Citations

Abstract Disclosure: R. Haider: None. M. Waqas: None. S. Khan: None. A. Ullah: None. M. Khawar: None. A. Qadeer: None. M. Talha: None. A. Batool: None. A. Khan: None. M.Z. Haider: None. R.W. Kirchoff: None. Background: Hypothyroidism and heart failure (HF) contribute significantly to mortality among older adults. Understanding mortality trends, including demographic, geographic, and socio-economic disparities, is crucial to inform healthcare policies and resource allocation. Methods: This study analyzed age adjusted mortality rates (AAMRs) from 1999 to 2022 for adults aged 55-85+ years. Age adjusted mortality rates (AMRs) per 1,000,000 population were stratified by gender, race, geographic location, and urbanicity. Trends were evaluated using Average Annual Percentage Change (APC) with 95% confidence intervals (CI), examining periods of decline and increase. Results: Between 1999 and 2022, 105,008 deaths were recorded among older adults (55-85+ years) due to hypothyroidism and heart failure (HF). The age-adjusted mortality rate (AAMR) initially declined from 1999 to 2016, marked by a significant drop between 2005 and 2008 (APC = -6.0, 95% CI: -7.6 to -3.0). However, mortality trends reversed post-2016, with a sharp increase (APC = 6.7, 95% CI: 5.5 to 8.4). Age-specific trends revealed declining crude mortality rates (CMR) across all groups until 2016, followed by increases, particularly in the 65-74 and 75-84 age brackets, with APCs of 14.1 (95% CI: 7.8 to 27.8) and 8.9 (95% CI: 3.8 to 21.8), respectively. Gender disparities showed men and women had similar trends, with declines until 2015-2016 followed by surges, with APCs of 6.8 (95% CI: 5.2 to 9.1) and 6.6 (95% CI: 4.6 to 11.1), respectively. Racial disparities highlighted steady declines until 2016, followed by increases in non-Hispanic Whites (APC = 10.4, 95% CI: 5.2 to 23.2) and Hispanics (APC = 7.5, 95% CI: 6.0 to 10.1). Geographically, the Midwest exhibited the highest AAMR (71.1), while the Northeast showed the lowest (51.4). State-level disparities revealed North Dakota with the highest AAMR (129.5), contrasting with Nevada, which had the lowest (20.4). Urban-rural differences showed similar trends, with notable AAMR increases in both settings post-2016. These results underscore significant demographic and regional disparities in hypothyroidism and HF-related mortality. Conclusion: While mortality from hypothyroidism and HF among older adults declined until 2016, trends have since reversed across all demographic and geographic strata. Addressing these rising rates require targeted interventions focusing on high-risk groups and areas. Presentation: Monday, July 14, 2025

Abstract Disclosure: A. Omayer: None. A. Sharif: None. A. Kc: None. S. Hoque: None. H. BaniHani: None. L. Khaled: None. A. Holeihel: None. U.A. Khawaja: None. Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus that is often managed with fluid resuscitation, insulin therapy, and correction of electrolyte imbalances. Bicarbonate therapy is commonly used to correct acidosis, but its effectiveness remains debated. This systematic review and meta-analysis aimed to assess the impact of bicarbonate therapy on clinical outcomes in DKA patients. Methods: Following the PRISMA guidelines, we performed a systematic review of studies assessing the use of bicarbonate therapy in DKA. We searched PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov for studies published up to August 2024. Studies were included if they involved DKA patients with initial pH ≤7.30 or glucose >250 mg/dL, and compared bicarbonate therapy with standard care. Data on outcomes were extracted, including pH levels, duration of hospital stay, time to resolution of acidosis, potassium levels, and incidence of hypoglycemia. We performed a meta-analysis using RevMan, with a random-effects model for most outcomes and fixed-effects for specific analyses. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), Cochrane's ROB-2 tool and The Joanna Briggs Institute (JBI) Scale for cohort studies, randomized controlled trials (RCTs) and case series respectively. Results: Eight studies, including 646 patients, met the inclusion criteria. The included studies were conducted in various countries and represented diverse populations, with sample sizes ranging from 20 to 232 participants. Participants' mean ages spanned from approximately 9.7 years to 45.8 years. The proportion of male participants varied significantly, from 40.6% to 54.3%. Bicarbonate therapy did not significantly improve pH levels (mean difference = -0.02, 95% CI [-0.13, 0.09], p = 0.7), time to resolution of acidosis (mean difference = 0.09 hours, 95% CI [-2.6, 2.79], p = 0.95), or potassium levels (mean difference = -0.10, 95% CI [-0.49, 0.29], p = 0.61). Bicarbonate therapy was associated with a marginally longer duration of hospital stay (mean difference = 13.63 hours, 95% CI [0.23, 27.03], p = 0.05), although the overall effect size was small. No significant difference was observed in the incidence of hypoglycemia (odds ratio = 2.62, 95% CI [0.59, 11.63], p = 0.20). High heterogeneity was observed across most outcomes, mainly due to variability in study protocols and patient populations. Conclusion: Bicarbonate therapy in DKA does not appear to provide significant clinical benefits in pH correction, resolution of acidosis, or potassium balance and may lead to a slightly prolonged hospital stay. Given the high heterogeneity of included studies, further well-designed trials are needed to establish more precise guidelines on bicarbonate use in DKA management. Presentation: Saturday, July 12, 2025

