United States

Background
Brainstem cavernous malformations (BSCM) are challenging lesions to treat surgically due to their eloquent location and proximity to critical neurovascular structures. Safe entry zones (SEZs) have emerged as important corridors for accessing these lesions while minimizing morbidity. This systematic review and meta-analysis aims to provide a comprehensive analysis of the surgical management of pontine BSCM with a focus on SEZs, clinical presentation, lesion characteristics, surgical approach, and clinical outcomes.
Methods
A systematic literature search was performed in PubMed for articles published from 1986 to June 2024 reporting on the surgical management of pontine BSCM. Data were extracted on patient demographics, clinical presentation, BSCM characteristics, surgical approach, use of SEZs, and clinical outcomes. Statistical analyses were performed to identify factors associated with improved outcomes.
Results
Fifty-seven studies with a total of 490 patients were included. The cohort was 54% female with an average age of 33.42±17.7 years. The most common presenting symptoms varied by location. Symptoms associated with a particular anatomical distribution included hemiparesis (p=.0128), hemipaesthesia (p=.0125) and diplopia (p=.001) in basilar pons, CN V palsy (p=.0140) in peritrigeminal pons, CN VII (p=.0247), CN IX (p=.001), CN X (p=.001) and vertigo (p=.006) in the inferior peduncular pons and tetraspasticity (p=.001) in the rhomboid pons. The two most common BSCM locations were peritrigeminal (31.25%) and rhomboid (33.13%). The average major diameter of BSCM was 19.05±8.75 mm and 5.3% of BSCM were developmental venous anomalies. The most frequently used surgical approaches were the suboccipital telovelar approach (31.8%), the retrosigmoid approach (18.7%), and the transpetrosal approach (6.05%) and the most commonly utilized SEZ was the lateral pontine zone (LPZ) (34.1%). Average follow-up was 4.0±4.4 years. Overall, gross total resection was achieved in 65.6% of cases, in cases utilizing the LPZ gross total resection was achieved in 82.8% of cases. Good clinical outcome (follow-up mRS&lt;2) was observed in 64.1% of patients, with an overall mortality rate of 1.0%. The use of SEZs for pontine BSCM was associated with improved clinical outcome (OR: 2.41, 95% CI: 1.279-4.546, p=.006). BSCM located in the middle peduncular pons were associated with an improved clinical outcome (OR: 6.759, 95% CI: 2.322-19.673, p=.0005), while BSCM located in the basilar pons were associated with a worse clinical outcome (OR:0.075, 95% CI: 0.010-0.584, p=.0133).
Conclusion
Surgical resection of pontine BSCM can be performed with low morbidity and mortality rates when utilizing SEZs and careful preoperative planning. The lateral pontine, supratrigeminal, and peritrigeminal SEZs are associated with high rates of complete resection and improved neurological outcomes. BSCM location dictates the choice of SEZ and surgical approach, emphasizing the importance of understanding the regional anatomy of the brainstem. Future studies with standardized reporting and longer follow-ups are needed to further refine surgical techniques, patient selection, and stratify outcomes based on anatomical distribution.


AMA Research Challenge 2024 

Surgical Management of Pontine Brainstem Cavernous Malformations: A Systematic Review and Meta-Analysis Emphasizing Safe Entry Zones and Clinical Outcomes

