start-ver=1.4 cd-journal=joma no-vol=71 cd-vols= no-issue=11 article-no= start-page=938 end-page=943 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250402 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mechanical Subpulmonary Support in Fontan Circulation: A Juvenile Porcine Experimental Model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Mechanical cavopulmonary assist (CPA) remains challenging for failing Fontan circulation. This study aimed to evaluate the hemodynamic impact of partial CPA using a juvenile porcine model. Six pigs (30?kg) underwent the Fontan procedure using a handmade Y-shaped graft. Total CPA was established by assisting both superior vena cava (SVC) and inferior vena cava (IVC) flow to the pulmonary artery, whereas partial CPA assisted only IVC flow using a centrifugal pump. Cavopulmonary assist flow was set to 100%, 50%, or 25% of pre-Fontan cardiac output (CO). Hemodynamics at baseline, after total CPA, and after partial CPA were compared using paired t-tests. Total CPA with 100% CO support increased CO and reduced SVC and IVC pressures compared to baseline (CO, 1.03 vs. 2.36?L/min; SVC pressure, 16.3 vs. 9.5?mm Hg; IVC pressure, 17.3 vs. 9.3?mm Hg, p < 0.05 for all). Partial CPA with 25% CO support increased CO and decreased IVC pressure, though SVC pressure increased (CO, 1.03 vs. 1.52?L/min; SVC pressure, 16.3 vs. 20.5?mm Hg; IVC pressure, 17.3 vs. 11.5?mm Hg, p < 0.05 for all). Although total CPA achieved optimal hemodynamics, partial CPA with 25% CO flow was effective, suggesting a feasible, noninvasive solution for patients with failing Fontan physiology. en-copyright= kn-copyright= en-aut-name=SakodaNaoya en-aut-sei=Sakoda en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KobayashiYasuyuki en-aut-sei=Kobayashi en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=EdakiDaichi en-aut-sei=Edaki en-aut-mei=Daichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KasaharaShingo en-aut-sei=Kasahara en-aut-mei=Shingo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KotaniYasuhiro en-aut-sei=Kotani en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=2 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=3 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=4 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= affil-num=5 en-affil=From the Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences and Okayama University Hospital kn-affil= END start-ver=1.4 cd-journal=joma no-vol=82 cd-vols= no-issue=10 article-no= start-page=1626 end-page=1637 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Redefining AT1 Receptor PET Imaging: Introducing the Radiotracer [18F]DR29 en-subtitle= kn-subtitle= en-abstract= kn-abstract=BACKGROUND: AT1R (angiotensin II type 1 receptors) are central to the renin-angiotensin system and are involved in regulating blood pressure and renal physiology. This study introduces [18F]DR29, a fluorine-18-labeled radiotracer for positron emission tomography imaging, to enable noninvasive visualization of AT1R expression. Its potential applications in understanding AT1R-associated renal processes are explored in healthy and hypertensive rat models.
METHODS: Radiolabeling was established, and biodistribution studies were conducted on healthy Wistar rats with and without the AT1R antagonist candesartan and transporter inhibitors. Dynamic positron emission tomography imaging assessed tracer specificity, and feasibility for renal AT1R quantification was explored using a hypertensive rat model.
RESULTS: [18F]DR29 was radiolabeled with a yield of 36}6%. High kidney uptake was observed, significantly reduced by candesartan (kidney-to-blood ratio, 0.43}0.01 versus 4.54}1.59 in vehicle, where vehicle refers to saline without any treatment). Transporter inhibition protocols targeting organic anion transporting polypeptides (liver) and organic anion transporters (kidneys) successfully reduced radiotracer clearance, increasing the specific accumulation of [18F]DR29 in the kidneys and improving renal imaging contrast. Positron emission tomography imaging revealed rapid kidney uptake and stable retention over 2 hours. In hypertensive rats, kidney uptake was higher, aligning with AT1R expression levels.
