Citations

Abstract Purpose Iliopsoas tendinitis following total hip arthroplasty (THA) has been described to result from acetabular component overhang as well as prominent femoral collars. Yet, a portion of patients experience iliopsoas tendinitis in the setting of well-positioned components. The purpose of this study was to assess anatomic factors predisposing to iliopsoas tendinitis after THA. Methods Patients with THAs performed at three academic institutions who subsequently underwent arthroscopic iliopsoas release were retrospectively reviewed from 2015 to 2025 and propensity matched in a 1:3 fashion to a control group of THAs without subsequent iliopsoas release. Controls were matched by age, surgery date, laterality, sex, surgical approach, and implanted femoral component. Patients with iliopsoas tendinitis and subsequent release (THA-IP) were evaluated for anterior acetabular component overhang and femoral collar overhang, when a collar was present. We also evaluated the absolute and relative profile of the lesser trochanter on anteroposterior radiographs, understanding that when less of the lesser trochanter is visualized, the trochanter is anatomically displaced posterolaterally, resulting in a more arduous route from the inner pelvic origin of the iliopsoas to its insertion on the femur. Results Forty-five patients (mean age: 57±11; 71% female; 19 direct anterior, 10 anterolateral, 16 posterior approach) undergoing THA-IP were analyzed and matched to 135 controls. Both groups demonstrated a median cup size of 54 mm and head size of 36 mm. Average time to iliopsoas release after THA was 4 years. Anterior cup overhang of >2 mm was present in 49% of THA-IP patients, with 18% having collared femoral components, and 9% demonstrating collar overhang of >2 mm. Overall, 19 THA-IP patients had <2 mm of cup and collar overhang and 26 patients had >2 mm of overhang. THA-IP patients with <2 mm of cup and collar overhang had significantly greater relative posterolateralization of the lesser trochanter compared to those with overhang of >2 mm (p=0.010) and to controls (p=0.037). Conclusion Visualizing “Less of the Lesser” on anteroposterior hip radiographs and associated posterolateralization of the lesser trochanter may be an anatomic risk factor for iliopsoas tendinitis following THA, even in the presence of satisfactorily positioned components.

Abstract Purpose To investigate clinical outcomes, including patient reported outcome measures (PROMs), subjective anterior groin pain and hip flexion strength, and reoperation rates following arthroscopic iliopsoas fractional lengthening after total hip arthroplasty (THA). Methods Patients who were indicated for arthroscopic iliopsoas fractional lengthening after ipsilateral THA were prospectively identified between 2023-2025 at a single institution. Pre- and post-operative PROMs, including Visual Analog Scale (VAS), Tegner activity scale, Single Assessment Numeric Evaluation (SANE), and subjective anterior groin pain and hip flexion strength were analyzed. Reoperations at final follow-up were also evaluated. Results A total of 44 hips in 41 patients (23 females and 18 males) were included (mean age: 64.7 ± 10.2, mean BMI: 29.9 ± 5.9 kg/m2). Fifty-five percent of patients underwent surgery on their right hip. The mean postoperative follow-up timeframe was 10.0 ± 7.1 months. There was a significant improvement in postoperative PROMs compared to pre-operative levels for VAS at rest (1.3 ± 1.9 vs. 2.9 ± 2.2), VAS with use (3.1 ± 3.8 vs. 8.0 ± 1.6), Tegner activity scale (2.9 ± 1.3 vs. 2.1 ± 1.1), and SANE (74.0 ± 20.3 vs. 47.9 ± 23.4) (p<0.001 for all). Over 90% of patients reported feeling much better or slightly better regarding their anterior groin pain at 2-weeks post-operatively (93%), 6 weeks post-operatively (90%), 3 months post-operatively (93%), and at final follow-up (91%). Regarding hip flexion strength, 73% reported feeling much better or slightly better at 2-weeks post-operatively, 95% at 6-weeks post-operatively, 85% at 3 months post-operatively, and 61% at final follow-up. Only 2 patients (5%) reported feeling much weaker at final follow-up. Two of 44 hips (5%) underwent reoperation at final follow-up. One patient underwent a 2-stage revision THA at 5 months postoperatively due to infection, while 1 patient underwent an open iliopsoas release with acetabular screw removal and liner exchange. Overall, the mean surgery satisfaction was 8.1 ± 2.6 on a scale of 1-10. Conclusion Patients who underwent arthroscopic iliopsoas fractional lengthening following THA demonstrated satisfactory postoperative outcomes, with over 90% reporting durably improved anterior groin pain and nearly two-thirds reporting increased hip flexor strength throughout follow-up.

