Publications by Year: 2021

2021

Schmidt, B. A. R., Zein, S. E., Cuoto, J., Al-Ibraheemi, A., Liang, M. G., Paltiel, H. J., Anderson, M. E., Labow, B. I., Upton, J., Fishman, S. J., Mulliken, J. B., Greene, A. K., Warman, M. L., & Kozakewich, H. (2021). Verrucous Venous Malformation-Subcutaneous Variant.. The American Journal of Dermatopathology, 43(12), e181-e184. https://doi.org/10.1097/DAD.0000000000001963 (Original work published 2021)

BACKGROUND: Verrucous venous malformation (VVM), previously called "verrucous hemangioma," typically involves the dermis and the subcutaneous fat. We have encountered patients with VVM confined to the hypodermis.

MATERIALS AND METHODS: During a nearly 20-year period, 13 patients, aged 2-17 years, presented with a subcutaneous mass in the limb without clinically obvious epidermal alterations. Consequently, operative excisions did not include the skin.

RESULTS: Histopathologically, the specimens were composed of blood-filled channels with morphologic characteristics of capillaries and veins that infiltrated adipose tissue. Aggregates often formed nodules with variable fibrosis and a component of large and radially oriented vessels. A diagnosis of VVM was supported by endothelial immunopositivity for GLUT-1 (25%-75% immunopositive channels in 16/16 specimens); D2-40 (1%-25% channels in 14/15 specimens); and Prox-1 (1%-50% of channels in 14/16 specimens). A MAP3K3 mutation was identified by droplet digital PCR in 3 of the 6 specimens.

CONCLUSIONS: Diagnosis of VVM in this uncommon location is challenging because of absence of epidermal changes and lack of dermal involvement. Imaging is not pathognomonic, and mimickers are many. Appropriate immunohistochemical stains and molecular analysis contribute to the correct diagnosis.

Vasunilashorn, S. M., Ngo, L. H., Dillon, S. T., Fong, T. G., Carlyle, B. C., Kivisäkk, P., Trombetta, B. A., Vlassakov, K. , V, Kunze, L. J., Arnold, S. E., Xie, Z., Inouye, S. K., Libermann, T. A., Marcantonio, E. R., & Group, R. S. (2021). Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study.. Journal of Neuroinflammation, 18(1), 103. https://doi.org/10.1186/s12974-021-02145-8 (Original work published 2021)

BACKGROUND: Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation.

METHODS: We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids.

RESULTS: Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline.

CONCLUSIONS: In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

Mortensen, S. J., Beeram, I., Florance, J., Momenzadeh, K., Mohamadi, A., Rodriguez, E. K., von Keudell, A., & Nazarian, A. (2021). Modifiable lifestyle factors associated with fragility hip fracture: a systematic review and meta-analysis.. Journal of Bone and Mineral Metabolism, 39(5), 893-902. https://doi.org/10.1007/s00774-021-01230-5 (Original work published 2021)

INTRODUCTION: Among the various hip fracture predictors explored to date, modifiable risk factors warrant special consideration, since they present promising targets for preventative measures. This systematic review and meta-analysis aims to assess various modifiable risk factors.

MATERIAL AND METHODS: We searched four online databases in September 2017. We included studies that reported on modifiable lifestyle risk factors for sustaining fragility hip fractures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The inclusion criteria consisted of (1) adult patients with osteoporotic hip fracture, (2) original study, (3) availability of full text articles in English, and (4) report of a modifiable lifestyle risk factor.

