Hippocampal Perfusion Affects Motor and Cognitive Functions in Parkinson Disease: An Early Phase 18 F-FP-CIT Positron Emission Tomography Study.

OBJECTIVE: We investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson disease (PD). METHODS: We recruited patients with newly diagnosed and nonmedicated PD and healthy participants who underwent dual phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography scans. Patients were classified into 3 groups according to hippocampal perfusion measured by standard uptake value ratios (SUVRs): (1) PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD-hippo-hypo), (2) PD hippocampal hyperperfusion group (1 SD above the mean; PD-hippo-hyper), and (3) the remaining patients (PD-hippo-normal). We compared the baseline cognitive performance, severity of motor deficits, hippocampal volume, striatal dopamine transporter (DAT) availability, and risk of dementia conversion among the groups. RESULTS: We included 235 patients (PD-hippo-hypo, n = 21; PD-hippo-normal, n = 157; PD-hippo-hyper, n = 57) and 48 healthy participants. Patients in the PD-hippo-hypo group were older and had smaller hippocampal volumes than those in the other PD groups. The PD-hippo-hypo group showed less severely decreased DAT availability in the putamen than the other groups despite similar severities of motor deficit. The PD-hippo-hypo group had a higher risk of dementia conversion compared to the PD-hippo-normal (hazard ratio = 2.59, p = 0.013) and PD-hippo-hyper (hazard ratio = 3.73, p = 0.006) groups, despite similar cognitive performance at initial assessment between groups. INTERPRETATION: Hippocampal hypoperfusion may indicate a reduced capacity to cope with neurodegenerative processes in terms of the development of motor deficits and cognitive decline in patients with PD. ANN NEUROL 2024;95:388-399.

Comparative risk of incident and recurrent acute anterior uveitis across different biological agents in patients with ankylosing spondylitis.

OBJECTIVE: To evaluate the comparative risk of incident and recurrent acute anterior uveitis (AAU) across different biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients with ankylosing spondylitis (AS). METHODS: A retrospective nationwide cohort study was conducted on 34 621 patients with AS without a previous history of AAU using a national claims database. Patients were followed-up from 2010 to 2021. The comparative risk of incident and recurrent AAU across different bDMARDs was examined using multivariable time-dependent Cox models and counting process (AG) models, respectively. RESULTS: The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident AAU (bDMARDs non-exposure as reference) were: adalimumab 0.674 (0.581-0.891), etanercept 1.760 (1.540-2.012), golimumab 0.771 (0.620-0.959), infliximab 0.891 (0.741-1.071), and secukinumab 1.324 (0.794-2.209). Compared with adalimumab exposure, etanercept (aHR = 2.553 [2.114-3.083]), infliximab (aHR = 1.303 [1.039-1.634]), and secukinumab exposures (aHR = 2.173 [1.273-3.710]) showed a higher risk of incident AAU. The aHRs and 95% CIs for recurrent AAU (bDMARDs non-exposure as reference) were: adalimumab 0.798 (0.659-0.968), etanercept 1.416 (1.185-1.693), golimumab 0.874 (0.645-1.185), infliximab 0.926 (0.729-1.177), and secukinumab 1.257 (0.670-2.359). Compared with adalimumab exposure, etanercept exposure (aHR = 1.793 [1.403-2.292]) was associated with a higher risk of recurrent AAU. CONCLUSION: Our data suggest preference for bDMARDs in the following order: adalimumab/golimumab > infliximab > secukinumab > etanercept (for incident AAU prevention) and adalimumab > golimumab/infliximab/secukinumab > etanercept (for recurrent AAU prevention).

Role of Enlarged Perivascular Space in the Temporal Lobe in Cerebral Amyloidosis.