Background Many guidelines list migraine with aura (MwA) as a contraindication to estrogen-containing combined hormonal contraceptives (CHCs) due to vascular risks. However, current evidence is based on small sample studies with potential influence by confounding factors. Additionally, few studies have examined the vascular risk associated with modern CHCs with lower dose estrogen, particularly in relation to aura status. The present study aims to investigate the vascular risk of modern CHCs in women with migraine with and without aura. Methods We used a de-identified electronic medical record database with 120 million patients across multiple health systems in the United States of America. We included female patients aged 18–45 years who received a migraine diagnosis code, had at least three office visits within three years, and were prescribed at least one migraine-specific medication within 6 months following the first outpatient visit. All data after 2010 were included. Patients with prior cardiovascular events were excluded. Our composite endpoint consisted of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism and intravenous thrombolytic administration. We stratified our analysis according to CHC exposure and aura status and compared the incidence of the endpoint with high-dimensional propensity score-matching between CHC users and non-users in (i) the overall cohort, (ii) MwA and (iii) migraine without aura (MwoA); between MwA and MwoA in (iv) patients prescribed CHCs; and in (v) those without CHC prescriptions. Results We included 5535 patients who received CHC prescriptions and 21,520 who did not. 114 (2.06%) of CHC users and 547 (2.54%) of CHC non-users had at least one vascular event. With propensity score-matched comparison, the composite endpoint did not significantly differ between CHC and non-CHC in the overall migraine group, those with MwA and the MwoA group. In those prescribed CHC, MwA and MwoA did not differ in all the outcomes. For CHC non-users, MwA was associated with a higher incidence of acute ischemic stroke (hazard ratio = 2.45; 95% confidence interval = 1.58–3.78; p < 0.001; n = 6201 in each group) and the composite endpoint (hazard ratio = 1.34; 95% confidence interval = 1.08–1.67; p = 0.008). Conclusions Our real-world study showed that exposure to modern CHC was not associated with a significant increase in vascular risk in women aged 18–45 years with migraine, MwA or MwoA who have no prior cardiovascular events. However, in those who never received CHC, MwA was associated with higher vascular risks compared to MwoA. While limitations exist using large scale electronic medical record databases for analysis, our results suggest that carefully designed prospective studies should be conducted to reassess the vascular risk associated with CHC use in women with migraine, especially MwA.

Radiation exposure to the eye during cancer treatment can lead to ocular radiation injury (ORI), a devastating condition that can have a profound and permanent impact on vision-related quality of life. Rodent models do not have adequate ocular anatomy to accurately simulate human ORI, and modeling in non-human primates is limited by logistical and ethical concerns. To improve future translational research investigating ways to treat or prevent ORI, we developed protocols for a tree shrew model of ORI. Northern tree shrews (Tupaia belangeri) were obtained by our laboratory. Custom housing and handling methods were developed, including custom body suits to maintain the tree shrew’s body temperature during procedures. Radiation delivery was optimized to accurately deliver radiation, and imaging was performed to observe fundus changes from ORI. Optimization of tree shrew handling, housing, anesthesia approaches, radiation delivery, and clinically-relevant ocular imaging permitted successful induction and assessment of ORI in tree shrews. With these protocols, tree shrews can be used as a highly relevant model organism with key anatomic features similar to humans to study ORI.

