Citations

Background: Cerebral microbleeds (CMBs) are associated with incident dementia, but the impact of specific CMB patterns is unclear. CMBs in lobar regions suggest cerebral amyloid angiopathy (CAA), which is sometimes accompanied by superficial siderosis (SS), while subcortical CMBs indicate hypertensive origins. This study investigates the association between CMB patterns and dementia risk in the community-based longitudinal Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Methods: All ARIC-NCS participants with a 3T research MRI at visit 5 (2011-13; aged 67-90) without intracerebral hemorrhage or dementia were included. CMB and SS presence and location were coded from T2* GRE sequences. Individuals were classified into one of four patterns: no CMBs, only subcortical, mixed (lobar and/or SS + subcortical), and only lobar and/or SS. Incident dementia diagnoses were defined by cognitive testing (in-person and telephone), informant interviews, and hospital discharge codes or death certificates. Cox proportional-hazards models assessed the association between the presence, patterns, and frequency of CMBs (0,1,2,3+), presence of SS, and incident dementia from visit 5 through 2020. Model covariates included demographics, vascular risk factors, and imaging markers of small vessel disease. Results: Among 1609 participants, 364 had CMBs (Table 1). Participants with CMBs tended to be older and female compared to those without CMBs. Compared to individuals with no CMBs, presence of any CMBs was associated with an increased risk of dementia (Table 2). Compared to individuals without CMBs, individuals with only lobar CMBs and/or SS had an increased risk of incident dementia, as did individuals with mixed CMBs, but individuals with subcortical-only did not. Participants with ≥3 CMBs of any variant had an increased risk of incident dementia vs no CMBs. Although SS was infrequent, its presence (vs no SS) was associated with an elevated risk of dementia. Conclusion: CMBs, particularly in a mixed or lobar and/or SS-only pattern, are linked to an increased risk of incident dementia. The number of recurrent CMBs and any SS also showed an increased dementia risk. These data support that dementia risk is high in individuals with a CAA-type CMB pattern, but also emphasize that a mixed pattern, not typical of CAA alone, is associated with a high risk of dementia. Further studies should evaluate mechanisms by which these different patterns contribute to dementia.

Abstract Background Studies aiming to synthetize data from literature are helpful to valid the robustness of associations, to assess the quality of the data, and, eventually, to propose recommendations. This is particularly evident for the huge amount of data reported for SARS-CoV-2. The aim of this study was to perform an umbrella review to identify the strength and validity of associations between variants of concern (VOCs) and pre-specified clinical outcomes in COVID-19 patients. Table 1 Effect size measures reported in the studies included in the review, divided by outcome. Acronyms: CI, confidence interval; OR: odds ratio; RR, risk ratio; cCFR, confirmed case-fatality risk; HFR, hospitalization-fatality risk; N/A, not available Methods An umbrella review according to the principles to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed searching multiple databases in January 2024. Peer reviewed systematic reviews considering ≥ 2 VOCs with a clinical outcome among death, hospitalization, severe disease, admission to intensive care unit (ICU), and mechanical ventilation were included. Data on study population and measures of association between clinical outcome and VOCs were considered. The quality of the studies was assessed through the AMSTAR-2 tool. The effect size measures with the confidence interval for each association between VOCs and clinical outcomes were reported. Subgroup analyses were performed, if possible. A citation matrix was used to assess the overlap between the systematic reviews included. Table 2 Risk of bias assessment of the included systematic reviews using the AMSTAR-2 score. In bold the key domains. Results A total of 11 studies were included in our review. 24 total comparison were considered, most regarding Omicron versus Delta (19/24), where Omicron was always associated with better clinical outcomes than Delta. The overall quality of the studies was low. None of the reviewed studies incorporated consideration of risk factors other than VOCs in evaluating clinical outcomes. The overlap between the included reviews is low, only 10% of them having a significant overlap ( > 15%). Conclusion Our umbrella review shows the lower hazard on human health of the Omicron compared to Delta variant. However, the quality of the reviews included were generally low and there is a lack of correction with other risk factors such as comorbidities and vaccination status. While our review provides valuable insights into the association between VOCs and clinical outcomes of SARS-CoV-2 infection, further research incorporating risk factor analysis and ensuring methodological rigor is warranted. Disclosures All Authors: No reported disclosures

