Background: COVID-19 manifested with a wide range of clinical symptoms, including asymptomatic or mild illness and life-threatening respiratory failure. We hypothesized that elevated predictors during intensive care unit (ICU) stays would independently predict mortality and the subsequent development of post-COVID-19 condition (PCC). Methods: In this retrospective cohort study, we evaluated the clinical and laboratory determinants of mortality using hospital records in severe COVID-19 patients in conjunction with their PCC in survivors by self-reported survey. This research was conducted at XX University Hospital, and adult patients with laboratory-confirmed SARS-CoV-2 infection by RT-PCR assay who required ICU admission for respiratory failure or hemodynamic instability were included. Biomarkers were monitored throughout ICU stay to evaluate dynamic changes and their association with mortality. Survivors were followed from ICU discharge to assess readmissions, vaccination status, and post-COVID-19 condition, including fatigue, sleep disturbance, physical exhaustion, concentration problems, and memory impairment. Post-ICU mortality and hospitalization due to cardiovascular, respiratory, neurological, or other complications were recorded. Results: A total of 273 critically ill patients were included, of whom 112 survived and 161 died during ICU stay. Non-survivors were older and had lower mean arterial pressure. Intubation was more frequent among non-survivors, and APACHE II scores were significantly higher in this group. Hospitalizations due to cardiovascular, respiratory, and neurological complications were particularly associated with increased hazard of death (HRs ≥2, p-values < 0.05). Patients who died after ICU discharge (31.5%) had higher rates of fatigue, physical exhaustion, and memory impairment, suggesting a strong correlation between biomarker derangements during ICU stay and PCC. Conclusions: The present study was specifically designed to address this critical gap by evaluating whether biomarker trajectories during ICU follow-up not only predict in-hospital mortality but also serve as early determinants of Post-COVID status in survivors.

Objective To evaluate whether common plasma proteomic pathways connect host genetic risk factors to incident age-related macular degeneration (AMD) in persons with AIDS. Design Nested case-control study. Participants Subset of persons enrolled in the Longitudinal Study of Ocular Complications of AIDS. Methods Baseline cryopreserved plasma specimens were assayed for inflammatory and cardiovascular proteins using the Olink Inflammation Explore Panels 1 to 2 and the Cardiometabolic Explore Panels 1 to 2. Age-related macular degeneration‑associated genetic variants were assessed using Applied Biosystems Taqman probes. Baseline proteomic profiles for 26 persons who subsequently developed incident intermediate-stage AMD after 5 to 10 years of follow-up and 49 controls without AMD matched for age, natal sex, race/ethnicity, and follow-up duration were compared. False discovery rate correction was performed with the Storey Q method, and both unsupervised gene ontology pathway enrichment and dedicated pathway analyses were performed. Age-related macular degeneration‑associated plasma protein levels were compared between AMD high-risk and AMD low-risk genotypes. Main Outcome Measures Incident intermediate-stage AMD. Results 371 (26%) of 1448 evaluable plasma proteins were associated with incident AMD at the false discovery rate Q < 0.05 threshold. Hallmark pathways significantly enriched in incident AMD included inflammation, complement, and fatty acid metabolism pathways. Complement factor H, a complement activation regulating protein with a genetic association with AMD, levels appeared to be associated with AMD (adjusted odds ratio: 0.12 per 2-fold increase, P = 0.055). Several related proteins in the Hallmark complement pathway were strongly associated with AMD, 16 including CD46, platelet-derived growth factor β, chemokine ligand 1, and CCL5 (all Q < 0.05), which have been linked to AMD risk in genetic studies. Among cholesterol homeostasis-related genes, lipoprotein lipase was associated with a decreased risk of AMD (adjusted odds ratio: 0.18 per 2-fold increase, Q = 0.008). Participants with AMD high-risk genotypes had elevated levels of shared proteins in inflammatory, complement, and fatty acid metabolism pathways. Conclusions Levels of several plasma proteins linked to the complement pathway and cholesterol homeostasis, which have been linked to AMD risk in genetic studies, are associated with incident AMD in people with AIDS. Plasma levels of shared inflammatory proteins linked to several different genetic AMD risk factors predicted AMD risk, suggesting common immunologic mechanisms linking genetic risk factors for AMD. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

De novo metastatic breast cancer (dnMBC) accounts for 3-10% of newly diagnosed cases, with 20-40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1-131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25-45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0-3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39-104) for GrA patients and 44 months (28-72) for GrB patients (HR 0.57, 95% CI 0.41-0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259-0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334-0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.

