5-year Cumulative Incidence Research Articles

Impact of Angiographically Detected Residual Trabeculation After Left Atrial Appendage Closure Using the WATCHMAN Device: Insight From the OCEAN-LAAC Registry.

Research on the impact of angiographically detected residual trabeculation after left atrial appendage closure (LAAC) is limited. To investigate the incidence, characteristics, and clinical implications of angiographically detected residual trabeculation after LAAC using the WATCHMAN device. We analyzed 1350 consecutive patients with atrial fibrillation undergoing LAAC using the WATCHMAN device from the OCEAN-LAAC registry, which is a prospective ongoing, multicenter Japanese registry. The inclusion criteria comprised patients who successfully underwent LAAC and whose presence or absence of residual trabeculation can be confirmed using a contrast medium. The clinical outcomes were compared between patients with and without angiographically detected residual trabeculation. Residual trabeculation was angiographically detected in 5.6% (75/1350 patients). At the procedure, the proportion of peri-device leak (PDL) was significantly higher in the residual trabeculation group than in the non-residual trabeculation group (20% vs. 5.1%, p < 0.001). However, the PDL and device-related thrombosis at 45 days and 1 year were comparable between the two groups (37% vs. 23%, p = 0.24; 28% vs. 31%, p = 0.84; 2.1% vs. 1.4%, p = 0.50; 6.9% vs. 6.0%, p = 0.69, respectively). The 3-year cumulative incidence of ischemic stroke, all cardiovascular death, and all-cause death were comparable between the two groups (5.7% vs. 5.5%, log-rank p = 0.96; 7.7% vs. 8.9%, log-rank p = 0.34, 31.4% vs. 22.3%, log-rank p = 0.71, respectively). The angiographically detected residual trabeculation rate was 5.6%, and this population had a significantly higher prevalence of PDL at the procedure. However, the presence of residual trabeculation did not contribute to PDL or device-related thrombosis at follow-up or affect the clinical outcomes.

Risk of recurrence in early-onset versus late-onset non-metastatic colorectal cancer, 2004–2019: a nationwide cohort study

The incidence of colorectal cancer (CRC) in individuals younger than 50 years of age (early-onset CRC) is increasing. Early-onset CRC often present at advanced stage, suggesting a more aggressive cancer course compared to late-onset CRC (age 50-79). This nationwide cohort study estimates the incidence of recurrence following early-onset CRC and late-onset CRC. The study included all Danish patients <80 years old operated for first-time Union for International Cancer Control (UICC) stage I-III CRC between January 2004 and December 2019. Recurrence status was determined by applying a validated algorithm to individual-level data from nationwide health registries. The 5-year cumulative incidence functions (CIF) of recurrence were reported for early-onset versus late-onset CRC. The difference in time to recurrence was estimated as a time ratio (TR) using an accelerated failure time model. Among 25,729 CRC patients, 1441 (5.6%) had early-onset CRC. Compared to late-onset CRC, early-onset was associated with advanced disease stages and higher treatment intensity. The 5-year CIF of recurrence was 29% (95% CI: 26%-31%) in early-onset versus 21% (95% CI: 21%-22%) in late-onset CRC. The higher CIF of recurrence for early-onset patients persisted in stage-stratified analysis. Time to recurrence was shorter in early-onset versus late-onset patients with TR=0.76 (95% CI: 0.67-0.85). The 5-year CIF of recurrence decreased from 2004 to 2019 for both early- and late-onset patients-most prominent for early-onset patients. Early-onset CRC was associated with higher incidence of recurrence at all disease stages. Indicating that the increased risk is not explained by delayed diagnosis. The excess risk diminished from 2004 to 2019, suggesting that early-onset CRC may achieve a similar recurrence risk as late-onset CRC in a contemporary setting. Aarhus University, Novo Nordisk Foundation, Innovation Fund Denmark, and the Danish Cancer Society.

Availability of transcatheter aortic valve implantation across hospitals and differences in strategies and clinical outcomes in patients with severe aortic stenosis.

