Recent advancements in image-enhanced endoscopy in the pancreatobiliary field.

Image-enhanced endoscopy (IEE) has advanced gastrointestinal disease diagnosis and treatment. Traditional white-light imaging has limitations in detecting all gastrointestinal diseases, prompting the development of IEE. In this review, we explore the utility of IEE, including texture and color enhancement imaging and red dichromatic imaging, in pancreatobiliary (PB) diseases. IEE includes methods such as chromoendoscopy, optical-digital, and digital methods. Chromoendoscopy, using dyes such as indigo carmine, aids in delineating lesions and structures, including pancreato-/cholangio-jejunal anastomoses. Optical-digital methods such as narrow-band imaging enhance mucosal details and vessel patterns, aiding in ampullary tumor evaluation and peroral cholangioscopy. Moreover, red dichromatic imaging with its specific color allocation, improves the visibility of thick blood vessels in deeper tissues and enhances bleeding points with different colors and see-through effects, proving beneficial in managing bleeding complications post-endoscopic sphincterotomy. Color enhancement imaging, a novel digital method, enhances tissue texture, brightness, and color, improving visualization of PB structures, such as PB orifices, anastomotic sites, ampullary tumors, and intraductal PB lesions. Advancements in IEE hold substantial potential in improving the accuracy of PB disease diagnosis and treatment. These innovative techniques offer advantages paving the way for enhanced clinical management of PB diseases. Further research is warranted to establish their standard clinical utility and explore new frontiers in PB disease management.

Cardiac resynchronization therapy-defibrillator implantation with shock lead placement in the left bundle branch area: a case report.

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing is a well-established therapy. Left bundle branch area pacing (LBBAP) is a safe technique providing physiological pacing, and LBBAP-optimized CRT (LOT-CRT) has been shown to provide better electrical resynchronization than traditional CRT. However, there are few reports on shock lead placement in the left bundle branch area (LBBA) during CRT-defibrillator (CRT-D) implantation. Case summary: A 76-year-old woman with heart failure from dilated cardiomyopathy presented with left bundle branch block pattern (QRS duration, 160 ms). Left ventricular ejection fraction was 21%. Cardiac resynchronization therapy-defibrillator implantation was performed due to worsening symptoms. By reshaping the Agilis HisPro catheter and adding a septal curve, the shock lead was placed deep into the ventricular septum, narrowing QRS duration to 114 ms. Left ventricular activation time was 84 ms. A defibrillation threshold test confirmed successful treatment without adverse events. At 6-month follow-up, left ventricular ejection fraction improved from 21 to 63%, with the patient's condition improving from New York Heart Association class III to class I. Discussion: It was reported that QRS narrowing in CRT was related to long-term mortality, and LOT-CRT further decreased QRS duration as compared with LBBP only or biventricular pacing and increased the response rate. Combining LBBAP with coronary sinus pacing can potentially achieve superior electrical resynchronization. Lack of a suitable tool for direct shock lead placement in LBBA necessitated additional LBBAP lead in conventional LOT-CRT. Our successful LOT-CRT-D procedure with minimal number of leads through Agilis HisPro catheter reshaping enabled direct LBBA shock lead placement.

Heart Failure score and outcomes in patients with preserved ejection fraction after catheter ablation for atrial fibrillation.

