Febuxostat enhances the efficacy of dasatinib by inhibiting ATP-binding cassette subfamily G member 2 (ABCG2) in chronic myeloid leukemia cells.

Dasatinib is a second-generation breakpoint cluster region-abelson 1 (BCR::ABL1) tyrosine kinase inhibitor (TKI) used for the treatment of chronic myeloid leukemia (CML). Overexpression of ATP-binding cassette subfamily G member 2 (ABCG2) in CML cells contributes to dasatinib resistance and poor chemotherapeutic responses. Considering that the xanthine oxidase inhibitor febuxostat has anti-ABCG2 activity, febuxostat may enhance the efficacy of dasatinib.

General Applicability of Existing College of American Pathologists Accreditation Requirements to Clinical Implementation of Machine Learning-Based Methods in Molecular Oncology Testing.

Context.—: The College of American Pathologists (CAP) accreditation requirements for clinical laboratory testing help ensure laboratories implement and maintain systems and processes that are associated with quality. Machine learning (ML)-based models share some features of conventional laboratory testing methods.

A multimodal generative AI copilot for human pathology.

Computational pathology has witnessed considerable progress in the development of both task-specific predictive models and task-agnostic self-supervised vision encoders. However, despite the explosive growth of generative artificial intelligence (AI), there have been few studies on building general-purpose multimodal AI assistants and copilots tailored to pathology. Here we present PathChat, a vision-language generalist AI assistant for human pathology.

Contribution of human organic anion transporter 3-mediated transport of a major linezolid metabolite, PNU-142586, in linezolid-induced thrombocytopenia.

Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for linezolid-induced thrombocytopenia using two real-world clinical databases and explored its underlying mechanism through in vitro and in vivo experiments. In a retrospective analysis of 150 linezolid-treated patients, multivariate analysis identified coadministration of lansoprazole, a proton pump inhibitor, as a significant independent risk factor for thrombocytopenia (odds ratio: 2.

Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

Background/aim: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports.

Proton Pump Inhibitors Ameliorate Oxaliplatin-induced Peripheral Neuropathy: Retrospective Analysis of Two Real-world Clinical Databases.

Background/aim: Chemotherapy-induced peripheral neuropathy (CIPN) due to oxaliplatin (L-OHP) is a major clinical problem. Effective and safe preventive strategies for CIPN are urgently needed. Although proton pump inhibitors (PPIs) have various off-target effects, their clinical impact on L-OHP-induced CIPN remains unclear.

A doxycycline-inducible CYP3A4-Caco-2 cell line as a model for evaluating safety of aflatoxin B1 in the human intestine.

Exposure of humans to aflatoxin B1 (AFB1) via ingestion of contaminated agricultural products is a major concern for human health throughout the world because epoxidized AFB1, biotransformed from AFB1 by hepatic CYP3A4, is strongly hepatotoxic and hepatocarcinogenic. Intestinal epithelial cells serve as a physical and physiological barrier against xenobiotics via their intercellular tight junction (TJ) seals and the metabolizing enzyme CYP3A4. However, the effect of AFB1 on the intestinal barrier remains unclear.

Repositioning of Lansoprazole as a Protective Agent Against Cisplatin-Induced Ototoxicity.

Cisplatin (CDDP) is a well-known chemotherapeutic drug approved for various cancers. However, CDDP accumulates in the inner ear cochlea via organic cation transporter 2 (OCT2) and causes ototoxicity, which is a major clinical limitation. Since lansoprazole (LPZ), a proton pump inhibitor, is known to inhibit OCT2-mediated transport of CDDP, we hypothesized that LPZ might ameliorate CDDP-induced ototoxicity (CIO).

Concomitant palonosetron ameliorates cisplatin-induced nephrotoxicity, nausea, and vomiting: a retrospective cohort study and pharmacovigilance analysis.

Background: Cisplatin (CDDP)-induced nephrotoxicity is the most important complication of CDDP treatment. 5-Hydroxytryptamine type 3 receptor antagonists (5-HTRAs) are widely used to prevent chemotherapy-induced nausea and vomiting (CINV). However, in patients with the triple antiemetic (neurokinin-1 receptor antagonist, 5-HTRA, and dexamethasone) therapy, the advantage of palonosetron in comparison with other 5-HTRAs on CDDP-induced nephrotoxicity and CINV remains unclear.

Proton Pump Inhibitors Ameliorate Capecitabine-induced Hand-Foot Syndrome in Patients With Breast Cancer: A Retrospective Study.

