Cost-effective endoscopic screening for gastric cancer in a cohort with low Helicobacter pylori prevalence.

BACKGROUND AND AIM: Periodic endoscopic screening for gastric cancer (GC) is widely performed in East Asia; however, the optimal screening strategy remains unclear. This study aimed to determine the most cost-effective endoscopic screening strategy for the detection and treatment of GC in a cohort with a low Helicobacter pylori prevalence. METHODS: The following data were retrospectively extracted from participants who received screening endoscopy between April 2019 and March 2023: age, H. pylori infection status, presence of intestinal metaplasia, pathological diagnosis of GC, and the interval between the most recent endoscopies. A Markov state transition model was constructed based on the cohort data. The cost-effectiveness of 15 strategies with different starting ages (40/50/60 years) and screening intervals (1/2/3/4/5 years) was compared. The net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) of quality-adjusted life-years gained by treatment were used as outcomes. RESULTS: A simulation model was constructed based on the cohort data of 94 137 participants (mean age 54.5 years, males 57.9%; 74.4% H. pylori-naïve, 94.2% intestinal metaplasia-negative). The results of the base-case analysis showed that the screening strategy of 4-year intervals starting at the age of 40 years had the highest NMB (97 401 578 yen). In both the Monte Carlo simulation and one-way sensitivity analysis with a varying probability of H. pylori infection status transition, the ICER was superior in the screening strategy every 4 years, starting at age 40 years. CONCLUSIONS: Our simulation showed that endoscopic screening at 4-year intervals starting at the age of 40 years was the most cost-effective method.

Prognostic Impact of the Ratio of Hemoglobin to Red Blood Cell Distribution Width in Patients after Acute Decompensated Heart Failure.

Objective The ratio of hemoglobin to red blood cell distribution width (Hb/RDW) is a simple and readily available tool associated with adverse outcomes in chronic heart failure (HF). However, the association between the Hb/RDW ratio and mortality in patients with acute decompensated HF (ADHF) is unclear. The goal of this study was to investigate the relationship between the Hb/RDW ratio and mortality in patients after ADHF. Methods This single-center study included clinical and laboratory data collected at baseline, with patients prospectively followed-up for a median period of 3.1 years. The patients were divided into two groups based on their median Hb/RDW ratio. Patients We evaluated 250 consecutive patients hospitalized for ADHF at Shinshu University Hospital between July 2014 and March 2019. Results In our study cohort (median age, 76 [66-83] years; 62.8 % male), all-cause death was observed in 91 patients (incidence rate: 12.7 per 100 patient-years). A Kaplan-Meier analysis revealed that patients in the lower Hb/RDW ratio group (<0.24, n=131) had worse outcomes compared to those in the higher group (≥0.24, n=119) (cumulative incidence 44.1% vs. 19.5%, respectively; log-rank, P <0.001). After adjusting for demographics, HF severity, and laboratory biomarkers, a lower Hb/RDW ratio was significantly associated with a higher risk of mortality (hazard ratio, 1.89; 95% confidence interval, 1.04-3.45; P = 0.038). Conclusion A lower Hb/RDW ratio is associated with an increased risk of mortality in patients after ADHF, thus indicating its potential utility in identifying patients at an elevated risk for future cardiovascular events.

Endoscopist's Satisfaction with the Insertion Phase of Colonoscopy Is a Potential Quality Indicator for Colorectal Polyp Detection: A Propensity Score Matching Study.

Quality indicators during the insertion phase of colonoscopy require exploration. Unsatisfactory insertion experiences cause endoscopist psychophysiological fatigue and affect the quality of their inspection. This comparative study used propensity score matching (PSM) to determine whether endoscopist satisfaction during scope insertion was related to polyp detection rate (PDR). Patients who underwent colonoscopy screening between April 2019 and December 2022 were enrolled in this study. The endoscopist satisfaction score (high and low) during the insertion phase in each examination was recorded based on the level of fatigue and presence of paradoxical scope movement. All examinations were classified into 2 groups: a high and a low satisfaction score group. After PSM with potential confounding factors related to polyp detection (endoscopist, insertion and withdrawal time, and sedative agent use), the PDR and adenoma detection rate (ADR) were compared. Overall, 4142 patients (average age, 54.1 years old; 54.4% male) underwent colonoscopies performed by twelve experienced endoscopists. Analysis using a logistic regression model revealed that a high satisfaction score during the insertion phase was an independent predictor of polyp detection (P < .001, odds ratio 1.79, 95% CI 1.41-2.33), whereas insertion time was not. After PSM, 513 patients from both groups were eligible for comparison. Polyp detection rate and ADR were significantly higher in the high-satisfaction group than in the low-satisfaction group (49.5% vs. 36.6%, P < .001; 35.1% vs. 27.1%, P = .007). The endoscopists' level of satisfaction with the insertion phase was shown to be a potential predictor of PDR in screening colonoscopy.