Introduction: The impact of locoregional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (dnBOMBC) is controversial. This study aims to assess the effect of LRT on survival, utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with dnBOMBC were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Further, patients who received LRT were divided into two subgroups: those who received ST after LRT (LRT+ST group) and those who received ST prior to LRT (ST+LRT group). Factors associated with disease progression, including solitary or multiple bone metastases, were analyzed. Results: There was a total of 744 patients with dnBOMBC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32–66, 25–75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs. 55 (44, 66), p = 0.0001]. There were no significant differences in grade, HER2 status, triple-negative status, receipt of hormonal therapy, or intervention to metastatic sites. During follow-up, 58% (n = 217) of patients in the ST group and 32% (n = 120) of patients in the LRT group died (p < 0.001). Local progression was observed in 20% of the patients in the ST group, whereas 9% progressed in the LRT group (p = 0.0001). Systemic progression occurred more in the ST group; 66% (n = 244) compared to 41% (n = 152) of patients in the LRT group (p < 0.001). The hazard of death was 64% lower in the LRT group than in the ST group (HR: 0.36, 95% CI: 0.29–0.45, p < 0.0001). The burden of metastatic disease differed significantly between the two groups, with a higher rate of solitary bone metastases in the LRT group compared to the ST group (50% vs. 24%, p < 0.001). However, the LRT group had better overall survival (OS) for both solitary (HR: 0.38, 95% Cl: 0.26–0.55) and multiple (HR: 0.38, 95% Cl: 0.29–0.51) bone metastasis patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST. Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p < 0.05). Conclusions: Analysis of this large multi-institutional patient cohort provides further evidence that LRT is associated with longer OS and lower locoregional recurrence rates in patients with dnBOMBC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor.

BACKGROUND:Current guidelines do not list definitive recommendations for postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). Increased data suggests de-escalation of radiation therapy (RT) in genomically defined biologically favorable luminal BCs. The goal of this study is to determine whether PMRT can be safely omitted for this specific subgroup of patients. METHODS AND MATERIALS:Two hundred and 2 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, HER2 negative BC who underwent mastectomy were retrospectively analyzed. No patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. Patients were divided into 2 groups: PMRT (n = 130) and no PMRT (n = 69). Groups were compared in terms of overall survival (OS), loco-regional recurrence (LRR) rate, and distant metastases (DM) in light of the Magee Equations Score (MS), menopausal status/age, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy. RESULTS:The majority of the patients had invasive ductal carcinoma (49%, n = 98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the 2 groups (P = .82, P = .28, P = .12, respectively). LVI was 19% (n = 39), and it was greater in the PMRT group (25% vs. 10%; P = .01). Patients in the PMRT group received more chemotherapy (66% vs. 30%; P < .001), had more grade 3 tumors (28% vs. 9%, P = .005), and were more premenopausal (49% vs. 22%; P = .0001). At a median follow-up of 51.3 months for the no PMRT group and 65.9 months for the PMRT group (P = .041), 9% (n = 6) of patients from the no PMRT group and 2% (n = 3) from the PMRT group developed LRR (P = .047). There was no difference in local recurrence (1% in no PMRT group vs. 2% in PMRT group; P = .7) and distant recurrence (7% in no PMRT group vs. 3% in PMRT group; P = .16) in patients who received PMRT and no PMRT. Further comparison of the LRR in the no PMRT and PMRT groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; P = .64). However, among patients with an MS ≥ 18, no PMRT group had a higher LRR rate compared to the PMRT group (11% vs. 2%; P = .01). In patients with an MS ≥ 18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95% CI 0.05-0.79; P = .02). CONCLUSIONS:Our findings imply that when considering PMRT for patients with pT3N0M0, HR-positive, and HER2-negative BC, clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS < 18 experience a comparable rate of recurrence irrespective of PMRT, while those with MS ≥ 18 have higher rates of LRR and thus should not omit PMRT.

