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We synthesized bis and tris(macrocycle)s in which a two- or three-fold macrocycle was fused and each adopted twisted forms with M- or P-helicity. According to the sense of twisting in each element, diverse conformations can be generated in a molecule. We present two types of conformational preferences. One is the innate preference for a helical form with an identical sense of twisting throughout the entire molecule. The other is the helical-sense preference for a particular sense of twisting. We were interested in the relationship between K-n and (K-1)(n), where K-n is an equilibrium constant for the conformational interconversion between two helical forms (MM and PP, MMM and PPP) and n is the number of elements, since we considered that the relationship could be a metric to see the interinfluence among these macrocyclic elements in a single molecule. Through VT measurements in H-1 NMR and CD spectroscopy, we attempted to quantify the helical-sense preferences induced in the fused macrocycles (n = 2 and 3) to compare K-n and (K-1)(n).

Background and Objective: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. Methods: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior pulmonary veins (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP) and conduction properties within the PVs were analyzed. Results: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI-dependent anisotropic conduction at the AF onset was visualized in a 3D-mapping. Onset of AF was site-specific with reproducibility in each individual. Mean ERP in LSPV in the AF inducible group was shorter than that in the AF non-inducible group (182 ± 55 ms vs 254 ± 51 ms, P

Aim To develop and validate a model for the early prediction of long-term neurological outcome in patients with non-traumatic out-of-hospital cardiac arrest (OHCA). Methods We analysed multicentre OHCA registry data of adult patients with non-traumatic OHCA who experienced return of spontaneous circulation (ROSC) and had been admitted to the intensive care unit between 2013 and 2017. We allocated 1329 (2013–2015) and 1025 patients (2016–2017) to the derivation and validation sets, respectively. The primary outcome was the dichotomized cerebral performance category (CPC) at 90 days, defined as good (CPC 1–2) or poor (CPC 3–5). We developed 2 models: model 1 included variables without laboratory data, and model 2 included variables with laboratory data available immediately after ROSC. Logistic regression with least absolute shrinkage and selection operator regularization was employed for model development. Measures of discrimination, accuracy, and calibration (C-statistics, Brier score, calibration plot, and net benefit) were assessed in the validation set. Results The C-statistic (95% confidence intervals) of models 1 and 2 in the validation set was 0.947 (0.930–0.964) and 0.950 (0.934–0.966), respectively. The Brier score of models 1 and 2 in the validation set was 0.0622 and 0.0606, respectively. The calibration plot showed that both models were well-calibrated to the observed outcome. Decision curve analysis indicated that model 2 was similar to model 1. Conclusion The prediction tool containing detailed in-hospital information showed good performance for predicting neurological outcome at 90 days immediately after ROSC in patients with OHCA.

We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA).This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR10), 'normal BCR' (10 ≤ BCR 20), 'high BCR' (20 ≤ BCR 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA.Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients.Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients.

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1–tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1+ limb-bud-like mesenchymal cells under defined xeno-free conditions, and the prospective assessment of the cells’ chondrogenic potential via the cell-surface markers CD90, CD140B and CD82. The cells, which proliferated stably and exhibited the potential to undergo chondrogenic differentiation, formed hyaline cartilaginous-like tissue commensurate to their PRRX1-expression levels. Moreover, we show that limb-bud-like mesenchymal cells derived from patient-derived induced hPSCs can be used to identify therapeutic candidates for type II collagenopathy and we developed a method to generate uniformly sized hyaline cartilaginous-like particles by plating the cells on culture dishes coated with spots of a zwitterionic polymer. PRRX1+ limb-bud-like mesenchymal cells could facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering. A protocol for the selective differentiation of human pluripotent stem cells into expandable PRRX1+ limb-bud-like mesenchymal cells allows for the prospective assessment of the cells’ chondrogenic potential and the formation of hyaline cartilaginous-like particles.

