Median Follow-up Time Research Articles

Interstitial HDR brachytherapy for anal cancer-results and quality of life.

While anal cancer is avery rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. Atotal of 96patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30v.3 and the specific QOL-ANL27 questionnaire. Local control was 85.5% at 5years, 83.4% at 10years, 83.4% at 15years, and 83.4% at 20years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to atoilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.

Proton beam therapy for craniopharyngioma: a systematic review and meta-analysis.

Craniopharyngioma is a rare and slow-growing benign sellar or parasellar epithelial tumor. The number of patients receiving proton beam therapy (PBT) has increased. This study aimed to systematically evaluate and analyze the comprehensive evidence regarding the safety and efficacy of PBT for craniopharyngioma. We searched four databases: the Cochrane Library, PubMed, Embase, and Web of Science. The period was from their inception to February 16, 2024. Two researchers independently screened the literature and extracted data. Among 486 candidate articles, eight studies were included in our study. Exactly 393 patients with craniopharyngioma underwent PBT in these studies. These studies reported data on survival and toxicity. The median sample size was 42.5 patients. The median age was9.1-37years; the female proportion was 48.9%, and the median follow-up time was 29-91.4months. All patients were treated once daily, five times a week, with a fraction of 1.8Gy (RBE) per session. The median total dose was 54.0Gy (RBE). The local control rates at 3 and 5years in these studies were 99% and 93%, respectively. The overall survival rates at 3 and 5years in these studies were both 100%. The incidence of acute and late toxicities was mainly grade 1-2. The main late toxicities included vascular and visual toxicities, hypothalamic obesity, endocrinopathy, and panhypopituitarism. PBT for craniopharyngioma, especially in children and adolescents, has shown impressive local control and acceptable acute and late toxicities.

The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era.

To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance. Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis. Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23-0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25-0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41-0.79, P = 0.001) were favorable prognostic factors for OS in PR patients. In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.

Risk of Recurrent Prolapse by Extent of Mesh Excision Procedures: A Multicenter Study.

There is limited evidence guiding surgeons in how much mesh to resect when treating mesh complications. The aim of the study was to compare rates of recurrent prolapse after mesh excisional surgical procedures for prolapse mesh complications. This multicenter, retrospective cohort study included patients, identified by Current Procedural Terminology codes, who were treated surgically for prolapse mesh complications at 8 institutions between 2010 and 2019. Excisional surgical procedures were categorized as major (total vaginal, extravaginal, and total mesh excisions) or minor (partial vaginal excisions and mesh revisions). The primary outcome was prolapse recurrence 1 year after mesh excision surgery. Secondary outcomes included long-term prolapse recurrence. Prolapse recurrence was evaluated by Kaplan-Meier survival analysis and Cox proportional hazards regression. Two hundred sixty-one patients met inclusion criteria with 188 (72%) undergoing minor and 73 (28%) major excisions, with a median follow-up time of 1.0 years. Groups differed in parity, location of implant surgery, and number of vaginal compartments involved in excision. Within the first year, major excisions had a higher prolapse recurrence rate (8.7%) than minor excisions (2.9%), P < 0.05. Adjusting for mesh implant type, the hazard ratio for pelvic organ prolapse was 6.1 in the major compared to minor excision. In the entire study period, prolapse recurrence was 33.8% and did not differ between groups. Patients undergoing major excision surgical procedures may have higher rates of prolapse at 1 year compared to those undergoing minor excisions. However, in long-term follow-up, recurrence rates were not different. Our findings may aid surgeons in expectation setting prior to excisional procedures.

Outcomes Associated with Novel Oral Anticoagulants and Warfarin in Patients with Cardiac Thrombus Following STEMI.