OBJECTIVE: Although growing evidence suggests that perivascular space (PVS) serves as a clearance route for amyloid and tau, the association between enlarged PVS (EPVS) and Alzheimer disease is highly inconsistent across studies. As the conventional visual rating systems for EPVS were insufficient to predict amyloid/tau/neurodegeneration (A/T/N) status, we developed a new rating scale for EPVS located in the temporal lobe (T-EPVS). METHODS: EPVS located in the basal ganglia (BG-EPVS), centrum semiovale (CS-EPVS), and T-EPVS was visually rated in 272 individuals (healthy controls, n = 96; mild cognitive impairment, n = 106; dementia, n = 70) who underwent structural magnetic resonance imaging (MRI) and dual positron emission tomography scans (18 F-flortaucipir and 18 F-florbetaben). T-EPVS and BG-EPVS were defined as high degree when the counts in any hemisphere were >10, and the CS-EPVS cutoff was >20. Logistic regression models were constructed to investigate whether the regional EPVS burden was predictive of A/T/N status. The derived models were externally validated in a temporal validation cohort (n = 195) that underwent MRI studies using a different scanner. RESULTS: Compared with those with low-degree T-EPVS (23/136, 16.9%), individuals with high-degree T-EPVS/CS-EPVS but low-degree BG-EPVS were more likely to exhibit amyloid positivity (46/56, 82.1%). High-degree T-EPVS burden (odds ratio [OR] = 7.251, 95% confidence interval [CI] = 3.296-15.952) and low-degree BG-EPVS (OR = 0.241, 95% CI = 0.109-0.530) were predictive of amyloid positivity. Although high-degree T-EPVS was associated with tau positivity, the association was no longer significant after adjusting for amyloid and neurodegeneration status. INTERPRETATION: Investigating the burden and topographic distribution of EPVS including T-EPVS may be useful for predicting amyloid status, indicating that impaired perivascular drainage may contribute to cerebral amyloidosis. ANN NEUROL 2023;93:965-978.

Trajectories of triglyceride-glucose index changes and their association with all-cause and cardiovascular mortality: a competing risk analysis.

BACKGROUND: The association between changes in insulin resistance, reflected by the triglyceride-glucose (TyG) index, and mortality remains unclear. This study investigated whether longitudinal trajectories of TyG index changes are associated with all-cause and cardiovascular disease (CVD) mortality. METHODS: This retrospective cohort study analyzed data from 233,546 adults aged ≥ 19 years from the Korea National Health Insurance Service-National Sample Cohort. Participants were categorized as having increasing, stable, or decreasing TyG index changes during a 4-year exposure period (2009-2014). Mortality outcomes were assessed during an 8.13-year follow-up period (2015-2021). Cox proportional hazards regression and competing risk analysis were used to evaluate all-cause and CVD mortality. RESULTS: A total of 7918 mortality events, including 651 CVD deaths, were recorded. Compared with the stable group, adjusted hazard ratios for all-cause mortality were 1.09 (95% CI 1.03-1.15) in the increasing group and 1.23 (95% CI 1.01-1.50) for CVD mortality. An increased TyG index was significantly associated with all-cause mortality in individuals aged < 50 years; men; and individuals with obesity, hypertension, diabetes, and/or dyslipidemia. For CVD mortality, significant associations were found in individuals aged 50-69 years, with obesity, with diabetes, or without dyslipidemia. CONCLUSION: An increasing TyG index from baseline during follow-up was independently associated with higher risks of all-cause and CVD mortality. Serial monitoring of TyG index changes could enhance risk stratification and inform targeted interventions to reduce insulin resistance, and ultimately lower mortality risk.

Sex differences in the relationship between serum total bilirubin and risk of incident metabolic syndrome in community-dwelling adults: Propensity score analysis using longitudinal cohort data over 16 years.

BACKGROUND: Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study. METHODS: Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40-69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline. RESULTS: With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80-1.24) for men and 0.80 (0.65-0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285). CONCLUSION: Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.

Association between substantia nigra degeneration and functional outcome in patients with basal ganglia infarction.

BACKGROUND AND PURPOSE: Cerebral infarction in the basal ganglia may cause secondary and delayed neuronal degeneration in the substantia nigra (SN). However, the clinical significance of SN degeneration remains poorly understood. METHODS: This retrospective observational study included patients with acute ischemic stroke in the basal ganglia on initial diffusion-weighted imaging who underwent follow-up diffusion-weighted imaging between 4 and 30 days after symptom onset. SN degeneration was defined as a hyperintensity lesion in the SN observed on diffusion-weighted imaging. We compared functional outcomes at 3 months between patients with and without SN degeneration. A poor outcome was defined as a score of 3-6 (functional dependence or death) on the modified Rankin Scale. RESULTS: Of 350 patients with basal ganglia infarction (median age = 74.0 years, 53.7% male), 125 (35.7%) had SN degeneration. The proportion of functional dependence or death was 79.2% (99/125 patients) in patients with SN degeneration, which was significantly higher than that in those without SN degeneration (56.4%, 127/225 patients, p < 0.001). SN degeneration was more frequent in patients with functional dependence or death (99/226 patients, 43.8%) than in those with functional independence (26/124 patients, 21.0%, p < 0.001). Multivariable logistic regression analysis showed a significant association between SN degeneration and functional dependence or death (odds ratio = 2.91, 95% confidence interval = 1.17-7.21, p = 0.021). CONCLUSIONS: The study showed that patients with degeneration of SN were associated with functional dependence or death at 3 months, suggesting that secondary degeneration is a predictor of poor stroke outcomes and a potential therapeutic target.