A novel predictive score model for successful weaning from mechanical circulatory support in patients with cardiogenic shock.

BACKGROUND: Clinical evidence regarding predictors of successful weaning from mechanical circulatory support (MCS) is lacking. This study aimed to create a simple risk score to predict successful weaning from MCS in patients with cardiogenic shock. METHODS: This retrospective single-center cohort study included 114 consecutive patients with cardiogenic shock treated with veno-arterial extracorporeal membrane oxygenation or IMPELLA between January 2013 and June 2023. Patients with out-of-hospital cardiac arrest were excluded. The primary endpoint was successful weaning from MCS defined as successful decannulation without the need for MCS re-implantation and survival to discharge. Multivariable logistic regression with a stepwise variable selection was performed to generate the prediction model. We first developed a general weaning score model, and then created a simple version of the score model using the same variables. RESULTS: Fifty-five patients were successfully weaned from MCS. The following variables measured during weaning evaluation were selected as the components of the weaning score model: acute myocardial infarction (AMI), mean blood pressure, left ventricular ejection fraction (LVEF), lactate level, and QRS duration. According to the results, we conducted a novel weaning score model to predict successful weaning from MCS: 1.774-2.090×(AMI)+0.062×[mean blood pressure (mmHg)]+0.139×[LVEF (%)]-0.322×[Lactate (mg/dl)]-0.066×[QRS (msec)]. The following variables were selected as the components of the simple version of the weaning score model: AMI, mean blood pressure ≥80 mmHg, lactate <10 mg/dL, QRS duration ≤95 msec, and LVEF >35%. CONCLUSIONS: We developed a simple model to predict successful weaning from MCS in patients with cardiogenic shock.

Treatment time limit for successful weaning from veno-arterial extracorporeal membrane oxygenation in cardiogenic shock.

AIMS: Knowing the upper time limit for successful weaning from temporary mechanical circulatory support in cardiogenic shock will help with decision-making regarding advanced heart failure (HF) therapy or considering withdrawal of care. The aim of this study was to investigate the association between the support duration and successful weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock. METHODS AND RESULTS: A retrospective single-centre cohort study was conducted between January 2013 and June 2023. It included 100 consecutive patients with cardiogenic shock who were treated with VA-ECMO. Patients with out-of-hospital cardiac arrest were excluded. The primary outcome was successful weaning from VA-ECMO (i.e., VA-ECMO decannulation and survival to discharge). The association between the length of support duration and the weaning success rate was analysed. Patients were divided into three groups according to ECMO support duration: Group A (≤7 days), Group B (8-14 days), and Group C (≥15 days). Multivariable logistic regression analysis was used to evaluate the impact of the length of support duration on successful weaning of VA-ECMO. The median age was 67 years, and 73% of study participants were male. The underlying aetiologies of cardiogenic shock were as follows: acute myocardial infarction, 50; fulminant myocarditis, 19; cardiomyopathy, 15; valvular heart disease, 8; and other, 8. Seventy-five patients (75%) were attempted to wean VA-ECMO, and 67 moved on to decannulation. In total, 43 (43%) patients were successfully weaned from VA-ECMO. The median length of ECMO support duration was 8 [3-15] days. Compared with those who underwent successful ECMO decannulation, those who did not had a significantly longer support duration of VA-ECMO (5 [3-9] days vs. 12 [3-22] days, P = 0.004). The weaning success rate was significantly higher in patients with short support duration; 58% (29/50), 40% (10/25), 16% (4/25) in Groups A, B, and C, respectively (P = 0.002). Overall, none of the patients supported for over 24 days (0/11) were successfully weaned from VA-ECMO. On multivariable logistic regression analysis, the length of support duration was independently associated with successful weaning after adjusting for age, sex, underlying aetiology, and left ventricular ejection fraction (odds ratio, 0.813 [per 3 days]; 95% confidence interval, 0.679-0.914; P = 0.025). CONCLUSIONS: Long support duration of VA-ECMO was significantly associated with a low rate of successful weaning in patients with cardiogenic shock. Patients who require VA-ECMO for over 1 week should start considering advanced HF therapy or withdrawal of care.

Association of blood group O with a recurrent risk for acute lower gastrointestinal bleeding from a multicenter cohort study.