The treatment of cardiac thrombus after ST-segment elevation myocardial infarction (STEMI) is anticoagulation. There is conflicting data on effectiveness and safety of novel oral anticoagulants (NOACs) vs. warfarin. Using the national Medicare data, we identified patients with an admission diagnosis of STEMI and cardiac thrombus within six months after STEMI. Patients were divided into two groups based on initial type of anticoagulation medication (NOACs vs. warfarin). The two main outcomes were ischemic stroke/transient ischemic attack (TIA) and bleeding. Follow-up was performed through the end of 2023. Kaplan-Meier (KM) Curves and Cox proportional hazard models were utilized. Of 881 patients prescribed anticoagulation after STEMI with subsequent cardiac thrombus, 496 patients were prescribed NOACs (56.3%) and 385 patients (43.7%) warfarin. For ischemic stroke, the median follow-up time was 177 days (95% CI: 148-193) for warfarin and 266 days (95% CI: 204-326) for NOACs. There was significantly lower risk of ischemic stroke or TIA in cardiac thrombus patients treated with NOACs compared to warfarin [HR 0.73 (0.57-0.93)]. For bleeding, the median follow-up time was 192 days (95% CI: 175-232) for warfarin and 277 days (95% CI: 212-332) for NOACs. There was also a lower risk of bleeding in patients treated with NOACs compared to warfarin [HR 0.78 (CI 0.66-0.92)]. In conclusion, STEMI patients with cardiac thrombus had lower risk of ischemic stroke and bleeding when treated with NOACs compared to warfarin. Prospective randomized studies are needed to confirm these findings and further examine the comparative effectiveness of different anticoagulant strategies.

Abstract B010: Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis

Abstract Introduction: Previous studies have demonstrated a role for assessing circulating tumor cells (CTC) in melanoma, but significant heterogeneity among studies has limited application in the clinical setting. We sought to evaluate the prognostic value of CTCs in advanced stage melanoma using a standardized CTC enumeration platform. Methods: A PubMed literature search was conducted up to March 2024. All studies evaluating CTC enumeration using CellSearchTM with outcomes data were included. Student's t-test was used to compare differences between groups. Hazard ratios (HR) were pooled using random effects model to assess the association of CTCs with overall survival (OS). I 2 statistic and Cochran’s Q test, sensitivity analyses, and Egger’s test of asymmetry were used to assess study heterogeneity, differential impact of individual studies, and publication bias, respectively. Results: Of the 12 studies identified, nine met inclusion criteria. A total of 678 patients were included, of which 337 (49.6%) were stage III and 342 (50.4%) were stage IV. The majority of studies reported CTC rates using a cut-off of ≥ 1 (6 studies, 66.7%), while three studies used ≥ 2 and five studies used both. Median follow-up time was available for six studies and ranged from 5.9-48 months (median 13.4). Average CTC detection rate (≥ 1 or 2) was 41% (SD 14.0) and was significantly higher using a cut-off of ≥ 1 (45.4%, SD 12.6) compared to ≥ 2 (26.1%, SD 2.7, p = 0.02). Pooled analysis of two studies demonstrated significantly worse OS with CTC ≥ 1 (HR 1.6, 95% CI: 1.0-2.6, p = 0.04). Similarly, pooled analysis of five studies with available HRs demonstrated significantly worse OS with CTC ≥ 2 (HR 2.1, 95% CI: 1.4-3.1, p = 0.0003). Among these five studies, moderate heterogeneity was observed (I2 = 43.4%), although this was not statistically significant (Q statistic p = 0.13). Sensitivity analyses confirmed the prognostic value of CTC ≥ 2, with pooled HRs ranging from 1.9-2.4 after consecutive omission of each study from the overall analysis. Conclusion: Regardless of the CTC cutoff used (≥ 1 or 2), presence of any CTCs was a strong prognostic marker in patients with advanced stage melanoma. Incorporation of CTC assessments in clinical practice may help risk stratify patients and guide treatment decisions. Further studies are needed to determine the optimal cut-off point for CTC status in assessing prognosis. Citation Format: Jennifer H. Chen, Hyunsoo Hwang, Bamboo Dong, Vanessa N. Sarli, Joshua R. Upshaw, Salyna Meas, Anthony Lucci. Prognostic value of circulating tumor cells in stage III and IV melanoma: A systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B010.

Phase Ib study of the oral PI3Kδ inhibitor linperlisib in patients with advanced solid tumors.