Abstract Background: [212Pb]VMT-a-NET is an alpha therapy agent targeting somatostatin receptor subtype 2 (SSTR2)-expressing tumors. Neuroendocrine tumors (NETs) generally express SSTR2 on their cell surface. Here, we report the results of a prospective, open-label, Phase I/IIa clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of [212Pb]VMT-a-NET [NCT05636618]. Methods: The study design follows a Bayesian dose-finding algorithm. Main inclusion criteria include histologically proven well-differentiated unresectable or metastatic NETs, radiological evidence of progression on at least one prior line of systemic therapy, demonstration of lesional SSTR2 expression on an FDA-approved SSTR PET. Main exclusion criteria include: prior treatment with systemic PRRT-based therapies. In the dose finding phase, participants can receive up to four cycles of [212Pb]VMT-a-NET at the assigned dose level. Participants are followed for dose-limiting toxicity (DLT) observation up to 42 days after the first cycle. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Here we report safety and preliminary efficacy data of participants enrolled in cohorts 1 and 2 at 92.5 MBq [2.5 mCi] and 185 MBq [5 mCi], respectively. Results: As of 30-Apr-2025 (data cut-off – DCO), a total of 42 participants were enrolled into the study. Nine of them were followed for DLT observation; thirty-three (33) additional participants were subsequently enrolled into cohort 2 to further evaluate safety and efficacy at the selected dose. For data analysis purposes, participants were divided into two different groups: a safety group and an efficacy group. The safety group included all participants enrolled by the DCO (n=42), while the efficacy group included only nine participants enrolled in cohort 1 (n=2) and cohort 2 (n=7) for DLT observation. Median follow up time for participants included in the safety group was 14 weeks (range:0,77); median follow up time for participants included in the efficacy group was 56 weeks (range: 6,77). In the safety group (n=42) we did not observe any DLTs, any grade 4 or 5 adverse events (AEs), any treatment-related discontinuations, any serious renal complications or myelosuppression, or any dysphagia. In the efficacy group (n=9) seven out of nine participants were with no progression as of the DCO, and four out of the seven participants enrolled in cohort 2 achieved a partial response (PR). Three PRs were confirmed, while one was pending confirmation at the time of DCO. Cohort 3, at a dose level of 222 MBq [6 mCi], has recently been opened for enrollment. Safety data for all treated participants and efficacy results for a mature subset will be presented at the congress. Conclusions: [212Pb]VMT-a-NET showed a favorable safety profile and promising clinical benefit for patients with advanced SSTR2-expressing NETs treated at the dose level of 185 MBq (5 mCi). The study is ongoing with cohort 3 currently open for enrollment. Citation Format: Vikas Prasad, Richard Wahl, Lilja Solnes, Savitha Balaraman, Gregory Sibley, Lowell Anthony, Brandon Mancini, Jason Starr, Vineeth Sukrithan, Chih-Yi Liao, Samuel Mehr, Lucia Baratto, Wenjing Yang, Alaa Hanna, Stephen Keefe, Markus Puhlmann, Thorvadur Halfdanarson. [212Pb]VMT-a-NET for somatostatin receptor subtype 2 (SSTR2)-expressing tumors: safety and preliminary efficacy results in patients with advanced neuroendocrine tumors (NETs) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C095 .

