Suzanne Tharin

All Publications

• microRNAs Refine Cortical Projection Neuron Subtype during Mammalian Development Siththanandan, V., Diaz, J., Lu, V., Gonzalez-Nava, N., Pasquina, L., MacDonald, J., Woodworth, M., Sahni, V., Sarnow, P., Palmer, T., Macklis, J., Tharin, S. WILEY. 2018: S276–S277

  View details for Web of Science ID 000446520900508

• Newly diagnosed glioblastoma: adverse socioeconomic factors correlate with delay in radiotherapy initiation and worse overall survival. Journal of radiation research Pollom, E. L., Fujimoto, D. K., Han, S. S., Harris, J. P., Tharin, S. A., Soltys, S. G. 2018

  Abstract

  The optimal time for starting radiation in patients with glioblastoma (GBM) is controversial. We aimed to evaluate postoperative radiotherapy treatment patterns and the impact of timing of radiotherapy on survival outcomes in patients with GBM using a large, national hospital-based registry in the era of Stupp chemoradiation. We performed a retrospective cohort study using the National Cancer Data Base and identified adults with GBM diagnosed between 2010 and 2013 and treated with chemoradiation. We classified time from surgery/biopsy to radiation start into the following categories: <15 days, 15-21 days, 22-28 days, 29-35 days, 36-42 days and >42 days. We assessed the relation between time to radiation start and survival using Cox proportional hazards modeling adjusting for clinically relevant variables that were selected a priori. We used multivariate logistic modeling to determine factors independently associated with receipt of delayed radiation treatment. A total of 12 738 patients met our inclusion criteria after our cohort selection process. The majority of patients underwent either gross total (n = 5270, 41%) or subtotal (n = 4700, 37%) resection, while 2768 patients (22%) underwent biopsy only. Median time from definitive surgery or biopsy to initiation of radiation was 29 days (interquartile range 24-36 days). For patients who had biopsy or subtotal resection, earlier initiation of radiation did not appear to be associated with improved survival. However, among patients who underwent gross total resection, there appeared to be improved survival with early initiation of radiation. Patients who initiated radiation within 15-21 days of gross total resection had improved survival (hazard ratio 0.82, 95% confidence interval 0.69-0.98, P = 0.03) compared with patients who had delayed (>42 days after surgery) radiation. There was also a trend (P = 0.07 to 0.12) for improved survival for patients who initiated radiation within 22-35 days of gross total resection compared with patients who had delayed radiation. Patients who were black, had Medicaid or other government insurance or were not insured, and who lived in metropolitan areas or further away from the treating facility had higher odds of receiving radiation >35 days after gross total resection. Patients who lived in higher income areas had higher odds of receiving radiation within 35 days of a gross total resection. In a large cohort of patients with GBM treated with chemoradiation, our data suggest a survival benefit in initiating radiotherapy within 35 days after gross total resection. Further research is warranted to understand barriers to timely access to optimal therapy.

  View details for DOI 10.1093/jrr/rrx103

  View details for PubMedID 29432548

• Surgical timing for cervical and upper thoracic injuries in patients with polytrauma JOURNAL OF NEUROSURGERY-SPINE Lubelski, D., Tharin, S., Como, J. J., Steinmetz, M. P., Vallier, H., Moore, T. 2017; 27 (6): 633–37

