Patient-years Of Follow-up Research Articles

Multi-focal dysplasia is associated with high recurrence rates after successful ablation of dysplastic Barrett's esophagus

Background & AimsBarrett's esophagus (BE) might recur after complete eradication of intestinal metaplasia (CEIM). We investigated factors associated with recurrence of BE after successful Radiofrequency ablation (RFA). MethodsA longitudinal study of BE patients with dysplasia treated with RFA from 2014 to 2021 in two large referral centers. Recurrence was identified in histologic specimens. Factors associated with post-RFA recurrence were analyzed using Cox regression analysis. ResultsA total of 728 patients with BE were identified, 118 had underwent RFA, and 113 had sufficient follow up time. Mean age was 63.7 (±11.7) years, 73.5% were males, 59.3% had long segment of BE, and 30.1% had multifocal dysplasia. During 340.8 patient-years of follow-up, 15 patients (13.3%) had recurrence of BE, which represent an incidence rate of 4.41% per patient-year. Incidence rate of recurrence with dysplasia was 1.17% per patient-year. Multifocal dysplasia, number of RFA sessions, and endoscopic resection before RFA were associated with risk of recurrence in univariate analysis. However, in cox regression analysis only multifocal dysplasia (HR 10.99; 95% CI 2.83–22.62, p = 0.001) was associated with post-RFA recurrence. ConclusionTotal recurrence rates after CEIM are low, and multifocal dysplasia before the ablative therapy is significantly associated with BE recurrence after CEIM. Patients with multifocal dysplasia should be monitored rigorously after successful ablation.

Identification of Neck Lymph Node Metastasis-Specific microRNA-Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis.

MicroRNAs (miRNAs) have attracted attention as non-invasive cancer biomarkers in various cancers; however, they have not been adequately investigated in oral squamous cell carcinoma (OSCC). This study investigated the diagnostic performance of serum-derived miRNAs at initial diagnosis for primary neck lymph node metastasis and the predictive performance for late neck lymph node metastasis based on long-term (up to approximately 8 years) follow-up of patients with OSCC. The expression of miRNAs in 40 patients with OSCC was quantified using real-time PCR (qPCR), and a comprehensive statistical analysis of the correlation of miRNA expression for primary and late neck lymph node metastases was performed. For the diagnosis of primary neck lymph node metastases, miR-423 and miR-125 were accurate. The miRNA index for primary metastasis diagnosis (miR-PM) calculated by regression analysis showed high diagnostic accuracy. The miR-5100 was useful for predicting late neck lymph node metastases. The miRNA index for late metastasis prediction (miR-LM) calculated using regression analysis showed high prediction accuracy. MiRNAs were useful for diagnosing primary neck lymph node metastases in OSCC and predicting late neck lymph node metastases. It may help to consider individualized treatment, including follow-up, surgical methods, and postoperative management.

Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia.

Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD. Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up. A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (p < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding. There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.

Blood pressure-lowering effects of SGLT2 inhibitors and GLP-1 receptor agonists for preventing of cardiovascular events and death in type 2 diabetes: a systematic review and meta-analysis.

To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of major cardiovascular event stratified by glucose-lowering drugs, baseline BP, glycated hemoglobin (HbA1c), and history of cardiovascular disease in patients with type 2 diabetes. We performed a systematic review of the MEDLINE and EMBASE databases search up to December 31, 2022, (PROSPERO, CRD42023400899) to identify all large-scale cardiovascular outcomes (CVO) trials of SGLT2i and GLP-1 RAs in which more than 1,000 patient-years of follow-up in each randomized group. Outcomes included all-cause mortality, major adverse cardiovascular event (MACE) and its component (cardiovascular death, myocardial infarction [MI], and stroke), heart failure, and renal failure. A random-effects meta-analyses were used to pool the estimates. Eighteen CVOTs (ten for SGLT2i and eight for GLP-1 RAs) with 127,606 patients with type 2 diabetes were included. Over 2.5years median follow-up, the average reduction of systolic BP was 2.2mmHg (mean difference [MD] - 2.2; 95% CI - 2.7 to - 1.7) with more important reduction (Pinteraction = 0.001) with SGLT2 inhibitors (- 2.9; - 3.4 to - 2.5) than with GLP-1 RAs (- 1.4; - 1.8 to - 1). With SGLT2i, every 5-mmHg reduction in systolic BP was associated with a significantly lower risk of mortality (hazard ratio[HR], 0.77; 95% CI 0.65-0.90), MACE (HR 0.81 [0.74-0.89]), cardiovascular death (HR 0.72 [0.59-0.88]), MI (HR 0.82 [0.71-0.95]), heart failure (HR 0.49 [0.42-0.57]), and renal failure (HR 0.46 [0.38-0.55]), while the association was not significant for stroke (HR 0.91 [0.69-1.19]). The corresponding effects for every 5-mmHg reduction in SBP with GLP-1 RAs were 0.65 (0.51-0.84) for all-cause mortality, 0.65 (0.56-0.76) for MACE, 0.62 (0.45-0.85) for CV death, 0.71 (0.52-0.76) for MI, 0.49 (0.35-0.69) for stroke, and 0.49 (0.35-0.66) for renal failure, while the association was not significant for heart failure (HR 0.82 [0.63-1.08]). In patients with type 2 diabetes, the hypotensive effects of SGLT2i and GLP-1 RAs were significantly associated with a reduction in mortality and cardiorenal events. These findings suggest that the lowering BP effect could be seen as an additive indicator of cardiovascular protection by SGLT2i and GLP-1 RAs drugs.

