Education & Certifications
Bachelor of Science, Brown University, Biochemistry (2018)
Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan.
2018; 23 (7): 1915–21
Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and lifespan observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration.
View details for DOI 10.1016/j.celrep.2018.04.063
View details for PubMedID 29768192
View details for PubMedCentralID PMC5991088
Fascial Hernia After Traumatic Tibial Shaft Fractures: A Cause of Chronic Leg Pain: A Report of 2 Cases.
JBJS case connector
; 10 (1): e0183
This report reviews 2 cases of chronic lower extremity pain after traumatic tibial shaft fractures treated with intramedullary nail fixation. After examination and radiographic evaluation, clinical suspicion and pressure manometry were used to identify fascial herniation and indicate patients for fasciotomy, which ultimately relieved pain.Lower extremity fascial hernias typically present with nonspecific chronic pain. Ultrasonography and magnetic resonance imaging (MRI) can be used to confirm diagnosis. However, in patients with implanted hardware, MRI may be ineffective in detecting hernias because of artifact. Clinical suspicion and pressure manometry are effective ways of identifying patients with this etiology of chronic pain.
View details for DOI 10.2106/JBJS.CC.19.00183
View details for PubMedID 32224669
- Marriage Status Predicts Hospital Outcomes Following Orthopedic Trauma GERIATRIC ORTHOPAEDIC SURGERY & REHABILITATION 2020; 11
Recognition and Management of Emergent Spinal Pathology Among First-Line Providers.
Spinal emergencies require prompt identification, management, and surgical referral (if needed) from first-line providers. Diagnostic delays from a failure to recognize emergency conditions can lead to adverse patient outcomes. The objective of this study was to understand the proficiency with which first-line providers can recognize and manage spinal conditions, particularly spinal emergencies. This was a cross-sectional analysis of 143 internal medicine, family medicine, emergency care, and neurology questionnaires collected at a single-site academic center. Participants were predominantly physicians (88.1%, n=126), with a smaller percentage of midlevel providers (11.9%, n=17). Only 35.0% (n=50) of respondents felt "very prepared" to handle spinal emergencies. Bivariate analyses revealed interdepartmental differences in clinical knowledge pertaining to the management of lumbar radiculopathy (P<.0001), epidural abscess (P=.0002), and cervical myelopathy (P<.0001). Following pairwise comparisons of interdepartmental differences, emergency medicine statistically outperformed internal medicine (P=.0007) and neurology (P<.0001) on initial management of lumbar radiculopathy, while also having markedly higher success in identifying and managing epidural abscess with respect to family medicine (P<.0001). The likelihood of appropriate initial treatment of cervical myelopathy was significantly higher for neurology than for emergency medicine (P<.0001). A minority of first-line providers reported being very prepared to handle spinal emergencies. Disparities exist between first-line provider specialties regarding clinical knowledge in managing and proficiently identifying emergent and nonemergent spinal conditions. Because appropriate handling of emergent spinal pathologies is essential to patient outcomes and optimal resource use, measures should be taken to further educate first-line providers regarding the spinal conditions they will be treating. [Orthopedics. 2020;43(x):xx-xx.].
View details for DOI 10.3928/01477447-20200404-07
View details for PubMedID 32271932
Hospital competitive intensity and perioperative outcomes following lumbar spinal fusion.