There was a scarcity of data evaluating variations in treatment approaches and clinical outcomes for severe aortic stenosis (AS) between medical centers with and without availability of transcatheter aortic valve implantation (TAVI). Current study population was 2993 patients with severe AS enrolled in the CURRENT AS Registry-2 (2581 patients from 10 TAVI centers; 412 patients from 10 non-TAVI centers). TAVI centers more frequently opted for the initial aortic valve replacement (AVR) strategy compared to non-TAVI centers (60% and 40%, P < 0.001). Among patients with the initial AVR strategy, TAVI centers disproportionately favored the initial TAVI strategy compared to non-TAVI centers (71% and 23%, P < 0.001). No significant differences were observed in the risk of a composite of all-cause death or heart failure hospitalization between TAVI and non-TAVI centers in the entire study population (cumulative 3-year incidence: 32.0% and 31.0%, P = 0.37; adjusted hazard ratios: 0.92, 95% confidence intervals: 0.74-1.15, P = 0.45) or in conservative, initial AVR, initial surgical AVR, and initial TAVI strata. A substantial disparity exists in the treatment strategies for patients with severe AS between TAVI and non-TAVI centers. TAVI centers tended to perform AVR, particularly TAVI, earlier and more frequently. However, there was no discernible distinction in the risk of the composite of all-cause death or HF hospitalization between TAVI and non-TAVI centers. UMINID: UMIN000034169.

Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results

The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results. To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors. In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020. Data from the National Health and Nutrition Examination Survey (NHANES) from the January 1, 2017, to December 31, 2018, cycle were used to compare the risk profile distribution with that of the general US population. Data analysis was performed from October 2023 to August 2024. Time-varying status of NCS results and risk score. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs for incidence and mortality of CRC. A total of 195 453 participants (median [IQR] age, 44 [37-56] years at baseline; 81% female) were followed up for a median (IQR) of 12 (6-20) years. Among 81 151 individuals with NCS results and 114 302 without endoscopy, 394 and 2229 CRC cases and 167 and 637 CRC deaths, respectively, were documented. Negative colonoscopy screening results were consistently associated with lower CRC incidence (HR, 0.51; 95% CI, 0.44-0.58) and mortality (HR, 0.56; 95% CI, 0.46-0.70) for 20 years. Among individuals with NCS results, those with an intermediate risk (scores, 6-7) and low risk (scores, 0-5) did not reach the 10-year cumulative incidence of CRC (0.78%) of the high-risk individuals (scores, 8-12) until 16 and 25 years after initial screening, respectively. These findings provide evidence for shared decision-making between patients and physicians to consider extending the rescreening intervals after an NCS result beyond the currently recommended 10 years, particularly for individuals with a low-risk profile. These results showed, as a proof of concepts, the importance of considering known CRC risk factors when making decisions for colonoscopy rescreening.

COMPARABLE OUTCOMES AFTER BUSULFAN- OR TREOSULFAN-BASED CONDITIONING FOR ALLO-HSCT IN CHILDREN WITH ALL – RESULTS OF FORUM

The superiority of TBI-based versus chemotherapy-conditioning for allo-HSCT in children with ALL has been established in the international, prospective phase-III FORUM study (#NCT01949129), randomizing 417 patients ≤ 18 years at diagnosis (4-21 years at HSCT) in CR, transplanted from HLA-matched sibling or unrelated donors. Due to the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the pre-specified comparison of outcomes of patients receiving busulfan-based (BU) or treosulfan-based (TREO) regimens from 2013 to 2018. 180 and 128 patients (median age 9.9 years) received BU/THIO/FLU or TREO/THIO/FLU, respectively. Data were analysed as of 02/2023, with a median follow-up of 4.2 years (range 0.3-9.1). Three-year overall survival was 0.71 (0.64-0.77) (BU/THIO/FLU) and 0.72 (0.63-0.79) (TREO/THIO/FLU), event-free survival was 0.60 (0.53-0.67) (BU/THIO/FLU) and 0.55 (0.46-0.63) (TREO/THIO/FLU), with both p = NS. The 3-year cumulative incidence of relapse (0.31 (0.25-0.38) BU, 0.36 (0.27-0.44) TREO, p = 0.779) and non-relapse mortality (0.08 (0.05-0.13) BU, 0.09 (0.05-0.15) TREO, p = 0.831) were comparable (p = NS). One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic GvHD or GvHD-free and relapse-free survival (0.48 (0.41-0.55) BU, 0.45 (0.37-0.54) TREO, p = 0.89) were recorded. Outcomes for CR1 or CR2 patients were similar irrespective of the regimen used. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for ALL patients > 4 years with contraindications or lack of access to TBI.

