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Volume 1, December
 
 

Therapeutics, Volume 1, Issue 1 (September 2024) – 6 articles

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10 pages, 697 KiB  
Review
Management of Left Atrial Tachyrhythms in the Setting of HFpEF with Pulsed-Field Ablation: Treating Fire with Water?
by Tyler Chinedu Chinyere and Ikeotunye Royal Chinyere
Therapeutics 2024, 1(1), 42-51; https://doi.org/10.3390/therapeutics1010006 - 23 Sep 2024
Viewed by 952
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 [...] Read more.
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. Full article
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8 pages, 1457 KiB  
Case Report
Continued Anticomplement Therapy: A Lifeline for Post-Renal-Transplant Patients with Complement-Mediated Hemolytic Uremic Syndrome
by Natasha Venugopal, Hyma V. Polimera, Jessica Santucci, Erik Washburn and Elizabeth Federici
Therapeutics 2024, 1(1), 34-41; https://doi.org/10.3390/therapeutics1010005 - 11 Sep 2024
Viewed by 563
Abstract
Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition [...] Read more.
Background: Complement-mediated hemolytic uremic syndrome (CM-HUS), formerly known as atypical HUS, is a rare but potentially fatal thrombotic microangiopathy (TMA) characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and acute kidney injury. It is primarily caused by complement dysregulation. The condition can progress to end-stage renal disease (ESRD), often necessitating kidney transplant. In rare instances, it can develop in post-renal-transplant patients. Methods: Here, we present the cases of two patients with ESRD status post kidney transplant who presented with thrombocytopenia, anemia, and acute kidney injury. In both cases, work-up was suggestive of CM-HUS, and stabilization was achieved with eculizumab. Discussion: The pathogenesis of CM-HUS involves dysregulation of the complement system, and complement inhibitors such as eculizumab can be used for initial management and relapse. The relapse rate following eculizumab treatment can range from 20 to 67%. Patients with a history of kidney transplant are more prone to relapse than those with native kidneys. Re-treatment with complement inhibitors has proven effective in managing relapses, and long-term continuation of complement inhibitor medications is recommended to prevent recurrence. Conclusions: CM-HUS is rare, especially in post-transplant patients, and can be potentially fatal. It is crucial for clinicians to recognize and treat this condition promptly. Management often involves complement inhibitors. The risk of relapse is particularly high in patients with a history of kidney transplant, but long-term continuation of these medications can prevent relapse. Full article
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12 pages, 1674 KiB  
Systematic Review
Safety and Efficacy of Primary EUS-Guided Choledochoduodenostomy for Malignant Distal Biliary Obstruction: A Systematic Review and Meta-Analysis
by Eugene Annor, Harishankar Gopakumar, Ishaan Vohra and Srinivas R. Puli
Therapeutics 2024, 1(1), 22-33; https://doi.org/10.3390/therapeutics1010004 - 12 Aug 2024
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Abstract
Background: Endoscopic retrograde cholangiopancreatography (ERCP) is preferred for biliary drainage in malignant distal biliary obstruction (MDBO). Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is considered a rescue therapy for failed ERCP. This study aims to evaluate the safety and efficacy of this technique as the primary [...] Read more.
Background: Endoscopic retrograde cholangiopancreatography (ERCP) is preferred for biliary drainage in malignant distal biliary obstruction (MDBO). Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is considered a rescue therapy for failed ERCP. This study aims to evaluate the safety and efficacy of this technique as the primary modality for MDBO biliary drainage. Methods: An electronic database search was conducted following PRISMA guidelines to identify studies on EUS-CDS for primary biliary drainage in MDBO. A meta-analysis was performed using random and fixed effects models. Results: We extracted data from 10 eligible studies comprising 519 patients. The mean age for the study was 70 years ± SD 2.66. The pooled technical success rate was 92.36% (95% CI = 88.39–95.56), and the clinical success rate was 88.91% (95% CI = 85.22–92.13). The pooled stent dysfunction rate was 13.66% (95% CI = 7.47–21.35), and the reintervention rate was 15.91% (95% CI = 11.00–21.54) of patients. The mean stent patency duration was 229.20 days ± SD 113.9. The total pooled adverse events rate was 17.50% (95% CI = 12.90–22.64), and 9.03% (95% CI = 4.43–15.05) was considered moderate to severe. Procedure-related pancreatitis had a pooled rate of 0%. The pooled adverse event rate of acute cholangitis was 6.84% (95% CI = 3.69–10.88), and for acute cholecystitis it was 2.61% (95% CI = 1.06–4.83). Conclusions: EUS-CDS demonstrates favorable outcomes when used as a primary approach in MDBO. With a long stent patency duration and no procedure-related acute pancreatitis, it may be considered the primary technique when expertise is available. Full article
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18 pages, 2262 KiB  
Article
Synergistic Antitumor Effects of 177Lu-Octreotide Combined with an ALK Inhibitor in a High-Risk Neuroblastoma Xenograft Model
by Arman Romiani, Daniella Pettersson, Nishte Rassol, Klara Simonsson, Hana Bakr, Dan E. Lind, Anikó Kovács, Johan Spetz, Ruth H. Palmer, Bengt Hallberg, Khalil Helou and Eva Forssell-Aronsson
Therapeutics 2024, 1(1), 4-21; https://doi.org/10.3390/therapeutics1010003 - 7 Aug 2024
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Abstract
Background/Objectives: Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitate the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in [...] Read more.
Background/Objectives: Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitate the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Methods: Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, and a combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Results: Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. An increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID down-regulated and HRK up-regulated on days 2 and 7, respectively. Conclusions: The data suggest that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide and could improve treatment outcomes in patients with HR-NB. Full article
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2 pages, 139 KiB  
Editorial
Welcome to Therapeutics: A Note from the Editor-in-Chief
by Nejat Düzgüneş
Therapeutics 2024, 1(1), 2-3; https://doi.org/10.3390/therapeutics1010002 - 18 Jun 2024
Viewed by 1067
Abstract
It is an honor to serve as the founding Editor-in-Chief of the open access journal Therapeutics [...] Full article
1 pages, 133 KiB  
Editorial
Publisher’s Note: Therapeutics as a Spin-Off Journal of Medicines
by Shu-Kun Lin
Therapeutics 2024, 1(1), 1; https://doi.org/10.3390/therapeutics1010001 - 11 May 2024
Viewed by 976
Abstract
We are publishing volume 11 of Medicines in 2024 [...] Full article
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