Variability in Cochlear Implantation Outcomes in a Large German Cohort With a Genetic Etiology of Hearing Loss.

The variability in outcomes of cochlear implantation is largely unexplained, and clinical factors are not sufficient for predicting performance. Genetic factors have been suggested to impact outcomes, but the clinical and genetic heterogeneity of hereditary hearing loss makes it difficult to determine and interpret postoperative performance. It is hypothesized that genetic mutations that affect the neuronal components of the cochlea and auditory pathway, targeted by the cochlear implant (CI), may lead to poor performance. A large cohort of CI recipients was studied to verify this hypothesis. This study included a large German cohort of CI recipients (n = 123 implanted ears; n = 76 probands) with a definitive genetic etiology of hearing loss according to the American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP) guidelines and documented postoperative audiological outcomes. All patients underwent preoperative clinical and audiological examinations. Postoperative CI outcome measures were based on at least 1 year of postoperative audiological follow-up for patients with postlingual hearing loss onset (>6 years) and 5 years for children with congenital or pre/perilingual hearing loss onset (≤6 years). Genetic analysis was performed based on three different methods that included single-gene screening, custom-designed hearing loss gene panel sequencing, targeting known syndromic and nonsyndromic hearing loss genes, and whole-genome sequencing. The genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5). CI recipients with pathogenic variants that influence the sensory nonneural structures performed at or above the median level of speech performance of all ears at 70% [monosyllable word recognition score in quiet at 65 decibels sound pressure level (SPL)]. When gene expression categories were compared to demographic and clinical categories (total number of compared categories: n = 30), mutations in genes expressed in the spiral ganglion emerged as a significant factor more negatively affecting cochlear implantation outcomes than all clinical parameters. An ANOVA of a reduced set of genetic and clinical categories (n = 10) identified five detrimental factors leading to poorer performance with highly significant effects ( p < 0.001), accounting for a total of 11.8% of the observed variance. The single strongest category was neural gene expression accounting for 3.1% of the variance. The analysis of the relationship between the molecular genetic diagnoses of a hereditary etiology of hearing loss and cochlear implantation outcomes in a large German cohort of CI recipients revealed significant variabilities. Poor performance was observed with genetic mutations that affected the neural components of the cochlea, supporting the "spiral ganglion hypothesis."

Prevalence and management of electrical lead abnormalities in cardiac implantable electronic device leads.

Electrical lead abnormalities (ELAs) can result in device malfunction, leading to significant morbidity in patients with cardiac implantable electronic devices (CIEDs). We sought to determine the prevalence and management of ELAs in patients with CIEDs. This was a retrospective cohort study of patients implanted with a CIED between 2012 and 2019 at a tertiary care center. The primary outcome was ELA defined as increased capture threshold (≥2× implantation value), decreased sensing (≤0.5 implantation value), change in impedance (>50% over 3 months), or nonphysiologic potentials. A secondary outcome of device clinic utilization was also collected. There were 2996 unique patients (35% female) included with 4600 leads (57% Abbott, 43% Medtronic). ELAs were observed in 135 (3%) leads, including 124 (92%) Abbott and 10 (7%) Medtronic leads (hazard ratio 9.25, P < .001). Mean follow-up was 4.5 ± 2.2 years. ELAs were associated smaller lead French size, atrial location, and Abbott leads. Lead revision was required in 28% of cases. Patients with lead abnormalities had 38% more in-clinic visits per patient year of follow-up compared with those without (P < .001). ELAs were more frequent in certain models, which increased rates of revision and follow-up. Identification of factors that mitigate these abnormalities to improve lead performance are required to improve care for these devices and provide efficient healthcare.

