Control Cohort Research Articles

Abstract 4123849: Respiratory Syncytial Virus (RSV) Cases Involving Hospitalization Are Associated with an Increased Risk of Myocardial Infarction and All−Cause Mortality Among Adults Aged 50 Years and Older

Background: Older adults and adults with comorbidities are at increased risk for severe respiratory syncytial virus (RSV) disease and related complications. Aims: To estimate the risk of myocardial infarction (MI) and all−cause mortality among adults aged ≥50 years hospitalized with RSV compared to those with no recent acute respiratory illness (ARI) and those hospitalized with influenza. Methods: Data from Optum’s de−identified Clinformatics® Data Mart Database were analyzed (October 2015–June 2023) in this retrospective cohort study. Adults aged ≥50 years with ≥12 months of continuous enrollment were assigned to cohorts based on RSV or influenza hospitalization (from ICD−10 codes; RSV and flu cohorts) or no recent ARI (control cohort). Index dates for RSV and flu cohorts were the start of an ARI that included hospitalization. Baseline characteristics were measured in the 12 months pre−index. MI (from ICD−10 codes) and all−cause mortality were measured during follow−up and compared between cohorts using time−varying coefficient multivariable adjusted Cox models (MI results accounted for the competing risk of death). Results: In the RSV cohort (n=14,759), mean age (76.5 years) and mean Charlson comorbidity index (CCI; 3.3) were higher than the flu (n=77,468; 75.4 years, CCI=2.9) and control (n=73,795; 69.5 years, CCI=1.0) cohorts. Adjusted HRs (95% CI) for MI and all−cause mortality risk were significantly higher in the RSV vs control cohort across follow−up, ranging from 30.96 (26.22–36.54) within 30 days post−index to 2.26 (2.04–2.51) >365 days post−index for MI and 10.77 (9.19–12.63) within 30 days post−index to 2.29 (2.18–2.42) >365 days post−index for mortality. Compared to the flu cohort, adjusted MI and mortality risk in the RSV cohort were lower during the 30 days post−index (MI: 0.87 [0.82–0.92]; mortality: 0.84 [0.78–0.90]) but higher >365 days post−index (MI: 1.11 [1.01–1.22]; mortality: 1.05 [1.01–1.10]). Conclusion: MI and all−cause mortality risk were higher for hospitalized RSV cases compared to controls. Smaller differences in outcomes were observed when comparing hospitalized RSV cases with hospitalized influenza cases, with varying direction over time. With existing evidence of increased MI and mortality risk after influenza and these findings on MI and mortality risk after RSV, future research should aim to further understand the impact of RSV on cardiovascular outcomes and assess the role of RSV prevention in lowering the risk of MI and mortality.

Stroke Risk Following Nonarteritic Anterior Ischemic Optic Neuropathy

ImportanceThe association between nonarteritic anterior ischemic optic neuropathy (NAION) and an increased risk of stroke has been a subject of debate. However, multinational studies on this topic are scarce.ObjectiveTo evaluate the short-term and long-term stroke risk after NAION compared with a matched control group.Design, Setting, and ParticipantsThis global, retrospective, population-based cohort study used aggregated electronic health records from January 1, 2004, through March 19, 2024, sourced from the Global Collaborative Network of TriNetX, which includes data from over 152 million patients across 17 countries. Patients in the study were followed up for a maximum duration of 10 years. Patients with NAION and age-related cataract were included in the analysis. Those with stroke before the diagnosis of NAION and age-related cataract were excluded. Propensity score matching was applied to balance age, sex, race, ethnicity, comorbidities, and medication use.ExposureInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code for NAION or age-related cataract.Main Outcomes and MeasuresThe primary outcome was the relative risk (RR) of stroke (ICD-10 code I60-63) in the NAION cohort vs the matched controls. Multivariable logistic regression analyses were applied to identify potential clinical factors associated with stroke within the NAION cohort.ResultsA total of 89 811 patients were identified in both the NAION (mean [SD] age, 57.2 [18.5] years; 38 678 men [43.1%]) and control (mean [SD] age, 57.0 [17.9] years; 40 014 men [44.6%]) cohorts after matching. The NAION cohort demonstrated a significantly higher all-stroke risk at all time points: 1 month (RR, 5.04; 95% CI, 4.41-5.78), 3 months (RR, 3.79; 95% CI, 3.40-4.21), 1 year (RR, 2.50; 95% CI, 2.32-2.70), 5 years (RR, 1.54; 95% CI, 1.45-1.63), and 10 years (RR, 1.33; 95% CI, 1.23-1.43). Sensitivity analysis in patients without comorbidities similarly revealed a significantly increased all-stroke risk across all intervals: 1 month (RR, 7.55; 95% CI, 4.74-12.03), 3 months (RR, 6.70; 95% CI, 4.48-10.04), 1 year (RR, 3.96; 95% CI, 2.94-5.34), 5 years (RR, 2.85; 95% CI, 2.18-3.72), and 10 years (RR, 1.68; 95% CI, 1.25-2.26). Among all the clinical factors of interest, only hypertension was consistently associated with all subtypes of stroke following NAION.Conclusions and RelevanceThis cohort study of patients with NAION found a significantly elevated risk of stroke compared with matched controls, independently of comorbidities. These findings underscore the importance of regular stroke workups following the onset of NAION.