Background
Brainstem cavernous malformations (BSCM) are challenging lesions to treat surgically due to their eloquent location and proximity to critical neurovascular structures. Safe entry zones (SEZs) have emerged as important corridors for accessing these lesions while minimizing morbidity. This systematic review and meta-analysis aims to provide a comprehensive analysis of the surgical management of pontine BSCM with a focus on SEZs, clinical presentation, lesion characteristics, surgical approach, and clinical outcomes.
Methods
A systematic literature search was performed in PubMed for articles published from 1986 to June 2024 reporting on the surgical management of pontine BSCM. Data were extracted on patient demographics, clinical presentation, BSCM characteristics, surgical approach, use of SEZs, and clinical outcomes. Statistical analyses were performed to identify factors associated with improved outcomes.
Results
Fifty-seven studies with a total of 490 patients were included. The cohort was 54% female with an average age of 33.42±17.7 years. The most common presenting symptoms varied by location. Symptoms associated with a particular anatomical distribution included hemiparesis (p=.0128), hemipaesthesia (p=.0125) and diplopia (p=.001) in basilar pons, CN V palsy (p=.0140) in peritrigeminal pons, CN VII (p=.0247), CN IX (p=.001), CN X (p=.001) and vertigo (p=.006) in the inferior peduncular pons and tetraspasticity (p=.001) in the rhomboid pons. The two most common BSCM locations were peritrigeminal (31.25%) and rhomboid (33.13%). The average major diameter of BSCM was 19.05±8.75 mm and 5.3% of BSCM were developmental venous anomalies. The most frequently used surgical approaches were the suboccipital telovelar approach (31.8%), the retrosigmoid approach (18.7%), and the transpetrosal approach (6.05%) and the most commonly utilized SEZ was the lateral pontine zone (LPZ) (34.1%). Average follow-up was 4.0±4.4 years. Overall, gross total resection was achieved in 65.6% of cases, in cases utilizing the LPZ gross total resection was achieved in 82.8% of cases. Good clinical outcome (follow-up mRS<2) was observed in 64.1% of patients, with an overall mortality rate of 1.0%. The use of SEZs for pontine BSCM was associated with improved clinical outcome (OR: 2.41, 95% CI: 1.279-4.546, p=.006). BSCM located in the middle peduncular pons were associated with an improved clinical outcome (OR: 6.759, 95% CI: 2.322-19.673, p=.0005), while BSCM located in the basilar pons were associated with a worse clinical outcome (OR:0.075, 95% CI: 0.010-0.584, p=.0133).
Conclusion
Surgical resection of pontine BSCM can be performed with low morbidity and mortality rates when utilizing SEZs and careful preoperative planning. The lateral pontine, supratrigeminal, and peritrigeminal SEZs are associated with high rates of complete resection and improved neurological outcomes. BSCM location dictates the choice of SEZ and surgical approach, emphasizing the importance of understanding the regional anatomy of the brainstem. Future studies with standardized reporting and longer follow-ups are needed to further refine surgical techniques, patient selection, and stratify outcomes based on anatomical distribution.

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Abstract Title
The Role of Irreversible Electroporation for Pancreatic Cancer

Background
Pancreatic cancer is one of the most aggressive cancers in the world, representing the fourth most frequent tumor-related cause of death in the Western world and the seventh leading cause of cancer death worldwide. Surgical resection offers the only chance of long-term survival, but only 15-20% of patients have potentially resectable disease at primary diagnosis. Due to proximity to critical anatomical structures, patients with locally advanced pancreatic cancer (LAPC) may be unable to undergo surgical resection. Furthermore, many patients with LAPC are treated like metastatic disease with systemic palliative chemotherapy, resulting in poor response. The aim of the present review was to evaluate the role of irreversible electroporation (IRE) in borderline resectable pancreatic cancer and LAPC.

Methods
A comprehensive review was performed using PubMed, Embase (OvidSP), Library of Congress, Lista (EBSCO), and Web of Science Core Collection. The initial search was conducted using the terms “Pancreatic Cancer” or “Pancreatic Adenocarcinoma” and “Irreversible Electroporation” in the title field, yielding 165 results. 140 articles were excluded because they focused on cancers not pertinent to the study, weren’t exclusive to human studies, combined open and percutaneous IRE data, or didn’t pertain to the study. The remaining 25 articles were examined for quality reporting data related to key inclusion materials, and 15 articles’ survival outcomes, safety, and efficacy results were included. The data extracted focused on outcomes related to progression free survival (PFS) and overall survival (OS) relating to IRE therapy, safety and efficacy compared to other ablation techniques, and induction chemotherapy regimen type and intensity. The primary endpoint was to determine whether IRE could safely and effectively improve PFS and OS in patients with LAPC. 