Acute Kidney Injury and Mid-term Outcomes After Extra-Cardiac Fontan Conversion.

The aim of this study was to investigate the association of postoperative acute kidney injury and unplanned re-admission rate due to heart failure at 2years follow-up in patients who had extra-cardiac Fontan conversion. This was a retrospective single-center study of patients who underwent conversion from classic Fontan to extra-cardiac Fontan between January 2014 and December 2021. Acute kidney injury was defined using the Kidney Disease Improving Global Outcomes criteria. A total of 47 patients underwent Fontan conversion. Acute kidney injury occurred in 22 patients (46.8%) and 5 patients with acute kidney injury needed renal replacement therapy. Unplanned re-admission rate at 2-year follow-up was significantly higher in patients with acute kidney injury even when renal function returned to baseline (8 [36.4%] vs. 3 [12.0%], p = 0.026 by the log-rank test). In conclusion, postoperative acute kidney injury after extra-cardiac Fontan conversion was associated with unplanned re-admission due to heart failure at 2-year follow-up even though renal function was recovered.

Mortality Trends Among Patientswith Rheumatoid Arthritis in Western Australia.

With scarce comparative data on mortality in Australian patients withrheumatoid arthritis (RA), we investigated temporal changes in standardized mortality rates for patients with RAusing longitudinal linked population-wide health data in Western Australia (WA) over the period 1980 to 2015. The study included 17,125 patients with a first-time hospital contact for RA (ICD-10-AM M05.00-M06.99 and ICD-9-AM 714.00-714.99) in the study period.Standardized mortality rate ratios (SMRRs) for the RA cohort versus the WA general population was estimated using direct age standardization.We analyzed temporal trends over with dates and causes provided by the WA Death Registry. During 356,069 patient-years of follow-up, a total of 8955 (52%) deaths occurred in the RA cohort. The SMRR was 2.24 (95% CI 2.15-2.34) in males and 3.09 (95% CI 3.00-3.19) in females over the study period. SMRR decreased since 2000 to 1.59 (95% CI 1.39-1.81) for the period 2011-2015. Median survival was 26.80years (95% CI 26.30-27.30), where age and comorbidity independently increased the risk of death. The leading causes of deaths were cardiovascular diseases (26.60%), cancer (16.80%), rheumatic diseases (5.80%), chronic pulmonary disease 491 (5.50%), dementia (3.00%), and diabetes 235 (2.6%). The mortality rate in patients with RAin WA has decreased but remains 1.59-times higher than in community counterparts, suggesting that there is room for further improvement. Comorbidity is the main modifiable risk factor to further reduce mortality in patientswith RA.

#3746 RISK OF PROGRESSIVE CHRONIC KIDNEY DISEASE WITH NEPHROSCLEROSIS ON KIDNEY BIOPSY DEFINED USING AGE-BASED VERSUS YOUNG ADULT-BASED THRESHOLDS