Patients with advanced solid tumors have a suboptimal prognosis. This study investigated the safety and feasibility of linperlisib, a selective phosphatidylinositol 3-kinase delta isoform (PI3Kδ) inhibitor, for treating patients with advanced solid tumors. In this phase Ib, single-arm, open-label, multi-center clinical trial, patients with histologically confirmed advanced solid tumors from eight centers in China were enrolled to receive oral linperlisib (80mg/day). The primary endpoint was safety. Between August 2019 and June 2022, 94 patients were enrolled in the trial and received the study treatment. The most common (≥ 20%) treatment emergent adverse events (TEAEs) of all grades irrespective of causality were increased aspartate aminotransferase (AST) (26.6%), proteinuria (26.6%), decreased appetite (25.5%), increased alanine aminotransferase (ALT) (22.3%), weight loss (21.3%), and anemia (21.3%). The most common grade ≥ 3 TEAEs were diarrhea (4.3%), increased AST (3.2%), increased ALT (3.2%), neutropenia (3.2%), anemia (3.2%), increased blood alkaline phosphatase (3.2%). The objective response rate (ORR) was 1.1% (95% confidence interval [CI] 0.0-5.8), and the disease control rate (DCR) was 37.2% (95% CI 27.5-47.8). As of the data cutoff, the median follow-up time was 4.2months (95% CI 2.8-6.9). The median progression-free survival (PFS) was 1.85months (95% CI 1.79-1.88). The median overall survival (OS) was not reached. Linperlisib showed an acceptable safety profile and preliminary clinical benefit in patients with a range of advanced solid tumors. Further studies of linperlisib safety and efficacy are warranted.

Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients. A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS). Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm3 vs. 6.3 cm3, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32). Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder.

Preliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption. To test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual. This cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD. The primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD. The primary outcome was AUD hospitalization analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)-related hospitalization, somatic hospitalization, and suicide attempt. The cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15). Among patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.

Long-Term Outcomes of Component Separation for Abdominal Wall Hernia Repair.

Component separation is a reconstructive technique used to facilitate midline closure of large or complex ventral hernias. Despite a contemporary surge in popularity, the incidence and long-term outcomes after component separation remain unknown. To evaluate the incidence and long-term outcomes of component separation for abdominal wall hernia repair. This cohort study examined 100% Medicare administrative claims data from January 1, 2007, to December 31, 2021. Participants were adults (aged ≥18 years) who underwent elective inpatient ventral hernia repair. Data were analyzed from January through June 2024. Use of component separation technique during ventral hernia repair. The primary outcomes were the incidence of component separation over time and operative recurrence rates up to 10 years after surgery for hernia repairs with and without component separation. The secondary outcome was rate of operative recurrence after component separation stratified by surgeon volume. Among 218 518 patients who underwent ventral hernia repair, the mean (SD) age of the cohort was 69.1 (10.9) years; 127 857 patients (58.5%) were female and 90 661 (41.5%) male. A total of 23 768 individuals had component separation for their abdominal wall hernia repair. The median (IQR) follow-up time after the index hernia surgery was 7.2 (2.7-10) years. Compared with patients who did not have a component separation, patients undergoing repair with component separation were slightly younger; more likely to be male; and more likely to have comorbidities, including obesity, and had surgeries that were more likely to be performed open and use mesh. Proportional use of component separation increased from 1.6% of all inpatient hernia repairs in 2007 (279 patients) to 21.4% in 2021 (1569 patients). The 10-year adjusted operative recurrence rate after component separation was lower (11.2%; 95% CI, 11.0%-11.3%) when compared with hernia repairs performed without component separation (12.9%; 95% CI, 12.8%-13.0%; P = .003). Operative recurrence was lower for the top 5% of surgeons by component separation volume (11.9%; 95% CI, 11.8%-12.1%) as opposed to the bottom 95% of surgeons by volume (13.6%; 95% CI, 13.4%-13.7%; P = .004). This study found that component separation was associated with a protective effect on long-term operative recurrence after ventral hernia repair among Medicare beneficiaries, which is somewhat unexpected given the intent of its use for higher complexity hernias. Surgeon volume, while significant, had only a minor influence on operative recurrence rates.

Survival status and prognostic factors analysis in patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension

Objective: To analyze the survival status and prognostic factors of patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension (HHT-PAH). Methods: This prospective study included patients diagnosed with HHT-PAH at the Fuwai Hospital of the Chinese Academy of Medical Sciences and Guangdong General Hospital from August 2009 to December 2019. Patients were followed up every 6 months±2 weeks, with all-cause mortality as the study endpoint. Multivariate Cox proportional hazards regression mode was used to further screen and validate the prognostic factors. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the survival time differences between patients with and without hepatic arteriovenous malformations. Results: A total of 18 HHT-PAH patients were included, with 14 females (77.8%) and a median age [M (Q1, Q3)] of 39 (32, 45) years. The median follow-up time was 129 (51, 156) months. During the follow-up period, 12 patients (66.7%) died, with a median survival time of 70 (32, 123) months. The 1-year, 3-year, 5-year, and 10-year survival rates were 100.0%, 70.8%(95%CI: 52.3%-96.0%), 53.1%(95%CI: 34.0%-83.0%), and 26.6%(95%CI: 10.6%-66.4%), respectively. HHT-PAH patients with hepatic arteriovenous malformations had a shorter median survival time than those without hepatic arteriovenous malformations [31.0 months (95%CI: 16.6-45.4 months) vs 84.0 months (95%CI: 54.4-113.6 months), P=0.024]. Cox proportional hazards regression analysis showed that hepatic arteriovenous malformation (HR=4.493, 95%CI: 1.064-18.978) was a risk factor for all-cause mortality in HHT-PAH patients. Conclusions: The 10-year survival rate of HHT-PAH patients is poor. The presence of hepatic arteriovenous malformations is a risk factor for mortality in HHT-PAH patients.

Abstract 4147606: The Risk of Cardiac Events Associated with Psychiatric Drugs in Patients with Long QT Syndrome.

Introduction: Long QT syndrome (LQTS) is a potentially life-threatening genetic heart disease. Patients with LQTS may also have co-existent mental health illnesses that may benefit from psychiatric medications. However, because many of these medications have QT-prolonging potential (www.crediblemeds.org), many of these patients receive suboptimal mental health care. Objective: To evaluate the frequency, management, and incidence of breakthrough cardiac events (BCEs) in patients with LQTS and concomitant mental health issues treated with psychiatric medications. Methods: A retrospective review was conducted on patients cared for in Mayo Clinic's Windland Smith Rice Genetic Heart Rhythm Clinic between 2000 and 2024 focusing on patients with LQTS and a concomitant psychiatric diagnosis requiring medication with known, possible or conditional risk of torsades de pointes (TdP). Electronic medical records were reviewed for data. BCEs were defined as LQTS-triggered syncope, seizures, appropriate ICD therapy, sudden cardiac arrest (SCA), or sudden cardiac death (SCD). Patients with missing information were excluded. Results: Overall, 195 /1899 LQTS patients [10%, 86 (43%) with LQT1, 83 (42%) with LQT2, and 16 (8%) with LQT3] had a concomitant psychiatric diagnosis requiring medication [150 female (76%), mean age at diagnosis 27 ± 18 years, median follow-up time 6.6 years (IQR 2.9-13)]. The most common psychiatric conditions were depression (71%), anxiety (62%), and ADHD (9%). The mean duration of therapy was 3.36 +/- 3.48 years and the most common medications used were fluoxetine (26%), sertraline (14%), and escitalopram (11%). There was no significant difference in QTc after starting the first psychiatric medication when compared to baseline (473 ± 33 vs 474 ± 35 ms, p=0.6). Prior to their LQTS diagnosis and while therefore untreated, 61/195 (31%) had at least 1 LQTS-associated cardiac event. This occurred in the setting of a psychiatric drug in 7 patients (11%). Following LQTS diagnosis and treatment, 14/195 patients (7%) have experienced a non-lethal BCE of which only 3/14 (21%) while on psychiatric medications. Conclusions: Although avoidance of medications with known QT-prolonging potential is prudent, attention to patient’s overall well-being besides just their LQTS must be given. After correct diagnosis and treatment, LQTS patients with concomitant mental health issues may be safely and effectively treated with medications known to prolong QTc.

