- Orthopaedic Surgery
Clinical Instructor, Orthopaedic Surgery
Honors & Awards
Russell Wilson Award for Most Outstanding Basic Science Research, Hospital for Special Surgery (2019)
Thomas Sculco Award for Professional Collaboration, Hospital for Special Surgery (Selected by Operating Room and Nursing Staff) (2019)
Distinguished Housestaff Award (Most Outstanding Resident of Graduating Class), Hospital for Special Surgery (Selected by Faculty) (2018)
Danckwerts-Pergamon Prize (Best PhD Thesis of Department), Chemical Engineering & Biotechnology Department at Cambridge University (2009)
Marshall Scholar, Marshall Aid Commemoration Commission (United Kingdom) (2006)
President’s Medalist (Valedictorian), University of Washington, University of Washington (2006)
Residency: Hospital for Special Surgery Orthopaedic Surgery Residency (2019) NY
Medical Education: Harvard Medical School (2014) MA
PhD, University of Cambridge, Chemical Engineering and Biotechnology (2009)
BS, University of Washington, Neurobiology, Biochemistry (2006)
Current Research and Scholarly Interests
My research interests are in the evaluation of biomaterials for modelling of spine related physiology and clinical use. I also have an interest in global health, specifically worldwide accessibility of spine care in low resource regions.
Patient Factors Affecting Emergency Department Utilization and Hospital Readmission Rates After Primary Anterior Cervical Discectomy and Fusion: A Review of 41,813 cases.
2019; 44 (15): 1078–86
Retrospective database analysis.To identify preoperative risk factors for emergency department (ED) visit and unplanned hospital readmission after primary anterior cervical discectomy and fusion (ACDF) at 30 and 90 days.Limited data exist to identify factors associated with ED visit or readmission after primary ACDF within the first 3 months following surgery.Patients undergoing ACDF from 2005 to 2012 were identified in the Statewide Planning and Research Cooperative System database. Multivariable regression models were created based on patient-level and surgical characteristics to identify independent risk factors for hospital revisit.Of 41,813 patients identified, 2514 (6.0%) returned to the ED within 30 days of discharge. Risk factors included age < 35, black race (OR 1.19), Charlson Comorbidity index score > 1, length of stay (LOS) greater than 1 day (OR 1.23), and fusion of > 2 levels (OR 1.17). Four thousand six hundred nine (11.0%) patients returned to the ED within 90 days. Risk factors mirrored those at 30 days. Patients having private insurance or those discharged to rehab were less likely to present to the ED. One thousand three hundred ninety-four (3.3%) patients were readmitted by 30 days. Risk factors included male sex, Medicare, or Medicaid insurance (OR 1.71 and 1.79 respectively), Charlson comorbidity index > 1, discharge to a skilled nursing facility (OR 2.90), infectious/pathologic (OR 3.296), or traumatic (OR 1.409) surgical indication, LOS > 1 day (OR 1.66), or in-hospital complication. 2223 (5.3%) patients were readmitted by 90 days. Risk factors mirrored those at 30 days. No differences in readmission were seen based on race or number of levels fused. Patients aged 18 to 34 were less likely to be readmitted versus patients older than 35.Insurance status, comorbidities, and LOS consistently predicted an unplanned hospital visit at 30 and 90 days. Although nondegenerative surgical indications and in-hospital complications did not predict ED visits, these factors increased the risk for readmission.3.
View details for DOI 10.1097/BRS.0000000000003058
View details for PubMedID 30973509
Discharge to inpatient facilities after lumbar fusion surgery is associated with increased postoperative venous thromboembolism and readmissions.
The spine journal : official journal of the North American Spine Society
2019; 19 (3): 430–36
Postdischarge care is a significant source of cost variability after posterior lumbar fusion surgery. However, there remains limited evidence associating postdischarge inpatient services and improved postoperative outcomes, despite the high cost of these services.To determine the association between posthospital discharge to inpatient care facilities and postoperative complications.A retrospective review of all 1- to 3-level primary posterior lumbar fusion cases in the 2010-2014 National Surgical Quality Improvement Program registry was conducted. Propensity scores for discharge destination were determined based on observable baseline patient characteristics. Multivariable propensity-adjusted logistic regressions were performed to determine associations between discharge destination and postdischarge complications, with adjusted odds ratios (OR) and 95% confidence intervals (CI).A total of 18,652 posterior lumbar fusion cases were identified, 15,234 (82%) were discharged home, and 3,418 (18%) were discharged to continued inpatient care. Multivariable propensity-adjusted analysis demonstrated that being discharged to inpatient facilities was independently associated with higher risk of thromboembolic complications (OR [95% CI]: 1.79 [1.13-2.85]), urinary complications, (1.79 [1.27-2.51]), and unplanned readmissions (1.43 [1.22-1.68]).Discharge to continued inpatient care versus home after primary posterior lumbar fusion is independently associated with higher odds of certain major complications. To optimize clinical outcomes as well as cost savings in an era of value-based reimbursements, clinicians and hospitals should consider further investigation into carefully investigating which patients might be better served by home discharge after surgery.