The spine journal : official journal of the North American Spine Society
2018; 18 (4): 626–31
Interhospital competition has been shown to influence the adoption of surgical techniques and approaches, clinical patient outcomes, and health care resource use for select surgical procedures. However, little is known regarding these dynamics as they relate to spine surgery.This investigation sought to examine the relationship between interhospital competitive intensity and perioperative outcomes following lumbar spinal fusion.This study used the Nationwide Inpatient Sample dataset, years 2003, 2006, and 2009.Patients were included based on the presence of the International Classification of Disease, Ninth Edition, Clinical Modification (ICD-9-CM) codes corresponding to lumbar spinal fusion, as well as on the presence of data on the Herfindahl-Hirschman Index (HHI).The outcome measures are perioperative complications, defined using an ICD-9-CM coding algorithm.The HHI, a validated measure of competition within a market, was used to assess hospital market competitiveness. The HHI was calculated based on the hospital cachement area. Multiple regression was performed to adjust for confounding variables including patient age, gender, primary payer, severity of illness score, primary versus revision fusion, anterior versus posterior approach, national region, hospital bed size, location or teaching status, ownership, and year. Perioperative clinical outcomes were assessed based on ICD-9-CM codes with modifications.In total, 417,520 weighted patients (87,999 unweighted records) were analyzed. The mean cachement area HHI was 0.31 (range 0.099-0.724). The average patient age was 55.4 years (standard error=0.194), and the majority of patients were female (55.8%, n=232,727). The majority of procedures were primary spinal fusions (92.7%, n=386,998) and fusions with a posterior-only technique (81.5%, n=340,271). Most procedures occurred in the South (42.5%, n=177,509) or the Midwest (27.0%, n=112,758) regions. In the multiple regression analysis, increased hospital competitive intensity was associated with an increased total complication rate (odds ratio [OR] 1.52, p<.0001), device-related complications (OR 1.46, p=.0294), genitourinary complications (OR 2.15, p=.0091), infection (OR 3.48, p<.0001), neurologic complications (OR 1.69, p=.0422), total charges (+29%, p=.0034), and inpatient hospital length of stay (LOS) (+16%, p=.0012). The likelihood of complications at state-owned hospitals (OR 2.81, p=.0001) was more highly associated with HHI than at private, non-profit hospitals (OR 1.39, p=.0050). The occurrence of complications at urban teaching hospitals (OR 2.14, p<.0001) was generally more associated with HHI than at urban non-teaching hospitals (OR 1.19, p=.2457).Increased interhospital competitive intensity is associated with increased odds of complications, increased total charges, and prolonged LOS following lumbar spine fusion. These differences are generally highest among state-owned and urban teaching hospitals. Differences in outcome related to hospital competition may be due to suboptimal resource allocation. Identifying differences in perioperative outcomes associated with hospital market competition is important in the contemporary environment of health care reimbursement reform and hospital consolidation. Perioperative outcome disparities between highly competitive and minimally competitive areas should be monitored and further studied.
View details for DOI 10.1016/j.spinee.2017.08.256
View details for PubMedID 28882522
Medical Crowdfunding for Patients Undergoing Orthopedic Surgery.
2018; 41 (1): e58–e63
Crowdfunding for medical expenses is growing in popularity. Through several websites, patients create public campaign profiles to which donors can contribute. Research on medical crowdfunding is limited, and there have been no studies of crowdfunding in orthopedics. Active medical crowdfunding campaigns for orthopedic trauma, total joint arthroplasty, and spine surgery were queried from a crowdfunding website. The characteristics and outcomes of crowdfunding campaigns were abstracted and analyzed. For this study, 444 campaigns were analyzed, raising a total of $1,443,528. Among the campaigns that received a donation, mean amount raised was $4414 (SE, $611). Multivariate analysis showed that campaigns with unspecified location (odds ratio, 0.26; P=.0008 vs West) and those for total joint arthroplasty (odds ratio, 0.35; P=.0003 vs trauma) had significantly lower odds of receipt of any donation. Description length was associated with higher odds of donation receipt (odds ratio, 1.13 per +100 characters; P<.0001). Among campaigns that received any donation, those with Southern location (-65.5%, P<.0001), international location (-68.5%, P=.0028), and unspecified location (-63.5%, P=.0039) raised lower amounts compared with campaigns in the West. Goal amount was associated with higher amount raised (+3.2% per +$1000, P<.0001). Resources obtained through crowdfunding may be disproportionately available to patients with specific diagnoses, those from specific regions, those who are able to craft a lengthy descriptive narrative, and those with access to robust digital social networks. Clinicians are likely to see a greater proportion of patients turning to crowdfunding as it grows in popularity. Patients may ask physicians for information about crowdfunding or request testimonials to support campaigns. Surgeons should consider their response to such requests individually. These findings shed light on the dynamics of medical crowdfunding and support robust personal and professional deliberation. [Orthopedics. 2018; 41(1):e58-e63.].
View details for DOI 10.3928/01477447-20171114-04
View details for PubMedID 29156070
Give me a SINE: how Selective Inhibitors of Nuclear Export modulate autophagy and aging.
Molecular & cellular oncology
2018; 5 (5): e1502511
Autophagy is a cellular recycling process leading to lysosomal degradation of damaged macromolecules, which can protect cells against aging. The transcription factor EB (TFEB), a major transcriptional regulator of genes involved in autophagy and lysosomal function, is emerging as an attractive target for pharmacological modulation. Recently, we demonstrated that inhibiting the function of nuclear export protein exportin 1 (XPO1 or CRM1) with RNAi or with selective inhibitors of nuclear export (SINE) results in the nuclear enrichment of TFEB and enhancement of autophagy in model organisms and human cells. In addition to current efforts to validate the use of SINE in cancer therapies, our work highlights the potential benefits of these drugs toward improving outcomes in neurodegenerative diseases and aging.
View details for DOI 10.1080/23723556.2018.1502511
View details for PubMedID 30263946
View details for PubMedCentralID PMC6154834