Publications by authors named "Masataka Taguri"

249 Publications

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease.

Sci Transl Med 2022 Jun 22;14(650):eabo4474. Epub 2022 Jun 22.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)-NAFLD, predicted incident HCC over up to 15 years of longitudinal observation. High-risk PLS-NAFLD was associated with IDO1 dendritic cells and dysfunctional CD8 T cells in fibrotic portal tracts along with impaired metabolic regulators. PLS-NAFLD was validated in independent cohorts of patients with NAFLD who were HCC naïve (HCC incidence rates at 15 years were 22.7 and 0% in high- and low-risk patients, respectively) or HCC experienced (de novo HCC recurrence rates at 5 years were 71.8 and 42.9% in high- and low-risk patients, respectively). PLS-NAFLD was bioinformatically translated into a four-protein secretome signature, PLSec-NAFLD, which was validated in an independent cohort of HCC-naïve patients with NAFLD and cirrhosis (HCC incidence rates at 15 years were 37.6 and 0% in high- and low-risk patients, respectively). Combination of PLSec-NAFLD with our previously defined etiology-agnostic PLSec-AFP yielded improved HCC risk stratification. PLS-NAFLD was modified by bariatric surgery, lipophilic statin, and IDO1 inhibitor, suggesting that the signature can be used for drug discovery and as a surrogate end point in HCC chemoprevention clinical trials. Collectively, PLS/PLSec-NAFLD may enable NAFLD-specific HCC risk prediction and facilitate clinical translation of NAFLD-directed HCC chemoprevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abo4474DOI Listing
June 2022

Rationale and design of a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group, investigator-initiated trial to investigate the efficacy and safety of elobixibat for chronic constipation.

BMJ Open 2022 May 30;12(5):e060704. Epub 2022 May 30.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.

Introduction: Chronic constipation (CC) is a functional disorder that negatively impacts the quality of life of patients. This is a protocol for a multicentre, 12-week, randomised, double-blind, placebo-controlled study to test the efficacy and safety of elobixibat (EXB) versus placebo in patients with CC.

Methods And Analysis: This will be a multicentre, double-blind, placebo-control, randomised controlled trial. A total of 100 adult patients with CC, diagnosed based on Rome IV criteria, who fulfil the inclusion/exclusion criteria will be enrolled. The patients will be randomly assigned to receive EXB (10 mg) or placebo treatment (n=50 per group). Blood tests and stool sampling will be performed 12 weeks following initiation of treatment and questionnaires will be issued to participants. The primary outcome will be the change in complete spontaneous bowel movements after 12 weeks of administration. The secondary outcomes will include the change in Japanese Patient Assessment of Constipation Quality of Life and absolute serum and faecal bile acid.

Ethics And Dissemination: Ethics approval has been obtained from Yokohama City University Certified Institutional Review Board before participant enrolment. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.

Protocol Version: V.3.0, 15 June 2021.

Trial Registration Number: ClinicalTrials.gov (number NCT04784780).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-060704DOI Listing
May 2022

Clinical risk factors for patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation.

Hematology 2022 Dec;27(1):620-628

Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment for myelodysplastic syndromes (MDS), although predicting post-transplant outcomes remains inconclusive. This study evaluated patients who underwent allo-HCT for MDS to identify prognostic factors and develop a clinical risk model.: We evaluated 55 patients between June 2000 and March 2015 to identify prognostic factors and develop a model for three-year overall survival (OS) and event-free survival (EFS). Cox regression analysis was performed on four factors: age ≥55 years; Hematopoietic Cell Transplant-Comorbidity Index >2; intermediate or worse cytogenetic status based on revised International Prognostic Scoring System; and unrelated donor status associated with poor OS in the univariate analysis. A clinical risk model was constructed using the sum of the regression coefficients and evaluated using receiver operating characteristic analysis and five-fold cross-validation.: Patient median age was 51 (range: 30-67) years. Median follow-up was 45.8 (range: 1.27-193) months; the three-year OS and EFS rates were 61.8% and 56.4%, respectively. The areas under the curves (AUCs) for OS and EFS were 0.738 and 0.778, respectively, and the average AUC for 50 times five-fold cross-validation were 0.711 and 0.723 for three-year OS and EFS, respectively.: A four-clinical-risk-factor model that could effectively predict post-transplantation outcomes and help decision-making in MDS treatment was developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/16078454.2022.2052601DOI Listing
December 2022

Efficacy of Adjuvant Chemotherapy With Tegafur-Uracil in Patients With Completely Resected, Node-Negative NSCLC-Real-World Data in the Era of Molecularly Targeted Agents and Immunotherapy.

JTO Clin Res Rep 2022 May 6;3(5):100320. Epub 2022 Apr 6.

Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.

Introduction: In Japan, adjuvant tegafur-uracil (UFT) chemotherapy is recommended for patients with completely resected, stage I NSCLC. This treatment requires real-world re-evaluation because of recent advances in target-based and immuno-oncological treatments and refinement of lung cancer staging.

Methods: The Japan Clinical Oncology Group (JCOG) 0707, a phase 3 trial comparing the benefits of UFT and S-1 (tegafur-gimeracil-oteracil) in patients with completely resected stage I NSCLC (T1 >2 cm and T2 in the TNM sixth edition), was conducted in Japan. A multicenter observational cohort study (Comprehensive Support Project for Oncology Research [CSPOR]-LC03) was also conducted for those patients excluded from JCOG 0707 during the study enrollment period. Physicians from institutions that participated in JCOG 0707 retrospectively assessed the medical records of each patient. The efficacy of UFT was evaluated in the CSPOR-LC03 cohort.

Results: In the entire study population (n = 5005), patients treated with UFT (n = 1549) had significantly longer overall survival (OS) than those without any adjuvant chemotherapy (n = 3338). There was no significant difference in OS between the patients treated with UFT (n = 1061) and those without adjuvant chemotherapy (n = 1484) in the JCOG 0707-eligible population (logrank = 0.755). For tumors without ground-glass attenuation and size greater than 3 cm, patients treated with UFT had significantly longer survival than those without adjuvant chemotherapy, on univariate but not on multivariate analysis.

