Daniel H. Wiznia’s research while affiliated with Yale University and other places

Introduction Knee osteoarthritis and hip osteoarthritis (OA) are orthopaedic conditions for which total joint arthroplasty (TJA) is the definitive treatment. The correlation of social determinants of health (SDOH) disparities with access to specialized health care such as TJA is of increasing interest. At our institution, SDOH screening was implemented in 2020. The purpose of this study was to identify whether patients with OA who screened positive for SDOH hardship (SDOH positive) were less likely to receive a subsequent TJA. Methods Patients with diagnosis of knee or hip OA who underwent SDOH screening from 2020 to 2023 were identified from our institutional record. The correlation of SDOH-positive screening relative to not screening positive (SDOH negative) with the likelihood of receiving TJA was assessed. The incidence of TJA in these two cohorts was evaluated using multivariable logistic regression controlling for age, sex, race, and ethnicity. Results A total of 2,981 patients were identified fitting the study criteria. The number of SDOH-positive patients was 1,122 (37.6%), and the number of SDOH-negative patients was 1,859 (62.4%). The SDOH-positive group had a significantly lower rate of TJA (9.9% vs. 14.8%, P < 0.0001). When individual SDOH were assessed, transportation insecurity, financial strain, and food insecurity were associated with decreased TJA incidence, with increasing financial strain corresponding to additional decreases in TJA incidence. On multivariable analysis, SDOH-positive status was identified as an independent negative predictor of TJA. Discussion Patients with knee or hip OA screening positive for SDOH disparities had decreased odds of receiving a subsequent TJA. As screening becomes increasingly more common, these findings illustrate how SDOH disparities correlate with access to orthopaedic care and demonstrate the need for intervention after screening, especially in SDOH categories where organizations can provide resources and support, such as access to transportation and food.

Background Osteonecrosis of the femoral head can be a debilitating disease leading to collapse of the femoral head and the subsequent need for a hip arthroplasty. Core decompression has emerged as a leading treatment to prevent collapse. Adjunctive therapies, such as bone graft, bone marrow aspirate concentrates, or synthetic bone substitutes are utilized to promote native bone regeneration. Determining the amount of bone resected and the volume of adjunct required is challenging, especially with newer minimally invasive reamers. Under- or over-filling the defect may impact progression of the disease or cause morbidity. Surgical technique We introduce a mathematical method to be utilized intraoperatively to calculate the volume of bone resected during core decompression with an expandable reamer. This method approximates the core decompression defect as two cylinders using measurements that can be easily taken during the procedure and can be adapted for use with any of the expandable reamer systems available. Using this technique, surgeons can calculate the size of the defect created, which can be used to personalize the amount of adjunct delivered to each patient. Conclusions When adjunctive therapies are used with core decompression to treat ONFH, care must be taken when filling the core decompression defect to avoid under- or over-filling the defect, potentially increasing the risk of complications or reducing the efficacy of the procedure. We provide a simple worksheet that can be used by surgeons to help determine how much adjunct should be used.

Linear and volumetric analysis are the typical methods to measure tumor size. 3D volumetric analysis has risen in popularity; however, this is very time and labor intensive limiting its implementation in clinical practice. This study aims to show that an AI-led approach can shorten the length of time required to conduct 3D volumetric analysis of VS tumors and improve image processing accuracy. From Yale New Haven Hospital and public patient recruitment, 143 MRIs were included in the ground truth dataset. To create the tumor models for the ground truth dataset, an image processing software (Simpleware ScanIP, Synopsys) was used. The helper (DPP V1.0) was trained using proprietary AI- and ML-based algorithms and information. A proof-of-concept AI model achieved a mean DICE score of 0.76 (standard deviation 0.21). After the final testing stage, the model improved to a final mean DICE score of 0.88 (range 0.74–0.93, standard deviation 0.04). Our study has demonstrated an efficient, accurate AI for 3D volumetric analysis of vestibular schwannomas. The use of this AI will enable faster 3D volumetric analysis compared to manual segmentation. Additionally, the overlay function would allow visualization of growth patterns. The tool will be a method of assessing tumor growth and allow clinicians to make more informed decisions.