CONCLUSIONS: These results support [18F]DR29 as a promising tool for the noninvasive evaluation of renal AT1R expression in healthy and diseased states. The findings lay the groundwork for clinical translation, offering potential applications in diagnosing and managing kidney-related diseases, including hypertension and other conditions involving AT1R dysregulation. en-copyright= kn-copyright= en-aut-name=ChenXinyu en-aut-sei=Chen en-aut-mei=Xinyu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraHiroyuki en-aut-sei=Kimura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SasakiTakanori en-aut-sei=Sasaki en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KlimekKonrad en-aut-sei=Klimek en-aut-mei=Konrad kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=M?hligSaskia en-aut-sei=M?hlig en-aut-mei=Saskia kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=Arias-LozaAnahi Paula en-aut-sei=Arias-Loza en-aut-mei=Anahi Paula kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NoseNaoko en-aut-sei=Nose en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YagiYusuke en-aut-sei=Yagi en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=RoweSteven P en-aut-sei=Rowe en-aut-mei=Steven P kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=LapaConstantin en-aut-sei=Lapa en-aut-mei=Constantin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WernerRudolf A. en-aut-sei=Werner en-aut-mei=Rudolf A. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HiguchiTakahiro en-aut-sei=Higuchi en-aut-mei=Takahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=2 en-affil=Agency for Health, Safety and Environment, Kyoto University kn-affil= affil-num=3 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Goethe University Frankfurt, University Hospital, Clinic for Radiology and Nuclear Medicine, Department of Nuclear Medicine kn-affil= affil-num=5 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital W?rzburg kn-affil= affil-num=6 en-affil=Department of Nuclear Medicine and Comprehensive Heart Failure Center (DZHI), University Hospital W?rzburg kn-affil= affil-num=7 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Molecular Imaging and Therapeutics, Department of Radiology, School of Medicine, University of North Carolina, Chapel Hill kn-affil= affil-num=10 en-affil=Nuclear Medicine, Faculty of Medicine, University of Augsburg kn-affil= affil-num=11 en-affil=Department of Nuclear Medicine, LMU Hospital, Ludwig-Maximilians-University of Munich kn-affil= affil-num=12 en-affil=Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=angiotensin II type 1 receptor kn-keyword=angiotensin II type 1 receptor en-keyword=organic anion transporters kn-keyword=organic anion transporters en-keyword=organic anion transporting polypeptides kn-keyword=organic anion transporting polypeptides en-keyword=renal imaging kn-keyword=renal imaging en-keyword=renin-angiotensin system kn-keyword=renin-angiotensin system END start-ver=1.4 cd-journal=joma no-vol=11 cd-vols= no-issue=5 article-no= start-page=e200293 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202510 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Vanishing White Matter Disease With EIF2B2 c.254T >A Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objectives
Typical MRI findings of vanishing white matter disease (VWM) include diffuse white matter lesions with cystic degeneration. However, mild cases may lack these typical features, posing diagnostic challenges.
Methods
We describe 2 of 3 individuals carrying the homozygous c.254T >A variant in EIF2B2 identified at our hospital, excluding 1 previously reported case.1 Genetic analyses were performed using whole-genome sequence or whole-exome sequence analysis, and detected variants were confirmed by direct nucleotide sequence analysis. Brain MRI findings and clinical features were reviewed for the 2 individuals along with other cases in the literature with the same variant.
Results
A 69-year-old woman presented with recurrent transient dizziness and secondary amenorrhea. MRI of the brain revealed small T2-hyperintense lesions confined to the subcortical white matter with hyperintensities on diffusion-weighted images and mildly elevated apparent diffusion coefficient values. A 28-year-old woman presented with transient dizziness and secondary amenorrhea. MRI of the brain showed mild T2-hyperintense lesions in the cerebral white matter with frontal predominance.
Discussion
This report highlights the clinically mild cases of VWM with subtle abnormalities on brain MRI who had the homozygous c.254T >A in EIF2B2, further expanding the clinical spectrum of VWM and underscoring the importance of genetic assessments in the diagnosis of individuals with mild clinical and MRI findings. en-copyright= kn-copyright= en-aut-name=KakumotoToshiyuki en-aut-sei=Kakumoto en-aut-mei=Toshiyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsukawaTakashi en-aut-sei=Matsukawa en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TokimuraRyo en-aut-sei=Tokimura en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsuboyamaYoko en-aut-sei=Tsuboyama en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HayashiYasufumi en-aut-sei=Hayashi en-aut-mei=Yasufumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MitsutakeAkihiko en-aut-sei=Mitsutake en-aut-mei=Akihiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IwataAtsushi en-aut-sei=Iwata en-aut-mei=Atsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MaedaMeiko Hashimoto en-aut-sei=Maeda en-aut-mei=Meiko Hashimoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=ShimizuJun en-aut-sei=Shimizu en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=GonoiWataru en-aut-sei=Gonoi en-aut-mei=Wataru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuiJun en-aut-sei=Mitsui en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=TsujiShoji en-aut-sei=Tsuji en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=TodaTatsushi en-aut-sei=Toda en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=10 en-affil=Department of Radiology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=13 en-affil=Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, The University of Tokyo kn-affil= END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=6 article-no= start-page=732 end-page=740 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202511 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Causal Approaches to Disease Progression Analyses en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidemiologic analyses that aim to quantify exposure effects on disease progression are not uncommon. Understanding the implications of these studies, however, is complicated, in part because different causal estimands could, at least in theory, be the target of such analyses. Here, to facilitate interpretation of these studies, we describe different settings in which causal questions related to disease progression can be asked, and consider possible estimands. For clarity, our discussion is structured around settings defined based on two factors: whether the disease occurrence is manipulable or not, and the type of outcome. We describe relevant causal structures and sets of response types, which consist of joint potential outcomes of disease occurrence and disease progression, and argue that settings where interventions to manipulate disease occurrence are not plausible are more common, and that, in this case, principal stratification might be an appropriate framework to conceptualize the analysis. Further, we suggest that the precise definition of the outcome of interest, in particular of what constitutes its permissible levels, might determine whether potential outcomes linked to disease progression are definable in different strata of the population. Our hope is that this paper will encourage additional methodological work on causal analysis of disease progression, as well as serve as a resource for future applied studies. en-copyright= kn-copyright= en-aut-name=Gon?alvesBronner P. en-aut-sei=Gon?alves en-aut-mei=Bronner P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=disease progression kn-keyword=disease progression en-keyword=causal inference kn-keyword=causal inference en-keyword=principal stratification kn-keyword=principal stratification en-keyword=controlled direct effects kn-keyword=controlled direct effects en-keyword=potential outcomes kn-keyword=potential outcomes END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250922 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Applicability of Effective Atomic Number (Z eff) Image Analysis of Coronary Plaques Measured With Photon- Counting Computed Tomography en-subtitle= kn-subtitle= en-abstract= kn-abstract=Objective: Coronary computed tomography (CT) allows the assessment of cardiovascular risk by imaging calcified plaques in coronary arteries. Because photon-counting CT (PC-CT) can analyze the effective atomic number (Zeff) of the subject, it is expected to be applied to the analysis of plaque components. The purpose of this study was to investigate the applicability of plaque analysis based on Zeff images with continuous gradation.