Conclusions: There was no significant difference in OS between the patients treated with UFT and those without adjuvant chemotherapy in the clinical trial-eligible population. Adjuvant UFT for patients with completely resected NSCLC may be recommended only in patients with a tumor without ground-glass attenuation and size greater than 3 cm. In patients with node-negative early NSCLC, further study is needed to select patients who will benefit from adjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtocrr.2022.100320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117917PMC
May 2022

Association between diabetes and adjuvant chemotherapy implementation in patients with stage III colorectal cancer.

J Diabetes Investig 2022 May 19. Epub 2022 May 19.

Division of Health Services Research, National Cancer Center Institute for Cancer Control, Chuo-ku, Tokyo, Japan.

Aims/introduction: Among colorectal cancer (CRC) patients, pre-existing diabetes is suggested to influence poor prognosis, but the impact on adjuvant chemotherapy implementation is largely unknown. We aimed to compare the implementation rate of adjuvant chemotherapy between CRC patients with and without pre-existing diabetes in a retrospective cohort study.

Materials And Methods: Colorectal cancer diagnosis information was obtained from the hospital-based cancer registry of patients with stage III CRC who underwent curative surgery in 2013 in Japan (n = 6,344). Health claims data were used to identify diabetes and chemotherapy. We examined the association between diabetes and the implementation rate of adjuvant chemotherapy using a generalized linear model adjusted for age, sex, updated Charlson Comorbidity Index, hospital type and prefecture. Furthermore, we applied a mediation analysis to examine the extent to which postoperative complications mediated the association.

Results: Of the 6,344 patients, 1,266 (20.0%) had diabetes. The mean ages were 68.2 and 71.3 years for patients without and with diabetes, respectively. Compared with those without diabetes, patients with diabetes were less likely to receive adjuvant chemotherapy (crude rate 58.9 and 49.8%; adjusted percentage point difference 4.6; 95% confidence interval 1.7-7.5). The difference was evident for patients aged <80 years, and larger for platinum-containing regimens than others. Mediation analysis showed that postoperative complications explained 9.1% of the inverse association between diabetes and adjuvant chemotherapy implementation.

Conclusions: We observed that patients with stage III CRC and diabetes are less likely to receive adjuvant chemotherapy than those without diabetes, and postoperative complications might partially account for the association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13837DOI Listing
May 2022

Combination of tofogliflozin and pioglitazone for NAFLD: Extension to the ToPiND randomized controlled trial.

Hepatol Commun 2022 May 16. Epub 2022 May 16.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

The incidence of nonalcoholic fatty liver disease (NAFLD) has recently increased and is related to obesity and the associated surge in type 2 diabetes mellitus (T2DM) and metabolic syndromes. This trial follows up on our previous work and forms part of the ToPiND study. We aimed to combine tofogliflozin and pioglitazone treatment for hepatic steatosis in patients with NAFLD and T2DM. In this open-label, prospective, single-center, randomized clinical trial, patients with NAFLD with T2DM and a hepatic fat fraction of ≥10% were assessed based on magnetic resonance imaging proton density fat fraction. Eligible patients received either 20 mg tofogliflozin or 15-30 mg pioglitazone orally, once daily for 24 weeks, followed by combination therapy with both medicines for an additional 24 weeks. The effects on diabetes mellitus and hepatic steatosis were examined at baseline and after the completion of monotherapy and combination therapy. Thirty-two eligible patients received the combination therapy of tofogliflozin and pioglitazone. The combination therapy showed additional improvement in glycated hemoglobin compared with each monotherapy group and showed improvement in steatosis, hepatic stiffness, and alanine aminotransferase levels compared with the tofogliflozin monotherapy group. Pioglitazone monotherapy-mediated increase in body weight decreased following concomitant use of tofogliflozin. The combination therapy resulted in lower triglyceride, higher high-density lipoprotein cholesterol, higher adiponectin, and higher ketone body levels. Conclusion: In addition to the additive effects of tofogliflozin and pioglitazone in patients with T2DM and NAFLD, combination therapy was suggested to reduce weight gain and induce cardioprotective effect. Further studies with more patients are needed to investigate the combination therapy of various drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep4.1993DOI Listing
May 2022

Effectiveness of Naldemedine Compared with Magnesium Oxide in Preventing Opioid-Induced Constipation: A Randomized Controlled Trial.

Cancers (Basel) 2022 Apr 24;14(9). Epub 2022 Apr 24.

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

Opioid-induced constipation (OIC) may occur in patients receiving opioid treatment, decreasing their quality of life (QOL). We compared the effectiveness of magnesium oxide (MgO) with that of naldemedine (NAL) in preventing OIC. This proof-of-concept, randomized controlled trial (registration number UMIN000031891) involved 120 patients with cancer scheduled to receive opioid therapy. The patients were randomly assigned and stratified by age and sex to receive MgO (500 mg, thrice daily) or NAL (0.2 mg, once daily) for 12 weeks. The change in the average Japanese version of Patient Assessment of Constipation QOL (JPAC-QOL) from baseline to 2 weeks was assessed as the primary endpoint. The other endpoints were spontaneous bowel movements (SBMs) and complete SBMs (CSBMs). Deterioration in the mean JPAC-QOL was significantly lower in the NAL group than in the MgO group after 2 weeks. There were fewer adverse events in the NAL group than in the MgO group. Neither significant differences in the change in SBMs between the groups nor serious adverse events/deaths were observed. The CSBM rate was higher in the NAL group than in the MgO group at 2 and 12 weeks. In conclusion, NAL significantly prevented deterioration in constipation-specific QOL and CSBM rate compared with MgO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers14092112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102438PMC
April 2022

gBOIN-ET: The generalized Bayesian optimal interval design for optimal dose-finding accounting for ordinal graded efficacy and toxicity in early clinical trials.