The Bahçeşehir population-based mammography screening program (BMSP) is an example of Türkiye’s first population-based screening program. This study aims to reveal the successful implementation of population-based secreening program in one of the low- and middle-income countries, Türkiye and long-term results of patients diagnosed with breast cancer during BMSP. This study was conducted between 2009 and 2019, in the Bahçeşehir county of Istanbul. Women between the ages of 40 and 69 living in this region were invited every two years to undergo clinical breast examination (CBE) and mammography screening. All data was recorded in a dedicated software program. Women diagnosed with breast cancer were followed as a separate cohort. During the 10-year screening period, 8,825 women were screened and 146 (1.7

Objective: To evaluate the associations of plasma inflammatory proteins with age-related macular degeneration (AMD) in persons with the AIDS, using a discovery-based proteomics approach. Design: A nested case-control study (analysis 1) and nested cohort study (analysis 2). Participants: Persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications with AIDS (LSOCA). Methods: Cryopreserved plasma specimens obtained at baseline were assayed for inflammatory proteins using the Olink Inflammation Explore Panel 1. In analysis 1, baseline proteomic profiles for 26 persons with AIDS and incident intermediate-stage AMD 5 to 10 years after baseline and 49 matched controls (matched for age, biologic sex, race/ethnicity, and follow-up) without AMD were compared. In analysis 2, 475 persons from LSOCA with baseline plasma inflammatory proteomic profile measurements were followed for incident cataract and mortality. Main Outcome Measures: Incident intermediate-stage AMD; incident cataract; and mortality. Results: Of 365 measurable plasma inflammatory proteins, 118 (32%) were associated with incident intermediate-stage AMD at the false discovery rate-adjusted Q < 0.05 level after adjustment for smoking, CD4+ T count, and plasma human immunodeficiency virus RNA level. Gene ontology pathway enrichment analysis identified the interleukin (IL)-1β pathway and wound healing pathways, including tissue inhibitor of metalloproteinase 3, as significantly associated with incident AMD. These associations were qualitatively different from those associated with incident cataracts, where elevated levels of inflammatory proteins were associated with a decreased risk of cataracts. A much broader number of inflammatory pathways, including those related to the adaptive immune system, were associated with mortality. Conclusions: Upregulation of the IL-1β pathway appears to be associated with an increased risk of incident AMD in persons with AIDS. Given the availability of inhibitors of this pathway, inhibition of the IL-1β pathway may provide a therapeutic avenue for treatment of AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[This corrects the article DOI: 10.1016/j.xops.2025.100794.].

The animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive.

The Fertile Crescent appears to be the most plausible region where the domestication of cats commenced through a mutually beneficial relationship between wild cats and early agrarian societies. These domesticated cats then journeyed across the globe mirroring the paths of human migration. An examination of mitochondrial DNA (mtDNA) control region-based mitotyping suggested that a significant majority, exceeding 80%, of globally sampled random-bred and pure-bred cats could be categorized into 12 predominant mitotypes. However, the extent of mitotype diversity within random-bred cats from regions proximate to the Fertile Crescent remains inadequately explored. In light of this we aimed to investigate the mitotype diversity in random bred cats sampled from various regions across Turkey. Additionally, we sought to establish a comparison with the mitotype profiles of locally recognized pure breeds, namely the Turkish Angora and Turkish Van. To unravel their evolutionary narratives, we engaged in comprehensive population genetics analyses at both the individual and mitotype-based levels. Our study encompassed a sample size of 240 specimens, forming the basis for both mitotyping and population genetics scrutiny. Our analysis yielded the identification of nine 'universal' mitotypes (A-J), alongside an 'outlier' mitotype group I. Notably mitotypes A and D emerged as particularly prevalent in contrast to the lesser occurrence mitotypes C, G, and H. With the realm of random bred cats the structure of haplotypes exhibited remarkable diversity presenting distinctions from Turkish Angora and Van breeds. Nucleotide diversity was higher compared to previous reports from Turkey and was one of the highest among reported world cat population estimates. Intriguingly, our investigations did not unveil any pronounced instances of strong selection, population expansions or contractions within any specific population or mitotype. To conclude, our study represents a pioneering effort in uncovering the mitotype profiles and haplotype structures inherent to both random-bred and pure breed cats in Turkey. This endeavor not only broadens our understanding of the feline genetic landscape within the region but also lays the foundation for future inquiries into the evolutionary trajectories and genetic legacies of these feline populations.