Aims It has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow‐up at outpatient care within 2 weeks after discharge affects the long‐term readmission rate and prognosis. Methods and results We reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two‐hundred and fifty‐nine patients who died in‐hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow‐up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow‐up and performed a propensity score‐matching analysis (n = 259 each). HF readmission during 2 year follow‐up was significantly less in the early follow‐up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447–0.935] as well as the composite outcome was less in the early follow‐up group (P = 0.01, HR = 0.643, 95% CI = 0.456–0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow‐up (P = 0.505, HR = 1.208, 95% CI = 0.692–2.106). Conclusions The present study demonstrates that an early follow‐up approach after discharge in CHF patients may improve the long‐term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge.

Background The pulmonary veins (PVs) have unique electrophysiological properties triggering and maintaining atrial fibrillation (AF). Bigeminal PV electrical activity (PV bigeminy) during sinus rhythm has been reported; however, its mechanisms and clinical implication remain unclear. We hypothesized that PV bigeminy indicates arrhythmogenic activities and influences clinical outcome. Methods and Results We retrospectively analyzed electrophysiological studies in 465 patients with AF who underwent first session PV isolation (PVI). PV bigeminy was observed in 30 PVs of 23 patients (4.9% of patients). PV bigeminy was observed in left inferior PV (LIPV) in 15 patients, which was the most prevalent, followed by left superior in seven and right superior in seven and right inferior in one. In response to atrial extra stimulus, the second PV potentials (PV2) showed decremental conduction properties, suggesting reentrant mechanisms involved (n = 5). Interestingly, AF was initiated from the 23 PVs with bigeminy in 21 patients (76.7% of 30 PVs with bigeminy), spontaneously or in response to drugs, which was significantly more prevalent from the AF initiation rate from each PV in the control 442 patients (182 firings in 1290 PVs, 14.1%, P, PV bigeminy is relatively rare but a unique electrophysiological finding that indicates arrhythmogenic PV triggering AF.

Summary Chondrodysplasias are hereditary diseases caused by mutations in the components of growth cartilage. Although the unfolded protein response (UPR) has been identified as a key disease mechanism in mouse models, no suitable in vitro system has been reported to analyze the pathology in humans. Here, we developed a three-dimensional culture protocol to differentiate hypertrophic chondrocytes from induced pluripotent stem cells (iPSCs) and examine the phenotype caused by MATN3 and COL10A1 mutations. Intracellular MATN3 or COL10 retention resulted in increased ER stress markers and ER size in most mutants, but activation of the UPR was dependent on the mutation. Transcriptome analysis confirmed a UPR with wide-ranging changes in bone homeostasis, extracellular matrix composition, and lipid metabolism in the MATN3 T120M mutant, which further showed altered cellular morphology in iPSC-derived growth-plate-like structures in vivo. We then applied our in vitro model to drug testing, whereby trimethylamine N-oxide led to a reduction of ER stress and intracellular MATN3., Highlights • A new induction method enables hypertrophic chondrocyte differentiation from iPSCs • Chondrodysplasia mutants show intracellular MATN3 or COL10 accumulation • Some, but not all, mutants have ER stress with an unfolded protein response • This induction system is applicable to transcriptomic analysis and drug development, Chondrodysplasias are highly heterogeneous genetic cartilage diseases. Here, Toguchida and colleagues establish a new induction system to differentiate hypertrophic chondrocytes from iPSCs and analyze these disorders in vitro. They found that different chondrodysplasia mutants, despite mutations being in the same gene, showed varying phenotypes and transcriptomic changes. This system provides an initial platform for further investigation and drug development.

Extracorporeal cardiopulmonary resuscitation (ECPR) is performed in refractory out-of-hospital cardiac arrest (OHCA) patients, and the eligibility has been conventionally determined based on three criteria (initial cardiac rhythm, time to hospital arrival within 45 minutes, and age75 years) in Japan. Owing to limited information, this study descriptively determined neurological outcomes after applying the three criteria among OHCA patients who underwent ECPR.This study conducted a post-hoc analysis of data from the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study. This was a multi-institutional prospective observational study of OHCA patients in Osaka Prefecture, Japan. All adult (aged ≥18 years) OHCA patients with internal medical causes treated with ECPR between 1 July 2012 and 31 December 2019 were evaluated. We described one-month neurological favourable outcomes based on the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age75 years), and we compared them using the chi-square test.Among 18,379 patients screened from the CRITICAL study database, we included 517 OHCA patients treated by ECPR; 311 (60.2%) patients met all three criteria. Favourable neurological outcomes were as follows: patients meeting no or one criterion: 2.3% (1/43), those meeting two criteria: 8% (13/163), and those meeting all criteria: 16.1% (50/311) (P-value = 0.004).In this study, approximately 60% of patients treated by ECPR met the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age75 years), and the greater the number of criteria met, the better were the neurological outcomes achieved.

