This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

This study aimed to investigate differences in intrinsic prefrontal functional connectivity according to the presence of cognitive impairment in patients with end-stage renal disease (ESRD) using functional near-infrared spectroscopy (fNIRS). Methods: We prospectively enrolled 37 patients with ESRD who had been undergoing hemodialysis for more than 6 months and had no history of neurological or psychiatric disorders. All patients with ESRD underwent the Korean version of the Montreal Cognitive Assessment (MoCA-K) to assess cognitive function. The NIRSIT Lite device (OBELAB Inc.) was used to acquire fNIRS data, and the NIRSIT Lite Analysis Tool program was used to process the data and generate a functional connectivity matrix. We obtained functional connectivity measures by applying graph theory to the connectivity matrix using the BRAPH (brain analysis using graph theory) program. Results: Of the 37 patients with ESRD, 23 had cognitive impairment, whereas 14 patients showed no cognitive impairment. Intrinsic prefrontal functional connectivity was significantly different between groups. Network measures of strength, global efficiency, and mean clustering coefficient were lower in ESRD patients with cognitive impairment than in those without cognitive impairment (4.458 vs. 5.129, p = 0.02; 0.397 vs. 0.437, p = 0.03; and 0.316 vs. 0.421, p = 0.003; respectively). There were no significant correlations between MoCA-K scores and clinical characteristics. Conclusion: We demonstrated a significant association between cognitive function and intrinsic prefrontal functional connectivity in patients with ESRD. ESRD patients with cognitive impairment have reduced connectivity and segregation in the prefrontal brain network compared to those without cognitive impairment.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background/Aims: The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. Methods: A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. Results: After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCAresponse rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41(n=97). The area under the receiver operating characteristic curve of URS in predicting UDCAresponse was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed accordingto the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). Conclusions URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Objective: We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on intra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. Methods: MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, resting-state functional magnetic resonance imaging scans, positron emission tomography scans with [18 F]flutemetamol, and bioelectrical impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network. Results: There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circumference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. Conclusion The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fat-related body composition measurements and FC in the MCI patients with Aβ accumulation.

Objective: We aimed to evaluate the impact of interaction between APOE ε4 carrier status and body composition measurements on intra- and inter-regional functional connectivity (FC) in mild cognitive impairment (MCI) patients with Aβ deposition. Methods: MCI patients with and without APOE ε4 allele (carrier, n=86; non-carrier, n=95) underwent neuropsychological battery, resting-state functional magnetic resonance imaging scans, positron emission tomography scans with [ 18 F] flutemetamol, and bioelectri-cal impedance analysis for measuring body composition. We employed a priori defined regions of interest to investigate the intra- and inter-network FC profiles of default mode network (DMN), central executive network (CEN), and salience network (SN). Results: There was a significant interaction of APOE ε4 carrier status with body fat mass index, visceral fat area, and waist-hip circumference ratio for inter-network FC between DMN and CEN, contributing higher fat-related body composition measurements in the APOE ε4 carrier with lower DMN-CEN FC. Conclusion The present results highlight the detrimental effect of APOE ε4 carrier status on the associations between the fatrelated body composition measurements and FC in the MCI patients with Aβ accumulation.