Publications by authors named "Matthew Cunningham"

102 Publications

Accounting for misclassified and unknown cause of death data in vital registration systems for estimating trends in HIV mortality.

J Int AIDS Soc 2021 09;24 Suppl 5:e25791

Institute for Health Metrics and Evaluation, Seattle, Washington, USA.

Introduction: Misclassification of HIV deaths can substantially diminish the usefulness of cause of death data for decision-making. In this study, we describe the methods developed by the Global Burden of Disease Study to account for the misclassified cause of death data from vital registration systems for estimating HIV mortality in 132 countries and territories.

Methods: The cause of death data were obtained from the World Health Organization Mortality Database and official country-specific mortality databases. We implemented two steps to adjust the raw cause of death data: (1) redistributing garbage codes to underlying causes of death, including HIV/AIDS by applying methods, such as analysis of multiple cause data and proportional redistribution, and (2) reassigning HIV deaths misclassified as other causes to HIV/AIDS by examining the age patterns of underlying causes in location and years with and without HIV epidemics.

Results: In 132 countries, during the period from 1990 to 2018, 1,848,761 deaths were reported as caused by HIV/AIDS. After garbage code redistribution in these 132 countries, this number increased to 4,165,015 deaths. An additional 1,944,291 deaths were added through correction of HIV deaths misclassified as other causes in 44 countries. The proportion of HIV deaths derived from garbage code redistribution decreased over time, from 0.4 in 1990 to 0.1 in 2018. The proportion of deaths derived from HIV misclassification correction peaked at 0.4 in 2006 and declined afterwards to 0.08 in 2018. The greatest contributors to garbage code redistribution were "immunodeficiency antibody" (ICD 9: 279-279.1; ICD 10: D80-D80.9) and "immunodeficiency other" (ICD 9: 279, 279.5-279.9; ICD 10: D83-D84.9, D89, D89.8-D89.9), which together contributed 77% of all redistributed deaths at their peak in 1995. Respiratory tuberculosis (ICD 9: 010-012.9; ICD 10: A10-A14, A15-A16.9) contributed the greatest proportion of all HIV misclassified deaths (25-62% per year) over the most years.

Conclusions: Correcting for miscoding and misclassification of cause of death data can enhance the utility of the data for analyzing trends in HIV mortality and tracking progress toward the Sustainable Development Goal targets.
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http://dx.doi.org/10.1002/jia2.25791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454675PMC
September 2021

Prevalence of Cannabidiol Use in Patients With Spine Complaints: Results of an Anonymous Survey.

Int J Spine Surg 2021 Aug 20;15(4):663-668. Epub 2021 Jul 20.

Hospital for Special Surgery, Spine Service, New York, New York.

Background: Cannabidiol (CBD) is a cannabis derivative that has been popularized as a medicinal product with analgesic and anti-inflammatory effects. Given the anecdotal observations that several patients have reported use of CBD for spine-related pain, this study was designed to characterize CBD consumption patterns and perceived effects in patients with spine-related complaints.

Methods: The study design was a cross-sectional survey. Over a 4-week period, an anonymous paper survey was administered to all patients presenting for evaluation by 1 of 9 spine surgeons at a single institution. Surveys were given upon registration for the office visit and collected by the office manager or nurse before evaluation by the surgeon. Patients were included regardless of surgical status (ie, preoperative, postoperative, or nonoperative) or region of pathology (lumbar, thoracic, or cervical). The survey consisted of multiple-choice questions on patient patterns of CBD use.

Results: Out of 300 surveys, 214 (71%) were completed. CBD use for spine-related pain was reported by 54 (25.2%) patients. CBD was initially used for potential relief of back pain (66.7%), neck pain (37.0%), leg pain (35.2%), and/or arm pain (9.3%). Users also sought improvements in insomnia (25.9%) and mood (18.5%). Oil was the most popular formulation (64.8%). CBD was most often consumed 2-5 times (40.7%) or 6-10 times (31.5%) per week. The most common source of initial recommendation for CBD was friends or family (75.9%). Reported benefits were pain relief (46.3%), improved sleep (33.3%), and reduced anxiety (20.4%); however, 24.1% of patients reported no benefit from CBD use. The most reported side effect was fatigue (7.4%). Most users (63.0%) would recommend CBD to a friend for pain relief.

Conclusion: CBD is already used by many patients, and further high-quality research on this supplement is essential.

Level Of Evidence: 4.

Clinical Relevance: CBD is a commonly used by spine patients as an off label treatment.
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http://dx.doi.org/10.14444/8087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375682PMC
August 2021

Public health utility of cause of death data: applying empirical algorithms to improve data quality.