Estimating prognosis of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) is essential for selecting candidates. The TiPS65 score can predict neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) treated with ECPR. We aimed to perform an external validation of this score.Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multicentred, nationwide, prospectively registered database, were analysed. All adult patients with OHCA and shockable rhythm and treated with ECPR between January 2018 to December 2019 were included. In the TiPS65 score, age, call-to-hospital arrival time, initial cardiac rhythm at hospital arrival, and initial pH value were used as predictors. The primary outcome was 30-day survival with favourable neurological outcomes (Cerebral Performance Category 1 or 2). Discrimination, using the C-statistic, and predictive performances of each score, such as sensitivity and specificity, were investigated.Of 590 included patients (517 [81.6%] men; median [interquartile range] age, 60 [50-69] years), 64 (10.8%) reported favourable neurological outcomes. The C-statistic of the TiPS65 score was 0.729 (95% confidence interval (CI): 0.672-0.786). When the cut-off of TiPS65 score was set to1, the sensitivity and specificity were 0.906 (95%CI: 0.807-0.965) and 0.430 (95%CI: 0.387-0.473), respectively; conversely, when the cut-off was set to3, they were 0.172 (95%CI: 0.089-0.287) and 0.971 (95%CI: 0.953-0.984), respectively.The TiPS65 score shows reasonable discrimination and predictive performances. This score can be supportive in the decision-making process for the selection of eligible patients for ECPR in clinical settings.

The recapitulation of bone formation via the in vitro generation of bone-like nodules is frequently used to understand bone development. However, current bone-induction techniques are slow and difficult to reproduce. Here, we report the formation of bone-like nodules within ten days, via the use of retinoic acid (RA) to induce the osteogenic differentiation of human induced pluripotent stem cells (hiPSCs) into osteoblast-like and osteocyte-like cells that create human bone tissue when implanted in calvarial defects in mice. We also show that the induction of bone formation depends on cell signalling through the RA receptors RARα and RARβ, which simultaneously activate the BMP (bone morphogenetic protein) and Wnt signalling pathways. Moreover, by using patient-derived hiPSCs, the bone-like nodules recapitulated the osteogenesis-imperfecta phenotype, which was rescued via the correction of disease-causing mutations and partially by an mTOR (mechanistic target of rapamycin) inhibitor. The method of inducing bone nodules may serve as a fast and reproducible model for the study of the formation of both healthy and pathological bone. A fast in vitro model of the formation of bone-like nodules, enabled by the retinoic-acid-mediated induction of the osteogenic differentiation of patient-derived induced pluripotent stem cells, recapitulates the osteogenesis-imperfecta phenotype.

BackgroundCongenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms inTBX6have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identifyTBX6variants in CS and SCD and examine their pathogenicity.MethodsWe recruited 200 patients with CS or SCD and investigatedTBX6variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments.ResultsWe identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions ofTBX6and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype.ConclusionsOur study suggests that bi-allelic loss of function variants ofTBX6cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss ofTBX6function.

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.