Results
IRE has demonstrated encouraging survival and response outcomes when combined with induction chemotherapy versus patient populations that receive chemotherapy and/or chemoradiation alone. The use of IRE with targeted therapies may enhance antitumor immunity and possibly improve survival outcomes compared to historical controls. Additionally, the combination of IRE with multiagent therapy has been associated with a low rate of serious adverse events, complications, and infections. 

Conclusion
Irreversible electroporation could improve overall survival and progression free survival when combined with multiagent therapy in patients with LAPC. The optimal management of patients with LAPC is evolving with the advent of improved IRE implementation, newer chemotherapeutics and immunotherapy. IRE has demonstrated itself to be a viable surgical intervention for patients with borderline resectable pancreatic cancer and LAPC.


The Role of Irreversible Electroporation (IRE) for Pancreatic Cancer

Metformin is one of the most prescribed medications in the United States, mainly due to its utility in treating patients with diabetes. Continued research into metformin’s mechanisms have yielded interesting findings on its cancer suppressing abilities, including its actions in prostate cancer. With these mechanisms in mind, we sought to investigate the potential effects of metformin use on PSA levels in patients with prostate cancer. Using the TriNetX research network, we collected data forming two cohorts of patients with diabetes and same-stage prostate cancer, with and without metformin treatment, cohort A and cohort B respectively. We found a difference between PSA and metformin usage. The mean serum PSA level among patients with the diagnosis of prostate cancer and metformin use in Cohort A (N=45,145) was 20.1 ± 17.8 and the mean serum PSA level for patients with the diagnosis of prostate cancer and no metformin use (N=440,464) was 34.3 ± 31, p<0.0002. We identified a significant decrease in the mean PSA level in metformin users compared to non-metformin users. Further investigation on the effects of metformin on PSA levels is needed to clarify metformin-induced dampening of PSA in screening for prostate cancer diagnosis.

PSA Down, Metastasis at Bay: Metformin's Impact on Prostate Cancer and Implications for Screening

Background
Frailty indices are well-established metrics used to assess physiologic reserve and predict peri- and post-operative morbidity and mortality. While multiple frailty tools exist, there is limited consensus regarding the most effective risk assessment tool in orthopaedic trauma. Although there is literature supporting the utility of the 5-Item Modified Frailty Index (mFI-5) in the orthopaedic trauma population, the newer Revised Risk Analysis Index (RAI-Rev) has not been evaluated in this population. This study sought to determine the applicability of RAI-Rev in the orthopaedic trauma population and compare the predictive discrimination for the RAI-Rev and mFI-5 for 30-day postoperative outcomes.

Methods
The ACSNSQIP data were queried from 2015 to 2020 for patients ≥ 18 with operatively treated fractures of the forearm, humerus, pelvis, acetabulum, femur, tibia, and hindfoot. Outcomes included a composite of major complications (death, sepsis, pulmonary embolism, ventilator use greater than 48 hours, return to operating room, unplanned re-intubation, acute postoperative renal failure, cardiac arrest, myocardial infarction, cerebrovascular accident, and graft failure), mortality, readmission, and wound complications. Frailty scores were stratified into four cohorts based on frailty levels, utilizing previously described cutoff scores. Multivariate analysis was used to assess the predictive value of frailty. Receiver operating characteristics curve analysis was quantified with C-statistic for discriminatory accuracy. 

Results
In total, 206,352 patients met inclusion criteria. Median age was 69 years old, with 64.2% (n = 132,514) being female. Multivariate regression analysis showed that increasing frailty tiers in both RAI-Rev and mFI-5 were independent predictors of mortality, major complications, readmission, and wound complications. The cohort with the highest degree of frailty in both RAI-Rev and mFI-5 had the greatest risk of poor outcomes. RAI-Rev had significantly superior predictive discriminatory thresholds compared to mFI-5 for predicting 30-day mortality (C-statistic: RAI-Rev (0.84) and mFI-5 (0.67), p <0.001), major complications (C-statistic: RAI-Rev (0.73) and mFI-5 (0.65), p <0.001), and readmission (C-statistic: RAI-Rev (0.68) and mFI-5 (0.63), p <0.001). However, mFI-5 outperformed RAI-Rev when predicting wound complications (C-statistic: RAI-Rev (0.52) and mFI-5 (0.55), p <0.001). 