Associations of Homeostatic Model Assessment for Insulin Resistance Trajectories With Cardiovascular Disease Incidence and Mortality.

BACKGROUND: Whether trends in insulin resistance changes are related to the risk of cardiovascular disease (CVD) incidence and mortality remains unclear. We aimed to examine the association of homeostatic model assessment for insulin resistance (HOMA-IR) trajectories with CVD incidence and mortality. METHODS: Data from 6755 adults aged 40 to 69 years in the Korea Epidemiology and Genome Study were analyzed. During the exposure period (2001-2006), participants were classified into the increasing HOMA-IR trajectory group and the stable HOMA-IR trajectory group using a latent class mixture model. During the event accrual period (2007-2018), information about CVD and mortality were collected. RESULTS: During the median 9.83-year event accrual period, there were 379 (5.6%) new-onset CVD, 535 (7.9%) all-cause mortality, 102 (1.5%) CVD mortality, and 47 (0.7%) major adverse cardiovascular event mortality cases. Compared with the stable HOMA-IR trajectory group, the fully adjusted hazard ratios (95% CIs) for the increasing HOMA-IR trajectory group were 1.59 (1.04-2.44) for incident CVD, 1.87 (1.30-2.69) for all-cause mortality, 2.33 (1.11-4.89) for CVD mortality, and 3.67 (1.38-9.76) for major adverse cardiovascular event mortality. CONCLUSIONS: An increasing HOMA-IR appears to be independently and positively related to incident CVD, all-cause mortality, CVD mortality, and major adverse cardiovascular event mortality. Early lifestyle interventions for individuals with increasing HOMA-IR trend could be a practical strategy to prevent CVD and CVD mortality.

Effect of 10 Minutes of Prewarming and Prewarmed Intravenous Fluid Administration on the Core Temperature of Patients Undergoing Transurethral Surgery under General Anesthesia.

Background: Patients undergoing transurethral urologic procedures using bladder irrigation are at increased risk of perioperative hypothermia. Thirty minutes of prewarming prevents perioperative hypothermia. However, its routine application is impractical. We evaluated the effect of 10 minutes of prewarming combined with the intraoperative administration of warmed intravenous fluid on patients' core temperature. Methods: Fifty patients undergoing transurethral bladder or prostate resection under general anesthesia were included in this study and were randomly allocated to either the control group or the prewarming group. Patients in the prewarming group were warmed for 10 minutes before anesthesia induction with a forced-air warming device and received warmed intravenous fluid during operations. The patients in control group did not receive preoperative forced-air warming and were administered room-temperature fluid. Participants' core body temperature was measured on arrival at the preoperative holding area (T0), on entering the operating room, immediately after anesthesia induction, and in 10-minute intervals from then on until the end of the operation (Tend), on entering PACU, and in 10-minute intervals during the postanesthesia care unit stay. The groups' incidence of intraoperative hypothermia, change in core temperature (T0 - Tend), and postoperative thermal comfort were compared. Results: The incidence of hypothermia was 64% and 29% in the control group and prewarming group, respectively (P = 0.015). Change in core temperature was 0.93 ± 0.3 °C and 0.55 ± 0.4 °C in the control group and prewarming group, respectively (P = 0.0001). Thermal comfort was better in the prewarming group (P = 0.004). Conclusions: Ten minutes of prewarming combined with warmed intravenous fluid significantly decreased the incidence of intraoperative hypothermia and resulted in better thermal comfort in patients undergoing transurethral urologic surgery under general anesthesia.