Biom J 2022 May 13. Epub 2022 May 13.

Department of Data Science, Yokohama City University, Yokohama, Japan.

One of the primary objectives of an oncology dose-finding trial for novel therapies, such as molecular targeted agents and immune-oncology therapies, is to identify an optimal dose (OD) that is tolerable and therapeutically beneficial for subjects in subsequent clinical trials. These new therapeutic agents appear more likely to induce multiple low- or moderate-grade toxicities than dose-limiting toxicities. Besides, efficacy should be evaluated as an overall response and stable disease in solid tumors and the difference between complete remission and partial remission in lymphoma. This paper proposes the generalized Bayesian optimal interval design for dose-finding accounting for efficacy and toxicity grades. The new design, named "gBOIN-ET" design, is model-assisted, simple, and straightforward to implement in actual oncology dose-finding trials than model-based approaches. These characteristics are quite valuable in practice. A simulation study shows that the gBOIN-ET design has advantages compared with the other model-assisted designs in the percentage of correct OD selection and the average number of patients allocated to the ODs across various realistic settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bimj.202100263DOI Listing
May 2022

Delivery balloon volume positively correlates with the diameter and effective orifice area of implanted SAPIEN 3.

J Cardiol 2022 Apr 22. Epub 2022 Apr 22.

Department of Cardiology, Sendai Kousei Hospital, Sendai, Miyagi, Japan; Department of Cardiovascular Surgery, School of Medicine, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan.

Background: In transcatheter aortic valve replacement (TAVR) using SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, CA, USA), some clinicians decrease or increase the delivery balloon volume (VOL) when deploying S3 or conducting post-dilatation. However, the effects of controlling VOL on transcatheter heart valve diameter (THVD) and valve function remain unclear. We assessed associations among VOL, THVD, and effective orifice area (EOA) of S3.

Methods: We enrolled patients undergoing TAVR using 23- and 26-mm S3 in Sendai Kousei Hospital between 2017 and 2019. VOL was controlled based on preprocedural computed tomography and intraprocedural transesophageal echocardiography (TEE). THVD were defined as the diameters of transcatheter heart valve at mid-level measured by TEE.

Results: In enrolled 332 patients (23-mm, n = 188; 26-mm, n = 144), one (0.3%) and two (0.6%) developed annulus rupture and moderate/severe paravalvular leak, respectively. VOL at deployment was positively correlated with THVD on deployment (23-mm, r = 0.44, p < 0.001; 26-mm, r = 0.57, p < 0.001) and EOA (23-mm, r = 0.23, p = 0.0019; 26-mm, r = 0.22, p = 0.0094). In multiple regression analyses, VOL and post-dilatation were significant determinants of THVD, although aortic annulus area, calcium volume, and pre-dilatation were not. The areas under the receiver operating characteristic curve that were used to evaluate the accuracy of the index obtained by dividing THVD by body surface area (indexed THVD) to predict patient-prosthesis mismatch (PPM) were 0.744 and 0.811 in the 23- and 26-mm cohorts, respectively. A cut-off indexed THVD of ≤11.5 and 12.1 mm/m well predicted PPM (23-mm, odds ratio, 5.20; 95% confidence interval, 1.33-20.3; 26-mm, odds ratio 14.1, 95% confidence interval 2.40-81.0).

Conclusion: VOL was positively correlated with THVD and EOA. Smaller indexed THVD was associated with a higher incidence of PPM. Controlling VOL under on-site THVD evaluation may be useful in reducing the PPM incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2022.03.011DOI Listing
April 2022

Experience of distance education for project-based learning in data science.

Jpn J Stat Data Sci 2022 Apr 9:1-11. Epub 2022 Apr 9.

Department of Data Science, Graduate School of Data Science, Yokohama City University, Yokohama, Japan.

Data science plays an important role in many fields. Project-based learning is an effective teaching approach because students can learn data science practices based on real-world problems and real-world data. Because of a pandemic of COVID-19, we provided project-based learning as distance education (synchronic distance education). In this study, we explain how we developed and conducted it and provide survey results from students. The survey showed about 30% of the students found it difficult to communicate with each other and with teachers. However, it suggested that they could communicate to some extent even by remote group work. We found that, in remote communication, it is important to see the faces of all the students (and teachers) on the Zoom screen when they discuss using screen sharing. There remain some challenges such as timing to start talking and casual questions to teachers. Although some issues should be improved, distance education for project-based learning in data science can be implemented effectively.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42081-022-00154-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s42081-022-00154-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994060PMC
April 2022

Comparison of the diagnostic performance of NBI, Laser-BLI and LED-BLI: a randomized controlled noninferiority trial.

Surg Endosc 2022 Apr 11. Epub 2022 Apr 11.

Endoscopy division, National Cancer Center Hospital, Tokyo, Japan.

Background And Aims: New image-enhanced endoscopy (IEE), blue Light Imaging (LED-BLI) is launched in USA and Europe, whereas Blue Laser Imaging (Laser-BLI) is available only Asian and some countries. No studies have directly compared the diagnostic accuracy of narrow band imaging (NBI), Laser-BLI and LED-BLI for colorectal tumors. The present study aimed to compare the diagnostic accuracy of the three methods for colorectal tumor using the NBI international colorectal endoscopic (NICE) classification and the Japanese NBI Expert Team (JNET) classifications.

Methods: This was a multi-center evaluator-blinded, randomized control trial of patients who underwent endoscopic colorectal tumor resection. The patients were randomly assigned to NBI, Laser-BLI or LED-BLI. Cropped images were sent to blinded external evaluators and diagnosed according to NICE and JNET classifications. The diagnostic accuracy of each endoscopy system was compared with non-inferiority test.

