Society for the Advancement of Transplant Anesthesia 的动态

Phosphodiesterase 5 inhibitor suppresses prostate weight increase in type 2 diabetic rats Hisato Kobayashi?1,?Xinmin Zha?2,?Keiko Nagase?2,?So Inamura?2,?Minekatsu Taga?2,?Yoshitaka Aoki?2,?Hideaki Ito?2,?Osamu Yokoyama?2 Affiliations?Expand PMID:?35367242?DOI:?10.1016/j.lfs.2022.120504 Free article Abstract Aims:?Hyperinsulinemia is an important causative factor of prostate enlargement in type 2 diabetes (T2D), however, clinically prostate weight increases during hypoinsulinemic condition. To investigate the pathogenesis of prostate enlargement and effects of phosphodiesterase 5 inhibitor (PDE5i), male Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as T2D and control, respectively. Materials and methods:?OLETF and LETO rats were treated with oral tadalafil (100 μg/kg/day) or vehicle for 12 wks from at the age of 36 wks. Key findings:?Prostate weight of OLETF rats was significantly higher than that of LETO at 36 wks, and increased at 48 wks. In OLETF rats, prostate blood flow was significantly lower at 48 wks versus 36 wks. Twelve-week-tadalafil treatment increased prostate blood flow and suppressed prostate weight increase in both strains. This change was inversely correlated with changes in prostate expressions of hypoxia-inducible factor-1 alpha (HIF-1α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Increases with age were observed in mRNA and/or protein levels of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-α) and cell growth factors insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-β); especially IL-6, TNF-α, IGF-1, bFGF and TGF-β increased with T2D. Tadalafil suppressed these cytokines and growth factors. Significance: These data suggest chronic ischemia caused by T2D leads to oxidative stress, resulting in prostate enlargement through upregulation of several cytokines and growth factors. Treatment with PDE5i improves prostate ischemia and might prevent enlargement via suppression of cytokines and growth factors in T2D.

Cirrhosis crash course video # 25 3 MUST KNOW KEY POINTS 1. ???????? ???? ?????? ???????????????????? ?????????????????? ?????? ???????????????? ???????? ??????-?????????? ?????????? ?????????????? ???? ?????????????????????????? ??????????????????? --> Liver transplantation 2. ?????????? ?????????????????????? ???????????? ???? ?????????????? ???? ???????????????? ???????? ?????????????????? ?????? ??????????????? (a) ACE inhibitors (b) Angiotensin receptor blockers (c) Non steroidal anti inflammatory drugs 2a. ?????? ???????????? ?????????? ?????????????????????? ???? ??????????????? --> Because they worsen the kidney function 3. ???????? ???? ?????? ?????????????????????? ?????????????????? ???? ???????????????? ???????? ??????????????????? --> 7 g/dL 3a. ?????? ???????????? ?????????? ???????????????? ?????? ?????? ???????????????????? ??????????????????????????? --> Because it increases the total pressure, which can lead to variceal bleeding. Please like, follow, and share this content Wanna help me the most -> please ???????????? Wanna see all my future posts? Hit the ???????? icon next to my profile Wanna see all my videos ?????????????????? here --> https://lnkd.in/gGg7KuBt

?? New Horizons in ATTR-Cardiomyopathy Treatment: A Re-Cap In light of Alnylam's recent sNDA submission for vutrisiran to treat ATTR with Cardiomyopathy (ATTR-CM), let’s recap the current landscape. Exciting progress in ATTR-CM brings fresh hope to patients. From stabilizing the TTR protein to innovative gene-silencing techniques and amyloid fibril disruption, various approaches are emerging. ?? Here’s where things stand: – Tafamidis (Vyndaqel/Vyndamax) has been the primary therapy since 2019, costing around $225,000 annually. – Acoramidis (AG10) is under FDA review with a decision expected by November 2024. If approved, it may provide a more affordable alternative to Tafamidis. (Gene-silencing therapies are making waves) – Vutrisiran recently submitted a supplemental NDA in October 2024, with longer dosing intervals expected to be advantageous. – Eplontersen (an antisense oligonucleotide) is in Phase III, with completion slated for mid-2025. – NTLA-2001, a CRISPR-based therapy, could shift treatment paradigms if its Phase III trial, set for 2027, proves successful. (Antibody-based fibril disruption might gain traction) – ALXN2220, an anti-TTR monoclonal antibody, is currently in Phase III and due to MOA may even complement existing treatments. – Some examples of other assets in earlier stages of development can be seen in the info/picture below... ?? Thoughts - Competition is Heating Up: Companies like BridgeBio, Alnylam, and Ionis are vying for the larger market share (vs incumbent Pfizer), given their advanced stages in development and the appetite for higher commercial potential of ATTR-CM vs ATTR-PN (≈10x bigger patient population). Surely, market access, pricing strategies, and payer negotiations will shape the landscape. However, the landscape is still evolving, with new players emerging that utilize similar or different technologies (e.g., mAbs, peptides), and an eye on the prize. ?? A side note on ATTRv involvement in CNS and ocular pathologies: Certain TTR mutations in hereditary ATTR (ATTRv), such as D18G and A25T, can lead to CNS amyloid deposition and leptomeningeal amyloidosis. The prevalence of CNS involvement in ATTRv is estimated to be low, affecting less than 10% of patients, but presents significant clinical challenges. Similarly, ocular manifestations like vitreous opacities and corneal deposits can occur and lead to visual disturbances. Current treatments primarily target liver TTR, which represents ≈90% of TTR, while CNS TTR is produced in the choroid plexus. In the brain, TTR helps transport thyroxine (T4) and may play a neuroprotective role, so strategies aimed at depleting TTR should consider its CNS functions. An interesting paper (https://lnkd.in/dwsB7nBA) discusses how longer lifespans from current ATTR treatments might make CNS and ocular manifestations more relevant over time, even if the underlying TTR mutation isn’t primarily associated with them. #biotech #ATTRCM #drugdevelopment #innovation #pharma