Application of machine learning for predicting lymph node metastasis in T1 colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: We review and analyze research on the application of machine learning (ML) and deep learning (DL) models to lymph node metastasis (LNM) prediction in patients with T1 colorectal cancer (CRC). Predicting LNM before radical surgery is important in patients with T1 CRC. However, current surgical treatment guidelines are limited. LNM prediction using ML or DL may improve predictive accuracy. The diagnostic accuracy of LNM prediction using ML- and DL-based models for patients with CRC was assessed. METHODS: We performed a comprehensive search of the PubMed, Embase, and Cochrane databases (inception to April 30th of 2022) for studies that applied ML or DL to LNM prediction in T1 CRC patients specifically to compare with histopathological findings and not related to radiological aspects. RESULTS: 33,199 T1 CRC patients enrolled across seven studies with a retrospective design were included. LNM was observed in 3,173 (9.6%) patients. Overall, the ML- and DL-based model exhibited a sensitivity of 0.944 and specificity of 0.877 for the prediction of LNM in patients with T1 CRC. Six different types of ML and DL models were used across the studies included in this meta-analysis. Therefore, a high degree of heterogeneity was observed. CONCLUSIONS: The ML and DL models provided high sensitivity and specificity for predicting LNM in patients with T1 CRC, and the heterogeneity between studies was significant. These results suggest the potential of ML or DL as diagnostic tools. However, more reliable algorithms should be developed for predicting LNM before surgery in patients with T1 CRC.

Trajectories of atherosclerotic cardiovascular disease risk scores as a predictor for incident chronic kidney disease.

BACKGROUND: The relationship between atherosclerosis and renal function is well established. Atherosclerotic cardiovascular disease (ASCVD) risk scores reflect atherosclerotic burden, which changes over time. We investigated the association between ASCVD risk trajectories and incident chronic kidney disease (CKD) using data from a large community-based Korean cohort with up to 16 years of follow-up. METHODS: We analyzed data from 5032 participants without CKD from the baseline survey of the Korean Genome and Epidemiology Study Ansan-Ansung cohort. Participants were categorized into stable or increasing ASCVD risk groups based on the revised ASCVD risk pooled cohort equation over a median period of exposure of 5.8 years. Incident CKD was defined as two consecutive events of an estimated glomerular filtration rate < 60 mL/min/1.73 m2. RESULTS: During a median 9.9 years of event accrual period, 449 (8.92%) new-onset CKD cases were identified. Multiple Cox proportional regression analyses showed that the hazard ratio (95% confidence interval) for incident CKD in the increasing group, compared to the stable group, was 2.13 (1.74-2.62) in the unadjusted model and 1.35 (1.02-1.78) in the fully-adjusted model. Significant relationships were maintained in subgroups of individuals in their 50s, without diabetes mellitus or hypertension. The prevalence of proteinuria was consistently higher in the increasing group than that in the stable group. CONCLUSIONS: An increasing trend in ASCVD risk scores independently predicted adverse renal outcomes in patients without diabetes mellitus or hypertension. Continuous monitoring of ASCVD risk is not only important for predicting cardiovascular disease but also for predicting CKD.

Comparative Analysis of Clinical Outcomes Using Propensity Score Matching: Coronavirus Disease 2019 vs. Seasonal Influenza in Korea.

BACKGROUND: The advent of the omicron variant and the formulation of diverse therapeutic strategies marked a new epoch in the realm of coronavirus disease 2019 (COVID-19). Studies have compared the clinical outcomes between COVID-19 and seasonal influenza, but such studies were conducted during the early stages of the pandemic when effective treatment strategies had not yet been developed, which limits the generalizability of the findings. Therefore, an updated evaluation of the comparative analysis of clinical outcomes between COVID-19 and seasonal influenza is requisite. METHODS: This study used data from the severe acute respiratory infection surveillance system of South Korea. We extracted data for influenza patients who were infected between 2018 and 2019 and COVID-19 patients who were infected in 2021 (pre-omicron period) and 2022 (omicron period). Comparisons of outcomes were conducted among the pre-omicron, omicron, and influenza cohorts utilizing propensity score matching. The adjusted covariates in the propensity score matching included age, sex, smoking, and comorbidities. RESULTS: The study incorporated 1,227 patients in the pre-omicron cohort, 1,948 patients in the omicron cohort, and 920 patients in the influenza cohort. Following propensity score matching, 491 patients were included in each respective group. Clinical presentations exhibited similarities between the pre-omicron and omicron cohorts; however, COVID-19 patients demonstrated a higher prevalence of dyspnea and pulmonary infiltrates compared to their influenza counterparts. Both COVID-19 groups exhibited higher in-hospital mortality and longer hospital length of stay than the influenza group. The omicron group showed no significant improvement in clinical outcomes compared to the pre-omicron group. CONCLUSION: The omicron group did not demonstrate better clinical outcomes than the pre-omicron group, and exhibited significant disease severity compared to the influenza group. Considering the likely persistence of COVID-19 infections, it is imperative to sustain comprehensive studies and ongoing policy support for the virus to enhance the prognosis for individuals affected by COVID-19.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Sarcopenia, a Risk Predictor of Postoperative Acute Kidney Injury in Elderly Patients after Hip Fracture Surgery: A Retrospective Analysis.