Results: A total of 619 colonic tumors were resected from 230 patients and evaluated by external four evaluators. The diagnostic accuracy of NBI for NICE 1, NICE 2, NICE 3 was 90.6%, 90.3% and 99.5%, respectively and for JNET 1, JNET 2A, JNET 2B and JNET 3, it was 94.6%, 72.0%, 79.2% and 99.1%, respectively. In non-inferiority test, Laser-BLI and LED-BLI revealed non-inferiority to NBI in all NICE and JNET categories (p<0.001).

Conclusions: Laser-BLI and LED-BLI had high diagnostic accuracy and non-inferiority of NBI, especially for hyperplastic polyp/sessile serrated lesion and low-grade dysplasia. This is first trial to compare the diagnostic accuracy with NBI, Laser-BLI and LED-BLI and useful to understand the position of each IEE. This trial was registered as UMIN000032107.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-022-09197-8DOI Listing
April 2022

Repeat conformation heterogeneity in cerebellar ataxia, neuropathy, vestibular areflexia syndrome.

Brain 2022 04;145(3):1139-1150

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa 236-0004, Japan.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slow-progressing multisystem neurodegenerative disorder. Biallelic AAGGG repeat expansion in RFC1 has been identified as causative of this disease, and repeat conformation heterogeneity (ACAGG repeat) was also recently implied. To molecularly characterize this disease in Japanese patients with adult-onset ataxia, we accumulated and screened 212 candidate families by an integrated approach consisting of flanking PCR, repeat-primed PCR, Southern blotting and long-read sequencing using Sequel II, GridION or PromethION. We identified 16 patients from 11 families, of whom seven had ACAGG expansions [(ACAGG)exp/(ACAGG)exp] (ACAGG homozygotes), two had ACAGG and AAGGG expansions [(ACAGG)exp/(AAGGG)exp] (ACAGG/AAGGG compound heterozygotes) and seven had AAGGG expansions [(AAGGG)exp/(AAGGG)exp] (AAGGG homozygotes). The overall detection rate was 5.2% (11/212 families including one family having two expansion genotypes). Long-read sequencers revealed the entire sequence of both AAGGG and ACAGG repeat expansions at the nucleotide level of resolution. Clinical assessment and neuropathology results suggested that patients with ACAGG expansions have similar clinical features to previously reported patients with homozygous AAGGG expansions, although motor neuron involvement was more notable in patients with ACAGG expansions (even if one allele was involved). Furthermore, a later age of onset and slower clinical progression were implied in patients with ACAGG/AAGGG compound heterozygous expansions compared with either ACAGG or AAGGG homozygotes in our very limited cohort. Our study clearly shows the occurrence of repeat conformation heterogeneity, with possible different impacts on the affected nervous systems. The difference in disease onset and progression between compound heterozygotes and homozygotes might also be suspected but with very limited certainty due to the small sample number of cases in our study. Studies of additional patients are needed to confirm this.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awab363DOI Listing
April 2022

Incidence, Clinical Characteristics, and Predictors of Cardiovascular Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

Oncologist 2022 May;27(5):e410-e419

Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan.

Background: Cardiovascular immune-related adverse events (CV-irAEs) associated with immune checkpoint inhibitors (ICIs) may have been underreported given that most previous reports were retrospective. We aimed to evaluate the incidence, clinical characteristics, and predictors of CV-irAEs and determine the feasibility of serial cardiac monitoring using a combination of B-type natriuretic peptide, cardiac troponin T, and electrocardiogram for the prediction of future symptomatic (grade ≥2) CV-irAEs.

Materials And Methods: This was a prospective observational study that included 129 consecutive patients with non-small-cell lung cancer who received ICI monotherapy at a single center. Serial cardiac monitoring was performed during ICI monotherapy.

Results: A total of 35 (27%) patients developed any grade ≥1 CV-irAEs with a median time of onset of 72 (interquartile range 44-216) days after ICI treatment initiation. Multivariate Fine-Gray regression analysis showed that prior acute coronary syndrome (adjusted hazard ratio [HR] 3.15 (95% [CI], 2.03-4.91), prior heart failure hospitalization (adjusted HR 1.65 [95% CI, 1.17-2.33]), and achievement of disease control (adjusted HR 1.91, [95% CI, 1.16-3.14]) were significantly associated with grade ≥1 CV-irAEs. Serial cardiac monitoring revealed that patients with preceding grade 1 CV-irAEs were associated with a significantly higher risk of onset of grade ≥2 CV-irAEs compared with those without preceding grade 1 CV-irAEs (HR: 6.17 [95% CI, 2.97-12.83]).

Conclusion: CV-irAEs were more common than previously recognized and have several predictors. Moreover, serial cardiac monitoring may be feasible for the prediction of future grade ≥2 CV-irAEs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/oncolo/oyac056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074992PMC
May 2022

Comments on 'A weighting analogue to pair matching in propensity score analysis' by L. Li and T. Greene.

Int J Biostat 2022 Mar 24. Epub 2022 Mar 24.

Graduate School of Data Science, Yokohama City University, Yokohama, Kanagawa, Japan.

Li and Greene (A weighting analogue to pair matching in propensity score analysis. Int J Biostat 2013;9:215-34) propose that estimates derived by the matching weight (MW) estimator are similar to those derived by the one-to-one propensity score matching estimator. The MW estimator has some useful properties, however, some regularity conditions need to be confirmed to derive an asymptotic distribution since the MW has a non-differentiable point. In this letter, we confirm the asymptotic distribution of the MW estimator and the sufficient conditions to achieve it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/ijb-2021-0090DOI Listing
March 2022

Predictive factors of postoperative fentanyl consumption in patients with inflammatory bowel disease: a retrospective cohort study.

BMC Anesthesiol 2022 03 11;22(1):70. Epub 2022 Mar 11.

Department of Anesthesiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.

Background: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, might present difficulties in achieving postoperative analgesia. Prior studies have suggested that patients with IBD undergoing major abdominal surgery require higher doses of perioperative opioids than do patients without IBD. Considering patients with IBD potentially require high-dose opioids, identifying those requiring higher opioid doses will allow clinicians to optimize the perioperative opioid dose and avoid insufficient pain management or complications of opioid overdose. Therefore, we conducted this study to identify predictive factors that might influence postoperative opioid consumption in patients with IBD.