Background Biomarkers of infection are measurable indicators that reflect the presence of an infection in the body. They are particularly valuable for detecting infections and tracking treatment responses. Previous transcriptome analysis of peripheral blood mononuclear cells (PBMCs) collected from patients during the active phase of diabetic foot infection identified the upregulation of several genes, including a neutrophil-specific cell surface glycoprotein, CD177, an Myb-related transcription factor 2 (MYBL2), and ribonucleotide reductase regulatory subunit M2 (RRM2). We aimed to investigate whether these observations in diabetic foot infections could be extrapolated to other musculoskeletal infections. Questions/purposes (1) Are the protein concentrations of CD177, MYBL2, and RRM2 elevated in serum or PBMCs of patients with musculoskeletal infections? (2) Do serum and PBMC concentrations of CD177, MYBL2, and RRM2 decrease in response to antibiotic therapy? (3) Can these biomarkers give diagnostic accuracy and differentiate patients with musculoskeletal infections from controls? Methods From April 2023 to June 2024, we treated 26 patients presenting with clinical symptoms and signs of acute musculoskeletal infections, including elevated inflammatory markers (white blood cell [WBC] and C-reactive protein [CRP]) and local changes such as swelling, erythema, tenderness or pain, warmth, purulent drainage, sinus tract, or wound leading to bone or hardware. Diagnosis included periprosthetic joint infection (PJI), foot and ankle infection (FAI), fracture-related infection (FRI), and septic arthritis of the native joints. Patients with chronic recurrent osteomyelitis, PJI, or FRI were excluded from the study. Among the 26 patients deemed potentially eligible, 19% (5) were excluded for the following reasons: prison inmate (1), unable to provide consent because of severe sepsis (1), mental illness (1), and declined to participate (2). Of the 81% (21) of patients who provided consent, cultures from 9.5% (2) were negative. These two patients were ultimately diagnosed with inflammatory arthritis: gout (1) and rheumatoid arthritis (1); thus, the musculoskeletal infection group for analysis consisted of 73.1% (19 of 26) of patients. A control group of 21 patients undergoing elective foot or ankle deformity correction surgery without infections or systemic inflammation was included. Because foot or ankle deformity is highly unlikely to influence the immunologic profile of the subjects, we believed that these patients would serve as an appropriate control group. Other than the absence of infection and the lower prevalence of diabetes mellitus, the control group was comparable to the study group in terms of demographics and clinical factors, including age and sex distribution. We collected blood samples from both patients and controls and quantified CD177, MYBL2, and RRM2 RNA transcription levels in the PBMC using qRT-PCR. We also assessed protein concentrations in the serum and PBMC using an enzyme-linked immunosorbent assay. A comparative analysis of the three biomarkers was performed on 19 patients with musculoskeletal infections with positive cultures and 21 controls to assess their diagnostic potential using the unpaired nonparametric t-test with the Mann-Whitney test. We obtained 8-week follow-up blood samples from seven patients with musculoskeletal infections who clinically healed. Healing was defined by normalization of inflammatory markers (WBC and CRP) and absence of swelling, erythema, local tenderness or pain, warmth, purulent drainage, sinus tract, or open wound. We performed a comparative analysis of the seven patients during active infection and after treatment to determine a change in the level of CD177, MYBL2, and RRM2 in their serum and PBMCs. These findings were also compared with those of the control group. We evaluated the diagnostic accuracy of CD177, MYBL2, and RRM2 for musculoskeletal infections using receiver operating characteristic (ROC) curve analysis. Results The musculoskeletal infections group showed a larger increased serum and PBMC concentrations of CD177, MYBL2, and RRM2 proteins compared with the control group. The mean protein concentrations of CD177, MYBL2, and RRM2 were increased in the serum and PBMC of the musculoskeletal infections group compared with the controls. Serum levels of all biomarkers investigated were higher in musculoskeletal infections group compared with the control group (CD177 227 [155 to 432] versus 54 [10 to 100], difference of medians 173, p < 0.01; MYBL2 255 [231 to 314] versus 180 [148 to 214], difference of medians 75, p < 0.01; RRM2 250 [216 to 305] versus 190 [148 to 255], difference of medians 60, p < 0.01). Similarly, PBMC levels of all biomarkers were higher in the musculoskeletal infections group (CD177 55.3 [39.1 to 80.5] versus 17.5 [10.5 to 27.5], difference of medians 37.8, p < 0.01; MYBL2 144 [114 to 190] versus 91 [70 to 105], difference of medians 53, p < 0.01; RRM2 168 [143 to 202] versus 100 [77.5 to 133], difference of medians 68, p < 0.01). Additionally, serum levels of all biomarkers decreased in seven patients with musculoskeletal infections after infection treatment (CD177 3080 [2690 to 3320] versus 4250 [3100 to 8640], difference of medians 1170, p < 0.01; MYBL2 4340 [4120 to 4750] versus 5010 [4460 to 5880], difference of medians 670, p < 0.01; RRM2 4350 [3980 to 5000] versus 5025 [4430 to 6280], difference of medians 675, p = 0.01). Similarly, PBMC levels of all biomarkers were lower after infection treatment (CD177 805 [680 to 980] versus 1025 [750 to 1610], difference of medians 220, p < 0.01; MYBL2 2300 [2100 to 2550] versus 2680 [2220 to 3400], difference of medians 380, p = 0.02; RRM2 2720 [2500 to 3200] versus 3350 [2825 to 4030], difference of medians 630, p < 0.01). The area under the ROC curve for diagnosing musculoskeletal infections in the serum and PBMC was as follows: CD177 95% confidence interval [CI] > 0.99 and > 0.99, MYBL2 95% CI > 0.99 and > 0.99, and RRM2 95% CI = 0.96 and > 0.99, respectively. Conclusion We may utilize blood-based tests for CD177, MYBL2, and RRM2 to aid in the diagnosis of musculoskeletal infections, particularly when arthrocentesis or obtaining tissue culture is challenging. They may also assist in monitoring treatment response. As some of these biomarkers may also be elevated in other inflammatory conditions, a large-scale clinical study is needed to confirm their reliability in differentiating musculoskeletal infections from other inflammatory conditions. Clinical Relevance CD177, MYBL2, and RRM2 proteins in blood samples may serve as novel biomarkers for diagnosing and monitoring treatment response in musculoskeletal infections.