Abstract 4136346: A Comparative Analysis of Esophageal Cooling for Preventing Esophageal Injury Post Atrial Fibrillation Catheter Ablation: A Systematic Review and Meta-analysis

Introduction: Thermal injury following atrial fibrillation catheter ablation is a rare but fatal complication. We aim to assess the safety profile of different forms of esophageal cooling methods versus standards of care. Methods: We searched PubMed, Cochrane Library, Scopus, and Web of Science databases for randomized controlled trials and cohort studies comparing esophageal cooling to Luminal esophageal temperature (LET) monitoring regarding esophageal thermal lesions (ETL) post atrial fibrillation ablation. Case reports, case series, reviews, conference abstracts and animal studies were excluded. Review manager software (version 5.4) was used to perform the meta-analysis. Results: We included 10 studies with 25662 patients in total: 14515 patients in the esophageal cooling group and 11147 patients in the LET group. Overall esophageal lesion analysis demonstrated no statistically significant difference between the esophageal cooling group and LET (RR = 0.72, 95% CI = 0.35 to 1.49, p-value = 0.38). Subgroup analysis showed no statistically significant difference for mild/moderate lesions (RR = 1.52, 95% CI = 0.80 to 2.90, p-value = 0.20). However, the subgroup analysis showed a statistically significant association between esophageal cooling and decreased severity of esophageal lesions compared with LET (RR = 0.29, 95% CI = 0.12 to 0.71, p-value = 0.007). Regarding AF recurrence, the pooled analysis showed no statistically significant difference between esophageal cooling group and LET (RR = 1.24, 95% CI = 0.95 to 1.61, p-value = 0.11). Conclusion: In patients undergoing AF catheter ablation, the implementation of esophageal cooling showed statistical significance in decreasing the severity of esophageal lesions compared to the LET group. Also, esophageal cooling demonstrated non-inferiority in AF recurrence compared to LET. Future research should focus on assessing the long-term effects of esophageal cooling during AF catheter ablation.

Abstract 4120743: MEK inhibition for recurring pulmonary valve stenosis in RASopathy patients

Backgound: The RASopathies are developmental syndromes resulting from variants in the RAS/mitogen-activated protein (MAPK) cascade. The vast majority of RASopathy-causing variants lead to a gain of function in RAS-MAPK signaling. This has motivated compassionate use of MEK inhibition (MEKi) for rare, but potentially lethal complications such as hypertrophic cardiomyopathy and lymphatic disease. However, the most recurrent cardiac complication in RASopathies is pulmonary valve stenosis (PVS). PVS may require balloon valvuloplasty (BV) and can recur over time. Research question: Can MEKi be successfully used for recurrent PVS in RASopathy-patients? Aim: To report compassionate use of MEKi (trametinib) in recurring RASopathy-associated PVS. Method: Retrospective, single-center study at CHU Sainte Justine, Montreal, from 2021 to 2024. Results: After informed parental consent for off-label compassionate use of trametinib, four patients with recurrence of severe PVS after balloon valvuloplasty (>= 80 mmHg) had a total of 5 treatment episodes. Three patients were female, and one patient was male. The following genotypes were represented: Case 1, RIT1 A77V; case 2, PTPN11 N308D; case 3, RIT1 F82V, del22q11dist; case 4, PTPN11 Q110G, dup Xp22.13 (VUS), dup 16p11.2. Initial BV was carried out between three weeks and 10 months of age. Recurrence of PVS was noted between 4 days and 6 months after BV. Peak gradients at recurrence measured 72 -96 mmHg, and decreased to 40 – 64 mmHg (Dp -10 to -40 mmHg) at one to three months after treatment. Treatment had to be stopped in three cases for cutaneous side effects, with a rapid second recurrence in one case, which again responded to MEKi. PVS residual gradients at latest follow-up ranged from 30 – 69 mmHg. In all four patients, repeat catheter intervention or surgery could be avoided. In three out of four RASopathy patients with severe recurrent PVS after initial BV, we observe mild or moderate residual PVS. The patient with residual severe PS also carries a del22q11.2dist, which renders her haploinsufficient for LZTR1, a potential disease/treatment modifier within the RAS-MAPK cascade. Conclusion: Our results potentially expand the indications for MEKi in selected cases of RASopathy-associated recurrence of PVS and suggest an alternative to surgery or repeat catheterization. However, this case series is limited by the lack of an adequate contemporaneous, genotyped control cohort and its retrospective nature.