Methods: This single-center, historical cohort study reviewed the medical records of all patients admitted to the IBD center of our institution for surgery and who used intravenous fentanyl patient-controlled analgesia (PCA) after open abdominal surgery between June 2013 and April 2017. Ultimately, 179 patients were enrolled in the analysis. Variables expected to influence and/or represent pain, analgesia, inflammation, disease condition, and extent of surgery were selected as potential explanatory variables for predicting postoperative opioid consumption. Multivariable linear regression analysis was used to examine the effect of independent variables on postoperative fentanyl consumption.

Results: Of the nine predictive variables selected using the stepwise-selection method, eight were significant. Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect on postoperative fentanyl consumption, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect. Preoperative use of opioids was a non-significant variable. The adjusted coefficient of determination was 0.302.

Conclusions: Intraoperative fentanyl consumption, current smoking, ulcerative colitis, administration of biologics during the month before surgery, and the use of supplementary analgesics had a significant increasing effect, whereas droperidol concentration in the PCA solution, age, and diabetes mellitus had a significant decreasing effect on postoperative fentanyl consumption. These factors should be considered when adopting postoperative intravenous fentanyl PCA administration for patients with IBD.

Trial Registration: Registry: UMIN Clinical Trials Registry.

Clinical Trial Number: UMIN000031198 . Date of registration: February 8, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12871-022-01606-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915481PMC
March 2022

Prospective observational study of the efficacy of oral uracil and tegafur plus leucovorin for stage II colon cancer with risk factors for recurrence using propensity score matching (JFMC46-1201).

BMC Cancer 2022 Feb 15;22(1):170. Epub 2022 Feb 15.

Department of Biomedical Statistics and Bioinformatics, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors.

Methods: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm.

Results: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW.

Conclusions: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes.

Trial Registration: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-022-09267-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845390PMC
February 2022

Estimation of Overall Survival with Subsequent Treatment Effect by Applying Inverse Probability of Censoring Weighting in the LATITUDE Study.

Eur Urol Open Sci 2022 Feb 6;36:51-58. Epub 2022 Jan 6.

Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, France.

Background: In the LATITUDE study (ClinicalTrials.gov, NCT01715285), compared with placebos, abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) provided significant overall survival (OS) benefit in high-risk metastatic castration-sensitive prostate cancer (mCSPC) patients. It is controversial whether survival benefits would remain if all patients in the placebo group subsequently received life-extending therapies.

Objective: To estimate treatment effect in the case of all patients in the placebo group receiving life-extending subsequent therapies.

Design Setting And Participants: A post hoc analysis of LATITUDE final-analysis data was carried out (setting and participants have been reported previously).

Intervention: AAP or placebos plus ADT.

Outcome Measurements And Statistical Analysis: We applied the inverse probability of censoring weighting (IPCW) method to represent the situation in which all patients in the placebo group would have received life-extending subsequent therapies. The OS hazard ratio (HR) of AAP versus placebos and associated 95% confidence interval (CI) were estimated using a Cox proportional hazards model.

Results And Limitations: Of the 581 eligible patients in the placebo group, 237 (40.8%) did not receive life-extending subsequent therapies. From the unadjusted intention-to-treat analysis, the HR for OS for AAP versus placebos was 0.661 (95% CI 0.564-0.775). Using IPCW to adjust for patients in the placebo group without life-extending subsequent therapies, the HR was 0.732 (95% CI 0.604-0.887). A limitation is a lack of proof that the Cox proportional hazards model for the absence of life-extending subsequent therapy is correctly specified for the IPCW method.

Conclusions: Treatment with AAP exerts OS benefit over placebos in high-risk mCSPC patients, regardless of whether life-extending subsequent therapy is given.

Patient Summary: In a previous study, high-risk metastatic castration-sensitive prostate cancer patients who received abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy generally survived longer than those given placebos. The benefit of adding AAP continues regardless of whether life-extending subsequent therapy is given.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euros.2021.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783036PMC
February 2022

Real-world data in elderly men from Yokosuka City 15 years after introducing prostate-specific antigen-based population screening.

Mol Clin Oncol 2022 Feb 20;16(2):38. Epub 2021 Dec 20.

Department of Urology, Yokosuka Kyosai Hospital, Yokosuka, Kanagawa 238-8558, Japan.

Mass screening based on prostate-specific antigen (PSA) reduces mortality in prostate cancer. However, the effectiveness of this screening in the elderly has not been demonstrated. In the city of Yokosuka, Japan, PSA screening has been conducted since 2001 and the present study examined the real-world status of PSA-based population screening in the elderly. It retrospectively evaluated 1,117 prostate cancer patients >75 years of age. The patients were divided into two groups: The screened group comprising patients diagnosed by PSA-based population screening or workplace screening and PSA follow-up patients at urology clinics; and the non-screened group comprising patients detected by other methods. Overall survival (OS), cancer-specific survival (CSS) and factors contributing to shorter CSS between the groups were compared. In patients >75 years of age, the screened group had significantly longer OS (171 vs. 154 months; P=0.019) and CSS (median not reached; P=0.020) but screening was not an independent factor associated with prolonged OS or CSS on multivariate analysis. The factors contributing to shorten CSS in the elderly were ≥T3 (odds ratio: 3.301 [1.704-6.369], P<0.001), M1 (odds ratio: 4.856 [2.809-8.393], P<0.001) and Gleason score ≥8 (odds ratio: 4.691 [2.479-8.876], P<0.001). In those with metastasis, PSA screening was not associated with prolonged OS or CSS. Real-world data 15 years after introducing PSA-based population screening was not an independent factor for both OS and CSS in multivariate analyses for patients >75 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2021.2471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739438PMC
February 2022

Effect of Nudge-Based Intervention on Adherence to Physician Visit Recommendations and Early Health Outcomes among Individuals Identified with Chronic Kidney Disease in Screens.