Negative Association Between Schizophrenia and Subsequent Cancer Diagnoses—A Retrospective Cohort Study from Germany

Background: Since previous studies have reported contradictory findings regarding the relationship between schizophrenia and cancer, we evaluated the association between schizophrenia and cancer diagnoses. Methods: In this retrospective cohort study, the IQVIA Disease Analyzer database was utilized to examine the incidence of cancer among patients aged over 18 years diagnosed with schizophrenia in German general practices from 2005 to 2022. Patients with schizophrenia were compared with those without the condition, with adjustments made for age, sex, index year of diagnosis, average annual practitioners visit frequency, and comorbidity. Kaplan–Meier curves were used to analyze the 10-year cumulative incidence of schizophrenia and cancer in total amongst patients with and without schizophrenia. Univariate Cox regression analysis was performed to calculate Hazard Ratios (HR) of cancer risk and their 95% confidence intervals (CI) of cancer in total and of specific cancer types. Results: Patients with schizophrenia (N = 13.711) had a lower incidence of cancer diagnosis compared to those without (N = 68.555). Specifically, 10.4% of patients with schizophrenia and 12.5% of patients without the condition were diagnosed with cancer (p &lt; 0.001). Cox regression analysis showed a significant association between schizophrenia and subsequent cancer in the total population (HR: 0.82; 95% CI: 0.76–0.90), and among men (HR: 0.70; 95% CI: 0.61–0.80), but not among women (HR: 0.94, 95% CI: 0.84–1.04). Analyses stratified by cancer type and sex revealed a strong and significant association between schizophrenia and a decreased risk of prostate cancer in men (HR: 0.38; 95% CI: 0.24–0.61). Furthermore, there was also a negative association between schizophrenia and colorectal cancer risk in men, but statistical significance was not reached (HR: 0.58; 95% CI: 0.37–0.93). Conclusions: This study demonstrates negative associations between schizophrenia and subsequent cancer, and more specifically in men for prostate and colorectal cancer. However, further research is required to explore the underlying reasons for these associations.

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial.

The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke. We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization. Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358). In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke. ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease: a multicentre, randomized, double-blind, phase 2 trial

BackgroundFailure of systemic corticosteroid therapy is common in patients with newly diagnosed acute graft-versus-host disease (aGVHD) above grade II. Mesenchymal stem cells (MSCs) have been used as a tolerable and potentially effective second-line therapy for steroid-refractory aGVHD (SR-aGVHD); however, well-designed, prospective, controlled studies are lacking.MethodsThis multicentre, randomized, double-blind, placebo-controlled, exploratory phase 2 study enrolled patients with SR-aGVHD above grade II from 7 centres. Patients were randomized 1:1 to receive umbilical cord-derived MSCs or placebo added to one centre’s choice of second-line agents (except for ruxolitinib). The agents were infused twice weekly. Patients with complete response (CR), no response (NR), or progression of disease (PD) at d28 received 8 infusions, and those with partial response (PR) received the above infusions for another 4 weeks. The per-protocol population consisted of patients who received ≥ 8 infusions. The primary endpoint was the overall response rate (ORR, CR + PR) at d28, analyzed in the per-protocol and intention-to-treat populations.ResultsSeventy-eight patients (median age 38, range 13–62) were enrolled: 40 in the MSC group and 38 in the control. Patients in the MSC group received a median of 8 doses, with a median response time of 14 days. In intention-to-treat analysis, ORR at d28 was 60% for MSC group and 50% for control group (p = 0.375). The 2-year cumulative incidence of moderate to severe cGVHD was marginally lower in the MSC group than in the control (13.8% vs. 39.8%, p = 0.067). The 2-year failure-free survival was similar between the MSC and control groups (52.5% vs. 44.4%, p = 0.43). In per-protocol analysis (n = 62), ORR at d28 was significantly greater in the MSC group than in the control group (71.9% vs. 46.7%, p = 0.043). Among patients with gut involvement, ORR at d28 was significantly greater in the MSC group than in the control (66.7% vs. 33.3%, p = 0.031). The adverse events incidences were similar between groups.ConclusionsIn this exploratory study, there was no superior ORR at d28 demonstrated in the MSC group compared with the control. However, MSCs showed a gradual treatment effect at a median of 2 weeks. Patients who completed 8 infusions may benefit from adding MSCs to one conventional second-line agent, especially those with gut involvement. MSCs was well tolerated in patients with SR-aGVHD.Trial registrationchictr.org.cn ChiCTR2000035740.

