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Patients with higher numbers of allergies have lower levels of anti-inflammatory cytokines and increased pain at the time of ACL reconstruction

Lipschultz, Robyn A; Moore, Michael; Montgomery, Samuel R; Wolfe, Isabel; Strauss, Eric
BACKGROUND:Synovial fluid biomarkers are well studied indicators of inflammation and healing in the setting of orthopedic injuries. However, it has not been studied if patients with one or more allergies have a difference in the concentrations of synovial fluid inflammatory cytokines compared to patients without allergies. The purpose of the current study is to analyze the concentration of 10 pro- and anti-inflammatory cytokines in the synovial fluid of isolated ACL injury patients with and without at least one allergy. STUDY DESIGN/METHODS:Retrospective Case-Control. METHODS:A database of patients who underwent surgery for isolated ACL injury between September 2011 and July 2023 was analyzed. All patients had SF aspirated from the operative knee prior to the surgical incision and the concentrations of pre- and anti-inflammatory biomarkers were quantified. From this cohort, 24 patients were identified to have allergies by chart review. These patients were matched 1:1 to 24 patients without allergies based on age and sex. RESULTS:There were no significant differences between the allergy and no allergy cohorts with respect to age (28.5 ± 10.3 vs. 29.5 ± 8.9, p = 0.76) and sex (70.8 % female vs. 70.8 % female, p = 1.00). The allergy cohort had a decreased concentration of TIMP-1 (492.41 ± 616.20 ng/mL vs. 1041.48 ± 942.04 ng/mL, p = 0.03) and IL-1Ra (101.70 ± 93.37 pg/mL vs. 359.94 ± 399.77 pg/mL, p = 0.01) compared to patients without allergies. A linear regression analysis found a significant association between increasing number of patients reported allergies and decreasing concentration of TIMP-1 (β = -231.59, p = 0.03) and IL-1Ra (β = -71.69p = 0.03) concentrations when controlling for age and sex. Finally, the allergy cohort was found to have a significantly higher value for the VAS pain scale at the time of surgery (26.84 ± 24.73 vs. 7.37 ± 10.98, p < 0.01) compared to those without an allergy. CONCLUSION/CONCLUSIONS:Patients undergoing ACL reconstruction with at least one allergy were found to have decreased concentrations of the anti-inflammatory cytokines TIMP-1 and IL-1Ra in their synovial fluid compared to those without allergies on the day of surgery. Furthermore, an increase in total number of allergies was found to be an associated with a decrease in TIMP-1 and IL-1Ra levels. Finally, the allergy cohort also had a higher value for the VAS pain scale at the time of surgery, implicating the role of a patient's innate immune system to their biologic and symptomatic response to injury.
PMID: 38176348
ISSN: 1873-5800
CID: 5628392

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis

Fu, Wenyu; Vasylyev, Dmytro; Bi, Yufei; Zhang, Mingshuang; Sun, Guodong; Khleborodova, Asya; Huang, Guiwu; Zhao, Libo; Zhou, Renpeng; Li, Yonggang; Liu, Shujun; Cai, Xianyi; He, Wenjun; Cui, Min; Zhao, Xiangli; Hettinghouse, Aubryanna; Good, Julia; Kim, Ellen; Strauss, Eric; Leucht, Philipp; Schwarzkopf, Ran; Guo, Edward X; Samuels, Jonathan; Hu, Wenhuo; Attur, Mukundan; Waxman, Stephen G; Liu, Chuan-Ju
Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.
PMCID:10794151
PMID: 38172636
ISSN: 1476-4687
CID: 5626502

The 50 Most Cited Publications in Adipose-Derived "Stem Cell Therapies" with Application in Orthopaedic Surgery