View details for DOI 10.1016/j.spinee.2018.05.044
View details for PubMedID 29864544
Consortium of Orthopaedic Academic Traumatologists: A Model for Collaboration in Orthopaedic Surgery.
Journal of orthopaedic trauma
2018; 32 Suppl 7: S3–S7
In March 2016, North American academic leaders with an interest in and commitment to the field of global orthopaedics met in Orlando, Florida, to gauge each institution's clinical, research, and educational programs in developing countries, establish the main limitations to participating in global health efforts, and assess areas of need for both the participating institutions and their international partners. After this inaugural meeting, a needs assessment survey was distributed to the group to better understand how to organize and unify the individual institutional global efforts. The results revealed that surgeons believed there was a vital need for improved communication, mentorship, and infrastructural support between North American universities. To this end, the Consortium of Orthopaedic Academic Traumatologists (COACT) was founded. The COACT seeks to promote a novel framework geared toward improving trauma care capacity by building collaborative partnerships among leading academic centers across the United States and Canada. The consortium represents a comprehensive partnership that promotes communication, collaboration, and advocacy through a central network to facilitate investigative, educational, and clinical services. Academic partners share best practices, resources, and opportunities in their international outreach projects in low- and middle-income countries in the field of orthopaedic trauma. Over the course of the past 2 years, the COACT has grown to more than 80 faculty, fellow, resident, and student members, representing over 20 orthopaedic institutions across North America.
View details for DOI 10.1097/BOT.0000000000001288
View details for PubMedID 30247390
Field evaluation of a prototype paper-based point-of-care fingerstick transaminase test.
2013; 8 (9): e75616
Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically-defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading-obtained in a target clinical environment, as performed by local practitioners-indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes.
View details for DOI 10.1371/journal.pone.0075616
View details for PubMedID 24098705
View details for PubMedCentralID PMC3787037
Endosomolytic anionic polymer for the cytoplasmic delivery of siRNAs in localized in vivo applications.
Advanced functional materials
2013; 23 (5)
The use of small interfering RNAs (siRNAs) to down-regulate the expression of disease-associated proteins carries significant promise for the treatment of a variety of clinical disorders. One of the main barriers to the widespread clinical use of siRNAs, however, is their entrapment and degradation within the endolysosomal pathway of target cells. Here we report the trafficking and function of PP75, a non-toxic, biodegradable, lipid membrane disruptive anionic polymer composed of phenylalanine derivatized poly(L-lysine iso-phthalamide). PP75 is readily endocytosed by cells, safely permeabilizes endolysosomes in a pH dependent manner and facilitates the transfer of co-endocytosed materials directly into the cytoplasm. The covalent attachment of siRNAs to PP75 using disulfide linkages generates conjugates that effectively traffic siRNAs to the cytoplasm of target cells both in vitro and in vivo. In a subcutaneous malignant glioma tumor model, a locally delivered PP75-stathmin siRNA conjugate decreases stathmin expression in tumor cells and, in combination with the nitrosourea chemotherapy carmustine, is highly effective at inhibiting tumor growth. PP75 may be clinically useful for the local delivery of siRNAs, in particular for the treatment of solid tumors.
View details for DOI 10.1002/adfm.201201945
View details for PubMedID 24273480
View details for PubMedCentralID PMC3834980
Optimizing siRNA efficacy through alteration in the target cell-adhesion substrate interaction.
Journal of biomedical materials research. Part A
2012; 100 (10): 2637–43
The clinical potential of short interfering RNA (siRNA) based therapeutics remains hindered by the challenge of delivering enough siRNA into the cytoplasm to yield a clinically relevant effect. Although much research has focused on optimizing delivery vehicles for this class of molecules, considerably less is known about the microenvironmental influences on the response of target cells to siRNA. The substrate to which cells adhere is one component of the microenvironment that can modulate cellular behavior. Here, we tested the hypothesis that modulating the properties of cellular adhesion substrates can alter siRNA efficacy. Specifically, cationic lipid complexed siRNA particles were applied to U251 cells seeded on alginate hydrogel surfaces with systematic variation in elastic modulus and integrin ligand arginine-glycine-aspartate (RGD) peptide density. These experiments revealed no change in siRNA-mediated eGFP knockdown over the elastic modulus range tested (53-133 kPa). However, an eightfold increase in RGD content of the alginate growth substrate resulted in an increase in siRNA knockdown efficacy from 25 ± 12% to 52 ± 10%, a more than twofold increase in silencing. Our results identify control of the cell-adhesion substrate interaction as a modulator of siRNA protein silencing efficacy.