RESULTS: Thirty-five studies, containing 1,508,366 subjects in total, were included in this study. The modifiable risk factors that were significantly associated with an increased risk of hip fracture were the following: weight < 58 kg (128 lbs) (pooled OR 4.01, 95% CI 1.62-9.90), underweight body mass index (BMI) (< 18.5) (pooled OR 2.83, 95% CI 1.82-4.39), consumption of ≥ 3 cups of coffee daily (pooled OR 2.27, 95% CI 1.04-4.97), inactivity (pooled OR 2.14, 95% CI 1.21-3.77), weight loss (pooled OR 1.88, 95% CI 1.32-2.68), consumption of ≥ 27 g (approx. > 2 standard drinks) alcohol per day (pooled OR 1.54, 95% CI 1.12-2.13), and being a current smoker (pooled OR 1.50, 95% CI 1.22-1.85). Conversely, two factors were significantly associated with a decreased risk of hip fracture: obese BMI (> 30) (pooled OR 0.58, 95% CI 0.34-0.99) and habitual tea drinking (pooled OR 0.72, 95% CI 0.66-0.80).

CONCLUSION: Modifiable factors may be utilized clinically to provide more effective lifestyle interventions for at risk populations. We found that low weight and underweight BMI carried the highest risk, followed by high coffee consumption, inactivity, weight loss, and high daily alcohol consumption.

Wu, M., Zheng, E. T., Anderson, M. E., Miller, P. E., Spencer, S. A., & Heyworth, B. E. (2021). Surgical Treatment of Solitary Periarticular Osteochondromas About the Knee in Pediatric and Adolescent Patients: Complications and Functional Outcomes.. The Journal of Bone and Joint Surgery. American Volume, 103(14), 1276-1283. https://doi.org/10.2106/JBJS.20.00998 (Original work published 2021)

BACKGROUND: Solitary osteochondromas, or osteocartilaginous exostoses (OCEs), represent the most common benign bone tumor. Despite frequently causing symptoms about the knee in younger populations, there is minimal previous literature investigating surgical treatment.

METHODS: We retrospectively reviewed the records of patients <20 years old who had undergone surgical treatment of symptomatic, pathologically confirmed, solitary periarticular knee OCE at a single pediatric center between 2003 and 2016. The clinical course, radiographic and pathological features, and complications were assessed. Prospective outreach was performed to investigate patient-reported functional outcomes.

RESULTS: Two hundred and sixty-four patients (58% male, 81% athletes) underwent excision of a solitary OCE about the knee at a mean age (and standard deviation) of 14.3 ± 2.24 years. Fifty-five percent of the procedures were performed by orthopaedic oncologists, 25% were performed by pediatric orthopaedic surgeons, and 20% were performed by pediatric orthopaedic sports medicine surgeons, with no difference in outcomes or complications based on training. Of the 264 lesions, 171 (65%) were pedunculated (versus sessile), 157 (59%) were in the distal part of the femur (versus the proximal part of the tibia or proximal part of the fibula), and 182 (69%) were medial (versus lateral). Postoperatively, 96% of the patients returned to sports at a median of 2.5 months (interquartile range, 1.9 to 4.0 months). Forty-two patients (16%) experienced minor complications not requiring operative intervention. Six patients (2%) experienced major complications (symptoms or disability at >6 months or requiring reoperation), which were more common in patients with sessile osteochondromas (p = 0.01), younger age (p = 0.01), and distal femoral lesions as compared with proximal tibial lesions (p = 0.003). Lesion recurrence was identified in 3 patients (1.1%). Overall, the median Pediatric International Knee Documentation Committee (Pedi-IKDC) and mean Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) scores were 97 (interquartile range, 93 to 99) and 16.7 ± 8.15, respectively, at a median duration of follow-up of 5.8 years.

CONCLUSIONS: In our large cohort of pediatric patients who underwent excision of solitary knee osteochondromas, most patients were male adolescent athletes. Most commonly, the lesions were pedunculated, were located in the distal part of the femur, and arose from the medial aspect of the knee. Regardless of surgeon training or lesion location, patients demonstrated excellent functional outcomes, with minimal clinically important postoperative complications and recurrences, although patients with sessile lesions and younger age may be at higher risk for complications.

LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Maier, S. P., & Wixted, J. J. (2021). Native Hip Septic Arthritis in the Setting of Postpartum Gynecologic Infection: A Case Report.. JBJS Case Connector, 11(2). (Original work published 2021)

CASE: A 34-year-old healthy G3P3 woman, 1.5 weeks postpartum, presented with hip pain, fever, and a rash. Clinical examination, laboratory testing, and microbiologic cultures identified bacterial arthritis of the right hip; obstetric/gynecologic examination and cultures identified endometrial, vaginal, and urinary tract infections caused by the same pathogen, group A streptococcus, likely contracted from her 5-year-old son who had streptococcal pharyngitis. She underwent successful surgical decompression of the hip with concurrent medical management of toxic shock syndrome (TSS).

CONCLUSIONS: Hematogenously spread septic arthritis may occur in the absence of positive blood cultures during the postpartum period, increasing the risk of developing TSS.

Smith, E. L., Dugdale, E. M., McAlpine, K., Habibi, A. A., Niu, R., Baratz, M. D., & Freccero, D. M. (2021). Bias Does Not Exist in Treating Knee Periprosthetic Joint Infection Among Patients With Substance Use Disorder.. Orthopedics, 44(3), e385-e389. https://doi.org/10.3928/01477447-20210414-10 (Original work published 2021)

Debridement, antibiotics with implant retention (DAIR), and 2-stage revision are standard surgical interventions for treating knee periprosthetic joint infection (PJI). Patients with substance use disorder (SUD), especially addictive drug use disorder (DUD), have been shown to receive inferior medical care in many specialties compared with nonusers. The authors identified patients with a diagnosis of PJI after knee arthroplasty who received either DAIR or 2-stage revision with the Nationwide Inpatient Sample (NIS) database from 2010 to 2014. Patients were stratified into 2 groups, patients with DUD and nonusers, based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria. Descriptive analysis was conducted to show the national trend for knee PJI treatment among the 2 patient groups. Multivariate logistic regression was used to compare the prevalence of DAIR and 2-stage revision between these 2 groups, adjusted for likely confounders, including age, sex, income, race, and comorbidities. Among the 11,331 patients with knee infection, 139 (1.23%) had DUD. Compared with nonusers, patients with DUD were significantly younger (P<.001), had more chronic conditions (P<.001), and were predominantly in lower income quartiles (P=.046). The 2 groups did not differ in sex and race (P=.072 and P=.091, respectively). The authors found that 30.22% of patients with DUD and 36.36% of nonusers received DAIR. The difference in these proportions was not statistically significant (P=.135). The results did not change after adjustment for confounding factors (P=.509). The findings suggested that bias does not exist among orthopedic surgeons who choose DAIR or 2-stage revision for knee PJI among patients with DUD. [Orthopedics. 2021;44(3):e385-e389.].

Ramkumar, D. B., Ercolano, L. B., Allar, B. G., Miller, P. E., Padua, H., & Anderson, M. E. (2021). Sclerotherapy for Aneurysmal Bone Cysts: Scale for Response.. Journal of Pediatric Orthopedics, 41(7), 444-449. https://doi.org/10.1097/BPO.0000000000001864 (Original work published 2021)

BACKGROUND: The objective of this study was to develop a response scale for aneurysmal bone cysts (ABCs) treated with sclerotherapy and determine its inter-rater reproducibility.

METHODS: Patients treated with sclerotherapy for an ABC between 1993 and 2014 were identified. An attending orthopaedic surgeon and an attending interventional radiologist independently reviewed the radiographic series for each patient and determined response to treatment using a novel grading system. Pain scores were collected from each visit. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). General estimating equations analysis was used to evaluate the relationship between radiographic and pain scores and outcome, to develop an algorithm for the study patient population. A receiver operating characteristic curve was constructed to evaluate the diagnostic performance of the radiographic and pain scores in identifying the necessity of further treatment. To quantify the diagnostic utility, the area under the receiver operating characteristic curve was estimated along with a 95% confidence interval (CI).

RESULTS: The inter-rater reliability was excellent for magnetic resonance imaging (ICC=0.83; 95% CI=0.74-0.89) and good for computed tomography/x-ray (ICC=0.69; 95% CI=0.51-0.81). The radiographic and pain scores proved to be independent predictors of treatment (P<0.001 and 0.004, respectively). An algorithm to determine the predictive probability for treatment versus observation in the study population was developed and tested based on these assessments. The area under the receiver operating characteristic curve of 0.85 (95% CI=0.79-0.92) indicated the good diagnostic performance of the algorithm.