RADT-18. DEDICATED 3D-FSE SEQUENCE-BASED RADIOSURGERY REDUCES DISTANT INTRACRANIAL RELAPSE RATES IN A HISTOLOGY-AGNOSTIC PATIENT COHORT

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a cornerstone in the treatment of brain metastasis (BM), despite a known risk of distant intracranial failure (DIF). Recent imaging advances, specifically, sensitive 3D-FSE sequences, have started to be incorporated into SRS practice; however, comparisons of outcomes to historical imaging approaches are limited. We evaluated the impact of adding 3D-FSE to MPRAGE in BM detection and prolongation of DIF in a histology-agnostic patient group. METHODS Outcomes of patients treated with SRS for BM between 01/2019-01/2024 were evaluated. MPRAGE sequences were obtained for all; 3D-FSE sequences were implemented in 02/2020. Median times to DIF were estimated using the Kaplan-Meier method. RESULTS 215 patients underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-FSE (primary cohort), compared to the control cohort (92 patients, 135 SRS courses, 462 BM). MPRAGE sequences revealed 1636 lesions in 307 patients (462 in 92 control cohort, 1174 in 215 primary cohort). In the primary cohort, an additional 282 lesions were identified with 3D-FSE (24% increase) by neuroradiologists and multidisciplinary review. There was a statistically significant prolongation in the median time to DIF between the cohorts (11.4 vs. 6.8 months, p=0.029), most pronounced in the 1-4 metastases subgroup (14.7 vs. 8.1 months, p=0.008) and in those with a single BM (36.4 vs. 10.9 months, p=0.001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-FSE (7.2 vs. 5.7 months, p=0.280), those who relapsed on chemotherapy or were off systemic therapy at least four weeks prior to SRS (including synchronous metastases) exhibited a trend towards longer time to DIF with 3D-FSE (14.7 vs. 7.9 months, p=0.057). CONCLUSIONS 3D-FSE added to MPRAGE lengthens time to DIF via improving BM detection, especially for limited BM, and those relapsing on systemic therapy with limited intracranial penetration or no systemic therapy.

Effects of Vitamin C Supplements on Clinical Outcomes and Hospitalization Duration for Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

Abstract Context Vitamin C has been used as an essential antioxidant to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the 2019 coronavirus disease (COVID-19), but its effect on clinical outcomes remains controversial and inconclusive. Objective The purpose of this study was to conduct a meta-analysis and systematic review to assess the effects of vitamin C supplementation on the severity of COVID-19 in hospitalized patients. Data Sources Web of Science, Embase, Cochrane Library, PubMed, CNKI, CSTJ, Wan fang, and CBM databases were searched for publications between January 2020 and December 2023 that met the inclusion criteria. Data Extraction The meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. A randomized controlled trial, cohort studies, and retrospective studies in which vitamin C supplementation was supplemented as monotherapy or in combination, compared with placebo, no treatment, or other standard treatment without vitamin C were included. Data Analysis After screening, 22 studies, with a total of 6831 patients, were selected for assessment. Odds ratios (ORs) with 95% CIs were calculated using fixed- and random-effects models. The meta-analysis showed significant effects of vitamin C on alleviating clinical outcomes in patients with COVID-19 (OR = 0.76, 95% CI = 0.65–0.89, P = .0007) but no shortening of the length of hospitalization (OR = 1.16, 95% CI = −0.13–2.44, P = .08) compared with the control group. Notably, vitamin C supplements significantly reduced the mortality risk (OR = 0.64, 95% CI = 0.51–0.80, P = .0001) and the incidence of severity (OR = 0.59, 95% CI = 0.43–0.80, P = .0006) in COVID-19 patients. Conclusion The findings suggest that vitamin C supplements may have a beneficial effect on clinical outcomes, as well as reducing severity and mortality in COVID-19 patients, but more clinical randomized controlled trials are needed to evaluate the role of vitamin C in treating COVID-19. Systematic Review Registration PROSPERO registration no. CRD42023491517.

