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Percutaneous coronary intervention (PCI) to the calcified bifurcation lesion is still a challenging issue even for experienced interventional cardiologists. In such bifurcation lesions, side branch compromise caused by carina-shift or plaque shift just following stent implantation or balloon dilatation is one of the most important complications. It remains unclear whether rotational atherectomy (RA) to the main vessel reduces the incidence of side branch compromise in the calcified bifurcation lesions. The aim of this retrospective study was to compare the incidence of side branch compromise/occlusion between PCI with versus without RA.This was a retrospective, single-center study. Side branch compromise/occlusion was defined as final Thrombolysis in Myocardial Infarction flow grade of side branch ≤2/≤1. We included 302 calcified bifurcation lesions, and divided those into the RA group (n = 140) and the non-RA group (n = 162) according to use of RA to the main vessel.The incidence of side branch compromise/occlusion was significantly less in the RA group than in the non-RA group (compromise: 6.4 % versus 14.2 %, p = 0.038; occlusion: 3.6 % versus 10.5 %, p = 0.017). RA was inversely associated with the incidence of side branch compromise [odds ratio (OR) 0.272, 95 % confidence interval (CI) 0.096-0.772, p = 0.014] and occlusion (OR 0.175, 95 % CI 0.049-0.628, p = 0.008).RA to the main vessel was associated with a lower incidence of side branch compromise/occlusion. RA to the main vessel only may be a reasonable approach to reduce the risk of side branch compromise/occlusion in calcified bifurcation lesions.

Periprocedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) is more frequently observed in true bifurcation lesions such as Medina (1,1,1) and (0,1,1). The aim of this study is to compare the incidence of PMI in elective PCI between Medina (1,1,1) and (0,1,1) bifurcation lesions. This was a retrospective, single-center study. We included 162 true bifurcation lesions, which were divided into the (1,1,1) group (n = 85) and the (0,1,1) group (n = 77). We compared the incidence of PMI between the two groups and performed multivariate logistic regression analysis using PMI as a dependent variable. The incidence of PMI was similar in the (1,1,1) group and the (0,1,1) group (12.9% versus 15.6%, P = 0.658). The final TIMI flow grade of the side branches and that of the main branches were also similar in the two groups. In multivariate logistic regression analysis, Medina classification (1,1,1) was not associated with PMI (odds ratio (OR), 0.996; 95% confidence interval (CI), 0.379-2.621; P = 0.994), but the angle of the side branch45° (OR, 3.569; 95% CI, 1.320-9.654; P = 0.012), lesion length in a main vessel (per 10-mm increase) (OR, 1.508; 95% CI, 1.104-2.060; P = 0.010), and absence of side branch protection (OR, 3.034; 95% CI, 1.095-8.409; P = 0.033) were significantly associated with PMI. In conclusion, the Medina (1,1,1) bifurcation lesions did not increase the incidence of PMI as compared to Medina (0,1,1). However, the narrow side branch angle, diffuse long lesion, and absence of side branch protection were significantly associated with PMI. We should pay attention to these high-risk features in the treatment of true bifurcation lesions.

Complications such as slow flow are frequently observed in percutaneous coronary intervention (PCI) with rotational atherectomy (RA). However, it remains unclear whether the high incidence of slow flow results in the high incidence of periprocedural myocardial infarction (PMI), reflecting real myocardial damage. The aim of this study was to compare the incidence of PMI between PCI with versus without RA using propensity score-matching. We included 1350 elective PCI cases, which were divided into the RA group (n = 203) and the non-RA group (n = 1147). After propensity score matching, the matched RA group (n = 190) and the matched non-RA group (n = 190) were generated. The primary interest was to compare the incidence of PMI between the matched RA and non-RA groups. Before propensity score matching, the incidence of slow flow and PMI was greater in the RA group than in the non-RA group. After matching, the incidence of slow flow was still greater in the matched RA group than in the matched non-RA group (16.8% vs. 9.5%, p = 0.048). However, the incidence of PMI was similar between the matched RA and matched non-RA group (7.4% vs. 5.3%, p = 0.528, standardized difference: 0.086). In conclusion, although use of RA was associated with greater risk of slow flow, use of RA was not associated with PMI after a propensity score-matched analysis. The fact that RA did not increase the risk of myocardial damage in complex lesions would have an impact on revascularization strategy for severely calcified coronary lesions.

Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). UMIN000027031 April 18, 2017

We report a rare case in which a peripherally inserted central catheter (PICC) asymptomatically penetrated the median nerve. The patient was a 71-year-old man who displayed no neurological symptoms until 4 days after PICC placement. An ultrasound scan revealed that the PICC had penetrated the median nerve. He underwent surgery to remove the catheter and had no sequelae. When placing a PICC, selecting the brachial vein as a puncture site is associated with a high risk of nerve injury. Furthermore, circumspect observation is needed until withdrawal as neurological symptoms may be absent even when the catheter has punctured a nerve.

Periprocedural myocardial infarction (PMI) is closely associated with long-term cardiovascular events. The factors associated with PMI are not fully understood. The purpose of this study was to investigate the determinants of PMI in contemporary elective percutaneous coronary intervention (PCI). Overall, 731 elective PCI was divided into the PMI (n = 27) and non-PMI (n = 704) groups. Univariate and multivariate logistic regression analysis was used to find factors associated with PMI. In the univariate analysis, PMI was associated with complex lesion characteristics, such as the lesion length, lesion angle, calcification, and Medina classification. In the multivariate logistic regression analysis, the lesion length (per 10-mm increase: odds ratio (OR), 1.477; 95% confidence interval (CI), 1.161‒1.879; P = 0.002), lesion angle ≥ 45° (versus lesion angle < 45°: OR, 4.244; 95% CI, 1.187‒15.171; P = 0.026), and Medina classification (0,1,1) / (1,1,1) (versus other lesions: OR, 14.843; 95% CI, 6.235‒35.334; P < 0.001) were significantly associated with PMI. Of the 24 lesions with lesion angle ≥ 45° in the PMI group, 14 had final TIMI flow grade ≤ 2 in side branches and 9 had transient slow flow in main branches/transient ST elevation during PCI. Of the 87 lesions with Medina classification (1,1,1) / (0,1,1), 19 had final TIMI grade ≤ 2 in side branches. In conclusion, the lesion length, lesion angle ≥ 45°, and Medina classification (0,1,1) / (1,1,1) were significantly associated with PMI in contemporary elective PCI. Preventing flow limitation in both side branches and main vessels in elective PCI for the diffuse long, angulated, or true bifurcation lesions is important.

Objective We aimed to investigate the association between the digit symbol test (DST) and clinical characteristics, including the nutritional status of liver cirrhosis patients. Methods Fifty-nine cirrhotic patients without a history of overt hepatic encephalopathy were retrospectively evaluated. We examined neuropsychological abnormalities (NPAs) using the DST. We also estimated the detailed nutritional status using the Food Frequency Questionnaire (FFQ). The patients were divided into two groups according to their DST status: patients with normal DST scores (DST-Nor group, n=45) and those with abnormal DST scores (DST-Abn group, n=14). The clinical and nutritional findings of the two groups were compared. Results Overall, 14 (23.7%) patients had a DST abnormality. There were significant differences between the two groups in serum albumin (Alb; p=0.0043), valine (Val; p=0.0016), leucine (Leu; p=0.0078), isoleucine (Ile; p=0.0022), the molar ratio of total branched-chain amino acids to tyrosine (BTR; p=0.00025), total-bilirubin (T-Bil; p=0.0071), prothrombin time (%) (PT; p=0.028), and serum sodium (Na; p=0.035). A multivariate analysis found the BTR to be the only independent predictor of a DST abnormality (hazard ratio, 9.24; p