Abstract The prognosis for patients afflicted with GBM has remained dismal in spite of decades of investigations, which speaks to the need to identify targets that drive essential functions in GBM, using well-tolerated, brain permeant inhibitors. Here we report our studies of MT-125, a small molecule inhibitor of non-muscle myosin IIA and IIB. MT-125 has high brain penetrance and an excellent safety profile; blocks GBM invasion and cytokinesis; and prolongs survival in murine GBM models. By impairing mitochondrial fission, MT-125 increases redox stress and induces DNA damage and ferroptosis; and these effects explain why this drug synergizes with radiotherapy in prolonging survival in murine GBM models. MT-125 also induces oncogene addiction to receptor tyrosine kinase (RTK) signaling through a mechanism that is also driven by redox stress, and it also synergizes with FDA-approved RTK and MAP Kinase pathway inhibitors in vitro. Furthermore, MT-125 also synergizes with an FDA approved, RTK inhibitor in vivo, with the combination producing long-term, tumor free survival in an aggressive, preclinical murine model of GBM. MT-125’s long-term administration is well-tolerated at doses well above what is predicted to be therapeutic in multiple mammalian species. These data provide a powerful rationale for the clinical development of NMII targeting therapeutics to treat cancer and demonstrates that MT-125 has strong clinical potential for the treatment of GBM.

Abstract Glioblastoma is a highly lethal malignancy with dismal overall survival and near universal recurrence despite maximal multimodal therapy. Patients with unmethylated O6-methylguanine methyltransferase (MGMT) promoters do not derive survival benefit from adjuvant temozolomide. Immunotherapies have revolutionized cancer care; however, this modality has yet to translate into survival benefits in glioblastoma in part due to both local and systemic immunosuppressive states. Here, we report the results of a phase 1 clinical trial (NCT04015700) evaluating the safety and feasibility of GNOS-PV01, a personalized DNA vaccination platform that safely immunized against up to 40 patient-specific neoantigens in a clinically relevant timescale following surgical resection and radiation for MGMT-unmethylated glioblastoma patients. Multisector tumor sampling at time of resection enabled personalized and spatially representative neoantigen identification through an established pipeline. In the nine participants receiving vaccines, there were no unexpected toxicities or serious adverse events with a median vaccine delivery time of 10 weeks post-radiation. The vaccination was strongly immunogenic and induced activation and expansion of both local infiltrating CD8+ and CD4+ T-cells and circulating peripheral T-cells. T-cell receptor sequencing revealed both expanded pre-existing populations as well as novel neoantigen-specific populations, suggesting that vaccination both reinvigorates pre-existing immunity and generates novel immune reactivity. We developed a new technology to profile T-cells at single-nuclei resolution from frozen tissue revealing that vaccination altered gene expression signatures involved in inflammatory response and lymphocyte activation in the tumor microenvironment. Exposure to dexamethasone greatly suppressed immune reactivity, while PD-1 blockade enhanced local immune responses. With respect to efficacy, one third of patients survived longer than 24 months with one long-term survivor living &gt;40 months from time of diagnosis, exceeding survival of recently published trials. Thus, our study demonstrates the safety, feasibility, and preliminary clinical efficacy of a personalized multivalent neoantigen vaccination platform in a devastating cancer.

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain in female athletes. There are limited data on midterm outcomes for female athletes undergoing hip arthroscopic surgery. Purpose: To evaluate return-to-sport rates and clinical outcomes in female athletes with FAI after primary hip arthroscopic surgery with labral repair and femoral osteochondroplasty. Study Design: Case series; Level of evidence, 4. Methods: A retrospective analysis of a single institution’s database was performed to identify female athletes who underwent primary hip arthroscopic surgery with labral repair and femoral osteochondroplasty from July 2011 to October 2019 with a minimum 5-year follow-up. Preoperative radiographs were evaluated for the lateral center-edge angle, Tonnis angle, Tonnis grade, and alpha angle. Patient-reported outcome measure (PROM) scores, including those for the modified Harris Hip Score, Hip Outcome Score, Tegner Activity Scale, and visual analog scale for pain, as well as patient satisfaction with surgery were analyzed postoperatively. Results: A total of 63 hips (27 left, 36 right) in 56 female patients (mean age, 21.6 ± 8.0 years; mean body mass index, 24.7 ± 4.8 kg/m 2 ) were included and followed for a mean of 8.4 ± 2.1 years (range, 5.0-13.2 years). Preoperatively, patients participated in basketball (n = 18), dance (n = 21), hockey (n = 8), and soccer (n = 12). Of the 56 patients, 41 attempted to return to sport. There were 28 (68%) female athletes who successfully returned to their preoperative sport. Of the total cohort, 21 (38%) patients cited non–hip-related factors for discontinuing their sport. All postoperative PROM scores improved significantly compared with preoperatively ( P ≤ .002) for patients with available preoperative data. Those who returned to sport had significantly improved Hip Outcome Score values compared with those who did not return to sport ( P ≤ .010). Conclusion: Female athletes who underwent primary hip arthroscopic surgery for FAI had significant improvements in PROM scores and moderate return-to-sport rates at a minimum 5-year follow-up. Most athletes discontinued sports because of non–hip-related factors, although hip-related issues were also cited. Our analysis highlights the need for thorough perioperative counseling and establishing appropriate patient expectations for female athletes before hip arthroscopic surgery.