EPCO-53. CHARACTERIZING THE FUNCTIONAL IMPACT OF GERMLINE-INHERITED RISK ALLELES IN GLIOMA EVOLUTION

Abstract Efforts to understand etiology of glioma led researchers to investigate associated genetic factors. Genome Wide Association Studies (GWAS) conducted to that end, uncovered an association of various single nucleotide polymorphisms (SNP) among hallmark oncogenes and tumor suppressors as risk variants in glioma incidence. Here, we perform in vitro modeling of four risk alleles/SNPs((rs723527 (EGFR), rs55705857 (MYC), rs7572263 (IDH1), rs78378222 (TP53)) mapped to non-coding regulatory regions of the genome, to assess their causal contribution to glioma evolution. To model the aforementioned risk alleles in an in-vitro system, we used a CRISPR-knock in strategy in human induced pluripotent stem cells (hiPSCs) and verified by Sanger sequencing. To study the effects of the risk alleles on brain cell types, we generated a cerebral organoid model from the edited and control lines and subjected them to downstream morphological and transcriptomic analyses. While we did not see morphological changes in the histological sections relative to controls at the early 14-day timepoint, we observed increased differentiation in both control and risk cohorts, along with an absence of neural rosettes, at the late 90-day timepoint. Bulk RNA-seq of the organoids at 14-days resulted in positive enrichment of oncogenic signaling pathways and negative enrichment of DNA repair pathways in the risk allele cohorts. Furthermore, single cell RNA seq of 14 and 90-day samples revealed a sharp decrease in neural stem cell clusters in both IDH and TP53 cohorts, while control organoids demonstrated robust production of immature neurons at 90 days. Overall, we observed a significant increase in differentiation into mature cell clusters in the control, relative to the risk allele organoids. Ongoing efforts are aimed at understanding this apparent differentiation block in the IDH and TP53 compartments, relative to control. Further analysis will lead to addressing key understudied areas of glioma etiology and associated mechanisms of risk incidence.

The potential impact of COVID-19 vaccination on patients with immune thrombocytopenic purpura: A protocol for systematic review and meta-analysis

Background Immune thrombocytopenic purpura (ITP) is a disease characterized by a decrease in platelet count, which can be triggered by various factors, including viral infections and vaccination. With the widespread vaccination against COVID-19, concerns have arisen regarding a possible link between the vaccine and the exacerbation of ITP. This study aims to comprehensively evaluate the impact of COVID-19 vaccination on ITP patients, including associated risks and outcomes. Methods A comprehensive search will be conducted in multiple electronic databases (including PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM) to identify relevant studies. This study will include randomized controlled trials, cohort studies, case-control studies, and case series evaluating the impact of COVID-19 vaccination on ITP patients. The primary outcome measure is the change in platelet count, while secondary outcome measures include the occurrence of thromboembolic events, bleeding complications, ITP recurrence rate, impact of ITP exacerbation, and adverse events. Data will be summarized and analyzed using Review Manager Software (RevMan) V.5.4. In addition, subgroup analyses will be performed to explore potential sources of heterogeneity. Results It is anticipated that different types of COVID-19 vaccines may have varying impacts on ITP patients, leading to potential differences in outcomes. This study aims to comprehensively evaluate the potential impact of COVID-19 vaccination on ITP patients and provide reference for clinical decision-making. Conclusions The results of this systematic review and meta-analysis will provide crucial information on COVID-19 vaccination for ITP patients and clinicians, contributing to guiding vaccination decisions and monitoring potential impacts after vaccination.

NCMP-26. PATIENTS WITH ANTI-HU/ANNA1 PARANEOPLASTIC NEUROLOGICAL DISORDERS DEVELOP PROGRESSIVE DISABILITY BUT HAVE INCREASED SURVIVAL

Abstract ANNA-1/Hu-IgG paraneoplastic neurological disorders (PND) are rare and factors associated with disability and survival outcomes are unknown. We aimed to 1) examine disability and survival in ANNA1/Hu-IgG PND and 2) compare survival to a control group of small cell lung cancer (SCLC) without PND. METHODS This is a retrospective cohort study of ANNA1/Hu-IgG+ with PND and a control cohort of SCLC without PND (n=1513). Cox proportional hazard models examined clinical predictors of disability and survival. Kaplan-Meier curves examined time to mortality and mRS>2. Cox proportional hazard models compared survival between ANNA1/Hu-IgG PND and SCLC without PND, adjusting for age, sex, cancer stage, and brain metastases. RESULTS Forty-five patients with ANNA/Hu1-IgG PND were included (73% female, mean age=63 years [SD=13]). Phenotypes included; neuropathy (16, 36%), ataxia (11, 24%), encephalitis (10, 22%), myasthenic syndromes (3, 7%), myelopathy (2, 4%), enteric neuropathy (2, 4%), myoclonus (1, 2%). Cancers were identified in 78%; SCLC (26, 74%), non-SCLC (4, 11%), other (5, 14%). Immunosuppressive therapy for PND was given in 53%. At 5-year follow-up, 74% had mRS>2. Limbic encephalitis had greater hazard of mRS>2 at last follow-up (HR=7.76, [95% CI=2.20-27.39], p=0.001). At 5-year follow-up, 58% had died. Survival was not influenced by phenotype nor immunosuppressive treatment. Patients with SCLC and ANNA1/Hu-IgG (n=26) were compared to SCLC without PND (n=1513) and had 54% lower hazard of death (adjusted HR =0.46, [95% CI = 0.28–0.76], p=0.003). In ANNA-1/Hu-IgG PND, most patients experienced disability and greater disability was associated with limbic encephalitis, suggesting a potential modifiable factor. However, patients with SCLC and ANNA1/Hu-IgG PND survived longer than patients with SCLC without ANNA1/Hu-IgG PND, suggesting a possible survival advantage due to earlier cancer detection (lead time bias) and/or increased antitumor immunity.