Changing treatment paradigms for membranous nephropathies Nephrology Dialysis Transplantation, Volume 39, Issue 12, December 2024, Pages 1938–1941, https://lnkd.in/ewBJmbgt Published: 19 June 2024 Membranous nephropathy (MN) is the most common cause of nephrotic syndrome (NS) in the non-diabetic adult population. The immunopathogenesis of MN is mostly related to the presence of anti-phospholipase A2 receptor (PLA2R) antibodies (Ab), however recent investigations have unveiled several new target antigens. The pathogenesis of MN primarily involves the formation and deposition of immune complexes, consisting of immunoglobulins and complement, leading to podocyte injury and disruption of the glomerular basement membrane leading to proteinuria, often progressing to NS and, if persistent, to kidney failure The search for novel and specific therapies in MN management remains imperative

This week the #FDA approved #Crexont, an extended-release formulation of levodopa/carbidopa from Amneal Pharmaceuticals to treat the tremors and dyskinesia associated with #Parkinson’s disease. Patients taking Crexont in the clinical trial has more Good On Time, meaning more time that they were not suffering from the incredibly disruptive movement symptoms of their disease. I have mixed feelings about symptomatic treatments like this. On one hand, having watched my mom fight with — and eventually succumb to — Parkinson’s disease, I deeply understand the value of having more time to read a book, or go for a walk, or play with the grandchildren. On the other hand, patients who respond to dopamine therapy are often still coherent enough to know that this is borrowed time, that their disease is still silently killing the cells in their brain, that someday there won’t be enough cells left to respond to the dopamine. And the years and dollars that went toward developing this incremental improvement on a 50-year-old therapeutic could have instead been invested in the search for a treatment that would actually slow or stop the progression of the disease. But if my mom were alive and could benefit from this drug, would she be glad that it is available? Absolutely. And so am I. #clinicaltrials #neuroscience #drugdiscovery #drugdevelopment

Pancreatic Adenocarcinoma: Long-Term Outcomes of Adjuvant Therapy in the ESPAC4 Phase III Trial

??Scientific paper: Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews Abstract: Aim The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC). Methods Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs). Results Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled... Continued on ES/IODE ?? https://etcse.fr/qsX ------- 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.

??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.

Tailored dose-dense adjuvant #chemotherapy improved recurrence-free survival, event-free survival, and distant disease-free survival at 10 years. https://brnw.ch/21wLsgH

?? RA Patients Embrace Bone Marrow Transplants Despite High Risks ?? In a groundbreaking study, patients battling severe rheumatoid arthritis (RA) are showing remarkable willingness to undergo allogeneic bone marrow transplantation (BMT), even in the face of significant risks, including mortality. This reflects a desperate search for effective treatments among those who have exhausted multiple therapies. ?? Key Insights: - A recent discrete choice experiment revealed that RA patients prioritize treatment efficacy over potential risks when considering BMT. - A striking 72% to 91% of participants expressed interest in transplantation if it meant halting disease progression. - Patients are prepared to tolerate increased mortality risks for better outcomes, highlighting their determination. This study underscores the potential for recruiting participants for BMT clinical trials and emphasizes the importance of aligning treatment options with patient values and risk tolerances. ?? Click on the link to learn more about this pivotal research and its implications! #BoneMarrowTransplant #ClinicalResearches #ClinicalTrials #HealthcareInnovation #PatientCare #RheumatoidArthritis #MarketAccess #MarketAccessToday