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1.
Front Pharmacol ; 15: 1364948, 2024.
Article in English | MEDLINE | ID: mdl-38694910

ABSTRACT

Morus alba L., a common traditional Chinese medicine (TCM) with a centuries-old medicinal history, owned various medicinal parts like Mori folium, Mori ramulus, Mori cortex and Mori fructus. Different medical parts exhibit distinct modern pharmacological effects. Mori folium exhibited analgesic, anti-inflammatory, hypoglycemic action and lipid-regulation effects. Mori ramulus owned anti-bacterial, anti-asthmatic and diuretic activities. Mori cortex showed counteraction action of pain, inflammatory, bacterial, and platelet aggregation. Mori fructus could decompose fat, lower blood lipids and prevent vascular sclerosis. The main chemical components in Morus alba L. covered flavonoids, phenolic compounds, alkaloids, and amino acids. This article comprehensively analyzed the recent literature related to chemical components and pharmacological actions of M. alba L., summarizing 198 of ingredients and described the modern activities of different extracts and the bioactive constituents in the four parts from M. alba L. These results fully demonstrated the medicinal value of M. alba L., provided valuable references for further comprehensive development, and layed the foundation for the utilization of M. alba L.

4.
Proc Natl Acad Sci U S A ; 121(12): e2310002121, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38470929

ABSTRACT

We develop information-geometric techniques to analyze the trajectories of the predictions of deep networks during training. By examining the underlying high-dimensional probabilistic models, we reveal that the training process explores an effectively low-dimensional manifold. Networks with a wide range of architectures, sizes, trained using different optimization methods, regularization techniques, data augmentation techniques, and weight initializations lie on the same manifold in the prediction space. We study the details of this manifold to find that networks with different architectures follow distinguishable trajectories, but other factors have a minimal influence; larger networks train along a similar manifold as that of smaller networks, just faster; and networks initialized at very different parts of the prediction space converge to the solution along a similar manifold.

5.
JACC Cardiovasc Interv ; 17(5): 622-631, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38479964

ABSTRACT

BACKGROUND: National quality reporting efforts after revascularization for peripheral artery disease (PAD) are ongoing. Validation of endpoints are necessary in national quality registries. OBJECTIVES: This study sought to examine the interrater reliability for the endpoint of major amputation at 1 year in the Vascular Quality Initiative (VQI) registry and the Medicare-linked Vascular Quality Initiative registry (VQI-VISION) against electronic health record (EHR) review. METHODS: Surgical or endovascular revascularization procedures between January 1, 2010, and December 31, 2017, in the VQI registry and VQI-VISION for 2 academic health systems were queried. Major amputation data were abstracted by trained data collectors for the VQI and derived from Current Procedural Terminology codes for VQI-VISION. Cases underwent protocolized adjudication for the endpoint of major amputation by EHR review. Paired tests were used to evaluate the sensitivity and specificity. Spearman's ρ and Cohen's κ were used to evaluate interrater reliability. RESULTS: Amputation endpoints for 1,936 revascularizations were examined. Compared with major amputation data in EHR review, the sensitivity for the VQI registry was 35.9% and the specificity was 99.4% (ρ = 0.53; κ = 0.48). For VQI-VISION, sensitivity was 67.7% and specificity was 98.9% (ρ = 0.75; κ = 0.74). For any amputation in VQI data, sensitivity was 35.3% and specificity was 99.3% (ρ = 0.53; κ = 0.46), and for VQI-VISION, they were 71.6% and 97.7%, respectively (ρ = 0.75; κ = 0.74). CONCLUSIONS: Almost two-thirds of the amputations in the VQI registry and one-third of amputations in VQI-VISION were missing at 1 year compared against adjudicated EHR review. In preparing for national reporting systems for major amputation tracking, data collection system reform is needed.