CONCLUSIONS: This novel grading system for radiographic response to sclerotherapy treatment demonstrates excellent to good inter-rater reliability giving providers a platform for discussion among themselves and with patients/parents. When incorporated with an assessment of pain, a predictive algorithm shows how this information could be used to determine the next steps after sclerotherapy treatment.

LEVEL OF EVIDENCE: Level IV-case series.

Jones, R. N., Tommet, D., Steingrimsson, J., Racine, A. M., Fong, T. G., Gou, Y., Hshieh, T. T., Metzger, E. D., Schmitt, E. M., Tabloski, P. A., Travison, T. G., Vasunilashorn, S. M., Abdeen, A., Earp, B., Kunze, L., Lange, J., Vlassakov, K., Dickerson, B. C., Marcantonio, E. R., & Inouye, S. K. (2021). Development and internal validation of a predictive model of cognitive decline 36 months following elective surgery.. Alzheimer’s & Dementia (Amsterdam, Netherlands), 13(1), e12201. https://doi.org/10.1002/dad2.12201 (Original work published 2021)

INTRODUCTION: Our goal was to determine if features of surgical patients, easily obtained from the medical chart or brief interview, could be used to predict those likely to experience more rapid cognitive decline following surgery.

METHODS: We analyzed data from an observational study of 560 older adults (≥70 years) without dementia undergoing major elective non-cardiac surgery. Cognitive decline was measured using change in a global composite over 2 to 36 months following surgery. Predictive features were identified as variables readily obtained from chart review or a brief patient assessment. We developed predictive models for cognitive decline (slope) and predicting dichotomized cognitive decline at a clinically determined cut.

RESULTS: In a hold-out testing set, the regularized regression predictive model achieved a root mean squared error (RMSE) of 0.146 and a model r-square (R2 ) of .31. Prediction of "rapid" decliners as a group achieved an area under the curve (AUC) of .75.

CONCLUSION: Some of our models could predict persons with increased risk for accelerated cognitive decline with greater accuracy than relying upon chance, and this result might be useful for stratification of surgical patients for inclusion in future clinical trials.

Weaver, M. J., Chaus, G. W., Masoudi, A., Momenzadeh, K., Mohamadi, A., Rodriguez, E. K., Vrahas, M. S., & Nazarian, A. (2021). The effect of surgeon-controlled variables on construct stiffness in lateral locked plating of distal femoral fractures.. BMC Musculoskeletal Disorders, 22(1), 512. https://doi.org/10.1186/s12891-021-04341-2 (Original work published 2021)

BACKGROUND: Nonunion following treatment of supracondylar femur fractures with lateral locked plates (LLP) has been reported to be as high as 21 %. Implant related and surgeon-controlled variables have been postulated to contribute to nonunion by modulating fracture-fixation construct stiffness. The purpose of this study is to evaluate the effect of surgeon-controlled factors on stiffness when treating supracondylar femur fractures with LLPs: 1. Does plate length affect construct stiffness given the same plate material, fracture working length and type of screws? 2. Does screw type (bicortical locking versus bicortical nonlocking or unicortical locking) and number of screws affect construct stiffness given the same material, fracture working length, and plate length? 3. Does fracture working length affect construct stiffness given the same plate material, length and type of screws? 4. Does plate material (titanium versus stainless steel) affect construct stiffness given the same fracture working length, plate length, type and number of screws?

METHODS: Mechanical study of simulated supracondylar femur fractures treated with LLPs of varying lengths, screw types, fractureworking lenghts, and plate/screw material. Overall construct stiffness was evaluated using an Instron hydraulic testing apparatus.

