Citations

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Abstract INTRODUCTION The genetic basis of sporadic early‐onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late‐onset Alzheimer's disease (LOAD) polygenic risk in EOAD. METHODS A LOAD polygenic score (PGS) was calculated in the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers. RESULTS Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset ( p = 0.106) or with cognitive performance ( p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal‐associated protein 25 (SNAP‐25) ( p = 2.3 × 10 −5 ). DISCUSSION While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology. Highlights LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal‐associated protein 25 (SNAP‐25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD.

Background: Arthroscopic treatment of excessive acetabular coverage with pincer morphology or coxa profunda can be challenging. In patients with excessive acetabular coverage with nondistractible hips, an outside-in capsuolotomy can be considered to gain safe and efficient intra-articular access to the hip. Indications: The indications for an outside-in capsulotomy include patients with acetabular retroversion, a lateral center-edge angle >40°, coxa profunda or protrusio, or stiff, older male patients who remain hip preservation candidates. Technique Description: The outside-in capsulotomy is performed once it is recognized that traction on the operative extremity will not provide adequate working space for safe intra-articular access. Traction is taken off the operative extremity, and an anterolateral portal is localized to the 12:00 position on the hip joint with the use of fluoroscopy. The camera is then placed in a juxta-capsular location, and a modified anterior portal is created under direct arthroscopic visualization. We then proceed with extracapsular dissection to identify the indirect head of the rectus. An outside-in capsulotomy is then performed parallel to the indirect head of the rectus, approximately 5 mm distal to its insertion on the acetabular rim. Prior to deep completion of the capsulotomy, the hip joint is flexed to 30° to protect the articular cartilage of the femoral head. Once intra-articular access is obtained, traction can be reapplied, and one can proceed with hip arthroscopy in a standard fashion. Results: This technique decreases the traction time needed, given that the capsulotomy is performed without traction applied. Additionally, the amount of force required for hip distraction is decreased once the capsuolotomy has been completed, through usual sectioning of the iliofemoral ligament. The presented technique is both safe and efficacious, with no published difference in complications as compared to standard inside-out access. A published series of patients with severe pincer morphology and lateral overcoverage who undergo hip arthroscopy with outside-in access demonstrates satisfactory postoperative improvements in patient-reported outcome measures. Discussion/Conclusion: The outside-in capsulotomy provides a means for safe access to the hip joint in otherwise limited or nondistractible hips.

Background/objectives: Improvements in esophageal adenocarcinoma (EAC) treatment have reduced mortality. While chemoradiation before surgery was previously a standard of care, updated guidelines recommend peri-operative chemotherapy without chemoradiation. Continued investigation into optimal non-operative treatment paradigms for patients who defer surgery or are not candidates for surgery and certain chemotherapy regimens is needed. The impact of induction chemotherapy prior to chemoradiation on survival and surgical outcomes remains unclear. This study assessed survival and surgical outcomes in a real-world cohort of EAC patients receiving induction chemotherapy before chemoradiation. Methods: This single-institution, IRB-approved, retrospective cohort study included patients with newly diagnosed stage II-IVb (oligometastatic for IVb) EAC who received definitive chemoradiation (radiation ≥ 40 Gy and two cycles of chemotherapy) +/− esophagectomy from 2007 to 2022. Patients receiving induction chemotherapy were compared to those who did not. Endpoints included survival and surgical outcomes. Results: A total of 141 EAC patients received definitive chemoradiation; 83 received induction chemotherapy before chemoradiation. Patients receiving induction chemotherapy were younger (p < 0.01) with slightly lower performance status (p = 0.27) and presented at a more advanced stage (p < 0.001). Median OS was 3.5 years in the induction chemotherapy group compared to 2.2 years (p = 0.10). There was no difference in pathologic complete response (p = 0.81), esophagectomy frequency (p = 0.87), or surgical downstaging between treatment groups (p = 0.84). Conclusions: In this real-world, single-institutional patient cohort investigating induction chemotherapy prior to chemoradiation in EAC, patients receiving induction chemotherapy did well but did not have a statistically significant improvement in survival outcomes or surgical outcomes. This study showed that significant numbers of real-world patients may not receive esophagectomy. Thus, prospective, randomized clinical trials are warranted to better delineate the efficacy and selection of patients for induction chemotherapy when non-operative approaches are favored.