J Am Soc Nephrol 2022 01 13;33(1):175-185. Epub 2021 Dec 13.

Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California, Los Angeles, California.

Background: Although CKD screening programs have been provided in many settings, little is known as to how we can effectively translate those screening programs into improved health.

Methods: We conducted a randomized clinical trial on national health screening for CKD in Japan between April 2018 and March 2019. A total of 4011 participants in CKD screening programs aged 40-63 years were randomly assigned to two interventions or the control, with a ratio of 2:2:1, respectively: () the nudge-based letter that contained a message on the basis of behavioral economics, () the clinical letter including general information about CKD risks, and () the control (informed only of the screening results). The main outcome was adherence to a recommended physician visit within 6 months of the intervention. The secondary outcomes were eGFR, proteinuria, and BP 1 year after the intervention.

Results: Compared with the control group, the probability of undergoing a recommended physician visit was higher among participants who received the nudge-based letter (19.7% for the intervention group versus 15.8% for the control; difference, +3.9 percentage points [pp]; 95% CI, +0.8 to +7.0; =0.02) and the clinical letter (19.7% versus 15.8%; difference, +3.9 pp; 95% CI, +0.8 to +7.0; =0.02). We found no evidence that interventions were associated with improved early health outcomes.

Conclusions: The behavioral economics intervention tested in this large RCT had limited effect on changing behavior or improving health outcomes. Although the approach has promise, this study demonstrates the challenge of developing behavioral interventions that improve the effectiveness of CKD screening programs. University Hospital Medical Information Network Clinical Trial Registry, UMIN000035230.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2021050664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763194PMC
January 2022

Rationale and Design of the Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study): Implications of Biologics against Rheumatoid Arthritis and the Vascular Complications, Subclinical Atherosclerosis.

Methods Protoc 2021 Nov 15;4(4). Epub 2021 Nov 15.

Department of Medical Science and Cardio-Renal Medicine, Graduate School of Medicine, Yokohama City University, Fukuura, Kanazawa-Ku, Yokohama 236-0004, Japan.

To explore the biological and immunological basis of human rheumatoid arthritis and human atherosclerosis, we planned and reported a detailed design and rationale for Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study) using highly sensitive, high-throughput, human autoantibody measurement methods with cell-free protein synthesis technologies. Our previous study revealed that subjects with atherosclerosis had various autoantibodies in their sera, and the titers of anti-Th2 cytokine antibodies were correlated with the severity of atherosclerosis. Because rheumatoid arthritis is a representative autoimmune disease, we hypothesized that both rheumatoid arthritis and atherosclerosis are commonly developed by autoantibody-mediated autoimmune processes, leading to incessant inflammatory changes in both articular joint tissues and vessel walls. We planned a detailed examination involving carotid artery ultrasonography, measurements of adhesion molecules, such as ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) for the evaluation of atherosclerosis progression, and high-throughput, high-sensitivity, autoantibody analyses using cell-free technologies, with detailed examinations of the disease activity of rheumatoid arthritis. Analyses of correlations and associations between biological markers and degrees of carotid atherosclerosis over time under consistent conditions may enable us to understand the biological and humoral immunity background of human atherosclerosis and autoimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/mps4040083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628894PMC
November 2021

Impact of Local Recurrence on Cause-Specific Death After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: Dynamic Prediction Using Landmark Model.

Int J Radiat Oncol Biol Phys 2022 04 26;112(5):1135-1143. Epub 2021 Nov 26.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Graduate School of Medicine, Kyoto, Japan.

Purpose: The purpose of this study was to assess the impact of local recurrence (LR) on cause-specific death (CSD) in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). A dynamic prediction model that incorporated LR as a time-dependent covariate was used.

Methods And Materials: This study included 535 stage I (cT1-T2aN0M0) NSCLC patients treated with SBRT from two institutions. We developed a landmark dynamic prediction model to estimate the probability of a CSD. This model determined the probability of surviving for an additional 3 years at different prediction time points during follow-up, given the history of recurrence status. The baseline covariates included in the model were age, sex, T stage, and histology, while the time-dependent covariates were LR and regional and/or distant recurrence (RDR) status.

Results: Overall, 137 patients (25.6%) died of lung cancer within a median follow-up of 4.1 years. Of the 195 patients who developed recurrence, 28, 125, and 42 patients had LR only, RDR only, and both, respectively. The landmark model showed that older age, advanced T stage, LR, and RDR were significantly associated with an increased risk of subsequent CSD. Among these covariates, LR (odds ratio [OR], 8.5; 95% confidence interval [CI], 6.0-12.0; P < .001) and RDR (OR, 11.6; 95% CI, 9.1-14.9; P < .001) demonstrated strong effects on CSD within 3 years after the prediction time points. The dynamic prediction provided information on the probability of future CSD according to individual recurrence status during follow-up.

Conclusions: Dynamic prediction using the landmark model showed that LR had a substantial impact on subsequent CSD, which was comparable to that of RDR. This result supports the notion that strategies to improve local control are reasonable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2021.11.025DOI Listing
April 2022

Impact of Baseline and Postprocedural Intravascular Ultrasound Findings on 1-Year Primary Patency After Drug-Coated Balloon Treatment of Femoropopliteal Lesions.

J Endovasc Ther 2022 Feb 15;29(1):66-75. Epub 2021 Nov 15.

Department of Cardiovascular Medicine, Sendai Kousei Hospital, Sendai, Japan.

Purpose: Drug-coated balloons (DCBs) are commonly used for endovascular treatment of femoropopliteal lesions. Here, we employed intravascular ultrasound (IVUS) to investigate the predictors of restenosis after DCB treatment.

Methods: This retrospective and single-center study was performed to examine 1-year primary patency after DCB treatment and to identify the risk factors for restenosis by analyzing clinical characteristics, angiographic findings, and IVUS measurements. We included 111 consecutive patients undergoing DCB treatment for de novo femoropopliteal lesions at our hospital from July 2018 to March 2020.