Bi, Andrew S; Hernandez, Hunter C; Oeding, Jacob F; Strauss, Eric J; Campbell, Kirk A; Jazrawi, Laith M; Kennedy, John G
Stem cell therapies have become widely popular in orthopaedic surgery, with a recent interest in adipose-derived therapeutics. Adipose-derived mesenchymal signaling cells (ADSCs) and micronized adipose tissue (MAT) are unique therapies derived from different processing methods. Characterizing the most influential studies in lipoaspirate research can help clarify controversies in definitions, identify core literature, and further collective knowledge for educational purposes. The Science Citation Index Expanded subsection of the Web of Science Core Collection was systematically searched to identify the top 50 most cited publications (based on citation/year) on orthopaedic ADSCs or MAT research. Publication and study characteristics were extracted and reported using descriptive statistics. Level of evidence was assessed for applicable studies, and Spearman correlations were calculated to assess the relationship between citation data and level of evidence. The top 50 articles were published between the years 2003 and 2020, with 78% published in the year 2010 or later. The mean number of citations was 103.1 ± 81.1. The mean citation rate was 12.4 ± 6.0 citations per year. Of the 21 studies for which level of evidence was assessed, the majority were level III (10, 47.6%). The single study design most common among the top 50 cited articles was in vitro basic science studies (17 studies, 34%). Twenty-nine articles (58%) were classified as basic science or translational. Application to treat knee osteoarthritis was the most common focus of studies (14 studies, 28%), followed by in vitro analysis of growth factor and cell signaling markers (11 studies, 22%). No correlation was found between rank, citation rate, or year of publication and level of evidence. This study provides a current landscape on the most cited articles in lipoaspirates in orthopaedic surgery. With the expansion of ADSCs and MAT in the past two decades, this study provides the first historical landmark of the literature and a launching point for future research. Studies should explicitly state their processing methodology and whether their study investigates ADSCs or MAT to avoid misinformation.
PMID: 36539212
ISSN: 1938-2480
CID: 5624212

High Rate of Patient Satisfaction with Either Telemedicine or Traditional Office-Based Follow-Up Visit After Arthroscopic Shoulder Surgery

Markus, Danielle H; Colasanti, Christopher A; Kaplan, Daniel J; Manjunath, Amit K; Alaia, Michael J; Strauss, Eric J; Jazrawi, Laith M; Campbell, Kirk A
PMID: 37318834
ISSN: 1556-3669
CID: 5605762

Increasing Diversity in Orthopaedic Surgery Residency: A Case Report of One Program's Experience Using Pipeline Programs

Owuor, Hans K; Strauss, Eric J; McLaurin, Toni; Zuckerman, Joseph D; Egol, Kenneth A
INTRODUCTION/UNASSIGNED:African American, Hispanic, Asian, and Pacific Islanders are groups who are underrepresented in medicine (URM groups). Similarly, although women comprise more than 50% of medical students in the United States, women comprise a smaller percentage of all orthopaedic surgery trainees. Therefore, underrepresented in orthopaedics (URiO) represents the URM groups and women. The purpose of this study is to examine the impact of specific steps to recruit a qualified, diverse trainee complement within a single academic orthopaedic surgery residency program between 2000 and 2023. We aim to explore changes in the representation of URiO during this period as well as explore the strategies and programs implemented by the department that may have impacted recruitment of a diverse complement of trainees. METHODS/UNASSIGNED:Match lists from a large, academic, orthopaedic surgery residency between 2000 and 2023 were collected and reviewed for racial and gender data. Match lists were then divided into 6-year quantiles to identify any trends in the recruitment of URiO students. Self-reported racial and gender data from Electronic Residency Application Service applicant reports and the Accreditation Council for Graduate Medical Education (ACGME) data books between 2018 and 2022 were collected and reviewed. In addition, the department's strategies implemented during the study period with the goal of enhancing URiO exposure to orthopaedic surgery were also explored. RESULTS/UNASSIGNED:The department implemented proactive strategies to increase exposure to orthopaedic surgery for URiO students. An increase in URiO representation was noted between 2000 and 2023 with Hispanic, Black/African American, and Native Hawaiian/Pacific Islander resident representation increasing by 5%, 11%, and 1%, respectively. In addition, women representation increased by 27% between 2000 and 2023. The overall attrition rate among URiO residents was 1% with only one resident not completing the program. Self-reported racial and gender data from ACGME data books demonstrated that Black/African American, Hispanic, and Native Hawaiian/Pacific Islander residents comprised 5%, 4%, and 0.04%, respectively, of orthopaedic surgery residents between 2018 and 2022. CONCLUSIONS/UNASSIGNED:These results provide insight for other programs to use similar strategies to potentially improve recruitment, retain, and provide support to URiO residents.
PMCID:11449418
PMID: 39371664
ISSN: 2472-7245
CID: 5730082