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain in young, active athletes. American football players place high demands on the hip due to the sport's requirements for pivoting, cutting, and loading in deep flexion. Although arthroscopic treatment of FAI in professional National Football League (NFL) players has shown favorable outcomes, football-specific outcomes in non-NFL athletes remain limited. Purpose: To report the return-to-sport (RTS) rates and functional outcomes at a minimum 2-year follow-up for active American football players competing at multiple levels after primary hip arthroscopy for FAI. Study Design: Case series; Level of evidence, 4. Methods: An institutional database was queried to identify all active American football players who underwent primary hip arthroscopy with labral repair between 2010 and 2023. Demographic characteristics, radiographic parameters, procedure details, complications, and reoperations were collected. Follow-up was completed at a minimum of 2 years to obtain updated patient-reported outcome measures (PROMs) as well as football-specific data, including current participation and RTS status. PROMs were reported as mean ± standard deviation, and categorical variables, including RTS, were reported as frequencies. Pre- versus postoperative PROMs were compared using t tests or Mann-Whitney U tests to assess outcomes. Results: In total, 49 hips in 38 male football players (age, 18.1 years; range, 14-26 years) were included. Most athletes played at the high school (74%) or college level (21%). A total of 51% played as linemen. Labral repair was performed in all cases. At a mean 7.6 years, mean modified Harris Hip Score was 90 ± 13, Hip Outcome Score–Activities of Daily Living was 95 ± 7, and Hip Outcome Score–Sport was 89 ± 17. Overall mean surgery satisfaction was 8.7 ± 1.7 (out of 10). Significant postoperative improvements were observed in all PROMs ( P ≤ .002). Twelve players (32%) did not attempt RTS due to other nonmedical factors and were excluded from return to sport analysis. A total of 23 (88%) players achieved RTS, and 3 players (12%) did not. Two players (8%) cited other injuries, and 1 player (4%) continued to have hip limitations. Four hips (8%) underwent reoperation at a mean 4.9 years postoperative. Conclusion: Amateur American football players undergoing primary hip arthroscopy for FAI demonstrated excellent patient-reported outcomes and a high RTS rate of 88%, when excluding those who did not return for nonmedical reasons, at a mean 7.6-year follow-up. Notable positional differences were observed across multiple levels of play. Although outcomes were generally favorable, both medical and nonmedical factors could limit return to sport, particularly among high school and college athletes.

Abstract Background Agitation is a clinically significant symptom contributing to behavioral and psychological symptoms of dementia (BPSD) but is poorly understood across the different syndromes related to Frontotemporal Lobar Degeneration (FTLD). This study investigates sex differences in agitation across FTLD‐related syndromes and its relationship to various neuropsychiatric symptoms (NPS). Method We analyzed data from 1,654 participants (916 males, 738 females; average ages 65.8 and 65.9, respectively) from the National Alzheimer's Coordinating Center (NACC) and ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study with a FTLD‐related syndrome: behavioral variant FTD (bvFTD), Primary Progressive Aphasia (non‐fluent variant (nfvPPA), semantic variant (svPPA)), Corticobasal syndrome (CBS) and Progressive Supranuclear Palsy (PSP). Participants’ symptoms were assessed using the Neuropsychiatric Inventory (NPI). Prevalence ratios and odds ratios were computed to assess the likelihood of NPS comorbidities when agitation was present in males and females. Principal Component Analysis (PCA) was performed to identify NPS associated with agitation and how they varied by sex. Result Males were more likely to experience anxiety (bvFTD: p <0.001, CBS: p <0.01, PSP: p <0.0001), apathy (nfvPPA: p <0.01, PSP: p <0.01), depression (bvFTD: p <0.0001, PSP<0.01), disinhibition (nfvPPA: p <0.0001), PSP: p <0.001), and motor symptoms (bvFTD: p <0.01, CBS: p <0.01) when agitation was present. In contrast, females had a higher likelihood of experiencing disinhibition in svPPA ( p <0.001). These findings suggest that agitation is associated with a wider range of NPS in males than in females. Agitation and NPS are especially prominent in males with PSP. Conclusion This study reveals significant sex differences in NPS in FTLD‐related syndromes when agitation is present. Males and especially PSP, are more likely to experience a broader range of NPS in association with agitation. These findings underscore the need for further investigation into the underlying mechanisms driving these sex differences, particularly focusing on the neurobiological impact of agitation, the recognition of symptoms in the presence of greater behavioral disturbances, and potential variations from informant reports. Understanding these factors will provide valuable insights into the role of agitation in the presentation of NPS across FTLD‐related syndromes. Ultimately, addressing these gaps will enhance our ability to effectively treat and manage agitation in both male and female patients with FTLD‐related syndromes.