Subject(s)
Endovascular Procedures , Peripheral Arterial Disease , Aged , Humans , United States , Treatment Outcome , Reproducibility of Results , Risk Factors , Postoperative Complications/surgery , Medicare , Vascular Surgical Procedures/adverse effects , Endovascular Procedures/adverse effects , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/surgery , Amputation, Surgical , Retrospective Studies
6.
J Vasc Surg ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38462063

ABSTRACT

OBJECTIVE: Peripheral artery disease (PAD) represents a high volume, high-cost burden on the healthcare system. The Centers for Medicare and Medicaid Services (CMS) has developed the Bundled Payments for Care Improvement-Advanced program, in which a single payment is provided for all services administered in a postsurgical 90-day episode of care. Factors associated with 30- and 90-day reinterventions after PAD interventions would represent useful data for both payors and stake holders. METHODS: We conducted a national cohort study of adults 65 years and older in the Vascular Quality Initiative and CMS linked dataset who underwent an open, endovascular, or hybrid revascularization procedure for PAD between January 1, 2010 to December 31, 2018. Procedures for acute limb ischemia and aneurysms were excluded. The primary outcome was 90-day reintervention. Reintervention at 30-days was a secondary outcome. Covariates of interest included demographic, comorbidities, and patient- and facility-level characteristics. Multivariable Cox regression was used to determine the association between patient- and facility-level characteristics and the risk of 30- and 90-day reinterventions. RESULTS: Among 42,429 patients (71.3% endovascular, 23.3% open, and 5.4% hybrid), median [IQR] age was 74 [69-80], 57.9% were male, and 84.3% were White. Chronic limb threatening ischemia (CLTI) was the operative indication in 40.4% of the procedures. Overall, 42.8% were completed in the outpatient setting (40.3% outpatient, 2.5% office-based lab). Over 70% of procedures for CLTI were completed as inpatient while 60% of the claudication interventions were done as outpatient. The 90-day reintervention rate was 14.5% and the 30-day reintervention rate was 5.5%. Compared to inpatient procedures, PAD interventions completed in the outpatient or office-based lab setting had significantly higher 90- and 30--day reintervention rates (ref - inpatient; outpatient 90d reintervention [HR 1.41 (95% CI 1.25-1.60)]; outpatient 30d reintervention [HR 1.90 (95% CI 1.62-2.24)]; office-based lab 90d reintervention [HR 2.09 (95% CI 1.82-2.41)]; office-based lab 30d reintervention [HR 3.54 (95% CI 3.17-3.94)]). Open and hybrid approaches demonstrated lower risk of reintervention compared to endovascular procedures at 30 and 90 days and, compared to aortoiliac disease, all other anatomic segments of disease were associated with higher 90-day reintervention but no difference was noted at 30 days. CONCLUSIONS: While outpatient PAD interventions may be convenient for patients and providers, the outpatient setting is associated with a significant risk of subsequent reintervention. Additional work is needed to understand how to improve the longevity of outpatient PAD interventions.

7.
Molecules ; 29(4)2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38398644

ABSTRACT

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.


Subject(s)
Plant Extracts , Zea mays , Blood Pressure , Medicine, Chinese Traditional , Phytochemicals/pharmacology , Plant Extracts/pharmacology
9.
J Vasc Surg ; 79(4): 875-886.e8, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38070783

ABSTRACT

OBJECTIVE: Analysis of regional data from the Vascular Quality Initiative (VQI) suggested improved survival for patients undergoing stent placement compared with balloon angioplasty and atherectomy. Using national data from the VQI linked to Medicare claims data through the Vascular Implant Surveillance and Interventional Outcomes Network program, this study aimed to compare the rates of mortality, reintervention, and amputation after endovascular interventions (atherectomy, stenting, and balloon angioplasty) for two separate cohorts: patients with chronic limb-threatening ischemia (CLTI) and patients with claudication. METHODS: This was a secondary data analysis of Society for Vascular Surgery National VQI data linked to Medicare claims, between October 2016 and December 2019. Patients aged ≥65 years with symptoms of claudication or CLTI and a diagnosis of occlusive disease were included. Urgent or emergent interventions or those with concurrent procedures (endarterectomy, bypass, or bilateral intervention) were excluded. Interventions were grouped into (1) balloon angioplasty only; (2) stent (with or without balloon angioplasty); or (3) atherectomy (alone, with or without stent, with or without balloon angioplasty). Propensity score-matched cohorts were constructed to conduct pairwise intervention comparisons of mortality, reintervention, and amputation rates. Multivariable logistic regression was used to derive propensity scores for each patient. Kaplan-Meier estimates and Cox proportional hazards ratios (HRs) (95% confidence interval [CI]) analyses were performed. RESULTS: A total of 9785 (2665 claudication, 7120 CLTI) eligible patients were identified. After propensity score matching for the CLTI group, 2826, 3608, and 2796 pairs of cases were used to compare balloon angioplasty vs atherectomy, balloon angioplasty vs stent, and stent vs atherectomy, respectively. No statistically significant difference in mortality was observed among all interventions. However, atherectomy was associated with a significant increase in reintervention rate compared with balloon angioplasty (HR, 1.22; 95% CI, 1.06-1.39; P = .01) and compared with stenting (HR, 1.27; 95% CI, 1.10-1.46; P < .01) within the first year after the index procedure. Of note, both atherectomy (HR, 0.82; 95% CI, 0.68-0.98; P < .05) and stenting (HR, 0.76; 95% CI, 0.64-0.90; P < .01) showed lower rates of major amputation when compared with balloon angioplasty within 1 year after the index procedure. In the claudication group, there were no significant differences observed among interventions for peripheral arterial disease for mortality, reintervention, or amputation rates. CONCLUSIONS: Further studies are needed to identify appropriate indications for atherectomy, because there may be a subset of patients with CLTI who benefit from this therapy with respect to amputation rates. Until then, caution should be exercised when using atherectomy because it is also associated with higher reintervention rates.