Abstract Background and Aims The tissue pathology of both aging and chronic kidney disease (CKD) is nephrosclerosis defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA). We sought to determine if risk of CKD outcomes is better predicted by age-based or young adult-based thresholds for nephrosclerosis. Method Using the Aging Kidney Anatomy study, living kidney donors, kidney tumor patients, and native kidney disease patients had kidney biopsy images analyzed morphometric to quantify %GSG, %IFTA, and IFTA foci density (Figure 1). Using normotensive donors, young (18-29 y) thresholds and age-based (18-29 y, 30-39 y, 40-49 y, 50-59 y, 60-69 y, 70+y) 95th percentile thresholds were defined. Progressive CKD was defined as a 40% decline in serum creatinine based estimated GFR or kidney failure (dialysis or transplantation) from a 4-month post-biopsy baseline (due to the nephrectomy event in tumor patients and due to the common occurrence of acute kidney injury in the native kidney disease patients at the time of biopsy). The age-adjusted risk of progressive CKD in tumor patients and native kidney disease patients was compared between those with nephrosclerosis that was “normal compared to young”, “normal for age but abnormal compared to young”, and “abnormal for age” (Figure 2). Results There were 2583 normotensive living kidney donors, 1363 tumor patients, and 314 native kidney disease patients studied. The 95th percentiles for 18-29y to 70+y age groups among normotensive donors were 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm2 for IFTA foci density. The risk of CKD outcomes did not differ between tumor patients and native kidney disease patients with nephrosclerosis “normal compared to young” versus “abnormal compared to young but normal for age” in both cohorts. Thus, these two categories were combined into “normal for age”. The risk of progressive CKD over a median 5.5 years follow-up for tumor patients was higher with %GSG, %IFTA, and IFTA foci density that was abnormal for age vs normal for age (HRs 2.28, 2.41, and 3.11, respectively, p&amp;lt;.0001 for all). The risk of progressive CKD over a median 7.2 years follow-up for native kidney disease patients was higher with %GSG, %IFTA, and IFTA density that was abnormal for age vs normal for age (HRs 1.87, 2.65, and 3.11, respectively, p&amp;lt;.0001 for all). Conclusion There is a substantial increase in nephrosclerosis from aging alone in healthy adults that is not prognostic for CKD outcomes. Age-based thresholds better identify clinically relevant CKD.

Outcome after microvascular decompression for trigeminal neuralgia in a single center—relation to sex and severity of neurovascular conflict

BackgroundTrigeminal neuralgia (TN), a severe type of facial pain, is mainly caused by a neurovascular conflict (NVC). The severity of the NVC seems associated with the outcome following microvascular decompression (MVD) surgery. This study aimed to investigate the outcome after MVD and whether it is affected by NVC severity and sex.MethodsTN patients (n = 109) were followed for 5 to 10 years after MVD. Barrow Neurology Index (BNI), Patients Global Impression of Change (PGIC), complications, and time to relapse were evaluated. The NVC severity was retrospectively reviewed from presurgical MRI. Demographic and clinical factors and NVC severity were analyzed for potential association with outcome after MVD.ResultsThe success rate (BNI ≤ 2) was 80% after 5 to 10 years follow-up for TN patients with severe NVC (grade 2–3) and 56% for TN patients with mild NVC (grade 0–1, P = 0.003). No sex difference was observed in outcome for patients with both mild (P = 0.924) and severe NVC (P = 0.883) respectively. Three patients (2.8%) during the hospital stay, and two patients (1.8%) at 6 weeks, experienced a complication requiring invasive treatment. At long-term 52/109 patients (47.7%) reported some type of persistent adverse event, of which the majority were mild and required no treatment.ConclusionsMVD offers an 80% probability of long-term pain relief in TN patients with severe NVC, with low frequency of serious complications. NVC severity significantly affects outcome after MVD, while no sex differences in outcome were found. In consistency with previous work, the results stress the importance of adequate neuroradiological assessment of the NVC for preoperative patient selection.

Comparative Study of Highly Cross-Linked Polyethylene Liner Wear by Hip Center Location Using Elevated Hip Center Technique in Crowe I to III Hip Dysplasia: Outcomes for a Minimum of Eighteen Years of Follow-Up

BackgroundThe literature has reported that supero-lateralization of the femoral head increases the rates of aseptic loosening and prosthesis revision. However, there are few reports on the influence of different hip center positions on liner wear with more than a 15-year follow-up period. MethodsFrom April 2000 to August 2003, 91 patients underwent 108 total hip arthroplasties using a highly cross-linked polyethylene liner combined with zirconia femoral head and cup components. Pelvic radiographs were used to assess the vertical and horizontal distances to the center of the hip and the amount of liner wear. Mean patient age at the time of surgery was 54 years (range, 33 to 73), and mean follow-up duration was 19 years (range, 18 to 21). ResultsAverage liner wear was 0.221 mm, with average annual wear of 0.012 mm/year. Mean vertical and horizontal distances for the hip center were 24.9 and 31.8 mm, respectively. There was no difference in linear wear between patients who had different hip center heights (<20, 20 to 30, and >30 mm), and quadrant partitioning showed no differences across the 4 quadrant zones. ConclusionAt a minimum of 18 years of follow-up in patients having developmental dysplasia of the hip who had different Crowe subtypes and different hip centers, elevated hip center and uncemented fixation techniques using a highly cross-linked polyethylene on ceramic components were associated with very low wear rates and excellent functional scores.

