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HIV-Associated Cryptococcal Meningitis: A Call for Action for New Treatment Options. hiv相关隐球菌脑膜炎：呼吁采取行动寻求新的治疗方案。

Therapeutics Pub Date : 2026-06-01 Epub Date: 2026-03-31 DOI: 10.3390/therapeutics3020009

Samuel Okurut, David B Meya

{"title":"HIV-Associated Cryptococcal Meningitis: A Call for Action for New Treatment Options.","authors":"Samuel Okurut, David B Meya","doi":"10.3390/therapeutics3020009","DOIUrl":"10.3390/therapeutics3020009","url":null,"abstract":"Cryptococcal meningitis occurs in 62% of persons with HIV-associated meningitis, making Cryptococcus an important cause of meningitis among adults with advanced HIV disease in regions with elevated prevalence of HIV. Despite efforts to advance treatment, the in-hospital death rate of 19% remains unprecedentedly high. Aggregate published clinical trial data evaluating cryptococcosis treatment with survival as the primary endpoint show a significant reduction in the proportion of survivors from diagnosis to 88.5% at 2 weeks of treatment and further to 74% survival at 10 weeks of follow-up (p = 0.001). Disease complications concomitant with unveiling symptoms and reoccurrence of fungal infections, deferment in treatment, and high prevalence of other comorbidities increase the risk of individuals succumbing to cryptococcal meningitis. Among clinical trials of cryptococcal meningitis, the World Health Organization-recommended standard of care was used to randomize participants to the control trial arm. The proportion of participants surviving in the trial was not statistically different between trial randomization arms. In summary, high in-hospital death rates and continued participants' deterioration post-hospital discharge are challenges for evidence-based new therapies seeking to improve outcomes.","PeriodicalId":520250,"journal":{"name":"Therapeutics","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13268590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148267890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel 2D/3D Hybrid Organoid System for High-Throughput Drug Screening in iPSC Cardiomyocytes. 用于iPSC心肌细胞高通量药物筛选的新型2D/3D混合类器官系统。

Therapeutics Pub Date : 2025-09-01 Epub Date: 2025-06-27 DOI: 10.3390/therapeutics2030011

Jordann Lewis, Basil Yaseen, Haodi Wu, Anita Saraf

{"title":"Novel 2D/3D Hybrid Organoid System for High-Throughput Drug Screening in iPSC Cardiomyocytes.","authors":"Jordann Lewis, Basil Yaseen, Haodi Wu, Anita Saraf","doi":"10.3390/therapeutics2030011","DOIUrl":"10.3390/therapeutics2030011","url":null,"abstract":"Background: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) allow for high-throughput evaluation of cardiomyocyte (CM) physiology in health and disease. While multimodality testing provides a large breadth of information related to electrophysiology, contractility, and intracellular signaling in small populations of iPSC-CMs, current technologies for analyzing these parameters are expensive and resource-intensive.Methods: We have designed a novel 2D/3D hybrid organoid system that can harness optical imaging techniques to assess electromechanical properties and calcium dynamics across CMs in a high-throughput manner. We validated our methods using a doxorubicin-based system, as the drug has well-characterized cardiotoxic, pro-arrhythmic effects.Results: This novel hybrid system provides the functional benefit of 3D organoids while minimizing optical interference from multilayered cellular systems through our cell-culture techniques that propagate organoids outwards into 2D iPSC-CM sheets. The organoids recapitulate contractile forces that are more robust in 3D structures and connectivity, while 2D CMs facilitate analysis at an individual cellular level, which recreated numerous doxorubicin-induced electrophysiologic and propagation abnormalities.Conclusions: Thus, we have developed a novel 2D/3D hybrid organoid model that employs an integrated optical analysis platform to provide a reliable high-throughput method for studying cardiotoxicity, providing valuable data on calcium, contractility, and signal propagation.","PeriodicalId":520250,"journal":{"name":"Therapeutics","volume":"2 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12893397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146184035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Management of Left Atrial Tachyrhythms in the Setting of HFpEF with Pulsed-Field Ablation: Treating Fire with Water? 用脉冲场消融术治疗高频心房颤动（HFpEF）时的左房心动过速：以水灭火？

Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-09-23 DOI: 10.3390/therapeutics1010006

Tyler Chinedu Chinyere, Ikeotunye Royal Chinyere

{"title":"Management of Left Atrial Tachyrhythms in the Setting of HFpEF with Pulsed-Field Ablation: Treating Fire with Water?","authors":"Tyler Chinedu Chinyere, Ikeotunye Royal Chinyere","doi":"10.3390/therapeutics1010006","DOIUrl":"https://doi.org/10.3390/therapeutics1010006","url":null,"abstract":"Atrial fibrillation (AF) in the setting of heart failure (HF) with preserved ejection fraction (HFpEF) is a prevalent comorbidity and is enabled by adverse left atrial (LA) remodeling, dilation, and scar tissue formation. These changes are facilitated by poor left ventricular compliance. A growing body of clinical evidence and medical guidelines suggest that managing atrial tachyrhythms with catheter ablation (CA) is paramount to treating concomitant HF. This recommendation is complicated in that thermal CA modalities, namely radiofrequency ablation and cryoablation, are both therapeutic via inducing additional scar tissue. AF treatment with thermal CA may compound the atrial scar burden for patients who already have extensive scars secondary to HFpEF. Therefore, thermal CA could act as \"gasoline\" to the slowly burning \"fire\" within the LA, increasing the rate of AF recurrence. Pulsed-field ablation (PFA), which utilizes high-voltage irreversible electroporation, is a non-thermal CA technique that is capable of disrupting reentrant microcircuits and arrhythmogenic foci without inducing significant scar burden. PFA has the potential to mitigate the strong fibrosis response to thermal CA that predisposes to AF by serving as \"water\" rather than \"gasoline\". Thus, PFA may increase the efficacy and durability of CA for AF in HFpEF, and subsequently, may decrease the risk of procedural complications from repeat CAs. In this article, we provide a summary of the clinical concepts underlying HFpEF and AF and then summarize the data to date on the potential of PFA being a superior CA technique for AF in the setting of comorbid HFpEF.","PeriodicalId":520250,"journal":{"name":"Therapeutics","volume":"1 1","pages":"42-51"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0