Dynamics of measurable residual disease for risk stratification and guiding allogeneic transplant in acute myeloid leukaemia patients with myelodysplasia-related mutations in first remission.

Accurate classification and risk prediction are critical for therapeutic decision-making in patients with acute myeloid leukaemia (AML). Myelodysplasia-related (MR) gene mutations are classified as adverse genetic factors by the European LeukaemiaNet-2022 guidelines. However, their prognostic value in de novo AML remains controversial. This study retrospectively analysed 188 patients with de novo AML-MR, stratifying them into four subgroups based on dynamic measurable residual disease (MRD) after induction, one or two courses of consolidation chemotherapy. The median follow-up was 36.8 months (4.6-73.7). Patients with persistent or recurrent MRD positivity after the second consolidation had the poorest 3-year relapse-free survival (RFS), overall survival (OS) and cumulative incidence of relapse compared to the other groups (p < 0.001). Multivariable analysis identified this high-risk group as an independent risk factor for both RFS and OS. We observed significant heterogeneity of OS benefit from allogeneic stem cell transplantation (allo-SCT) by MRD-risk groups, with substantial OS advantage for patients in subgroup D (3-year OS: allo-SCT 70.0% vs. 18.2% without, p < 0.001) but no benefit for others (p = 0.047 for interaction). This study underscores the importance of dynamic MRD in refining risk stratification and identifying de novo AML patients with MR mutations who would benefit from allo-SCT during the first complete remission.

Incidence and Characterization of Secondary CNS Lymphoma in 1,972 Patients with DLBCL - A Danish Nationwide Cohort Study.

Secondary CNS involvement (SCNSL) is a rare manifestation of diffuse large B-cell lymphoma (DLBCL) with a poor prognosis. We present updated data from a nationwide study on the incidence and clinical characteristics of SCNSL. The incidence of SCNSL was calculated considering death or relapse without SCNSL as competing risks. Risk factors associated with SCNSL were identified using a cause-specific Cox proportional hazards model. A total of 1972 patients with DLBCL were included and 68 (3.4%) of these experienced SCNSL at first relapse. The crude 1- and 2-year cumulative incidence of SCNSL was 2.0% (95% CI, 1.5-2.7) and 2.6% (95% CI, 2.0-3.4). For patients with a high-risk CNS International Prognostic Index (CNS-IPI) score, the 1- and 2-year cumulative incidence was 6.4% and 7.5%. The number and location of extranodal (EN) sites was the most significant predictor of SCNSL. Specific EN sites associated with increased risk were bone marrow, heart, kidneys/adrenal glands, ovaries, testes and uterus. Median overall survival (OS) after SCNSL was 3.2 months. SCNSL within six months after end of primary treatment (EOT) was associated with a higher baseline CNS-IPI score and worse OS compared to SCNSL more than six months after EOT. Patients with a combination of low-risk CNS-IPI and late-onset SCNSL had the most favorable prognosis. In conclusion, updated real-world population-based data on SCNSL at first relapse, adjusted for competing risks, demonstrated a lower incidence of SCNSL than previously reported, with the number and location of EN sites being the most significant predictors of SCNSL.

A prophylactic tyrosine kinase inhibitor strategy based on measurable residual disease pre-transplantation for Ph+ acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A prospective multicenter cohort study.

Relapse is the major cause of treatment failure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of a prophylactic tyrosine kinase inhibitor (TKI) strategy on relapse in this population. Patients were assigned to prophylactic or control groups based on measurable residual disease (MRD) pre-transplantation. The primary endpoint was the cumulative incidence of relapse. A total of 110 patients with Ph+ ALL undergoing allo-HSCT were enrolled in this prospective study. Thirty-eight patients with positive MRD pre-transplantation were included in the prophylactic group, and 72 with negative MRD pre-transplantation were included in the control group. The 4-year cumulative incidence of relapse was 25.3% (95% CI: 12.1%-41.0%) and 20.3% (11.6%-30.7%; HR = 1.272, 95% CI: 0.551-2.940, p = .549), and non-relapse mortality was 10.5% (3.3%-22.7%) and 9.7% (4.2%-17.9%; HR = 1.094, 95% CI: 0.320-3.738, p = .928) in the prophylactic and control groups. The 4-year overall survival was 71.8% (53.2%-84.1%) and 84.1% (72.9%-90.9%; HR = 1.746, 95% CI: 0.741-4.112, p = .196), and leukemia-free survival was 64.1% (45.8%-77.7%) and 70.0% (57.6%-79.4%; HR = 1.212, 95% CI: 0.607-2.421, p = .585) in the prophylactic and control groups. Our results suggest that prophylactic TKI post-HSCT in patients with positive MRD pre-transplantation can produce outcomes comparable to negative MRD pre-transplantation without TKI post-HSCT.