WED-204 - Ten years follow-up of patients with chronic hepatitis B and hepatitis D infection

WED-204 - Ten years follow-up of patients with chronic hepatitis B and hepatitis D infection

P.043 Long-term safety, tolerability, and efficacy of efgartigimod in patients with Generalized Myasthenia Gravis: concluding analyses from ADAPT+

Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.

The trajectory of statin compliance after coronary artery bypass grafting surgery

Abstract Funding Acknowledgements Type of funding sources: None. Background The current guidelines about dyslipidemia classify coronary artery bypass grafting surgery (CABG) patients, as a very high-risk population. This is translated to a LDL-target ≤ 55mg/dL, based on observational studies that demonstrate better vein graft patency and deceleration of the native vessels’ atherosclerosis. Despite the well-defined benefit, the compliance of statin therapy at the secondary prevention is ailing. Purpose To capture and evaluate the trajectory of statin compliance during 4 years follow-up in patients after CABG, in a middle-income country. Methods This is a single-center, cohort, observational study, conducted in 365 consecutive post-CABG patients, from 2018-2021. We used data from the electronical files of the patients and the national electronical prescription platform, after consent. The follow-up period was divided: t1 = 6 months, t2 = 1 year, t3= 2 years, t4 = 3 years, and t5= 4 years. We defined as potent statin therapy the administration of ≥ 40mg of atorvastatin, ≥ 20mg of rosuvastatin or the concomitant use of ezetimibe. Results We included 365 patients, 52 females (14.4%). The median age was 69 years (ΙQR: 47-84). The indication for CABG was 65.7% an acute coronary syndrome and 34.3% stable coronary disease. At baseline, the mean LDL value was 108mg/dL, whereas one month post procedure was 71mg/dL, indicating reduction: Δ=34%. Alas, the achieved post-CABG LDL-level still is beyond the target of ≤ 55mg/dL. At t0 (discharge) the percentage of prescribed statins was 81%, but only in 68% of them, the statin was high potent. At t1 the rate of the compliance raised up to 92.5% and the potency rate to 74.6%. At t2 the compliance and the potency remained high, 94.3% and 74.8% respectively. At t3 the compliance is rather stable (92.3%) but the rate of potency declines (64%) and decline further at t4 (89% and 58% respectively). Finally, at t5 both indexes depleted (81% and 57.1%, respectively). The rate of escalation to a potent statin was: t1= 36.3%, t2= 13.9%, t3 = 12.4%, t4 = 3.8%, t5=2.1%. The de-escalation rate was: t1= 13.9%, t2= 2.4%, t3 = 7.3%, t4 = 0.8%, t5=0.1%. The prescribed statin remained the same at t1= 50.8%, t2= 83.6%, t3 = 76.6%, t4 = 79% and t5=75%. The rate of permanent discontinuation was null during the first year, 4.1% at 2 years, 18.2% at 3 years and 19.5% at 4 years. Conclusions The LDL level one-month post-CABG, remains out of target and a further 22% reduction is needed. We highlight the significant rate of prescribed statin at discharge and substantial compliance which is rather sustained during the follow-up period. Nota bene the rate of potency lessens over time, whereas the rate of permanent discontinuation raises, implying that as the patient enters a "stabilized period" at 2 years post-surgery, the eagerness to maintain high-potent statin therapy, declines. This real-world practice subtracts the pleiotropic benefits of potent statins, not only over the ongoing atherosclerosis.

Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58–0.90 respectively OR = 2.24, 95% CI 1.60–3.13).We found significant correlation for change in ECAC volume with diabetes (β = 0.46, 95% CI 0.03–0.89) and baseline ECAC volume (β = 0.81, 95% CI 0.73–0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48–3.16), age (OR = 2.00, 95% CI 1.19–3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20–11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (β = 0.92, 95% CI 1.59–7.02), use of oral hypoglycemic drugs (β = 0.86, 95% CI 0.12–1.59) and baseline ICAC volume (β = 0.71, 95% CI 0.55–0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer

PurposeTo report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). MethodsPatients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported. ResultsIn 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40–0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56–0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49–0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature. ConclusionsNiraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.

