1509 Background: Medicaid expansion under the Affordable Care Act has been shown to increase insurance coverage and early-stage cancer diagnoses for young adults (YAs), the age group with the highest uninsured rate. We examined whether Medicaid expansion was associated with increased receipt of timely, guideline-concordant treatment and survival among YA women newly diagnosed with breast cancer, the most common YA cancer diagnosis. Methods: Using the National Cancer Database, we identified 51,675 women aged 18-39 years who were diagnosed with breast cancer in 2011-2018. We applied the difference-in-differences (DD) method to estimate outcome changes pre vs. post Medicaid expansion, in expansion- vs. non-expansion states. Linear probability models estimated associations of Medicaid expansion with receipt of guideline-concordant treatment – including any endocrine therapy among women with ER-positive or PR-positive breast cancer, and any chemotherapy or targeted therapy among women with ER-negative and PR-negative breast cancer – and initiation of guideline-concordant treatment (surgery, chemotherapy, or targeted therapy for stage I-III diagnoses, and systemic therapy for stage IV diagnoses) <60 days after diagnosis. Flexible parametric survival models were used to estimate 2-year overall survival. DD models also adjusted for age, race/ethnicity, rurality, zip code-level income, comorbidity, and diagnosis year, with standard errors clustered at the state level. Analyses were stratified by stage at diagnosis (stage I-III vs. IV). Results: Of the subset of women with stage I-III ER-positive or PR-positive breast cancer, the percentage receiving endocrine therapy increased in expansion states (85.20% pre-expansion to 86.46% post-expansion), but decreased in non-expansion states (84.32% to 82.79%), resulting in a net increase of 2.42 percentage points (ppt; 95% CI = 0.56 to 4.28) associated with Medicaid expansion in the adjusted DD model. Among all women with stage I-III breast cancer, the percentage with treatment initiation <60 days after diagnosis decreased less in expansion states (84.10% pre-expansion to 82.36% post-expansion) than in non-expansion states (86.95% to 83.98%), resulting in a net reduction of 1.61 ppt (95% CI = 0.05 to 3.18) in treatment delays associated with Medicaid expansion. Notably, the 2-year overall survival increased in expansion states (96.84% pre-expansion to 96.99% post-expansion), but decreased in non-expansion states (97.24% to 96.30%), resulting in a net survival increase of 1.00 ppt (95% CI = 0.21 to 1.79) associated with Medicaid expansion. Conclusions: Among YA women with stage I-III breast cancer, Medicaid expansion was associated with increased receipt of guideline-concordant treatment, reduced delays in treatment initiation, and improved 2-year survival.
Intervention Design of High-Intensity Interval Training in Individuals With Spinal Cord Injury: Narrative Review and Future Perspectives
Background Individuals with spinal cord injury (SCI) have lower levels of physical activity compared to the nondisabled population. Exercise guidelines recommend moderate or vigorous exercise to improve cardiovascular health and reduce cardiometabolic risk factors in persons with SCI. High-intensity interval training (HIIT) is a popular exercise choice and encompasses brief periods of vigorous exercise paired with intermittent periods of recovery. Objectives This review describes the available literature on HIIT for individuals with SCI, including differences in protocol design and suggested areas of further investigation. Methods Our institution’s library system performed the comprehensive search. The primary keywords and phrases used to search included spinal cord injury, high-intensity interval training, tetraplegia, paraplegia, and several other related terms. Results Initially 62 records were screened, and 36 were deemed outside the scope of this review. Twenty-six studies published between 2001 and 2021 fulfilled the eligibility criteria and were divided among two researchers for review and analysis. All records required persons with SCI and a standardized HIIT intervention. Study design varied widely with respect to mode of exercise, prescribed intensity, duration of performance intervals, and session duration. This variability necessitates further investigation into the specifics of a HIIT prescription and the associated outcomes for persons with SCI. Conclusion Standardization of HIIT protocols may lead to more robust conclusions regarding its effects on cardiorespiratory fitness as well as mitigation of cardiometabolic risk factors. Meta-analyses will eventually be needed on proper dosing and session parameters to improve cardiorespiratory fitness and cardiometabolic risk factors.
Improving Mechanical Properties of Tendon Allograft through Rehydration Strategies: An In Vitro Study
Allogenic tendons grafts sourced from intrasynovial tendons are often used for tendon reconstruction. Processing is achieved through repetitive freeze–thaw cycles followed by lyophilization. Soaking the lyophilized tendon in saline (0.9%) for 24 h is the standard practice for rehydration. However, data supporting saline rehydration over the use of other hydrating solutions are scant. The purpose of the current study was to compare the effects of different rehydration solutions on biomechanical properties of lyophilized tendon allograft. A total of 36 canine flexor digitorum profundus tendons were collected, five freeze–thaw cycles followed by lyophilization were performed for processing, and then divided into three groups rehydrated with either saline solution (0.9%), phosphate-buffered saline (PBS), or minimum essential medium (MEM). Flexural stiffness, tensile stiffness, and gliding friction were evaluated before and after allograft processing. The flexural moduli in both fibrous and fibrocartilaginous regions of the tendons were measured. After lyophilization and reconstitution, the flexural moduli of both the fibrocartilaginous and non-fibrocartilaginous regions of the tendons increase significantly in the saline and MEM groups (p < 0.05). Compared to the saline and MEM groups, the flexural moduli of the fibrocartilaginous and non-fibrocartilaginous regions of tendons rehydrated with PBS are significantly lower (p < 0.05). Tensile moduli of rehydrated tendons are significantly lower than those of fresh tendons for all groups (p < 0.05). The gliding friction of rehydrated tendons is significantly higher than that of fresh tendons in all groups (p < 0.05). There is no significant difference in either tensile moduli or gliding friction between tendons treated with different rehydration solutions. These results demonstrate that allograft reconstitution can be optimized through careful selection of hydrating solution and that PBS could be a better choice as the impact on flexural properties is lower.
Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer
Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year.
(036) Outcomes of Penile Prosthesis Implantation after Transgender Phalloplasty: A Single Center Study
Abstract Introduction Many transmen chose to pursue penile prosthesis (PP) implantation as a stage of genital gender affirming surgery. The prosthesis facilitates penetrative intercourse, as the neophallus lacks rigid erectile tissue. While PP placement is a well-established and relatively low-risk surgical treatment option for erectile dysfunction is the cis-male population, published series of post-phalloplasty prosthesis placement have demonstrated a higher rate of complications and subsequent explant. Objective To demonstrate that an integrated surgical team that participates in all stages of phalloplasty creation can improve penile prosthesis outcomes in transmen. Methods We performed a retrospective review of all transmen who underwent PP implantation at our institution from January 2015 through October 2021, yielding a cohort of 44 men. Men who underwent phalloplasty for another reason (trauma, infection, priapism) were excluded. Both malleable (MPP) and inflatable (IPP) prostheses were included in the cohort. Home phalloplasty refers to phalloplasty performed at our institution, and outside phalloplasty at another institution. The surgical technique emphasizes exclusion of urinary flora from the operative field and avoiding excess anchor material to minimize niduses for infection. We analyzed preoperative, operative, and post-operative characteristics, stratified by whether the phalloplasty was performed at our institution. We also performed logistic regression for predictors of explant in the cohort. Results Cohort characteristics and outcomes are represented in Table 1. 44 PPs were implanted 28 at our institution, 16 at an outside institution. Average age was 32 and 33 in the cohorts, respectively. IPPs were more commonly implanted than MPP. Notably, operative time was significantly lower if the phalloplasty had been constructed at our institution (p=0.014). 16 men total required explant, 7/28 (25%) in the home phalloplasty group and 9/16 (56.3%) in the outside phalloplasty group. Predictors of explantation are shown in Table 2. Significant predictors included age (p=0.013), smoking (p=0.030), operative time (p=0.007), whether the phalloplasty was performed at our institution (p=0.043), and the number of pre-PP revision surgeries (p=0.047). On multivariate logistic regression including all variables significant on univariate analysis, only age (p=0.032) and operative time (p=0.010) remained significant predictors. Conclusions We present a large post-phalloplasty penile prosthesis cohort, demonstrating exceedingly low infection rate and improved explant rate in a cohort of men who all underwent both phalloplasty and prosthesis placement with the same surgical team. Our analysis suggests that phalloplasty characteristics, patient characteristics, and operative time can influence penile prosthesis outcomes. Disclosure No
109. Comparing the Postoperative Adhesion Prevention Effectiveness of Collagen-glycosaminoglycan (GAG), Hyaluronic Acid (HA), and Pentamidine Using a Turkey In Vivo Model
Survival outcomes following autologous stem cell transplant with melphalan 140mg/m
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versus 200mg/m
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preparative regimens in patients with multiple myelo
The objective of this study was to examine the effect of pulling angle on time-zero mechanical properties of intact infraspinatus tendon or infraspinatus tendon repaired with the modified Mason-Allen technique in a canine model in vitro. Thirty-six canine shoulder samples were used. Twenty intact samples were randomly allocated into functional pull (135°) and anatomic pull (70°) groups (n = 10 per group). The remaining sixteen infraspinatus tendons were transected from the insertion and repaired using the modified Mason-Allen technique before being randomly allocated into functional pull or anatomic pull groups (n = 8 per group). Load to failure testing was performed on all specimens. The ultimate failure load and ultimate stress of the functional pulled intact tendons were significantly lower compared with anatomic pulled tendons (1310.2 ± 167.6 N vs. 1687.4 ± 228.2 N, p = 0.0005: 55.6 ± 8.4 MPa vs. 67.1 ± 13.3 MPa, p = 0.0334). For the tendons repaired with the modified Mason-Allen technique, no significant differences were observed in ultimate failure load, ultimate stress or stiffness between functional pull and anatomic pull groups. The variance of pulling angle had a significant influence on the biomechanical properties of the rotator cuff tendon in a canine shoulder model in vitro. Load to failure of the intact infraspinatus tendon was lower at the functional pulling position compared to the anatomic pulling position. This result indicates that uneven load distribution across tendon fibers under functional pull may predispose the tendon to tear. However, this mechanical character is not presented after rotator cuff repair using the modified Mason-Allen technique.
Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma
PURPOSE Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis. METHODS Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529 ). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. RESULTS The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event. CONCLUSION Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.