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Salvianolic acid A (Sal A), a water-soluble ingredient in Danshen, has various biological activities. Sal A and its impurities have similar physical and chemical properties, as well as strong reducibility; therefore, they are difficult to prepare and purify. In this study, high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography. Furthermore, HPLC-DAD tandem ECD and HPLC-DAD tandem MS methods were used for non-volatile organic impurity analysis, ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product. The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry, and their contents were quantified as well. Following the principles of ISO Guides 342009 and 352005, a Sal A reference material was certified, covering homogeneity studies, stability studies, characterization, and uncertainty estimations.Cemiplimab (Libtayo®) is an antibody immunotherapy that stimulates an anti-cancer response via programmed cell death protein-1 (PD-1) blockade. It is the first approved treatment in the USA and EU for patients with locally advanced (laCSCC) or metastatic (mCSCC) cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiotherapy. Approval was based largely on positive results from the phase II EMPOWER-CSCC 1 trial in this patient population. In this pivotal trial, treatment with intravenous cemiplimab 3 mg/kg once every 2 weeks or 350 mg once every 3 weeks resulted in a clinically significant objective response rate across laCSCC and mCSCC patient groups. Furthermore, responses appear to be durable, as the median duration of response has not yet been reached. Similarly, the median overall survival has also not yet been reached as of the latest data cut-off date. The safety and tolerability profile of cemiplimab was acceptable, with most immune-related adverse events being clinically manageable with appropriate therapy or discontinuation of cemiplimab. Overall, cemiplimab has a durable, clinically significant effect and an acceptable tolerability and safety profile. As the first approved treatment for this indication, cemiplimab represents a welcome therapeutic advance for patients with advanced CSCC.Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomicat of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.Edge restenosis has still been reported after second-generation drug-eluting stent (DES) implantation. It was more likely attributable to post-procedural angiographic results than to the patient's background. The aim of this study was to develop and internally validate a prediction model for restenosis in proximal edge after 2nd-generation DES stent implantation using angiographic data. Data were obtained from several post-marketing surveillance (PMS) studies of the cobalt-chromium everolimus-eluting stent (CoCr-EES) and platinum-chromium everolimus-eluting stent (PtCr-EES), second-generation DES, in Japan. Angiographic analysis was conducted at baseline and after 8 or 12 months. We focused on the proximal edge of angiographic analysis. The main outcome was restenosis defined as ≥ 50% diameter stenosis at follow-up. The predictive performance of the prediction model based on multivariable logistic regression was assessed in terms of discrimination and calibration, which were internally validated by the bootstrap method. We also performed decision curve analysis to assess threshold of predicted probability of restenosis at which additional intervention was considered. Among 2053 lesions in 1860 patients, restenosis rates in proximal edge was 2.8%. The final model was constructed with % post-procedural diameter stenosis (DS) and post-procedural reference diameter (RD) as strong predictors for edge restenosis. Discrimination and calibration were satisfactory with optimism-corrected C-statistics 0.75. Predicted probability between 0.03 and 0.24 was preferable threshold for restenosis treatments. Our prediction model can be used to obtain valid prediction for restenosis in proximal edge, assisting to know complete stent coverage of lesion.This study evaluated the level of metals in edible plants, their chemical forms in the soil, and the associated health risk in Enyigba lead-zinc mining vicinity in Ebonyi State, Nigeria. Soil sample, Telfairia occidentalis and Amaranthus hybridus were collected from mining sites (Ishiagu-Enyigba and Elinwobvu-Enyigba) and non-mining site (Ekawoke-control) and analyzed using standard protocols. The results showed that a high percentage of Cd, Pb, Fe, and Zn were associated with non-residual fraction, while Cu, Cr, and Ni were bounded with residual fraction. The order of mobility and bioavailability of the metals was as follows Pb > Cd > Fe > Zn > Cr > Ni > Cu. Geoaccumulation index (Igeo) indicated moderate to strong pollution of the mining sites with Cd Cu, Pb, and Zn. The most significant contributor to hazard index (HI) was ingestion of edible plants; followed by ingestion, dermal-contact, and then inhalation of soil particles. HI values for Cd (1.32), Cr (1.05), and Pb (1.97-2.04) for children in the sites exceeded United States Environmental Protection Agency (USEPA) safe limit (HI > 1). Total cancer risk (TCR) for adults and children via soil inhalation or soil ingestion were below USEPA safe limit (TCR 1.0 × 10-4). These results strongly indicated associated noncarcinogenic and carcinogenic health risk of these metals from the soil and the edible plants around Enyigba mining sites vicinity to humans especially children, this calls for concern.Introduction Oral formulations of docetaxel have successfully been developed as an alternative for intravenous administration. Co-administration with the enzyme inhibitor ritonavir boosts the docetaxel plasma exposure. In dose-escalation trials, the maximum tolerated doses for two different dosing regimens were established and dose-limiting toxicities (DLTs) were recorded. The aim of current analysis was to develop a pharmacokinetic (PK)-toxicodynamic (TOX) model to quantify the relationship between docetaxel plasma exposure and DLTs. Methods A total of 85 patients was included in the current analysis, 18 patients showed a DLT in the four-week observation period. A PK-TOX model was developed and simulations based on the PK-TOX model were performed. Results The final PK-TOX model was characterized by an effect compartment representing the toxic effect of docetaxel, which was linked to the probability of developing a DLT. Simulations of once-weekly, once-daily 60 mg and once-weekly, twice-daily 30 mg followed by 20 mg of oral docetaxel suggested that 14% and 34% of patients, respectively, would have a probability >25% to develop a DLT in a four-week period. Conclusions A PK-TOX model was successfully developed. This model can be used to evaluate the probability of developing a DLT following treatment with oral docetaxel and ritonavir in different dosing regimens.OBJECTIVES We aimed to assess the ability of radiomics, applied to not-enhanced computed tomography (CT), to differentiate mediastinal masses as thymic neoplasms vs lymphomas. METHODS The present study was an observational retrospective trial. Inclusion criteria were pathology-proven thymic neoplasia or lymphoma with mediastinal localization, availability of CT. Exclusion criteria were age less then 16 years and mediastinal lymphoma lesion less then 4 cm. We selected 108 patients (MF = 4761, median age 48 years, range 17-79) and divided them into a training and a validation group. Radiomic features were used as predictors in linear discriminant analysis. We built different radiomic models considering segmentation software and resampling setting. Clinical variables were used as predictors to build a clinical model. Scoring metrics included sensitivity, specificity, accuracy and area under the curve (AUC). Wilcoxon paired test was used to compare the AUCs. RESULTS Fifty-five patients were affected by thymic neoplasia and 53 by lymphoma. read more In the validation analysis, the best radiomics model sensitivity, specificity, accuracy and AUC resulted 76.2 ± 7.0, 77.8 ± 5.5, 76.9 ± 6.0 and 0.84 ± 0.06, respectively. In the validation analysis of the clinical model, the same metrics resulted 95.2 ± 7.0, 88.9 ± 8.9, 92.3 ± 8.5 and 0.98 ± 0.07, respectively. The AUCs of the best radiomic and the clinical model not differed. CONCLUSIONS We developed and validated a CT-based radiomic model able to differentiate mediastinal masses on non-contrast-enhanced images, as thymic neoplasms or lymphoma. The proposed method was not affected by image postprocessing. Therefore, the present image-derived method has the potential to noninvasively support diagnosis in patients with prevascular mediastinal masses with major impact on management of asymptomatic cases.PURPOSE This manuscript reports on a preliminary experience concerning emborrhoid in patients affected by cirrhotic portal hypertension; furthermore, a novel customized technique of coils release, named "Spaghetti technique," is described. MATERIALS AND METHODS Five patients with chronic anemia due to internal hemorrhoidal bleeding and cirrhotic portal hypertension were treated. Clinics and hemoglobin values were evaluated to objectively assess clinical conditions up to 3 months follow-up. Embolizations were performed with fibered coils, oversized, released stretched and not packed. RESULTS Technical success, intended as occlusion of all superior hemorrhoidal artery branches, was 100%. In two patients, inferior hemorrhoidal arteries were embolized too. No patients reported major or minor complications. At 3-month follow-up, clinical improvement was obtained in four of the five patients; hemoglobin values improved or remained stable in the whole sample. CONCLUSIONS Based on this limited experience, emborrhoid seems to be safe and effective at 3-month follow-up to improve symptoms in patients with cirrhotic portal hypertension and chronic anemia due to hemorroidal bleeding; the stretched fashion to release oversized coils provides effective embolization.
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