Results: The primary patency rate was found to be 80.0% at 1 year. The Cox proportional hazard multivariate analysis revealed that restenosis was independently associated with chronic total occlusion (CTO; p < 0.001), circumferential calcification (p = 0.023), and smaller postprocedural minimum lumen area (MLA; p = 0.036). Furthermore, receiver operating characteristic curve analysis showed that the cutoff value of postprocedural MLA to prevent restenosis was 12.7 mm, with an area under the curve of 0.774 (p< 0.001). The multivariate analysis indicated that patients with a postprocedural MLA below 12.7 mm (n = 44) had a significantly smaller distal reference vessel size (p < 0.001) compared to those with a postprocedural MLA over 12.7 mm (n = 67).

Conclusions: Restenosis after DCB treatment was shown to correlate with CTO, circumferential calcification, and postprocedural MLA as evaluated by IVUS. Moreover, smaller vessel sizes might represent a particular challenge to the DCB strategy due to the difficulty of restoring a sufficient postprocedural lumen area by balloon dilatation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/15266028211058683DOI Listing
February 2022

Prediction of lateral lymph node metastasis using OSNA method for mesorectal lymph nodes in low rectal cancer: A prospective study by the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC1801).

J Surg Oncol 2022 Mar 27;125(3):457-464. Epub 2021 Oct 27.

Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan.

Background And Objectives: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM.

Methods: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%.

Results: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%.

Conclusions: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26730DOI Listing
March 2022

Exposure to PM and Lung Function Growth in Pre- and Early-Adolescent Schoolchildren: A Longitudinal Study Involving Repeated Lung Function Measurements in Japan.

Ann Am Thorac Soc 2022 05;19(5):763-772

National Institute for Environmental Studies, Ibaraki, Japan.

Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 μm in aerodynamic diameter (PM) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. To examine long-term effects of PM within the 4-year average concentration range of 10-19 μg/m on lung function growth with repeated measurements of lung function tests. Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM, was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-μg/m increases in the PM concentration on relative growth per each 10-cm increase in height. The overall annual mean PM level was 13.5 μg/m (range, 10.4-19.0 μg/m). We found no association between any of the lung function growth indicators and increases in PM levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O or NO did not change the null results. This nationwide longitudinal study suggests that concurrent, long-term exposure to PM at concentrations ranging from 10.4 to 19.0 μg/m has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202104-511OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116336PMC
May 2022

Large-Scale Fandom-based Gamification Intervention to Increase Physical Activity: A Quasi-experimental Study.

Med Sci Sports Exerc 2022 01;54(1):181-188

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA.

Purpose: Gamification, the use of game design elements in nongame contexts, in combination with insights from behavioral economics, has been applied increasingly to behavior change interventions. However, little is known about the effectiveness or scalability of this approach, especially in the long term. We tested a large-scale smartphone-based intervention to encourage physical activity among Japanese baseball fans using gamification techniques that leveraged fandom and interteam competition inherent in sports.

Methods: A quasi-experimental study was conducted among fans of the Japanese Pacific League. The app, Pa-League Walk, included gamification elements, such as competition between opposing teams' fans based on total daily step counts on game days (>60,000 free downloads since March 2016). We analyzed daily steps of 20,052 app users, supplemented by online survey data of 274 users and 613 matched controls. Difference-in-differences estimators evaluated change in daily steps before and after app installation in users versus matched controls.

Results: Users' daily steps increased by 574 (95% confidence interval, 83-1064) steps 3 months after installation, compared with controls. The increase was maintained for up to 9 months (559 (99-1018) more steps per day vs baseline), attenuating over a longer follow-up. Positive effect modification was found by high-frequency of the app use (P < 0.001) but not by other covariables (P ≥ 0.14) such as education or income. Days with 10,000-step achievement increased from 24.4% to 27.5% after the additional introduction of incentives (digital player photographs; P < 0.001).

Conclusions: Using existing fandom and solidarity, the gamification app increased physical activity at scale among baseball fans, including people with lower socioeconomic status underrepresented in traditional health programs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1249/MSS.0000000000002770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677610PMC
January 2022

De novo ARF3 variants cause neurodevelopmental disorder with brain abnormality.

Hum Mol Genet 2021 12;31(1):69-81

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan.

An optimal Golgi transport system is important for mammalian cells. The adenosine diphosphate (ADP) ribosylation factors (ARF) are key proteins for regulating cargo sorting at the Golgi network. In this family, ARF3 mainly works at the trans-Golgi network (TGN), and no ARF3-related phenotypes have yet been described in humans. We here report the clinical and genetic evaluations of two unrelated children with de novo pathogenic variants in the ARF3 gene: c.200A > T (p.Asp67Val) and c.296G > T (p.Arg99Leu). Although the affected individuals presented commonly with developmental delay, epilepsy and brain abnormalities, there were differences in severity, clinical course and brain lesions. In vitro subcellular localization assays revealed that the p.Arg99Leu mutant localized to Golgi apparatus, similar to the wild-type, whereas the p.Asp67Val mutant tended to show a disperse cytosolic pattern together with abnormally dispersed Golgi localization, similar to that observed in a known dominant negative variant (p.Thr31Asn). Pull-down assays revealed that the p.Asp67Val had a loss-of-function effect and the p.Arg99Leu variant had increased binding of the adaptor protein, Golgi-localized, γ-adaptin ear-containing, ARF-binding protein 1 (GGA1), supporting the gain of function. Furthermore, in vivo studies revealed that p.Asp67Val transfection led to lethality in flies. In contrast, flies expressing p.Arg99Leu had abnormal rough eye, as observed in the gain-of-function variant p.Gln71Leu. These data indicate that two ARF3 variants, the possibly loss-of-function p.Asp67Val and the gain-of-function p.Arg99Leu, both impair the Golgi transport system. Therefore, it may not be unreasonable that they showed different clinical features like diffuse brain atrophy (p.Asp67Val) and cerebellar hypoplasia (p.Arg99Leu).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddab224DOI Listing
December 2021

A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis.