Risk of Age-Related Macular Degeneration in Patients with Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome (UPEXS)

Objective: To investigate any relationships between exfoliation syndrome or exfoliation glaucoma and age-related macular degeneration utilizing the Utah population database. Design: This was a retrospective, case–control cohort study. Subjects, Participants, and/or Controls: We identified 3405 patients diagnosed with exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) during a dilated eye exam within the UHealth system from 1996 to 2021, whose dry or wet age-related macular degeneration (AMD) status was assessed. A population-based control pool of 257,714 UHealth patients with no XFS/XFG diagnosis and a dilated eye exam history from 1996 to 2021 was compiled, with its patients randomly selected and individually matched 3:1 to cases based on sex and age at index diagnosis of their respective case. Methods: A covariate analysis was performed of characteristics and risk factors associated with XFS/XFG, which included race/ethnicity, residence location, partner/marital status, and family history of XFS/XFG, obesity, tobacco use, alcohol use, osteoporosis/vitamin D deficiency, primary/essential hypertension, ocular hypertension, and cataract surgery. Main Outcome Measure: We studied the trends of non-exudative (dry) or exudative (wet) AMD in a large Utah population study of XFS/XFG patients and controls. Results: Of 3396 XFS/XFG patients, as well as 10,179 individually matched 3:1 control patients, 64% were female and the average age of XFS onset was 74.3 yrs. In a univariate model, we observed a very modest increased risk of wet AMD in XFS/XFG patients (odds ratio, OR = 1.14, 95% confidence interval (CI) 0.99–1.32), which did not achieve statistical significance (p = 0.07). After adjusting for the main effects of potential confounders, there was no greater presentation of AMD in XFS/XFG patients when compared with controls (dry AMD: OR = 0.94, 95% CI 0.85–1.05, p = 031; wet AMD: OR = 0.98, 95% CI 0.83–1.14, p = 0.76). In XFS/XFG patients compared to controls, the risk of having cataract surgery was elevated (OR = 2.39, 95% CI 2.18–2.62). However, after accounting for an interaction with AMD, XFS/XFG patients who underwent cataract surgery did not exhibit an increased risk of either dry or wet AMD (dry AMD: OR = 0.91, 95% CI 0.80–1.03; wet AMD: OR = 0.89, 95% CI 0.75–1.07). The risk of AMD in XFS/XFG patients vs. controls showed no association with osteoporosis/vitamin D deficiency for dry (OR 0.78 95% CI 0.66–0.92 p = 0.004) or wet AMD (OR = 0.72 95% CI 0.56–0.92 p = 0.01), while we found a borderline positive association with both dry and wet AMD if they had osteoporosis/vitamin D deficiency. Conclusion: Using the Utah Population Database, we found that a cataract surgery history significantly impacts the association between AMD and XFS, and that vitamin D deficiency/osteoporosis is a significant confounder of the association. However, no direct association between XFS and AMD was found in this study.

Beyond conventional imaging: A systematic review and meta-analysis assessing the impact of computed tomography perfusion on ischemic stroke outcomes in the late window.

Non-contrast cranial computed tomography (NCCT) and CT angiogram (CTA) have become essential for endovascular treatment (EVT) in acute stroke. Patient selection may improve when CT perfusion (CTP) imaging is also added for patient selection. We aimed to analyze the effects of implementing CTP in acute ischemic stroke (AIS) patients' treatment to assess whether stroke outcomes differ in the late window. We searched the PubMed, Embase, and Web of Sciences databases to obtain articles related to CTA and CTP in EVT. Collected patient data were split into two groups: the CTP and control (NCCT + CTA) cohorts. Primary outcomes evaluated were modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhages (sICHs), mortality, and successful recanalization. There were 14 studies with 5809 total patients in the final analysis: 2602 received CTP and 3202 were in the control group. CTP/CTA patients showed significantly lower rates of 90-day stroke-related mortality (odds ratio (OR) = 0.72, 95% confidence interval (CI) = 0.60-0.87, p < 0.01) and significantly higher successful recanalization (OR = 1.42, 95% CI = 1.06-1.94, p < 0.01) compared with CTA-only patients. Analysis of other outcomes including functional independence (mRS = 0-2), critical times, and intracranial hemorrhages was non-significant (p > 0.05). The study highlights the usefulness of CTP-guided therapy as a supplementary tool in EVT selection in the late window. Although the addition of CTP resulted in lower mortality, the favorable outcomes did not improve. Further evidence is required to establish a clearer understanding of the potential advantages or limitations of incorporating CTP in stroke imaging.