The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04-1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04-1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

BACKGROUND: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). METHODS: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. RESULTS: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%. CONCLUSIONS: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage.

Sessile serrated lesion prevalence and factors associated with their detection: a post-hoc analysis of a multinational randomized controlled trial from Asia.

BACKGROUND: Sessile serrated lesions (SSLs) are associated with an increased risk of colorectal cancer. Data on the prevalence of SSLs in Asia are limited. We performed this study to estimate the prevalence of SSLs in Asia and to explore endoscopic factors that are associated with SSL detection. METHODS: This is a post-hoc analysis of a multicenter randomized controlled trial from four Asian countries/regions that compared adenoma detection rates using linked-color imaging (LCI) and white-light imaging. Colonoscopies were performed in an average-risk population for screening, diagnostic examination, or polyp surveillance. Patients with SSLs were compared against those without SSLs to evaluate for possible predictors of SSL detection using Firth's logistic regression. RESULTS: 2898 participants (mean age 64.5 years) were included in the analysis. The estimated prevalence of SSLs was 4.0% (95%CI 3.4%-4.8%), with no sex or age group differences. On multivariable analysis, use of LCI (adjusted odds ratio [aOR] 1.63, 95%CI 1.10-2.41), experienced endoscopists (aOR 1.94, 95%CI 1.25-3.00), use of transparent cap (aOR 1.75, 95%CI 1.09-2.81), and longer withdrawal time (aOR 1.06, 95%CI 1.03-1.10) were independently associated with SSL detection. Synchronous adenoma detection (aOR 1.89, 95%CI 1.20-2.99) was also predictive of SSL detection. CONCLUSION: The prevalence of SSLs in Asia is 4.0%. Use of LCI or a transparent cap, greater endoscopist experience, and longer withdrawal time were all associated with increased SSL detection.

Linked color imaging improves colorectal lesion detection especially for low performance endoscopists: An international trial in Asia.

BACKGROUND AND AIM: Linked color imaging (LCI) is an image-enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. METHODS: In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high-definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. RESULTS: We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥ 5000 colonoscopies) and by 43 non-experts (experience of < 5000 colonoscopies), respectively. Both expert and non-expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P < 0.001; non-expert, 56.6% vs 46.4%; P < 0.001). LCI had no effect on sessile serrated lesion detection rate in non-experts (3.1% vs 2.5%; P = 0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR < 50%. CONCLUSIONS: This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non-experts and is even more beneficial for endoscopists with relatively low detection performance using WLI.

Analysis of the Characteristics of Coexisting Lesions in Colorectal Cancer Patients in an International Study: A Subgroup Analysis of the ATLAS Trial.

INTRODUCTION: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. METHODS: We retrospectively reviewed 3,050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2,958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSLs], and SSLs with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). RESULTS: A multivariate analysis showed that HGA (odds ratio [95% confidence interval] 4.29 [2.16-8.18]; p < 0.01), LGAV (3.02 [1.16-7.83], p = 0.02), and age (1.04 [1.01-1.06], p = 0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94-16.0], p < 0.01) and HGA (4.46 [1.95-10.20], p < 0.01) in males and HGA (4.82 [1.47-15.80], p < 0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31-365.0], p = 0.03) was significant for right-sided CRC, and HGA (5.22 [2.39-11.4], p < 0.01) and LGAV (3.46 [1.13-10.6], p = 0.02) were significant for left-sided CRC. CONCLUSIONS: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting.

Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB biogenesis.

Daily Diet and Nutrition Risk Factors for Gastric Cancer Incidence in a Japanese Population.

Background/Aims: : Nutritional factors associated with gastric cancer (GC) are not completely understood. We aimed to determine the effect of nutrient intake on the incidence of GC. Methods: : This was a post hoc analysis of a prospective trial that evaluated modalities for GC screening in participants aged 30 to 74 years living in high-risk areas for GC in Japan between June 2011 and March 2013. The patients were followed up for GC incidence for 6 years. All participants completed a self-administered food frequency questionnaire (FFQ) upon enrollment before GC screening. Daily nutrient intake was calculated from the FFQ and dichotomized at each cutoff value using receiver operating characteristic analysis. Risk factors associated with GC incidence were investigated in terms of nutrient intake and participant characteristics using Cox proportional hazards regression analysis. Results: : Overall, 1,147 participants were included in this analysis. The median age was 62 years, and 50.7% of the participants were men. The median follow-up period was 2,184 days. GC was detected in 25 participants during the follow-up. Multivariate Cox proportional hazards regression analysis revealed that the intake of sodium (adjusted hazards ratio [aHR], 3.905; 95% confidence interval [CI], 1.520 to 10.035; p=0.005) and vitamin D (aHR, 2.747; 95% CI, 1.111 to 6.788, p=0.029) were positively associated with GC incidence, whereas the intake of soluble dietary fiber (aHR, 0.104; 95% CI, 0.012 to 0.905; p=0.040) was inversely associated with GC incidence. Conclusions: : Daily high intake of sodium and vitamin D and low soluble dietary fiber intake are associated with GC incidence.

