Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

Purpose: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Materials and Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). Conclusion The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Objective: We developed the Indoor Cognitive Training combined with Physical Activity (ICT-PA) program, incorporating memory registration, navigation, and image recall through wearable sensors and Bluetooth Low Energy tags, aimed at enhancing cognitive function and physical activity in elderly individuals with mild cognitive impairment (MCI). Methods: Thirty-six elderly individuals over 60 years diagnosed with MCI participated in a 6-week ICT-PA program. The primary outcome measure was the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery Total Score 1 (CERAD-TS1), and the secondary outcome measures were the Mini-Mental State Examination (MMSE), Subjective Memory Complaints Questionnaire (SMCQ), and Korean version of the Geriatric Depression Scale (GDS-KR). Changes in scores before and after the program were analyzed using paired t-tests. Program satisfaction was evaluated using a 5-point Likert scale. Results: CERAD-TS1 scores significantly improved after ICT-PA training (pre 57.3±11.3; post 60.3±13.1; p=0.006), while MMSE, SMCQ and GDS-KR scores remained unchanged. Subgroup analysis showed significant CERAD-TS improvements in the compliance group (>360 minutes of ICT-PA use) (pre 58.5±11.7; post 62.7±12.9; p=0.002). The average program satisfaction score was 7.7±1.6 out of 10. Data are presented as mean±standard deviation. Conclusion The ICT-PA program effectively improved cognitive functions in MCI patients, with high satisfaction rates.

Purpose: The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). Materials and Methods: In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. Results: Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Purpose: The patient perception of study medication (PPSM) questionnaire consists of 12 questions designed to quantify patient satisfaction with the efficacy of study treatment by focusing on specific changes that patients experience during the study period. This study aimed to develop a Korean version of the PPSM questionnaire. Methods: The linguistic validation process consisted of obtaining permission for translation, forward translation, reconciliation, backward translation, cognitive debriefing, and proofreading. Two independent bilingual translators translated the original version of the questionnaire, and a panel discussed and combined the 2 versions. Another independent translator performed backward translation of the reconciled version, after which 15 patients underwent the cognitive debriefing. Results: The 12 questions and 4 response scales of the PPSM questionnaire were forward translated into 2 Korean versions. The terms were adjusted to conceptually equivalent expressions in Korean. After backward translation, the panel made minor changes to the forward translations for brevity and better readability. No difficulties were experienced during cognitive debriefing by 15 patients, and all items were reported to be generally easy to understand. Conclusions The Korean version of the PPSM questionnaire has been successfully translated and validated. The questionnaire is appropriate for assessing symptom satisfaction in patients that undergo benign prostatic hyperplasia pharmacotherapy.

Purpose: We investigated the clinicopathological features and management for superficial nonampullary duodenal tumors (SNADTs). The safety and feasibility of laparoscopic management, especially laparoscopic endoscopic cooperative surgery (LECS), were evaluated. Methods: A total of 59 patients with SNADTs who underwent operations from January 2009 to December 2018 at all 8 institutions of the Catholic Medical Center were identified in our comprehensive multi-institutional database. Clinicopathological and surgical data on the 4 anatomical regions of the duodenum were collected and compared.Characteristics of laparoscopic procedure (laparoscopy-only) and LECS procedures were also compared. Results: There were significantly more asymptomatic patients with tumors in the first and second vs. third and fourth duodenal regions. Gastrointestinal stromal tumors (GISTs), carcinoids, and ectopic pancreatic tumors were identified in 32, 12, and 5 cases, respectively. Forty-two patients (71.2%) underwent laparoscopy. Of patients undergoing laparoscopy, the LECS group exhibited significantly more endophytic features and smaller tumor sizes (P < 0.001 and P < 0.001, respectively). Although no significant difference in the wedge resection or postoperative complication rate was seen between the 2 groups (P = 0.096 and P = 0.227, respectively), the wedge resection rate was higher, and the complication rate lower, in the LECS group than the conventional laparoscopic surgery group. Conclusion Most of the SNADTs located in proximal duodenum were detected incidentally. GISTs were the most common diagnoses of SNADTs in all locations. In treating these tumors, laparoscopic resection is safe and feasible. Especially, LECS may be ideal for treating small endophytic tumors, minimizing over-resection and postoperative complications.

Purpose: We investigated the role of prostate-specific antigen (PSA) variation as a predictor of prostate cancer in patients who underwent prebiopsy multiparametric magnetic resonance imaging (MRI). Materials and Methods: The clinicopathological data of 266 patients with PSA ≤20 ng/mL who underwent prebiopsy MRI and prostate biopsy between September 2019 and February 2021 were included. PSA variation was defined as the difference in PSA values taken when a prostate biopsy was recommended and performed (median 20 days). Receiver operating characteristic (ROC) curves and area under the ROC curves (AUCs) for predicting prostate cancer were analyzed through 4 models that considered conventional clinical variables and PSA variation. Results: Of the 258 patients, 166 (64.3%) were diagnosed with prostate cancer. The prostate cancer (+) group had a lower median PSA variation (-0.09 mg/mL vs. -0.27 ng/mL, p=0.006) and higher proportion of patients with PSA variation within -0.54 to 0.05 ng/mL (40 ng/mL [range, 24.1%] vs. 9 ng/mL [9.8%], p=0.002) than the prostate cancer (-) group. There was no significant difference in the duration between the 2 PSA measurements. When PSA variation and conventional variables, such as age, PSA density, prostate biopsy history, number of target lesions, were considered, the highest AUC value was 0.870. In a subgroup analysis of patients with PSA ≤10 ng/mL, the highest AUC value was 0.860 when PSA variation and conventional variables were considered. Conclusions A large PSA variation within 1 month was a negative predictor of prostate cancer among patients who underwent prebiopsy MRI.