PO-02-047 OUTCOMES OF CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE REMOVAL WITHOUT REIMPLANTATION IN PEDIATRIC PATIENTS

Patients with cardiovascular implantable electronic device (CIED) may no longer meet indications for pacing during follow up. This population represents a challenge for physicians since no guidelines stipulate acceptable indication for CIED removal without reimplantation. Little is known about the risk of significant cardiac events in children who undergo CIED removal. The present study aims to investigate the outcomes in a population having undergone CIED removal without immediate reimplantation before the age of 18 years at our institution. We retrospectively searched for consecutive patients <18 years of age who underwent CIED removal at the Hospital for Sick Children from Jan 2007 to Dec 2022. The primary outcome of significant cardiac event was defined as symptomatic bradycardia with documented high grade atrioventricular block (AVB) or sinus pause, syncope of presumed cardiac origin, ventricular arrhythmia with hemodynamic compromise, or sudden death of presumed arrhythmic etiology. Of 667 patients who underwent CIED implantation at our institution during the study period, a total of 14 (2.1%) patients (9 males [64.3%]) underwent explantation without immediate reimplantation. The majority of patients (N=9; 64.3%) had structural heart disease, with the most common indication for implantation being post-op AVB (N=5; 35.7%) followed by sinus node dysfunction (SND, N=4; 28.6%). During a median follow-up of 2.2 years (IQR 0.4–6.7), significant cardiac event occurred in 3 (21.4%) patients aged 13.5 years (IQR 6.4–17.9) at a median of 0.7 years (IQR 0.6–3.2) after explantation. Two patients had recurrence of their post-operative AVB 7 and 8 months after explantation respectively, both presenting with self-resolving syncope and documented prolonged pause on implantable loop recorder (ILR). One patient known for left atrial isomerism who had been paced for SND developed new complete AVB 3.2 years after his device has been explanted, which represented a new indication for pacing. There were no aborted or sudden death during the 48.7 patient-years of follow-up. In a small cohort of pediatric patients, CIED explantation without reimplantation was a safe practice that required careful patient selection. An ILR should be considered at the time of explant to facilitate monitoring over time. Further studies are required to identify predictive factors for cardiac events in this specific population.

Long-Term Safety, Tolerability, And Efficacy of Efgartigimod in Patients with Generalized Myasthenia Gravis: Concluding Analyses from the ADAPT+ Study (S5.006)

Long-Term Safety, Tolerability, And Efficacy of Efgartigimod in Patients with Generalized Myasthenia Gravis: Concluding Analyses from the ADAPT+ Study (S5.006)

Ultrafiltration Rate Levels in Hemodialysis Patients Associated with Weight-Specific Mortality Risks.

We hypothesized that the association of ultrafiltration rate with mortality in hemodialysis patients was differentially affected by weight and sex and sought to derive a sex- and weight-indexed ultrafiltration rate measure that captures the differential effects of these parameters on the association of ultrafiltration rate with mortality. Data were analyzed from the US Fresenius Kidney Care (FKC) database for 1 year after patient entry into a FKC dialysis unit (baseline) and over 2 years of follow-up for patients receiving thrice-weekly in-center hemodialysis. To investigate the joint effect of baseline-year ultrafiltration rate and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions and constructed contour plots of weight-specific mortality hazard ratios over the entire range of ultrafiltration rate values and postdialysis weights (W). In the studied 396,358 patients, the average ultrafiltration rate in ml/h was related to postdialysis weight (W) in kg: 3W+330. Ultrafiltration rates associated with 20% or 40% higher weight-specific mortality risk were 3W+500 and 3W+630 ml/h, respectively, and were 70 ml/h higher in men than in women. Nineteen percent or 7.5% of patients exceeded ultrafiltration rates associated with a 20% or 40% higher mortality risk, respectively. Low ultrafiltration rates were associated with subsequent weight loss. Ultrafiltration rates associated with a given mortality risk were lower in high-body weight older patients and higher in patients on dialysis for more than 3 years. Ultrafiltration rates associated with various levels of higher mortality risk depend on body weight, but not in a 1:1 ratio, and are different in men versus women, in high-body weight older patients, and in high-vintage patients.

Atrial Fibrillation Detected before or after Stroke: Role of Anticoagulation.

Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk. Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation. Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death. Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54.