BMC Med Inform Decis Mak 2021 06 2;21(1):175. Epub 2021 Jun 2.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

Background: Accurate, comprehensive, cause-specific mortality estimates are crucial for informing public health decision making worldwide. Incorrectly or vaguely assigned deaths, defined as garbage-coded deaths, mask the true cause distribution. The Global Burden of Disease (GBD) study has developed methods to create comparable, timely, cause-specific mortality estimates; an impactful data processing method is the reallocation of garbage-coded deaths to a plausible underlying cause of death. We identify the pattern of garbage-coded deaths in the world and present the methods used to determine their redistribution to generate more plausible cause of death assignments.

Methods: We describe the methods developed for the GBD 2019 study and subsequent iterations to redistribute garbage-coded deaths in vital registration data to plausible underlying causes. These methods include analysis of multiple cause data, negative correlation, impairment, and proportional redistribution. We classify garbage codes into classes according to the level of specificity of the reported cause of death (CoD) and capture trends in the global pattern of proportion of garbage-coded deaths, disaggregated by these classes, and the relationship between this proportion and the Socio-Demographic Index. We examine the relative importance of the top four garbage codes by age and sex and demonstrate the impact of redistribution on the annual GBD CoD rankings.

Results: The proportion of least-specific (class 1 and 2) garbage-coded deaths ranged from 3.7% of all vital registration deaths to 67.3% in 2015, and the age-standardized proportion had an overall negative association with the Socio-Demographic Index. When broken down by age and sex, the category for unspecified lower respiratory infections was responsible for nearly 30% of garbage-coded deaths in those under 1 year of age for both sexes, representing the largest proportion of garbage codes for that age group. We show how the cause distribution by number of deaths changes before and after redistribution for four countries: Brazil, the United States, Japan, and France, highlighting the necessity of accounting for garbage-coded deaths in the GBD.

Conclusions: We provide a detailed description of redistribution methods developed for CoD data in the GBD; these methods represent an overall improvement in empiricism compared to past reliance on a priori knowledge.
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http://dx.doi.org/10.1186/s12911-021-01501-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170729PMC
June 2021

Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1.

Sci Rep 2021 04 15;11(1):8271. Epub 2021 Apr 15.

HSS Research Institute, Hospital for Special Surgery, 515 E 71st Street, New York, NY, 10021, USA.

Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.
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http://dx.doi.org/10.1038/s41598-021-87665-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050288PMC
April 2021

University of Washington School of Medicine.

Acad Med 2020 Sep;95(9S A Snapshot of Medical Student Education in the United States and Canada: Reports From 145 Schools):S542-S546

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http://dx.doi.org/10.1097/ACM.0000000000003455DOI Listing
September 2020

Patients with abnormal microarchitecture have an increased risk of early complications after spinal fusion surgery.

Bone 2021 02 4;143:115731. Epub 2020 Nov 4.

Endocrinology and Metabolic Bone Disease Service, Hospital for Special Surgery, New York, NY, United States of America. Electronic address:

Spine fusion is one of the most common orthopedic surgeries, with more than 400,000 cases performed annually. While these procedures correct debilitating pain and deformities, complications occur in up to 45%. As successful fusion rests upon early stability of hardware in bone, patients with structural skeletal deficits may be at particular risk for complications. Few studies have investigated this relationship, and none have used higher order imaging to evaluate microstructural mechanisms for complications. Standard DXA measurements are subject to artifact in patients with spinal disease and therefore provide limited information. The goal of this prospective study was to investigate pre-operative bone quality as a risk factor for early post-operative complications using high resolution peripheral QCT (HR-pQCT) measurements of volumetric BMD (vBMD) and microarchitecture. We hypothesized that patients with low vBMD and abnormal microarchitecture at baseline would have more skeletal complications post-operatively. Conversely, we hypothesized that pre-operative DXA measurements would not be predictive of complications. Fifty-four subjects (mean age 63 years, BMI 27 kg/m) were enrolled pre-operatively and followed for 6 months after multi-level lumbar spine fusion. Skeletal complications occurred in 14 patients. Patients who developed complications were of similar age and BMI to those who did not. Baseline areal BMD and Trabecular Bone Score by DXA did not differ. In contrast, HR-pQCT revealed that patients who developed complications had lower trabecular vBMD, fewer and thinner trabeculae at both the radius and tibia, and thinner tibial cortices. In summary, abnormalities of both trabecular and cortical microarchitecture were associated the development of complications within the first six months following spine fusion surgery. Our results suggest a mechanism for early skeletal complications after fusion. Given the burgeoning number of fusion surgeries, further studies are necessary to investigate strategies that may improve bone quality and lower the risk of post-operative complications.
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http://dx.doi.org/10.1016/j.bone.2020.115731DOI Listing
February 2021

Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers.

Clin Exp Allergy 2020 12 4;50(12):1391-1399. Epub 2020 Oct 4.

Institute of Infection, Immunity and Inflammation, Glasgow University, Glasgow, UK.

Background: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP.

Objective: To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP.

Methods: Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production.

