Citations

Abstract Endometriosis (EMS) is an estrogen-dependent, chronic inflammatory disease in which endometrial-like tissue grows outside the uterus, leading to pelvic pain, dysmenorrhea, dyspareunia, and infertility. Increasing evidence shows that these symptoms do not arise from the presence of ectopic tissue alone. Rather, they reflect a sustained neuroimmune process in which inflammatory, neural, and stromal pathways continuously interact. Within the peritoneal cavity of EMS, immune activation elevates cytokines such as IL-1β, IL-6, and TNF-α, which stimulate production of neurotrophic mediators including NGF, BDNF, and IGF-1. These signals induce sensory-nerve sprouting, lower nociceptor thresholds, and convert lesions into hyperinnervated, pain-generating structures. Once these fibers infiltrate lesions, they release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP). Rather than simply transmitting nociceptive signals, these neurons actively reshape the lesion microenvironment. SP and CGRP amplify inflammation, promote immune-cell recruitment, and drive epithelial–mesenchymal transition and myofibroblast differentiation, accelerating the fibrotic remodeling characteristic of deep infiltrating endometriosis. This neuropeptide-driven activity strengthens the lesion’s neuroimmune profile and forms a feed-forward loop in which inflammation, nerve growth, and fibrosis reinforce one another over time. Persistent nociceptive input from sensitized lesions produces downstream changes in the central nervous system. Within the spinal cord, activated microglia and astrocytes release proinflammatory mediators that enhance excitatory signaling and diminish inhibitory tone. With continued input, spinal and cortical circuits undergo neuroplastic changes that give rise to central sensitization, hyperalgesia, allodynia, and the cross-organ sensitization that links pain across the uterus, bladder, bowel, and pelvic floor. These long-range effects explain why pain may persist even when visible lesions are small or surgically removed. Together, these findings position endometriosis as a chronic systemic neuroimmune disorder maintained by reciprocal signaling between immune cells, sensory neurons, and central pain networks. Viewing EMS through this lens highlights multiple therapeutic entry points. Targeting NGF–TrkA and CGRP–RAMP1 signaling, modulating macrophage and B-cell function, dampening glial activation, or applying neuromodulatory techniques offers a more rational pathway to interrupt the self-reinforcing neuroimmune loop that sustains pain. Integrating immunologic and neurobiologic evidence therefore provides a foundation for mechanism-based therapies capable of delivering more durable relief and improving long-term quality of life. Citation Format: Ariana F. Rahman. Endometriosis as a Neuroimmune Disorder: Integrating Inflammation, Innervation, and Sensitization [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A062.

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.

BACKGROUND AND OBJECTIVES: The purpose of this study was to analyze the impact of patient-specific rods on mechanical complications after adult thoracolumbar spinal deformity surgery. METHODS: A consecutive series was analyzed of 200 adult thoracolumbar spinal deformity patients. Half of the patients (n = 100) had surgery just before implementing patient-specific rods, and the other 100 patients had surgery immediately after adoption of patient-specific rods. All patients had instrumented fusions from the thoracic spine to the pelvis. Mechanical complications were defined as rod fracture, proximal junctional kyphosis, proximal junctional failure (revision surgery requiring proximal fusion extension), and/or revision surgery for rod fracture or pseudoarthrosis. Minimum follow-up was 2 years. RESULTS: A total of 200 patients were included with a median (IQR) age of 68 (61, 73), body mass index of 28 (25, 32), and 73% were female. The patients with patient-specific rods compared with those without had less preoperative kyphosis (39° vs 44°, P = .01), a higher median number of rods (4 vs 2, P = .04), more often a combined anterior-posterior approach (61% vs 46%, P = .047), more commonly a upper instrumented vertebra vertebroplasty (67% vs 45% P = .003), and postoperatively had less thoracic kyphosis (45% vs 49%, P = .02). Patient-specific rod patients had a lower rate of mechanical complications (29% vs 47%, P = .01), a lower rate of rod fracture (3% vs 16%, P = .003), and shorter operative times (215 minutes vs 250 minutes, P = .04). On multivariable analysis, the only 2 independent predictors of reducing the rate of mechanical complications were the utilization of patient-specific rods (odds ratio 0.47, P = .013, CI 0.26-0.85) and lower postoperative thoracic kyphosis (odds ratio 1.02, P = .04, CI 1.00-1.05). CONCLUSION: In a consecutive series of adult thoracolumbar spinal deformity patients, patient-specific rods reduced the odds of mechanical complications by over 50%. Adoption of patient-specific rods should be considered to optimize patient outcomes after adult spinal deformity surgery.

Abstract Glioblastoma (GBM) is an aggressive, high-grade glioma with a near-universally fatal prognosis. Therapeutic failure is often attributed to the highly selective blood brain barrier (BBB), the diffuse infiltrative nature of the tumor, and the marked intratumoral heterogeneity of GBM. Although antibody drug conjugates ADCs have shown promise for high grade gliomas such as GBM, efficacy is limited by ADC size. Aptamers—short, synthetic, single-stranded DNA or RNA molecules—can be ∼6-fold lower in molecular weight than IgG antibodies and have the potential to cross the intact BBB. Unlike other nucleic acid-based therapies, aptamer function arises from three-dimensional shape rather than genetic coding. Here we aim to replace the targeting component of the ADC paradigm with a DNA aptamer, thus creating an aptamer-drug conjugate (ApDC). We employed in vivo SELEX using an orthotopic patient-derived xenograft (PDX) GBM mouse model and a vast (∼100 trillion 80-mer sequences) ApDC library. We report the results from this first in vivo ApDC selection of its kind. We characterize target tissue binding ex vivo , cell association, biodistribution, and pharmacokinetics from this selection. This study exemplifies an unbiased approach to a problem that rational design has yet to overcome, offering a new direction for GBM therapeutic development.

As plastic surgery has grown, leaders within the field have advocated transforming plastic surgery divisions into independent departments. This shift raises critical questions regarding departmental identity, resource allocation, and potential administrative conflicts. The purpose of this study was to explore the potential implications of these institutional hierarchies from the perspective of plastic surgery program chairs. An anonymous online survey was distributed to chairs of accredited plastic surgery programs. Thirty-five of 103 (34.0%) individuals responded to the online questionnaire. Twenty-eight of 33 (84.8%) programs were classified as divisions of surgery, whereas 5 of 33 (15.2%) were independent departments. Nine of 28 (32.1%) respondents believed their division had lost patients to other surgical specialties because their program was not an independent department. Eighteen of 33 (54.5%) respondents believed that plastic surgery is negatively impacted when institutional programs are not independent departments. Respondents who indicated losing patients to other specialties, compared with those who did not, were 22.4 times more likely to be critical of institutional hierarchies ( P =0.004). Respondents from independent departments were 12.6 times more likely to also express a negative view ( P =0.049). Our findings provide a nuanced understanding of the institutional structures within plastic surgery programs. The extent to which institutional hierarchies negatively impact plastic surgery remains unclear. The significant association between patient loss and negative perceptions implies that direct clinical or financial repercussions strongly shape opinions. Moreover, chairs from independent departments may be more critical of institutional hierarchies because they have a deeper appreciation for the advantages that come with departmental status.