A positive margin following tumor resection (i.e., surgical removal of a cancerous tumor) indicates that cancer may remain in the body and can require a re-operation. This study is part of a larger project designing a technology to support the intraoperative evaluation of margins. This study explores the goals, decisions, information needs, and system requirements of a surgeon performing breast cancer surgery. We conducted semi-structured interviews with 11 breast surgeons to understand how they currently perform resections and then performed a qualitative thematic analysis. We identified three main goals and 13 subgoals. The three main goals are: treating cancer, meeting patient needs, and meeting institutional needs. Surgeons made multiple decisions to accomplish each sub goal and required multiple information elements to make these decisions. Our results will inform the design of the new technology and a sociotechnical systems-based analysis to ensure the technology fits in surgeon workflow.

Objectives: To evaluate return-to-sport (RTS) rates and patient reported outcome measures (PROMs) following hip arthroscopy for femoroacetabular impingement (FAI) in active football players with a minimum of 5-years follow-up. Methods: All active football players who underwent hip arthroscopy for FAI from 2010-2019 were identified. Preoperative radiographic measures including lateral center edge angle, Tönnis angle, alpha angle, and acetabular depth were obtained. Patients were evaluated for post-operative RTS and revision surgery data at final follow-up. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), HOS Activities of Daily Living (HOS-ADL), HOS Sports Specific Subscale (HOS-Sports), Tegner Activity Scores, Visual Analogue Scale (VAS) for pain, and surgery satisfaction were collected at a minimum 5-year follow-up. Descriptive and comparative statistical analysis was performed using R software (version 4.4.1). Results: Sixty-six hips from 53 male patients were included. The mean age was 20.4 ± 6.4 years and mean BMI was 27.3 ± 6.6 kg/m² (Table 1). Mean follow-up was 8.7 ± 2.8 years. The majority (60%) were high school players and 19% were college players. Figure 1 displays the most commonly affected positions which included wide receiver (32%), defensive lineman (26%), and tight end or offensive lineman (16%). There were 11 bilateral cases and 2 revisions. The mean lateral center edge angle was 31.6º ± 6.4, the mean Tönnis angle was 5.0º ± 5, and the mean alpha angle was 63.2º ± 12.7. There was significant improvement in all PROMs from baseline to a minimum 5-year follow-up (p<0.04). Fifty-four percent of athletes returned to football postoperatively and the average overall surgery satisfaction rating was 8.1/10. Among those who didn’t return, 14% cited hip-related reasons, while 67% cited non-hip related reasons such as priorities changing or graduating (Figure 2). Athletes who returned to football had significantly higher mean HOS-ADL (p=0.049), HOS-Sport (p=0.042), and Tegner level before surgery (p=0.023) compared to those who did not return (Table 2). Conclusions: Football players undergoing hip arthroscopy for FAI demonstrate significant improvements in outcome scores at a minimum 5-year follow-up with a moderate return-to-sport rate. Athletes who are able to return to football report higher patient reported outcomes compared to those who do not. Player position may also influence incidence and outcomes. Although football players demonstrate significant improvements following hip arthroscopy, the moderate RTS rates highlights the demanding nature of the sport and need for improved perioperative counseling.

