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Background: Anamorelin was approved in Japan in 2021 to treat cancer cachexia associated with non‐small cell lung, gastric, pancreatic, or colorectal cancers. Post‐marketing surveillance is being conducted to evaluate the real‐world safety and effectiveness of anamorelin. Methods: This prospective, observational surveillance registered all patients who started treatment with anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were defined as main safety specifications. Body weight (BW) and appetite were assessed as effectiveness specifications. Results: This analysis was based on data as of January 21, 2023. The safety and effectiveness analysis sets included 6016 and 4511 patients, respectively. Treatment‐related adverse events in ≥1% of patients were hyperglycemia (3.9%) and nausea (2.6%). The incidences of hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were 4.8%, 1.2%, and 1.1%, respectively. The mean changes (standard error [SE]) in BW from baseline to weeks 3, 12, 24, and 52 were 0.64 (0.05) kg, 1.19 (0.12) kg, 1.40 (0.21) kg, and 1.42 (0.39) kg, respectively. The mean changes (SE) in Functional Assessment of Anorexia/Cachexia Treatment 5‐item Anorexia Symptom Scale total scores from baseline to weeks 3, 12, 24, and 52 were 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), and 5.3 (0.47), respectively, exceeding the clinically meaningful improvement score (2.0 points). Conclusion: The overall safety of anamorelin raised no new safety concerns, although continued caution may be required for hyperglycemia and nausea. Improvements in BW and appetite were also observed in real‐world clinical settings. [ABSTRACT FROM AUTHOR]

A one-month-old baby boy with a complete atrioventricular septal defect underwent pulmonary artery banding. A high take-off of the left coronary artery, overlooked on the echocardiogram, was identified. It was compressed by the right pulmonary artery that was dilated owing to pulmonary artery banding. The patient developed severe heart failure, and a Lecompte maneuver was performed. The procedure helped effectively treat this congenital heart disease with a high take-off coronary artery compressed by the right pulmonary artery. [ABSTRACT FROM AUTHOR]

This is the first report of total arch replacement to repair re-coarctation. A 14-year-old boy with hypoplastic left heart syndrome developed re-coarctation, severe stenosis of neck vessels, and right ventricle dysfunction after a Norwood procedure. We performed total arch replacement; the postoperative course was unremarkable. He was followed up until 18 years of age and did not need re-intervention. Using artificial blood vessels in total arch replacement is rarely indicated but can be safely achieved when required. Mismatch between patient and graft size may be an issue in the future. [ABSTRACT FROM AUTHOR]

Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history.Case Presentation: A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8.Conclusions: This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals. [ABSTRACT FROM AUTHOR]

Biatrial drainage of the right superior vena cava resulting from a sinus venosus defect is a rare congenital malformation. It can result in severe desaturation although a sinus venosus defect usually presents as a left-to-right shunt. A male baby was noted to have cyanosis while nursing and was referred to us for medical treatment on his second day of life. Echocardiography showed that most of the blood flowing through the superior vena cava drained into the left atrium. He underwent successful surgery to correct this defect at the age of 2 years. [ABSTRACT FROM AUTHOR]

Abstract: Acidification of the lumen of intracellular organelles is important for post-transcriptional processing, endosomal maturation, receptor recycling, and vesicle trafficking, being regulated by an intricate balance between H+ influx through vacuolar-type H+-ATPase and efflux through ion channels and transporters, such as the Na+/H+ exchanger (NHE). The eukaryotic NHE family comprises two major subgroups, one residing in the plasma membrane and the other in intracellular organelles. While mammalian intracellular NHE isoforms are localized to various organelles, including the mid-trans-Golgi compartments, early and late endosomes, and recycling endosomes, Nhx1p, the sole NHE in yeast, has been reported to be localized predominantly to the late endosomal/prevacuolar compartment. Here, using live cell imaging, we demonstrated that Nhx1p is localized to the trans-Golgi network compartments, late endosomes, and recycling endosomes, similar to mammalian intracellular NHE isoforms. Loss of Nhx1p led to accumulation of components of the retromer and endosomal sorting complex required for transport complexes, but not trans-Golgi compartments, in aberrant prevacuolar compartments. Importantly, Nhx1p was also required for recycling of the plasma membrane vesicle SNAP receptor Snc1p. These observations suggest that Nhx1p plays an important role in regulation of the luminal pH of various intracellular organelles, and that this regulation is critical for the protein recycling pathway as well as the endocytic pathway. [Copyright &y& Elsevier]

