Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock.

Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKIδ-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKIδ-ATP complex and higher product affinity to CKIδ-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKIδ identified aurintricarboxylic acid (ATA) as a temperature-sensitive kinase activator. Docking simulation of ATA and mutagenesis experiment revealed K224D/K224E mutations in CKIδ that impaired product binding and temperature-compensated primed phosphorylation. Importantly, K224D mutation shortens behavioral circadian rhythms and changes the temperature dependency of SCN's circadian period. Interestingly, temperature-compensated phosphorylation was evolutionary conserved in yeast. Molecular dynamics simulation and X-ray crystallography demonstrate that an evolutionally conserved CKI-specific domain around K224 can provide a structural basis for temperature-sensitive substrate and product binding. Surprisingly, this domain can confer temperature compensation on a temperature-sensitive TTBK1. These findings suggest the temperature-sensitive substrate- and product-binding mechanisms underlie temperature compensation.

Risk of map-like redness development after eradication therapy for Helicobacter pylori infection.

BACKGROUND: Map-like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map-like redness in patients who received eradication, and the risk factors for the development of map-like redness remain unclear. We hence aimed to investigate the incidence rate of map-like redness at 1-year post H. pylori eradication, and evaluated its associations with map-like redness and gastric cancer in relation with gastric condition. MATERIALS AND METHODS: Endoscopic severity of gastritis and map-like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy. RESULTS: The incidence rate of map-like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%-30.4%). Patients who developed map-like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map-like redness. On multivariate analysis, risk of map-like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155-6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070-3.547). Characteristics of H. pylori-positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001-1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340-8.484), and with occurrence of map-like redness after eradication therapy (OR: 2.432, 95% CI: 1.264-4.679). CONCLUSIONS: Map-like redness is observed in one fourth of patients at 1-year post eradication. Patients who developed map-like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.

Endoscopic program with a scoring system for surveillance of metachronous esophageal cell carcinoma for older patients considering risk factors after endoscopic resection.

BACKGROUND: This study evaluated the association between the risk factors and prognosis for metachronous esophageal squamous cell carcinoma (ESCC) after endoscopic resection (ER) of esophageal cancer in older patients. METHODS: We conducted a retrospective observational study of 127 patients with ESCC who underwent ER from 2015 to 2020. Patients were classified as non-older (≤ 64 years), early older (65-74 years), and late older (≥ 75 years). We analyzed factors associated with poor overall survival and metachronous ESCC after ER using multivariate Cox regression analysis. A metachronous ESCC prediction scoring system was examined to validate the surveillance endoscopy program. RESULTS: Body mass index (BMI) and Charlson Comorbidity Index (CCI) were significant risk factors for poor overall survival in the multivariate analysis (p = 0.050 and p = 0.037, respectively). Multivariate analysis revealed that age of < 64 years, Lugol-voiding lesions (grade B/C), and head and neck cancer were significantly related to metachronous ESCC (p = 0.035, p = 0.035, and p = 0.014, respectively). In the development cohort, BMI < 18.5 kg/m2, CCI > 2, age < 64 years, Lugol-voiding lesions (grade B/C), and head and neck cancer were significantly related to metachronous ESCC, and each case was assigned 1 point. Patients were classified into low (0, 1, and 2) and high (> 3) score groups based on total scores. According to Kaplan-Meier curves, the 3-year overall survival was significantly lower in the high-score group than in the low-score group (91.5% vs. 100%, p = 0.012). CONCLUSIONS: We proposed an endoscopic surveillance scoring system for metachronous ESCC considering BMI and CCI in older patients.

Underwater endoscopic submucosal dissection for colorectal tumors decreases the incidence of post-electrocoagulation syndrome.