Abstract Background Staging disease severity in dementia research requires input from an informant. The Clinical Dementia Rating Sum of Boxes (CDR) is the most used instrument for staging in Alzheimer's Disease (AD); but has been expanded to stage patients with frontotemporal lobar degeneration (FTLD) with the CDR PLUS NACC‐FTLD. An informant effect on the CDR has been reported in AD. The aim of this study is to evaluate whether informant characteristics influence the CDR PLUS NACC‐FTLD in a large cohort of participants with frontotemporal dementia (FTD). Method We included participants with a FTLD‐related syndrome from the ALLFTD study. We included participants with a CDR PLUS NACC‐FTLD higher than 0, information on the Montreal Cognitive Assessment (MoCA) scores, and the Neuropsychiatric Inventory Questionnaire (NPI‐Q). We performed a conditional growth model using multilevel linear regression analysis. We performed an exploratory stratified analysis by patient sex. Result We included 1411 participants, totalling 2063 visits. The patient's age at the initial visit was 64.7±9.4 years and 44.0% were females. Females were 69.2% of the informants, and the relationship was 79.1% spouse or partner, 10.6% children, 4.1% were siblings and 6.2% other. The CDR PLUS NACC‐FTLD scores were affected by informant characteristics. The CDR PLUS NACC‐FTLD scores were 0.41 (CI 95%:0.08 to 0.75) higher with female informants. The frequency of visits was associated with a CDR PLUS NACC‐FTLD score 0.86 higher (CI 95%:0.17 to 0.56) when visiting at least once a week, 1.46 higher (CI 95%:0.46 to 2.47) when visiting daily, and 0.83 higher (CI 95%:0.06 to 1.60) when living with the patient compared with visiting less than once a week. As expected, CDR‐FLTD scores increased with lower MoCA and higher NPI‐Q scores. In the stratified analysis by sex, we found that female informant was associated with higher CDR PLUS NACC‐FTLD scores only when patients were male. Conclusion We found that the CDR PLUS NACC‐FTLD is influenced by informant sex and frequency of visits in patients with FTLD‐related syndromes. These results are similar to those observed in AD patients and underscore the need to recognize that informant characteristics may impact dementia severity scales.

Abstract Introduction Periacetabular osteotomy (PAO) is a complex reconstructive procedure performed to address acetabular dysplasia. Postoperative pain management is challenging due to surgical invasiveness and the need to limit opioid use. Regional and local anesthesia are commonly used but may be short-lived, increasing opioid requirements. However, methadone is a long-acting analgesic that may offset these limitations. This is the first study to evaluate methadone use in PAO with arthroscopy, comparing efficacy and opioid consumption of three different anesthetic regimens: (1) lumbar plexus catheter with a single shot intrathecal hydromorphone (LP+HM) (2) locally administered intraoperative soft tissue periarticular injection with ropivacaine, epinephrine, and ketorolac (arthroplasty block [AP]), and (3) AP with intraoperative methadone (AP+M). Methods We retrospectively reviewed PAO with arthroscopy cases from 2022 to 2025 at a single tertiary center. All cases were performed by the same surgeon and anesthesia team and managed on the same postoperative floor. Patients were categorized into three groups: (1) LP+HM, (2) AP, and (3) AP+M. Primary outcomes were 48-hour morphine milligram equivalents (MME) and total inpatient opioid consumption. Length of stay (LoS), operative time, VAS pain scores at 24h and 48h, and antiemetic use were also collected. Results Fifty PAO procedures were identified. The mean age was 16.0±2.3 years, 96% were female, and mean BMI was 22.8±4.4 kg/m2. No significant differences were seen between groups. The addition of methadone to the arthroplasty block regimen (AP+M) resulted in significantly lower 48-h MME compared to AP alone (55.9 mg vs 83.3 mg, p=0.030), but did not differ significantly from LP+HM (39.0mg, p=0.593). Total inpatient opioid consumption was also significantly reduced in the AP+M (69.3 mg) and LP+HM (66.7 mg) groups compared to AP (110.5 mg, p=0.012). Similarly, 24-hour pain scores were significantly lower in the AP+M (3.6±1.9) and LP+HM (3.7±2.1) groups compared to AP (6.4±1.6, p=0.041). Length of stay was comparable across groups (p=0.39). Conclusion Intraoperative methadone added to the arthroplasty block provided comparable analgesia and reduced total opioid use compared to arthroplasty block alone. These findings support methadone as an adjunct to periarticular anesthesia for improving pain control and reducing opioid use in hip preservation surgery.

