Hodge, David O.

Purpose: The goal of this study was to determine changes in best-corrected visual acuity (BCVA), refractive error, and central corneal thickness (CCT) during the first decade after Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: Outcomes of all consecutive eyes undergoing DSAEK for Fuchs endothelial corneal dystrophy (FECD) were reviewed; eyes with untreatable comorbidities before DSAEK were excluded. DSAEK was performed through a temporal incision and all eyes were pseudophakic postoperatively. Changes in BCVA, manifest spherical equivalent, manifest cylinder (vector analysis), and CCT were assessed by using generalized estimating equation models. Results: BCVA improved between 6 months (0.18 ± 0.12 logarithm of the minimum angle of resolution (logMAR); Snellen equivalent, 20/30) and 5 years (0.10 ± 0.10 logMAR; 20/25; n = 74, P < 0.001) and then remained stable at 10 years (0.09 ± 0.10 logMAR, n = 48, P = 0.22). There was a myopic shift of −0.20 ± 0.51 D between 6 months and 5 years (n = 65, P = 0.002) that remained stable at 10 years (−0.09 ± 0.44 D; 20/25; n = 34, P = 0.33). Manifest cylinder drifted with-the-rule between 6 months and 5 years (n = 65, P < 0.001) and between 5 and 10 years (n = 34, P < 0.001). CCT was stable between 6 months (672 ± 57 μm) and 5 years (677 ± 55 μm, n = 67, P = 0.47), but increased at 10 years (702 ± 60 μm, n = 39, P = 0.001). Conclusions: Excellent BCVA can be achieved during the first decade after DSAEK for FECD, although improvement seems to plateau after 5 years. Changes in manifest refractive error were not clinically significant. The gradual increase in CCT was consistent with longer-term changes found after other types of keratoplasty.

Background: Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic implications. The aims of this study were to identify whether MRD or interictal serum CGRP levels impacted neuroimaging findings for those with CADASIL. Materials and Methods: A cross-sectional analysis was performed. The primary outcomes were neuroimaging differences associated with MRD among those with migraine or interictal serum CGRP levels of those with and without migraine. MRD was defined by 2 migraine disability scales (Migraine Disability Assessment, Headache Impact Test-6). Retrospective brain magnetic resonance imaging was reviewed (average 1.7 ± 2.0 y before enrollment). Rank-sum and χ2 tests were used. Results: Those with migraine (n=25, vs. n=14 without) were younger [median 49 (25 to 82) y vs. 60 (31 to 82) y, P<0.007], had fewer cerebral microbleeds (0 to 31 vs. 0 to 50, P=0.02) and less frequently had anterior temporal lobe T2 hyperintensities [68% (17/25) vs 100% (14/14), P=0.02]. MRD scale outcomes had no significant radiographic associations. Interictal serum CGRP did not differ (migraine: n=18, 27.0±9.6 pg/mL vs. no migraine: n=10, 26.8±15.7 pg/mL, P=0.965). Conclusions: Migraine may forestall microangiopathy in CADASIL, though possibly independent of severity as measured by MRD. Interictal serum CGRP did not differ in our cohort suggesting CGRP may not be vital to migraine pathophysiology in CADASIL. Larger studies are needed to account for age differences.

616 Background: Cholangiocarcinoma (CCA) is an aggressive, heterogenous group of neoplasms that arise from the epithelial lining of bile ducts that have dismal poor prognosis. A recent epidemiological study in the United States demonstrated a steady increase in the incidence of cholangiocarcinoma from 2001 to 2017 with a predominant increase in the intrahepatic sub-type (iCCA). We sought to evaluate the future incidence of cholangiocarcinoma stratified based on the subtype, age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of cholangiocarcinoma (ICD-0-3 Site: C220, C21, and C240) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future cholangiocarcinoma incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 12,737 and 8,395 patients with iCCA and extra-hepatic cholangiocarcinoma (eCCA) were included in the final analysis. The median age of iCCA cohort was 64 (range: 20-79) years and 46.4% were females whereas in eCCA the median age was 66 (range: 20-79) years and 43.8% were females. The overall observed age-adjusted incidence of iCCA between 2000-2017 was 1.07, which is predicted to increase to 2.13 by 2029 (99% increase) with a predominant increase in incidence rate observed in the age groups 70-79 and White males and females. Interestingly, incidence rate remained stable in Black and Asian males and in Asian females. Similarly, as compared to 2001-2017, the incidence of eCCA is projected to increase from 0.74 to 1.01 by 2029 (36.5% increase) with predominant increase noted in Black and Hispanic cohorts. In contrast, we noticed a relatively stable and decreasing incidence rate in White and Asian females, respectively. Conclusions: We predict an overall increased incidence of both iCCA and eCCA over the next decade especially in certain subgroups warranting the urgent need for preventive strategies. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.

