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21 result(s) for "Therien, Aaron D."
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Exploring the drivers of price variation in orthopaedic radical bone tumor resection: A nationwide database study
Radical resection of bone tumors is a clinically effective but costly procedure. Despite the implementation of federal price transparency mandates, little is known about the nationwide variation in negotiated prices for these specialized oncologic surgeries. This study aimed to quantify the variation in negotiated rates for radical resection of the humerus and femur/knee and identify associated hospital, payor, and state-policy drivers. This cross-sectional study analyzed hospital-negotiated payor rates from the Turquoise Health database for current procedural terminology (CPT) codes 24150 (humerus resection) and 27365 (femur/knee resection). Multivariate linear regression was used to determine the associations between hospital size and type, payor class, and state-level policies (Medicaid expansion, Certificate of Need [CoN] laws, All-Payer Claims Database [APCD] mandates, and Nurse Practitioner [NP] scope of practice) on negotiated payor rates. A total of 285,857 negotiated rates were analyzed. Significant price variation was observed across all factors. Large hospitals (>1000 beds) and Critical Access Hospitals (for femur/knee resection only) had significantly higher rates. CoN laws were associated with higher prices for both procedures (+$348.25 and +$667.98, respectively), as were APCD mandates for femur/knee resections (+$1231.24). Medicare Advantage plans paid inconsistently compared to commercial plans, paying more for humerus but substantially less for femur/knee resections. Negotiated prices for radical bone tumor resection are highly variable and influenced by a complex interplay of market dynamics, challenging the assumption that price transparency alone can standardize healthcare costs for specialized care.
Spatial biology analysis reveals B cell follicles in secondary lymphoid structures may regulate anti-tumor responses at initial melanoma diagnosis
B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. Flow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs. B cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival. These data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN.
No Postoperative Difference Between Bone-Block Versus All–Soft Tissue Quadriceps Tendon Autografts for Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis
Background: Quadriceps tendon autografts are increasingly used for anterior cruciate ligament reconstruction (ACLR), harvested either with a patellar bone block (quadriceps tendon bone block [QTBB]) or as an all–soft tissue graft (quadriceps tendon soft tissue [QTST]). However, comparative data on outcomes remain limited and heterogeneous. Hypothesis: It was hypothesized that there would be no significant differences in patient-reported outcomes, objective stability, return to sports, or complication rates between QTBB and QTST grafts used for primary ACLR. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review of 4 databases (PubMed, Embase, Scopus, and SportDISCUS) was conducted through November 2024. Studies reporting outcomes after primary ACLR using QTBB or QTST autografts were included (Levels 1-4 evidence). Random-effects meta-analyses pooled outcomes for each graft; meta-regression compared grafts while adjusting for follow-up duration and publication year. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I), and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: A total of 44 studies (n = 2083; QTBB = 1104; QTST = 979) met the inclusion criteria with a mean follow-up of 29 months. International Knee Documentation Committee scores averaged 79.7 (95% CI, 74.8-84.6) for QTBB and 85.4 (95% CI, 80.9-89.8) for QTST autografts (β = 5.2; P = .11). There were no significant between-group differences in Lysholm, Tegner, or Knee injury and Osteoarthritis Outcome Score subscale scores. Instrumented laxity (KT-1000/2000) was higher for QTBB (1.75 mm [1.30-2.21]) versus QTST grafts (0.50 mm [0.35-0.65]) (β = −1.25 mm; P = 0.087), although this difference was not statistically significant and QTST results were driven by a single high-volume cohort. No significant differences were found in Lachman, pivot-shift, or anterior drawer grades. Return to sports (RTS) rates were 82% for QTBB and 81% for QTST grafts (P = .82). Graft failure (both 6%), anterior knee pain (8% vs 7%), and infection (~1%) rates were comparable (all P > .70). Heterogeneity was high for patient-reported outcome measures (I2 >75%) but low for complications. Most studies had a moderate risk of bias, and the certainty of evidence was graded as very low across outcomes due to inconsistency, imprecision, and the observational nature of included studies. Conclusion: This systematic review and meta-analysis found no clinically meaningful differences in short-term patient-reported outcomes, graft integrity, RTS rates, or complications between QTBB and QTST grafts in primary ACLR.