Methods: Zeff images were generated from virtual monoenergetic images (VMIs) obtained by PC-CT. Zeff values were derived from the difference between linear attenuation coefficients (ƒÊ) at low and high energies using an in-house program. Coronary CT images of 64 plaques in 10 patients were analyzed. The Zeff score, calculated as the sum of Zeff values within the plaque region, was calculated and compared with the conventional Agatston score and mean coronary artery calcium (CAC) score.
Results: The systematic uncertainty of Zeff images was estimated to be }0.08. The Zeff score of actual patient data showed strong positive correlations with the conventional Agatston and mean CAC scores. The Zeff score uses all voxel data in the plaque area, whereas conventional scores consider only data from voxels with a CT value >130. We found that the conventional scores excluded 39% of the plaque area, and the Zeff score permitted the analysis of low- and high-density plaques.
Conclusions: Zeff imaging was shown to be applicable to plaque analysis that reflects the entire plaque volume. This study demonstrated its technical feasibility as a compositional analysis method using the Zeff image. en-copyright= kn-copyright= en-aut-name=AsaharaTakashi en-aut-sei=Asahara en-aut-mei=Takashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MitaniMana en-aut-sei=Mitani en-aut-mei=Mana kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=KimotoNatsumi en-aut-sei=Kimoto en-aut-mei=Natsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=NishigamiRina en-aut-sei=Nishigami en-aut-mei=Rina kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TakegamiKazuki en-aut-sei=Takegami en-aut-mei=Kazuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=MorimitsuYusuke en-aut-sei=Morimitsu en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AkagiNoriaki en-aut-sei=Akagi en-aut-mei=Noriaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyoshiToru en-aut-sei=Miyoshi en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KanazawaYuki en-aut-sei=Kanazawa en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IguchiToshihiro en-aut-sei=Iguchi en-aut-mei=Toshihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HayashiHiroaki en-aut-sei=Hayashi en-aut-mei=Hiroaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=2 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University kn-affil= affil-num=4 en-affil=Graduate School of Medical Sciences, Kanazawa University kn-affil= affil-num=5 en-affil=Department of Radiological Technology, Yamaguchi University Hospital kn-affil= affil-num=6 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Medical Support Department, Division of Radiology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Faculty of Life Science, Kumamoto University kn-affil= affil-num=10 en-affil=Department of Radiological Technology, Faculty of Health Sciences, Okayama University kn-affil= affil-num=11 en-affil=College of Transdisciplinary Sciences for Innovation, Kanazawa University kn-affil= en-keyword=effective atomic number image kn-keyword=effective atomic number image en-keyword=photon-counting computed tomography kn-keyword=photon-counting computed tomography en-keyword=virtual monoenergetic images kn-keyword=virtual monoenergetic images en-keyword=coronary CT kn-keyword=coronary CT en-keyword=coronary plaques kn-keyword=coronary plaques en-keyword=Agatston score kn-keyword=Agatston score END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250905 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Double-blind randomized noninferiority study of the effect of pharyngeal lidocaine anesthesia on EUS en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and objectives: EUS is typically performed under sedation, often with concomitant analgesics to reduce pain. Traditionally used pharyngeal anesthesia, commonly with lidocaine, may cause pharyngeal discomfort and allergic reactions. This study investigated whether lidocaine-based pharyngeal anesthesia is necessary for EUS under sedation with analgesics.