Abstract Korpinen, M, Magee, M, Dulak-Sigler, C, Fields, JB, Jagim, AR, King, E, Burke, A, and Jones, MT. Seasonal changes in neuromuscular performance across a training year in women collegiate lacrosse athletes. J Strength Cond Res 39(11): 1186–1193, 2025—Body composition and athlete load management are vital to adequate training stimuli and to mitigate neuromuscular (NM) fatigue. Research is limited regarding NM performance (NMP) in women lacrosse athletes. Therefore, the purpose of this study was to investigate changes in NMP in women lacrosse athletes across a training year. Collegiate women lacrosse athletes ( n = 9, mean ± SD ; age = 19.1 ± 0.9 years, height = 168.4 ± 6.8 cm, body mass = 68.0 ± 8.1 kg) completed countermovement jump (CMJ) and isokinetic strength (IS) testing of dominant and nondominant legs 4 times throughout the season: preseason start, preseason end, in-season end, and off-season end to assess NMP. Measures included (a) CMJ output variables of reactive strength index modified (RSImod), jump height, relative values of braking force, peak power, peak propulsive force, impulse; (b) CMJ strategy variables of time-to-takeoff, eccentric duration, concentric duration, relative braking time, CMJ depth; and (c) IS relative peak torques of quadriceps and hamstrings musculature. Secondary measures including body composition variables of body mass, % body fat (%BF), and fat-free mass. Repeated measures ANOVA with Bonferroni post hoc analysis assessed changes in CMJ and IS parameters to determine patterns in NMP ( p < 0.05). Changes observed from preseason start to offseason end included increased CMJ depth ( p = 0.019), relative braking time ( p = 0.009), and %BF ( p = 0.01). The IS variables increased throughout the training year, except for a decrease during preseason, perhaps indicative of overreaching. Negative changes in alternative CMJ variables and body composition reduced NMP, which highlights the importance of off-season program design and implementation to elicit desired training adaptations.

ImportanceReceipt of anthracycline-based chemotherapy and statin therapy have been found to be associated with deterioration of cognitive function in patients with cancer.ObjectiveTo assess the association of statins with attention, verbal fluency, and executive function in patients receiving doxorubicin treatment for cancer.Design, Setting, and ParticipantsThis secondary analysis of the Preventing Anthracycline Cardiovascular Toxicity With Statins randomized clinical trial, conducted across 31 US community and academic sites from February 5, 2014, through September 24, 2020, involved participants with stage I to IV lymphoma or stage I to III breast cancer undergoing doxorubicin treatment. The data analysis was conducted between August 1, 2024, and April 4, 2025.InterventionsParticipants were randomized (1:1) to receive a daily 40-mg dose of atorvastatin or placebo before initiating doxorubicin treatment and then continued for 24 months.Main Outcomes and MeasuresAttention, executive function, and verbal fluency were assessed using the Trail Making Test part A (TMT-A) and part B (TMT-B) and the Controlled Oral Word Association test, respectively. Time to complete the assessments were modeled using a linear mixed model, while errors (counts) were modeled using a generalized linear mixed model assuming a Poisson distribution.ResultsA total of 238 participants (mean [SD] age, 49 [12] years; 217 female [91.2%]) were randomized to the statin (n = 118) or placebo (n = 120) groups. Values for TMT-A at 6 and 24 months were similar between the statin group (mean, 32.5 seconds [95% CI, 29.4-35.7 seconds] and 29.8 seconds [95% CI, 26.4-33.2 seconds], respectively) and the placebo group (mean, 28.4 seconds [95% CI, 25.2-31.5 seconds] and 27.8 seconds [95% CI, 24.5-31.0 seconds], respectively). From before treatment to 24 months after treatment, statin recipients had a significant mean improvement of 10.2 seconds for TMT-B (95% CI, 1.9-18.5 seconds), whereas placebo recipients had a nonsignificant improvement of only 0.2 seconds for TMT-B (95% CI, −8.5 to 8.1 seconds). Analysis of the time-by-treatment interaction showed no significant difference between groups. For Controlled Oral Word Association scores in the same period, both the placebo and statin groups showed a mean improvement of 3.62 points (95% CI, 1.71-5.54 points) and 4.74 points (95% CI, 2.69-6.79 points), respectively, with no difference between groups.Conclusions and RelevanceThis secondary analysis of a randomized clinical trial suggests that the receipt of statins during doxorubicin therapy for lymphoma or breast cancer was not associated with worsening cognitive functions over 24 months. Within-group analyses suggested that statins may have contributed to better executive function on the TMT-B.Trial RegistrationClinicalTrials.gov Identifier: NCT01988571