Background/aim: Hand-foot syndrome (HFS) is the most common adverse event associated with capecitabine, and its pathogenesis is known to be associated with inflammation. Proton pump inhibitors (PPIs) reportedly exert anti-inflammatory effects; however, the impact of PPIs on capecitabine-induced HFS needs to be clarified in the clinical setting. In the present study, we retrospectively investigated the efficacy and safety of PPIs in patients with breast cancer receiving capecitabine.

Cytomegalovirus skin disease in a kidney transplant patient.

A 44-year-old man with a history of renal transplantation presented with right lower abdominal wall swelling, redness and pain. A bacterial abscess was drained, and he was discharged home with oral antibiotics. After failing to improve, he returned to the hospital, where he was briefly treated with intravenous antibiotics and discharged home again.

Effect of number of medications and complexity of regimens on medication adherence and blood pressure management in hospitalized patients with hypertension.

Introduction: Good adherence of antihypertensives is recommended for the accomplishment of hypertension therapy. The number of medications and characteristics contributing to medication regimen complexity, such as dosage forms and dosing frequency, are known to influence medication adherence. However, the effect of medication regimen complexity on the therapeutic efficacy of medicines remains to be clarified.

Correlation of Coagulation Parameters With Clinical Outcomes During the Coronavirus-19 Surge in New York: Observational Cohort.

Importance: COVID-19 has caused a worldwide illness and New York became the epicenter of COVID-19 in the United States from Mid-March to May 2020.

Objective: To investigate the coagulopathic presentation of COVID and its natural course during the early stages of the COVID-19 surge in New York. To investigate whether hematologic and coagulation parameters can be used to assess illness severity and death.

Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study.

Background: The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration.

An Integrated In Silico and In Vivo Approach to Identify Protective Effects of Palonosetron in Cisplatin-Induced Nephrotoxicity.

Cisplatin is widely used to treat various types of cancers, but it is often limited by nephrotoxicity. Here, we employed an integrated in silico and in vivo approach to identify potential treatments for cisplatin-induced nephrotoxicity (CIN). Using publicly available mouse kidney and human kidney organoid transcriptome datasets, we first identified a 208-gene expression signature for CIN and then used the bioinformatics database Cmap and Lincs Unified Environment (CLUE) to identify drugs expected to counter the expression signature for CIN.

Temporary decrease in tacrolimus clearance in cytochrome P450 3A5 non-expressors early after living donor kidney transplantation: Effect of interleukin 6-induced suppression of the cytochrome P450 3A gene.

Tacrolimus is important for immunosuppression in kidney transplantation. In this historical cohort and in vitro study, we evaluated the changes in tacrolimus pharmacokinetics early after living donor kidney transplantation and the effects of interleukin (IL)-6 on cytochrome P450 3A4 (CYP3A4) and cytochrome P450 3A5 (CYP3A5) expression. In the historical cohort study, 22 patients who met the inclusion criteria were classified into CYP3A5 expressors and non-expressors (n = 16 and 6, respectively).

Anticoagulation in COVID-19: Effect of Enoxaparin, Heparin, and Apixaban on Mortality.

Background:  Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity.

Objective:  We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity.

Idarubicin, an Anthracycline, Induces Oxidative DNA Damage in the Presence of Copper (II).

Background/aim: The aim of the present study was to investigate whether idarubicin (IDR) induces oxidative DNA damage in the presence of copper (II).

Materials And Methods: DNA damage was evaluated by pBR322 plasmid DNA cleavage. The formation of oxidative stress markers [O and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] was analysed.

Concomitant lansoprazole ameliorates cisplatin-induced nephrotoxicity by inhibiting renal organic cation transporter 2 in rats.

Cisplatin is used widely for the treatment of multiple solid tumors. Cisplatin-induced nephrotoxicity is caused by renal accumulation of cisplatin via human organic cation transporter 2 (hOCT2). As lansoprazole, a proton pump inhibitor, is known to inhibit hOCT2 activity, lansoprazole might ameliorate cisplatin-induced nephrotoxicity.

Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein.

Methotrexate (MTX) is an antifolate agent used for the treatment of various malignancies and is eliminated by breast cancer resistance protein (BCRP). Because febuxostat (FBX) is known to inhibit BCRP activity, FBX might exacerbate MTX-related adverse effects. In this study, we examined the drug-drug interaction between FBX and MTX in BCRP-expressing membrane vesicles.

Maternal Blood Concentration of Tadalafil and Uterine Blood Flow in Pregnancy.

Tadalafil for treatment of fetal growth restriction (FGR) or preeclampsia is given once a day orally. The drug kinetics of tadalafil were investigated to determine the ideal dosage to promote uterine blood flow. Materials and Methods: We recruited five pregnant women with FGR or preeclampsia before administration of tadalafil, all of which were administered tadalafil (20 mg/day, once-daily dosing).