Abstract Background Little is known regarding outcomes for patients prescribed antibiotics on discharge from the hospital to nursing homes (NHs). We quantified the association between suboptimal antibiotic prescribing and clinical outcomes at discharge to NHs. Methods This was a multicenter, retrospective cohort study of adult (age >18 years) patients prescribed systemic antibiotics on discharge from 9 acute care hospitals in Oregon, Washington, and Wisconsin to a NH from 2016 – 2018. Study data were electronically extracted from hospital and NH electronic health records and supplemented with chart review. Suboptimal antibiotic therapy was determined by an infectious disease pharmacist or physician using clinical information (e.g., antibiotic regimen, indication, and culture results) available at discharge. Outcomes included emergency department (ED) visits, hospital readmissions, or Clostridioides difficile infection (CDI) within 30 days of hospital discharge. Comparison of outcomes between patients with suboptimal and non-suboptimal antibiotic therapy were tested by chi-squared tests. Results Among 280 included patients, mean (SD) age was 76.0 (11.5) years, 35.7% (n=100) were male, and median (IQR) inpatient length of stay was 6 (4-9) days. The most prevalent antibiotic indications were urinary tract infections (n =109, 38.9%), lung indications (n=60, 21.4%), and prophylaxis (n=29, 10.4%). Among 317 antibiotic prescriptions, the most frequently prescribed antibiotic classes were cephalosporins (n=83, 29.6%), fluoroquinolones (n=57, 20.4%), and beta-lactam/beta-lactamase-inhibitors (n=40, 14.3%). Fifty-eight patients (20.7%) were prescribed suboptimal antibiotic therapy on hospital discharge. There were no significant differences in the frequency of 30-day ED visits (14% vs 11%, p=0.76) or hospital readmission (19% vs 18%, p=0.94) between patients prescribed and not prescribed suboptimal antibiotics; however, suboptimal antibiotics were significantly associated with CDI within 30 days of discharge (10% vs 2%, p=0.01). Conclusion Suboptimal antibiotic prescribing on discharge to NHs was associated with increased risk of CDI within 30 days of discharge. This finding may inform interventions to improve antibiotic prescribing on discharge to NHs. Disclosures YoungYoon Ham, PharmD, Gilead: Honoraria Jon P. Furuno, PhD, Merck & Co., Inc: Grant/Research Support

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT. Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75–100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (modified Rankin Scale (mRS), 0–2). Secondary outcomes included excellent functional outcome at 90 days (mRS, 0–1), mortality, and day 1 post-MT National Institutes of Health Stroke Scale (NIHSS) score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH). Results: Among 1354 patients, 150 were on pre-stroke low-dose aspirin. After applying inverse probability of treatment weighting (IPTW), aspirin use was associated with significantly better functional outcomes (mRS, 0–2: odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.14 to 3.12) and lower 90-day mortality (OR = 0.56, 95% CI = 0.32 to 1.00). The aspirin group had lower NIHSS scores on day 1 (β = −1.5, 95% CI = −2.8 to −0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI = 0.60 to 1.43). Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Background Mild cognitive impairment (MCI) represents a stage between cognitively normal and Alzheimer's disease. Despite much published research on MCI, there continues to be a knowledge gap of volumetric brain changes in MCI versus cognitively normal (CN) in racially diverse, community-based samples. Objective The study aimed to understand differences in volume of selected brain regions in individuals with MCI versus those who are cognitively normal. Methods This was a cross-sectional study with 1835 participants, which sampled all cognitively impaired participants (n = 667) and a subsample of cognitively normal participants from the ARIC neurocognitive study (ARIC-NCS). All individuals underwent a brain MRI. Two models (5 versus 22 regions of interest [ROI]) were built to analyze differences in brain volume between cognitively normal and MCI, and among 3 cognitive domains (memory, language, executive function). Using previous visits data, we estimated the standard deviations of 20-year cognitive decline equivalent to the difference in brain volume between MCI and CN. Results Every lobe was significantly smaller in individuals with MCI, with the largest difference observed in the temporal lobe. Moreover, there was a significant difference between MCI and CN in every subregion within the temporal lobe. The difference in volume between CN and MCI was equivalent to the total brain volume difference associated with a 1.24 standard deviation greater long-term cognitive decline. Conclusions Loss of volume in all cortical lobes, but particularly in the temporal lobe, was associated with MCI. Additionally, significant volume differences were observed in the temporal lobe in all three cognitive domains.