Methods: A double-blind, randomized, noninferiority study was conducted on EUS cases that met the selection criteria. Patients were randomly assigned to receive either 5 sprays of 8% lidocaine (lidocaine group: LG) or saline spray (placebo group: PG) as endoscopy pretreatment. The primary outcome was EUS tolerability, analyzed separately for endoscopists and patients, with a noninferiority margin set at 15%. Secondary outcomes included endoscopist and patient satisfaction, midazolam/pethidine doses, number of gag events, number of esophageal insertion attempts, use of sedative/analgesic antagonists, interruptions due to body movements, throat symptoms after endoscopy, and sedation-related adverse events.
Results: Favorable tolerance was 85% in LG and 88% for PG among endoscopists (percent difference: 3.0 [95% confidence interval, ?6.6 to 12.6]) and 90% in LG and 91% in PG among patients (percent difference, 0.94 [95% confidence interval, ?7.5 to 9.4]). Both groups exceeded the noninferiority margin (P = 0.0002 for endoscopists and patients). Patient satisfaction was significantly higher in PG (P = 0.0080), but no intergroup differences were found in other secondary outcomes.
Conclusions: PG was noninferior to LG for pharyngeal anesthesia during EUS with sedation and analgesics. These results suggest that pharyngeal anesthesia with lidocaine can be omitted when performing EUS under sedation with concomitant analgesics. Omitting pharyngeal anesthesia with lidocaine may prevent discomfort and complications caused by pharyngeal anesthesia, shorten examination times, and reduce medical costs. en-copyright= kn-copyright= en-aut-name=FujiiYuki en-aut-sei=Fujii en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MatsumotoKazuyuki en-aut-sei=Matsumoto en-aut-mei=Kazuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaradaKei en-aut-sei=Harada en-aut-mei=Kei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=HattoriNao en-aut-sei=Hattori en-aut-mei=Nao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoRyosuke en-aut-sei=Sato en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ObataTaisuke en-aut-sei=Obata en-aut-mei=Taisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumiAkihiro en-aut-sei=Matsumi en-aut-mei=Akihiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MiyamotoKazuya en-aut-sei=Miyamoto en-aut-mei=Kazuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=UchidaDaisuke en-aut-sei=Uchida en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=HoriguchiShigeru en-aut-sei=Horiguchi en-aut-mei=Shigeru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TsutsumiKoichiro en-aut-sei=Tsutsumi en-aut-mei=Koichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MitsuhashiToshiharu en-aut-sei=Mitsuhashi en-aut-mei=Toshiharu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OtsukaMotoyuki en-aut-sei=Otsuka en-aut-mei=Motoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=2 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=3 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=4 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=5 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=6 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=7 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=8 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=9 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=10 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=11 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= affil-num=12 en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital kn-affil= affil-num=13 en-affil=Department of Gastroenterology and Hepatology, Okayama University Hospital kn-affil= en-keyword=EUS kn-keyword=EUS en-keyword=Lidocaine kn-keyword=Lidocaine en-keyword=Tolerance kn-keyword=Tolerance END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=5 article-no= start-page=686 end-page=689 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202509 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=L or M1?Critical Challenges in Mediation Analysis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Methods for causal mediation analysis have developed dramatically over the past few decades.1?7 In the causal mediation literature, several causal quantities?or estimands?have been proposed, including natural direct and indirect effects, interventional direct and indirect effects, and separable direct and indirect effects. As another possible causal estimand, Chen and Lin8 proposed separable path-specific effects, which is an extension of the separable effects framework to cases that involve multiple ordered mediators. In this commentary, I briefly discuss the newly proposed method from a broader perspective on causal mediation analysis. For readers less familiar with common causal mediation approaches, please see related literature.1?3,9?11 en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=36 cd-vols= no-issue=3 article-no= start-page=374 end-page=380 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202505 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effect Modification in Settings with gTruncation by Deathh en-subtitle= kn-subtitle= en-abstract= kn-abstract=Epidemiologic studies recruiting individuals with higher-than-population-average mortality can be affected by gtruncation by death,h whereby the outcome of interest (e.g., quality of life) is considered not to be defined for individuals who die before the end of follow-up. Here, we use the potential outcomes framework and principal stratification to derive conditions under which the survivor average causal effect, an estimand defined for the galways-survivorsh stratum, is modified by a variable that represents a possible common cause of survival and the outcome of interest and by a variable that only affects survival. Further, we show that this principal effect can be expressed as a weighted average of this treatment effect for individuals with each level of these variables, and that these weights depend not only on the relative frequencies of the levels in the total population but also on the galways-survivorsh principal stratum. We also discuss the implications of this work for the transportability of the survivor average causal