JAK Inhibitor Upadacitinib Induces Remission in Refractory Immune-Related Colitis Triggered by CTLA-4 and PD-1 Inhibitor Combination Therapy in Malignant Pleural Mesothelioma: A Case Report.

Background: Immune checkpoint inhibitors have demonstrated efficacy against various cancers; however, there is a rising incidence of immune-related colitis. Some cases of immune-related colitis prove resistant to treatment, even with the administration of glucocorticoids or infliximab, and there is currently no established standard treatment for such cases.

Case: The patient, a 73-year-old male, had undergone combination therapy for malignant pleural mesothelioma for 2 years, utilizing both ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor).

A Practical Method for Predicting Compound Brain Concentration-Time Profiles: Combination of PK Modeling and Machine Learning.

Given the aging populations in advanced countries globally, many pharmaceutical companies have focused on developing central nervous system (CNS) drugs. However, due to the blood-brain barrier, drugs do not easily reach the target area in the brain. Although conventional screening methods for drug discovery involve the measurement of (unbound fraction of drug) brain-to-plasma partition coefficients, it is difficult to consider nonequilibrium between plasma and brain compound concentration-time profiles.

Midterm Clinical Outcomes after Isolated Surgical and Transcatheter Aortic Valve Replacement in Low-Risk Patients with Aortic Stenosis.

Purpose: This study aimed to compare the clinical outcomes of isolated surgical aortic valve replacement (SAVR) and transfemoral (TF)-transcatheter aortic valve replacement (TAVR) in low-risk aortic stenosis (AS) patients.

Methods: A total of 696 low-risk (Society of Thoracic Surgeons score <4%) AS patients underwent isolated SAVR or TF-TAVR at five centers. After 1:1 propensity score matching, 159 pairs were identified.

Prediction of Inhibitory Activity against the MATE1 Transporter via Combined Fingerprint- and Physics-Based Machine Learning Models.

Renal secretion plays an important role in excretion of drug from the kidney. Two major transporters known to be highly involved in renal secretion are MATE1/2 K and OCT2, the former of which is highly related to drug-drug interactions. Among published in silico models for MATE inhibitors, a previous model obtained a ROC-AUC value of 0.

Correlation Between the Effects of CO Laser and Histopathological Analysis in Vocal Cord Lesions: An Observational Study.

Lasers are based on the principle of light amplification by empowering atoms to store and emit light in a coherent form. Through their effect on tissues, lasers reduce hemorrhage allowing the surgeon to work in a clear field with precise removal of the tissues. Irradiation of the soft tissues by lasers produces thermal effects on the surrounding healthy tissues which can make histopathological examination difficult.

Neurite outgrowth promotion in PC12 cells by 24()-ethyllophenol from .

We examined the mechanism by which 24()-ethyllophenol (MAB28) isolated from the branches of caused neurite outgrowth in rat pheochromocytoma cells (PC12). MAB28 significantly promoted neurite outgrowth to a similar degree as the positive control, nerve growth factor (NGF). After incubation with MAB28 in PC12 cells, phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and cyclic AMP response element-binding protein was detected, but the time course of phosphorylation was different from that induced by NGF.

Development of a Novel In Silico Classification Model to Assess Reactive Metabolite Formation in the Cysteine Trapping Assay and Investigation of Important Substructures.

Predicting whether a compound can cause drug-induced liver injury (DILI) is difficult due to the complexity of drug mechanism. The cysteine trapping assay is a method for detecting reactive metabolites that bind to microsomes covalently. However, it is cumbersome to use 35S isotope-labeled cysteine for this assay.

In vivo mitral valve repair for the transplanted donor heart in orthotopic heart transplantation.

A 53-year-old woman with the dilated phase of hypertrophic cardiomyopathy underwent orthotopic heart transplantation. The donor heart was evaluated as normal preoperatively without mitral regurgitation or the left atrium dilation, transplanted using the modified bicaval technique. Although the heart beat satisfactorily after aortic declamping, massive mitral regurgitation was observed without any prolapse or annular dilation.

Development of Novel Methods for QSAR Modeling by Machine Learning Repeatedly: A Case Study on Drug Distribution to Each Tissue.

Artificial intelligence is expected to help identify excellent candidates in drug discovery. However, we face a lack of data, as it is time-consuming and expensive to acquire raw data perfectly for many compounds. Hence, we tried to develop a novel quantitative structure-activity relationship (QSAR) method to predict a parameter more precisely from an incomplete data set via optimizing data handling by making use of predicted explanatory variables.