  Abstract

  OBJECTIVE Few studies have investigated the advantages of early spinal stabilization in the patient with polytrauma in terms of reduction of morbidity and mortality. Previous analyses have shown that early stabilization may reduce ICU stay, with no effect on complication rates. METHODS The authors prospectively observed 340 polytrauma patients with an Injury Severity Score (ISS) of greater than 16 at a single Level 1 trauma center who were treated in accordance with a protocol termed "early appropriate care," which emphasizes operative treatment of various fractures within 36 hours of injury. Of these patients, 46 had upper thoracic and/or cervical spine injuries. The authors retrospectively compared patients treated according to protocol versus those who were not. Continuous variables were compared using independent t-tests and categorical variables using Fisher's exact test. Logistic regression analysis was performed to account for baseline confounding factors. RESULTS Fourteen of 46 patients (30%) did not undergo surgery within 36 hours. These patients were significantly more likely to be older than those in the protocol group (53 vs 38 years, p = 0.008) and have greater body mass index (BMI; 33 vs 27, p = 0.02), and they were less likely to have a spinal cord injury (SCI) (82% did not have an SCI vs 44% in the protocol group, p = 0.04). In terms of outcomes, patients in the protocol-breach group had significantly more total ventilator days (13 vs 6 days, p = 0.02) and total ICU days (16 vs 9 days, p = 0.03). Infection rates were 14% in the protocol-breach group and 3% in the protocol group (p = 0.2) Total complications trended toward being statistically significantly more common in the protocol-breach group (57% vs 31%). After controlling for potential confounding variables by logistic regression (including age, sex, BMI, race, and SCI), total complications were significantly (p < 0.05) greater in the protocol-breach group (OR 29, 95% CI 1.9-1828). This indicates that the odds of developing "any complication" were 29 times greater if treatment was delayed more than 36 hours. CONCLUSIONS Early surgical stabilization in the polytrauma patient with a cervical or upper thoracic spine injury is associated with fewer complications and improved outcomes. Hospitals may consider the benefit of protocols that promote early stabilization in this patient population.

  View details for DOI 10.3171/2017.4.SPINE16933

  View details for Web of Science ID 000416894200005

  View details for PubMedID 28984515

• Evidence for use of Teriparatide in Spinal Fusion Surgery in Osteoporotic Patients. World neurosurgery Chaudhary, N., Lee, J. S., Wu, J. Y., Tharin, S. 2016

  Abstract

  Osteoporosis is defined as a bone mineral density (BMD) less than 2.5 standard deviations below the mean BMD at peak bone mass, or the presence of a fragility fracture. In the setting of osteoporosis, early hardware loosening is thought to cause decreased spinal fusion rates. The two mainstays of osteoporosis treatment are bisphosphonates and Teriparatide. Teriparatide, a form of synthetic parathyroid hormone (PTH), is an anabolic agent that increases osteoblast activity and, thereby, bone mass. Preclinical studies in animal models show that Teriparatide increases spinal fusion rates. Early clinical studies show that teriparatide both increases spinal fusion rates and decreases hardware loosening in the setting of postmenopausal osteoporosis. Ongoing additional trials will help formulate preoperative screening recommendations, determine the optimal duration of pre- and post-operative Teriparatide treatment, and investigate its utility in men.

  View details for DOI 10.1016/j.wneu.2016.11.135

  View details for PubMedID 27923758

• Cervical Spondylotic Myelopathy CLINICAL SPINE SURGERY Iyer, A., Azad, T. D., Tharin, S. 2016; 29 (10): 408-414

  Abstract

  Cervical spondylotic myelopathy (CSM) is a degenerative disease that represents the most common spinal cord disorder in adults. The natural history of the disease can be insidious, and patients often develop debilitating spasticity and weakness. Diagnosis includes a combination of physical examination and various imaging modalities. There are various surgical options for CSM, consisting of anterior and posterior procedures. This article summarizes the literature regarding the pathophysiology, natural history, and diagnosis of CSM, as well as the various treatment options and their associated risks and indications.

  View details for Web of Science ID 000388489300010

  View details for PubMedID 27352369

• Symptomatic Anterior Cervical Osteophyte Causing Dysphagia: Case Report, Imaging, and Review of the Literature. Cure¯us Chen, Y., Sung, K., Tharin, S. 2016; 8 (2)

  Abstract

  Anterior cervical osteophytes are found in 20-30% of elderly patients. Rarely, severe osteophytes can cause dysphagia, dysphonia, and dyspnea. Here, we illustrate a case of severe dysphagia caused by a large post-traumatic osteophyte with oropharyngeal swallow study showing a significant mass effect on the pharynx and resolution following osteophytectomy. We also review the literature regarding the etiology, diagnosis, and treatment of symptomatic anterior cervical osteophytes.