Background and Objectives: Hip fracture surgery, which affects quality of life, can be a major challenge in geriatric populations. Although sarcopenia is known to be associated with postoperative outcomes, there are few studies on the association between sarcopenia and postoperative acute kidney injury (AKI) in this population. We investigated the association between sarcopenia and postoperative AKI in elderly patients following hip fracture surgery. Materials and Methods: We retrospectively reviewed the records of patients who underwent hip fracture surgery at our institution from March 2019 to December 2021. Patients under the age of 65, patients with no preoperative computed tomography (CT) scans and patients with inappropriate cross-sectional images for measurement were excluded. The psoas-lumbar vertebral index (PLVI), which is the ratio of the average area of both psoas muscles to the area of the fourth lumbar vertebral body, was measured from preoperative CT scans. Sarcopenia was defined as a PLVI within the lowest 25% for each sex, and patients were categorized into sarcopenic and nonsarcopenic groups. The occurrence of AKI was determined based on the serum creatinine level within postoperative day 7 using the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and the occurrence of AKI. Results: Among the 348 enrolled patients, 92 patients were excluded, and 256 patients were analyzed. The PLVI cutoff values for defining sarcopenia lower than 25% for male and female patients were 0.57 and 0.43, respectively. The overall incidence of AKI was 18.4% (47 patients), and AKI occurred more frequently in sarcopenic patients than in nonsarcopenic patients (29.7% vs. 14.6%, p = 0.007). According to the multivariate logistic regression, which included all variables with a p value < 0.05 in the univariate analysis and adjusted for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) physical status, sarcopenia was revealed to be an independent predictor of postoperative AKI (odds ratio = 5.10, 95% confidence interval = 1.77-14.77; p = 0.003). Conclusions: Preoperative sarcopenia, which corresponds to the lowest quartile of PLVI values, is associated with postoperative AKI among elderly patients who underwent hip fracture surgery.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

Relationship between tamoxifen and cataracts: a nationwide cohort study of women in South Korea.

PURPOSE: Although prospective randomized clinical trials have reported that the use of prophylactic tamoxifen in patients at a high risk of breast cancer is associated with an increased risk of cataracts development, such findings are inconsistent. This study aimed to clarify the relationship between adjuvant tamoxifen use and cataracts risk using a nationwide longitudinal population-based registry. METHODS: This retrospective cohort study was conducted using the Korean National Health Insurance claims database over a 15-year period (January 2007-December 2021). Data from all female patients diagnosed with ductal carcinoma in situ (DCIS) between 2009 and 2015 were extracted. We evaluated the incidence of cataracts diagnosis and surgery after adjuvant tamoxifen administration in patients with DCIS. RESULTS: A total of 43,434 patients who met the inclusion criteria were diagnosed with DCIS between 2009 and 2015. Data from 2849 patients receiving tamoxifen and 1615 patients not receiving tamoxifen were analyzed before matching. After matching for comorbidities, type of breast surgery, and age, both groups consisted of 1597 patients. Both before and after matching, adjuvant tamoxifen was not a significant factor for an increased risk of cataracts diagnosis alone or with surgery. CONCLUSION: Our study showed that adjuvant tamoxifen was not a risk factor for increased cataracts diagnosis and surgery in patients with DCIS. This finding provides a basis for physicians to reduce their ocular toxicity concerns regarding the risk of patients developing cataracts by tamoxifen treatment.

MRI-visible Dilated Perivascular Space in the Brain by Age: The Human Connectome Project.