BACKGROUND AND AIMS: Underwater endoscopic submucosal dissection (U-ESD) is a recently developed procedure that has the potential to prevent post-ESD coagulation syndrome (PECS) owing to its heat-sink effect. We aimed to clarify whether U-ESD decreases the incidence of PECS compared with conventional ESD (C-ESD). METHODS: A total of 205 patients who underwent colorectal ESD (C-ESD: 125; U-ESD: 80) were analyzed. Propensity score matching analysis was performed to adjust for patient backgrounds. Ten C-ESD and two U-ESD patients with muscle damage or perforation during ESD were excluded when comparing PECS. The primary outcome was to compare the incidence of PECS between the U-ESD and C-ESD groups (54 matched pairs). Secondary outcomes were to compare procedural outcomes between the C-ESD and U-ESD groups (62 matched pairs). RESULTS: Among the 78 patients who underwent U-ESD, PECS occurred in only one patient (1.3%). Adjusted comparisons between the U-ESD and C-ESD groups demonstrated a significantly lower incidence of PECS in the U-ESD group (0% vs 11.1%; P = 0.027). Median dissection speed was significantly faster in the U-ESD than in the C-ESD group (10.9 mm2 /min vs 6.9 mm2 /min; P < 0.001). En bloc and complete resection rates were 100% in the U-ESD group. Although perforation and delayed bleeding occurred in one patient each (1.6%) as adverse events in the U-ESD group, there were no differences compared with the C-ESD group. CONCLUSIONS: Our study demonstrates that U-ESD effectively decreases the incidence of PECS and is a faster and safer method for colorectal ESD.

Targeted Metabolomic Profiling of Plasma Samples in Gastric Cancer by Liquid Chromatography-Mass Spectrometry.

INTRODUCTION: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. METHODS: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. RESULTS: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865-0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797-0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. CONCLUSION: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.

Factors associated with long-term efficacy of lubiprostone for chronic constipation.

The prevalence of chronic constipation in Japan is increasing, and is presently almost 1 in 5 people. Because constipation is common, especially in older patients, to avoid adverse events and polypharmacy, simple treatments at low doses are generally desired. Although the chloride channel activator lubiprostone is candidate drug that may solve these problems, factors associated with the long-term efficacy of lubiprostone monotherapy for chronic constipation in treatment-naive patients remain unclear. We here retrospectively investigated the clinical characteristics and factors of patients who achieved long-term constipation improvement with lubiprostone monotherapy. Seventy-four patients with chronic constipation treated with lubiprostone monotherapy (24 or 48 µg/day) from January 2017 to August 2018 were reviewed. Patient characteristics and clinical time-courses were compared between those who sustained improvement for 6 months, and those who became refractory to treatment. In 54 patients (76.1%), constipation improved by lubiprostone administration for 6 months. On multivariate analysis, a significant clinical factor associated with sustained improvement was a starting lubiprostone dose of 24 µg/day (odds ratio: 5.791; 95% confidence interval: 1.032-32.498; p = 0.046). A starting lubiprostone dose of 24 µg/day has efficacy to improve chronic constipation and to prevent adverse events of nausea and diarrhea in Japanese patients.

New scoring system to distinguish deep invasive submucosal and muscularis propria colorectal cancer during colonoscopy: a development and global multicenter external validation study (e-T2 Score).

BACKGROUND AND AIMS: Diagnostics to differentiate deep submucosal invasive (invasion depth ≥1000 µm [T1b]) colorectal cancer (CRC) from muscularis propria invasive (T2) CRC are limited. We aimed to establish and validate a scoring system that differentiates T1b from T2. METHODS: A multicenter retrospective cross-validation study was performed. Four hundred sixty-one consecutive pathologically confirmed T1b or T2 CRCs were divided into the development (T1b, 222; T2, 189) and internal validation (T1b, 31; T2, 19) cohorts. Eight potential endoscopic findings were evaluated using the development cohort: loss of lobulation, deep depression, demarcated depressed area, protuberance within the depression, expanding appearance, fold convergency, erosion or white plaque, and Borrmann type 2 or 3 tumor. A scoring system that differentiates T1b from T2 was developed, and diagnostic performance was tested using the internal validation cohort by 8 endoscopists. External validation was conducted using 50 CRC images by 4 endoscopists from other institutions, including outside of Japan. RESULTS: Multivariate analysis identified the following 5 independent predictive endoscopic findings of T2 CRC: deep depression (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.07-4.04), demarcated depressed area (OR, 4.40; 95% CI, 1.39-13.9), 4-fold convergency or more (OR, 3.41; 95% CI, 1.90-6.11), erosion or white plaque (OR, 8.28; 95% CI, 2.77-24.7), and Borrmann type 2 or 3 tumor (OR, 8.76; 95% CI, 3.58-21.5). The area under the receiver-operating characteristic curve (AUROC) was .90 (95% CI, .87-.93) in the development cohort, .80 (95% CI, .76-.85) in the internal validation, and .76 (95% CI, .69-.83) in the external validation. CONCLUSIONS: We established and validated a new scoring system to differentiate T1b from T2 CRC using 5 simple endoscopic findings.