DNA methylation classifier to diagnose pancreatic ductal adenocarcinoma metastases from different anatomical sites

BackgroundWe have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other malignancies. Therefore, our focus was to investigate whether the PAAD-iCCA-Classifier can be used to diagnose PAAD metastases from other sites.MethodsFor this scope, the anomaly detection filter of the initial classifier was expanded by 8 additional mimicker carcinomas, amounting to a total of 10 carcinomas in the negative class. We validated the updated version of the classifier on a validation set, which consisted of a biological cohort (n = 3579) and a technical one (n = 15). We then assessed the performance of the classifier on a test set, which included a positive control cohort of 16 PAAD metastases from various sites and a cohort of 124 negative control samples consisting of 96 breast cancer metastases from 18 anatomical sites and 28 carcinoma metastases to the brain.ResultsThe updated PAAD-iCCA-Classifier achieved 98.21% accuracy on the biological validation samples, and on the technical validation ones it reached 100%. The classifier also correctly identified 15/16 (93.75%) metastases of the positive control as PAAD, and on the negative control, it correctly classified 122/124 samples (98.39%) for a 97.85% overall accuracy on the test set. We used this DNA methylation dataset to explore the organotropism of PAAD metastases and observed that PAAD liver metastases are distinct from PAAD peritoneal carcinomatosis and primary PAAD, and are characterized by specific copy number alterations and hypomethylation of enhancers involved in epithelial-mesenchymal-transition.ConclusionsThe updated PAAD-iCCA-Classifier (available at https://classifier.tgc-research.de/) can accurately classify PAAD samples from various metastatic sites and it can serve as a diagnostic aid.

Where Should We Intervene, 20 Years Later? Case–Control and Prospective Cohort Designs Provide Similar Answers

In 2000, this journal published an influential case–control study identifying dynamic risk factors for sexual recidivism (Hanson &amp; Harris, 2000). In 2017, updated recidivism information for the same sample was obtained with an average follow-up of 20 years. The current study compared the risk factors that differentiated between sexual recidivists and nonrecidivists between the two research designs: original case–control and updated prospective cohort. Of the 82 comparisons, 50 favored the prospective design while 32 favored the case–control; however, most of the differences were small and nonsignificant. Static and dynamic risk factors were approximately equivalent between study designs. Factors identified as sex-specific (e.g., sexual deviancy) were also equivalent between designs while general risk factors (e.g., substance use) were more likely identified in the prospective design. Overall, case–control studies can be used for the identification of risk factors, especially for low base rate behaviors such as sexual recidivism.

Exploring the ceRNA network involving AGAP2-AS1 as a novel biomarker for preeclampsia

Preeclampsia (PE) is an important research subject in obstetrics. Nevertheless, the underlying mechanisms of PE remain elusive. PE-related expression datasets (GSE96983, GSE96984 and GSE24129) were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differentially expressed messenger RNAs (DE-mRNAs), DE-microRNA (DE-miRNAs) and DE-long non-coding RNA (DE-lncRNAs) between PE and control cohorts were identified, and the ceRNA network was constructed. Then candidate hub genes were obtained through five algorithms by the protein-protein intersection (PPI) network of the mRNAs. Further, five hub genes were identified by receiver operating characteristic (ROC) curve and gene expression profiles: DAXX, EFNB1, NCOR2, RBBP4 and SOCS1. The function of 5 hub genes was analyzed and the interaction between drugs and hub genes was predicted. A total of 5 small molecule drugs were predicted, namely benzbromarone, 9,10-phenanthrenequinone, chembl312032, insulin and aldesleukin. AGAP2-AS1 was mainly located in exosome and cytoplasm. Agap2-as1-related regulatory subnetworks were extracted from ceRNA networks which included 41 mRNAs, 2 miRNAs and 1 lncRNA, including the regulated relationship pairs AGAP2-AS1-hsa-miR-497-5p-SRPRB, and AGAP2-AS1-hsa-miR-195-5p-RPL36. In summary, we constructed a competitive endogenous RNA (ceRNA) network to identify five potential biomarkers (DAXX, EFNB1, NCOR2, SOCS1 and RBBP4) of PE. The in-depth analysis of the AGAP2-AS1 regulatory network will help to uncover more important molecules closely related to PE and provide a scientific Reference.

A scoping review of the integration of non-medical prescribing for acute common clinical conditions by community pharmacists

