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Br J Ophthalmol 2004;88:494-496. doi: 10.1136/bjo.2003.027136 Aim: To report a new form of retinopathy that was observed in patients who had undergone percutaneous coronary intervention (PCI) following acute myocardial infarction [...]

Lentiviral vectors (LVs) are used in cell and gene therapies due to their ability to transduce both dividing and non-dividing cells while carrying a relatively large genetic payload and providing long-term gene expression via gene integration. Current cultivation methods produce titers of 105–107 transduction unit (TU)/mL; thus, it is necessary to concentrate LVs as well as remove process- and product-related impurities. In this work, we used a packaging cell line WinPac-RD-HV for LV production to simplify upstream processing. A direct capture method based on ion-exchange chromatography and cellulose nanofibers for LV concentration and purification was developed. This novel scalable stationary phase provides a high surface area that is accessible to LV and, therefore, has potential for high-capacity operation compared to traditional bead-based supports. We were able to concentrate LVs 100-fold while achieving a two-log removal of host cell protein and maintaining up to a 90% yield of functional vector.

The use of recombinant lentivirus pseudotyped with the coronavirus Spike protein of SARS-CoV-2 would circumvent the requirement of biosafety-level 3 (BSL-3) containment facilities for the handling of SARS-CoV-2 viruses. Herein, we describe a fast and reliable protocol for the transient production of lentiviruses pseudotyped with SARS-CoV-2 Spike (CoV-2 S) proteins and green fluorescent protein (GFP) reporters. The virus titer is determined by the GFP reporter (fluorescent) expression with a flow cytometer. High titers (>1.00 E+06 infectious units/ml) are produced using codon-optimized CoV-2 S, harbouring the prevalent D614G mutation and lacking its ER retention signal. Enhanced and consistent cell entry is achieved by using permissive HEK293T/17 cells that were genetically engineered to stably express the SARS-CoV-2 human receptor ACE2 along with the cell surface protease TMPRSS2 required for efficient fusion. For the widespread use of this protocol, its reagents have been made publicly available.Graphic abstract:Production and quantification of lentiviral vectors pseudotyped with the SARS-CoV-2 Spike glycoprotein

The antigenic variability of influenza presents many challenges to the development of vaccines and immunotherapeutics. However, it is apparent that there are epitopes on the virus that have evolved to remain largely constant due to their functional importance. These more conserved regions are often hidden and difficult to access by the human immune system but recent efforts have shown that these may be the Achilles heel of the virus through development and delivery of appropriate biological drugs. Amongst these, single domain antibodies (sdAbs) are equipped to target these vulnerabilities of the influenza virus due to their preference for concave epitopes on protein surfaces, their small size, flexible reformatting and high stability. Single domain antibodies are well placed to provide a new generation of robust analytical reagents and therapeutics to support the constant efforts to keep influenza in check.

Prognosis for fulminant myocarditis with cardiogenic shock refractory to conventional therapy is poor. This report describes mechanical circulatory support with extracorporeal membrane oxygenation as an effective alternative for treating fulminant myocarditis with circulatory collapse. [ABSTRACT FROM AUTHOR]

Selpercatinib is a selective rearranged during transfection (RET) kinase inhibitor effective for the treatment of RET-positive non-small cell lung cancer, thyroid cancer, and other cancers. However, its clinical use requires careful management because of dose-dependent adverse effects and pharmacokinetic interactions. Given the multiple factors influencing selpercatinib blood levels, we hypothesized that establishing a therapeutic drug monitoring system for selpercatinib could help reduce adverse events and optimize efficacy. Therefore, we herein developed a high-performance liquid chromatography-ultraviolet (HPLC-UV) method for measuring selpercatinib blood levels to facilitate therapeutic drug monitoring in clinical practice. Proteins were precipitated with acetonitrile, and selpercatinib and the internal standard (gefitinib) were separated via HPLC-UV. The calibration curve was linear over 0.5-8.0 µg/mL with a coefficient of determination (r²) equaling 0.9996. Intra- and interday validation coefficients were both under 2.80%. The corresponding measurement precision ranged from - 1.50% to 12.60% and - 1.32% to 7.50%, respectively, with recoveries exceeding 94.43%. Thus, this study establishes a simple and sensitive method for quantifying selpercatinib in human plasma. Future studies will analyze plasma samples from patients treated with selpercatinib and utilize this method to explore the relationships among plasma concentration, efficacy, and adverse events to define the therapeutic concentration range.