effect. en-copyright= kn-copyright= en-aut-name=Gon?alvesBronner P. en-aut-sei=Gon?alves en-aut-mei=Bronner P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Comparative Biomedical Sciences, Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Causal inference kn-keyword=Causal inference en-keyword=Effect modification kn-keyword=Effect modification en-keyword=Principal stratification kn-keyword=Principal stratification en-keyword=Transportability kn-keyword=Transportability END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=6 article-no= start-page=801 end-page=804 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Preventable Fraction in the Context of Disease Progression en-subtitle= kn-subtitle= en-abstract= kn-abstract=The relevance of the epidemiologic concept of preventable fraction to the study of the population-level impact of preventive exposures is unequivocal. Here, we discuss how the preventable fraction can be usefully understood for the class of outcomes that relate to disease progression (e.g., clinical severity given diagnosis), and, under the principal stratification framework, derive an expression for this quantity for this type of outcome. In particular, we show that, in the context of disease progression, the preventable fraction is a function of the effect on the postdiagnosis outcome in the principal stratum in the unexposed group who would have disease regardless of exposure status. This work will facilitate an understanding of the contribution of principal effects to the impact of preventive exposures at the population level. en-copyright= kn-copyright= en-aut-name=Gon?alvesBronner P. en-aut-sei=Gon?alves en-aut-mei=Bronner P. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Comparative Biomedical Sciences, Faculty of Health and Medical Sciences, University of Surrey kn-affil= affil-num=2 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Counterfactual framework kn-keyword=Counterfactual framework en-keyword=Disease progression kn-keyword=Disease progression en-keyword=Disease severity kn-keyword=Disease severity en-keyword=Preventable fraction kn-keyword=Preventable fraction en-keyword=Principal stratification kn-keyword=Principal stratification END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=11 article-no= start-page=1992 end-page=2000 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202411 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=INVESTIGATION OF THE PATHOPHYSIOLOGY OF EPIRETINAL MEMBRANE FOVEOSCHISIS: Analysis of Longitudinal Changes in Visual Functions, Retinal Structures, and Retinal Traction Force en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To analyze the pathophysiology of epiretinal membrane foveoschisis (FS) by evaluating the longitudinal changes in visual function and several optical coherence tomography parameters.
Methods: The medical records of 33 consecutive patients (35 eyes) with untreated epiretinal membrane foveoschisis were retrospectively reviewed. Best-corrected visual acuity, M-CHARTS score, and optical coherence tomography parameters including epiretinal membrane area, maximum depth of retinal folds, FS area, and FS circularity were evaluated.
Results: A wide range of FS area changes was observed at the final follow-up visit (59.68%?240.45% of the baseline FS area). In the FS enlargement group, best-corrected visual acuity and mean M-CHARTS scores significantly worsened and maximum depth of retinal folds significantly increased over time, whereas in the FS non-enlargement group, no significant change was observed in the best-corrected visual acuity, mean M-CHARTS scores, or maximum depth of retinal folds during the follow-up period. Multivariate logistic regression analyses revealed that maximum depth of retinal folds (odds ratio: 1.05, 95% confidence interval: 1.00?1.10, P = 0.048) and FS circularity (odds ratio: 0.91, 95% confidence interval: 0.83?1.00, P = 0.043) were significantly associated with FS enlargement.
Conclusion: Epiretinal membrane foveoschisis encompasses diverse pathophysiologies. Since visual functions do not worsen in some cases, monitoring the changes in visual functions and retinal morphology over time is recommended to determine surgical indications. en-copyright= kn-copyright= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasudaYuki en-aut-sei=Masuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HosokawaMio M. en-aut-sei=Hosokawa en-aut-mei=Mio M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=en-face imaging kn-keyword=en-face imaging en-keyword=epiretinal membrane kn-keyword=epiretinal membrane en-keyword=epiretinal membrane foveoschisis kn-keyword=epiretinal membrane foveoschisis en-keyword=foveoschisis kn-keyword=foveoschisis en-keyword=lamellar macular hole kn-keyword=lamellar macular hole en-keyword=metamorphopsia kn-keyword=metamorphopsia en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=retinal fold kn-keyword=retinal fold en-keyword=retinal traction kn-keyword=retinal traction END start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=10 article-no= start-page=1785 end-page=1792 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202410 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=MIXED PATHOPHYSIOLOGIES OF LAMELLAR MACULAR HOLES AND RELATED DISEASES: A Multimodal Optical Coherence Tomography?Based Study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To investigate the characteristics of mixed pathophysiologies in lamellar macular holes (LMHs) and related diseases using multimodal optical coherence tomography.
Methods: Overall, 126 eyes diagnosed with LMH, epiretinal membrane foveoschisis, or macular pseudohole using the horizontal B-scan image according to the definition proposed by Hubschman et al in 2020 were analyzed using multimodal optical coherence tomography imaging including horizontal and vertical 5-line B-scan, radial scan, and macular three-dimensional volume scan images. If at least two diagnostic criteria for LMH, epiretinal membrane foveoschisis, or macular pseudohole were satisfied in these scans, the patient was diagnosed as having a gmixed type.h Retinal traction force was quantitatively evaluated by measuring the maximum depth of the retinal folds using en-face images.
