operative time by avoiding temporalis muscle incision and closure during procedure. RESULTS: After performing hospital chart review, a total of 7 patients were found who underwent this hemicraniectomy technique for severe TBI. Of these, 5 patients had this performed on the left side, and 2 patients had this performed on the right side. Six of the patients had an accompanying subdural hematoma, whereas 1 patient had no intracranial hemorrhage present. CONCLUSIONS: In each case, both the superficial temporal and postauricular arteries were preserved, and rapid healing of the scalp flap occurred. In addition to providing a large bone window to allow the brain to swell, this technique has the potential to reduce complications of wound healing by preserving the vascular supply of the scalp flap and reduce operative times by minimizing temporalis muscle dissection.

Uhm, S.J., Hall, J.A. and Herrington, J.D. (2020). “Severe and prolonged hypocalcemia after a single dose of denosumab for metastatic breast cancer with diffuse bone involvement without prior calcium/vitamin D supplementations.” J Oncol Pharm Pract Oct 21;1078155220964550. [Epub ahead of print].

Full text of this article.

INTRODUCTION: Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia. CASE REPORT: A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia.Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk. DISCUSSION: Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors’ knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.

Hamandi, M., Lanfear, A.T., Squiers, J.J., George, T., Harrington, K., Szerlip, M.A., DiMaio, J.M. and Smith, R.L. (2020). “Double Valve Replacement in Patients with Mitral Annular Calcification and Aortic Stenosis.” Ann Thorac Surg Oct 31;S0003-4975(20)31839-7. [Epub ahead of print].

Full text of this article.

Mitral annular calcification (MAC) is a degenerative process of the fibrous structure of the mitral valve (MV). Surgical MV replacement in the presence of MAC is technically challenging due to high calcium burden and is associated with prohibitive operative mortality. There is no standard management strategy for patients with severe aortic stenosis and severe MV disease with MAC. We report a case series of three patients who underwent concomitant surgical, transatrial implantation of a transcatheter heart valve in the mitral position and transcatheter aortic valve replacement.

Hamandi, M., Amiens, P., Grayburn, P.A., Al-Azizi, K., van Zyl, J.S., Lanfear, A.T., Rabilloud, M., Riche, B., Gopal, A., Szerlip, M.A., Potluri, S., DiMaio, J.M., Mack, M.J., Harbaoui, B. and Lantelme, P. (2020). “Usefulness of Thoracic Aortic Calcium to Predict 1-Year Mortality After Transcatheter Aortic Valve Implantation.” Am J Cardiol Nov 2;S0002-9149(20)31177-2. [Epub ahead of print].

Full text of this article.

In patients who underwent transcatheter aortic valve implantation (TAVI), vascular disease is associated with increased risk of mortality. Thoracic aortic calcification (TAC), an objective surrogate of vascular disease, could be a predictor of mortality after TAVI. We aimed to analyze the association between TAC burden and 1-year all-cause mortality in patients who underwent TAVI in a US population. From July 2015 through July 2017, a retrospective review of TAVI procedures was performed at Baylor Scott & White-The Heart Hospital, Plano, Texas. Patients were analyzed for comorbidities, cardiac risk factors, and 30-day and 1-year all-cause mortality. Restricted cubic splines analysis was used to define low, moderate, and high TAC categories. The association between TAC and survival was evaluated using unadjusted and adjusted Cox models. A total of 431 TAVI procedures were performed, of which TAC was measured in 374 (81%) patients. Median (interquartile range) age was 82 (77, 87) years, and 51% were male. Median (interquartile range) STS PROM was 5.6 (4.1, 8.2) %. Overall 30-day and 1-year all-cause mortality was 1% and 10%, respectively. TAC was categorized as low (<1.6 cm(3)), moderate (1.6 to 2.9 cm(3)), and high (>2.9 cm(3)). At 1 year, all-cause mortality was 16% in patients with high TAC compared with 6% in the low and moderate TAC categories (p = 0.008). Unadjusted and adjusted Cox regression analysis showed a significant increase in mortality for patients with high TAC compared with low TAC (hazard ratio 2.98, 95% confidence interval [1.34-6.63]), but not significant compared with moderate TAC group. TAC is a predictor of late mortality after TAVI. In conclusion, adding TAC to preoperative evaluation may provide an objective, reproducible, and potentially widely available tool that can help in shared decision-making.