AIMS: Atrial fibrillation (AF) is frequently associated with heart failure with preserved ejection fraction (HFpEF), but the diagnosis and prediction of the outcomes of HFpEF are difficult. Notably, the Heart Failure Association of the European Society of Cardiology proposed the use of the HFA-PEFF score in the diagnosis of HFpEF. This study aimed to assess the prognostic value of the pre- and post-procedural HFA-PEFF scores in patients with preserved ejection fraction (EF) after catheter ablation (CA) for AF. The primary endpoint was a composite of cardiac hospitalization for cardiovascular events and all-cause mortality. The secondary endpoint was AF recurrence. METHODS AND RESULTS: Overall, 354 patients with AF and preserved EF who underwent CA as well as blood tests and transthoracic echocardiography 2 weeks before and 6 months after CA from January 2018 to December 2019 were retrospectively enrolled in the study. In the 354 participants, univariate analysis showed that the post-procedural HFA-PEFF score was associated with a 3-year risk of the primary endpoint (hazard ratio [HR] = 3.73; 95% confidence interval [CI] = 2.07-6.73; P < 0.001), whereas the pre-procedural HFA-PEFF score was not (HR = 1.24, 95% CI = 0.82-1.86, P = 0.307). Further, the association between the post-procedural HFA-PEFF score and primary endpoint was not modified even after including other relevant variables into the score. Similar to the primary endpoint, the post-procedural HFA-PEFF score was associated with the 3-year risk of AF recurrence (P < 0.001). CONCLUSIONS: In patients with preserved EF undergoing AF ablation, the HFA-PEFF score at 6 months after CA was associated with the primary endpoint and AF recurrence at the 3-year follow-up.

In situ XAFS-XRD study of the Zr-Y2O3 interaction at extra-high temperatures.

The in situ measurement technique for a metal/metal-oxide mixture at extra-high temperature above 2000 K has been desired in the field of nuclear safety engineering. In the present study, we succeeded in simultaneous XAFS-XRD measurements of the Zr oxidation [Zr + O → Zr(O) + ZrO2] up to 1952 K and ZrO2-Y2O3 reaction from 1952 to 2519 K. The chemical shift during Zr oxidation was observed in the absorption spectra around the Zr K-edge, and the interatomic cation-cation and cation-oxygen distances obtained by the fitting analysis of EXAFS during the Y2O3-ZrO2 reaction are explained. Also, the temperature dependency of the anharmonic effect was investigated by comparing the fitted second- and third-order cumulants with the theoretical ones in which the Morse potential was applied as an interatomic potential, giving a good explanation about the local structure dynamics. Finally, the applicability of the developed system to investigation of nuclear fuel materials, such as UO2-Zr, is discussed.

Intracardiac echocardiography guided simultaneous atrial fibrillation ablation and Micra implantation 14 days after Watchman FLX implantation.

Key Clinical Message: Atrial fibrillation ablation, including pulmonary vein isolation immediately after left atrial appendage closure (LAAC), is a rare and challenging issue. Intracardiac echocardiography guidance can help identify the LAAC device position for safe atrial fibrillation ablation without LAAC device-related adverse events even immediately after LAAC device implantation. Abstract: Early phase atrial fibrillation (AF) ablation after left atrial appendage closure (LAAC) is a rare and challenging issue. Here, we present a case illustrating the feasibility of AF ablation under intracardiac echocardiography guidance immediately after LAAC device implantation without LAAC device-related adverse events.

Tadalafil for Treatment of Fetal Growth Restriction: A Review of Experimental and Clinical Studies.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Simulation-based evaluation of personalized dosing approaches for anti-FGFR/KLB bispecific antibody fazpilodemab.

Personalized dosing approaches play important roles in clinical practices to improve benefit: risk profiles. Whereas this is also important for drug development, especially in the context of drugs with narrow therapeutic windows, such approaches have not been fully evaluated during clinical development. Fazpilodemab (BFKB8488A) is an agonistic bispecific antibody which was being developed for the treatment of nonalcoholic steatohepatitis. The objective of this study was to characterize the exposure-response relationships of fazpilodemab with the purpose of guiding dose selection for a phase II study, as well as to evaluate various personalized dosing strategies to optimize the treatment benefit. Fazpilodemab exhibited clear exposure-response relationships for a pharmacodynamic (PD) biomarker and gastrointestinal adverse events (GIAEs), such as nausea and vomiting. Static exposure-response analysis, as well as longitudinal adverse event (AE) analysis using discrete-time Markov model, were performed to characterize the observations. Clinical trial simulations were performed based on the developed exposure-response models to evaluate probability of achieving target PD response and the frequency of GIAEs to inform phase II dose selection. Dynamic simulation of personalized dosing strategies demonstrated that the AE-based personalized dosing is the most effective approach for optimizing the benefit-risk profiles. The approach presented here can be a useful framework for quantifying the benefit of personalized dosing for drugs with narrow therapeutic windows.