Introduction: Demographic disparities in musculoskeletal (MSK) health exist in the US. Racial representation in advertising has been shown to influence consumer behavior and buying patterns. Direct-to-consumer advertising that does not target a racially diverse audience may exacerbate MSK disparities by failing to reach minorities. We explore the hypothesis that minorities are underrepresented in direct-to-consumer MSK advertisements in this cross-sectional analysis. Methods: Using magazines from four databases, eight health-related magazine types were selected and advertisement categories were established. Racial distribution was analyzed using Pearson’s Chi-squared and Chi-squared tests. Fisher’s Exact test was used when >20% of cells had expected frequencies <5. Significance was set at α = 0.05. Results: Of the advertisements featuring at least one model, 68.5% featured a white-presenting model, followed by 17.6% with a black model. Further, 92.7% of advertisements were monoethnic or monoracial with an overrepresentation of white models (p < 0.001). Black models were overrepresented as athletes (p < 0.001) and underrepresented in advertisements for pain relief (p < 0.001). Hispanic/Latinx and Asian models were underrepresented across all advertisement categories (p < 0.001). Discussion: The causes of musculoskeletal health disparities are multifactorial. One potential influence is adjacent industries such as MSK health-related advertisements. When controlling for US population demographics, white models were overrepresented and minority race models were underrepresented, demonstrating racioethnic disparities in MSK advertising. Improving the racial and ethnic diversity of models within MSK advertisements may serve to improve patient perceptions of orthopaedic products and services and improve MSK disparities.

Purpose Given the importance of musculoskeletal knowledge but the limited orthopaedic instruction offered in medical school, our Orthopaedic Surgery Department developed a three-week clerkship for interested students. This study assesses the clerkship’s impact on medical student musculoskeletal knowledge through administration of the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination. Methods Medical students enrolled in the orthopaedic surgery clerkship between February 2019 and May 2024 were asked to participate in pre- and post-clerkship surveys using the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination. Raw and weighted scores were computed according to the guidelines provided by Freedman and Bernstein. Averaged scores were used to compute mean pre- and post-test scores. Results There were 64 responses to the pre-test and 33 responses to the post-test. The mean pre-test weighted score was 54% with 12 students (18.8%) passing. The mean post-test score was 70% with 17 students (51.5%) passing. Raw scores showed that musculoskeletal knowledge improved from pre-test (M = 55.13, SD = 19.90) to post-test (M = 70.22, SD = 14.70; p < .001). The results comparing weighted scores showed that the participants’ musculoskeletal knowledge also improved from pre-test (M = 52.86, SD = 21.12) to post-test (M = 67.11, SD = 19.02; p < .001). Conclusion While students demonstrated improved musculoskeletal knowledge after completing our institution’s orthopaedic surgery clerkship, almost half of the students did not pass the post-test. Most of the students who did not pass the post-test expressed definite or possible interest in pursuing an orthopaedic surgery residency.