Results: Mixed types constituted 34.1% of the cases. The LMH-related mixed group demonstrated intermediate characteristics between the epiretinal membrane foveoschisis/macular pseudohole and true LMH groups in terms of retinal traction and LMH-specific features and had a significant positive correlation between the maximum depth of the retinal folds and mean M-CHARTS scores (P = 0.034).
Conclusion: A thorough optical coherence tomography analysis is necessary to accurately diagnose LMH and related diseases. A significant positive correlation was observed between the maximum depth of the retinal folds and the degree of metamorphopsia in the LMH-related mixed group. en-copyright= kn-copyright= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KanzakiYuki en-aut-sei=Kanzaki en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MoritaTetsuro en-aut-sei=Morita en-aut-mei=Tetsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MasudaYuki en-aut-sei=Masuda en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=HosokawaMio M. en-aut-sei=Hosokawa en-aut-mei=Mio M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=en-face imaging kn-keyword=en-face imaging en-keyword=epiretinal membrane kn-keyword=epiretinal membrane en-keyword=epiretinal membrane foveoschisis kn-keyword=epiretinal membrane foveoschisis en-keyword=lamellar macular hole kn-keyword=lamellar macular hole en-keyword=metamorphopsia kn-keyword=metamorphopsia en-keyword=mixed type kn-keyword=mixed type en-keyword=optical coherence tomography kn-keyword=optical coherence tomography en-keyword=retinal fold kn-keyword=retinal fold en-keyword=retinal traction kn-keyword=retinal traction END start-ver=1.4 cd-journal=joma no-vol=33 cd-vols= no-issue=4 article-no= start-page=294 end-page=301 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202307 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Role of lymphadenectomy during primary surgery for kidney cancer en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose of review
Lymph node dissection (LND) during radical nephrectomy (RN) for renal cell carcinoma (RCC) is not considered as a standard. The emergence of robot-assisted surgery and effective immune checkpoint inhibitors (ICI) in recent years may change this and lymph node (LN) staging has become easier and has a clinical impact. In this review, we aimed to reconsider the role of LND today.

Recent findings
Although the extent of LND has still not been well established, removal of more LN seems to provide better oncologic outcomes for a select group of patients with high-risk factors such as clinical T3-4. Adjuvant therapy using pembrolizumab has been shown to improve disease free survival if complete resection of metastatic lesions as well as the primary site is obtained in combination. Robot assisted RN for localized RCC has been widespread and the studies regarding LND for RCC has been recently appeared.

Summary
The staging and surgical benefits and its extent of LND during RN for RCC remains unclear, but it is becoming increasingly important. Technologies that allow an easier LND and adjuvant ICI that improve survival in LN-positive patients are engaging the role of LND, a procedure that was needed, but almost never done, is now indicated sometimes. Now, the goal is to identify the clinical and molecular imaging tools that can help identify with sufficient accuracy who needs a LND and which LNs to remove in a targeted personalized approach. en-copyright= kn-copyright= en-aut-name=BekkuKensuke en-aut-sei=Bekku en-aut-mei=Kensuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KawadaTatsushi en-aut-sei=Kawada en-aut-mei=Tatsushi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YanagisawaTakafumi en-aut-sei=Yanagisawa en-aut-mei=Takafumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KarakiewiczPierre I. en-aut-sei=Karakiewicz en-aut-mei=Pierre I. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ShariatShahrokh F. en-aut-sei=Shariat en-aut-mei=Shahrokh F. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= affil-num=1 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= affil-num=4 en-affil=Cancer Prognostic and Health Outcomes Unit, Division of Urology, University of Montreal Health Center kn-affil= affil-num=5 en-affil=Department of Urology, Comprehensive Cancer Center, Medical University of Vienna kn-affil= en-keyword=lymph node dissection kn-keyword=lymph node dissection en-keyword=lymph node metastasis kn-keyword=lymph node metastasis en-keyword=lymphadenectomy kn-keyword=lymphadenectomy en-keyword=lymphadenopathy kn-keyword=lymphadenopathy en-keyword=Renal cell carcinoma kn-keyword=Renal cell carcinoma END start-ver=1.4 cd-journal=joma no-vol=35 cd-vols= no-issue=4 article-no= start-page=469 end-page=472 dt-received= dt-revised= dt-accepted= dt-pub-year=2024 dt-pub=202407 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Errors in the Calculation of the Population Attributable Fraction en-subtitle= kn-subtitle= en-abstract= kn-abstract=One of the common errors in the calculation of the population attributable fraction (PAF) is the use of an adjusted risk ratio in the Levin formula. In this article, we discuss the errors visually using wireframes by varying the standardized mortality ratio (SMR) and associational risk ratio (aRR) when the prevalence of exposure is fixed. When SMR >1 and SMR > aRR, the absolute bias is positive, and its magnitude increases as the difference between SMR and aRR increases. By contrast, when aRR > SMR > 1, the absolute bias is negative and its magnitude is relatively small. Moreover, when SMR > aRR, the relative bias is larger than one, whereas when SMR < aRR, the relative bias is smaller than one. Although the target population of the PAF is the total population, the target of causation of the PAF is not the total population but the exposed group. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Okayama University of Science kn-affil= en-keyword=Attributable fraction kn-keyword=Attributable fraction en-keyword=Bias kn-keyword=Bias en-keyword=Causality kn-keyword=Causality en-keyword=Counterfactual model kn-keyword=Counterfactual model en-keyword=Potential outcomes kn-keyword=Potential outcomes END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=2 article-no= start-page=182 end-page=194 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=20231208 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium?glucose cotransporter 2 inhibitors revealed prominent therapeutic effects on diabetic kidney disease. Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid (AA) transporters in the apical membranes of PTCs. We investigated the beneficial effects of reduced influx of AAs into PTCs in diabetes and obesity model of Cltrn?/y mice.