View details for DOI 10.1002/jbm.a.34202
View details for PubMedID 22615234
View details for PubMedCentralID PMC3685857
The influence of aromatic side-chains on the aqueous properties of pH-sensitive poly(L-lysine iso-phthalamide) derivatives.
Journal of biomaterials science. Polymer edition
2010; 21 (12): 1573–88
The endosomal membrane has proven to be a challenging barrier for the delivery of therapeutic biomacromolecules, including DNA, siRNA and proteins, which are taken up by endosomes but cannot freely diffuse across lipid bilayers. Anionic polymers that undergo conformational changes and become membrane disruptive in low-pH environments have the potential to assist in the delivery of these biomacromolecules across the endosomal membrane to the cytosol. Such endosomolytic polymers have been synthesized through the grafting of hydrophobic side-chains to a poly(L-lysine iso-phthalamide) backbone. The phenylalanine grafted form of poly(L-lysine iso-phthalamide) has a pH-sensitive membrane disruptive profile corresponding to the pH range of maturing endosomes and, thus, has a favourable endosomolytic profile. In order to understand the influence of hydrophobicity versus pi-pi interactions mediated by aromatic rings, a tyrosine grafted form of poly(L-lysine iso-phthalamide) was synthesized and its aqueous pH-sensitive properties, cytotoxicity and endosomal disruptive capacity were compared to phenylalanine-grafted poly(L-lysine iso-phthalamide). The similarity between these two polymers' properties, despite the large difference in hydrophobicity between their side-chains, supports the conclusion that the aromatic character of sidechains in poly(L-lysine iso-phthalamide) is an important property, as opposed to hydrophobicity alone, in determining the effectiveness of acidic pH triggered endosomolysis.
View details for DOI 10.1163/092050609X12519805626194
View details for PubMedID 20537242
The role of hydrophobic amino acid grafts in the enhancement of membrane-disruptive activity of pH-responsive pseudo-peptides.
2009; 30 (10): 1954–61
pH-responsive polymers have been synthesised by grafting l-valine (PV-75), l-leucine (PL-75) and l-phenylalanine (PP-75) onto the pendant carboxylic acid moieties of a pseudo-peptide, poly(l-lysine iso-phthalamide), at a stoichiometric degree of substitution of 75 mol%. The effect of such modification on the pH-, concentration- and time-dependent cell membrane-disruptive activity of the grafted polymers has been investigated using a haemolysis model. At 0.025 mg mL(-1), the grafted polymers were almost non-haemolytic at pH 7.4, but mediated considerable membrane lysis after 60 min in the pH range characteristic of early endosomes, which ranked in the order: PP-75 > PL-75 > PV-75 > poly(l-lysine iso-phthalamide). PP-75 was 35-fold more lytic on a molar basis than the membrane-lytic peptide melittin. With increasing concentration, the grafted polymers showed an increased ability to lyse cell membranes and caused noticeable membrane disruption at physiological pH. The mechanism of the polymer-mediated membrane destabilisation has been investigated. The in-vitro cytotoxicity of the grafted polymers has been assessed using a propidium iodide fluorescence assay. It has been demonstrated by confocal microscopy that the grafted polymers can induce a significant release of endocytosed materials into the cytoplasm of HeLa cells, which is a feature critical for drug delivery applications.
View details for DOI 10.1016/j.biomaterials.2008.12.036
View details for PubMedID 19138797
View details for PubMedCentralID PMC3038271
Effect of L-leucine graft content on aqueous solution behavior and membrane-lytic activity of a pH-responsive pseudopeptide.
2009; 10 (9): 2601–8
A series of pH-responsive polymers have been synthesized by grafting L-leucine onto the pendant carboxylic acid groups of the linear pseudopeptide, poly(L-lysine iso-phthalamide). The effect of the degree of grafting on aqueous solution properties, cell membrane-disruptive activity, and in vitro cytotoxicity was examined by UV-visible and fluorescence spectroscopy, hemolysis, alamar blue staining, and propidium iodide fluorescence assays. Modification of poly(L-lysine iso-phthalamide) with < or =23.6 mol % L-leucine caused a marginal effect on the pH-mediated hydrophobic association and hemolytic activity. Increasing the degree of grafting from 31.9 to 61.2 mol % resulted in polymers with progressively enhanced hydrophobic association and cell membrane disruption, thus confirming that the pH responsiveness and the extent of hydrophobic association and membrane disruption of the polymers can be modulated by varying the degree of grafting with hydrophobic amino acids. The pH responses were demonstrated to be concentration-dependent. At certain degrees of leucine grafting, the polymers were nonmembrane-lytic at physiological pH but mediated considerable membrane lysis at endosomal pH values (5.0-6.8), a feature critical for potential drug delivery applications.
View details for DOI 10.1021/bm900534j
View details for PubMedID 19642668