Results: KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P = .01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P < .001. KL-6 correlated with IgG antibody titre in those with symptoms, r = .591, P = .006. High KL-6, irrespective of symptom category, was associated with higher antibody (P = .006) and lymphocyte proliferation (P = .041), and lower CD4+ T lymphocyte proportion (P = .032).

Conclusion And Clinical Relevance: Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.
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http://dx.doi.org/10.1111/cea.13744DOI Listing
December 2020

Slippery liquid infused fluoropolymer coating for central lines to reduce catheter associated clotting and infections.

Sci Rep 2020 09 11;10(1):14973. Epub 2020 Sep 11.

FreeFlow Medical Devices LLC, Lancaster, PA, USA.

Thrombosis and infections are two grave, interrelated problems associated with the use of central venous catheters (CVL). Currently used antibiotic coated CVL has limited clinical success in resisting blood stream infection and may increase the risk of emerging antibiotic resistant strains. We report an antibiotic-free, fluoropolymer-immobilized, liquid perfluorocarbon-coated peripherally inserted central catheter (PICC) line and its effectiveness in reducing catheter associated thrombosis and pathogen colonization, as an alternative to antibiotic coated CVL. Commercially available polyurethane PICC catheter was modified by a three-step lamination process, with thin fluoropolymer layers to yield fluoropolymer-polyurethane-fluoropolymer composite structure before applying the liquid perfluorocarbon (LP). This high throughput process of modifying commercial PICC catheters with fluoropolymer is quicker, safer and shows higher thromboresistance than fluorinated, omniphobic catheter surfaces, produced by previously reported self-assembled monolayer deposition techniques. The LP immobilized on the fluoropolymer is highly durable in physiological flow conditions for over 60 days and continue to resist Staphylococcus colonization.
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http://dx.doi.org/10.1038/s41598-020-71711-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486915PMC
September 2020

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

Inj Prev 2020 10 24;26(Supp 1):i125-i153. Epub 2020 Aug 24.

Department of Pharmacy, Adigrat University, Adigrat, Ethiopia.

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria.

Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced.

Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes.

Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
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http://dx.doi.org/10.1136/injuryprev-2019-043531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571362PMC
October 2020

New Strategies in Enhancing Spinal Fusion.

HSS J 2020 Jul 2;16(2):177-182. Epub 2020 Feb 2.

Department of Orthopedic Surgery, Hospital for Special Surgery, 535 E. 70th St, New York, NY 10021 USA.

The biologic steps involved in creating a bony fusion between adjacent segments of the spine are a complex and highly coordinated series of events. There have been significant advancements in bone grafts and bone graft substitutes in order to augment spinal fusion. While autologous bone grafting remains the gold standard, allograft bone grafting, synthetic bone graft substitutes, and bone graft enhancers are appropriate in certain clinical situations. This article provides an overview of the basic biology of spinal fusion and strategies for enhancing fusion through innovations in bone graft material.
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http://dx.doi.org/10.1007/s11420-020-09749-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253544PMC
July 2020

Unintentional injuries in Mexico, 1990-2017: findings from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 1;26(Supp 1):i154-i161. Epub 2020 Apr 1.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

Background: To date, the burden of injury in Mexico has not been comprehensively assessed using recent advances in population health research, including those in the Global Burden of Disease Study 2017 (GBD 2017).

Methods: We used GBD 2017 for burden of unintentional injury estimates, including transport injuries, for Mexico and each state in Mexico from 1990 to 2017. We examined subnational variation, age patterns, sex differences and time trends for all injury burden metrics.

Results: Unintentional injury deaths in Mexico decreased from 45 363 deaths (44 662 to 46 038) in 1990 to 42 702 (41 439 to 43 745) in 2017, while age-standardised mortality rates decreased from 65.2 (64.4 to 66.1) in 1990 to 35.1 (34.1 to 36.0) per 100 000 in 2017. In terms of non-fatal outcomes, there were 3 120 211 (2 879 993 to 3 377 945) new injury cases in 1990, which increased to 5 234 214 (4 812 615 to 5 701 669) new cases of injury in 2017. We estimated 2 761 957 (2 676 267 to 2 859 777) disability-adjusted life years (DALYs) due to injuries in Mexico in 1990 compared with 2 376 952 (2 224 588 to 2 551 004) DALYs in 2017. We found subnational variation in health loss across Mexico's states, including concentrated burden in Tabasco, Chihuahua and Zacatecas.

Conclusions: In Mexico, from 1990 to 2017, mortality due to unintentional injuries has decreased, while non-fatal incident cases have increased. However, unintentional injuries continue to cause considerable mortality and morbidity, with patterns that vary by state, age, sex and year. Future research should focus on targeted interventions to decrease injury burden in high-risk populations.
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http://dx.doi.org/10.1136/injuryprev-2019-043532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571365PMC
October 2020

Erratum to Incidence and Risk Factors for Major Surgical Complications in Patients With Complex Spinal Deformity: A Report From an SRS GOP Site [Spine Deformity 3 (2015) 57-64].