Acceptable clinical outcomes despite high reoperation rate at minimum 12-month follow-up after concomitant arthroscopically assisted anterior cruciate ligament reconstruction and medial meniscal allograft transplantation

Shankar, Dhruv S.; Vasavada, Kinjal D.; Avila, Amanda; DeClouette, Brittany; Aziz, Hadi; Strauss, Eric J.; Alaia, Michael J.; Jazrawi, Laith M.; Gonzalez-Lomas, Guillem; Campbell, Kirk A.
Background: Single-stage medial meniscus allograft transplantation (MAT) with concomitant anterior cruciate ligament reconstruction (ACLR) is a technically challenging procedure for management of knee pain and instability in younger patients, but clinical and functional outcomes data are sparse. The purpose of this study was to assess surgical and patient-reported outcomes following concomitant ACLR and medial MAT. Methods: We conducted a retrospective case series of patients who underwent medial MAT with concomitant primary or revision ACLR at our institution from 2010 to 2021 and had minimum 12-month follow-up. Complications, reoperations, visual analog scale (VAS) pain, satisfaction, Lysholm score, return to sport, and return to work outcomes were assessed. Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference, Pain Intensity, and Physical Function Scores were used to measure patients"™ functional status relative to the US population. P-values < 0.05 were considered significant. Results: The cohort consisted of 17 knees of 16 individual patients. The cohort was majority male (82.4%) with mean age of 31.9 years (range 19"“49 years) and mean body mass index (BMI) of 27.9 kg/m2 (range 22.5"“53.3 kg/m2). Mean follow-up time was 56.8 months (range 13"“106 months). Most patients underwent revision ACLR (64.7%). The 1-year reoperation rate was high (23.5%), with two patients (11.8%) tearing their meniscus graft. Patient-reported outcomes indicated low VAS pain (mean 2.2), high satisfaction (mean 77.9%), and fair Lysholm score (mean 81.1). Return to work rate was high (92.9%), while return to sport rate was low (42.9%). Postoperative PROMIS scores were comparable or superior to the national average and correlated significantly with patient satisfaction (p < 0.05). Conclusions: The concomitant ACLR and MAT procedure is associated with excellent knee pain and functional outcomes and high rate of return to work after surgery, though the 1-year reoperation rate is high and rate of return to sport is low. Level of evidence: IV.
SCOPUS:85146131298
ISSN: 2234-0726
CID: 5408462

The Fifty Most Cited Publications on Concentrated Bone Marrow Aspirate With Application in Orthopedic Surgery