Conclusion
RAI-rev demonstrated superior predictability of postoperative morbidity, mortality, and readmission rates compared to mFI-5, but was less effective in predicting surgical site complications. These findings demonstrate the utility of RAI-Rev in anticipating postoperative complications in the setting of orthopaedic trauma, where optimizing surgical candidate selection is not always possible. Assessing the predicted morbidity and mortality through RAI-Rev may allow surgeons to mitigate postoperative complications in patients undergoing surgical fixation of traumatic injuries.

Comparison of Revised Risk Analysis Index and 5-Item Modified Frailty Index as Predictors of Mortality and Morbidity in Orthopaedic Trauma

Background
Mind-wandering is a pervasive human brain state and, when in excess, may promote negative affect and neuropsychiatric conditions. Mindfulness meditation may promote alternate brain states, improving affect and reducing stress. An understanding of the neural basis between these brain states could thus advance treatment of neuropsychiatric conditions. Patients with epilepsy suffer from high rates of neuropsychiatric conditions including anxiety and depression that may be mediated by mind-wandering and improved by mindfulness meditation. Patients with drug-resistant epilepsy routinely undergo intracranial recordings using stereo electroencephalography (sEEG) to locate and treat the anatomical origin of seizures. SEEG recordings over several days in these patients therefore afford a unique opportunity to study the effects of mind-wandering and mindfulness on the human brain. 

Methods
To explore the neural basis of mindfulness meditation versus mind-wandering, we enrolled eight patients in a trial of structured mindfulness meditation and open mind-wandering who underwent sEEG within the mesial temporal lobe for seizure localization. Electrophysiology was compared between mind-wandering and mindfulness separately for epileptic and non-epileptic tissue. Using fitting-one-over-f modeling, periodic components of electrophysiology were compared in canonical frequency bands of theta (4-8Hz), alpha (8-13Hz), beta (13-30Hz), and gamma (30-55Hz). Aperiodic components of the power spectra were assessed by the model offset, knee, and exponent. 

Results
We found a significant reduction in gamma power (30-55Hz) within the mesial temporal lobe during mindfulness meditation compared with mind-wandering in non-epileptic (p=1.20E-4) but not in epileptic brain (p=0.352).There was also a significant difference between epileptic versus non-epileptic brain in difference in gamma power between conditions (p=0.011). There were no significant changes in power across any frequency band within epileptic mesial temporal brain tissue between brain states. Conversely, there were significant differences between mind-wandering and mindfulness within epileptic brain in aperiodic components (offset, knee, and exponent, all p<0.05), while no differences in aperiodic components were seen in non-epileptic brain (all p>0.70). 

Conclusion
Intracranial electrophysiologic modulations between brain state (mind-wandering versus mindfulness) may differ between epileptic and non-epileptic brain tissue. Modulations in gamma activity in non-epileptic brain may represent functional changes in brain state, while aperiodic changes in epileptic brain may modulate propensity for seizures.

Mesial Temporal Electrophysiology between Mind-Wandering and Mindfulness Meditation

Background
Glaucoma is defined by damage to the optic nerve that results in visual field (VF) loss widely considered to be irreversible. However, in a landmark clinical trial for glaucoma known as the Ocular Hypertension Treatment Study (OHTS)(1), reversal of VF loss was observed but assumed to be caused by artifact. We tested the assumption of whether vision loss is always irreversible.

