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Thrane Celik posted an update 6 months ago
AV-45 (florbetapir f18, Amyvid) is an FDA-approved PET imaging agent targeting Aβ plaques in the brain for diagnosis of Alzheimer’s disease (AD). Its metabolites led to a high background in the brain and large bone uptake of F-, produced from dealkylation of the PEG chain. To slow down the in vivo metabolism, we report the design, synthesis, and evaluation of a highly deuterated derivative, D15FSP, and compared it with N-methyl-deuterated D3FSP and nondeuterated AV-45. D15FSP displayed excellent binding affinity (K i = 7.52 nM) to Aβ aggregates. In vitro autoradiography of D15FSP, D3FSP, and AV-45 showed excellent binding to Aβ plaques in human AD brain sections. Biodistribution studies displayed lower bone uptake at 120 min for D15FSP compared to that for D3FSP and AV-45 (1.44 vs 4.23 and 4.03%ID/g, respectively). As the highly deuterated D15FSP displayed excellent Aβ binding affinity, high initial brain penetration, and lower bone retention, it might be suitable for PET imaging in detecting Aβ plaques.Synthetic endoperoxide antimalarials, such as 1,2,4-trioxolanes and 1,2,4,5-tetraoxanes, are promising successors for current front-line antimalarials, semisynthetic artemisinin derivatives. However, limited solubility of second-generation analogues in biological-relevant media represents a barrier in clinical development. We present methodology for the synthesis of nonlinear analogues of second-generation tetraoxane antimalarials E209 and N205 to investigate reduced molecular symmetry on in vitro antimalarial activity and physicochemical properties. While maintaining good antimalarial activity and metabolic stability, head-to-head comparison of linear and nonlinear counterparts showed up to 10-fold improvement in FaSSIF solubility for three of the four analogues studied. Pharmacokinetic studies in rats comparing a selected nonlinear analogue 14a and its parent N205 showed improvement on oral absorption and exposure in vivo with more than double the AUC and a significant increase in oral bioavailability (76% versus 41%). These findings provide support for further in vivo efficacy studies in preclinical animal species.Lead optimization in structure-based drug design ultimately requires that the therapeutic agent be evaluated in the cellular context. However, the in vivo control of the target structure remains unyielding to computational modeling. This situation may change as transformer technologies enable a deconstruction of in vivo cooperativity steering drug-induced protein folding.We present the case of a 79-year-old male, who was initially treated for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the right eyelid, and later for disease relapse in the stomach. During follow up, he was noted to have developed left arm nodules just medial to the proximal biceps muscle, which were found to be multiply enlarged lymph nodes on subsequent ultrasound imaging. Excisional biopsy of these nodes revealed MALT lymphoma. He was initially referred for consideration of radiation, but a restaging F-18 fluorodeoxyglucose positron emission tomography integrated with computed tomography (F-18 FDG PET/CT) further identified a focus of suspicious uptake in left calf, which was later also biopsy proven to be MALT lymphoma. His disease was upstaged as the result of this later finding, and the overall recommendation for treatment changed to favor systemic treatment with Rituximab.Schwannomas of the prostate are a rare entity and usually diagnosed incidentally following surgical management of presumed benign prostate hyperplasia or prostate adenocarcinoma. We present a case of sporadic periprostatic schwannoma diagnosed in conjunction with multifocal prostate adenocarcinoma on pre-operative multiparametric magnetic resonance imaging.Mass lesions presenting at the craniocervical junction often present a unique challenge due to the complex anatomic arrangement limiting access for tissue diagnosis. The transoral approach has predominantly been used for percutaneous vertebroplasty of high cervical vertebrae with limited literature describing image guided biopsy for bony lesions in this region in the pediatric patient. We describe a technique of computed tomography guided transoral biopsy of a poorly differentiated chordoma located at the C1-C2 level in a 5-year-old child, and review this diagnosis.
Much of the literature about the costs of metastatic pancreatic cancer is focused on the Medicare population, but the cost in the commercially insured population is not well-documented. Differences in treatment patterns between commercially insured and Medicare patients with metastatic pancreatic cancer can provide insights into healthcare utilization and the total cost of care.
To compare the total cost of care for commercially insured versus Medicare patients with metastatic pancreatic cancer who are receiving National Comprehensive Cancer Network (NCCN)-recommended treatment regimens.
We identified 3904 patients (mean age at diagnosis, 56 years) with metastatic pancreatic cancer using
diagnosis codes in claims data in the 2014-2018 MarketScan commercial database and 28,063 patients (mean age at diagnosis, 73 years) with metastatic pancreatic cancer in the 2014-2017 Medicare Parts A, B, and D 100% research identifiable data files. We calculated the total cost of care and resource utilization by NCCbut the components of the total cost varied. These results can inform clinical guidelines and pathways for pancreatic cancer therapy as new evidence and treatment options emerge, and in the context of increasing value-based care models.
Statin Therapy for Patients with Cardiovascular Disease (SPC) is a Centers for Medicare & Medicaid Services Star measure added to Medicare Part C (Medicare Advantage) plans in 2019 to incentivize statin use for secondary prevention of cardiovascular disease (CVD). The measure assesses statin dispensing and adherence in patients with atherosclerotic CVD (ASCVD). Clinical pharmacists are well-positioned to affect positively a health system’s performance on the SPC measure.
To assess the effect of telephone outreach by clinical pharmacists on moderate- or high-intensity statin prescribing in patients with ASCVD.
Patients in managed care health plans who meet the SPC measure criteria and are not currently receiving a moderate- to high-intensity statin therapy were contacted by a clinical pharmacist through telephone outreach. selleck kinase inhibitor If appropriate, they were prescribed a statin by a clinical pharmacist. The primary outcome measure was the proportion of patients who meet the SPC measure classification and had 1 confirmed prescription fill for a moderate- or high-intensity statin after intervention by a clinical pharmacist.
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