Spine Deform 2019 Mar;7(2):377

Spine and Scoliosis Surgery, Hospital for Special Surgery, 535 E. 70th Street, New York, NY, 10021, USA.

The corresponding author regret that co-author name was incorrectly published as "Elias C. Papadopoulus" in the article. The correct name of the author should be displayed as "Elias C. Papadopoulos".
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http://dx.doi.org/10.1016/j.jspd.2018.11.011DOI Listing
March 2019

Erratum to Surgical Risk Stratification Based on Preoperative Risk Factors in Severe Pediatric Spinal Deformity Surgery [Spine Deformity 2 (2014) 340-349].

Spine Deform 2019 Mar;7(2):378

Adult and Pediatric Spine and Scoliosis Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.

The corresponding author regret that co-author name was incorrectly published as "Elias C. Papadopoulus" in the article. The correct name of the author should be displayed as "Elias C. Papadopoulos".
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http://dx.doi.org/10.1016/j.jspd.2018.11.010DOI Listing
March 2019

The Scope Of Three-Dimensional Digital Visualization Systems In Vitreoretinal Surgery.

Clin Ophthalmol 2019 24;13:2093-2096. Epub 2019 Oct 24.

Florida Retina Institute, Orlando, FL, USA.

Introduction: Significant advances in three-dimensional (3D) imaging technology have allowed for the incorporation of 3D digital displays into medical and surgical devices. Despite initial adoption of the NGENUITY 3D Visualization System in vitreoretinal surgery, there are limited publications regarding its use. The generally accepted main benefits include improved ergonomics, enhanced surgical team communication and education, reduced retinal phototoxicity, increased depth of field, and display image manipulation. Despite these potential benefits, many retina specialists have questioned its universal applicability to a wide variety of vitreoretinal surgeries.

Objective: To report on the variety of indications and surgical efficacy of the NGENUITY 3D Visualization System in vitreoretinal surgery via a review of surgical experience at two vitreoretinal practices in both the academic and community settings.

Methods: A retrospective review was conducted of consecutive surgical cases performed on the NGENUITY 3D Visualization System at Massachusetts Eye and Ear Infirmary and Florida Retina Institute from June 1st, 2017 to November 1st, 2018. Age, presenting diagnosis, surgical procedure, and intraoperative details were recorded.

Results: 272 vitreoretinal surgeries on the Alcon NGENUITY 3D Visualization System were identified between June 1st, 2017 and November 1st, 2018 at the participating institutions. A detailed breakdown of the indications for surgery and related procedures is reported. During all 272 cases on the 3D digital system, there were no complications attributed to the visualization system.

Conclusion: This series illustrates the diversity of vitreoretinal surgeries that can be performed on this system without compromising surgical viewing or increasing surgical complications. The Alcon NGENUITY 3D Visualization System possesses favorable ergonomics, illumination levels, depth of field, display filters, and trainee experience.
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http://dx.doi.org/10.2147/OPTH.S213834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818135PMC
October 2019

Locally Applied Simvastatin as an Adjunct to Promote Spinal Fusion in Rats.

Spine (Phila Pa 1976) 2019 Aug;44(15):1042-1048

Hospital for Special Surgery, New York, NY.

Study Design: Basic Science.

Objective: To determine if locally delivered simvastatin can enhance bone formation in a rat spinal fusion model.

Summary Of Background Data: The bone-anabolic properties of statins in fracture healing are well established, however, few studies have evaluated the impact of locally delivered statins in spinal fusion.

Methods: We formulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles by adapting previously published techniques. Two types of nanoparticles were created: simvastatin nanoparticles (SimNP) and nanoparticles without simvastatin (BlankNP). Drug elution from SimNP was characterized. Osteoblastic differentiation was analyzed using MC3T3-E1 cells cultured in differentiation medium containing SimNP or BlankNP. Forty male 12 week old outbred Wistar rats underwent uninstrumented posterolateral fusion using iliac crest bone graft and BlankNP, SimNP or simvastatin drug. X-rays to assess bone formation were obtained at 4 weeks and 9 weeks post-operatively. Spines were explanted at 9 weeks for micro-CT analysis, and a blinded manual assessment of fusion (MAF).

Results: SimNP achieved a release efficiency of 74.1% with ∼50% release occurring in the first day. Simvastatin and SimNP treated cells showed significantly greater expression of osteopontin (OPN) and osteocalcin (OCN). On micro-CT analysis, SimNP animals had higher bone volume and percent bone volume (bone volume/total volume) than control animals. SimNP rats had higher X-ray scores at 4 weeks (p=0.010) and 9 weeks (p<0.001) relative to BlankNP. MAF showed that SimNP had a higher fusion rate than BlankNP (42.9% vs. 0%, p=0.006).