Methods
Given the inherent variability of VF testing, a prevailing challenge is distinguishing true improvement from random noise. Permutation of pointwise linear regression (PoPLR)(2) is a statistical method that determines whether an observed VF trend is a true phenomenon. PoPLR determined the prevalence of eyes with VF outcome (improvement, deterioration, or stability) with the threshold for random variation at 5%. Archetypal analysis (AA)(3) is an unsupervised machine learning technique that decomposes an individual VF into patterns of glaucomatous defects. Longitudinal trends of glaucomatous defect were measured with linear regression. To assess whether learning effect is confounder for improvement, reliability indices including false positive rate (FPR), false negative rate (FNR), and fixation losses (FL) were compared across VF outcomes using one-way ANOVA. We also analyzed structural differences by comparing rates of significant thinning of retinal nerve fiber layer (RNFL) using Chi-Square analysis. A p-value less than 0.05 was considered statistically significant.

Results
This study isolated 886 eyes from 619 patients, of which 106 eyes (11.96%), 331 eyes (37.36%) and 449 eyes (50.68%) demonstrated VF improvement, deterioration, and stability, respectively. Eyes exhibiting VF improvement had significantly decreased representation of superior altitudinal defect (-0.05%/year, p<0.001), inferotemporal defect (-0.08%/year, p=0.013), and inferonasal defect (-0.12%/year, p<0.001). There was no significant difference in FPR (p=0.203), FNR (p=0.631), or FL (p=0.105) across VF outcomes. VF improvement was found to have a lower rate of significant RNFL thinning compared to VF deterioration (11.1% vs. 42.2%, p<0.001).

Conclusion
Reversal of glaucomatous vision loss is a true phenomenon as VF improvement occurred more often than random variation and was accompanied by a decrease in classic glaucomatous defects with preserved RNFLT integrity. Furthermore, learning effect was not a significant confounder for improvement. Future research will assess which treatments (medication vs. surgery) can optimize reversal of glaucomatous vision loss and therefore aid clinical decision-making.

References
1. Keltner JL, Johnson CA, Quigg JM, et al. Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Arch Ophthal. 2000;118(9):1187-1194. https://jamanetwork.com/journals/jamaophthalmology/article-abstract/413586
2. O’Leary N, Chauhan BC, Artes PH. Visual field progression in glaucoma: estimating the overall significance of deterioration with permutation analyses of pointwise linear regression (PoPLR). Invest Ophthalmol Vis Sci. 2012;53(11):6776-6784. doi:10.1167/iovs.12-10049
3. Elze T, Pasquale LR, Shen LQ, Chen TC, Wiggs JL, Bex PJ. Patterns of functional vision loss in glaucoma determined with archetypal analysis. J R Soc Interface. 2015;12(103). doi:10.1098/rsif.2014.1118

Reversal of Glaucomatous Vision Loss Detected By Unsupervised Machine Learning

Abstract Title: Glioblastoma Multiforme Tumor Volume and Persistence of Chimeric Antigen Receptor T Cells Following Treatment

Background: Glioblastoma Multiforme (GBM) is one of the most common and aggressive high-grade primary brain tumors that arises from the glial cells of the central nervous system and occurs most often in the frontal and temporal lobes. Despite current treatment options, long-term prognosis of GBM remains low with no significant improvement rates. Chimeric antigen receptor (CAR)-expressing T cells target the B cell marker CD19 and have shown increased efficacy in B cell lymphomas, acute lymphoblastic leukemia, and chronic lymphocytic leukemia
suggesting benefits in GBM. B7-Homologue3 (B7-H3) is a type 1 transmembrane glycoprotein that shares homologous domains with PD-L1 and recently gained increased attention as an important immune checkpoint molecule. B7-H3 is highly expressed in GBM, contributing to tumor invasiveness, metastatic potential, and poor outcomes, making it an ideal target for immune therapies. This study aims to quantify the persistence of CAR-T cells in the context of GBM tumor volume following neurosurgical debulking procedure.