Methods Cltrn+/y and Cltrn?/y mice at age 5 weeks were assigned to standard diet and streptozotocin and high-fat diet (STZ-HFD)?treated groups.
Results At age 22?23 weeks, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared with standard diet-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn?/y compared with STZ-HFD-Cltrn+/y. At age 20 weeks, urinary albumin creatinine ratio was significantly reduced in STZ-HFD-Cltrn?/y compared with STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of AAs such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu, and Pro. In PTCs in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 ƒÊm or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn?/y. Phospho-mTOR and inactive form of phospho-transcription factor EB were reduced in STZ-HFD-Cltrn?/y compared with STZ-HFD-Cltrn+/y.
Conclusions The reduction of AAs influx into PTCs inactivated mTOR, activated transcription factor EB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn?/y mice. en-copyright= kn-copyright= en-aut-name=KanoYuzuki en-aut-sei=Kano en-aut-mei=Yuzuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamaguchiSatoshi en-aut-sei=Yamaguchi en-aut-mei=Satoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MiseKoki en-aut-sei=Mise en-aut-mei=Koki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawakitaChieko en-aut-sei=Kawakita en-aut-mei=Chieko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OnishiYasuhiro en-aut-sei=Onishi en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurookaNaoko en-aut-sei=Kurooka en-aut-mei=Naoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SugawaraRyosuke en-aut-sei=Sugawara en-aut-mei=Ryosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AlbuayjanHaya Hamed Hassan en-aut-sei=Albuayjan en-aut-mei=Haya Hamed Hassan kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakatsukaAtsuko en-aut-sei=Nakatsuka en-aut-mei=Atsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=EguchiJun en-aut-sei=Eguchi en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=WadaJun en-aut-sei=Wada en-aut-mei=Jun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=11 en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=diabetes mellitus kn-keyword=diabetes mellitus en-keyword=diabetic nephropathy kn-keyword=diabetic nephropathy en-keyword=metabolism kn-keyword=metabolism en-keyword=obesity kn-keyword=obesity en-keyword=tubular epithelium kn-keyword=tubular epithelium END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=4 article-no= start-page=585 end-page=593 dt-received= dt-revised= dt-accepted= dt-pub-year=2023 dt-pub=202304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=IMPACT OF MACULAR INTRARETINAL HEMORRHAGE AND MACULAR HOLE ON THE VISUAL PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE en-subtitle= kn-subtitle= en-abstract= kn-abstract=Purpose: To compare the effects of macular intraretinal hemorrhage (IRH) and macular hole (MH) on best-corrected visual acuity (BCVA) after displacement of submacular hemorrhage (SMH) due to retinal arterial macroaneurysm (RAM) rupture.
Methods: This multicenter retrospective study included 48 eyes with SMH due to RAM rupture. Cases underwent vitrectomy to displace SMH and were followed up for 6 months. We classified cases according to the presence of IRH and MH and compared the postoperative BCVA among the groups.
Results: We classified the eyes into IRH(+)MH(+) group (10 eyes), IRH(+)MH(?) group (23 eyes), and IRH(?)MH(?) group (15 eyes). The postoperative BCVA was significantly worse in the IRH(+)MH(+) and IRH(+)MH(?) groups than in the IRH(?)MH(?) group (0.91 } 0.41 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/163, 0.87 } 0.45, 20/148, and 0.18 } 0.21, 20/30, respectively; P < 0.001). The postoperative central retinal thickness was significantly lower in the IRH(+) group (IRH(+)MH(+) and IRH(+)MH(?) groups combined) than in the IRH(?) group (IRH(?)MH(?) group) (121.4 } 70.1 ?m and 174.3 } 32.9 ?m, respectively, P = 0.008). The postoperative external limiting membrane and ellipsoid zone continuities were significantly discontinuous in the IRH(+) group (P < 0.001, P = 0.001, respectively). The multiple linear regression analysis showed that both IRH(+)MH(+) and IRH(+)MH(?) were associated with the postoperative BCVA (regression coefficient, 0.799 and 0.711, respectively; P < 0.001 for both).