Abstract 4136762: Association Between Circadian Rest/Activity Rhythms and Incident Dementia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Alterations in circadian rest/activity rhythms (RARs) are common among older adults. RARs can be derived from accelerometry data and are routinely used as proxy measures. Evidence suggests that altered (e.g., fragmented, delayed) RARs may be risk factors for dementia. However, results have been mixed. Using data from the ARIC Study, a community-based cohort, we assessed the association between RARs and incident dementia. Methods: ARIC participants without dementia who wore the Zio XT ECG Patch in 2016-17 for &gt; 3 days were included. RARs were obtained from an accelerometer within the Zio XT ECG Patch and measures of interdaily stability (IS; consistency), intradaily variability (IV; fragmentation), and relative amplitude (RA; strength) were derived. Dementia cases were identified through 2020 using in-person and phone-based cognitive assessments, hospitalization discharge codes, or death certificates. Cox proportional hazards models were used. Results: Of the 2,183 participants (mean [SD] age 79 [4.5] years, 58% female, 24% identified as Black), 176 (8%) developed dementia. Median follow-up time was 3 years and mean Zio XT ECG Patch wear time was 12 days. After multivariable adjustment, lower RA and higher IV were associated with incident dementia (HRs [95% CIs] per 1-SD increment: 0.65 [0.56-0.76], 1.19 [1.02-1.38]). No significant association between IS and dementia was noted; however, there was an interaction by race (p=0.03). Stratified results were not significant, but effect estimates were in opposite directions: (HRs [95% CIs] per 1-SD increment in IS: 0.78 [0.59-1.02] in Black participants and 1.17 [0.96-1.41] in white participants, respectively). No interactions by sex or APOEε4 were noted (p&gt;0.10). Conclusion: In this community-based cohort of older adults, weaker circadian rhythm strength and fragmentation were associated with dementia risk. The association between IS and dementia may differ by race; however, this needs to be further examined in future research. Overall, measures of circadian RARs may be risk factors for dementia. Additional research is warranted to determine whether they can be novel targets for dementia prevention.

Association between mammographic breast density and outcome in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy.

To analyze the relationship between mammographic breast density and tumor response and outcome at follow-up, in terms of overall survival (OS) and disease-free survival (DFS), in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy (NACT). A total of 228 women (mean age, 47.6years ± 10 [SD]; range: 24-74years) with invasive breast cancer who underwent NACT were included in this observational retrospective study. Clinical, radiological and histopatological data were retrieved. Categorization of breast density was performed by two radiologists in consensus on mammography acquired at the time of diagnosis according to BI-RADS categories. Association between density categories and tumor response was analyzed in the overall population and in subgroups defined by menopausal status, tumor phenotype and stage at diagnosis. Kaplan-Meier (KM) curves were used to estimate the OS and DFS probabilities. Subgroup analyses based on menopausal status and tumor phenotype were performed. A total of 30 patients (13.2%) achieved pathological complete response (pCR). No association between density categories and pCR was found (P = 0.973), even at subgroups analysis. The median follow-up time was 92months. Patients with dense breast showed the longest DFS (P = 0.0094), results confirmed in premenopausal patients (P = 0.0024) and in triple negative breast cancers (P = 0.0292). Density category did not show a statistically significant association with OS. Breast cancer patients receiving NACT with extremely dense breasts showed better DFS. No evidence of breast density as a predictive marker for complete pathological response or as a prognostic factor in terms of OS was found.

A Novel Preoperative Classification System for Selecting Suitable Surgeries in Liver Transplant Patients with Portal Vein Cavernous Transformation

Background To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT). Methods This retrospective observational study analyzed data from allograft LTs performed for various liver diseases Results The study included 22 males and 4 females with LT indications comprising cirrhosis (n = 9), hepatocellular carcinoma (n = 12), PVCT (n = 2), liver failure from fulminant hepatitis B (n = 1), dysfunction of transplanted liver (n = 1), and chronic rejection of transplanted liver (n = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1–C5). In total 16 simple operations were performed on C1–C3 cases and 9 complex operations on C4–C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively (p = 0.526). Conclusion The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Abstract 4134778: Myocardial Recovery and Survival after Weaning of Left Ventricular Assist Device Therapy in Patients with Toxic and non-Toxic Cardiomyopathy, A Canadian Experience

Left ventricular assist devices (LVAD) are increasingly used in refractory heart failure, mainly as a bridge to transplant or as destination therapy. LVAD unloading of the left ventricle (LV) can also promote myocardial recovery leading to improvement of the LV systolic function, allowing LVAD explantation. However, parameters associated with LVAD weaning and long-term outcomes are not well documented. The aim of this study was to assess the clinical and echocardiographic characteristics of weaned patients and to evaluate their event-free survival post-explantation. We conducted a single-center retrospective study recruiting patients who underwent a second or third generation LVAD implantation at a Canadian cardiology center between November 2009 and October 2021. A total of 98 patients underwent LVAD implantation during this period. All patients were on guideline-directed medical therapy (GDMT). Fourteen patients (14%) had significant LV recovery and were explanted/decommissioned after a median support time of 309 days (range 55-595 days). Toxic cardiomyopathy, defined as abuse of amphetamines (n=2), energy drinks (n=2) or multiple substances (n=6), was the most likely diagnosis in 10 of the weaned patients (71%). The LVEF was significantly higher and the left ventricular end-diastolic diameter (LVEDD) was significantly lower in weaned patients compared to unweaned patients after 3 months of support. Myocardial recovery manifested as pump thrombosis in 4 of the weaned patients (29%). Prior to explantation, 12 patients had a decrease in GDMT doses to minimize post explantation vasoplegia. After explantation, median follow-up time was 40 months (range 8-109 months) and the majority of patients were anticoagulated for 3 months. At last follow up, the LVEF was 44±6% and no patient had a LVEF below 35%. All patients were NYHA I or II and no death, heart transplant, or mechanical support initiation occurred. LVAD therapy can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially young patients with toxic and non-ischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months following implantation is associated with successful weaning. Pump thrombosis seems to be associated with LV reverse remodeling and weaning of mechanical support in certain patients. Weaned patients maintain satisfactory LVEF recovery after explantation and have good long-term event-free survival.