Cost-effectiveness analysis of single colonoscopy versus single fecal test for colorectal cancer diagnosis and treatment.

BACKGROUND AND AIM: Regular endoscopy or fecal immunochemical test (FIT) is ideal for screening colorectal cancer. However, only a limited number of individuals undergo regular screening. This study aimed to compare the cost-effectiveness of a single colonoscopy with a single FIT performed for colorectal cancer screening. METHODS: A microsimulation model was constructed based on real-world observational data collected from three institutions between 2019 and 2022 that compared colonoscopy-based screening with FIT-based screening. The total costs of diagnosis and treatment of the detected lesions using the two strategies were calculated. The incremental cost-effectiveness ratio (ICER) per life year gained (LYG) of the colonoscopy-based strategy was calculated. RESULTS: Data from 11 407 patients undergoing colonoscopies and 59 176 patients undergoing FITs were used to establish a model. In the base case analysis of screening strategies, colonoscopy was more cost-effective than FIT (ICER 415 193 yen/LYG). The ICER of the colonoscopy-based strategy among 60- to 69-year-old patients was lowest at 394 200 yen/LYG, whereas that in 20- to 29-year-old patients was highest. Monte Carlo simulations showed that the colonoscopy-based strategy was more cost-effective than the FIT-based strategy (net monetary benefit [NMB]: 5 695 957 yen vs 5 348 253 yen). When the adenoma detection rate in the colonoscopy was over 30% or the positive FIT rate was lower than 8.6% in the FIT-based strategy, the NMB of the colonoscopy-based strategy exceeded that of the FIT-based strategy. CONCLUSION: In the microsimulation model, colonoscopy is recommended as a one-time screening procedure in patients aged >60 years with >30% ADR or <8.6% positive FIT rate.

Diagnostic performance of deep-learning-based virtual chromoendoscopy in gastric neoplasms.

BACKGROUNDS: Cycle-consistent generative adversarial network (CycleGAN) is a deep neural network model that performs image-to-image translations. We generated virtual indigo carmine (IC) chromoendoscopy images of gastric neoplasms using CycleGAN and compared their diagnostic performance with that of white light endoscopy (WLE). METHODS: WLE and IC images of 176 patients with gastric neoplasms who underwent endoscopic resection were obtained. We used 1,633 images (911 WLE and 722 IC) of 146 cases in the training dataset to develop virtual IC images using CycleGAN. The remaining 30 WLE images were translated into 30 virtual IC images using the trained CycleGAN and used for validation. The lesion borders were evaluated by 118 endoscopists from 22 institutions using the 60 paired virtual IC and WLE images. The lesion area concordance rate and successful whole-lesion diagnosis were compared. RESULTS: The lesion area concordance rate based on the pathological diagnosis in virtual IC was lower than in WLE (44.1% vs. 48.5%, p < 0.01). The successful whole-lesion diagnosis was higher in the virtual IC than in WLE images; however, the difference was insignificant (28.2% vs. 26.4%, p = 0.11). Conversely, subgroup analyses revealed a significantly higher diagnosis in virtual IC than in WLE for depressed morphology (41.9% vs. 36.9%, p = 0.02), differentiated histology (27.6% vs. 24.8%, p = 0.02), smaller lesion size (42.3% vs. 38.3%, p = 0.01), and assessed by expert endoscopists (27.3% vs. 23.6%, p = 0.03). CONCLUSIONS: The diagnostic ability of virtual IC was higher for some lesions, but not completely superior to that of WLE. Adjustments are required to improve the imaging system's performance.

Gastric cancer detection rates using GI endoscopy with serologic risk stratification: a randomized controlled trial.