Background Dilated perivascular spaces (dPVS) are associated with aging and various disorders; however, the effect of age on dPVS burden in young populations and normative data have not been fully evaluated. Purpose To investigate the dPVS burden and provide normative data according to age in a healthy population, including children. Materials and Methods In this retrospective study, three-dimensional T2-weighted brain MRI scans from the Human Connectome Project data sets were used for visual grading (grade 0, 1, 2, 3, 4 for 0, 1-10, 11-20, 21-40, and >40 dPVS on a single section of either hemispheric region) and automated volumetry of dPVS in basal ganglia (BGdPVS) and white matter (WMdPVS). Linear and nonlinear regression were performed to assess the association of dPVS volume with age. Optimal cutoff ages were determined with use of the maximized continuous-scale C-index. Participants were grouped by cutoff values. Linear regression was performed to assess the age-dPVS volume relationship in each age group. Normative data of dPVS visual grades were provided per age decade. Results A total of 1789 participants (mean age, 35 years; age range, 8-100 years; 1006 female participants) were evaluated. Age was related to dPVS volume in all regression models (R2 range, 0.41-0.55; P < .001). Age-dPVS volume relationships were altered at the mid-30s and age 55 years; BGdPVS and WMdPVS volumes negatively correlated with age until the mid-30s (ß, -1.2 and -7.8), then positively until age 55 years (ß, 3.3 and 54.1) and beyond (ß, 3.9 and 42.8; P < .001). The 90th percentile for dPVS grades was grade 1 for age 49 years and younger, grade 2 for age 50-69 years, and grade 3 for age 70 years and older (overall, grade 2) for BGdPVS, and grade 3 for age 49 years and younger and grade 4 for age 50 years and older (overall, grade 3) for WMdPVS. Conclusion Dilated perivascular spaces (dPVS) showed a biphasic volume pattern with brain MRI, lower volumes until the mid-30s, then higher afterward. Grades of 3 or higher and 4 might be considered pathologic dPVS in basal ganglia and white matter, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Bapuraj and Chaudhary in this issue.

Machine-Learning Algorithms Using Systemic Inflammatory Markers to Predict the Oncologic Outcomes of Colorectal Cancer After Surgery.

BACKGROUND: This study aimed to investigate the clinical significance of machine-learning (ML) algorithms based on serum inflammatory markers to predict survival outcomes for patients with colorectal cancer (CRC). METHODS: The study included 941 patients with stages I to III CRC. Based on random forest algorithms using 15 compositions of inflammatory markers, four different prediction scores (DFS score-1, DFS score-2, DFS score-3, and DFS score-4) were developed for the Yonsei cohort (training set, n = 803) and tested in the Ulsan cohort (test set, n = 138). The Cox proportional hazards model was used to determine correlation between prediction scores and disease-free survival (DFS). Harrell's concordance index (C-index) was used to compare the predictive ability of prediction scores for each composition. RESULTS: The multivariable analysis showed the DFS score-4 to be an independent prognostic factor after adjustment for clinicopathologic factors in both the training and test sets (hazard ratio [HR], 8.98; 95% confidence interval [CI] 6.7-12.04; P < 0.001 for the training set and HR, 2.55; 95% CI 1.1-5.89; P = 0.028 for the test set]. With regard to DFS, the highest C-index among single compositions was observed in the lymphocyte-to-C-reactive protein ratio (LCR) (0.659; 95% CI 0.656-0.662), and the C-index of DFS score-4 (0.727; 95% CI 0.724-0.729) was significantly higher than that of LCR in the test set. The C-index of DFS score-3 (0.725; 95% CI 0.723-0.728) was similar to that of DFS score-4, but higher than that of DFS score-2 (0.680; 95% CI 0.676-0.683). CONCLUSIONS: The ML-based approaches showed prognostic utility in predicting DFS. They could enhance clinical use of inflammatory markers in patients with CRC.

Patent Foramen Ovale and Risk of Recurrence in Stroke of Determined Etiology.