Methods: For imaging, a radiology software known as the mint Lesion was utilized to provide Tumor Response Assessment by Criteria (TRAC) reports that consist of volumetric measurements of the tumor lesions (target enhancing lesions, non-target enhancing lesions, and non-target non-enhancing lesions). The Response Assessment in Neuro-Oncology (RANO) criteria is used as a radiologic assessment of treatment response in high-grade gliomas. Fluorescence-activated cell sorting (FACS) is a type of flow cytometry technique that uses highly specific antibodies labeled with fluorescence conjugates. FACS analysis takes a sample
mixture of cells and sorts them into different populations based on their specific biomarkers and fluorescence characteristics and with the help of Cytek Aurora, separates the cells into various groups to provide a graphical representation.

Results: B7-H3 CAR-T cell persistence was increased in patients with a larger post-surgical tumor volume. CAR-T cells remained detectable till the end of the cycle (Day 28) for all subjects. This was reflected through the ratio of the percentage of CD8 CAR-T cells and the follow-up tumor volume. Increased B7-H3 CAR-T cell persistence was demonstrated with a larger ratio and reflected a larger post-surgical tumor volume.

Conclusion: To conclude, B7-H3 CAR-T cells are highly persistent in patients with a large post-surgical tumor volume making CAR-T cell therapy a more promising regimen in patients with the first recurrence of glioblastoma.

Glioblastoma Multiforme Tumor Volume and Persistence of Chimeric Antigen Receptor T Cells Following Neurosurgical Debulking

Abstract Title: Advancements in Nanomedicine: A Study on Lipid Nanoparticle Reliability and Formulation Optimization

Background: Lipid nanoparticles (LNP) have emerged as vital tools for delivering nucleic acids like messenger RNA (mRNA) and small interfering RNA (siRNA), playing a key role in the development of COVID-19 vaccines and RNA interference (RNAi)-based therapies for diseases including cancer and cardiovascular disorders. Despite their potential, inquiries into the comparative formulation efficiencies of LNPs when encapsulating siRNA versus mRNA payloads remain limited. Noteworthy challenges endure in optimizing LNP formulations, ensuring stability, scalability, and the mitigation of potential side effects. This study explores the encapsulation efficiency of LNPs for siRNA and mRNA, aiming to enhance the formulation of vaccines and gene therapies. We hypothesize that there is a difference in formulation efficiency and stability between siRNA and mRNA. Specific Aims: Aim 1: Compare the difference in formulation efficiency between siRNA and mRNA. Aim 2: Assess the stability of mRNA-LNP at room temperature.

Methods: Using siRNA targeting Firefly Luciferase and mRNA for NanoLuciferase, we prepared lipid formulations with ALC-0315, DSPC, cholesterol, and PEG-DMG. Following dialysis against PBS, we assessed cholesterol content, siRNA/mRNA concentration, and encapsulation efficiency through RiboGreen assays and determined particle size and polydispersity index (PDI) to evaluate stability. 
Results: In our experimental investigations, we have demonstrated the encapsulation formulation efficiencies for various components. Specifically, the encapsulation formulation efficiency for siRNA targeting Luciferase was found to be 85-95% (N=8, P<0.05), while that for mRNA encoding NanoLuciferase yielded a value of 80-90% (N=7, P<0.05). Furthermore, a comparative examination between siRNA and mRNA revealed distinct data regarding encapsulation formulation efficiency. Our findings also encompassed particle size measurements, indicating that siRNA-LNP had longer stability at room temperature compared to mRNA-LNP. mRNA-LNP had a significant increase in particle size compared to siRNA-LNP. The results pertaining to PDI showed that mRNA-LNP had a significant increase in PDI over a 12-hour time period.

Conclusion: These results provide valuable insights into the encapsulation properties and stability profiles of various components within lipid nanoparticles, contributing to the advancement of nanoparticle-based drug delivery systems. To further expand on these findings and advance research and therapeutic applications, future investigations may encompass evaluating encapsulation efficiency with plasmid DNA, exploring novel ionizable cationic lipids, and extending studies to encompass larger animal models.

Advancements in Nanomedicine: A Study on Lipid Nanoparticle Reliability and Formulation Optimization

Purpose
Excess visceral fat and altered lipid metabolism are both associated with prostate cancer progression. Our aim was to determine if a weight loss lifestyle intervention using diet and exercise changed the intake of dietary fat and nutrients, the fatty acid composition and signaling pathways of periprostatic adipose tissue (PPAT), and the sphingolipid signature in the blood in men with prostate cancer. 