Trends in Peripheral Artery Disease, Lower Extremity Revascularization, and Lower Extremity Amputation in Incident Type 2 Diabetes: A Danish Population-Based Cohort Study.

To examine trends in peripheral artery disease (PAD), lower-extremity (LE) revascularization, and LE amputation in patients with incident type 2 diabetes. This cohort study included patients in Denmark diagnosed with type 2 diabetes in 1996-2015 and followed until 2020. Patients were age and sex matched with as many as three general population individuals. Outcomes comprised 5-year cumulative incidences of first-time PAD, LE revascularization, and LE amputation. Age- and sex-adjusted hazard ratios (aHRs) were computed using Cox regression. The cohort comprised 349,454 patients with incident type 2 diabetes (53% male; median age 62 years) and 1,025,054 general population individuals. Among patients with diabetes, decreases in 5-year cumulative incidence of PAD (from 6.2 to 3.4%; aHR 0.55 [95% CI 0.52-0.57]), LE revascularization (from 0.8 to 0.6%; aHR 0.80 [95% CI 0.71-0.90]), and LE amputation (from 1.0 to 0.4%; aHR 0.45 [95% CI 0.40-0.51]) occurred from 1996-2000 to 2011-2015. LE amputation decreased at all amputation levels (hip/thigh, knee/lower leg, and ankle/foot/toe) during the study period. In the general population, 5-year cumulative incidence remained stable (1.2-1.5% for PAD, ∼0.4% for LE revascularization, and ∼0.2% for LE amputation). However, the relative rates of all outcomes were two- to threefold higher in patients with diabetes than matched individuals in 2011-2015. In recent decades, the cumulative incidence of LE complications substantially decreased in patients with incident type 2 diabetes while remaining stable in the general population.

Clinical Outcomes According to Aortic Stenosis Management: Insights From Real-World Practice.

Real-world data regarding clinical outcomes according to aortic stenosis (AS) management are scarce. Therefore, we aimed to investigate long-term management across the spectrum of outpatients with AS. Between May 2016 and December 2017, consecutive outpatients with mild (peak aortic velocity, 2.5-2.9 m/s), moderate (3-3.9 m/s), and severe AS (≥4 m/s) were included by 117 cardiologists in the VALVENOR (Follow-Up of a Cohort of Patients With Valvular Aortic Stenosis in the Nord-pas-de-Calais Region) study and followed-up for aortic valve replacement (AVR) and modes of death. Among 2704 patients included, 1156 (42.7%) had mild, 1121 (41.5%) moderate, and 427 (15.8%) severe AS. After a median follow-up of 5 years, 993 AVRs (488 surgical and 505 transcatheter) and 1098 deaths occurred. The 5-year cumulative incidence of AVR or of the composite of death or AVR was 13.3% and 45.2% in mild AS, 45.5% and 75.3% in moderate AS, and 62.8% and 90.6% in severe AS, respectively. Of the 292 patients who met the criteria for AVR but were not treated, AVR was considered futile in 137 patients and 155 patients refused AVR. Mortality rates after 3 years were high: 86% for anticipated futility and 72.3% for refusal. While patients at anticipated futility showed a well-balanced proportion of cardiovascular and noncardiovascular deaths, cardiovascular deaths predominated among those who refused AVR. At 5-year follow-up, only two thirds of patients with severe AS underwent AVR. Patients with untreated severe AS experienced high mortality rates, mostly cardiovascular for patients who declined AVR. This advocates for better patient education based on shared decision making and for optimizing AS quality of care, from diagnosis to treatment.

Local Recurrence and Survival in Patients With Melanoma >2 mm in Thickness at Difficult Sites Treated With 1-cm Versus 2-cm Margins.