Researchers across research domains have traditionally used two different methods to characterize the emission sources of pollution in the atmosphere. One of the widely used methods in the area of air pollution utilizes the ratio of elements in aerosol, namely PM2.5. The other method used in the climate related research is the oxidative ratio (OR = –ΔO2/ΔCO2) in air. In this study, these two methods were simultaneously applied for the first time to estimate the source of PM2.5 pollution. During a week-long pollution event occurred in the Tokyo Metropolitan area, Japan, two concentration maxima were observed in the temporal plot of PM2.5. The slope of the linear regression line for Pb versus Ni concentration plot during the first PM2.5 concentration maximum was approximately 4 times larger than the second, indicating that the former was dominated by Pb-rich emission sources, i.e., coal combustion. The OR in air measured during the corresponding concentration maxima were 1.33 and 1.51, suggesting the prevai...

BACKGROUND AND AIM Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second-line therapeutic option in these patients. This study aimed to evaluate the long-term outcome(s) of combined UDCA and bezafibrate therapy in UDCA-refractory PBC patients and identify prognostic factors. METHODS Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long-term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis. RESULTS Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK-PBC-risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma-glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis-related symptoms or liver-related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis-related symptoms and liver-related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM

Unsteady drag, unsteady lift, and movement of one or two moving particles caused by the passage of a planar shock wave are investigated using particle-resolved simulations of viscous flows. The particle motion analysis is carried out based on particle-resolved simulations for one or two particles under a shock Mach number of 1.22 and a particle Reynolds number of 49, and the particle migration and fluid forces are investigated. The unsteady drag, unsteady lift, and particle behavior are investigated for different densities and particle configurations. The time evolution of the unsteady drag and lift is changed by interference by the planar shock wave, Mach stem convergence, and the shock wave reflected from the other particle. These two particles become closer after the shock wave passes than in the initial state under most conditions. Two particles placed in an in-line arrangement approach each other very closely due to the passage of a shock wave. On the other hand, two particles placed in a side-by-side arrangement are only slightly closer to each other after the shock wave passes between them. The pressure waves resulting from Mach stem convergence of the upstream particle and the reflected shock waves from the downstream particle are the main factors responsible for the force in the direction that pushes the particles apart. The wide distance between the two particles attenuates these pressure waves, and the particles reduce their motion away from each other.

We herein report a 49-year-old woman with a perivascular epithelial cell tumor (PEComa) of the pancreas. Imaging studies demonstrated a relatively well-demarcated mass, measuring approximately 40 mm in diameter, located in the pancreatic tail. It was heterogeneously enhanced almost to the same degree as the surrounding pancreatic tissue in both the arterial and portal venous phases. We performed endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using the AcquireⓇ 22-gauge needle and preoperatively obtained a definitive diagnosis with a sufficient sample. Clinicians should consider pancreatic PEComa in their differential diagnosis of patients with a pancreatic mass.

Background A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC. Methods Four weeks after MCT 60 mg kg−1 administration i.v., right ventricular systolic pressure (RVSP), systolic BP (SBP), mean BP (MBP), cardiac index (CI), and pulmonary vascular resistance index (PVRI) were measured. PHC defined as an RVSP exceeding or equal to SBP was induced by changing the fraction of inspiratory oxygen to 0.1. Rats were subsequently treated by vasopressin, phenylephrine, or norepinephrine, followed by assessment of systemic haemodynamics, isometric tension of femoral and pulmonary arteries, cardiac function, blood gas composition, and survival. Results PHC was associated with increased RV dilatation and paradoxical septal motion. Vasopressin increased MBP [mean (standard error)] from 52.6 (3.8) to 125.0 (8.9) mm Hg and CI from 25.4 (2.3) to 40.6 (1.8) ml min−1 100 g−1 while decreasing PVRI. Vasopressin also improved RV dilatation, oxygenation, and survival in PHC. In contrast, phenylephrine increased MBP from 54.8 (2.3) to 96.8 (3.2) mm Hg without improving cardiac pump function. Norepinephrine did not alter MBP. Vasopressin contracted femoral but not pulmonary arteries, whereas phenylephrine contracted both arterial beds. Hence, improvements with vasopressin in PHC might be associated with decreased PVRI and selective systemic vasoconstriction. Conclusions In this rat model of a PHC, vasopressin, but not phenylephrine or norepinephrine, resulted in better haemodynamic and vascular recovery.