Highlights: [•] A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. [•] V-ATPase-dependent luminal acidification is required for Wsc1p recycling. [•] Activity of V-ATPase might be required for cargo recognition by the retromer complex. [Copyright &y& Elsevier]

Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient. [ABSTRACT FROM AUTHOR]

Background: Drug-drug interactions (DDIs) increase the incidence of adverse drug reactions (ADRs). In a previous report, we revealed that the incidence of potential DDIs due to the same CYP molecular species in one prescription exceeds 90% among patients taking six or more drugs and that CYP3A4 markedly influences the increase in the number of potential DDIs in clinical practice. However, the factors contributing to an increased number of potential DDIs in prescriptions from multiple clinical departments remain poorly clarified., Methods: This observational study was performed at five pharmacies in Okayama Prefecture, Japan. Patients who visited these pharmacies from 11 April 2022 to 24 April 2022 were included, except those who had prescriptions only from a single clinical department. A stratified analysis was performed to determine the incidence of CYP3A4-related potential DDIs according to the number of drugs taken. Additionally, factors associated with an increase in the number of drugs involved in CYP3A4-related potential DDIs were identified using multiple linear regression analysis. In this study, potential DDIs for the prescription data subdivided by clinical department, containing two or more drugs, were used as control data., Results: Overall, 372 outpatients who received prescriptions from multiple clinical departments were included in the current study. The number of drugs contributing to CYP3A4-related potential DDIs increased with an increase in the number of clinical departments. Notably, in cases taking fewer than six drugs, prescriptions from multiple clinical departments had a higher frequency of CYP3A4-related potential DDIs than those in prescriptions subdivided by clinical department. Multiple regression analysis identified "Cardiovascular agents", "Agents affecting central nervous system", and "Urogenital and anal organ agents" as the top three drug classes that increase CYP3A4-related potential DDIs., Conclusion: Collectively, these results highlight the importance of a unified management strategy for prescribed drugs and continuous monitoring of ADRs in outpatients receiving prescriptions from multiple clinical departments even if the number of drugs taken is less than six., (© 2024. The Author(s).)

Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Background: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history., Case Presentation: A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8., Conclusions: This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Acidification of the lumen of intracellular organelles is important for post-transcriptional processing, endosomal maturation, receptor recycling, and vesicle trafficking, being regulated by an intricate balance between H+ influx through vacuolar-type H+-ATPase and efflux through ion channels and transporters, such as the Na+/H+ exchanger (NHE). The eukaryotic NHE family comprises two major subgroups, one residing in the plasma membrane and the other in intracellular organelles. While mammalian intracellular NHE isoforms are localized to various organelles, including the mid-trans-Golgi compartments, early and late endosomes, and recycling endosomes, Nhx1p, the sole NHE in yeast, has been reported to be localized predominantly to the late endosomal/prevacuolar compartment. Here, using live cell imaging, we demonstrated that Nhx1p is localized to the trans-Golgi network compartments, late endosomes, and recycling endosomes, similar to mammalian intracellular NHE isoforms. Loss of Nhx1p led to accumulation of components of the retromer and endosomal sorting complex required for transport complexes, but not trans-Golgi compartments, in aberrant prevacuolar compartments. Importantly, Nhx1p was also required for recycling of the plasma membrane vesicle SNAP receptor Snc1p. These observations suggest that Nhx1p plays an important role in regulation of the luminal pH of various intracellular organelles, and that this regulation is critical for the protein recycling pathway as well as the endocytic pathway., (Copyright © 2011 Elsevier B.V. All rights reserved.)