Abstract Background Treatment of HER-2 positive metastatic breast cancer (MBC) involves the use of HER-2-targeted therapy in combination with cytotoxic chemotherapy and/or hormone therapy. Treatment duration for HER2-targeted agents is not standardized, and patients are often kept on these drugs indefinitely. Drug holidays can be initiated due to poor tolerance of drug or can be considered when trying to limit drug toxicity. Our study aims to determine the safety of utilizing drug holidays for patients receiving HER2-targeted therapies and the effect on overall survival and disease progression. Methods Study Design This retrospective study included patients who were diagnosed with metastatic HER2 positive breast cancer and had complete clinical and survival data available within UPMC Magee Women’s Hospital. The patients were divided into two groups based on whether they had a drug holiday or not. A drug holiday was defined as the temporary cessation of antiHER2 therapy for a minimum of three months in patients receiving HER2-targeted treatments. This involved the discontinuation of earlier- and later-line medications without considering the cessation of hormone therapy. Statistical Analysis The chi-square test or Fisher's exact test was used to compare categorical variables and the Mann-Whitney U test was used to compare continuous variables. The results were reported as proportions for categorical variables and as medians with 25th-75th percentiles for continuous variables. Survival rates and Hazard ratios were estimated using Kaplan-Meier log-rank tests and Cox models, respectively. The significance level was set at p < 0.05 for all analyses. Results 83 patients with HER2+ MBC treated with HER2-targeted therapy were identified, of which 54 patients were in the drug holiday group. Of noted patient variables, there was no significant difference in the tumor histology, distribution of estrogen receptor (ER) status (p= 0.38) and progesterone receptor (PR) status (p = 0.64). The use of hormonotherapy, immunotherapy, radiotherapy to the primary tumor, and radiotherapy to metastasis did not significantly differ between the two groups (p > 0.05 for all comparisons). Subgroup analysis was conducted within the hormonotherapy subgroup to assess the survival difference in the no drug holiday group and to evaluate the impact of drug holiday on antiHER2 therapy cessation while continuing hormonotherapy. There was a trend towards a higher proportion of patients who were deceased in the no drug holiday group (62%) compared to the drug holiday group (42%), although this difference did not reach statistical significance (p = 0.16). The disease status differed significantly between the two groups (p < 0.0001). In the no-drug holiday group, 72% of patients had progressive disease, while 20% had stable disease with the anti-HER2 therapy and 7% had no-evidence of disease. In contrast, the drug holiday group had a higher proportion of patients with no-evidence of disease (48%) compared to progressive disease (38%) and stable disease (14%). The drug holiday group demonstrated higher overall survival (61% with median follow-up 1719 days 25th-75th percentile: 963-2222) compared to the no drug holiday group (39% with median follow-up time of 803 days 25th-75th percentile: 216-1510) (p= 0.04). Conclusion Overall, our findings suggest that utilization of a drug holiday in stable and NED HER2+ MBC is not associated with decreased survival. Analysis within the hormonotherapy subgroup indicated no survival difference in the drug holiday group, highlighting the potential for cessation of antiHER2 therapy while continuing hormonotherapy in this specific subgroup. However further prospective studies with long drug holiday intervals, larger sample size, and control of other potential confounding factors are needed to validate these results. Citation Format: Saba Kurtom, Kazim Senol, Qurat Ul Ain Sabih, Efe Sezgin, Adam Brufsky, Vikram Gorantla, Shannon Puhalla, Atilla Soran. Drug Holidays in Patients with HER-2 Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-03.