Abstract Introduction Non-medical prescribing enhances patient care, safety, and medication accessibility, while also maximising expertise1. Some evidence exists for a variety of factors at individual, organisational, regulatory, and policy levels impacting the implementation of PP in community pharmacy2. Common clinical conditions (CCC) can be defined as ‘a broad range of self-limiting conditions that are more complex in their diagnosis and treatment than minor ailments and management that often involves the need for prescription medicines’. Aim To collate and characterise literature on the integration of non-medical prescribing for acute common clinical conditions by community pharmacists. Method This scoping review followed the Arksey and O’Malley framework. The review team comprised a doctoral student (LK), a research fellow (TJ) and a professor of pharmacy (SC), all with experience of review methodology, community pharmacy research and /or practice. Eligibility criteria, search databases and terms were defined. Medline, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature and Google Scholar were searched for full text, English language, peer reviewed original papers, randomised controlled trials, cross-sectional and cohort studies, papers reporting empirical data from primary research and review articles including systematic reviews /scoping reviews /narrative reviews from January 2006 to October 2023. The (global) focus was on services delivered by pharmacists and pharmacy team members in community pharmacy for the management of CCC, using non-medical prescribing rights. Search terms included “independent prescrib*”, “pharm* independent prescri*”, “pharm* prescrib*”, “non-medical prescri*, “non-medical prescri*”, “pharm* supplementary prescri*” and “collaborative prescrib*”. Following screening and full text review a narrative synthesis approach3 was used to address the aim which involved: preliminary synthesis through data extraction and tabulation of key study characteristics, exploration of relationships and differences across the studies and finally evaluation of the robustness of the synthesis. The Consolidated Framework for Implementation Research provided a theoretical lens to support synthesis, identifying barriers and facilitators for integration. All steps were independently checked by two review team members. Ethics approval was not required because this was a scoping review. Results From a total 1018 records identified, 10 papers remained after removal of duplicates, title /abstract screening and full text review. The majority of studies were from Canada and the aims and linked outcomes of studies focused on pharmacists’ views and experiences, evaluation of safety, effectiveness, and patient satisfaction. A range of CCCs were included with a focus on antibiotic prescribing. A wide range of barriers and facilitators to implementation were identified including “regulatory constraints” and “fiscal challenges” at a macro socio-organisational level and a plethora of dichotomous challenges within organisations including a lack of clarity on the pharmacist’s scope of practice and linked consumer confusion, staffing levels and workload, with specific mention of paperwork and access to patient records. Conclusion The small number of studies included indicates that there is a paucity of research in this area. There is a need for increased efforts to consider this topic further and identify ways to address the challenges for further widespread implementation and uptake of such services.

Efficacy of four internal fixation devices on femoral neck fractures in young adults: A systematic review and network meta-analysis

Background: The primary treatment of femoral neck fracture in young adults is internal fixation. The high complication rate after femoral neck fracture greatly affects the life of patients. There are many internal fixation devices for femoral neck fracture, but each has its advantages and disadvantages. Our aim was to determine the best internal fixation for young people with femoral neck fractures. Methods: We searched 5 databases from January, 2016 to December, 2023. Randomized controlled trials and cohort studies that met the inclusion criteria were assessed for quality using the RoB.2 and ROBINS-I scales, respectively. The network meta-analysis was conducted within a Bayesian framework utilizing a random effect model. Data analysis was performed using the “multinma” package within the R 4.2.0 software. Results: A network meta-analysis of 34 studies involving 2291 patients was conducted. Results indicated that the inverted triangular cannulated screws demonstrated the lowest intraoperative bleeding volume (surface under the cumulative ranking curve [SUCRA] = 0.8732) based on the SUCRA. The medial buttress plate (MBP) exhibited superior efficacy in improving the Harris hip score (SUCRA = 0.8465), reducing complications (SUCRA = 0.9251), and accelerating fracture healing time (SUCRA = 0.8111). Additionally, the femoral neck system was ranked highest in terms of operation time (SUCRA = 0.7749) and femoral neck shortening (SUCRA = 0.7933). Conclusion: This network meta-analysis findings indicated that MBP resulted in superior postoperative hip function, reduced complication rate, faster fracture healing time. Considering the good physical condition of young adults, surgeon may consider utilizing MBP to achieve improved postoperative outcomes.

The effects of pre-operative anti-osteoporotic use on total joint arthroplasty complications: A national database study

BackgroundThe current study aims to analyze the effect of pre-operative non-bisphosphonate anti-osteoporotic drugs on complication and revision rates following total joint arthroplasty (TJA). MethodsA retrospective cohort analysis of the PearlDiver (PearlDiver Technologies, Colorado Springs, CO) database was performed. The database was queried to identify all patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) with history of hip or knee osteoarthritis and either osteopenia or osteoporosis. The treatment groups consisted of patients prescribed non-bisphosphonate and bisphosphonate osteomodulatory agents for 1 year prior to and following surgery. The treatment groups were matched to control cohorts by age, gender, and comorbidities. Chi-square analyses were used to compare outcomes between paired cohorts. ResultsThere were no statistically significant differences (p ≤ 0.05) in risk of aseptic loosening, broken prosthesis, dislocation of prosthetic joint, periprosthetic fracture, periprosthetic osteolysis, postoperative infection, full or partial revision, or stress fracture between both the non-bisphosphonate and bisphosphonate groups following THA or TKA. Comparisons between both groups and control cohort also yielded no significant differences. ConclusionThe current study detected no significant differences in early post-operative complications following TJA between patients treated with different classes of anti-osteoporotic medications versus untreated osteopenic/osteoporotic patients. Further research is required to fully understand the impact of osteomodulatory medications on TJA outcomes. Analysis should continue to ensure a high-quality standard of care and aim to better understand outcomes for such patients requiring TJA.

Smartphone-Based Cognitive Behavioral Therapy and Customized Sound Therapy for Tinnitus: A Randomized Controlled Trial.