Cardiogenic shock with bradycardia due to beta-blockers is well-documented; however, this condition in association with arotinolol is unreported. We present a case of cardiogenic shock resulting from delayed arotinolol clearance caused by bile duct obstruction. A man in his 60s presented to our hospital with jaundice. We suspected acute obstructive suppurative cholangitis; however, the patient did not exhibit fever or abdominal symptoms. Based on the physical examination results, we concluded the patient was in cardiogenic shock as a consequence of delayed arotinolol elimination. We attempted to maintain organ perfusion using norepinephrine and dopamine, with minimal response. On initiating isoproterenol, the heart rate stabilised. After tapering off isoproterenol, endoscopic retrograde cholangiopancreatography (ERCP) was performed. Subsequent serum arotinolol level measurement revealed a significant reduction in the elimination half-life before and after ERCP. In cases of cardiogenic shock associated with arotinolol, presumably eliminated via the bile duct, it is crucial to consider potential delayed elimination and to appropriately time ERCP., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Competing Interests: Declarations. Conflict of interest: Haruka Noma, Naoyuki Otani, Shigeru Toyoda, and Takanori Yasu declare that they have no conflicts of interest. Ethical approval: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1964 and later versions. Informed consent: The study participant gave informed consent for all procedures and for publication of this report.

Background: The efficacy of a combination therapy consisting of venetoclax (VEN) and azacytidine (AZA) for newly diagnosed acute myeloid leukemia (AML) has been confirmed in elderly patients. However, the clinical data on VEN for pediatric AML are limited. A combination therapy consisting of crushed VEN tablets and AZA (VEN/AZA) was administered to two children with recurrent AML. The pharmacokinetics of VEN were then analysed., Case Presentation: [Patient 1] A 1-year-old, male patient who experienced an AML relapse following an allogeneic hematopoietic stem cell transplantation received three courses of VEN/AZA. At the initial dosage of VEN (8 mg/kg), the minimum plasma concentration (C min ) was only 0.44 µg/ml, which was far less than the optimal C min of 1.2 µg/ml. Subsequent dose-escalation to 10 mg/kg only achieved C min 0.42 µg/ml. [Patient 2] A 3-year-old, female patient in whom infantile acute lymphoblastic leukemia was originally diagnosed experienced a recurrence in the form of AML after lineage-switching. Three courses of VEN/AZA were administered with the same therapeutic drug monitoring as in Case 1. The C min of VEN was 0.15 µg/ml at 8 mg/kg. Afterwards, voriconazole 16 mg/kg/day was begun for a concomitant fungal infection together with VEN 2 mg/kg. This combination finally achieved C min 1.14 µg/ml probably through CYP3A4 inhibition by voriconazole. In terms of safety, only grade 4 hematological adverse events were observed in both patients. In terms of efficacy, patient 1 and patient 2 achieved stable disease status for two months and six months, respectively., Conclusion: Pediatric patients may scarcely achieve effective plasma concentration of VEN when crushed tablets are used at the same dosage as in adults., Competing Interests: Declarations. Conflict of interest: The authors state explicitly that there are no conflicts of interest in connection with this article. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oral anticancer drugs are standard treatments for many cancers and are expected to remain widely used. Owing to the super-aged nature of the Japanese society, the number of elderly patients with cancer is rapidly increasing. Poor adherence to oral medications owing to physical limitations and swallowing difficulties in elderly patients with cancer is a major problem affecting treatment. Therefore, a survey was conducted on the size of oral anticancer drugs marketed in Japan, and the actual prescription patterns were investigated using receipt data. The total diameter of oral anticancer drugs increased with the year of launch, with a significant increase in the long diameter of tablets. In Japan, oral anticancer drugs in tablet form with a long diameter of ≥7 mm and a total diameter of ≥21 mm accounted for 84.2% and 56.8%, respectively, of all oral anticancer drugs in tablet form. In addition, 96.8% and 42% of oral anticancer drugs in tablet form prescribed to people aged ≥65 years had a long diameter of ≥7 mm and a total diameter of ≥21 mm, respectively. Most drugs were larger than those that can be easily taken by the elderly. Furthermore, information on tablet crushing or simple suspension administration was lacking; these methods are clinically used when elderly patients have difficulty taking their medications. The results of this study suggest that adherence to oral anticancer medications may be reduced in elderly patients. Future studies should evaluate adherence to oral anticancer medicines among elderly patients.

Objective: Dual-antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population., Methods: This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use., Results: Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported., Conclusion: This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Hokushin General Hospital (Receipt No. 2023003). Written informed consent was waived and the information was disclosed in an opt-out manner using a document posted in our hospital, where the option to withdraw from this study was also provided. Consent for publication: Not Applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)