Visceral Adipose Tissue Percentage Compared to Body Mass Index as Better Indicator of Surgical Outcomes in Women With Obesity and Endometrial Cancer.

STUDY OBJECTIVE: To assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DESIGN: Retrospective observational cohort study. SETTING: Mie University Hospital, Japan. PATIENTS: Of the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. INTERVENTIONS: We investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). MEASUREMENTS AND MAIN RESULTS: Abdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = -0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (ß = 0.338 vs 0.267, ß = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. CONCLUSION: VAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.

Successful direct pacing of the left bundle branch area with ICD lead using steerable delivery sheath.

Recently, conduction system pacing has been performed in patients with impaired cardiac function. We report a case in which a DF4 implantable cardioverter defibrillator lead was screwed directly into the left bundle branch area with the support of a steerable delivery sheath.

Late cardiac tamponade after a helix-based active fixation leadless pacemaker implantation.

Although the late cardiac tamponade in leadless pacemaker implantation (LPI) is rare, we encountered such an incident in patient with AVEIR-VR™ system on hemodialysis and warfarinization. When LPI with active fixation system, we should aim for successful single-attempt deployment using electrical premapping to prevent cardiac tamponade including the late phase.

Membrane transporters in drug development and as determinants of precision medicine.

The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions.

Applications of Advanced Natural Language Processing for Clinical Pharmacology.

Natural language processing (NLP) is a branch of artificial intelligence, which combines computational linguistics, machine learning, and deep learning models to process human language. Although there is a surge in NLP usage across various industries in recent years, NLP has not been widely evaluated and utilized to support drug development. To demonstrate how advanced NLP can expedite the extraction and analyses of information to help address clinical pharmacology questions, inform clinical trial designs, and support drug development, three use cases are described in this article: (1) dose optimization strategy in oncology, (2) common covariates on pharmacokinetic (PK) parameters in oncology, and (3) physiologically-based PK (PBPK) analyses for regulatory review and product label. The NLP workflow includes (1) preparation of source files, (2) NLP model building, and (3) automation of data extraction. The Clinical Pharmacology and Biopharmaceutics Summary Basis of Approval (SBA) documents, US package inserts (USPI), and approval letters from the US Food and Drug Administration (FDA) were used as our source data. As demonstrated in the three example use cases, advanced NLP can expedite the extraction and analyses of large amounts of information from regulatory review documents to help address important clinical pharmacology questions. Although this has not been adopted widely, integrating advanced NLP into the clinical pharmacology workflow can increase efficiency in extracting impactful information to advance drug development.

Combined effects of high atrial septal pacing and reactive atrial antitachycardia pacing for reducing atrial fibrillation in sick sinus syndrome.

Background: It is unknown whether atrial fibrillation (AF) burden varies by pacing site in patients with reactive atrial antitachycardia pacing (rATP). We aimed to compare AF burden in patients with high atrial septal pacing (HASp) via delivery catheter and right atrial appendage pacing (RAAp) in patients with sick sinus syndrome (SSS). Methods: We retrospectively identified 109 patients with a history of paroxysmal AF and SSS who had received dual-chamber pacemaker implantation between January 2017 and December 2019, of whom 39 and 70 patients had HASp and RAAp, respectively. rATP was initiated after a 1-month post-implantation run-in period. Results: Patients with HASp had a significantly shorter P-wave duration during atrial pacing than those with RAAp (99.3 ± 10.4 vs. 116.0 ± 14.3 ms, p < .001). During the 3-year follow-up period, the incidence of an AF lasting longer than 1 or 7 days was significantly lower (hazard ratio [HR], 0.45; p = .016; HR, 0.24; p = .004) than in those with RAAp. The median time of AF/AT per day in the follow-up periods was significantly shorter in the HASp group than in the RAAp group (10 vs. 18 min/day, p = .018). Atrial lead division did not occur in the HASp group during the follow-up period. Conclusions: HASp via delivery catheter is as safe as RAAp, and HASp combined with rATP is effective for reducing AF burden in patients with SSS and paroxysmal AF.