Patients with pancreatic ductal adenocarcinoma (PDAC) that have a history of other primary malignancies are not well documented. The current study therefore aimed to evaluate the clinicopathological characteristics of patients with PDAC with or without a history of other primary malignancies. A total of 102 patients with surgically treated PDAC that presented with or without a history of other primary malignancies were retrospectively analyzed. A total of 25 patients (24.5%) had a history of other primary malignancies (age, with history of other primary malignancy vs. without, 74.2 vs. 68.9 years; P=0.005) and the reason for consultation (P

Background Induction of atrial fibrillation (AF)/atrial tachycardia (AT) by atrial burst pacing following ablation procedure may reflect the presence of residual substrates in the atria that maintain AF. However, the relation between the inducibility and left atrial low voltage area (LVA) has not been established. Methods Fifty-nine patients (65 years old, 43 males) with persistent AF who underwent pulmonary vein isolation (PVI)-based ablation were studied. All patients underwent left atrial voltage mapping during sinus rhythm and atrial burst pacing after PVI. Atrial burst pacing was performed with 30-beat at an amplitude of 10V from the ostium of the coronary sinus; increasing from 240 to 320 ppm in steps of 20 ppm or failure to 1:1 atrial capture. Inducibility was defined as AF/AT lasting more than 5 minutes following burst pacing. Left atrial LVA and other co-variates were analyzed with regard to burst pacing positivity. Results AF/AT was induced by burst pacing in 23 patients (39%). Univariate analysis revealed that past history of stroke, CHADS2 score and presence of left atrial LVA were significantly associated with the inducibility of AF/AT. Multivariate analysis revealed that only the presence of LVA was associated with the inducibility (OR 1.5: per 10% increase; p=0.04). We focused on the relationship between the extent of LVA and burst positivity. AF/AT inducibility increased as low voltage area increased, and it was as high as 72.7% when low voltage area was more than 20% (P Conclusions Presence of left atrial LVA is an independent predictor of atrial tachyarrhythmia inducibility after PVI in patients with persistent AF. A large amount of low voltage area is related to AT inducibility rather than AF. Extent of LVA and burst positivity Funding Acknowledgement Type of funding source: None

Background/Introduction It has been reported that heart failure (HF) readmission has not declined even with current cardiology practice in the last 10 years. It has been also reported that HF readmission tends to occur shortly after discharge. This may be due to overwork and excessive salt intake after discharge. In other words, it is conceivable that patient factors are largely attributable, which should be intervene for better clinical outcomes. Purpose We hypothesized and investigated whether an early follow-up visit at outpatient care within 2 weeks after discharge affects the re-admission rate and prognosis in patients with decompensated HF. Methods We retrospectively investigated consecutive 407 hospitalized patients due to decompensated HF. After exclusion of 99 patients with in-hospital death, transfer to another hospital and readmission within 2 weeks after discharge, consecutive 308 out of 407 patients were investigated. Two-year clinical outcomes after discharge were collected and analyzed. An early follow-up was defined as an outpatient care visit within 2 weeks after discharge with the adjustment of drugs and/or the lifestyle guidance, if necessary. A setting of early follow-up in each patient was according to a physician's discretion. Results One hundred-twenty eight patients underwent early follow-up visits and other 180 patients were without it. An univariate analysis showed that the early follow-up was significantly associated with a lower HF readmission rate during 2 years (17.1% in the early follow-up group, 34.4% in the control group, p≤0.001, OR=0.397, 95% CI=0.230–0.685, Figure) and a 2-year composite adverse outcome (all cause death and HF readmission; 18.7% vs. 40.5%, p Conclusions The present study suggests that an early follow-up approach after discharge in decompensated HF patients may improve the long-term prognosis. These results were not dependent on whether a medication adjustment was performed or not. An early follow-up may help improve patient factors of HF worsening. Main results Funding Acknowledgement Type of funding source: None

SummaryChondrodysplasias are hereditary diseases caused by mutations in the components of growth cartilage. Although the unfolded protein response (UPR) has been identified as a key disease mechanism in mouse models, no suitablein vitrosystem has been reported to analyze the pathology in humans. Here, utilizing human chondrodysplasia-specific iPSCs, we examined the UPR caused by mutations inMATN3orCOL10A1. In growth plate-like structures formed from iPSC-derived sclerotomein vivo, the hypertrophic zone was disrupted, and induced hypertrophic chondrocytesin vitroshowed varying levels of ER stress depending on the mutation. Autophagy inducers and chemical chaperones succeeded in reducing ER stress only in some mutants, while transcriptome analysis revealed many mutation-specific changes in genes involved in apoptosis, metabolism, and protein trafficking. In this way, our system has allowed the precise evaluation of the UPR caused by each mutation, opening up new avenues for treatment of individual chondrodysplasia patients.