Multimodality analysis confers a prognostic benefit of a T-cell infiltrated tumor microenvironment and peripheral immune status in patients with melanoma
BackgroundWe previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also received anti-PD-1 after lerapolturev. In preclinical models lerapolturev induces intratumoral innate inflammation that engages antitumor T cells. In the current study, prelerapolturev and postlerapolturev tumor biopsies and blood were evaluated for biomarkers of response.MethodsThe following analyses were performed on tumor tissue (n=11): (1) flow cytometric assessment of immune cell density, (2) NanoString Digital Spatial profiling of protein and the transcriptome, and (3) bulk RNA sequencing. Immune cell phenotypes and responsiveness to in vitro stimulation, including in vitro lerapolturev challenge, were measured in peripheral blood (n=12).ResultsThree patients who received anti-PD-1 therapy within 30 days of lerapolturev have a current median progression-free survival (PFS) of 2.3 years and had higher CD8+T cell infiltrates in prelerapolturev tumor biopsies relative to that of 7 patients with median PFS of 1.6 months and lower CD8+T cell infiltrates in prelerapolturev tumor biopsies. In peripheral blood, four patients with PFS 2.3 years (including three that received anti-PD-1 therapy within 30 days before lerapolturev and had higher pretreatment tumor CD8+T cell infiltrates) had significantly higher effector memory (CD8+, CCR7-, CD45RA-) but lower CD8+PD-1+ and CD4+PD-1+ cells compared with eight patients with median PFS 1.6 months. In addition, pretreatment blood from the four patients with median PFS 2.3 years had more potent antiviral responses to in vitro lerapolturev challenge compared with eight patients with median PFS 1.6 months.ConclusionAn inflamed pretreatment tumor microenvironment, possibly induced by prior anti-PD-1 therapy and a proficient peripheral blood pretreatment innate immune response (antiviral/interferon signaling) to lerapolturev was associated with long term PFS after intratumoral lerapolturev in a small cohort of patients. These findings imply a link between intratumoral T cell inflammation and peripheral immune function.Trial registration numberNCT03712358.
Physis-sparing rotationplasty as a salvage procedure after failed allograft in paediatric osteosarcoma
Classic rotationplasty technique uses femoral and tibial osteotomies to resect portions of the distal femur and proximal tibia, most commonly in the setting of malignancy. The procedure involves rotating the lower extremity 180° to transform the ankle into a new hinge (knee) joint. This case describes an example of rotationplasty as a limb salvage option following a failed distal femoral reconstruction in a paediatric patient with osteosarcoma. Additionally, to reduce the likelihood of revision for malalignment, a tibial osteotomy was not performed, and the intramedullary nail was kept in a dynamically locked position, preserving the potential for growth through the proximal tibial physis in the rotated limb. This modification demonstrates that sacrificing the proximal tibial physis is not always necessary when performing rotationplasty, offering young patients both disease control and gradual growth of the operative limb with less importance on speculative growth calculations preoperatively.
Use of a magnetic intramedullary nail for axial compression in endoprosthetic reconstruction of the humerus: a description of technique
Pathological fractures, both completed and impending, of the humeral diaphysis from primary or metastatic disease demand a reconstruction that restores stability while preserving shoulder function and alleviating pain. Conventional reconstructive approaches include the use of long-stemmed endoprosthetic devices, plate-and-screw fixation or intramedullary nailing, all of which can be limited in their success when residual bone is short or biologically weak. This case study details the management of a patient with metastatic leiomyosarcoma who presented with refracture through a previously cement-augmented lesion. Following resection, the diaphyseal defect was spanned using a custom humeral cage. A NuVasive PRECICE magnetically controlled intramedullary nail, pre-lengthened before insertion, was placed through the cage and shortened intraoperatively to achieve axial compression between the cage and bone segments. At the 6 month follow-up, the patient had excellent shoulder range of motion, apparent ingrowth into the cage, and he was able to resume activities of daily living with minimal pain.
Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection
BackgroundIn melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood.MethodsFluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g., tumor) or by fluorescent cell subset markers (e.g., CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune-related proteins were collected and normalized to account for system variation and ROI area. ResultsTumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years.ConclusionWe demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.