Subject(s)
Angioplasty, Balloon , Peripheral Arterial Disease , Humans , Aged , United States , Chronic Limb-Threatening Ischemia , Medicare , Risk Factors , Ischemia/diagnostic imaging , Ischemia/surgery , Treatment Outcome , Intermittent Claudication/diagnostic imaging , Intermittent Claudication/surgery , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/surgery , Angioplasty, Balloon/adverse effects , Retrospective Studies , Limb Salvage
10.
J Am Coll Radiol ; 21(2): 295-308, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37922972

ABSTRACT

OBJECTIVE: To identify independent predictors of all-cause and cancer-specific mortality after ablation or surgical resection (SR) for small hepatocellular carcinomas (HCCs), after adjusting for key confounders. METHODS: Using Surveillance, Epidemiology, and End Results Program-Medicare, HCCs less than 5 cm treated with ablation or SR in 2009 to 2016 (n = 956) were identified. Univariate and multivariable Cox regression models for all-cause and cancer-specific mortality were performed including demographics, clinical factors (tumor size, medical comorbidities, and liver disease factors), social determinants of health, and treatment characteristics. We also determined the most influential predictors of survival using a random forest analysis. RESULTS: Larger tumor size (3-5 cm) is predictive of all-cause (hazard ratio [HR] 1.31, P = .002) and cancer-specific mortality (HR 1.59, P < .001). Furthermore, chronic kidney disease is predictive of all-cause mortality (HR 1.43, P = .013), though it is not predictive of cancer-specific death. Multiple liver disease factors are predictive of all-cause and cancer-specific mortality including portal hypertension and esophageal varices (HRs > 1, P < .05). Though Asian race is protective in univariate models, in fully adjusted, multivariable models, Asian race is not a significant protective factor. Likewise, other social determinants of health are not significantly predictive of all-cause or cancer-specific mortality. Finally, treatment with SR, in later procedure years or at high-volume centers, is protective for all-cause and cancer-specific mortality. In machine learning models, year procedure was performed, ascites, portal hypertension, and treatment choice were the most influential factors. DISCUSSION: Treatment characteristics, liver disease factors, and tumor size are more important predictors of all-cause and cancer-specific death than social determinants of health for small HCCs.


Subject(s)
Carcinoma, Hepatocellular , Hypertension, Portal , Liver Neoplasms , Aged , Humans , United States/epidemiology , SEER Program , Retrospective Studies , Medicare , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/surgery , Treatment Outcome
11.
J Vasc Surg ; 79(4): 748-754.e2, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38013041