BACKGROUND AND AIMS: Efforts have been made to develop an endoscopic screening system incorporating serologic gastric cancer (GC) risk stratification (ABC classification) alongside annual population-based GC screening using barium. We conducted a randomized controlled trial (RCT) to compare GC detection rates between the Ba-Endo group, which underwent annual barium tests for primary screening followed by detailed endoscopic examinations, and the ABC-Endo group, where endoscopy intervals were determined based on individual gastric cancer risk in the ABC classification. METHODS: In total, 1206 individuals from Yurihonjo and Nikaho City, Akita Prefecture, were randomized through the minimization method using sex and age as allocation factors. The intervention study was conducted for both groups over 5 years. The Ba-Endo group received annual barium tests, and the ABC-Endo group underwent EGD at different intervals: group A, EGD only at entry; group B, EGD once every 3 years; group C, EGD once every 2 years; and group D, EGD every year. RESULTS: There were 24 detected GC lesions, with a GC detection rate of 1.9%. GC detection rates in the Ba-Endo and ABC-Endo groups were 2.0% and 1.8%, respectively, with no significant differences between groups (P = 1.0). However, the rate of GC cured by endoscopic resection alone was 41.6% in the Ba-Endo group and was significantly higher at 90.9% in the ABC-Endo group (P = .02). CONCLUSIONS: There were no differences between the Ba-Endo and ABC-Endo groups in GC detection rates. However, the rate of detected GCs that could be cured by endoscopic resection alone was significantly higher in the ABC-Endo group. (Clinical trial registration number: UMIN000005962.).

The inter-laboratory validation study of EpiSensA for predicting skin sensitization potential.

The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within- (WLR) and between-laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non-sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.

Reconstructed human epidermis-based testing strategy of skin sensitization potential and potency classification using epidermal sensitization assay and in silico data.

The hazards and potency of skin sensitizers are traditionally determined using animal tests such as the local lymph node assay (LLNA); however, significant progress has been made in the development of non-animal test methods addressing the first three mechanistic key events of adverse outcome pathway in skin sensitization. We developed the epidermal sensitization assay (EpiSensA), which is a reconstructed human epidermis-based assay, by measuring four genes related to critical keratinocyte responses during skin sensitization. Four in vitro skin sensitization test methods (EpiSensA, direct peptide reactivity assay [DPRA], KeratinoSens™, and human cell line activation test [h-CLAT]) were systematically evaluated using 136 chemicals including lipophilic chemicals and pre/pro-haptens, which may be related to assay-specific limitations. The constructed database included existing and newly generated data. The EpiSensA showed a broader applicability domain and predicted the hazards with 82.4% and 78.8% accuracy than LLNA and human data. The EpiSensA could detect 76 out of 88 sensitizers at lower concentrations than the LLNA, indicating that the EpiSensA has higher sensitivity for the detection of minor sensitizing constituents. These results confirmed the potential use of the EpiSensA in evaluating a mixture of unknown compositions that can be evaluated by animal tests. To combine different information sources, the reconstructed human epidermis-based testing strategy (RTS) was developed based on weighted multiple information from the EpiSensA and TImes MEtabolism Simulator platform for predicting Skin Sensitization (TIMES-SS; RTSv1) or Organization for Economic Cooperation and Development (OECD) QSAR Toolbox automated workflow (RTSv2). The predictivities of the hazards and Globally Harmonized System (GHS) subcategories were equal to or better than the defined approaches (2 out of 3, integrated testing strategy [ITS]v1, and ITSv2) adopted as OECD Guideline 497.

An algorithm-based active cleansing protocol can reduce the bowel preparation time for screening colonoscopy: A propensity score matching study.

BACKGROUND: Methods that minimize the time for on-site bowel preparation before colonoscopy are needed. We prospectively validated that a novel algorithm-based active cleansing (ABAC) protocol could reduce the time for preparation compared with the conventional method. METHODS: This was an open-label, multicenter, prospective comparative study from April to October 2021. The study compared the bowel preparation time for colonoscopy between patients instructed with the ABAC protocol and control groups. Patients in the ABAC protocol group as well as the control group were administered 2000 mL of polyethylene glycol (PEG) within 2 hours. After the first two hours, patients in the protocol group voluntarily took 300 ml of the solution without the instruction of nursing staff depending on the number of defecations in the first 2 hours. The intervention and control groups were adjusted for background characteristics by propensity score matching (PSM). RESULTS: After adjustment by PSM, 174 patients in each of the two groups were included in the final analysis. In the intention-to-treat analysis, the preparation time was significantly shorter in the intervention group than that in the control group (126.3 ± 32.7 min vs. 144.9 ± 39.9 min, P = 0.018). The proportion of additional PEG intake was significantly higher in the intervention group (16 [9.2%] vs. 6 [3.4%], P = 0.047). The number of defecations was also higher in the intervention group than in the control group (7.8 ± 2.5 vs. 6.3 ± 2.2, P = 0.001). CONCLUSIONS: Simple active instruction protocol is effective to reduce on-site bowel preparation time and nursing staff labor for colonoscopy.