Risk factors for recurrent biliary obstruction following endoscopic biliary stenting in patients with unresectable ampullary cancer: A multicenter retrospective study.

OBJECTIVES: Unresectable ampullary cancer (AC) is a rare disease entity. The risk factors for recurrent biliary obstruction (RBO) following endoscopic biliary stenting (EBS) for unresectable AC remain unknown. In this study we aimed to evaluate the cumulative RBO rate and to identify risk factors for RBO following palliative EBS in patients with unresectable AC. METHODS: This multicenter retrospective observational study enrolled consecutive patients with unresectable AC who had undergone palliative EBS between April 2011 and December 2021. The cumulative rate of and risk factors for RBO following palliative EBS were evaluated via multivariate analysis. RESULTS: The study analysis comprised 107 patients with a median age of 84 years (interquartile range 79-88 years). Plastic stents (PSs) and self-expandable metal stents (SEMSs) were placed in 53 and 54 patients, respectively. Functional success was accomplished in 104 (97.2%) patients. Of these, RBO occurred in 62 (59.6%) patients, with obstruction and complete/partial migration occurring in 47 and 15 patients, respectively. The median time to RBO was 190 days. Multivariate analysis showed that PS was associated with a higher rate of RBO compared to SEMS (hazard ratio [HR] 2.48; P < 0.01) and that the presence of common bile duct stones/sludge immediately after EBS was an independent risk factor for RBO (HR 1.99; P = 0.04). CONCLUSIONS: The use of SEMS compared to PS during EBS reduced the time to RBO in patients with unresectable AC. Common bile duct stones/sludge immediately after EBS was a risk factor for RBO.

Deletion of Trps1 regulatory elements recapitulates postnatal hip joint abnormalities and growth retardation of Trichorhinophalangeal syndrome in mice.

Trichorhinophalangeal syndrome (TRPS) is a genetic disorder caused by point mutations or deletions in the gene-encoding transcription factor TRPS1. TRPS patients display a range of skeletal dysplasias, including reduced jaw size, short stature, and a cone-shaped digit epiphysis. Certain TRPS patients experience early onset coxarthrosis that leads to a devastating drop in their daily activities. The etiologies of congenital skeletal abnormalities of TRPS were revealed through the analysis of Trps1 mutant mouse strains. However, early postnatal lethality in Trps1 knockout mice has hampered the study of postnatal TRPS pathology. Here, through epigenomic analysis we identified two previously uncharacterized candidate gene regulatory regions in the first intron of Trps1. We deleted these regions, either individually or simultaneously, and examined their effects on skeletal morphogenesis. Animals that were deleted individually for either region displayed only modest phenotypes. In contrast, the Trps1Δint/Δint mouse strain with simultaneous deletion of both genomic regions exhibit postnatal growth retardation. This strain displayed delayed secondary ossification center formation in the long bones and misshaped hip joint development that resulted in acetabular dysplasia. Reducing one allele of the Trps1 gene in Trps1Δint mice resulted in medial patellar dislocation that has been observed in some patients with TRPS. Our novel Trps1 hypomorphic strain recapitulates many postnatal pathologies observed in human TRPS patients, thus positioning this strain as a useful animal model to study postnatal TRPS pathogenesis. Our observations also suggest that Trps1 gene expression is regulated through several regulatory elements, thus guaranteeing robust expression maintenance in skeletal cells.

Unraveling the hidden complexity: Exploring dental tissues through single-cell transcriptional profiling.

Understanding the composition and function of cells constituting tissues and organs is vital for unraveling biological processes. Single-cell analysis has allowed us to move beyond traditional methods of categorizing cell types. This innovative technology allows the transcriptional and epigenetic profiling of numerous individual cells, leading to significant insights into the development, homeostasis, and pathology of various organs and tissues in both animal models and human samples. In this review, we delve into the outcomes of major investigations using single-cell transcriptomics to decipher the cellular composition of mammalian teeth and periodontal tissues. The recent single-cell transcriptome-based studies have traced in detail the dental epithelium-ameloblast lineage and dental mesenchyme lineages in the mouse incisors and the tooth germ of both mice and humans; unraveled the microenvironment, the identity of niche cells, and cellular intricacies in the dental pulp; shed light on the molecular mechanisms orchestrating root formation; and characterized cellular dynamics of the periodontal ligament. Additionally, cellular components in dental pulps were compared between healthy and carious teeth at a single-cell level. Each section of this review contributes to a comprehensive understanding of tooth biology, offering valuable insights into developmental processes, niche cell identification, and the molecular secrets of the dental environment.

Use of human Caco-2 cells and HPAE-PAD for α-glucosidase assay.