ABSTRACT

BACKGROUND: The mortality after ruptured abdominal aortic aneurysm (rAAA) repair is high, despite improvements in perioperative care, centralization of emergency vascular surgical services, and the introduction of endovascular aneurysm repair (EVAR). The diameter of intact AAA has been shown to be a predictor of short- and long-term survival. The aim of this study was to analyze the impact of AAA diameter on mortality for rAAA repair using contemporary data collected from the International Consortium of Vascular Registries and compare outcomes by sex and the type of repair patients received. METHODS: Prospective registry data on repair of rAAA from seven countries were collected from 2010 to 2016. The primary outcome was perioperative mortality after EVAR and open surgical repair (OSR). Data were stratified by type of repair and sex. Logistic regression models were used to estimate odds ratio (OR) for the association between AAA diameter and perioperative mortality and the association between type of repair and mortality. Multivariable logistic regression models were used to adjust for differences in patient characteristics. RESULTS: The study population consisted of 6428 patients with a mean age ranging from 70.2 to 75.4 years; the mean AAA diameter was 7.7 ± 1.8 cm. Females had a significantly smaller AAA diameter at presentation compared with males (6.9 ± 1.6 cm vs 7.9 ± 1.8 cm; P < .001). who underwent OSR had larger AAA diameters compared with those who underwent EVAR (P < .001). Females who underwent repair were significantly older (P < .001). Males were more likely to have cardiac disease, diabetes mellitus, and renal impairment. Overall, AAA diameter was a predictor of mortality in univariate and multivariate analysis. When analyzing EVAR and OSR separately, the impact of AAA diameter per cm increase on mortality was apparent in both males and females undergoing EVAR, but not OSR (EVAR: male OR, 1.09 [95% confidence interval, 1.03-1.16] and EVAR: female OR, 1.17 [95% confidence interval, 1.02-1.35]). The early mortality rate for males and females who underwent EVAR was 18.9% and 25.9% (P < .001), respectively. The corresponding mortality for males and females who underwent OSR was 30.2% and 38.6% (P < .001), respectively. CONCLUSIONS: In these real-world international data, there is a significant association between rAAA diameters and early mortality in males and females. This association was more evident in patients undergoing EVAR, but not shown in OSR. Despite improvements in overall AAA repair outcomes, the risk of mortality after rAAA repair is consistently higher for females.


Subject(s)
Aortic Aneurysm, Abdominal , Aortic Rupture , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Male , Female , Aged , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Risk Factors , Endovascular Procedures/adverse effects , Treatment Outcome , Aortic Rupture/diagnostic imaging , Aortic Rupture/surgery , Registries , Retrospective Studies , Postoperative Complications/surgery
13.
Cancer Epidemiol Biomarkers Prev ; 33(1): 20-32, 2024 01 09.
Article in English | MEDLINE | ID: mdl-37870412

ABSTRACT

Surgical innovations for cancer treatment may penetrate differentially across racial and ethnic groups and contribute to disparities in health and health care quality. We summarized the current evidence of racial and ethnic disparities in robot-assisted surgery (RAS) and minimally invasive surgery (MIS) use in four major pelvic cancer treatments. We identified studies related to racial and ethnic disparities in RAS and/or MIS use in the treatment of prostate, endometrial, bladder, and rectal cancers during 2001 to 2022 from PubMed, EMBASE, and the Cochrane database. Twenty-eight studies were selected (prostate = 7, endometrial = 14, bladder = 1, rectal = 5, multiple cancers = 1) and all were retrospective. Thirteen and 23 studies examined racial and ethnic differences in individual patients' receipt of RAS and MIS, respectively. Black patients were less likely to receive RAS/MIS than White patients in most studies. Hispanic patients were less likely to receive RAS/MIS than White patients in just over half of the studies. Studies of Asian patients were few and reported mixed results. Three studies examined disparities on the center level and found that racial and ethnic minority prostate cancer patients were less likely to be treated at RAS-performing or high-technology facilities. More work is needed to improve understanding of the mechanisms underlying racial and ethnic disparities in RAS and MIS use and their impact on disparities in health outcomes.


Subject(s)
Pelvic Neoplasms , Robotic Surgical Procedures , Male , Humans , United States , Ethnicity , Retrospective Studies , Healthcare Disparities , Minority Groups , Minimally Invasive Surgical Procedures
14.
Ann Surg Oncol ; 31(2): 1373-1383, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37880515

ABSTRACT

BACKGROUND: We sought to determine whether the differences in short-term outcomes between patients undergoing robot-assisted radical prostatectomy (RARP) and those treated with open radical prostatectomy (ORP) differ by race and ethnicity. METHODS: This observational study used New York State Cancer Registry data linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer during 2008-2018. We used logistic regression to examine the association between race and ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic), surgical approach (RARP, ORP), and postoperative outcomes (major events, prolonged length of stay [pLOS], 30-day re-admission). We tested interaction between race and ethnicity and surgical approach on multiplicative and additive scales. RESULTS: The analytical cohort included 18,926 patients (NHW 14,215 [75.1%], NHB 3195 [16.9%], Hispanic 1516 [8.0%]). The average age was 60.4 years (standard deviation 7.1). NHB and Hispanic patients had lower utilization of RARP and higher risks of postoperative adverse events than NHW patients. NHW, NHB, and Hispanic patients all had reduced risks of adverse events when undergoing RARP versus ORP. The absolute reductions in the risks of major events and pLOS following RARP versus ORP were larger among NHB {relative excess risk due to interaction (RERI): major events -0.32 [95% confidence interval (CI) -0.71 to -0.03]; pLOS -0.63 [95% CI -0.98 to -0.35]) and Hispanic (RERI major events -0.27 [95% CI -0.77 to 0.09]; pLOS -0.93 [95% CI -1.46 to -0.51]) patients than among NHW patients. The interaction was absent on the multiplicative scale. CONCLUSIONS: RARP use has not penetrated and benefited all racial and ethnic groups equally. Increasing utilization of RARP among NHB and Hispanic patients may help reduce disparities in patient outcomes after radical prostatectomy.