Bilateral quadratus lumborum blockade (QLB) using ultrasound guidance has been introduced as an abdominal truncal block to improve postoperative analgesia and quality of recovery (QoR) after abdominal surgery, but efficacy remains controversial. The primary aim of this study was to evaluate the efficacy of posterior QLB on the postoperative QoR, and secondarily to evaluate postoperative pain after gynaecological laparoscopic surgery (LS). This study was a single-centre randomized controlled trial. QLB group patients underwent bilateral posterior quadratus lumborum injections with 25–30 mL of 0.25% levobupivacaine after induction of general anaesthesia; the control group underwent no block. Both groups were administered fentanyl-based intravenous patient-controlled analgesia postoperatively. The postoperative QoR was measured using the Quality of Recovery 40 (QoR-40) questionnaire score; postoperative pain was evaluated using the visual analogue scale (VAS) and the cumulative postoperative fentanyl dose. Thirty-one and 29 patients were randomised to the QLB and control groups, respectively. The intraoperative remifentanil dosage was significantly less in the QLB group. The median (interquartile range) for the QoR-40 score was not different between the groups: 154 (133–168) in the QLB group and 158 (144–172) in the control group. There were no statistically significant differences in secondary outcome variables. Single-shot QLB did not improve the QoR or postoperative pain in patients managed by multimodal analgesia after gynaecological LS.

A two-hit hypothesis has been proposed to describe the pathophysiology of lipoid congenital adrenal hyperplasia. In previous studies using conventional steroidogenic acute regulatory protein (Star) gene knockout (KO) mice, adrenocortical lipid accumulation was already prominent at birth. Thus, the two-hit hypothesis was verified in the gonads of Star KO mice but not in the adrenal cortices. We generated time-dependent conditional Star KO mice induced by tamoxifen (TAM) injections and analyzed the adrenal cortices of the mice histologically and endocrinologically before, 24 hours after, and 8 weeks after TAM. We performed RNA sequencing analyses of the adrenal glands before and 8 weeks after TAM and histologically analyzed autologous adrenal cortices of TAM-induced Star KO mice with transplantation of wild-type adrenal gland. Lipid accumulation was scattered 24 hours after TAM and was prominent 8 weeks after TAM. Steroidogenic capacity decreased sequentially after TAM. Gene expression related to steroid biosynthesis significantly decreased 8 weeks after TAM compared with that before TAM. TAM-induced Star KO mice with adrenal transplantation showed normal ACTH levels and mild lipid accumulation. These results showed that the steroidogenic capacity decreased without histological change (the first hit) and declined with histological change (the second hit). Thus, we visualized the two-hit hypothesis in the adrenal cortex. The key feature of the secondary decline of steroidogenic capacity might be the decreased gene expression related to steroid biosynthesis after lipid accumulation exacerbated by ACTH hypersecretion.

Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition.In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air.A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups.Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031).UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

Gastrointestinal decompression is generally applied to a non-strangulated acute small bowel obstruction (NSASBO). Although long tube (LT) placement and administration of Gastrografin through a nasogastric tube (NGT-G) have shown advantages over NGT alone in previous studies, no studies appear to have compared LT and NGT-G. In this multicenter, randomized controlled trial, patients with NSASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018 at 11 Japanese institutions. The primary endpoint was non-inferiority of NGT-G compared to LT for non-surgery rate, and the lower limit of the 95% confidence interval for the non-surgery rate (−15%) was set as the lower margin for inferiority of NGT-G compared to LT. In total, 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed in the present trial. The non-surgery rate was 87.4% in the LT group and 91.1% in the NGT-G group, with a 3.7% difference between NGT-G and LT (95.3%CI − 5.55 to 12.91; non-inferiority P = 0.00002923). On the other hand, the non-surgery rate with pure NGT-G alone (76.8%) that represents non-cross-over NGT-G without subsequent LT was significantly lower than that with LT (P = 0.039). Median procedure time was significantly shorter with NGT-G (1 min) than with LT (25 min; P

