MD Biologix’s Post

Dosing in #PRP is a hot topic. We should strive to stay current, but remember foundational principles so we do not go too far with current trends. Heavy emphasis on hot topics has a history of swinging the pendulum too far in the field of #orthobiologics Here is a brief list of #orthobiologics trends that were at one time associated with strong (nearly dogmatic) beliefs, but now those views have softened as we have learned. 1) Activation- some believed PRP needed activation with calcium chloride or thrombin. Interestingly, without any gold-standard study to reference, this topic seems to have all but disappeared from present discussions. 2) Leukocytes- there was a belief that leukocytes must be avoided in the joint. But when BMAC or APS were brought forward, leukocytes were again absent from the conversation. Now, we've come back to admitting maybe some WBCs are helpful. There are at least 2 comparative studies demonstrating that there is no difference between LP- vs LR-PRP for knee OA (both by Filardo et al). 3) Mesenchymal stem cells- early adopters of BMAC touted the MSC content. Then came the realization that BMAC has almost no MSCs in it and that any therapeutic benefit came from sources like IRAP (which comes from the leukocytes!) Present day, there is a strong emphasis on "PRP dosing". Those advocating "high dose" only are not addressing a very large body of literature including the only positive FDA study for knee OA that used a series of lower concentration PRP injections (https://lnkd.in/egkKTqVw) Not only are there multiple RCTs showing that a series of low concentration PRP injections improves outcomes for knee OA (see previous posts for references), but there's more to PRP than the platelet count. I'll cover these other important variables in future posts. Have a great week and keep learning! *PRP for OA is off-label. These posts are intended for education only and do not constitute medical advice*

🚨 In continuous renal replacement therapy, the use of micafungin or caspofungin requires some attention due to unexpected alterations of their efficacy. Here under some recent scientific advances justifying an adapted treatment for patients. There is an increasing body of knowledge supporting the concern regarding the simultaneous use of caspofungin or micafungin and filters used in continuous renal replacement therapy (CRRT). These substances are differentially sequestrated in filters used in CRRT depending on the chemical composition of the filters. In vitro studies provided meaningful information: 1️⃣ In 2019, Purohit et al reported that 22% of caspofungin was adsorbed by the circuit used in CRRT (important ratio if you compare to the 3.5% unbound fraction of #caspofungin in plasma (1). 2️⃣ In 2020, preliminary results on the unbound concentrations of caspofungin and micafungin in the central compartment (CC) by means of NeckEpur methodology using a crystalloid solution and a polyacrylonitrile filter showed  the rapid and complete disappearance of caspofungin and micafungin from the CC without quantifiable amounts in cumulative effluents, features suggestive of an unknown route of elimination (2). 3️⃣ In 2023, confirmation of an extensive sequestration of caspofungin in a polyacrylonitrile derived filter using NeckEpur methodology (3). The Drug Sequestration Rate (DSR) was minimally mitigated by an about 3-fold increase in unbound caspofungin concentrations. 4️⃣ Regarding micafungin, a study in 2017 assessed micafungin sequestration in an in vitro model combining ECMO and CRRT using a polysulfone-derived filter (4). Extensive micafungin sequestration was observed only in the polysulfone-derived filter and not in the ECMO circuit. 5️⃣ In 2024, NeckEpur methodology showed a rapid and complete sequestration of micafungin in a polysulfone-derived filter. In contrast, in a polyacrylonitrile-derived filter, micafungin sequestration eliminated 50% of the initial dose (results presented at the annual congress of the French Society of Anesthesia and Intensive care 2024 (SFAR - Société française d'anesthésie et de réanimation) and at the Consensus, News & Perspectives on organ replacements (Journées CAPSO) at Bordeaux)   These findings suggest difficulties in using echinocandins during sessions of CRRT: ⚠️ Facing a polyacrylonitrile filter, micafungin should be considered instead of caspofungin. The best dosage regimen of micafungin remains to be determined, however. ⚠️ Facing a polysulfone-derived filter, micafungin should not be recommended. Sequestration of #caspofungin in a #polysulfone-derived filter is an unaddressed question. 📑 References below in the first comment. #echinocandins #caspofungin #micafungin #CRRT #sequestration

