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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

Background: Massive weight loss after bariatric surgery (BS) often results in excess skin, leading to physical discomfort and impaired quality of life (QoL). Body contouring surgery (BCS) addresses these issues by restoring body image, improving function, and enhancing overall QoL, but its added value on patient-reported outcome measures (PROMs) remains underexplored. Methods: A systematic search of PubMed, Scopus, Embase, Web of Science, and Cochrane databases was conducted from inception to March of 2025. Studies comparing PROMs between patients undergoing BS alone and those undergoing BS + BCS were included. Retrieved studies were assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Outcomes were pooled using random effects models. Results: Fifteen non-randomized studies involving 7339 patients were included (BS, 4339 [59.1%]; BS + BCS, 3000 [40.9%]). Patients undergoing BS + BCS had a significantly greater percentage of total weight loss (mean difference [MD], 4.40% [95% CI, 1.69, 7.10]; P < 0.01). BODY-Q improvements favored the BS + BCS group in body image, physical, psychological, sexual, and social function (MD, 16.07 [95% CI, 12.14, 20.0]; P < 0.01). Among patients receiving only BS, those desiring BCS reported lower body satisfaction (MD, −0.40 [95% CI, −0.70, −0.10]; P < 0.01) and lower appraisal of excess skin scores (standardized MD, −1.09 [95% CI, −1.83, −0.36]; P = 0.02) than those without desire for BCS. Conclusions: BCS after BS yields substantial improvements in overall QoL. These findings highlight the importance of BCS as a fundamental element of comprehensive postbariatric care that significantly enhances long-term patient satisfaction and drives durable multidimensional recovery.

560 Background: Early diagnosis remains a critical challenge in oncology, particularly for the five deadliest cancers: lung, breast, prostate, colorectal, and pancreatic. These cancers often present with nonspecific symptoms, leading to repeated healthcare visits without a timely suspicion of malignancy. Artificial intelligence (AI) offers an opportunity to augment clinical decision-making and support earlier identification of cancer. C the Signs , an AI cancer prediction platform, has been widely adopted across the UK with substantial evidence supporting its ability to identify cancer at earlier stages. Methods: This retrospective study assessed the performance of C the Signs in intercepting cancer earlier than physician diagnosis. De-identified electronic medical records were accessed via the Mayo Data Platform, spanning a 20-year period from January 1, 2002 to December 31, 2021. The study cohort included 55,375 patients diagnosed with lung, breast, prostate, colorectal or pancreatic cancer. The primary outcome was the proportion of cases identified earlier by the AI model, measured in annual increments up to five years prior to physician diagnosis. Additional analyses were conducted across the five target cancer types. Results: The C the Signs platform identified 14,528 patients (26.2%) with cancer earlier than the original physician diagnosis. Early identification occurred across multiple time points: 8.9% in year 1, 4.7% in year 2, 4.4% in year 3, 4.3% in year 4, and 3.9% in year 5. Across cancer types, the highest early interception rate was observed in prostate cancer (31.7%), while breast cancer showed the lowest impact (21.0%). Conclusions: Use of the C the Signs AI cancer prediction platform demonstrated meaningful improvements in early cancer interception, particularly for lung and prostate cancers. These findings highlight the potential of AI tools to enhance early diagnosis and support timely clinical interventions, offering a scalable solution to improve cancer outcomes across populations.