Abstract Purpose: The role of tumor-infiltrating lymphocytes (TIL) remains unclear in hormone receptor (HR)–positive/HER2-negative breast cancer, particularly in young patients, whose immune microenvironment could be altered by age-related host and tumor differences. Experimental Design: Patients with stage I to III HR-positive/HER2-negative tumors were identified from a prospective cohort study of patients with breast cancer diagnosed at age ≤40 years. Multiplexed immunofluorescence and semiautomated quantitative software measured cytotoxic T, non–CD8 T, T regulatory, exhausted T, and PDL1+ cells in stroma and tumor. Univariate analyses assessed differences in clinicopathologic characteristics by high versus low immune infiltration, divided based on median. TIL subtypes were evaluated as a continuous variable per 10% increase in Cox regression analyses for invasive breast cancer–free survival, distant disease–free survival (DDFS), and overall survival, adjusted for clinicopathologic parameters. Results: Among 390 patients, high immune infiltration was associated with increasing age, Black race, grade 3 tumors, and metaplastic or micropapillary histologic subtypes. Over a median follow-up of 8 years, higher stromal and intratumoral non–CD8 T-cell infiltration, T regulatory–cell infiltration, and PDL1 expression were associated with improved invasive breast cancer–free survival. Higher intratumoral non–CD8 T-cell infiltration, T regulatory–cell infiltration, and PDL1 expression were associated with improved DDFS; higher stromal PDL1 expression was also associated with improved DDFS. Higher intratumoral cytotoxic T-cell infiltration and PDL1 expression were associated with improved overall survival. Conclusions: Characterization of immune subpopulations could help refine the prognostic value of TILs in young patients with HR-positive breast cancer, who may benefit from risk stratification for treatment individualization. See related commentary by Salgado and Kok, p. 2133

