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220 Background: There is a critical need to identify biomarkers of response and resistance to 177Lu-PSMA-617. Post-hoc analyses of VISION have explored the prognostic and predictive value of select clinical parameters. However, we are still in the early stages of deciphering which molecular changes are associated with favorable or adverse treatment outcomes. Methods: We conducted a retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC), who received 177Lu-PSMA-617 at Mayo Clinic in Rochester, Minnesota, in the interval of March 2022 to March 2023. We included patients who provided research authorization, had a baseline PSA of at least 2 ng/mL, received at least 2 cycles of treatment, and had circulating tumor DNA (ctDNA) genomic profiling performed by Guardant (83 gene panel) within 60 days of treatment initiation. Clinical, laboratory, genomic, and radiomic parameters were abstracted by trained research personnel. Two independent analyses of “response” and “resistance” were performed. Response to treatment was defined as 50% or greater decrease in PSA from baseline (PSA50 response: dichotomized yes versus no), and resistance was defined as non-decreasing or rising PSA during treatment (PSA non-response: dichotomized yes versus no). Associations between gene alterations and response and resistance were evaluated via Fisher’s exact tests. Results: Between March 2022 and March 2023, 273 patients received cycle 1 of 177Lu-PSMA-617. A total of 108 patients met the inclusion criteria. The median number of cycles at data cutoff was 6 (IQR: 4,6) with 57 (53%) patients receiving all 6 planned cycles. The median PSA at baseline was 16.65 ng/ml (IQR: 5.20, 66.12). A total of 65 patients (60%) experienced a PSA50 response. No molecular alterations were associated with a higher rate of PSA50 response; however, alterations in ARID1A, AR, and CHEK2 were associated with lack of PSA50 response (Fisher’s exact p < 0.05). Of the 108 evaluable patients, 20 (19%) met criteria for PSA non-response. Alterations in AR, ARID1A, MYC, TP53, CHEK2, ATM, EGFR, and NOTCH1 were significantly associated with PSA non-response (Fisher’s exact p < 0.05); in each case, the presence of the alteration was positively associated with resistance (i.e., more instance of PSA non-response). No biomarkers were found to be inversely associated with PSA non-response. Conclusions: ctDNA assessed by commercially available, targeted sequencing panels prior to treatment may be useful in identifying the patients least likely to benefit from 177Lu-PSMA-617. Further work is ongoing to integrate ctDNA findings with clinical parameters in the hopes of understanding the factors mediating response and resistance to therapy.

175 Background: It is well-known that patients with liver metastases from metastatic castration resistant prostate cancer (mCRPC) have poorer or transient responses to many forms of systemic therapy. Data on outcomes following treatment with Lutetium-177–PSMA-617 is scarce. The VISION trial reports hazard ratios for overall survival in the subgroup of patients with liver metastases without disclosing the absolute duration of survival. Using real-world clinical data, we examine this important subgroup of patients, describing their PSA response rates and survival. Methods: A single institution database was assembled to include all patients receiving 177-Lu-PSMA-617 at Mayo Clinic Rochester, MN, and starting treatment in the interval of March 2022 to March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were categorized based on the presence or absence of measurable liver metastases on their baseline PSMA PET scan. Best PSA response while on treatment was annotated and reported as percent decline from baseline. Survival was calculated from date of first cycle of 177-Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (liver metastases versus no liver metastases) were compared using Chi square test and Kaplan-Meier method, respectively. Those with available pre-treatment circulating tumor DNA (ctDNA) genomic profiling, performed by Guardant (83 gene panel), were assessed for the presence of pathogenic and likely pathogenic alterations. Findings are summarized using descriptive statistics. Results: The overall cohort consisted of 212 patients, including 29 (14%) with liver metastases on pre-treatment PSMA PET/CT. The median number of cycles received was 4 (range, 1-6) for patients with liver metastases and 6 (range, 1-6) for those without hepatic involvement. The observed PSA50 response trended lower for those with liver metastases (34.5% [10/29] versus 51% [94/183], p= 0.091). At median (IQR) follow-up of 10 (8-12) months, there was a numerical but not statistically significant difference in median OS (11.28 months versus NR, p=0.066). In the exploratory analysis of baseline ctDNA, BRCA2 copy number loss was relatively enriched among patients with liver metastases (4 of 19, 21%) versus patients without liver disease (5.7%, 9/158). Conclusions: Our data suggest that the presence of liver metastases predict poorer outcomes in patients receiving Lutetium-177–PSMA-617 treatment, which is similar to data reported with other forms of systemic therapy for mCRPC. To maximize the anti-tumor activity of radioligand therapy in the liver, combination approaches should be explored.

AbstractIntroductionPrevious bronchoalveolar lavage fluid (BALF) proteomic analysis has evaluated limited numbers of subjects for only a few proteins of interest, which may differ between asthma and normal controls. Our objective was to examine a more comprehensive inflammatory biomarker panel in quantitative proteomic analysis for a large asthma cohort to identify molecular phenotypes distinguishing severe from nonsevere asthma.MethodsBronchoalveolar lavage fluid from 48 severe and 77 nonsevere adult asthma subjects were assessed for 75 inflammatory proteins, normalized to BALF total protein concentration. Validation of BALF differences was sought through equivalent protein analysis of autologous sputum. Subjects' data, stratified by asthma severity, were analysed by standard statistical tests, principal component analysis and 5 machine learning algorithms.ResultsThe severe group had lower lung function and greater health care utilization. Significantly increased BALF proteins for severe asthma compared to nonsevere asthma were fibroblast growth factor 2 (FGF2), TGFα, IL1Ra, IL2, IL4, CCL8, CCL13 and CXCL7 and significantly decreased were platelet‐derived growth factor a‐a dimer (PDGFaa), vascular endothelial growth factor (VEGF), interleukin 5 (IL5), CCL17, CCL22, CXCL9 and CXCL10. Four protein differences were replicated in sputum. FGF2, PDGFaa and CXCL7 were independently identified by 5 machine learning algorithms as the most important variables for discriminating severe and nonsevere asthma. Increased and decreased proteins identified for the severe cluster showed significant protein–protein interactions for chemokine and cytokine signalling, growth factor activity, and eosinophil and neutrophil chemotaxis differing between subjects with severe and nonsevere asthma.ConclusionThese inflammatory protein results confirm altered airway remodelling and cytokine/chemokine activity recruiting leukocytes into the airways of severe compared to nonsevere asthma as important processes even in stable status.

AbstractIntroductionAtrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. Periprocedural conduction system damage was a primary concern during AVNRT ablation. This study aimed to assess the incidence of permanent atrioventricular (AV) block and the success rate associated with different types of catheters in slow pathway ablation.MethodA literature search was performed to identify studies that compared various techniques, including types of radiofrequency ablation (irrigated and nonirrigated) and different sizes of catheter tip cryoablation (4, 6, and 8‐mm), in terms of their outcomes related to permanent atrioventricular block and success rate. To assess and rank the treatments for the different outcomes, a random‐effects model of network meta‐analysis, along with p‐scores, was employed.ResultsA total of 27 studies with 5110 patients were included in the analysis. Overall success rates ranged from 89.78% to 100%. Point estimation showed 4‐mm cryoablation exhibited an odds ratio of 0.649 (95%CI: 0.202–2.087) when compared to nonirrigated RFA. Similarly, 6‐mm cryoablation had an odds ratio of 0.944 (95%CI: 0.307–2.905), 8‐mm cryoablation had an odds ratio of 0.848 (95%CI: 0.089–8.107), and irrigated RFA had an odds ratio of 0.424 (95%CI: 0.058–3.121) compared to nonirrigated RFA.ConclusionOur study found no significant difference in the incidence of permanent AV block between the types of catheters. The success rates were consistently high across all groups. These findings emphasize the potential of both RF ablation (irrigated and nonirrigated catheter) and cryoablation as viable options for the treatment of AVNRT, with similar safety and efficacy profile.

Background: The Schnur scale used body surface area (BSA) to determine the amount of breast tissue resection in reduction mammaplasty, resulting in a greater requirement of breast weight removal in patients with larger BSA. The authors aimed to demonstrate BSA variance among women with similar mastectomy weights and the range of mastectomy weights among women with comparable BSAs. Methods: A retrospective chart review of patients who underwent mastectomy from October of 2021 to June of 2022 was performed. Patients were included if they underwent skin-sparing or nipple-sparing mastectomy with a minimum specimen weight of 700 g. Patient’s BSA, body mass index (BMI), mastectomy weight, and Schnur weight requirement (SWR) were collected. Results: A total of 130 patients (194 breasts) were included. There was significant variance in mean BSA, BMI, SWR, and SWR-to–mastectomy weight ratio among women with similar mastectomy weights. BSA varied by as much as 0.82 units, BMI varied by as much as 32 kg/m2, and SWR varied by as much as 1365 g within the same mastectomy weight group. There was also significant variance in mastectomy weights among women with comparable BSA, especially in BSA groups greater than 2.20, with the greatest range in mastectomy weights being 1684 g. Conclusions: Analysis of mastectomy patients showed no predictable relationship between BSA and breast weight. There was significant variance in the BSA of patients with similar breast weights, and conversely in breast weights of patients with comparable BSA. Therefore, strict adherence to the Schnur weight requirement can prevent patients with macromastia from receiving breast reductions.

AbstractBackgroundMost studies on the relationship between neuropsychiatric symptoms (NPS) and cognitive decline focus on NPS data collected over a short period of time. To better understand the association between NPS and cognitive decline, including their temporal relationship, it is important to know NPS status across a person’s life.MethodWe utilized the unique Rochester Epidemiology Project medical record linkage system that has captured medical records as far back as 1907, to abstract the psychiatric history of 1810 cognitively unimpaired participants in the population‐based Mayo Clinic Study of Aging (MCSA). Trained nurse abstractors ascertained the presence of exposure to three common NPS (anxiety, depression, and unspecified emotional distress [UED]), both before and after entry into the MCSA. We conducted Cox Proportional Hazards (PH) models using age as the time scale and adjusting for sex, education, and APOE E4 allele for each NPS in predicting mild cognitive impairment (MCI), or dementia. Additional analyses considering medication use (yes/no) and timing of NPS were also run.ResultAnxiety (Hazard Ratio [HR] = 1.47, p<0.001), depression (HR = 1.36, p = 0.001), and UED (HR = 1.22, p = 0.039) were associated with a higher risk of MCI. These associations were present regardless of medication use for anxiety (With medication: HR = 1.51, p<0.001; without medication: HR = 1.41, p = 0.015), and for those taking medications for depression (With medication: HR = 1.47, p<0.001; without medication: 1.09, p = 0.597). Anxiety was associated with MCI regardless of timing of onset with the strongest relationship being for those with onset of anxiety before 65 that persisted into later life (HR = 1.88, p = 0.004). Depression was associated regardless of timing of onset if the depression was present in late life too. The results were similar for the outcome of dementia (Anxiety: HR = 1.62, p<0.001; depression: HR = 1.31, p = 0.040; UED: HR = 1.37, p = 0.014). The associations accounting for medication use and timing of NPS were similar for the outcome of dementia too.ConclusionNPS is associated with progression to MCI and dementia. Both medication use and timing of NPS might play a role in these associations.