BACKGROUND Accurate monitoring of tumor progression is crucial for optimizing outcomes in NF2-related schwannomatosis (NF2-SWN). Standard 2D linear analysis on MRIs is less accurate than 3D volumetric analysis, but 3D volumetric analysis is time-consuming, so it is not widely utilized. To shorten the time required for 3D volumetric analysis, our lab has been developing an automated AI-driven 3D volumetric tool. OBJECTIVE The objective of our study was to survey and interview clinicians treating NF2-SWN to understand their views on current 2D analysis and to gather insights for our 3D volumetric analysis tool's design. METHODS Surveys and interviews were conducted with clinicians experienced in treating NF2. Interviews were examined for the following themes: (1) the state of tumor monitoring and 2D analysis, (2) utility of 3D visualization, (3) features for interactive 3D modeling, and (4) lack of a gold standard for 3D accuracy. A Likert scale questionnaire was used to survey clinician’s level of agreement with 25 statements related to 2D and 3D tumor analyses. RESULTS 14 clinicians completed a survey, and 12 clinicians were interviewed. Specialties ranged across neurosurgery, neuroradiology, neurology, oncology and pediatrics. Both surveys and interviews revealed concerns around the variability and subjectivity of 2D analysis. Clinicians felt that 3D volumetric analysis addresses these concerns but expressed uncertainty about how it could be interpreted clinically. Clinicians recommended features for the tool, such as interactive 3D models, visualization of neighboring anatomic structures, and the ability to monitor growth using visual cues. CONCLUSIONS Clinicians were overall in favor of adoption of 3D volumetric analysis techniques for measuring analyze VS tumors but expressed concerns regarding the novelty and inexperience surrounding these techniques. However, clinicians felt that the abilities to visualize tumors with reference to critical structures, to overlay structures, to interact with 3D models, and to visualize areas of slow versus rapid growth in 3D would be valuable contributions to clinical practice. Overall, clinicians provided valuable insights for designing a 3D volumetric analysis tool for VS tumor growth. These findings may also apply to other CNS tumors, offering broader utility in tumor growth assessments.

Glucocorticoids (GCs) are the most prescribed anti-inflammatory and immunosuppressive drugs. However, their use is often limited by substantial side effects, such as GC-induced osteoporosis (GIO) with the underlying mechanisms still not fully understood. In this study, we identify Tau as a low-affinity binding receptor for GCs that plays a crucial role in GIO. Tau deficiency largely abolished bone loss induced by high-dose dexamethasone, a synthetic GC, in both inflammatory arthritis and GIO models. Furthermore, TRx0237, a Tau inhibitor identified from an FDA-approved drug library, effectively prevented GIO. Notably, combinatorial administration of TRx0237 and dexamethasone completely overcame the osteoporosis adverse effect of dexamethasone in treating inflammatory arthritis. These findings present Tau as a previously unrecognized GC receptor with low affinity, and provide potential strategies to mitigate a spectrum of GC-related adverse effects, particularly osteoporosis. Cell Research (2024) 0:1-22; https://doi.

Background The decision to undergo total knee arthroplasty (TKA) is complex, requiring patients to consider the risks and benefits of surgery. It is the clinician’s responsibility to educate patients on their treatment decisions. Patient decision-making aids are a tool for clinicians to utilize with their patients to improve their patients' understanding of their condition and treatment options. With increased emphasis on patient-centered healthcare, implementation of a shared decision-making aid in adult reconstruction clinical practice may help patients make better informed decisions. Purpose Given that the orthopaedic surgery clinic is the primary setting where a patient decides whether to pursue non-operative treatment versus surgery, patients and clinicians in this setting may benefit from the use of a shared decision-making tool (SDMT). The primary goal of this study was to evaluate the utility of a patient-specific SDMT on the patient’s decision regarding knee osteoarthritis (OA) management. Methods A randomized prospective clinical trial was conducted to evaluate the impact of a SDMT regarding treatment for knee OA. Patients were randomized to an intervention arm with the implementation of a patient-specific SDMT or a control arm with a standard of care (SOC) clinic appointment without the use of the tool. The impact of the SDMT was assessed by evaluating patients on Patient-Reported Outcome measures, and their attitudes towards non-operative and operative interventions. Results Both the patient-specific SDMT and control groups demonstrated a statistically significant increase in post-visit understanding of their disease progression. Patients in the SDMT group demonstrated a significant increase in the proportion of patients who would be “extremely likely” to pursue non-operative treatment post-visit. Comparisons between SDMT and control groups demonstrated a significant inclination for the SDMT cohort to enroll in non-operative, conservative management such as corticosteroid or hyaluronic acid injections. Conclusion Use of a patient specific customizable SDMT tool in an adult reconstruction clinic positively impacted patient attitudes toward receiving non-operative treatment for OA and, more importantly, patient understanding of disease post-visit. Trial Registration: This randomized controlled study (ID: NCT05411939, Registered 04/15/2023 at clinicaltrials.gov) was approved by the institutional review board at our university (HIC# 2000032637) and used the CONSORT checklist.