  View details for DOI 10.7759/cureus.473

  View details for PubMedID 27004150

• Anterolateral approach to the upper cervical spine: Case report and operative technique. Head & neck Song, Y., Tharin, S., Divi, V., Prolo, L. M., Sirjani, D. B. 2015; 37 (9): E115-9

  Abstract

  Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. © 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

  View details for DOI 10.1002/hed.23951

  View details for PubMedID 25522016

• A microfluidic device to investigate axon targeting by limited numbers of purified cortical projection neuron subtypes INTEGRATIVE BIOLOGY Tharin, S., Kothapalli, C. R., Ozdinler, P. H., Pasquina, L., Chung, S., Varner, J., Devalence, S., Kamm, R., Macklis, J. D. 2012; 4 (11): 1398-1405

  Abstract

  While much is known about general controls over axon guidance of broad classes of projection neurons (those with long-distance axonal connections), molecular controls over specific axon targeting by distinct neuron subtypes are poorly understood. Corticospinal motor neurons (CSMN) are prototypical and clinically important cerebral cortex projection neurons; they are the brain neurons that degenerate in amyotrophic lateral sclerosis (ALS) and related motor neuron diseases, and their injury is central to the loss of motor function in spinal cord injury. Primary culture of purified immature murine CSMN has been recently established, using either fluorescence-activated cell sorting (FACS) or immunopanning, enabling a previously unattainable level of subtype-specific investigation, but the resulting number of CSMN is quite limiting for standard approaches to study axon guidance. We developed a microfluidic system specifically designed to investigate axon targeting of limited numbers of purified CSMN and other projection neurons in culture. The system contains two chambers for culturing target tissue explants, allowing for biologically revealing axonal growth "choice" experiments. This device will be uniquely enabling for investigation of controls over axon growth and neuronal survival of many types of neurons, particularly those available only in limited numbers.

  View details for DOI 10.1039/c2ib20019h

  View details for Web of Science ID 000311069200008

  View details for PubMedID 23034677

• Cervical spine arthroplasty: fact or fiction: the absence of need for arthroplasty. Clinical neurosurgery Tharin, S., Benzel, E. C. 2012; 59: 82-90

  View details for PubMedID 22960518

• Functional brain mapping and its applications to neurosurgery NEUROSURGERY Tharin, S., Golby, A. 2007; 60 (4): 185-201

  Abstract

  Functional brain mapping may be useful for both preoperative planning and intraoperative neurosurgical decision making. "Gold standard" functional studies such as direct electrical stimulation and recording are complemented by newer, less invasive techniques such as functional magnetic resonance imaging. Less invasive techniques allow more areas of the brain to be mapped in more subjects (including healthy subjects) more often (including pre- and postoperatively). Expansion of the armamentarium of tools allows convergent evidence from multiple brain mapping techniques to bear on pre- and intraoperative decision making. Functional imaging techniques are used to map motor, sensory, language, and memory areas in neurosurgical patients with conditions as diverse as brain tumors, vascular lesions, and epilepsy. In the future, coregistration of high resolution anatomic and physiological data from multiple complementary sources will be used to plan more neurosurgical procedures, including minimally invasive procedures. Along the way, new insights on fundamental processes such as the biology of tumors and brain plasticity are likely to be revealed.

  View details for DOI 10.1227/01.0000255386.95464.52

  View details for Web of Science ID 000245607100001

  View details for PubMedID 17415154

• The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans. Journal of biology Su, C., Tharin, S., Jin, Y., Wightman, B., Spector, M., Meili, D., Tsung, N., Rhiner, C., Bourikas, D., Stoeckli, E., Garriga, G., Horvitz, H. R., Hengartner, M. O. 2006; 5 (4): 9-?