Melanoma guidelines recommend surgical excision with 2-cm margins for melanomas >2 mm in thickness. However, this procedure may be problematic at critical anatomic sites. We aimed to compare the outcomes of wide (2 cm) versus narrow (1 cm) excision margins in patients with melanoma >2 mm in thickness near critical structures. We retrospectively examined 736 patients undergoing excision with wide versus narrow margins at the National Cancer Institute in Milan, Italy, between 2001 and 2015. A total of 265 (36.0%) patients received a wide local excision-82 (30.9%) with linear repair and 183 (69.1%) with flap or graft reconstruction. A total of 471 (64.0%) patients received a narrow excision-320 (67.9%) with linear repair and 151 (32.1%) with flap or graft reconstruction (P<.001). The 10-year overall survival rate was 69.5% (95% CI, 63.3%-76.2%) in the wide group and 68.7% (95% CI, 63.8%-74.0%) in the narrow group (P=.462); 10-year crude cumulative incidence (CCI) of local recurrence was 5.4% (95% CI, 3.2%-9.2%) in the wide and 8.8% (95% CI, 6.4%-12.1%) in the narrow group (P=.150). Multivariable Fine-Gray modeling of the CCI of local recurrence showed that Breslow thickness (P=.010) was the only statistically significant parameter. Multivariable Cox models for overall survival showed that age (P<.001), Breslow thickness (P<.001), and sentinel lymph node status (P=.019) were statistically significant covariates. Excision margin was not a significant parameter affecting patients' outcome. Wide local excision with 1-cm margins for melanoma >2 mm in thickness was not associated with an increased risk of local recurrence and did not affect overall survival.

Incidence of Central Serous Chorioretinopathy and its Association with Gynecological Diseases in Women: a Population-based Nested Case–Control Study

Purpose: Although the exact pathogenesis of central serous chorioretinopathy (CSC) remains unclear, some factors are known to be sex-specific. We aimed to investigate the incidence and systemic associations for CSC in women. Methods: This population-based nested case–control study included East Asian women whose medical claims data were obtained from the Korean National Health Insurance Service database. Patients newly diagnosed with CSC between 2017 and 2019 were assigned to the CSC group and matched to healthy controls in a 1:4 ratio by age, gender, and index date. The incidence of CSC in women and its association with gynecologic comorbidities and corticosteroid use before the index date (2008-2017) were analyzed. Results: The study matched 3,789 patients with CSC with 15,156 controls. The 3-year cumulative incidence of CSC in women was 27.13 (95% confidence interval [CI], 27.06–27.19) per 100,000 people. Multivariate logistic analysis showed a significantly increased association of CSC in patients with pre-eclampsia (adjusted odds ratio [aOR], 2.66; 95% CI, 1.86–3.81) (P&lt;0.001), endometriosis (aOR, 1.19; 95% CI, 1.03–1.38) (P&lt;0.001), steroid injections alone (aOR, 1.29; 95% CI, 1.16–1.43) (P&lt;0.001), and combination use of oral and injected steroid (aOR, 1.34; 95% CI, 1.23–1.47) (P&lt;0.001) compared to the controls. Conclusions: This study provides nationwide population-based data on the incidence of CSC in Asian women and suggests that exposure to specific gynecological comorbidities and intensive corticosteroid use are associated with the development of CSC in women.

Abstract 4136632: Impact of Postoperative Atrial Fibrillation on Long-term Clinical Outcomes in Patients after Coronary Artery Bypass Grafting

Background: The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes has not been adequately evaluated yet. Methods: Among consecutive 14927 patients who underwent their first coronary revascularization in the CREDO-Kyoto PCI/CABG Registry Cohort-3 (2011-2013), the study population consisted of 1483 patients who underwent CABG after excluding those with prior AF. POAF was defined as newly documented AF during hospitalization for CABG. The primary outcome measure was all-cause death after discharge. The median clinical follow-up was 5.7 (interquartile range, 4.4-6.6) years. Results: POAF was observed in 337 patients (23%). Multivariable logistic regression analysis indicated that age &gt;=75 years (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.24-2.10; P&lt;0.001) and cardiopulmonary bypass (CPB) use (OR, 1.40; 95%CI, 1.09-1.79; P=0.01) were independent predictors of POAF. Of the 1400 patients discharged alive among the study population, the POAF group included more older patients, patients with prior stroke, and patients prescribed beta-blockers and oral anticoagulants than the non-POAF group. The cumulative 5-year incidence of all-cause death was 15.9% in the POAF group and 13.0% in the non-POAF group (Log-rank P=0.38). After adjusting for confounders, the adjusted risk for all-cause death was almost neutral (adjusted HR, 0.96; 95%CI, 0.70-1.31; P=0.81). The cumulative 5-year incidence of stroke was significantly higher in the POAF group than in the non-POAF group (8.0% versus 4.2%; Log-rank P=0.02), and the adjusted risk of stroke in the POAF group relative to the non-POAF group tended to be higher (adjusted HR: 1.58, 95%CI, 0.99-2.53; P=0.057). However, the cumulative 5-year incidence of major bleeding was significantly higher in the POAF group than in the non-POAF group (14.6% versus 10.7%; Log-rank P=0.01). Even after adjusting for confounders, the excess risk of major bleeding in the POAF group was significant (adjusted HR, 1.42; 95%CI, 1.01-2.00; P=0.041). Conclusions: Advanced age and CPB use were associated with POAF occurrence. POAF was not associated with long-term mortality after discharge. However, it tended to be associated with a higher risk for stroke and was associated with a significantly higher risk for major bleeding. Further study would be needed to clarify the appropriate management of POAF after CABG.