Endoscopic drainage with a metallic stent for obstructive jaundice caused by bile duct metastasis of breast cancer: A case report.

Key Clinical Message: Bile duct metastasis of breast cancer is rare. It often causes obstructive jaundice which makes the patient interrupt state of treatment. Endoscopic drainage for obstructive jaundice is effective and less invasive treatment option also in this case. Abstract: A 66-year-old breast ductal carcinoma patient developed obstructive jaundice, presenting with epigastric discomfort and dark-colored urine. Computed tomography and endoscopic retrograde cholangiopancreatography revealed bile duct stenosis. Brushing cytology and tissue biopsy confirmed bile duct metastasis, a self-expandable metallic stent was placed/replaced endoscopically, and chemotherapy was continued, extending the patient's life.

Comparison of surgical outcomes between robot-assisted laparoscopic hysterectomy and conventional total laparoscopic hysterectomy in gynecologic benign disease: a single-center cohort study.

We compared the surgical outcomes of robot-assisted laparoscopic hysterectomy (RAH) and total laparoscopic hysterectomy (TLH). This single-center cohort study compared 139 RAH cases from January, 2017 to September, 2021 and 291 TLH cases between January, 2015 and December, 2020. We retrospectively evaluated surgical outcomes, including total operative time (defined as the time from port wound incision to port wound closure), net operative time (defined as the time from the start of pneumoperitoneum to the end of pneumoperitoneum), estimated blood loss, weight of excised uterus (±adnexa), and overall complications, and the relationship between surgeon experience and operative time, net operative time, and blood loss in RAH and TLH. There was no significant difference in the total operative time between the two groups. Regardless of surgeon experience, the net operative time was significantly shorter in the RAH group than in the TLH group (p <0.001) and the estimated blood loss was significantly lower in RAH cases than in TLH cases (p = 0.01). The net operative time per uterine weight was shorter in the TLH group than that in the RAH group; however, there was no significant difference. RAH resulted in statistically better surgical outcomes in terms of net operative time and blood loss, regardless of surgeon experience. However, net operative time and blood loss also seem to be significantly affected by uterus weight. Large trials are imperative to determine the more effective surgical approach between RAH and TLH for different patient subsets.

Oxidation-induced nanolite crystallization triggered the 2021 eruption of Fukutoku-Oka-no-Ba, Japan.

Nanometer-sized crystals (nanolites) play an important role in controlling eruptions by affecting the viscosity of magmas and inducing bubble nucleation. We present detailed microscopic and nanoscopic petrographic analyses of nanolite-bearing and nanolite-free pumice from the 2021 eruption of Fukutoku-Oka-no-Ba, Japan. The nanolite mineral assemblage includes biotite, which is absent from the phenocryst mineral assemblage, and magnetite and clinopyroxene, which are observed as phenocrysts. The boundary between the nanolite-bearing brown glass and nanolite-free colorless glass is either sharp or gradational, and the sharp boundaries also appear sharp under the transmitted electron microscope. X-ray absorption fine structure (XAFS) analysis of the volcanic glass revealed that the nanolite-free colorless glass records an oxygen fugacity of QFM + 0.98 (log units), whereas the nanolite-bearing brown glass records a higher apparent oxygen fugacity (~ QFM + 2). Thermodynamic modelling using MELTS indicates that higher oxygen fugacities increase the liquidus temperature and thus induced the crystallization of magnetite nanolites. The hydrous nanolite mineral assemblage and glass oxygen fugacity estimates suggest that an oxidizing fluid supplied by a hot mafic magma induced nanolite crystallization in the magma reservoir, before the magma fragmentation. The oxidation-induced nanolite crystallization then enhanced heterogeneous bubble nucleation, resulting in convection in the magma reservoir and triggering the eruption.