Conclusion: We were able to validate that sustained release of simvastatin via a PLGA nanoparticle. SimNP was able to induce an increase in mineralization as well as an increase in markers of bone formation. X-ray analysis, micro-CT quantification, and MAF assessment of SimNP treated rats showed significantly greater bone formation and fusion mass strength relative to vehicle treated animals. Simvastatin may be a safe, cost-effective bone anabolic agent for use in spinal fusion.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000003020DOI Listing
August 2019

Additional Risk Factors for Adding-On After Selective Thoracic Fusion in Adolescent Idiopathic Scoliosis: Implication of Lowest Instrumented Vertebra Angle and Lumbosacral Takeoff.

Spine Deform 2018 Mar - Apr;6(2):164-169. Epub 2017 Oct 23.

FOCOS Orthopedic Hospital, 8 Teshie St, Pantang, Accra, Ghana.

Study Design: Retrospective chart and radiographic review.

Objective: The purpose of this study was to identify any additional risk factors adding-on after selective thoracic fusion in adolescent idiopathic scoliosis (AIS).

Summary Of Background Data: Previous studies have shown that the proper selection of lowest instrumented vertebra (LIV) is critical in preventing adding-on (AD) phenomenon after selective thoracic fusion (STF). However, even after selecting the correct LIV, AD can still occur.

Methods: This is a retrospective review of 380 consecutive AIS patients who underwent corrective surgery by a single surgeon. LIV was chosen as stable vertebra (SV) or SV-1 if intersected by the center sacral vertical line (CSVL). One hundred thirty-five patients were identified who had complete radiographic images stored in PACS. After Lenke 5, anterior or combined surgeries, TL fusion, and hybrid construct were excluded, two groups were identified out of 78 patients who received STF with all pedicle screw construct: Adding-on (AD) and Control. AD was defined as >5° angle of the superior endplate of LIV-1 to the inferior endplate of LIV+1 between postoperation and the final follow-up. We analyzed the values for the AD group and compared them with those for the control group to identify risk factors not previously defined.

Results: Patients with other complication and follow-up less than 2 years were excluded, and there remained 11 patients in AD (14%), and 8 in the control group. There was no significant difference between the 2 groups in terms of demographic data, LIV selection, and curve types. In AD, there was significant curve progression within fused segments. Even though lumbosacral takeoff (LSTO) was not significantly different, (LIV-H)+LSTO and LIV-H (LIV horizontal) showed significant difference.

Conclusion: After excluding the effect of known risk factors for AD, LIV-H angle, and LIV-H mismatch with LSTO were found to be the additional risk factors for AD. In addition to consideration of other risk factors such as LIV selection or Risser stage, these risk factors should be considered.
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http://dx.doi.org/10.1016/j.jspd.2017.08.008DOI Listing
December 2018

Building Consensus: Development of Best Practice Guidelines on Wrong Level Surgery in Spinal Deformity.

Spine Deform 2018 Mar - Apr;6(2):121-129. Epub 2017 Oct 18.

New York-Presbyterian The Allen Hospital, 5141 Broadway, New York, NY 10034, USA.

Study Design: Consensus-building using the Delphi and nominal group technique.

Objective: To establish best practice guidelines using formal techniques of consensus building among a group of experienced spinal deformity surgeons to avert wrong-level spinal deformity surgery.

Summary Of Background Data: Numerous previous studies have demonstrated that wrong-level spinal deformity occurs at a substantial rate, with more than half of all spine surgeons reporting direct or indirect experience operating on the wrong levels. Nevertheless, currently, guidelines to avert wrong-level spinal deformity surgery have not been developed.

Methods: The Delphi process and nominal group technique were used to formally derive consensus among 16 fellowship-trained spine surgeons. Surgeons were surveyed for current practices, presented with the results of a systematic review, and asked to vote anonymously for or against item inclusion during three iterative rounds. Agreement of 80% or higher was considered consensus. Items near consensus (70% to 80% agreement) were probed in detail using the nominal group technique in a facilitated group meeting.

Results: Participants had a mean of 13.4 years of practice (range: 2-32 years) and 103.1 (range: 50-250) annual spinal deformity surgeries, with a combined total of 24,200 procedures. Consensus was reached for the creation of best practice guidelines (BPGs) consisting of 17 interventions to avert wrong-level surgery. A final checklist consisting of preoperative and intraoperative methods, including standardized vertebral-level counting and optimal imaging criteria, was supported by 100% of participants.

Conclusion: We developed consensus-based best practice guidelines for the prevention of wrong-vertebral-level surgery. This can serve as a tool to reduce the variability in preoperative and intraoperative practices and guide research regarding the effectiveness of such interventions on the incidence of wrong-level surgery.

Level Of Evidence: Level V.
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http://dx.doi.org/10.1016/j.jspd.2017.08.005DOI Listing
December 2018

Independent and mentored video review of OSCEs.

Clin Teach 2019 02 5;16(1):23-29. Epub 2018 Jan 5.

Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, Washington, USA.