Risk stratification for ventricular tachyarrhythmia in patients with nonischemic cardiomyopathy.

The implantable cardioverter defibrillator reduces mortality among patients with heart failure (HF) due to ischemic heart disease. Clinical trial data have called into question the benefit of an ICD in patients with HF due to nonischemic cardiomyopathy (NICM). We developed a risk stratification score for ventricular tachyarrhythmia (VTA) among patients with NICM receiving a primary prevention ICD. The study population comprised 1515 patients with NICM who were enrolled in the landmark MADIT trials. Fine and Gray analysis was used to develop a model to predict the occurrence of VTAs and ICD therapies while accounting for the competing risk of non-arrhythmic mortality. External validation was carried out in the RAID Trial population. Four risk factors associated with increased risk for VTA were identified: male sex, left ventricular ejection fraction ≤25%, no indication for cardiac resynchronization therapy with a defibrillator (CRT-D), and Black race. A score was generated based on this model, and patients were stratified into low (N = 390), intermediate (N = 728), and high-risk (N = 387) groups. The 5-year cumulative incidences of VTA were 15%, 24%, and 42%, respectively. Application of score groups for the secondary endpoints of Fast VT or VF and Appropriate ICD Shock revealed similar findings. Recurrent event analysis yielded consistent results. The AUC in the validation cohort for the endpoint of Appropriate ICD Shock was 69.3. Our study shows that patients with NICM can be risk stratified using demographic and clinical variables and may be used when evaluating such patients for a primary prevention ICD.

Abstract 4137644: Association of Prolonged QTc with Development of Heart Failure after Hematopoietic Stem Cell Transplantation

Background: Use of hematopoietic stem cell transplantation (HSCT) continues to rise in the United States, particularly in older age groups; however, HSCT is associated with various cardiovascular complications including heart failure (HF). We sought to examine whether prolonged QTc prior to HSCT was associated with the risk of HF post-HSCT. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center (RUMC) between 2008-2019. In this analysis, only patients from the UMHS site were included (n=2,435). Baseline electrocardiogram (EKG) data were recorded prior to transplant (median (IQR) 14 (3, 30) days). QTc prolongation was defined per CTCAE grading criteria as Normal (&lt;440ms), Grade 1 (440-480ms), and Grade ≥2 (&gt;480ms). The primary outcome was new-onset HF defined as a diagnosis documented by health care providers after the date of hospitalization for HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT cardiovascular risk score. Results: Of the 2,435 patients (mean age at HSCT 55±13.4 years; 59.7% male; 90.5% White), 534 (21.9%) had long QTc pre-HSCT. Of those, 440 were Grade 1 and 94 were Grade ≥2. In all, 138 HF events occurred over median period of 2.3 (1.0-5.3) years. The 5-year cumulative incidence of HF was 5.0% in patients with normal QTc, 8.4% in patients with Grade 1 QTc prolongation, and 19.0% in patients with Grade ≥2 QTc prolongation (Figure). Patients with Grade 1 and Grade ≥2 prolongation had a 1.57 (95% CI: 1.05, 2.33) and 2.71 (95% CI: 1.51, 4.86) times higher risk of HF, respectively, compared to those with normal QTc. Conclusions: In this contemporary cohort of adult HSCT patients, those with QTc prolongation prior to HSCT had a higher incidence of HF compared to normal QTc, with greater degree of prolongation associated with higher risk. These findings highlight the importance of accounting for the QTc as part of the pre-transplant cardiovascular evaluation