Physeal-Sparing Soft Tissue Realignment in Pediatric Patellofemoral Instability Patients: A Review of Treatment Options and Outcomes
Patellofemoral instability is a common condition in children, with an annual incidence of approximately 50 cases per 100,000 children. Instability of the patella involves a number of structures, such as the medial patellofemoral ligament and the vastus medialis obliquus, which can be used for patellar realignment in soft tissue, physeal-sparing procedures. In this rapid review, we aim to review the surgical interventions, post-operative outcomes, and associated surgical complications of global soft tissue procedures in the management of patellofemoral instability. A search of the Medline database was conducted to identify studies evaluating the treatment and outcomes of global treatment of pediatric patellofemoral instability. The included studies analyzed the surgical management of patellofemoral instability in pediatric patients, utilizing soft tissue global procedures and reported functional outcomes, return to sport or play, and post-operative complications. A total of eight studies were included, comprising a cohort of 270 pediatric and adolescent patients and 334 knees. The average patient age was 10.6 years, with 60.4% (163/270) patients being female, and the mean follow-up duration was 58.4 months. Of the eight studies, two examined the three-in-one procedure, three examined the four-in-one procedure, one examined a combination of medial and lateral release, and two examined the Galeazzi procedure. This review underscores the variety of global physeal-sparing surgical procedures available for treating patellofemoral instability. While outcomes are generally favorable, with high rates of return to sport, recurrent residual instability and recurrent dislocation remain significant challenges, with residual instability affecting nearly half of patients. Future research should focus on exploring long-term outcomes, optimizing patient selection, and identifying the causes of recurrent instability to further enhance patient outcomes and reduce complication rates.
Multisite Study of the Management of Musculoskeletal Infection After Trauma: The MMUSKIT Study
The optimal duration and choice of antibiotic for fracture-related infection (FRI) is not well defined. This study aimed to determine whether antibiotic duration (≤6 vs >6 weeks) is associated with infection- and surgery-free survival. The secondary aim was to ascertain risk factors associated with surgery- and infection-free survival. We performed a multicenter retrospective study of patients diagnosed with FRI between 2013 and 2022. The association between antibiotic duration and surgery- and infection-free survival was assessed by Cox proportional hazard models. Models were weighted by the inverse of the propensity score, calculated with a priori variables of hardware removal; infection due to , , or species; and flap coverage. Multivariable Cox proportional hazard models were run with additional covariates including initial pathogen, need for flap, and hardware removal. Of 96 patients, 54 (56.3%) received ≤6 weeks of antibiotics and 42 (43.7%) received >6 weeks. There was no association between longer antibiotic duration and surgery-free survival (hazard ratio [HR], 0.95; 95% CI, .65-1.38; = .78) or infection-free survival (HR, 0.77; 95% CI, .30-1.96; = .58). Negative culture was associated with increased hazard of reoperation or death (HR, 3.52; 95% CI, 1.99-6.20; < .001) and reinfection or death (HR, 3.71; 95% CI, 1.24-11.09; < .001). Need for flap coverage had an increased hazard of reoperation or death (HR, 3.24; 95% CI, 1.61-6.54; = .001). The ideal duration of antibiotics to treat FRI is unclear. In this multicenter study, there was no association between antibiotic treatment duration and surgery- or infection-free survival.
Exploring the drivers of price variation in orthopaedic radical bone tumor resection: A nationwide database study
BackgroundRadical resection of bone tumors is a clinically effective but costly procedure. Despite the implementation of federal price transparency mandates, little is known about the nationwide variation in negotiated prices for these specialized oncologic surgeries. This study aimed to quantify the variation in negotiated rates for radical resection of the humerus and femur/knee and identify associated hospital, payor, and state-policy drivers.MethodsThis cross-sectional study analyzed hospital-negotiated payor rates from the Turquoise Health database for current procedural terminology (CPT) codes 24150 (humerus resection) and 27365 (femur/knee resection). Multivariate linear regression was used to determine the associations between hospital size and type, payor class, and state-level policies (Medicaid expansion, Certificate of Need [CoN] laws, All-Payer Claims Database [APCD] mandates, and Nurse Practitioner [NP] scope of practice) on negotiated payor rates.ResultsA total of 285,857 negotiated rates were analyzed. Significant price variation was observed across all factors. Large hospitals (>1000 beds) and Critical Access Hospitals (for femur/knee resection only) had significantly higher rates. CoN laws were associated with higher prices for both procedures (+ 348.25 and + 667.98, respectively), as were APCD mandates for femur/knee resections (+1231.24). Medicare Advantage plans paid inconsistently compared to commercial plans, paying more for humerus but substantially less for femur/knee resections.DiscussionNegotiated prices for radical bone tumor resection are highly variable and influenced by a complex interplay of market dynamics, challenging the assumption that price transparency alone can standardize healthcare costs for specialized care.