Oeding, Jacob F; Hernandez, Hunter C; Bi, Andrew; Kennedy, John G; Jazrawi, Laith M; Strauss, Eric J; Campbell, Kirk C
BACKGROUND:Concentrated bone marrow aspirate (cBMA) has garnered widespread and increasing attention in recent years. We aimed to characterize the most influential articles in cBMA research while clarifying controversies surrounding its use and clinical efficacy and identifying important areas on which to focus future research efforts. METHODS:The Science Citation Index Expanded subsection of the Web of Science Core Collection was systematically searched to identify the top 50 most cited publications on orthopedic cBMA research. Publication and study characteristics were extracted, and Spearman correlations were calculated to assess the relationship between citation data and level of evidence. RESULTS:The top 50 articles were published between the years 1996 and 2018, with 58% published in the year 2010 or later. Of the 29 studies for which level of evidence was assessed, the majority were Level IV (24, 83%). Twenty-one articles (42%) were classified as basic science or translational (9 cell culture, 8 animal study, and 4 using human blood samples). Application to treat cartilage defects was the most common focus of studies (17 studies, 34%), followed by analysis of cBMA composition (14 studies, 28%). No correlation was found between rank, citation rate, or year of publication and level of evidence. CONCLUSIONS:The most influential articles on cBMA are recent and consist of a majority low-level of evidence studies. Cohort studies were the most common study type among the top 50 most cited articles, while basic science articles were relatively less common. These results suggest a rapidly evolving field with the potential to better explain inconsistent clinical results with improved understanding and documentation of basic science concepts in addition to large-scale, prospective clinical trials. Orthobiologics and especially cBMA holds great promise for the future, and higher-level clinical trials will help better define the best clinical uses for this treatment.
PMID: 36122693
ISSN: 1938-2480
CID: 5335312

Return to Play After Knee Articular Cartilage Restoration: Surgical Options, Rehabilitation Protocols, and Performance Outcomes

Triana, Jairo; Li, Zachary I; Rao, Naina; Kingery, Matthew T; Strauss, Eric J
PURPOSE OF REVIEW/OBJECTIVE:Numerous cartilage restoration techniques have proven to be effective in the treatment of articular cartilage defects. The ultimate goal of these procedures is to improve pain and function, thereby increasing the likelihood of a patient's return to physical activity. Postoperative rehabilitation is a key component for a successful and expedient return to activities. The purpose of this article is to review the current literature regarding common surgical options, rehabilitation protocols, and performance outcomes after operative treatment of articular cartilage defects. RECENT FINDINGS/RESULTS:Studies have demonstrated improved short- to long-term outcomes in a majority of techniques. However, the clinical benefits of microfracture are short-lived, which has led to the use of alternative procedures. Rehabilitation protocols are not standardized, but emphasis has been placed on bracing, weightbearing, early continuous passive range of motion, and strengthening to improve function. There is growing evidence to suggest that accelerated rehabilitation after matrix-induced autologous chondrocyte implantation may result in superior outcomes compared to delayed rehabilitation. Overall, most techniques result in satisfactory rates of return to play, though existing comparative studies typically include patients with heterogeneous pathology, complicating effective synthesis of outcomes data. In appropriately selected patients, cartilage restoration procedures after articular cartilage injury result in favorable patient-reported clinical outcomes and high rates of return to play. While studies emphasize the critical role that rehabilitation plays with respect to outcomes after surgery, there are substantial inconsistencies in protocols across techniques.
PMCID:10733247
PMID: 37804418
ISSN: 1935-973x
CID: 5736052

Cartilage Biopsy for Autologous Cell-Based Repair of the Knee in the Wide-Awake Setting Using Needle Arthroscopy

Savage-Elliott, Ian; Kingery, Matthew T; Azam, Mohammad T; Lowe, Dylan T; Strauss, Eric J
Chondral and osteochondral lesions of the knee are a commonly occurring pathology that can pose challenges to the treating surgeon. For the appropriate cartilage injury, autologous cell-based articular cartilage repair techniques have shown promising results. However, these treatments traditionally require 2 separate surgical procedures. Recent advances in needle arthroscopy technology have made it possible to conduct the first stage of autologous chondrocyte implantation surgery in the wide-awake office setting, mitigating cost and resource utilization. The purpose of this technical note is to serve as a proof of concept and describe the process of obtaining a cartilage sample in the wide-awake patient using a needle arthroscope.
PMCID:10714369
PMID: 38094953
ISSN: 2212-6287
CID: 5589342

The Minimal Clinically Important Difference: Response [Comment]

Bloom, David A; Kaplan, Daniel J; Mojica, Edward; Strauss, Eric J; Gonzalez-Lomas, Guillem; Campbell, Kirk A; Alaia, Michael J; Jazrawi, Laith M
PMID: 37917815
ISSN: 1552-3365
CID: 5606652