Subject(s)
Health Status Disparities , Prostatic Neoplasms , Robotic Surgical Procedures , Humans , Male , Middle Aged , Ethnicity , Prostatectomy/adverse effects , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/surgery , Robotic Surgical Procedures/adverse effects , Aged , Treatment Outcome
15.
J Patient Saf ; 19(7): 465-468, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37729644

ABSTRACT

BACKGROUND: Evidence suggests that more women are harmed by implantable medical devices than men. It is unknown whether this difference includes gender-specific devices. METHODS: In this study, we examine the differences in reported adverse events between 6 female- and 5 male-specific implantable devices from the Manufacturer and User Facility Device Experience (MAUDE) database from 1993 to 2018. Primary endpoints were injury type (life-threatening, disability, death) and the rate of device evaluation by the manufacturer. Proportions of valid entries across these variables were compared using either the Fisher exact test or χ2 test. RESULTS: Female-specific devices had higher rates of life-threatening outcomes (1.6% versus 0.3%, P < 0.001), disabilities (5.0% versus 4.3%, P < 0.001), and deaths (0.6% versus 0.1%, P < 0.001) compared with the male-specific devices. Of the 8159 devices that were evaluated by the manufacturer, 56% were female specific while 44% were male specific. Female-specific devices were evaluated far less frequently by the manufacturer (4.5% versus 38.2%, P < 0.001). CONCLUSIONS: Increased adverse events reports for female-specific devices and associated high-grade complications necessitates improved postmarket surveillance.


Subject(s)
Health Facilities , Prostheses and Implants , United States , Humans , Female , Male , Databases, Factual , Prostheses and Implants/adverse effects
16.
J Vasc Surg ; 78(6): 1513-1522.e1, 2023 12.
Article in English | MEDLINE | ID: mdl-37657686

ABSTRACT

OBJECTIVE: Lower extremity revascularization (LER) for peripheral artery disease is complicated by the frequent need for readmission. However, it is unclear if readmission to a nonindex LER facility (ie, a facility different from the one where the LER was performed) compared with the index LER facility is associated with worse outcomes. METHODS: This was a national cohort study of older adults who underwent open, endovascular, or hybrid LER for peripheral artery disease (January 1, 2010, to December 31, 2018) in the Vascular Quality Initiative who were readmitted within 90 days of their vascular procedure. This dataset was linked to Medicare claims and the American Hospital Association Annual Survey. The primary outcome was 90-day mortality and the secondary outcome was major amputation at 90 days after LER. The primary exposure was the location of the first readmission after LER (categorized as occurring at the index LER facility vs a nonindex LER facility). Generalized estimating equations logistic regression models were used to assess the association between readmission location and 90-day mortality and amputation. RESULTS: Among 42,429 patients who underwent LER, 33.0% were readmitted within 90 days. Of those who were readmitted, 27.3% were readmitted to a nonindex LER facility, and 42.2% of all readmissions were associated with procedure-related complications. Compared with patients readmitted to the index LER facility, those readmitted to a nonindex facility had a lower proportion of procedure-related reasons for readmission (21.5% vs 50.1%; P < .001). Most of the patients readmitted to a nonindex LER facility lived further than 31 miles from the index LER facility (39.2% vs 19.6%; P < .001) and were readmitted to a facility with a total bed size of <250 (60.1% vs 11.9%; P < .001). Readmission to a nonindex LER facility was not associated with 90-day mortality or 90-day amputation. However, readmission for a procedure-related complication was associated with major amputation (90-day amputation: adjusted odds ratio, 3.33; 95% confidence interval, 2.89-3.82). CONCLUSIONS: Readmission after LER for a procedure-related complication is associated with subsequent amputation. This finding suggests that quality improvement efforts should focus on understanding various types of procedure-related failure after LER and its role in limb salvage.