To measure α-glucosidase activity, rat intestinal acetone powder is commonly used as a source of α-glucosidase, and the mutarotase-glucose oxidase (GOD) methods commonly used to quantitate glucose produced by enzymatic hydrolysis of the substrates. In this study, we compared human Caco-2 cell extracts with rat intestinal acetone powder extracts. We also compared high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with the mutarotase-GOD method. The sensitivity of HPAE-PAD was higher than that of mutarotase-GOD. The glucose concentration quantified by HPAE-PAD was similar to that quantified using the mutarotase-GOD method. In the maltase reaction, 1-deoxynojirimycin (1-DNJ) exerted a more potent inhibitory effect on human enzymes than on rat enzymes. This order was reversed during the sucrase reaction. These results suggested that the combined use of Caco-2 cell extracts and HPAE-PAD is advantageous for use in α-glucosidase-related basic research.

Non-dilated left ventricular cardiomyopathy vs. dilated cardiomyopathy: clinical background and outcomes.

AIMS: Non-dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non-left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC-REF) in comparison with those with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We retrospectively included 363 patients with newly diagnosed non-ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31 mm/m2 in men and ≦34 mm/m2 in women) were categorized as NDLVC-REF (n = 80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC-REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end-diastolic diameter was smaller in patients with NDLVC-REF than in those with DCM at all time points after diagnosis. During the median follow-up period of 68.8 months (interquartile range: 33.0-93.7 months), 44 patients experienced cardiac events. The Kaplan-Meier curves showed no significant differences in the probability of cardiac events among NDLVC-REF and DCM patients (P = 0.349). However, patients with NDLVC-REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC-REF without LV dilatation (P = 0.049). CONCLUSIONS: There was no significant difference in the incidence of cardiac events between NDLVC-REF and DCM. Among NDLVC-REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC-REF and DCM patients may require equivalent attention to follow-up and regular assessment of LV function.

Efficacy of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Clinical Parameters in Patients with Heart Failure.

Background and Objectives: Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors have been approved as an oral drug for treating anemia in chronic kidney disease (CKD). However, the clinical effect of HIF-PH inhibitors in patients with heart failure (HF) is unclear. Thus, this study investigated the effect of HIF-PH inhibitors in patients with HF and CKD. Materials and Methods: Thirteen patients with HF complicated by renal anemia who were started on vadadustat were enrolled. Clinical parameters were compared before and 1 month after vadadustat was started. Results: The mean left ventricular ejection fraction was 49.8 ± 13.9%, and the mean estimated glomerular filtration rate was 29.4 ± 10.6 mL/min/1.73 m2. The hemoglobin level was significantly increased (9.7 ± 1.3 mg/dL vs. 11.3 ± 1.3 mg/dL, p < 0.001), and the N-terminal prohormone of B-type natriuretic peptide was significantly decreased after the introduction of vadadustat [4357 (2651-15182) pg/mL vs. 2367 (1719-9347) pg/mL, p = 0.002]. Furthermore, the number of patients with New York Heart Association functional class ≥ 3 was also decreased after the introduction of vadadustat [8 (61.5%) vs. 1 (7.7%), p = 0.008]. No thromboembolic adverse events or new tumors were observed in any patient during the study period. Conclusions: The introduction of vadadustat in patients with HF complicated by renal anemia led to improvements in anemia and symptoms of HF.

Efficacy and safety of endoscopic ultrasound-guided gallbladder drainage without dilation by using a 0.035-inch stiff guidewire.

Endoscopic ultrasound-guided gallbladder drainage for patients with cholecystitis and high surgical risk is commonly performed by dilating the fistula before inserting the delivery sheath; however, this carries an increased risk of peritonitis. To overcome this problem, we developed a new technique that did not require dilation, using a 0.035-inch stiff guidewire, and retrospectively evaluated the efficacy and safety of this technique. This retrospective case series report collected data on non-surgical patients who underwent endoscopic ultrasound-guided gallbladder drainage for various indications at Steel Memorial Muroran Hospital between November 2020 and October 2022. A total of 71 patients were included (mean age 83 ± 7.6 years; 33 women and 38 men). Breakthrough of the delivery sheath without dilation of the fistula was successful in 97.2% (n = 69) of patients. The success rate of stent placement was 98.6% (n = 70), as was the clinical success rate. Complications occurred in 2.8% (n = 2) of patients. Early and late adverse events occurred in 2.8% (n = 2) and 12.7% (n = 9) of patients, respectively. The mean procedure time was 24.8 ± 9.3 min. If a 0.035-inch stiff guidewire is used, the dilation procedure can be omitted in the endoscopic ultrasound-guided gallbladder drainage using self-expandable metal stents.

Characteristics and incidence of cardiac events across spectrum of age in cardiac sarcoidosis.