Diagnostic efficacy of the Japan NBI Expert Team classification with dual-focus magnification for colorectal tumors.

BACKGROUND AND AIMS: The Japan NBI Expert Team (JNET) classification is the first unified classification criteria for colorectal tumors using magnifying narrow-band imaging (NBI) in Japan. However, the diagnostic stratification ability of the JNET classification with dual-focus magnifying NBI (DF-JNET) has remained obscure. The aim of this study was to validate the diagnostic stratification ability of DF-JNET for colorectal tumors in two Japanese referral centers. METHODS: A multicenter retrospective image evaluation study was conducted by three experienced endoscopists, including an original JNET member who was also involved in establishing the diagnostic criteria. A total of two images, namely, one representative non-magnified white light image and one representative DF-NBI image for each of the 557 consecutive lesions were used in the evaluation study. The diagnostic value of DF-JNET was calculated based on the evaluation data. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of DF-JNET Type 1 for differentiating between non-neoplastic and neoplastic lesions were 78.1%, 98.6%, 89.1%, 96.8%, and 95.9%, respectively; of Type 2A lesions for differentiating low-grade dysplasia from others were 98.0%, 76.5%, 94.9%, 89.7%, and 94.1%, respectively; of Type 2B lesions for differentiating high-grade dysplasia and shallow submucosal invasive carcinoma from others were 43.5%, 99.1%, 66.7%, 97.6%, and 96.8%, respectively; and of Type 3 lesions for differentiating deep submucosal invasive carcinoma from others were 83.3%, 99.5%, 62.5%, 99.8%, and 99.3%, respectively. CONCLUSIONS: All DF-JNET types had an over 90% diagnostic accuracy for the histological prediction of colorectal tumors. DF-JNET might contribute to appropriate treatment choices, such as endoscopic resection or surgery, not only in Japan but also in Western countries in which the use of optical zoom endoscopy is limited.

Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study.

BACKGROUND: A new scoring system, the BEST-J score, using ten risk factors to assign cases to different post-endoscopic submucosal dissection (ESD) risk groups for bleeding, has been shown to be accurate for risk stratification. We first aimed to validate the BEST-J score at four hospitals not specialized in performing ESD and then aimed to identify other risk factors for post-ESD bleeding. METHODS: We evaluated the incidence of post-ESD bleeding in 791 cases of early gastric cancer (EGC) between October 2013 and December 2020 as a retrospective, multi-center observational study conducted at four hospitals. Multivariate logistic regression models to examine the effect of independent variables on post-ESD bleeding firstly included ten possible factors raised by the BEST-J score and secondly included statistically significant (p < 0.01) in univariate analysis. The prediction accuracy of the model was evaluated by receiver-operating characteristic analysis and the areas under the curve (AUC). RESULTS: The incidence of post-ESD bleeding was 4.8% (38/791, 95% confidence interval [CI] 3.4-6.5%). On multivariate analysis, the risk factors were P2Y12 receptor antagonist (odds ratio [OR]: 5.870, 95% CI 1.624-21.219), warfarin (8.382, 1.658-42.322), direct oral anticoagulant (DOAC) (8.980, 1.603-50.322), and tumor location in lower third of stomach (2.151, 1.012-4.571), respectively. When we categorized cases into low-risk by BEST-J score, intermediate-risk, high-risk, and very high-risk groups, the bleeding rates were 2.8%, 7.3%, 12.8%, and 19.0%, respectively. The AUC for our cohort was 0.713 (95% CI 0.625-0.802) for the BEST-J score. In the multivariate analysis in our cohort, the risks were age, body mass index, P2Y12 receptor antagonist, warfarin, DOAC, respectively. DISCUSSION: The BEST-J score is equally accurate in risk stratification of patients with EGC for post-ESD bleeding at non-specialized facilities for ESD as in specialized hospitals. BMI and age may be helpful additional risk factors at hospitals not specialized.

Efficacy of endoscopic clip closure for nonperforated muscle layer exposure during esophageal endoscopic submucosal dissection.