Abstract 4138488: Association Between Guideline-directed Medical Therapy and Reintervention Risk at 2 Years Following Peripheral Vascular Interventions

Introduction: Patients with peripheral artery disease (PAD) undergoing peripheral vascular interventions (PVI) face frequent reinterventions. The association between the use of guideline-directed medical therapy (GDMT) and reintervention risk is unclear, we therefore aimed to study the association between GDMT and 2-year reintervention risk using the largest national vascular registry. Methods: PVI procedures in patients with claudication or chronic limb-threatening ischemia between 2017-2018 were abstracted from the Vascular Quality Initiative (VQI) registry. GDMT was defined as statin, antiplatelet, and ACE/ARB if hypertensive prescribed at discharge. Reintervention was obtained from Medicare claims data. Propensity score of no GDMT vs. GDMT was calculated using 22 preprocedural variables followed by 1:1 matching of patients. The 2-year cumulative incidence of reintervention and subhazard ratios (sHR) for 2-year reintervention risk in no GDMT vs. GDMT were assessed using Aalen-Johansen method and Fine-Gray model, respectively, to account for the competing risk of death. Results: A total of 13,244 patients (6,622 by GDMT group) were included after 1:1 matching (mean age 72.0 ± 9.9, female 38.9%, white 79.4% Black or African American 15.3%) . At 2 years, the cumulative incidence of reintervention was 43.0% (95% CI 41.0%-44.9%) for patients with no GDMT vs. 41.2% (95%CI 39.4-43.0) for the GDMT group (P=0.293). Not receiving GDMT was not associated with 2-year risk of reintervention (sHR: 1.03 95%CI 0.97-1.10; P=0.293). Conclusion: Around 40% of patients undergoing a PVI will have a reintervention at 2 years. The receipt of GDMT at discharge was not associated with a lower reintervention risk at 2 years, as currently assessed. Further granular measures of GDMT should integrate adherence information, as well as information on other lifestyle and cardiovascular risk management to obtain a more complete assessment of a potential association with reintervention risk.

Abstract 4124839: Does Anticoagulation Status Before LAA Thrombus Detection Influence Stroke Risk?

Introduction: Thrombus in the left atrial appendage (LAA) is known to be one of the risk factors for ischemic stroke, and after the detection of LAA thrombus, anticoagulation therapy is usually administered. However, the role of anticoagulation therapy before the detection of LAA thrombus in the prognosis is still unclear. Hypothesis: We assessed the hypothesis that the anticoagulation status at the time of LAA thrombus detection with transesophageal echocardiography (TEE) affects the future incidence of ischemic stroke. Methods: Patients who underwent TEE and were found to have LAA thrombus were included. Patients were divided into two groups based on their anticoagulation status before TEE. To exclude strokes that might occur due to the detected LAA thrombus itself, landmark analysis was performed by excluding patients who had a stroke or died within 30 days after detection of the LAA thrombus. The difference in the 7-year cumulative incidence of ischemic stroke was assessed using the Gray-test. Fine-Gray proportional hazard regression was utilized to assess the impact of anticoagulation status on ischemic stroke. Results: Among 183 patients detected with LAA thrombus, 15 suffered ischemic stroke or death within 30 days of detection, and 168 patients were included in this study. Of these, 58 patients were treated with anticoagulation therapy before the index detection of LAA thrombus (PreAC group). Patients in the PreAC group were older (median 76 years [interquartile range 51-88 years] vs. 74 years [38-89 years], P = 0.032) than those in the non-PreAC group. The rates of CHA2DS2-VASc score ≥ 2 (93% vs. 89%, P = 0.582), male sex (64% vs. 70%, P = 0.488), and history of atrial fibrillation (98% vs. 95%, P = 0.667) were similar between the two groups. The cumulative ischemic stroke rate was higher in the PreAC group than in the non-PreAC group (P = 0.048, Figure). Even after adjusting for CHA2DS2-VASc score, anticoagulation therapy before detection of LAA thrombus was significantly associated with the cumulative incidence of ischemic stroke (P = 0.049). Conclusions: Anticoagulation status before the detection of LAA thrombus is a determinant of a higher incidence of ischemic stroke. The background mechanisms suggesting a tendency toward thrombus generation even when treated with anticoagulation are proposed.