Intranasal Administration for Brain-Targeting Delivery Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review [1] provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design–related insights. Cyclodextrins are mentioned only as possible additives to improve the drug solubility but no examples are mentioned. Here are some recent examples for in situ forming gels applied for nasal delivery from the literature: Hyaluronic Acid-Incorporated Thermosensitive Nasal in situ Gel of Meclizine Hydrochloride with HPBCD [2] Gellan Gum-based Nasal In-situ Gel Formulation of Fexofenadine HCl with BCD [3] Poloxamer-based Mucoadhesive-Thermosensitive In Situ Gel for Clonazepam with HPBCD [4] References https://lnkd.in/d5-niFim https://lnkd.in/dGbDvZFx https://lnkd.in/du9JiCiB https://lnkd.in/dA8j9RnE

α-synuclein antibody 5G4 identifies idiopathic REM-sleep behavior disorder in abdominal skin biopsies Highlights • 5G4 synuclein antibody identifies PD and iRBD subjects in skin biopsies. • 5G4-positivity in iRBD was irrespective of the calculated prodromal PD probability. • Higher overall load of 5G4-positive structures was detected in iRBD compared to PD. • Distribution of 5G4-positive structures in dermis of patients with PD and iRBD showed the same percentage trend. IAPRD Secretariat Log in : https://lnkd.in/g7T6gfSX

Ocular Therapeutix Inc hosted an Investor Day where it highlighted clinical development progress with Axpaxli for wet age-related macular degeneration (wet AMD) and non-proliferative diabetic retinopathy (NPDR) and updated its corporate strategy. During its Investor Day, the company noted the SOL-1 study has 60 study sites active and 151 subjects enrolled in various stages of loading and randomization as of June 7, 2024. The study is being conducted under a Special Protocol Assessment (SPA) with the US FDA. The Company intends to randomize 300 treatment naïve patients in the SOL-1 study, comparing a single implant (450µg) to a single aflibercept injection (2mg) after all patients have received two loading doses of aflibercept. Read More: https://ow.ly/I1QN50SiUCN

There have been increasing concerns about the risk of aspiration during endoscopy procedures due to retained gastric residue with GLP-1 RA use. In a recent study with Elisabetta Patorno Deborah J. Wexler and colleagues in BMJ, we found no increased risk of pulmonary aspiration during upper gastrointestinal endoscopy among adults with type 2 diabetes using GLP-1 RA. However, GLP-1 RA use was associated with a higher risk of discontinuation of endoscopy. These findings provide important insights for clinical decision-making and patient safety during routine diagnostic procedures. 📝 You can read the full article here:  Glucagon-like peptide-1 receptor agonists before upper gastrointestinal endoscopy and risk of pulmonary aspiration or discontinuation of procedure: cohort study

📃Scientific paper: Effect of total parathyroidectomy in patients with secondary hyperparathyroidism: a retrospective study Abstract: Purpose To investigate the therapeutic efficacy, feasibility, and safety of total parathyroidectomy (tPTX) in the treatment of secondary hyperparathyroidism (SHPT). Methods The clinical data of 34 SHPT patients admitted to the Department of Nephrology, Yuxi People’s Hospital, from January 2018 to January 2021 who had received tPTX, were retrospectively analyzed. The indications for tPTX were severe SHPT that did not respond to medical treatment and was ineligible for kidney transplantation. tPTX without autotransplantation was adopted to compare the level of symptom relief and changes in serum intact parathyroid hormone (iPTH), blood calcium, and blood phosphorus pre- and postoperatively. Results In 34 patients, 142 parathyroid glands were removed, including 21 ectopic parathyroid glands (14.78%). Six patients (17.64%, 6/34) had supernumerary parathyroid glands. At 6 h postoperatively, arthralgia and bone pain were significantly reduced to almost zero in 94.12% (32/34) of patients. At 24 h postoperatively, relief of bone pain and improvement of limb movement were observed in 100% (34/34) of patients, and pruritus almost disappeared in 86.36% (19/22) of patients. There were significant differences in iPTH ( χ 2 = 134.93, P  < 0.05), calcium ( χ 2 = 23.02, P  < 0.05), and phosphorus ( χ 2 = 102.11, P  < 0.05) levels preoperatively and 40 min, 24 h, 1 week, half a year, and last available (> 1 year) postoperatively. The patients were followed up for 15–47 months (medi... Continued on ES/IODE ➡️ https://etcse.fr/N2X1V ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Published today in Frontiers in Cardiovascular Medicine, our original research « Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial »! Co-written with Sophie Degrauwe, Federico Carbone, Yazan Musayeb, Nathalie Lauriers, Valgimigli Marco, and especially many thanks to my mentor Juan F. Iglesias who guided, supported and taught me a lot in the writing of this original research. Cardiology Geneva University Hospitals HUG - Hôpitaux Universitaires de Genève Our study delves into the interaction between opioids and P2Y12 inhibitors in acute coronary syndrome. 🔍 Aim: We aimed to uncover how varying doses of fentanyl and morphine influence the effectiveness of ticagrelor in patient with STEMI undergoing primary PCI. 💡 Main result : Our findings reveal a significant dose-dependent relationship between fentanyl administration and ticagrelor-induced platelet inhibition. Surprisingly, this correlation did not extend to morphine. 🎯Relevance: Prior literature has not reported these specific differences between fentanyl and morphine doses on the pharmacodynamics and pharmacokinetics of ticagrelor in patients with STEMI. 🚀 Next direction : how this interaction on opioids and P2Y12 inhibitors can be translated into improved patient outcomes in STEMI management needs further research. We believe that judicious use of fentanyl instead of morphine may potentially enhance the efficacy of ticagrelor, marking a significant step forward in acute coronary syndrome care. #STEMI #ticagrelor #fentanyl #platelets #FrontiersInCardiovascularMedicine