Multi-year enzyme expression in patients with mucopolysaccharidosis type VI after liver-directed gene therapy.

Mucopolysaccharidosis type VI (MPS VI) is due to a deficiency of the lysosomal enzyme arylsulfatase B (ARSB) that results in multi-organ accumulation of glycosaminoglycans (GAGs). Limitations of current treatments prompted the development of a liver-directed gene therapy clinical trial for MPS VI. We report the long-term follow-up of patients with MPS VI who discontinued enzyme replacement therapy (ERT) and received a single intravenous infusion of high-dose (6×1012 genome copies/kg) recombinant adeno-associated virus serotype 8 (AAV8) vector expressing ARSB under the control of a liver-specific promoter (ClinicalTrials.gov: NCT03173521). Primary outcomes were safety and urinary GAG excretion. Secondary outcomes were endurance and respiratory function. Median follow-up time was 45months (n= 4, three females and one male; age range: 5-10 years). No late-emergent safety events were observed. Patients showed sustained serum ARSB activity (38%-67% of mean healthy reference values), a modest increase in urinary GAG concentrations, and no relevant changes in endurance, cardiac, or pulmonary function. In one of the four patients, ERT was restarted because of elevated urinary GAGs without decreased serum ARSB activity up to about 2.5 years after gene transfer. Liver and spleen size remained within the reference ranges. A single intravenous administration of AAV8.TBG.hARSB was safe and resulted in sustained ARSB expression and a modest increase in urinary GAGs in most patients, thus supporting liver-directed gene therapy for MPS VI. This study was sponsored by the Telethon Foundation ETS, the European Union, the Isaac Foundation, and the Italian Ministry of University and Research.

Abstract 4135993: Body Composition and Mortality Throughout the Reproductive Cycle: Findings from the Multi-Ethnic Study of Atherosclerosis

Introduction: Changes in body composition throughout the reproductive cycle accelerate during the 2 years following the final menstrual period (FMP), known as the menopausal transition (MT). During MT, an increase in fat mass (FM) and a decrease in fat free mass (FFM) are usually seen, but the relationship between these changes and cardiovascular events is not well understood. We aim to explore how FM and FFM are associated with cardiovascular events and total mortality across the reproductive cycle in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: This study included 3439 women from exam 1 of MESA. Outcomes of interest were either MACE (heart failure, myocardial infarction, coronary revascularization, cardiac arrest, or stroke) or all-cause mortality. Equations to determine FM and FFM at exam 1 were validated with the NHANES 2003 population and derived from regression models based on bioelectrical impedance analysis results at exam 5 and anthropometric and demographic measures. Women were divided into 3 groups based on time since FMP: reproductive phase (before FMP), MT phase (&lt;2 years after FMP), and late menopause phase (&gt;2 years after FMP). Adjusted Cox multivariate models assessed the association between FM, FFM and MACE or all-cause mortality. Results: Median follow-up time was 14.1 years. FM was associated with MACE in the late menopause group, whereas FFM was not associated with MACE (Table). With respect to all-cause mortality, FM had a positive association (HR=1.19, P=0.03) while FFM had a negative association (HR=0.68, P=0.04) in the MT phase. The late menopause group showed similar relationships between FM, FFM, and all-cause mortality. The reproductive group showed no significant associations (Table). Conclusion: In this cohort, FM is associated with a higher risk of mortality whereas FFM is associated with a lower risk. We observed these associations to be more pronounced during the MT, a time of accelerated body composition change. Our results suggest and will need further investigation to confirm that the MT may be a critical time in the female lifespan to initiate interventions which positively impact muscle mass with a view to improving survival.