Abstract Background: In current guidelines, there is no definite recommendation regarding postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). The goal of this study is to determine whether PMRT could be safely omitted for a specific subgroup of those patients. Methods and Materials: There were 202 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, Her2 neu (-) BC who underwent mastectomy, were analyzed retrospectively. None of the patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. The patients were divided into two groups, PMRT (+) (n=130) and PMRT (-) (n=69). Groups were compared in terms of overall survival, loco-regional recurrence rate, and distant metastases regarding Magee score (MS) (< 18 are considered low risk) (https://path.upmc.edu/onlineTools/mageeequations.html), menopausal status, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy. Results: The majority of the patients had invasive ductal carcinoma (49%, n=98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the two groups (p=0.82, p=0.28, p=0.12, respectively). LVI was 49% (n=98) and it was greater in PMRT (+) group (25% vs. 10%; p=0.01). PMRT (+) patients received more chemotherap(66% vs. 30%; p< 0.001), had more grade 3 tumors (28% vs. 9%, p=0.005), and more premenopausal (49% vs. 22%; p=0.0001). At a median follow-up of 51.3 months for the PMRT (-) group and 65.9 months for the PMRT (+) group (p=0.041), 9% (n=6) of patients from the PMRT (-) group and 2% (n=3) from the PMRT (+) group developed locoregional recurrence (LRR) (p=0.047). There was no difference in local recurrence (1% in PMRT (-) group vs. 2% in PMRT (+); p=0.7) and distant recurrence (7% in PMRT (-) group vs. 3% in PMRT (+); p=0.16) between patients who received PMRT and not had PMRT. Further comparison of the LRR in the PMRT (-) and PMRT (+) groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; p=0.64). However, among patients with a Magee score ≥18, the PMRT (-) group had a higher LRR rate compared to the PMRT (+) group (11% vs. 2%; p=0.01). In patients with an MS≥18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95%CI 0.05 – 0.79; p=0.02). Conclusions: Our findings imply that when considering PMRT for BC with pT3N0M0, HR (+), and Her2 neu (-), clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS< 18 receiving PMRT or not appear to experience a comparable rate of recurrence. Citation Format: Atilla Soran, Caleb King, Parul N. Barry, Rohit Bhargava, Hasan Karanlik, Melis Gultekin, Ferah Yiıdız, Aykut Soyder, Berk Goktepe, Kazim Senol, Caglar Guzel, Ebru Sen Oran, Levent Yeniay, Ahmet Dağ, Selman Emiroglu, Didem Can Trabulus, Alper Coskun, Neslihan Cabioglu, Hagigat Veliyeva, N. Zafer Utkan, Berkay Demirors, Efe Sezgin, John A. Vargo. PMRT Decision with low prediction of genomic test score in pT3N0M0 luminal breast cancer: Protocol MF22-02: International multicenter real-world data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-04.

ABSTRACT Background: Many methods have been developed for localizing non-palpable breast lesions. This study investigated the success rate and surgical results of the magnetic seed (Magseed) and radiofrequency identification (RFID) method, which are relatively new compared to standard wire-guided localizations. Materials and Methods: 20 simulation (10 Magseed, 10 RFID) models were created using turkey breasts and raisins. Raisins containing magnetic seed and RFID tags were placed on the turkey breast. Sentimag® probe was used for the Magseed group, and Faxitron LOCalizer™ System device was used in the RFID group. Both methods were evaluated in terms of accuracy in detecting breast lesion localization, operation times, excised tissue weights, total resection volume, surgical margin negativity, and re-excision rates. Results: Lesion localization success in both techniques was 100%. While procedure times were statistically significantly shorter in the Magseed group, incision lengths were shorter in the RFID group ( P = 0.013, P = 0.007, respectively). No statistically significant difference was found between the groups for the weight of the removed parts, total resection volume, and surgical margin distance ( P > 0.05). Conclusion: In this feasibility study, it was concluded that neither the RFID nor Magseed methods had a significant advantage over each other, in terms of localization detection and surgical margin negativity, and both methods could be used successfully for localization.