Exposure of the muscle layer during endoscopic submucosal dissection (ESD) in the esophagus can lead to complications such as fever and pain. Although closure with endoscopic clips is widely used when perforation is a major complication, its value when the exposed muscle layer is not perforated is unclear. Data for 104 lesions in 104 patients who underwent esophageal ESD between 2008 and 2020 were retrospectively analyzed. Patients with multiple tumors, those who experienced procedure-related adverse events such as aspiration pneumonitis, perforation during ESD, or delayed bleeding, and those in whom the muscle layer was not exposed were excluded. The clinical course of inflammation after ESD in patients in whom the muscle layer was exposed was examined according to whether endoscopic clips were used for closure. A significantly greater number of patients had a temperature ≤ 37.5°C in the clip closure group than in the nonclip closure group (≤37.5°C/≥37.6°C, 47/14 vs. 25/18, respectively, P = 0.040). Furthermore, significantly more patients in the clip closure group had a white blood cell count ≤10,000/µL (≤10,000/µL/>10,000/µL, 51/10 vs. 21/22, P < 0.001) and a C-reactive protein level < 1.0 mg/dL (<1.0 mg/dL/≥1.0 mg/dL, 40/21 vs. 36/7, P = 0.040) in the 24 hour post-ESD. The results were not changed after propensity score matching. Closure with endoscopic clips reduces inflammation after esophageal ESD with nonperforated muscle layer exposure. Even if there is no obvious perforation during ESD, closure of the exposed muscle layer with endoscopic clips may contribute to the clinical course post-ESD.

Predictive Factors of Postendoscopic Submucosal Dissection Electrocoagulation Syndrome and the Utility of Computed Tomography Scan after Esophageal Endoscopic Submucosal Dissection.

BACKGROUND/AIMS: Recently, postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) has attracted attention. However, the criteria for computed tomography (CT) scanning following esophageal endoscopic submucosal dissection (ESD) are unclear. In this study, we aimed to identify the predictive factors of PEECS and the usefulness of CT scanning after esophageal ESD. METHODS: A total of 245 lesions in 223 patients who underwent esophageal ESD between February 2008 and October 2018 were retrospectively analyzed. Patients with double cancers, those who experienced procedural accidents, such as aspiration pneumonitis or perforation, and those who were unable to undergo CT were excluded from the study. PEECS evaluation items included body temperature (≤37.7°C = 1 point, ≥37.8°C = 2 points), white blood cell count (<10,800/µL = 1 point, ≥10,800/µL = 2 points), and chest pain (numerical rating scale [NRS] ≤4 = 1 point, NRS ≥5 = 2 points). Scores of ≥5 points were categorized as the PEECS-positive group, and scores of ≤4 points were categorized as the PEECS-negative group. The degree of mediastinal emphysema on CT was stratified into 5 grades, in which grades 0 and 1 were considered as the "low-grade" group, and grades 2, 3, and 4 were considered as the "high-grade" group. We analyzed the prognostic factors of high-grade mediastinal emphysema, including the presence or absence of PEECS. RESULTS: The PEECS-positive group comprised 18 out of the 163 patients (11.0%), and mediastinal emphysema was stratified into grades 0 (94), 1 (51), 2 (12), 3 (5), and 4 (1 patient). Three independent risk factors for the onset of PEECS were identified, as follows: resected area ≥750 mm2 (OR 7.28, 95% CI 1.42-37.33, p = 0.017), treatment duration ≥75 min (OR 10.26, 95% CI 1.20-87.77, p = 0.034), and muscle layer exposure (OR 10.92, 95% CI 2.22-53.74, p = 0.003). Two independent predictive factors of high-grade mediastinal emphysema were identified, which were PEECS positivity (OR 4.31, 95% CI 1.29-14.41, p = 0.018), and muscle layer exposure (OR 4.08, 95% CI 1.18-14.06, p = 0.026). CONCLUSIONS: A large resected area, prolonged treatment duration, and muscle layer exposure are risk factors for the onset of PEECS. Mediastinal emphysema was observed in 43% of patients following ESD. When marked clinical symptoms of PEECS appear, high-grade mediastinal emphysema may be observed, and therefore CT should be performed in these cases.

Rebleeding Risk of Acute Hemorrhagic Rectal Ulcer: A Multicenter Retrospective Study.