Current protocols for the differentiation of human pluripotent stem cells (hPSCs) into chondrocytes do not allow for the expansion of intermediate progenitors so as to prospectively assess their chondrogenic potential. Here we report a protocol that leverages PRRX1-tdTomato reporter hPSCs for the selective induction of expandable and ontogenetically defined PRRX1

To dually functionalize monodisperse cores with luminescence and mesopores, hydrolysis and condensation of tetraethyl orthosilicate in the presence of a double chain cationic surfactant of didodecyldimethylammonium bromide (DDAB) were applied to monodisperse silica cores with an average size smaller than 100 nm. Highly monodisperse core-shell particles were obtained by uniform coating of the cores with silica shell. Calcination of the silica shell at 500 °C to remove the incorporated DDAB surfactant provided the shells with mesoporous and luminescent properties without using any phosphors. The size of mesopores could be expanded by using dihexadecyldimethylammonium bromide (DHAB) with alkyl chains longer than DDAB. The combination of silica shell formation and calcination was also applied to monodisperse polymer cores, which created monodisperse, luminescent, hollow mesoporous silica particles (HMSs) with a sub-100 nm cavity inside. The emission intensity of mesoporous shell measured with an excitation wavelength of 365 nm could be sharply increased by an increase in the volume of mesoporous shell formed on the silica cores, implying that the luminescent centers derived from organic residue homogeneously distributed in the mesoporous shell.

Summary Background Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy greatly influences patients' postoperative course. Several evaluation methods have been used to assess the risk of clinically relevant POPF (CR-POPF) after pancreatoduodenectomy namely, the original, alternative, and updated alternative fistula risk scores (o-FRS, a-FRS, and ua-FRS, respectively). Methods We enrolled 106/179 patients who underwent pancreatoduodenectomy in our institution between April 2013 and Mar 2018. CR-POPF was defined as grade B and C POPF according to the 2016 definitions of the International Study Group on Pancreatic Surgery. Results Pancreatic gland texture was the only significant risk factor for CR-POPF (p = 0.007). The CR-POPF incidence increased significantly according to the risk groups defined by both o-FRS (p = 0.004) and a-FRS (p = 0.004). The area under the curve for o-FRS, a-FRS, and ua-FRS was 0.693, 0.693, and 0.671, respectively. Conclusion o-FRS, a-FRS, and ua-FRS were almost equally useful for risk evaluation for CR-POPF after pancreatoduodenectomy. Further studies, especially for preoperative objective evaluation of pancreatic gland texture, are needed for more useful and accurate risk evaluation.

Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl− currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl− channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.

Background Atrial functional mitral regurgitation (AFMR) occurs in patients with atrial fibrillation. However, morphological mechanisms of AFMR are poorly understood. Purpose The purpose of this study was to examine the morphological characteristics in patients with AFMR. Methods Among consecutive 795 patients undergoing initial radiofrequency catheter ablation (RFCA) at our hospital, twenty-five patients with persistent AF accompanied by AFMR (≥ moderate) before RFCA (AFMR group) were studied. Age-matched 25 patients with persistent AF without MR were defined as a control group. Results Left ventricular ejection fraction (LVEF) was lower and left atrium volume index was larger in the AFMR group (Table). Mitral valve annulus diameter and length of anterior mitral leaflet (AML) were similar between groups, whereas length of posterior mitral leaflet (PML) was significantly shorter in the AFMR group. Smaller tethering angle of AML (γ in the figure) and shorter tethering height were significantly associated with the occurrence of AFMR, which were different from morphology of functional mitral regurgitation in patients with dilated LV. Multiple regression analysis revealed that less tenting height (p Echocardiographic parameters AFMR (n=25) Control (n=25) P value Age, y 69±8 66±10 NS Male, n (%) 9 (36) 20 (80) P=0.001 LVEF,% 60±9 67±6 P=0.004 LAD, mm 44±5 41±7 NS LAVI, ml/m2 56±17 41±13 P Conclusions AFMR occurs in patients with unique morphological features, such as less tethering height and LA dilatation toward the posterior.