AIM Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged

In this study, direct numerical simulation of the flow around a rotating sphere at high Mach and low Reynolds numbers is conducted to investigate the effects of rotation rate and Mach number upon aerodynamic force coefficients and wake structures. The simulation is carried out by solving the three-dimensional compressible Navier–Stokes equations. A free-stream Reynolds number (based on the free-stream velocity, density and viscosity coefficient and the diameter of the sphere) is set to be between 100 and 300, the free-stream Mach number is set to be between 0.2 and 2.0, and the dimensionless rotation rate defined by the ratio of the free-stream and surface velocities above the equator is set between 0.0 and 1.0. Thus, we have clarified the following points: (1) as free-stream Mach number increased, the increment of the lift coefficient due to rotation was reduced; (2) under subsonic conditions, the drag coefficient increased with increase of the rotation rate, whereas under supersonic conditions, the increment of the drag coefficient was reduced with increasing Mach number; and (3) the mode of the wake structure becomes low-Reynolds-number-like as the Mach number is increased.

Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy. The immunostimulant was not a secondary metabolite, as expected, but the structure was a nanoparticle formed by a polysaccharide. In addition, we clarified the immune effect of the nanoparticle. Intake of the nanoparticle by phagocytosis resulted in immunostimulant effects by increasing the genes and proteins of inflammatory cytokines in macrophage cells. The immunostimulant effects were inhibited by a phagocytosis inhibitor, cytochalasin D. To the best of our knowledge, this study is the first to describe the discovery of a nanoparticle in boiling herbal water extracts and its immunostimulant properties. This study will provide additional understanding of the efficacy of herbal medicine, in that the immunostimulant nanoparticle universally exists in boiling herbal water extracts. Thus, traditional herbal medicine may be an oldest known nanomedicine. Furthermore, this study suggests that the immunostimulant nanoparticle simply can be obtained from herbal medicine only by ultracentrifugation. We hope that this simple strategy will substantially contribute to drug development, including vaccine adjuvant, in the future., Highlights • Nanoparticles are universally present in boiling herbal water extracts. • Nanoparticles are obtained from these extracts by ultracentrifugation. • Nanoparticles are mainly composed of polysaccharides. • Nanoparticles have an immunostimulatory effect on macrophage cells. • This effect is exhibited by the phagocytosis of exogenous nanoparticles.

Background: The risk factors for rapid growth and early metastasis of papillary thyroid carcinoma (PTC) and the role of coexisting Graves’ disease in the clinical course of PTC remain uncertain in children. Case Description: We report on a Japanese girl, whose PTC rapidly grew and metastasized within 4 years. Graves’ disease was diagnosed by the presence of serum TSH receptor antibodies at 8 years of age when thyroid ultrasonography detected no nodules. After 4 years of effective treatment with thiamazole, multifocal nodules – up to 47 mm in diameter – were detected on thyroid ultrasonography. Chest CT scan revealed multiple metastatic lesions in the lung. After total thyroidectomy, PTC was pathologically diagnosed. The patient underwent two courses of radioactive iodine (RAI) treatment, but the pulmonary metastatic lesions did not take up the RAI. Molecular analyses of the PTC tissue identified a TFG/NTRK1 chimeric gene and disclosed the preserved expression of TSHR and the reduced expression of SLC5A5 compared with non-tumor thyroid tissue. Conclusions: Rapid growth and early metastasis of PTC with coexisting Graves’ disease in this patient can be related to a combination of multiple factors including preserved TSHR expression, reduced SLC5A5 expression, and TFG/NTRK1 rearrangement.