Background: Video review of OSCE (objective structured clinical examination) performance allows students to analyse their performance, identify actions and behaviours for correction or reinforcement, and develop a plan for improvement of clinical skills. Student perceptions of the utility of independent and mentored video review are unknown.

Methods: We created a pilot programme of post-OSCE structured video review. Students were randomised to mentored (M) or independent (I) review. In the mentored group, a faculty member facilitated the process. Both groups completed an assessment rubric and created an action plan. We examined student perceptions of the process, helpful elements of each type of review and perceived impact after a follow-up OSCE.

Results: The mentored group (n = 12) was more comfortable watching themselves than the independent group (n = 11); using a five-point Likert scale, where 1 indicates 'strongly disagree' and 5 indicates 'strongly agree': 3.5 ± 1.2 (I) versus 4.5 ± 0.2 (M) (p = 0.02). The mentored group more strongly agreed that their clinical skills would improve: 3.6 ± 1.1 (I) versus 4.9 ± 0.2 (M) (p < 0.01). After the follow-up OSCE, the mentored group (n = 10) tended to feel more strongly that their clinical skills had improved compared with the independent group (n = 9): 3.6 ± 1.3 (I) versus 4.3 ± 0.7 (M) (p = 0.14).

Discussion: This pilot study demonstrates the utility of using a structured framework for post-OSCE video review, both for the assessment of performance and for the development of a behavioural action plan. There are advantages to using a mentor-guided model, but further study is needed to determine whether actual OSCE performances improve as a consequence. Video review of OSCE performance allows students to analyse their performance.
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http://dx.doi.org/10.1111/tct.12755DOI Listing
February 2019

Arsenic exposure during embryonic development alters the expression of the long noncoding RNA growth arrest specific-5 (Gas5) in a sex-dependent manner.

Neurotoxicol Teratol 2018 Mar - Apr;66:102-112. Epub 2017 Nov 11.

Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States. Electronic address:

Our previous studies suggest that prenatal arsenic exposure (50ppb) modifies epigenetic control of the programming of the glucocorticoid receptor (GR) signaling system in the developing mouse brain. These deficits may lead to long-lasting consequences, including deficits in learning and memory, increased depressive-like behaviors, and an altered set-point of GR feedback throughout life. To understand the arsenic-induced changes within the GR system, we assessed the impact of in utero arsenic exposure on the levels of the GR and growth arrest-specific-5 (Gas5), a noncoding RNA, across a key gestational period for GR programming (gestational days, GD 14-18) in mice. Gas5 contains a glucocorticoid response element (GRE)-like sequence that binds the GR, thereby decreasing GR-GRE-dependent gene transcription and potentially altering GR programming. Prenatal arsenic exposure resulted in sex-dependent and age-dependent shifts in the levels of GR and Gas5 expression in fetal telencephalon. Nuclear GR levels were reduced in males, but unchanged in females, at all gestational time points tested. Total cellular Gas5 levels were lower in arsenic-exposed males with no changes seen in arsenic-exposed females at GD16 and 18. An increase in total cellular Gas-5 along with increased nuclear levels in GD14 arsenic-exposed females, suggests a differential regulation of cellular compartmentalization of Gas5. RIP assays revealed reduced Gas5 associated with the GR on GD14 in the nuclear fraction prepared from arsenic-exposed males and females. This decrease in levels of GR-Gas5 binding continued only in the females at GD18. Thus, nuclear GR signaling potential is decreased in prenatal arsenic-exposed males, while it is increased or maintained at levels approaching normal in prenatal arsenic-exposed females. These findings suggest that females, but not males, exposed to arsenic are able to regulate the levels of nuclear free GR by altering Gas5 levels, thereby keeping GR nuclear signaling closer to control (unexposed) levels.
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http://dx.doi.org/10.1016/j.ntt.2017.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856585PMC
January 2020

Treatment for Degenerative Lumbar Spondylolisthesis: Current Concepts and New Evidence.

Curr Rev Musculoskelet Med 2017 Dec;10(4):521-529

Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA.

Purpose Of Review: Current guidelines for the optimal treatment degenerative spondylolisthesis are weak and based on limited high-quality evidence.

Recent Findings: There is some moderate evidence that decompression alone may be a feasible treatment with lower surgical morbidity and similar outcomes to fusion when performed in a select population with a low-grade slip. Similarly, addition of interbody fusion may be best suited to a subset of patients with high-grade degenerative spondylolisthesis, although this remains controversial. Minimally invasive techniques are increasingly being utilized for both decompression and fusion surgeries with more and more studies showing similar outcomes and lower postoperative morbidity for patients. This will likely be an area of continued intense research. Finally, the role of spondylolisthesis reduction will likely be determined as further investigation into optimal sagittal balance and spinopelvic parameters is conducted. Future identification of ideal thresholds for sagittal vertical axis and slip angle that will prevent progression and reoperation will play an important role in surgical treatment planning. Current evidence supports surgical treatment of degenerative spondylolisthesis. While posterolateral spinal fusion remains the treatment of choice, the use of interbodies and decompressions without fusion may be efficacious in certain populations. However, additional high-quality evidence is needed, especially in newer areas of practice such as minimally invasive techniques and sagittal balance correction.
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http://dx.doi.org/10.1007/s12178-017-9442-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685964PMC
December 2017

Bilateral Retinal Detachments After Intravitreal Injection of Adipose-Derived 'Stem Cells' in a Patient With Exudative Macular Degeneration.