  Abstract

  The nematode Caenorhabditis elegans has been used extensively to identify the genetic requirements for proper nervous system development and function. Key to this process is the direction of vesicles to the growing axons and dendrites, which is required for growth-cone extension and synapse formation in the developing neurons. The contribution and mechanism of membrane traffic in neuronal development are not fully understood, however.We show that the C. elegans gene unc-69 is required for axon outgrowth, guidance, fasciculation and normal presynaptic organization. We identify UNC-69 as an evolutionarily conserved 108-amino-acid protein with a short coiled-coil domain. UNC-69 interacts physically with UNC-76, mutations in which produce similar defects to loss of unc-69 function. In addition, a weak reduction-of-function allele, unc-69(ju69), preferentially causes mislocalization of the synaptic vesicle marker synaptobrevin. UNC-69 and UNC-76 colocalize as puncta in neuronal processes and cooperate to regulate axon extension and synapse formation. The chicken UNC-69 homolog is highly expressed in the developing central nervous system, and its inactivation by RNA interference leads to axon guidance defects.We have identified a novel protein complex, composed of UNC-69 and UNC-76, which promotes axonal growth and normal presynaptic organization in C. elegans. As both proteins are conserved through evolution, we suggest that the mammalian homologs of UNC-69 and UNC-76 (SCOCO and FEZ, respectively) may function similarly.

  View details for PubMedID 16725058

• Regulation of calcium binding proteins calreticulin and calsequestrin during differentiation in the myogenic cell line L6 JOURNAL OF CELLULAR PHYSIOLOGY THARIN, S., Hamel, P. A., Conway, E. M., Michalak, M., Opas, M. 1996; 166 (3): 547-560

  Abstract

  In this report we defined the structural and temporal limits within which calreticulin and calsequestrin participate in the muscle cell phenotype, in the L6 model myogenic system. Calreticulin and calsequestrin are two Ca2+ binding proteins thought to participate in intracellular Ca2+ homeostasis. We show that calsequestrin protein and mRNA were expressed when L6 cells were induced to differentiate, during which time the level of expression of calreticulin protein did not change appreciably. Calreticulin mRNA levels, however, were constant throughout L6 cell differentiation except for slight decline in the mRNA levels at the very late stages of L6 differentiation (day 11-12). We also show that the two Ca2+ binding proteins are coexpressed in differentiated L6 cells. Based on its mobility in SDS-PAGE, L6 rat skeletal muscle cells in culture expressed cardiac isoform of calsequestrin. In the mature rat skeletal muscle, calreticulin and calsequestrin were localized to sarcoplasmic reticulum (SR). Calreticulun, but not calsequestrin, staining was also observed in the perinuclear region. These data suggest that expression of calreticulin and calsequestrin may be under different control during myogenesis in rat L6 cells in culture.

  View details for Web of Science ID A1996TX60300009

  View details for PubMedID 8600158

• WIDESPREAD TISSUE DISTRIBUTION OF RABBIT CALRETICULIN, A NONMUSCLE FUNCTIONAL ANALOG OF CALSEQUESTRIN CELL AND TISSUE RESEARCH THARIN, S., Dziak, E., Michalak, M., Opas, M. 1992; 269 (1): 29-37

  Abstract

  Calreticulin was identified in a variety of rabbit tissues by Western blot analysis. Indirect immunofluorescence studies on cultured cells or frozen sections from the corresponding tissues revealed that the protein was distributed to the endoplasmic reticulum or sarcoplasmic reticulum. Calreticulin was found to be an abundant calcium-binding protein in non-muscle and smooth muscle cells and a constituent calcium-binding protein in cardiac and skeletal muscle. From the immunoblot data, calreticulin may exist as an isoform in rabbit neural retina. The present study establishes the ubiquity of calreticulin in intracellular calcium binding.

  View details for Web of Science ID A1992JB37000004

  View details for PubMedID 1423482