142 Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 vascular endothelial growth factor receptors (VEGFRs -1, -2, -3) that is approved by the US FDA and in the EU, UK, and Japan for previously treated metastatic colorectal cancer (mCRC), regardless of biomarker status. FRESCO-2 (NCT04322539) met its primary endpoint demonstrating significantly improved overall survival (OS) with F + best supportive care (BSC) vs placebo (P) + BSC. This subgroup analysis assessed landmark survival of all FRESCO-2 patients (pts), and baseline (BL) characteristics and safety data of pts treated with F who had OS ≥10 months (mos) compared with the intent-to-treat (ITT) population (pop). Methods: Pts were randomized 2:1 to receive F 5 mg or matching P, by mouth, once daily, 3 weeks on, 1 week off, + BSC. Pts had received prior chemotherapy, anti-VEGF therapy and, if RAS wild type, anti-EGFR therapy; and had prior exposure to trifluridine/tipiracil (TAS-102) and/or regorafenib. The hazard ratio (HR) between the two treatment arms was calculated from a stratified Cox proportional hazard model with treatment group as the only covariate in the model. Results: In the ITT pop, OS was improved with F vs P (HR 0.66); OS rates (95% confidence intervals [CIs]) at 6 and 9 mos were 60.4% (55.9–64.9) vs 41.5% (35.0–48.0) and 41.1% (36.4–45.8) vs 28.2% (22.1–34.3), respectively. Progression-free survival (PFS) rates (95% CIs) at 6 and 9 mos were 23.8% (19.7–28.0) vs 1.1% (0–2.6) and 11.3% (8.1–14.6) vs 0.5% (0–1.6), respectively. Of 461 pts who received F, 113 (24.5%) had OS ≥10 mos (range 10.0–18.9) with a median duration of F treatment of 6.3 mos (range 0.7–19.1). Among pts receiving F, a higher proportion (≥10% difference) of pts with OS ≥10 mos had no liver metastases (mets) and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 at BL compared with the ITT pop (Table). In pts with OS ≥10 mos, 61.9% experienced a grade ≥3 treatment-emergent adverse event compared with 62.7% in the ITT pop. Conclusions: Longer-term OS and PFS rates at 6 and 9 mos were higher with F vs P in the FRESCO-2 ITT pop. The data show a higher proportion of pts with OS ≥10 mos had an absence of liver mets and ECOG PS 0 at BL than the ITT pop. The safety profile of F in pts with OS ≥10 mos was consistent with the ITT pop. Clinical trial information: NCT04322539 . BL characteristics of pts treated with F with OS ≥10 mos vs ITT pop. BL characteristic Pts with OS ≥10 mos (n=113) ITT pop(n=461) ECOG PS (0 / 1), % 54.0 / 46.0 42.5 / 57.5 Median time since 1 st CRC diagnosis, mos 52.0 47.2 Primary tumor location at 1 st diagnosis (colon / rectum / both), % 51.3 / 35.4 / 13.3 60.5 / 31.0 / 8.5 Primary site at 1 st diagnosis (colon left / colon right), % 42.5 / 15.9 41.6 / 21.0 Liver mets, % 58.4 73.5 Median duration of mCRC, mos 42.7 37.9 Prior lines of therapy for mCRC (≤3 / >3), % 26.5 / 73.5 27.1 / 72.9 Prior TAS-102, % 46.9 52.1 Prior regorafenib, % 12.4 8.7