Materials and Methods
Forty men scheduled for radical prostatectomy (RP) were randomized into intervention (n=20) or active control (n=20) arms in a phase II trial. Participants in the intervention adhered to a lifestyle intervention using diet and exercise for 4-16 weeks before and 6-months after RP. Participants in the active control arm were given standard of care and standardized educational materials. Blood samples, dietary information, and health metrics of participants were collected at three time points: baseline (4-16 weeks prior to RP), 1 week prior to RP, 6 months after RP. PPAT biopsies were collected at the time of RP. Fatty acid analysis of PPAT was performed using flame-ionization gas chromatography. RNA from third passage adipose stromal cells (ASCs) were isolated using a RNeasy kit (Qiagen). RNA samples were analyzed using nCounter® PanCancer Immune Panel (NanoString). Sphingolipids were analyzed in plasma via Xevo GS-X2 quadrupole time-of-flight mass spectrometers using a 2D column configuration.

Results
The weight management program produced clinically significant weight loss in the intervention group compared to the control arm, with 5.5% weight loss from baseline to surgery. Dietary intake of myristic acid, palmitic acid, margaric acid, stearic acid, linoleic acid, arachidic acid, and linolelaidic acid significantly decreased in the intervention group from baseline to pre-surgery; between arm changes were significant. Oleic acid consumption significantly increased in the intervention group; between arm changes were significant. ASC transcriptomic analysis revealed lower gene expression of COLEC12 and higher expression of IL-17F, and biological mapping of transcriptome data using Ingenuity Pathway Analysis predicted inhibition of leptin and IL-6 signaling in the intervention group. The plasma sphingolipid signature significantly decreased in the intervention group and did not change in the control group. 

Conclusions
Our study demonstrated significant changes in the intake of dietary fatty acids which did not correlate with effects on the composition of the PPAT. Clinically significant weight loss produced transcriptomic changes in the PPAT, with downregulation of pathways associated with PCa progression. The improved plasma sphingolipid signature in the intervention suggests favorable changes in lipid metabolism protective against prostate cancer progression.

Exploring the Role of a Lifestyle Intervention on Periprostatic Adipose Tissue and Fat Metabolism in Men with Prostate Cancer

Background 
Despite advancements in treatment, laryngeal cancer survival rates remain largely unchanged due to late-stage detection. Screening and monitoring patients with laryngeal leukoplakia, a precursor to malignancy, is invasive, costly, and requires repeated visits to otolaryngology clinics, which impede timely laryngeal cancer detection. Field cancerization theory suggests that when cancer develops, subcellular changes occur proximal and distal to the site of malignancy. Elastic scattering spectroscopy (ESS), a real-time, non-invasive tool capable of differentiating tissue microarchitecture, may therefore be able to detect (and screen for) laryngeal cancer by easily measuring tissue changes in the oral cavity. This preliminary study tested whether ESS measurements obtained in the oral cavity could accurately differentiate between patients who have laryngeal cancer versus laryngeal leukoplakia. 
Methods
Under an Institutional Review Board approved protocol, 20 patients were enrolled; 10 patients with laryngeal cancer and 10 patients with laryngeal leukoplakia. All patients were clinically assessed and categorized per standard clinical practice. Patient demographics were collected, including age, race, sex, and smoking history. ESS spectral measurements were taken in several sub-anatomical sites within patients’ oral cavities. A machine-learning algorithm was developed to classify patients based on ESS spectra obtained from patients with benign laryngeal leukoplakia and from patients with laryngeal cancer. Specificity, sensitivity, negative predictive value (NPV), hit-to-climb ratio (HCR), and area under the curve (AUC) were calculated. Additional algorithms stratified spectral data by sub-anatomic site and patients’ smoking status to further refine diagnostic capability. 
Results 
The overall algorithm had a sensitivity=77%, specificity=56%, NPV=62.5%, HCR=1.73, and AUC=0.63. Stratifying by former and active smokers, algorithm sensitivities were 82% and 80%, respectively. Analysis by sub-anatomical location showed that an algorithm based exclusively on lateral tongue spectra had an AUC of 0.76, with further stratification by former and active smokers demonstrating AUCs of 0.95 and 0.81, sensitivities of 97% and 81%, and specificities of 80% and 71%, respectively. Additionally, a mucosal lip-based algorithm showed a sensitivity of 90%, specificity of 80% and NPV of 80% in former smokers. 
Conclusion 
ESS algorithms demonstrated high sensitivity in differentiating patients with leukoplakia versus squamous cell carcinoma when subclassified by smoking status and sub-anatomical site within the oral cavity. Utilization of ESS as a real-time, non-invasive screening tool may provide prompt detection of malignancy in non-specialized settings, potentially leading to timely diagnosis, treatment, and increased survivability. A follow-up study with a larger sample size.