Abstract Introduction The utilization of total hip arthroplasty (THA) in skeletally immature patients remains controversial, with an open triradiate cartilage traditionally perceived as a relative contraindication due to concerns of acetabular fixation and component loosening. Early evidence suggests that THA may be a feasible option in this patient population yielding favorable short-term outcomes, however larger series and mid-term data are lacking. This study presents the largest series of THA in patients with open triradiate cartilage to date with mid-term clinical, radiographic, and patient-reported outcomes. Methods A retrospective review of our institutional Total Joint Registry identified 19 patients (22 hips) who underwent THA while having an open triradiate cartilage growth plate between the year 2000 and 2024. Skeletal maturity was assessed utilizing the modified Oxford bone age and all patients had a score of “1” or “2” on the triradiate cartilage stage of maturation. Demographics, surgical characteristics, implant data, radiographic parameters, and clinical outcomes were collected. Functional hip scores were assessed via the Harris Hip Score (HHS). Kaplan-Meier analysis was performed to analyze reoperation rates. Results The average age at surgery was 14 years (SD=1.68), the average BMI was 24 (SD=7.1) and 64% were male. Mean follow-up was 6.05 years (range 1-15). The mean modified Oxford bone age for this cohort was 23 (SD=1.4). The most common indications for THA were avascular necrosis (64%), degenerative joint disease (27%), and neoplasia (9%). Preoperatively, 54.5% of patients utilized gait aids. Postoperatively, all patients reported independent ambulation without assistive devices with an average HHS of 91.65 (SD=11.42). Ninety-six percent of implants were stable at final radiographic follow up. Both reported complications involved acetabular cup loosening, requiring revision of the acetabular component. Conclusion This study presents the largest cohort in the literature of patients who underwent THA with open triradiate cartilage. Our results highlight high patient reported outcomes and low revision rates at mid-term follow up. All patients had excellent implant fixation without radiographic signs of loosening at final radiographic follow up. These results support the use of THA in skeletally immature patients without the need to delay THA for closure of the triradiate cartilage.

Abstract Introduction Periacetabular osteotomy (PAO) is performed in the setting of hip dysplasia to increase acetabular coverage of the femoral head and improve joint biomechanics and longevity. PAO fixation is generally achieved with two or three 4.5 mm screws, as compared to the generally more substantial plate and screw constructs used in the setting of acetabular fractures or pelvic ring injuries. The purpose of this study was to evaluate postoperative changes in hip joint center medialization and lateral acetabular coverage following PAO, understanding that these radiographic measures are generally used to guide intra-operative assessment of correction. Methods A retrospective chart review of 100 consecutive PAOs during 2021-2023 at a single academic institution by four surgeons was performed. Perioperative radiographs and fluoroscopy images were evaluated to measure lateral center edge angle (LCEA), Tönnis angle, and medialization of the hip joint center. The hip joint center was measured at one-third of the diameter of the femoral head from inferior to superior, to the ilioischial line, as previously validated by Fowler and colleagues. Results One hundred PAOs in 87 patients (87% female, mean age: 23.0 years) were included. Average preoperative radiographic parameters were 19.9° for LCEA, 12.5° for Tönnis angle, and 12.6 mm for distance from the femoral head to ilioischial line. Ninety-four cases (94%) used three screws, and 6 cases (6%) used two screws for unstable fragment fixation. On immediate postoperative films, average correction was to 28.3° for LCEA, 4.9° for Tönnis angle, and 1.9 mm of pre- to postoperative femoral head medialization (p≤0.001). Patients were radiographically followed for an average of 13.3 months, with an average time to radiographic union of 7.1 months. During the course of follow-up, LCEA increased to 29.3°, Tönnis angle remained to 5.0° (p=0.47), and medialization increased to 2.7 mm (p≤0.02), suggesting further significant but clinically modest increases in lateral coverage and femoral head medialization. Conclusion While the majority of lateral acetabular coverage and femoral head medialization occurs intra-operatively at the time of PAO, patients undergo modest but statistically significant postoperative increases in lateral coverage and medialization prior to radiographic union.