Background: Clinical characteristics and the risk of cardiovascular events in patients with cardiac sarcoidosis (CS) according to the age of initial diagnosis are unclear. Methods: This study is a sub-analysis of the ILLUMINATE-CS registry, which is a retrospective, multicenter registry that enrolled patients with CS between 2001 and 2017. Patients were divided into three groups according to the tertile of age at the time of initial diagnosis of CS. The study compared the clinical background at the time of CS diagnosis and the incidence rate of cardiac events across age categories. Results: A total of 511 patients were analyzed in this study. In baseline, older patients were more likely to be female. History of hypertension, heart failure admission, and atrioventricular block were more common in patients with older age. There was no significant difference in the history of ventricular arrhythmias and left ventricular ejection fraction among all age groups. During a median follow-up period of 3.2 [IQR: 1.7-4.2] years, 35 deaths, 56 heart failure hospitalization, and 98 fatal ventricular arrhythmias was observed. The incidence rate of all-cause death and heart failure hospitalization was significantly higher in patients with older age (p < 0.001), while there was no significant difference in the incidence rate of ventricular arrhythmia among age groups (p = 0.74). Conclusions: In patients with CS, the risk of all-cause death and heart failure hospitalization was higher in older patients compared with other age groups; however, the risk of ventricular arrhythmia was comparable across all age groups.

Mechanical circulatory support in cardiogenic shock.

Cardiogenic shock is a complex and diverse pathological condition characterized by reduced myocardial contractility. The goal of treatment of cardiogenic shock is to improve abnormal hemodynamics and maintain adequate tissue perfusion in organs. If hypotension and insufficient tissue perfusion persist despite initial therapy, temporary mechanical circulatory support (t-MCS) should be initiated. This decade sees the beginning of a new era of cardiogenic shock management using t-MCS through the accumulated experience with use of intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO), as well as new revolutionary devices or systems such as transvalvular axial flow pump (Impella) and a combination of VA-ECMO and Impella (ECPELLA) based on the knowledge of circulatory physiology. In this transitional period, we outline the approach to the management of cardiogenic shock by t-MCS. The management strategy involves carefully selecting one or a combination of the t-MCS devices, taking into account the characteristics of each device and the specific pathological condition. This selection is guided by monitoring of hemodynamics, classification of shock stage, risk stratification, and coordinated management by the multidisciplinary shock team.

Detailed Clinical Characteristics, Interventions, and Long-Term Outcomes of Patients With Gastric Cancer Who Received the Best Supportive Care Without Any Anticancer Treatment.

Background: Due to the lack of studies, the long-term prognoses of unfit patients with gastric cancer (GC) who did not receive any aggressive cancer treatment (best supportive care [BSC] cases) remain unclear, especially for those with potentially curable GC. We conducted this observational study to capture the real-world data of characteristics and outcomes for BSC cases. Method: Consecutive clinical records of patients with GC diagnosed at Steel Memorial Muroran Hospital from January 2017 to December 2021 were analyzed. Result: Of 481 patients diagnosed with GC, 91 (18.9%) were BSC cases. The median overall survival (OS) was 12.4, 8.3, and 2.5 months for clinical stage (cStage) I, II-III, and IV, respectively. Patients with potentially curable GC (cStage I-III) had significantly longer OS than those with incurable disease (cStage IV), with a hazard ratio for death of 0.29 (95% confidence interval: 0.18-0.47). Conclusion: Our report provides useful information for decision-making for unfit patients with GC in daily clinical practice.

Determination of Peak Oxygen Uptake in Patients with Acute Myocardial Infarction: The Role of Arterial Stiffness in Cardio-Vascular-Skeletal Muscle Coupling.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardio-skeletal muscle coupling during exercise was then elucidated. Upon discharge, we measured exercise capacity using cardiopulmonary exercise testing (CPX), assessed arterial stiffness with the cardio-ankle vascular index (CAVI), and determined body composition to assess the skeletal muscle mass of 101 patients with AMI. Patients were categorized based on their CAVI scores into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0-8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and VO2 Peak during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply causes systemic exercise limits in patients with AMI. This suggests that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Effects of a visual search task in a virtual reality space with a moving background on spatial cognition and standing balance in patients with left hemiparetic stroke.

We examined effects of a visual search task (VST) in virtual reality (VR) with a moving background on spatial cognition and standing balance in left hemiparetic strokes. The VST with background deviation was allocated to Case A. In Case B, the VST without the deviation was performed. As a results, in Case A, the reaction time of VST was shortened in the paretic space and ability of weight-shift to the paretic side was improved. In conclusion, the VST in the VR with a spatial manipulation may improve spatial cognition and standing balance in left hemiparetic strokes.