Ophthalmic Surg Lasers Imaging Retina 2017 09;48(9):772-775

A 77-year-old woman with exudative macular degeneration underwent bilateral intravitreal injections of "stem cells" at a clinic in Georgia. One month and 3 months after injection, she developed retinal detachments in the left and right eyes, respectively. Increased awareness within the medical community of such poor outcomes is critical so that clinics offering untested practices that have been shown to be potentially harmful to patients can be identified and brought under U.S. Food and Drug Administration oversight. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:772-775.].
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http://dx.doi.org/10.3928/23258160-20170829-16DOI Listing
September 2017

Distal Fusion Level Selection in Scheuermann's Kyphosis: A Comparison of Lordotic Disc Segment Versus the Sagittal Stable Vertebrae.

Global Spine J 2017 May 7;7(3):254-259. Epub 2017 Apr 7.

Columbia University Medical Center, New York, NY, USA.

Study Design: Retrospective study.

Objective: To compare 2 methods of selecting the lowest instrumented vertebra (LIV) on the rates of revision surgery for distal junctional kyphosis (DJK) following treatment for Scheuermann's kyphosis (SK).

Methods: A retrospective review of patients who have undergone surgical treatment for SK was performed. Forty-four patients were divided into 2 groups based on intervention: Group 1 (n = 26) included patients who had an LIV distal to or at the sagittal stable vertebrae (SSV), and Group 2 (n = 18) included patients who had an LIV proximal to the SSV. For each group, demographic, radiographic, and revision surgery data was analyzed.

Results: The average follow-up was 3.1 years. There were no differences among demographic variables between the groups. Preoperative and postoperative thoracic kyphosis, lumbar lordosis, and sagittal balance were not different between groups. Postoperatively, Group 1 demonstrated a significantly greater average lordotic disc angle below the LIV compared with Group 2 (Group 1, -6.2 ± 4.3° vs Group 2, -2.9 ± 5.8°; = .02). In a subgroup analysis, extending fusions to the sagittal stable vertebra rather than the first lordotic disc resulted in fewer distal LIV complications necessitating revision surgery compared with fusing short of the SSV (5% vs 36.3%, = .04).

Conclusion: The SSV method may reduce complications secondary to distal junctional failure, but at the expense of incorporating additional motion segments in a typically young population.
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http://dx.doi.org/10.1177/2192568217699183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476354PMC
May 2017

Assessment of Vertebral Curves Using the Manual Post-It Technique.

Clin Spine Surg 2017 04;30(3):E148-E151

*Department of Orthopaedic Surgery, Hospital for Special Surgery †Weill Cornell Medical College, New York, NY.

Study Design: A prospective study of a new technique.

Objective: The aims of this study were to report a manual technique for measuring vertebral curves on digital spine radiographs, and to assess the agreement of this technique with that of digital software for measuring vertebral curves.

Summary Of Background Data: Modern picture archiving and communication systems (PACS) typically include software for evaluating radiographic measurements. However, in the outpatient spine setting, patients may present with radiographs stored on a physical disc, which may not include software for measuring vertebral curves. Certain smartphone applications may be used to determine curve magnitude; however, the need exists for an accurate manual technique to measure vertebral curves on digital radiographs in the absence of available analytic software or smartphone technology.

Methods: We prospectively reviewed anteroposterior and lateral spine radiographs of 24 spinal deformity patients. Two independent observers measured Cobb angles for: (1) the major coronal curve; (2) the thoracic kyphosis (T2-T12); and (3) the lumbar lordosis (T12-S1). Measurements were made: (1) digitally using our institution's PACS; and (2) by a manual technique, which involves placement of an adhesive Post-It note directly on the computer screen, transcribing the angle onto the Post-It note with a pencil, and measuring the angle with a handheld goniometer. Intraclass correlation coefficients (ICCs) were calculated to determine the agreement between the 2 methods.

Results: For both observers, the agreement between the digital PACS and manual Post-It techniques was graded as excellent for both coronal and sagittal plane curves (all ICCs>0.9). Interobserver reliability between the 2 observers was also graded as excellent for both the PACS and Post-It techniques (all ICCs>0.9).

Conclusions: The Post-It technique for measuring Cobb angles demonstrated excellent agreement with the PACS system in our series of spinal deformity patients. Curves on digital radiographs can be accurately measured using a convenient manual technique.
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http://dx.doi.org/10.1097/BSD.0000000000000070DOI Listing
April 2017

Does adolescent obesity affect surgical presentation and radiographic outcome for patients with adolescent idiopathic scoliosis?