Abstract BACKGROUND Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome characterized by development of multiple neoplasms, including central nervous system (CNS) hemangioblastomas, renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNETs), and retinal hemangioblastomas. Belzutifan, a hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor, has demonstrated efficacy in treating VHL-associated tumors. This study evaluates our institutional experience with belzutifan in patients with VHL-related tumors. MATERIAL AND METHODS We conducted a retrospective cohort study across three Mayo Clinic sites, including patients aged ≥18 years with genetically confirmed VHL disease who received belzutifan between October 2021 and March 2025. Clinical/radiological data, and adverse events (AEs) were extracted from electronic health records. Tumor responses were assessed using RECIST v1.1 criteria for RCC, pNET, CNS hemangioblastoma. Retinal hemangioblastoma responses were evaluated through ophthalmologic assessments. RESULTS Forty-five patients were included (median age 44 58% female). Sixty-seven percent had RCC, 91% had CNS hemangioblastomas, 53% had pNETs, and 62% had retinal hemangioblastomas. The median duration of belzutifan therapy was 22.6 months (range 1.0-41.4 months). Among patients with RCC (n=26), overall response rate (ORR) was 19% and median time to best response (MTBR) was 7.4 months. Five patients had partial response (PR), 15 had stable disease (SD), and 1 had progressive disease (PD). For CNS hemangioblastomas (n=41), ORR was 12%, MTBR was 6.2 months. 5 patients had PR, 30 had SD, and none had PD. For pNET (n=17), ORR was 41%, MTBR was 8.2 months. One patient had CR, 6 patients had PR, 6 had SD, none had PD. For retinal hemangioblastomas (n=28), 6 (21%) showed improvement, 9 (32%) remained stable, and 3 (11%) showed progression. MTBR was 6.7 months. Treatment-related AEs occurred in 98% of patients. Common AEs included anemia (89%), fatigue (80%), hypoxia (18%), and headache (13%). Grade 3 AEs were observed in 20% of patients, including anemia (7%), hypoxia (9%), fatigue (4%), pneumonitis (2%), loss of consciousness (2%). One patient experienced a grade 4 event (status epilepticus). Anemia management involved iron supplementation (n=11), RBC transfusion (n=3), dose reduction (n=2), treatment holiday (n=8), permanent discontinuation (n=1). Hypoxia management included dose reduction (n=1), treatment holiday (n=3), discontinuation (n=1). CONCLUSION Belzutifan shows clinical activity across various VHL-associated neoplasms in real-world practice, with a manageable safety profile. The lower ORR compared to the phase III trial may reflect differences in baseline disease, including lower tumor burden in our cohort. These findings support its continued use in VHL disease, with attention to monitoring and managing treatment-related AEs.

ImportancePatients with metastatic castration–resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.ObjectiveTo investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.Design, Setting, and ParticipantsThis retrospective cohort study used the deidentified Flatiron-Health electronic health record–derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.ExposuresAge, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.Main Outcomes and MeasuresThe receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.ResultsOf 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).Conclusions and RelevanceThis retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

BACKGROUND AND OBJECTIVES: The therapeutic approach for small- and medium-sized vestibular schwannoma (VS) with normal hearing function remains controversial, with limited comparative data regarding hearing outcomes after stereotactic radiosurgery (SRS) or observation (OBS). We evaluated the serviceable hearing preservation, loss of American Academy of Otolaryngology-Head and Neck Surgery class A hearing, and tumor control (TC) across individuals with Koos grade I and II VSs and normal hearing at presentation who underwent SRS or OBS. METHODS: In this multicenter international study, we retrospectively analyzed the hearing, radiological, and neurological outcomes of patients who underwent SRS (SRS group) or OBS (OBS group). The cohorts were matched using propensity scores based on age, sex, tumor volume, pure-tone average, and speech discrimination score at a 1:1 ratio without replacement. RESULTS: After matching, each group comprised 57 patients. The median follow-up was 49 and 37 months for the SRS and the OBS groups, respectively ( P = .3). The 5- and 9-year serviceable hearing preservation rates in the SRS group were 76.2% and 42.4% vs 56.1% and 16.8% in the OBS group ( P = .17). Class A preservation occurred in 57.9% (33/57) of the SRS and 52.6% (30/57) of the OBS cohorts ( P = .70). Regarding the TC rates, SRS was associated with significantly higher TC rates ( P < .0001). CONCLUSION: We found that SRS is significantly superior regarding TC and provided noninferior hearing outcomes compared with OBS in VS patients with American Academy of Otolaryngology-Head and Neck Surgery class A hearing at presentation. Therefore, we suggest performing SRS in individuals with VS and normal hearing function.

ABSTRACTWith the global rollout of COVID‐19 vaccines, vaccine safety remains a priority. Emerging concerns have raised the potential risk of a long COVID‐like syndrome following vaccination, informally called long Vax and provisionally termed post‐COVID‐19 vaccination syndrome (PCVS). Our narrative review describes the putative manifestation, pathophysiology, and therapeutic approaches of PCVS based on the available evidence, mostly from case reports/series and observational studies. Our review noted that PCVS typically manifests within days to weeks post‐vaccination, with symptoms lasting months to years. PCVS may present as recognized diagnoses such as postural orthostatic tachycardia syndrome (POTS), small‐fibre neuropathy (SFN), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), or as long‐term sequelae of myocarditis, vaccine‐induced thrombotic thrombocytopaenia (VITT), or immune thrombocytopaenia purpura (ITP). Symptomatically, PCVS overlaps with long COVID, such as fatigue and brain fog, but PCVS may involve more frequent paraesthesia and less dyspnoea. We also review pathophysiological hypotheses of PCVS, focussing on the vaccine‐derived spike protein and related immune responses. Finally, we discuss potential therapies used to treat patients with PCVS or related conditions, primarily documented in case reports/series, which could guide future clinical research. Overall, PCVS remains a poorly understood condition that requires more research to elucidate its prevalence, prognosis, risk factors, and treatments.