A Novel Intraoperative CT Navigation System for Spinal Fusion Surgery in Lumbar Degenerative Disease: Accuracy and Safety of Pedicle Screw Placement.

In recent years, intraoperative computed tomography (CT) navigation has become widely used for the insertion of pedicle screws in spinal fusion surgery. However, conventional intraoperative CT navigation may be impaired by infrared interference between the infrared camera and surgical instruments, which can lead to the misplacement of pedicle screws. Recently, a novel intraoperative CT navigation system, NextAR, has been developed.

Procedural selection strategy and clinical outcomes in mitral valve surgery with concomitant aortic valve replacement in elderly patients.

Introduction: In the context of double-valve surgery for elderly high-risk patients involving both the aortic and mitral valves, a clinically significant problem has been that no clear criteria or surgical strategies have been reported for the selection of mitral valve plasty (MVP) or mitral valve replacement (MVR) for mitral valve disease management during surgical aortic valve replacement (SAVR) to achieve better clinical outcomes. This study investigated valve durability and survival using our surgical strategy for mitral valve disease with concomitant SAVR in elderly patients.

Methods: Eighty-six patients aged > 65 years (mean 75 years) who underwent a double-valve procedure for mitral valve surgery with concomitant SAVR from 2010 to 2022 were reviewed.

Adjunctive posterior wall isolation for the treatment of persistent and longstanding persistent atrial fibrillation (CORNERSTONE AF) trial: Design and rationale.

Background: A left atrial posterior wall isolation (LAPWI) is one of the atrial fibrillation (AF) ablation strategies.

Hypothesis: We hypothesized that an additional empirical LAPWI would increase the freedom from recurrent atrial arrhythmias as compared to standard AF ablation in persistent AF patients.

Methods: The CORNERSTONE AF study is a prospective, randomized, multicenter study investigating patients with AF persisting for >7 days and <3 years undergoing first-time AF ablation.

Autologous concentrated growth factor mediated accelerated bone healing in root-end microsurgery: A multicenter randomized clinical trial.

Introduction: Concentrated growth factor (CGF) is a new-generation autologous platelet concentrate that promotes tissue regeneration and has anti-inflammatory properties. This randomized multicenter trial aimed to evaluate the effects of CGF on bone healing in combination with root-end microsurgery.

Methods: Healthy adult patients indicated for root-end microsurgery were randomly assigned to either the CGF or control (no CGF implantation) groups.

Serum leucine-rich alpha-2 glycoprotein in monitoring disease activity and intestinal mucosal healing for biotherapy-naïve cases with ulcerative colitis.

Background And Aim: Serum leucine-rich alpha-2 glycoprotein level has been reported to be a useful biomarker in assessing mucosal healing in patients undergoing biotherapy, where mucosal lesions caused by ulcerative colitis are difficult to assess endoscopically. However, no such reports have been reported in biotherapy-naïve cases.

Methods: Sixty-eight patients with ulcerative colitis (UC) who were biotherapy-naïve at Kindai University Hospital between October 2021 and October 2022 were enrolled.

Primary Malignant Lymphoma of the Cauda Equina Diagnosed after Decompression for Lumbar Spinal Stenosis: A Case Report.

Primary malignant lymphoma confinement to the cauda equina is rare. Only 14 cases of primary malignant lymphoma in the cauda equina have been reported. In these cases, the clinical features were similar to those of lumbar spinal canal stenosis (LSCS).

Development of a 2D-QSAR Model for Tissue-to-Plasma Partition Coefficient Value with High Accuracy Using Machine Learning Method, Minimum Required Experimental Values, and Physicochemical Descriptors.

Background: The demand for physiologically based pharmacokinetic (PBPK) model is increasing currently. New drug application (NDA) of many compounds is submitted with PBPK models for efficient drug development. Tissue-to-plasma partition coefficient (K) is a key parameter for the PBPK model to describe differential equations.

Prediction of Compound Plasma Concentration-Time Profiles in Mice Using Random Forest.

Pharmacokinetic (PK) parameters such as clearance (CL) and volume of distribution (Vd) have been the subject of previous predictive models. However, having information of the concentration over time profile explicitly can provide additional value like time above MIC or AUC, etc., to understand both the efficacy and safety-related aspects of a compound.