Abstract 4137424: Circulating Levels of the Pro-Fibrotic Collagen Hormone Endotrophin are Associated with the Risk of Experiencing Major Adverse Cardiovascular Events in Individuals with Type 2 Diabetes – The Thousand&amp;2 Study

Introduction: Cardiovascular disease (CVD) complications are the leading cause of mortality in individuals with type 2 diabetes (T2D). Abnormal extracellular matrix (ECM) remodelling leads to the release of ECM protein fragments into circulation, reflecting these complications. Endotrophin, a pro-fibrotic and -inflammatory hormone, released during collagen type 6 formation, has been linked to adverse outcomes in T2D, but not previously in a long-term perspective. Aim: To assess the 12-year prognostic value of circulating endotrophin levels, measured by PRO-C6, to predict the risk of major adverse cardiovascular events (MACE) in a large cohort of individuals with T2D. Methods: Endotrophin levels were measured with the NordicPRO-C6™ ELISA in 909 serum samples from the Thousand&amp;2 study, which was initiated in 2011 and examined individuals with T2D, with and without known CVD. Clinical data were collected at baseline. Follow-up was 100% complete and performed on the 1 st of May 2024 with the registration of data on MACE from the Danish national registers. The primary outcome was MACE, defined as incident events of hospital admission for ischemic heart disease, heart failure, stroke, or all-cause mortality. PRO-C6 was split into tertiles and examined for survival probability by Kaplan-Meier analysis. Univariate Cox proportional hazard regression analysis was conducted to examine the association between PRO-C6 and the risk of MACE. A multivariable Cox model was additionally conducted, adjusted for age at baseline, sex, systolic blood pressure, duration of diabetes, HbA1c, estimated glomerular filtration rate, use of statins, albuminuria status, and current or prior smoking. Results: The baseline mean (±SD) age of the cohort was 64 (±10) years, 66% were males, mean (±SD) PRO-C6 was 11.9 (±7.01) ng/ml, the median follow-up time was 10.6 years, and number of MACE recorded was 472. The risk of experiencing MACE was significantly higher in the third tertile compared to the first and second tertile (Log-Rank p &lt; 0.001). In the univariate Cox model, the estimated hazard ratio (HR), corresponding to a 2-fold increase of PRO-C6, was HR [95% Confidence Interval(CI)] = 2.1 [1.8-2.4], P &lt;0.001. In the fully adjusted Cox model, PRO-C6 remained significantly associated with the risk of MACE (HR [95% CI] = 1.5 [1.2-1.8], P &lt;0.001). Conclusion: Elevated circulating endotrophin is associated with MACE in T2D, independent of common risk factors.

Long term outcomes from the early days of minimally invasive thymoma surgery for Myasthenia Gravis patients: a follow-up of 19 years

BackgroundLong-term survival outcomes are crucial for accurately determining the effectiveness of treatment in an indolent disease like thymoma. We aimed to analyze the clinical findings in terms of survival and relapse patterns with a median follow up of 105 months (8.7 years) in patients with thymoma and myasthenia gravis who underwent minimally invasive surgery between 2002 and 2015.MethodsA total of 59 pathologically confirmed Masaoka Stage I and II thymoma patients with Myasthenia Gravis (MG) who underwent minimally invasive thymoma resection were included in this study. Primary aim of this study is to evaluate recurrences, overall and disease free survival in patients with a thymoma and MG in the long run. We also aimed to study the changes in Myasthenia Gravis medication during the follow-up.ResultsThe mean age of the patients was 47.6 +/13.5 years. Seventeen patients were at Masaoka Stage I and 42 were at Masaoka Stage II. The median follow-up time was 105 months. The mean size of the tumor was 3.6 cm +/16.2 cm. Twenty-one patients (35%) received adjuvant radiotherapy. There was no postoperative mortality and median length of hospital stay was 4 days. Two patients developed recurrences both presented with pleural metastases. Eight patients died because of non-oncologic pathologies. 10-year disease free survival and overall survival rates were calculated to 96.6% and 86.4% respectively.ConclusionThe 10-year survival analysis and current myasthenic status of stage I-II thymoma patients with myasthenia gravis who underwent minimally invasive surgery demonstrate that these procedures are both safe and effective.