Conclusion: Both IRH and MH were poor prognostic indicators in cases with SMH due to RAM rupture. en-copyright= kn-copyright= en-aut-name=DoiShinichiro en-aut-sei=Doi en-aut-mei=Shinichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KimuraShuhei en-aut-sei=Kimura en-aut-mei=Shuhei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SaitoShoko en-aut-sei=Saito en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=InoueMakoto en-aut-sei=Inoue en-aut-mei=Makoto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SakuraiToshiya en-aut-sei=Sakurai en-aut-mei=Toshiya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KoboriAkira en-aut-sei=Kobori en-aut-mei=Akira kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=HisatomiToshio en-aut-sei=Hisatomi en-aut-mei=Toshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ImaiHisanori en-aut-sei=Imai en-aut-mei=Hisanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=KuriyamaShoji en-aut-sei=Kuriyama en-aut-mei=Shoji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=TakasuIppei en-aut-sei=Takasu en-aut-mei=Ippei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=HosokawaMio Morizane en-aut-sei=Hosokawa en-aut-mei=Mio Morizane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=ShiodeYusuke en-aut-sei=Shiode en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=MatobaRyo en-aut-sei=Matoba en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MorizaneYuki en-aut-sei=Morizane en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Kyorin Eye Center, Kyorin University School of Medicine kn-affil= affil-num=4 en-affil=Kyorin Eye Center, Kyorin University School of Medicine kn-affil= affil-num=5 en-affil=Department of Ophthalmology, Tane Memorial Eye Hospital kn-affil= affil-num=6 en-affil=Department of Ophthalmology, Fukui Red Cross Hospital kn-affil= affil-num=7 en-affil=Department of Ophthalmology, Chikushi Hospital, Fukuoka University kn-affil= affil-num=8 en-affil=Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine kn-affil= affil-num=9 en-affil=Otowa Eye Center kn-affil= affil-num=10 en-affil=Takasu Eye Clinic kn-affil= affil-num=11 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=12 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=13 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=14 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=15 en-affil=Department of Ophthalmology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=macular intraretinal hemorrhage kn-keyword=macular intraretinal hemorrhage en-keyword=macular hole kn-keyword=macular hole en-keyword=submacular hemorrhage kn-keyword=submacular hemorrhage en-keyword=retinal arterial macroaneurysm kn-keyword=retinal arterial macroaneurysm en-keyword=fluffy sign kn-keyword=fluffy sign en-keyword=tissue plasminogen activator kn-keyword=tissue plasminogen activator END start-ver=1.4 cd-journal=joma no-vol=32 cd-vols= no-issue=6 article-no= start-page=838 end-page=845 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=202111 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Marginal Sufficient Component Cause Model - An Emerging Causal Model With Merits? en-subtitle= kn-subtitle= en-abstract= kn-abstract=For decades, the sufficient cause model and the counterfactual model have shaped our understanding of causation in biomedical science, and the link between these two models has enabled us to obtain a deeper understanding of causality. Recently, a new causal model?the marginal sufficient component cause model?was proposed and applied in the context of interaction or mediation. The proponents of this model have emphasized its utility in visualizing the presence of gagonismh (a subtype of mechanistic interaction) in the counterfactual framework, claiming that the concept of agonism has not been clearly defined in causal inference and that agonistic interaction cannot be visualized by the conventional sufficient cause model. In this article, we illustrate that careful scrutiny based on the conventional sufficient cause model yields further insights into the concept of agonism in a more biologic sense. We primarily focus on the following three points: a) gagonismh defined in the counterfactual model can be visualized as sets of sufficient causes in the conventional sufficient cause model; b) although the so-called independent competing assumption or no redundancy assumption may seem irrelevant in the marginal sufficient component cause model, researchers do need to assume that potential completion times of relevant marginal sufficient causes differ; c) possibly differing potential completion times of marginal sufficient causes cannot be discerned until their hidden mechanistic paths are considered in the conventional sufficient cause model. In this rapidly progressing field of research, decades after its introduction, the sufficient cause model retains its worth. en-copyright= kn-copyright= en-aut-name=SuzukiEtsuji en-aut-sei=Suzuki en-aut-mei=Etsuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamamotoEiji en-aut-sei=Yamamoto en-aut-mei=Eiji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= affil-num=1 en-affil=Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Okayama University of Science kn-affil= en-keyword=Agonism kn-keyword=Agonism en-keyword=Causality kn-keyword=Causality en-keyword=Counterfactual model kn-keyword=Counterfactual model en-keyword=Mediation kn-keyword=Mediation en-keyword=Potential outcomes kn-keyword=Potential outcomes en-keyword=Sufficient cause model kn-keyword=Sufficient cause model END