Stereotactic radiosurgery was associated with a higher obliteration rate compared with embolization in patients with eloquent brain arteriovenous malformations, whereas there was no evidence of a difference in functional outcomes or complications after adjustment.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) often present with associated mild hyperprolactinemia, described in literature as "stalk effect." The presence of preoperative hyperprolactinemia caused by tumor compression of the pituitary stalk and endocrinological outcomes has been noted; however, a detailed investigation on the impact on perioperative endocrinological outcome is lacking. The authors aimed to determine whether elevated preoperative serum prolactin concentrations are associated with increased risk of perioperative pituitary dysfunction in patients with NFPAs undergoing endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a single-center retrospective cohort study of patients who underwent ETS for NFPAs between January 2013 and April 2023. Patients were divided into two groups based on preoperative prolactin concentrations: normal or hyperprolactinemic (prolactin values above upper limit of reference range, adjusted for sex). Outcomes included perioperative endocrinological function and surgical outcomes. Multivariable analysis was conducted to identify factors associated with perioperative endocrinological function outcomes. RESULTS Of 244 patients (140 [57%] males; median age 59 years) with a median follow-up of 65 months, 131 (54%) had hyperprolactinemia. Compared with patients with normal preoperative prolactin levels (n = 113), the hyperprolactinemia group had similar tumor size (median diameter 2.5 cm vs 2.3 cm, p = 0.102) but higher rates of cavernous sinus invasion (99% vs 91%, p = 0.035), pituitary stalk deviation (95% vs 74%, p = 0.001), stalk bending (14% vs 1%, p = 0.001), preoperative secondary hypothyroidism (39% vs 22%, p = 0.005), and adrenal insufficiency (AI; 34% vs 22%, p = 0.048). Postoperatively, the hyperprolactinemia group showed higher rates of new secondary hypothyroidism (16% vs 7%, p = 0.048) and new permanent AI (16% vs 6%, p = 0.046). Multivariable analysis revealed preoperative high prolactin as an independent predictor of preoperative secondary hypothyroidism (OR 1.83, 95% CI 1.17–3.44; p = 0.046) and its postoperative deterioration (OR 2.65, 95% CI 1.02–7.69; p = 0.042). Maximum tumor diameter was also a significant predictor of various endocrinological dysfunctions both pre- and postoperatively. CONCLUSIONS Preoperative hyperprolactinemia in patients with NFPA is associated with higher risks of specific perioperative endocrinological dysfunction and pronounced pituitary stalk deviation. These findings highlight the utility of preoperative prolactin levels as a biomarker for predicting postoperative endocrinological outcomes, potentially enhancing risk assessment and guiding personalized perioperative management.

Metastatic meningioma exhibits diverse dissemination patterns across organ systems (lungs, bone, liver, soft tissue, etc), with molecular imaging—particularly gallium 68 DOTA Tyr3-octreotide PET/CT—playing a pivotal role in detection, characterization, and guiding management.

Background: Hypertension is a major risk factor for cardiovascular disease, yet nearly 46% of adults with hypertension remain undiagnosed. Without timely intervention, it can lead to severe complications, including stroke, heart failure, and kidney disease. In sub-Saharan Africa (SSA), hypertension prevalence varies widely from 19.3% in Eritrea to 39.6% in Seychelles. Urbanization has played a key role in increasing hypertension rates through its impact on diet, physical activity, and obesity. Still, urban-rural differences remain modest. Understanding demographic and lifestyle predictors is crucial for SSA's targeted prevention and control efforts. Methods: We conducted a cross-sectional analysis using nationally representative, de-identified data from the Demographic and Health Surveys (2016–2024) in five SSA countries: Lesotho, Tanzania, Gabon, Benin, and South Africa. Adults aged ≥18 years with valid blood pressure and covariate data were included (N=38,085). Blood pressure was measured three times, and the average of the second and third readings was used when available. Hypertension was defined per the 2017 ACC/AHA guidelines (SBP ≥130 mmHg or DBP ≥80 mmHg). Independent variables included age, sex, BMI, education, wealth index, smoking status, and recent caffeine intake. Results: Urban residents (n=20,773) had a higher hypertension prevalence than rural residents (n=17,312) (44.8% vs. 36.7%, p<0.001), along with higher median BMI (24.9 vs. 22.3 kg/m 2 ) and obesity rates (23.5% vs. 11.3%). South Africa exhibited the highest rates (urban 68%, rural 61%), while Tanzania and Lesotho had the lowest (~39–40%). In pooled multivariable analysis, hypertension odds increased steadily with age (OR 4.57 for ≥60 vs 18–24, p<0.001). Obesity demonstrated a dose–response relationship: Class III obesity was associated with a fivefold increase in risk (OR 5.38, p<0.001). Men had higher odds than women (OR 1.65, p<0.001). Secondary education and middle wealth status conferred modest increases in risk. Caffeine use was marginally significant; smoking was not. Predictor importance ranked: age > BMI > sex > wealth > education > smoking > caffeine. Conclusion: Hypertension is highly prevalent in both urban and rural SSA, with age and obesity emerging as the most powerful predictors. South Africa stands out with younger adults most affected. Early detection, awareness campaigns, and obesity-focused interventions are needed to mitigate the growing burden of hypertension in SSA.