Med (N Y) 2021 07 21;2(7):836-850.e10. Epub 2021 Apr 21.

Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, U.S.

Background: Accurate non-invasive prediction of long-term hepatocellular carcinoma (HCC) risk in advanced liver fibrosis is urgently needed for cost-effective HCC screening; however, this currently remains an unmet need.

Methods: A serum-protein-based prognostic liver secretome signature (PLSec) was bioinformatically derived from previously validated hepatic transcriptome signatures and optimized in 79 patients with advanced liver fibrosis. We independently validated PLSec for HCC risk in 331 cirrhosis patients with mixed etiologies (validation set 1 [V1]) and thereafter developed a score with clinical prognostic variables. The score was then validated in two independent cohorts: validation set 2 (V2): 164 patients with advanced liver fibrosis due to hepatitis C virus (HCV) infection cured after direct-acting antiviral therapy; validation set 3 (V3): 146 patients with advanced liver fibrosis with successfully-treated HCC and cured HCV infection.

Findings: An 8-protein blood-based PLSec recapitulated transcriptome-based hepatic HCC risk status. In V1, PLSec was significantly associated with incident HCC risk (adjusted hazard ratio [aHR], 2.35; 95% confidence interval [CI], 1.30-4.23). A composite score with serum alpha-fetoprotein (PLSec-AFP) was defined in V1, and validated in V2 (adjusted odds ratio, 3.80 [95%CI, 1.66-8.66]) and V3 (aHR, 3.08 [95%CI, 1.78-5.31]; c-index, 0.74). PLSec-AFP outperformed AFP alone (Brier score, 0.165 vs. 0.186 in V2; 0.196 vs. 0.206 in V3, respectively).

Conclusions: The blood-based PLSec-AFP can accurately stratify patients with advanced liver fibrosis for long-term HCC risk and thereby guide risk-based tailored HCC screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.medj.2021.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312635PMC
July 2021

Increased Plasma Levels of Myosin Heavy Chain 11 Is Associated with Atherosclerosis.

J Clin Med 2021 Jul 16;10(14). Epub 2021 Jul 16.

Department of Physiology, Tokyo Medical University, 6-6-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

Many studies have revealed numerous potential biomarkers for atherosclerosis, but tissue-specific biomarkers are still needed. Recent lineage-tracing studies revealed that smooth muscle cells (SMCs) contribute substantially to plaque formation, and the loss of SMCs causes plaque vulnerability. We investigated the association of SMC-specific myosin heavy chain 11 (myosin-11) with atherosclerosis. Forty-five patients with atherosclerosis and 34 control subjects were recruited into our study. In the atherosclerosis patients, 35 patients had either coronary artery disease (CAD) or peripheral artery disease (PAD), and 10 had both CAD and PAD. Coronary arteries isolated from five patients were subjected to histological study. Circulating myosin-11 levels were higher in the CAD or PAD group than in controls. The area under the receiver operating characteristic curve of myosin-11 was 0.954. Circulating myosin-11 levels in the CAD and PAD group were higher than in the CAD or PAD group, while high-sensitivity C-reactive protein concentrations did not differ between these groups. Multinomial logistic regression analyses showed a significant association of myosin-11 levels with the presence of multiple atherosclerotic regions. Myosin-11 was expressed in the medial layer of human atherosclerotic lesions where apoptosis elevated. Circulating myosin-11 levels may be useful for detecting spatial expansion of atherosclerotic regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10143155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304775PMC
July 2021

Comparison of unenhanced magnetic resonance imaging and ultrasound in detecting very small hepatocellular carcinoma.

World J Hepatol 2021 Jun;13(6):699-708

Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.

Background: In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years.

Aim: To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously.

Methods: In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US.

Results: The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US ( < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S was identified in 51.7%.

Conclusion: Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4254/wjh.v13.i6.699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239491PMC
June 2021

Elobixibat Effectively Relieves Chronic Constipation in Patients with Cancer Regardless of the Amount of Food Intake.

Oncologist 2021 10 16;26(10):e1862-e1869. Epub 2021 Jul 16.

Department of Oncology, Yokohama City University, Yokohama, Japan.

Background: Constipation is a common, distressing complication in patients with cancer receiving palliative care. Elobixibat is a novel inhibitor of the ileal bile acid transporter that is used to treat chronic constipation by stimulating bowel function. However, its efficacy in patients with cancer has not been examined. This study investigated the drug's effectiveness in patients with cancer with chronic constipation.

Patients And Methods: This prospective-sampling, single-center, observational study included hospitalized patients with cancer diagnosed, using the Rome IV criteria, with chronic constipation. Within 2 weeks of hospitalization, each participant was administered elobixibat (5-15 mg) daily until discharge. Spontaneous bowel movements (SBMs), complete spontaneous bowel movements (CSBMs), Bristol stool form scale (BSFS) scores, and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) scores were assessed before and after elobixibat administration. We also evaluated the relationship between the amount of food consumed and the SBM frequency.

Results: Among the 83 participants, the mean pre- and post-treatment frequencies of daily SBMs were 0.3 and 1.2 (p < .0001) and those of CSBMs were 0.1 and 0.6 (p < .0001), respectively. The mean pretreatment BSFS score was 1.6, whereas the post-treatment value was 3.5 (p < .0001); the mean PAC-QOL score (overall) improved from 1.01 to 0.74 (p = .01). There was no significant change in the daily SBM frequency between fasting and feeding states (1.2 vs. 1.3; p = .8), and there was no correlation between the amount of food intake and the SBM frequency after elobixibat administration (r = .03). Serious adverse events were not observed.

Conclusion: This study showed that elobixibat is safe and effective for patients with cancer with chronic constipation, regardless of the food intake amount.

Implications For Practice: Elobixibat was effective at relieving chronic constipation in patients with various cancers. Serious adverse events were not observed, and the relief of constipation was independent of variation in food intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/onco.13879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488789PMC
October 2021
-->