Differentiating Laryngeal Cancer from Laryngeal Leukoplakia using Elastic Scattering Spectroscopy of the Oral Cavity: A Pilot Study

Purpose/Objective(s): In the era of rituximab, large B-cell lymphoma (LBCL) with secondary skeletal involvement has been associated with worse overall survival (OS) and higher relapse rates. Prospective data suggest an improvement in progression-free survival (PFS), and OS in patients with skeletal involvement treated with consolidative radiation (RT). Despite these positive results, real-world adoption of skeletal radiation and associated oncologic outcomes, need to be better characterized. We hypothesized that RT for patients with skeletal involvement from LBCL remains underutilized, leading to the detriment of OS.

Materials/Methods:
We conducted a retrospective analysis using the National Cancer Database for patients with LBCL with bone involvement with chemotherapy +/- RT from 2016-2020. Due to limitations on how skeletal involvement was coded prior to 2016, we excluded data from previous years. Patients who did not receive rituximab+chemotherapy, had prior malignancy, unknown RT treatment, or unknown follow-up were excluded. Patients who received palliative doses of RT (<30 Gy) were also excluded. Receipt of radiation treatment was defined as skeletal (SRT), non-skeletal (NSRT), or none. Trends in the utilization of RT were assessed using linear and logistic regressions. Survival analysis was performed using Cox regression and Kaplan-Meier methods.

Results:
A total of 641 patients met the inclusion criteria, with 8.7% receiving SRT, 7.2% receiving NSRT, and 84.1% without RT. In 2016, 80.6% and 13.9% of patients received no RT and SRT, respectively. In 2020, 84.9% and 7.9% of patients received no RT (slope: 1.1%/yr; p=0.141) and SRT (slope: -1.6%/yr; p=0.186), respectively. No patient or clinical factors were associated with receipt of either SRT or RT in general. Median follow-up was 2.6 years (IQR: 1.1-4.2 years). The 3-yr OS rates in the SRT, NSRT, and no RT cohorts were 87.0% (95% CI 74.7–93.6%), 83.4% (95% CI 68.1–91.8%), and 72.6% (95% CI 68.5–76.3%), respectively. Relative to no RT, receipt of SRT was associated with improved OS on univariable Cox regression (HR: 0.41; p=0.020) and multivariable (MVA) Cox regression (HR: 0.44; p=0.032). In comparison, relative to no RT, receipt of NSRT was not associated with improved OS on univariable Cox regression (HR: 0.54; p=0.087) or multivariable (MVA) Cox regression (HR: 0.55; p=0.098). Factors associated with OS on MVA included age and Charlson Deyo score. Other factors including race, ethnicity, insurance type, hospital type, and IPI score were not significant.

Conclusion:
Consistent with prospective data, SRT conferred a statistically significant improvement in OS, with a numerical improvement similar to prior prospective analyses. Despite this benefit, rates of consolidative RT to skeletal sites are low and potentially decreasing. Future studies should further elucidate the benefit of consolidative RT for patients with LBCL with skeletal involvement and barriers to such treatment.

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