Objective Acute hemorrhagic rectal ulcer (AHRU) is characterized by sudden, painless, and massive bleeding from rectal ulcers. To date, few studies have analyzed the risk factors for AHRU rebleeding. In this study, we clarified the risk factors of rebleeding after initial hemostasis of AHRU through a multicenter study. Methods A total of 149 patients diagnosed with AHRU between January 2015 and May 2020 at 3 medical centers were enrolled. We retrospectively investigated the following factors: age, sex, body mass index (BMI), performance status (PS), Charlson Comorbidity Index (CCI), comorbidities, medications, laboratory examinations, endoscopic findings, view of the entire rectum on endoscopy, hemostasis method, blood transfusion history, shock, instructions for posture change after initial hemostasis, and clinical course. Results Rebleeding was observed in 35 (23%) of 149 patients. A multivariate analysis showed that significant factors for rebleeding were PS 4 [odds ratio (OR), 5.23; 95% confidence interval (CI), 1.97-13.9; p=0.001], a blood transfusion history (OR, 3.66; 95% CI, 1.41-9.51; p=0.008), low an estimated glomerular filtration rate (eGFR) levels (OR, 0.98; 95% CI, 0.97-0.99; p=0.001), poor view of the whole rectum on endoscopy (OR, 0.33; 95% CI, 0.12-0.90; p=0.030), and use of monopolar hemostatic forceps (OR, 4.89; 95% CI, 1.37-17.4; p=0.014). Conclusion Factors associated with rebleeding of AHRU were a poor PS (PS 4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Significance of rescue hybrid endoscopic submucosal dissection in difficult colorectal cases.

BACKGROUND/AIMS: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). METHODS: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. RESULTS: Resection time was significantly shorter in the following order: RH-ESD (149 [90-197] minutes) >C-ESD (90 [60-140] minutes) >SH-ESD (52 [29-80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%-30%]) than in the en bloc resection group (40% [20%-60%]). CONCLUSION: RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

Visibility of early gastric cancers by texture and color enhancement imaging using a high-definition ultrathin transnasal endoscope.

We evaluated whether texture and color enhancement imaging (TXI) using a high-definition ultrathin transnasal endoscope (UTE) improves the visibility of early gastric cancer (EGC) compared with white-light imaging (WLI). This study included 31 EGCs observed by TXI mode 2 using a high-definition UTE prior to endoscopic submucosal dissection. The first outcome was to compare the color differences based on Commission Internationale de l'Eclairage L*a*b* color space between EGCs and the surrounding mucosa by WLI and TXI using the UTE (objective appearance of EGC). The second outcome was to assess the visibility of EGCs by WLI and TXI using the UTE in an image evaluation test performed on 10 endoscopists (subjective appearance of EGC). Color differences between EGCs and non-neoplastic mucosa were significantly higher in TXI than in WLI in all EGCs (TXI: 16.0 ± 10.1 vs. WLI: 10.2 ± 5.5 [mean ± standard deviation], P < 0.001). Median visibility scores evaluated by 10 endoscopists using TXI were significantly higher than those evaluated using WLI (TXI: 4 [interquartile range, 4-4] vs. WLI: 4 [interquartile range, 3-4], P < 0.001). TXI using high-definition UTE improved both objective and subjective visibility of EGCs compared with WLI.

Long-term Follow-up of Affected Residents After Lifting Evacuation Orders in Fukushima Prefecture, Japan: Findings from an Interview-Based Psychological Survey.

We examined the relationship between social support and psychological variables, and investigated the status of social support among villagers whose evacuation order had been lifted. The survey used for the analysis is the data of FY 2018 and 2019. In fiscal year 2018, a written questionnaire was posted to 4828 registered residents of Iitate Village and 1405 valid responses were received. The main finding (in joint assessment by local and external experts) was the 'need for professional support' (191 respondents, 13.6%). Multivariate analysis found that among those living in permanent housing outside the village, the need for support was significantly more likely for those without emotional support, or instrumental support, and those not providing support. The 2019 follow-up showed a slight improvement in perceived social support (PSS). The associations between perceived social support and living environment suggest the need to strengthen social support measures in areas where evacuation orders are yet to be lifted, which will provide useful information with which to examine the effects of future support efforts.