OBJECTIVE: Patent foramen ovale (PFO) is often found in stroke patients with determined etiologies. PFO may be the actual cause of stroke in some of them. We determined whether the risk of recurrent ischemic stroke differs with PFO status in stroke patients with determined etiologies. METHODS: This study included consecutive patients with stroke of determined etiology who underwent transesophageal echocardiography. We compared the rates of recurrent cerebral infarction in patients with versus without PFO, and according to PFO-Associated Stroke Causal Likelihood (PASCAL) classification. RESULTS: Of 2,314 included patients, 827 (35.7%) had PFO. During a median follow-up of 4.4 years, cerebral infarction recurred in 202 (8.7%). In multivariate modified Cox regression analyses, recurrence of infarction did not significantly differ between patients with PFO and those without PFO (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.64-1.17, p = 0.339). Interaction analysis showed a significant effect of PFO in patients aged <65 years (adjusted p for interaction = 0.090). PFO was independently associated with a decreased risk of recurrent infarction in patients younger than 65 years (HR = 0.41, 95% CI = 0.20-0.85, adjusted p = 0.016). Patients with probable PFO-associated stroke on the PASCAL classification had a significantly lower risk of recurrent infarction than those without PFO (HR = 0.31, 95% CI = 0.10-0.97, p = 0.044). INTERPRETATION: Considering the generally low risk of recurrence in PFO-associated stroke, PFO may be the actual cause of stroke in some patients with determined etiologies, especially younger patients or those with PFO features of probable PFO-associated stroke. ANN NEUROL 2022;92:596-606.

Sex differences in the relationship between platelet count and type 2 diabetes risk in community-dwelling adults: Longitudinal findings over 14 years.

AIMS: Emerging evidence suggests that platelet count predicts the development of type 2 diabetes; however, there is conflicting evidence concerning the relationship in men and women. This study aimed to assess the longitudinal association between platelet count and the incidence risk of type 2 diabetes. MATERIALS AND METHODS: Among 10,030 participants, 7325 participants (3439 men and 3886 women) without diabetes were selected from the Korean Genome and Epidemiology Study. Platelet count quartiles were divided as follows: Q1 ≤219, Q2, 220-254, Q3, 255-296 and Q4 ≥297 (x103 /ml) for men and ≤232, 233-266, 267-305 and ≥306 (x103 /µL) for women. The hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes were calculated using multiple Cox proportional hazards regression models according to sex-specific platelet count quartiles. RESULTS: During the biennial follow-up period from 2001 to 2002 to 2013-2014, 750 male participants (21.8%, 750/3439) and 730 female participants (18.8%, 730/3886) had newly developed type 2 diabetes. For women, compared to the reference first quartile, the HRs for incident type 2 diabetes in the second, third, and fourth platelet count quartiles were 1.20 (0.96-1.50), 1.21(0.97-1.51), and 1.47 (1.18-1.82) after adjusting for age, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and HOMA-IR. However, these positive relationships were not observed in men after adjusting for the same co-variables. CONCLUSIONS: Platelet count was independently associated with an increased risk of incident type 2 diabetes only in women.

Differential Implications of Cerebral Hypoperfusion and Hyperperfusion in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes. OBJECTIVE: This study investigated whether cerebral regions with hypoperfusion and hyperperfusion have differential effects on motor and cognitive symptoms in PD using early-phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (18 F-FP-CIT) positron emission tomography (PET) scans. METHODS: We enrolled 394 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET scans. Indices reflecting associated changes in regional cerebral hypoperfusion and hyperperfusion on early-phase 18 F-FP-CIT PET scans were calculated as PD[hypo] and PD[hyper] , respectively. The associations of PD[hypo] and PD[hyper] on motor and cognitive symptoms at baseline were assessed using multivariate linear regression. Also, Cox regression and linear mixed models were performed to investigate the effects of baseline PD[hypo] and PD[hyper] on longitudinal outcomes. RESULTS: There was a weak correlation between PD[hypo] and PD[hyper] (γ = -0.19, P < 0.001). PD[hypo] was associated with baseline Unified Parkinson's Disease Rating Scale Part III scores (ß = -1.02, P = 0.045), rapid increases in dopaminergic medications (ß = -18.02, P < 0.001), and a higher risk for developing freezing of gait (hazard ratio [HR] = 0.67, P = 0.019), whereas PD[hyper] was not associated. Regarding cognitive function, PD[hypo] was more relevant to the baseline cognitive performance levels of visuospatial, memory, and frontal/executive function than PD[hyper] . However, greater PD[hyper] was associated with future dementia conversion (HR = 1.43, P = 0.004), whereas PD[hypo] was not associated. CONCLUSIONS: These findings suggest that PD[hypo] and PD[hyper] may differentially affect motor and cognitive functions in patients with PD. © 2023 International Parkinson and Movement Disorder Society.