Safety and Efficacy of Selexipag for Pediatric Pulmonary Arterial Hypertension in Japanese Patients - An Open-Label Phase 2 Study.

Background: Selexipag, an oral prostacyclin (PGI) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.

Methods And Results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration.

Krebs von den Lungen-6 surveillance in immune checkpoint inhibitor-induced pneumonitis.

Background: The immune-related adverse event (irAE), pneumonitis, is a potentially fatal complication of immune checkpoint inhibitors (ICIs). Preventing its progression is crucial, emphasizing the need for effective screening tests. We evaluated the feasibility of using Krebs von den Lungen-6 (KL-6), a marker for interstitial pneumonitis, as a screening tool for pneumonitis.

Evaluation of the Efficacy and Accuracy of Super-Flexible Three-Dimensional Heart Models of Congenital Heart Disease Made via Stereolithography Printing and Vacuum Casting: A Multicenter Clinical Trial.

Three-dimensional (3D) printing is an advanced technology for accurately understanding anatomy and supporting the successful surgical management of complex congenital heart disease (CHD). We aimed to evaluate whether our super-flexible 3D heart models could facilitate preoperative decision-making and surgical simulation for complex CHD. The super-flexible heart models were fabricated by stereolithography 3D printing of the internal and external contours of the heart from cardiac computed tomography (CT) data, followed by vacuum casting with a polyurethane material similar in elasticity to a child's heart.

Vasospastic Angina in Adolescents: A Case Report of a 15-Year-Old Boy.

This case report describes a 15-year-old boy who presented with vasospastic angina (VSA). His symptoms included chest and back pain, nausea, and respiratory distress. After undergoing diagnostic tests, including coronary angiography and an acetylcholine provocation test, the patient was diagnosed with VSA.

Epigenetic repression of de novo cysteine synthetases induces intra-cellular accumulation of cysteine in hepatocarcinoma by up-regulating the cystine uptake transporter xCT.

Background: The metabolic reprogramming of amino acids is critical for cancer cell growth and survival. Notably, intracellular accumulation of cysteine is often observed in various cancers, suggesting its potential role in alleviating the oxidative stress associated with rapid proliferation. The liver is the primary organ for cysteine biosynthesis, but much remains unknown about the metabolic alterations of cysteine and their mechanisms in hepatocellular carcinoma cells.

Dosing Time-Dependent Difference in the Suppressive Effect of Empagliflozin on the Development of Mechanical Pain Hypersensitivity in Diabetic Mice.

A problem for patients with diabetes is the rise of complications, such as peripheral neuropathy, nephropathy, and retinopathy. Among them, peripheral neuropathy, characterized by numbness and/or hypersensitivity to pain in the extremities, is likely to develop in the early stages of diabetes. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, exerts hypoglycemic effects by preventing glucose reabsorption in proximal tubular cells.

Outcomes of Veno-Arterial Extracorporeal Membrane Oxygenation With Percutaneous Left Ventricular Unloading in Fulminant Myocarditis.

Fulminant myocarditis requiring peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has a high mortality rate. We investigated clinical outcomes of combined use of VA-ECMO and percutaneous left ventricular assist device (VAD) (Impella) for fulminant myocarditis in 104 consecutive patients enrolled in the Japan Registry for Percutaneous VAD (J-pVAD) between October 2017 and January 2020. Patients were followed until hospital discharge and predictors of survival were analyzed with a Cox proportional hazards model.

Inhibition of Tumor-Derived C-C Motif Chemokine Ligand 2 Expression Attenuates Tactile Allodynia in NCTC 2472 Fibrosarcoma-Inoculated Mice.

Neuropathic pain associated with cancers is caused by tumor growth compressing and damaging nerves, which would also be enhanced by inflammatory factors through sensitizing nociceptor neurons. A troublesome hallmark symptom of neuropathic pain is hypersensitivity to innocuous stimuli, a condition known as "tactile allodynia", which is often refractory to NSAIDs and opioids. The involvement of chemokine CCL2 (monocyte chemoattractant protein-1) in cancer-evoked neuropathic pain is well established, but opinions remain divided as to whether CCL2 is involved in the production of tactile allodynia with tumor growth.

Senescence-induced alteration of circadian phagocytic activity of retinal pigment epithelium cell line ARPE-19.

Renewal of retinal photoreceptor outer segments is conducted through daily shedding of distal photoreceptor outer segment tips and subsequent their phagocytosis by the adjacent retinal pigment epithelium (RPE) monolayer. Dysregulation of the diurnal clearance of photoreceptor outer segment tips has been implicated in age-related retinal degeneration, but it remains to be clarified how the circadian phagocytic activity of RPE cells is modulated by senescence. In this study, we used the human RPE cell line ARPE-19 to investigate whether hydrogen peroxide (HO)-induced senescence in ARPE-19 cells alters the circadian rhythm of their phagocytic activity.

Short-Term Outcomes of Impella Support in Japanese Patients With Cardiogenic Shock Due to Acute Myocardial Infarction - Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD).

Background: The Impellapercutaneous left ventricular assist device has been available in Japan since 2017. This is the first large-scale registry study to analyze the efficacy and safety of Impella in Japanese patients with acute myocardial infarction with cardiogenic shock (AMICS).

Methods and results: The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) has registered all consecutive Japanese patients treated with Impella.

Automated analysis method to assess pulmonary blood flow distribution using conventional X-ray angiography.

Quantitative assessment of the right-to-left ratio of pulmonary blood flow distribution is important for determining the clinical indications for treating pulmonary arterial branch stenosis. A novel theory was recently proposed that can be used to quantitatively assess the right-to-left ratio on conventional X-ray angiography images. In the proposal, further developments were indicated, especially automated calculation.

Three-year experience of catheter-based micro-axial left ventricular assist device, Impella, in Japanese patients: the first interim analysis of Japan registry for percutaneous ventricular assist device (J-PVAD).

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.

Basis for diurnal exacerbation of neuropathic pain hypersensitivity and its application for drug development.

In addition to diurnal rhythms in physiology and behavior, a variety of pathological conditions also exhibit marked day-night changes in symptom intensity, exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke and chronic pain disorders. Currently, novel therapeutic approaches are facilitated by the development of chemical compounds targeted to key proteins that cause diurnal exacerbation of pathological events. Neuropathic pain is a chronic condition that occurs by tumor-induced nerve compression, cancer cell infiltration into the nerve, diabetes and herpes virus infection.

Identification of metabolomic profile related to adult Fontan pathophysiology.

Background: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups.

Methods And Results: We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry.

A novel diagnostic approach for assessing pulmonary blood flow distribution using conventional X-ray angiography.

Objective: Quantitative assessment of pulmonary blood flow distribution is important when determining the clinical indications for treating pulmonary arterial branch stenosis. Lung perfusion scintigraphy is currently the gold standard for quantitative blood flow measurement. However, it is expensive, cannot provide a real-time assessment, requires additional sedation, and exposes the patient to ionizing radiation.

Ventricular myocardial response to exercise in patients with Fontan circulation.

Background: Exercise stress echocardiography has been used to assess myocardial reserve in various heart diseases. This study examined the ventricular myocardial response to exercise in Fontan patients using exercise stress echocardiography.

Methods: Twenty-five Fontan patients and 19 control subjects underwent semi-supine bicycle exercise stress echocardiography in this prospective, single-center, cross-sectional study.