615 Background: Accounting for 90% of primary liver cancers, HCC is the fourth-most common cause of cancer-related deaths in the United States. While the vaccination against hepatitis B and awareness on hepatitis C transmission possibly decreased the incidence of HCC in Eastern World, there was an uptrend in the HCC incidence the Western World over the past few years possibly related to metabolic causes. With this changing paradigm of hepatocellular carcinoma, it is important to estimate its future burden stratified based on the age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of HCC (ICD-0-3 Site: C220 and 228; codes: 8170-8175) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future HCC incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 76029 patients with HCC were included in the final analysis. The median age was 62 (range: 20-79) years with male predominance (70%). The overall observed age-adjusted incidence of HCC between 2000-2017 was 6.22, which is predicted to increase to 9.03 by 2029 with a predominant increase in incidence rate observed in the age groups 70-79 and White males. Interestingly, we noticed a progressive decrease in incidence rate in Asian cohort (both males and females) and Black males. Incidence rates by sub-groups based on the age, sex, and race are summarized in the Table. Conclusions: We predict an overall increased incidence of hepatocellular carcinoma over the next decade in the United States, predominantly in 70-79 years age group irrespective sex and race, with an exception to Asian cohort probably representing differential risk factors. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.[Table: see text]

Background Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. Patients/Methods Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013–November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. Results This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16–2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41–2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05–1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08–2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00–1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46–0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45–0.84; p = 0.002) were associated with fewer major bleeding outcomes. Conclusion Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.

Abstract Aims Our goal was to evaluate a previously validated artificial intelligence–augmented electrocardiography (AI-ECG) screening tool for left ventricular systolic dysfunction (LVSD) in patients undergoing high-sensitivity-cardiac troponin T (hs-cTnT). Methods and results Retrospective application of AI-ECG for LVSD in emergency department (ED) patients undergoing hs-cTnT. AI-ECG scores (0–1) for probability of LVSD (left ventricular ejection fraction ≤ 35%) were obtained. An AI-ECG score ≥0.256 indicates a positive screen. The primary endpoint was a composite of post-discharge major adverse cardiovascular events (MACEs) at two years follow-up. Among 1977 patients, 248 (13%) had a positive AI-ECG. When compared with patients with a negative AI-ECG, those with a positive AI-ECG had a higher risk for MACE [48 vs. 21%, P &lt; 0.0001, adjusted hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11–1.75]. This was largely because of a higher rate of deaths (32 vs. 14%, P &lt; 0.0001; adjusted HR 1.26, 95% 0.95–1.66) and heart failure hospitalizations (26 vs. 6.1%, P &lt; 0.001; adjusted HR 1.75, 95% CI 1.25–2.45). Together, hs-cTnT and AI-ECG resulted in the following MACE rates and adjusted HRs: hs-cTnT &lt; 99th percentile and negative AI-ECG: 116/1176 (11%; reference), hs-cTnT &lt; 99th percentile and positive AI-ECG: 28/107 (26%; adjusted HR 1.54, 95% CI 1.01–2.36), hs-cTnT &gt; 99th percentile and negative AI-ECG: 233/553 (42%; adjusted HR 2.12, 95% CI 1.66, 2.70), and hs-cTnT &gt; 99th percentile and positive AI-ECG: 91/141 (65%; adjusted HR 2.83, 95% CI 2.06, 3.87). Conclusion Among ED patients evaluated with hs-cTnT, a positive AI-ECG for LVSD identifies patients at high risk for MACE. The conjoint use of hs-cTnT and AI-ECG facilitates risk stratification.

AbstractAdvances have dated the genetic testing initially offered to evaluate for hereditary breast and ovarian cancer risks. Previous research has demonstrated that many patients have not updated testing. This study reviewed the incidence of additional analysis after an uninformative BRCA1/2 result and offered updated testing with limited barriers to those who had not completed. After viewing an educational video and providing informed consent, eligible patients were mailed a saliva collection kit to complete an 84‐gene hereditary cancer panel at no personal cost. A total of 704 patients had completed BRCA1/2 only testing between 2001 and 2020. Fifteen percent (N = 102) of the 671 patients with an uninformative BRCA1/2 result had already completed expanded testing. Most, 74 of 102 (73%), had been rereferred to medical genetics during a clinical visit related to cancer care. Those who had already completed additional testing were more likely to have a personal history of cancer (92% vs. 79%, p = 0.002) and live locally (p = 0.032). Invitation to complete updated testing through this study was sent to 372 people, and 116 (31%) consented to participate. For 142 of the 256 who did not proceed with testing through the study, proof of receipt of research information was available. In total, 22 pathogenic variants were reported in 21 of the 226 patients with updated testing from before and including our study: ATM (4), CHEK2 (4), LZTR1 (1), MUTYH (3), NBN (1), NF1 (1), NTHL1 (1), PALB2 (4), PMS2 (1), RAD50 (1), and SPINK1 (1). Many potential barriers of retesting were eliminated by removing personal costs or travel requirements. Still, only about 30% of patients agreed to participate, and a significant portion elected not to proceed. Future research could focus on the discovery of other factors that dissuade patients and what measures may better inform them on potential benefits.

AbstractBackgroundClinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear.MethodsDemographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020).ResultsOut of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person‐years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients.ConclusioniPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.