Objectives: Historically, horizontal cleavage meniscus tears have been debrided with single leaflet preservation, but more recently this has been challenged by repair of these tear types. While circumferential meniscus repair with all-inside and inside-out instrumentation has been described, there remains a paucity of literature regarding the clinical outcomes of this technique. Our purpose was to assess clinical outcomes and reoperation rates of circumferential meniscus repair for horizontal cleavage tears at minimum 2-year follow-up. Methods: Patients with isolated horizontal cleavage tears of the meniscus (Fig. 1a) undergoing primary circumferential meniscus repair (Fig. 1b), including both inside-out and all-inside suturing techniques, at a single institution between 2015 and 2022 were eligible for inclusion and analyzed retrospectively. Arthroscopic images and operative notes were examined to confirm circumferential meniscal repair. Patient demographics, surgery details, and clinical findings were extracted from the institutional electronic medical records. Exclusion criteria consisted of patients not consenting for research, less than 2-years of clinical follow-up, and concurrent ipsilateral repair of a non-horizontal cleavage tear. Patients were not excluded if they had a concomitant anterior cruciate ligament reconstruction (ACLR). Thirty-seven patients met the criteria for inclusion in this study. Knees were analyzed for laterality, number of sutures, suturing technique, concurrent injuries, concurrent procedures, and surgical history. Visual Analogue Scale (VAS) for pain, Tegner, and International Knee Documentation Committee (IKDC) scores were collected at minimum 2-year follow-up and analyzed. Return to sport (RTS) and revision surgery were analyzed. Results: Thirty-seven patients (25 male, 12 female; mean age, 29.4 ± 12.4 years) who underwent circumferential meniscal repair of a horizontal cleavage tear were included in the study and followed for a mean of 6.2 years (range, 2.2-9.3 years, Table 1). There was a total of 38 knees (23 right, 15 left). One patient (3%) had bilateral circumferential meniscal repair surgeries done at separate times. Three (16%) patients failed primary repair and had secondary partial meniscectomy. Similar numbers of circumferential meniscal repairs were performed on lateral and medial menisci, 21 (55%) and 17 (45%), respectively. An average number of 3 ± 2 sutures were used at the time or repair with one of 38 menisci (3%) having a hybrid combination of both all-inside and inside-out suture technique, 24 menisci (63%) had all-inside technique, and 13 menisci (34%) had inside-out technique. Concurrent procedures included 4 ACL reconstructions (3 autograft, 1 allograft), and 8 chondroplasties (4 patella, 2 trochlea, 1 medial femoral condyle, and 1 unspecified, Table 2). At the time of final follow-up, patients reported mean Tegner activity scores of 6.2 ± 2.3, VAS pain with rest of 1.0 ± 2.0, VAS pain with use of 2.5 ± 2.7, and IKDC of 81.6 ± 18.6. When asked, using a VAS Five Point scale, how their knee is currently compared to before their surgery, 14 (74%) feel much better than before surgery, 2 (11%) feel slightly better than before surgery, 1 (5%) feels no change when compared to before their surgery, 2 (11%) feel slightly worse than before surgery, and no one felt much worse than before surgery. Sixteen patients were involved in sports before their surgery. Of those that played sports before their surgery, 14 (88%) returned to sport (Table 3). The most common sports played were hockey (19%), volleyball (19%), tennis (13%), and football (13%). Levels of sport played before surgery included 7 (44%) recreational, 6 (38%) high school, 2 (13%) college, and 1 (6%) club. Levels of sport played after surgery for those who returned to sport included 6 (43%) recreational, 2 (14%) high school, 5 (36%) college, and 1 (7%) club with a significant increase in levels of sport played after surgery ( p ≤ 0.006) compared to before surgery. Conclusions: At an average of 6-years of follow up, there was an 84% success rate of circumferential meniscal repair for horizontal cleavage tears. Most patients who play sports, return to sport and do so at the same or higher level and report successful PROMs. Circumferential meniscal repairs should be considered for patients with horizontal cleavage tears.