To evaluate the efficacy of a smartphone-based application providing tinnitus-specific cognitive behavioral therapy and customized sound therapy for tinnitus. In a prospective randomized controlled trial, the treatment group participated in daily sound therapy and weekly interactive CBT modules, and the control group did not receive the program (waitlisted). Outcome measures after 8 weeks included the Tinnitus Functional Index (TFI), Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI). Ninety-two patients (mean age = 57.2 ± 11.9 years) were included. The treatment (n = 47) and control (n = 45) cohorts had similar TFI, PHQ-9, GAD-7, PSS, and PSQI scores at presentation (all P > .05). Treatment-group patients had significantly higher improvements than controlled patients in their TFI (16.7 ± 14.9 vs 1.9 ± 10.8, P < .001), PHQ-9 (1.9 ± 4.2 vs -0.7 ± 3.4, P = .002), GAD-7 (1.1 ± 3.6 vs -0.9 ± 3.3, P = .009), and PSQI scores (2.5 ± 3.2 vs -1.1 ± 2.1, P < .001). Treatment-group subjects also significantly improved in 7 of the 8 TFI domains (all P < .05). TFI improvements of ≥20 occurred in 18 (38.3%) treatment subjects. Of the 9 treatment-group patients presenting with moderate-severe depression, 4 (44.4%) improved to minimal depression. Of the 4 treatment-group patients with moderate-severe anxiety, 2 (50.0%) improved to minimal anxiety. Of the 17 treatment-group patients with moderate-severe sleep difficulties, 10 (55.6%) had considerable sleep improvement. This novel smartphone application providing cognitive behavioral therapy and customized sound therapy was effective in reducing symptom severity and improving anxiety, sleep, and mood for tinnitus patients.

Elevated risk of end-stage kidney disease in stroke patients: A population-based observational study.

Estimating the incidence of end-stage kidney disease (ESKD) in stroke survivors is important to assess and predict clinical course, improve post-stroke quality of life, and ultimately reduce health burden. Our objective was to assess the risk of ESKD in patients compared to a matched stroke-free control cohort. A nationwide retrospective cohort study was conducted in 315,326 stroke subjects and 390,781 matched stroke-free control subjects. Health examination results and claims data were collected from the Korean National Health Insurance Service during 2010-2018. Cox proportional hazard models were used to assess the risk of ESKD in the stroke cohort. During a mean follow-up period of 4.3 years, the incidence of ESKD was 1.83 per 100,000 person-years in the stroke cohort versus 0.57 per 100,000 person-years in the control cohort. The stroke cohort exhibited a significantly higher risk of developing ESKD compared to the matched control, with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval (CI) = 1.67-1.93). Stroke survivors were associated with a higher risk of developing ESKD, regardless of the severity of disability (aHRs of 1.93, 95% CI = 1.69-2.21 for severe disability; 1.71, 95% CI = 1.41-2.07 for mild disability; and 1.78, 95% CI = 1.65-1.92 for no disability), compared to the matching control cohort. The elevated risk was observed in both hemorrhagic stroke (aHR = 1.96, 95% CI = 1.73-2.23) and ischemic stroke (aHR = 1.75, 95% CI = 1.62-1.89). This study demonstrates that stroke patients have a significantly higher risk of incident ESKD. This highlights the need for heightened clinical awareness and improved monitoring of kidney function in this population.

Complications of total knee arthroplasty in patients with prior anterior cruciate ligament reconstruction compared to a matched cohort

BackgroundCurrent literature reports a 500 % increase in reoperation in total knee arthroplasty (TKA) after anterior cruciate ligament reconstruction (ACLR). The purpose of this study is to determine the effect of ACLR on subsequent TKA. MethodsThis retrospective case control study included 30 patients that underwent TKA following an ACLR who were matched 3:1 to a control cohort at a single tertiary academic center between January 1, 2011 and January 1, 2021. The electronic medical records were queried for demographics, complications, history of ACLR, and range of motion (ROM) preoperatively and postoperatively at 3 months and 1 year. Student's t-tests and Fisher's exact tests were used for analysis (α = 0.05). ResultsThe mean ROM between the ACLR and control groups preoperatively, at 3 months and at 1 year postoperatively were 108.2° v 104.8° (p = 0.42), 114.0° v 111.8° (p = 0.51), and 115.3° v 115.8° (p = 0.88). At 1 year, 9 of 30 (30 %) ACLR patients decreased ROM versus 14 of 90 (15.6 %) control patients (mean loss of 21.4° v 11.9°, p = 0.076). No difference in complication rate was found (10 % v 11.1 %, p = 1). Complications in the ACLR group included open debridement and capsular release for stiffness after 2 failed manipulations under anesthesia (MUA), lysis of adhesions for patellar clunk, and revision surgery for flexion instability. No control patients required MUA. ConclusionThis study demonstrated that TKA following ACLR is without an increased risk of complications. However, ACLR patients should be followed closely since loss of ROM can be large.