Background: The objective in epithelial ovarian cancer is to reach maximal cytoreduction with no visible residual tumor. Tumor detection during cytoreductive surgery depends on visual inspection, palpation, or blind biopsy, methods that lack reliability for identifying microscopic disease. Although the importance of microscopic disease in epithelial ovarian cancer is controversial, it may harbor chemoresistant cells and explain the high recurrence rates. Fluorescence-guided surgery (FGS) is an emerging approach. However, the potential in ovarian cancer remains underexplored; the majority of the existing evidence pertains to gastrointestinal tumors and a limited group of ovarian cancer patients. Their comparative effectiveness is still uncertain. Objective: To systematically review and evaluate the role of fluorescence-guided surgical techniques in detecting microscopic disease in ovarian cancer and compare their efficacy to total peritonectomy. Data Sources: A systematic search was made in three databases (PubMed, Web of Science, and Embase). The search was conducted from 1975 to 2024, including randomized controlled trials, observational studies, and conference abstracts in the last 25 years. Study Selection: Clinical studies published in English involving ovarian cancer patients undergoing FGS or total peritonectomy were included. Case reports, reviews, animal studies, and studies involving mixed cancer populations without ovarian cancer-specific data were excluded. Two independent reviewers screened 631 studies, yielding 12 eligible studies for final analysis. Data Extraction and Synthesis: Data were extracted and synthesized in accordance with PRISMA and MOOSE guidelines, using random-effects models for independent analysis. Sensitivity, specificity, positive predictive value (PPV), and odds ratios (ORs) were grouped, accompanied by subgroup analyses based on the fluorescence agent employed. For quality assessment, we utilized the NIH quality tool. Main Outcome(s) and Measure(s): The primary outcome was the rate of change in surgical management due to fluorescence guidance or total peritonectomy. Secondary outcomes comprised lesion-level sensitivity, specificity, and PPV. Safety outcomes included adverse events associated with fluorescence agents. Results: There were 12 studies involving 429 ovarian cancer patients. FGS improved the detection of microscopic disease compared to standard visualization methods, with a pooled sensitivity of 0.77. Folate receptor-targeted agents had high sensitivity (84%) but low specificity (26%). Aminolevulinic acid (5-ALA) showed superior diagnostic accuracy with a sensitivity of 84% and a specificity of 96%. Total peritonectomy showed no significant advantage over FGS for detecting microscopic disease. The adverse events were mild, with no serious events reported. We observed a high heterogeneity across studies and methodologies. Conclusions and Relevance: Fluorescence-guided surgery utilizing fluorescence tracers demonstrates potential in improving the detection of microscopic disease and may change surgical management in epithelial ovarian cancer, particularly with 5-ALA. Variability in performance and limited data on survival outcomes necessitates additional research. Total peritonectomy does not offer further advantage in the detection of microscopic disease. Future trials should focus on standardizing methodology and evaluating the effects of microscopic disease removal on survival outcomes. Registration: The study was registered to PROSPERO as CRD42024578274.

Background Current randomized controlled trials are investigating the efficacy and safety of mechanical thrombectomy (MT) in patients with medium vessel occlusion (MeVO) stroke. Whether best medical management (MM) is more efficient than unsuccessful vessel recanalization during MT remains unknown. Methods This was a retrospective cohort study using data from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. Only patients with occlusion of the distal branches (M2 and M3) of the middle cerebral artery territory were included. Unsuccessful MT was defined as a modified Thrombolysis in Cerebral Infarction score of 0–2a. Propensity score matching was used to control for confounders. The primary outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after treatment. Multivariable regression analysis was used to assess factors associated with the primary outcome. Results Of 2903 patients screened for eligibility, 532 patients were analyzed (266 per group) after propensity score matching. The MM group had superior functional outcomes, with 32% achieving mRS 0–1 at 90 days compared with 21% in the MT group (P=0.011). Patients in the MM group also had significantly lower rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 16%, P<0.001) and any hemorrhage (18% vs 48%, P<0.001). On multivariable regression, unsuccessful MT was associated with reduced odds of functional independence (OR 0.50, 95% CI 0.29 to 0.85, P=0.011) and increased odds of sICH (OR 4.32, 95% CI 1.84 to 10.10, P<0.001). Mortality rates were similar between groups (27% in MM vs 29% in MT, P=0.73). Conclusion Unsuccessful MT for MeVO was linked to worse outcomes than best MM. These findings highlight the risks of prolonged attempts and emphasize the importance of efficient procedural decision-making to reduce complications and improve patient outcomes.