J Pediatr Orthop B 2017 Jan;26(1):53-58

aHospital for Special Surgery bWeill Cornell Medical College, New York, New York, USA.

The purpose of this study was to test a hypothesis that overweight patients with adolescent idiopathic scoliosis present with larger curves and achieve less surgical correction than do healthy weight counterparts. A total of 251 individuals were grouped by BMI into overweight (BMI% ≥85) and healthy weight (BMI% <85) groups. Overweight patients demonstrated significantly larger intraoperative blood loss (P=0.041), although there was no significant difference in the number of intraoperative transfusions. Major curves and surgical correction were similar between the two groups. A greater postoperative thoracic kyphosis at latest follow-up may suggest a worsening sagittal profile in these individuals postoperatively.
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http://dx.doi.org/10.1097/BPB.0000000000000351DOI Listing
January 2017

ACANTHAMOEBA ENDOPHTHALMITIS AFTER RECURRENT KERATITIS AND NODULAR SCLERITIS.

Retin Cases Brief Rep 2017 Spring;11(2):180-182

*Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada; †VitreoRetinal Surgery, PA, Minneapolis, Minnesota; ‡Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa city, Iowa; and §Department of Ophthalmology, Omics Laboratory, Iowa City, Iowa.

Purpose: To describe the clinical course of a patient with Acanthamoeba keratitis, who despite prompt treatment progressed to histopathology-confirmed Acanthamoeba retinitis and endophthalmitis.

Methods: Case report.

Results: A healthy 30-year-old male wearing soft contact lens was diagnosed with Acanthamoeba keratitis and treated medically and surgically over the course of 1 year with presumed resolution of the infection. Yet, his infection recurred with documented spread to sclerokeratitis, and overwhelming endophthalmitis. Concerns about extra-ocular spread prompted a therapeutic enucleation with histopathologic evidence of Acanthamoeba organisms throughout the globe.

Conclusion: This is a case of a severe recurrent Acanthamoeba infection presenting initially as keratitis, followed by sclerokeratitis and histolopathology-confirmed endophthalmitis. This case demonstrates that despite persistent medical and surgical intervention, eradication of organisms may not be possible.
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http://dx.doi.org/10.1097/ICB.0000000000000323DOI Listing
September 2017

Variations in Occipitocervical and Cervicothoracic Alignment Parameters Based on Age: A Prospective Study of Asymptomatic Volunteers Using Full-Body Radiographs.

Spine (Phila Pa 1976) 2016 Dec;41(23):1837-1844

Orthopedic Surgery, Hospital for Special Surgery, New York, NY.

Study Design: Cross-Sectional Cohort Study OBJECTIVE.: To describe age-stratified normative values of novel occipitocervical, cervical, and cervicothoracic alignment parameters.

Summary Of Background Data: Full-body radiographic images obtained without stitching or vertical distortion represent an ideal method to evaluate occipitocervical alignment and horizontal gaze.

Methods: One hundred twenty adults with no back or neck symptoms were recruited. Age, sex, body mass index, Neck Disability Index (NDI), and Oswestry Disability Index scores were recorded. Radiographic parameters measured included: center sacral vertebral line, chin brow vertical angle (CBVA), orbital tilt (OrT), orbital slope, occipital slope (OS), occipital incidence, occiput-C2 (O-C2) lordosis, cervical lordosis (C2-C7, CL), T1 slope (TS), neck tilt, thoracic inlet angle (TIA), cervicothoracic kyphosis (C6-T4), and C2-C7 sagittal vertical axis (C2-7 SVA). Interobserver reliability was calculated for all measurements (intraclass correlation coefficient, ICC). A Pearson correlation was used to determine relationships between variables.

Results: A total of 115 patients were analyzed; average age as 50.1 years (range 22-78). All measured variables had an ICC >0.6. CL (r = -0.33, P < 0.001), TS (r = 0.42, P < 0.001), TIA (r = 0.24, P = 0.010), and C7 SVA (r = 0.48, P < 0.001) all increased with age. OrT (r = -0.88, P < 0.001) and OS (r = 0.73, P < 0.001) were both strongly correlated with CBVA and each other (r = -0.83, P ≤ 0.001). Both measures were also correlated with the C2-C7 SVA (OrT, r = 0.41, P < 0.001; OS, r = -0.29, P = 0.002) and O-C2 angle (OrT, r = 0.46, P < 0.001; OS, r = -0.28, P = 0.003). C6-T4 angulations was negatively correlated with NDI scores in this population (r = -0.25, P = 0.007).

Conclusion: We present age-based normative values for occipitocervical, cervicothoracic, and cervical alignment parameters using a novel biplanar radiographic imaging technique. We introduce measures of craniocervical alignment that might provide surgeons with an intuitive way to account for the position of the orbit when planning cervical deformity correction.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000001644DOI Listing
December 2016
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