INTRODUCTION:Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS. MATERIALS AND METHODS:Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1). RESULTS:In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels. CONCLUSIONS:Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.

Abstract Introduction: The impact of loco-regional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (BC) is controversial. The aim of this study is to assess the effect of LRT on survival utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with de novo metastatic BC with bone-only metastases were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Patients who received LRT were divided into two groups: those who received ST after LRT (LRT+ST arm) and those who received ST prior to LRT (ST+LRT arm). Solitary or multiple bone metastases were classified, and factors associated with disease progression were analyzed. Results: There were a total of 744 patients with de novo bone-only metastatic BC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs 55 (44, 66), p=0.0001]. There were no significant differences in grade, Her2 neu and triple negative status, receipt of hormonal therapy and intervention to metastatic sites. During follow-up, 58% (n=217) of patients in ST arm and 32% (n=120) of patients in LRT arm died (p< 0.001). Local progression was observed in 20% of the patients in the ST arm whereas it was 9% in the LRT arm (p=0.0001). Systemic progression occurred more in ST arm; 66% (n=244) compared to 41% (n=152) of patients in LRT group (p< 0.001). The Hazard of death was 64% lower in LRT group than in ST group (HR: 0.36, 95% CI: 0.29-0.45), p<0.0001). The burden of metastatic disease was significantly different between groups with the solitary bone metastasis rate higher in LRT group than the ST only group (50% vs 24%, p< 0.001). However, the LRT group had better overall survival for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastases patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST.Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p< 0.05). Conclusion: Analysis of this large multi-institutional patient cohort provides further evidence that LRT improves overall survival and lowers loco-regional recurrence in patients with de novo bone-only metastatic BC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Didem Can Trabulus, Jamila Alazhri, Kazim Senol, Berk Goktepe, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dağ, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabıoğlu, Levent Yeniay, N. Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Berkay Demirors, Efe Sezgin, Vahit Ozmen, Anthony Lucci. Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-12.

Purpose Reducing renal ischemia is crucial for the function and survival of grafts from nonheartbeat donors, as it leads to inflammatory responses and tubulointerstitial damage. The primary concern with organs from nonheartbeat donors is the long warm ischemia period and reperfusion injury following renal transplantation. This study had two main goals; one goal is to determine how Necrostatin-1 targeting the PANoptosome affects PANoptosis in the nonheart-beating donor rat model. The other goal is to find out if Necrostatin-1 can protect the kidney from ischemic injury for renal transplantation surgery. Methods Twenty-four rats were grouped randomly as control and Necrostatin-1 in this experimental animal study, and we administered 1.65 mg/kg of Necrostatin-1 intraperitoneally to the experimental group for 30 minutes before cardiac arrest. We removed the rats’ left kidneys and measured various oxidative stress marker measures such as malondialdehyde, superoxide dismutase, catalase, GPx, and 8-hydroxy-2-deoxyguanosine levels. We then subjected the tissues to immunohistochemical analysis, electron microscopy, and histopathological analysis. Findings The Necrostatin-1 group had a lower total tubular injury score (P < .001) and less Caspase-3, gasdermin D, and mixed lineage kinase domain-like protein expression. Additionally, the apoptotic index of the study group was lower (P < .001). Furthermore, the study group had higher levels of superoxide dismutase and GPx (P < .05), whereas malondialdehyde levels were reduced (P = .009). Electron microscopy also revealed a significant improvement in tissue structure in the Necrostatin-1 group. Conclusion Necrostatin-1 protects against ischemic acute kidney injury in nonheart-beating donor rats by inhibiting PANoptosis via the blockade of RIPK1. As a result of this, Necrostatin-1 may offer novel opportunities for protecting donor kidneys from renal ischemia-reperfusion injury during transplantation in patients with end-stage kidney disease requiring a renal transplantation.