What happens to inflammatory mediators in the blood when treated with dupilumab? An exploratory study examined plasma samples from three patients with moderate to severe prurigo nodularis before and after at least six months of dupilumab treatment. All patients showed clinically significant improvements following treatment. The downregulated proteins included cytokines associated with T helper (Th) 1 (IFN-γ, TNF-α), Th2 (IL-4, IL-13), and Th17/Th22 (IL-6, IL-22) signaling. Additionally, markers of innate immunity (IL-19, Toll-like receptor 1, nitric oxide synthase 2), immune cell migration (CCL20, CD177), and fibrosis (IL-11, IL-22) were reduced. Plasma cytokine levels of IL-11, nitric oxide synthase 2, IL-13, IL-4, and IFN-γ showed the strongest correlations with the severity of pruritus. This reduction in systemic inflammatory proteins may be related to immune and fibrosis pathways. #prurigonodularis #prurigo #raredermatology

🌟Introducing Edulis Therapeutics: Revolutionizing Gastrointestinal Medicine🌟 Join me on an exciting journey as we explore groundbreaking innovations in healthcare. Edulis Therapeutics is developing an endoscopic drug delivery system to further their mission of transforming care for millions of patients worldwide in the field of gastrointestinal medicine. Let's dive into how Edulis is reshaping the landscape of healthcare with precision, innovation, and a commitment to improving lives. Their roadmap showcases a promising future, with ongoing developments in therapeutic devices and programs targeting various disease areas, including Crohn's Disease and Inflammatory Bowel Disease. While some projects are still in the preclinical phase, Edulis is dedicated to advancing these innovations to bring meaningful solutions to patients in need. Let's delve into the future of gastrointestinal medicine together! Company Name: Edulis Therapeutics Innovative Solutions: Edulis Therapeutics introduces a groundbreaking endoscopic drug delivery system for gastrointestinal disorders. Problem: Traditional drug administration methods often lack precision, leading to systemic side effects and high costs for gastrointestinal patients. Solutions: Edulis' solution: a thin, bioresorbable implant delivers medication directly to the affected gastrointestinal areas, ensuring optimal outcomes with minimal side effects. Target Audience: Over 1 million patients globally, alongside healthcare specialists in gastroenterology, endoscopy, and gastrointestinal surgery. Innovative Aspects: Precise Drug Delivery: Thin design and bioresorbable polymer ensure accurate medication delivery. Long-term Management: Edulis implants offer sustained therapeutic management for up to 12 months, reducing interventions. Reduced Complications and Costs: Minimizing side effects, Edulis lowers healthcare costs for gastrointestinal disorders. Doctor-Friendly Innovation: User-friendly design ensures accessibility for GI clinicians. Impact: Edulis' system aims to improve the lives of millions suffering from gastrointestinal disorders by advancing solutions that are currently in the trial stage, promising transformative benefits. Related Facts: Globally, millions suffer from inflammatory bowel diseases. Edulis addresses these challenges with precise drug delivery and long-term management solutions. Website: https://www.edulis.xyz/ #HealthcareInnovation #GastrointestinalMedicine #EdulisTherapeutics