RESULTS: Stiffness was 15 % higher comparing 13-hole to the 5-hole plates (995 N/mm849N vs. /mm, p = 0.003). The use of bicortical nonlocking screws decreased overall construct stiffness by 18 % compared to bicortical locking screws (808 N/mm vs. 995 N/mm, p = 0.0001). The type of screw (unicortical locking vs. bicortical locking) and the number of screws in the diaphysis (3 vs. 10) did not appear to significantly influence construct stiffness (p = 0.76, p = 0.24). Similarly, fracture working length (5.4 cm vs. 9.4 cm, p = 0.24), and implant type (titanium vs. stainless steel, p = 0.12) did also not appear to effect stiffness.

DISCUSSION: Using shorter plates and using bicortical nonlocking screws (vs. bicortical locking screws) reduced overall construct stiffness. Using more screws, using unicortical locking screws, increasing fracture working length and varying plate material (titanium vs. stainless steel) does not appear to significantly alter construct stiffness. Surgeons can adjust plate length and screw types to affect overall fracture-fixation construct stiffness; however, the optimal stiffness to promote healing remains unknown.

Chung, K. C., Kim, H. M., Malay, S., Shauver, M. J., & Group, W. (2021). Comparison of 24-Month Outcomes After Treatment for Distal Radius Fracture: The WRIST Randomized Clinical Trial.. JAMA Network Open, 4(6), e2112710. https://doi.org/10.1001/jamanetworkopen.2021.12710 (Original work published 2021)

IMPORTANCE: Distal radius fractures (DRFs) are common injuries among older adults and can result in substantial disability. Current evidence regarding long-term outcomes in older adults is scarce.

OBJECTIVE: To compare outcomes across treatment groups at 24 months among adults with DRFs who participated in the WRIST trial.

DESIGN, SETTING, AND PARTICIPANTS: The Wrist and Radius Injury Surgical Trial (WRIST) randomized, international, multicenter trial was conducted from April 1, 2012, through December 31, 2016. Participants were adults aged 60 years or older with isolated, unstable DRFs at 24 health systems in the US, Canada, and Singapore. Data analysis was performed from March 2019 to March 2021.

INTERVENTIONS: Participants were randomized to open reduction and volar locking plate system (VLPS), external fixation with or without supplementary pinning (EFP), and percutaneous pinning (CRPP). The remaining participants chose closed reduction and casting.

MAIN OUTCOMES AND MEASURES: The primary outcome was the 24-month Michigan Hand Outcomes Questionnaire (MHQ) summary score. Secondary outcomes were scores on the MHQ subdomains hand strength and wrist motion.

RESULTS: A total of 304 adults were recruited for the study, and 187 were randomized to undergo surgery, 65 to VLPS, 64 to EFP, and 58 to CRPP; 117 participants opted for closed reduction and casting. Assessments were completed at 24 months for 182 participants (160 women [87.9%]; mean [SD] age, 70.1 [8.5] years). Mean MHQ summary scores at 24 months were 88 (95% CI, 83-92) for VLPS, 83 (95% CI, 78-88) for EFP, 85 (95% CI, 79-90) for CRPP, and 85 (95% CI, 79-90) for casting, with no clinically meaningful difference across groups after adjusting for covariates (χ23 = 1.44; P = .70). Pain scores also did not differ across groups at 24 months (χ23 = 2.64; P = .45). MHQ summary scores changed from 82 (95% CI, 80-85) to 85 (95% CI, 83-88) (P = .12) between 12 and 24 months across groups. The rate of malunion was higher in the casting group (26 participants [59.1%]) than in the other groups (4 participants [8.0%] for VLPS, 8 participants [17.0%] for EFP, and 4 participants [9.8%] for CRPP; χ23 = 43.6; P < .001), but malunion was not associated with the 24-month outcome difference across groups.

CONCLUSIONS AND RELEVANCE: The study did not find clinically meaningful patient-reported outcome differences 24 months after injury across treatment groups, with little change between 12 and 24 months. These findings suggest that long-term outcomes need not necessarily be considered in deciding between treatment options. Patient needs and recovery goals that fit to relative risks and benefits of each treatment type will be more valuable in treatment decision-making.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01589692.