Subject(s)
Patient Readmission , Peripheral Arterial Disease , United States , Humans , Aged , Cohort Studies , Medicare , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/surgery , Limb Salvage
17.
Molecules ; 28(16)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37630367

ABSTRACT

Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao (MO) and Astragalus membranaceus (Fisch.) Bug. (ME) are two primary sources of the Astragalus herb, also known as "Huangqi" in China, which is widely applied to treat hypertension, glomerulonephritis, ischemic heart disease, and diabetes mellitus. As two different sources of the Astragalus herb, the chemical profiles of MO and ME may be different. Previous studies showed abundant differences in chemical composition between MO and ME. Therefore, the by-products of MO and ME, such as Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao flower (MOF) and Astragalus membranaceus (Fisch.) Bug. flower (MEF), may have different phytochemical profiles. In this paper, a metabolomics method combined with ultra-high-performance liquid chromatography and electrospray ionization/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze the components of MOF and MEF. Consequently, the results of principal component analysis (PCA) showed that MOF and MEF could be separated clearly. In total, 31 chemical markers differentiating MOF and MEF were successfully identified, including 22 flavonoids, 8 isoflavones and 1 benzopyran. Among them, the contents of 18 components, including Calycosin, Cyanidin-3-O-glucoside, Quercetin, Rutin, Kaempferol, Formononetin, Isomucronulatol and Prim-O-glucosylcimifugin in MEF, were significantly higher than in MOF. In turn, the contents of another 13 components, covering Biochanin A, Tectoridin, Isomucronulatol-7-O-glucoside, Liquiritin, Rhamnetin, etc., were lower in the MEF group than that in the MOF group. It is worth noting that flavonoids, especially flavonoid glycosides, were the primary active chemical ingredients in MOF and MEF. The 18 ingredients in MEF with a higher level carried out diverse activities, like anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor activities, which led us to speculate that MEF may have greater pharmacological effects and potential development prospects than MOF. The present results displayed that the contents of ingredients in the two different species of plants were radically different, and there was significant uniqueness to the components of MOF and MEF. Our study not only provides helpful chemical information for further quality assessment and active mechanism research of MOF and MEF but also offers scientific support for the resource utilization of MOF and MEF.


Subject(s)
Astragalus Plant , Astragalus propinquus , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Phytochemicals/pharmacology , Flavonoids
18.
Clin Transl Sci ; 16(10): 1997-2009, 2023 10.
Article in English | MEDLINE | ID: mdl-37596814

ABSTRACT

Receptor-interacting protein 1 (RIP1) is a key regulator of multiple signaling pathways that mediate inflammatory responses and cell death. RIP1 kinase activity mediates apoptosis and necroptosis induced by tumor necrosis factor (TNF)-α, Toll-like receptors, and ischemic tissue damage. RIP1 has been implicated in several human pathologies and consequently, RIP1 inhibition may represent a therapeutic approach for diseases dependent on RIP1-mediated inflammation and cell death. GDC-8264 is a potent, selective, and reversible small molecule inhibitor of RIP1 kinase activity. This phase I, randomized, placebo-controlled, double-blinded trial examined safety, pharmacokinetics (PKs), and pharmacodynamics (PDs) of single- (5-225 mg) and multiple- (50 and 100 mg once daily, up to 14 days) ascending oral doses of GDC-8264 in healthy volunteers, and also tested the effect of food on the PKs of GDC-8264. All adverse events in GDC-8264-treated subjects in both stages were mild. GDC-8264 exhibited dose-proportional increases in systemic exposure; the mean terminal half-life ranged from 10-13 h, with limited accumulation on multiple dosing (accumulation ratio [AR] ~ 1.4); GDC-8264 had minimal renal excretion at all doses. A high-fat meal had no significant effect on the PKs of GDC-8264. In an ex vivo stimulation assay of whole blood, GDC-8264 rapidly and completely inhibited release of CCL4, a downstream marker of RIP1 pathway activation, indicating a potent pharmacological effect. Based on PK-PD modeling, the GDC-8264 half-maximal inhibitory concentration for the inhibition of CCL4 release was estimated to be 0.58 ng/mL. The favorable safety, PKs, and PDs of GDC-8264 support its further development for treatment of RIP1-driven diseases.


Subject(s)
Receptor-Interacting Protein Serine-Threonine Kinases , Signal Transduction , Humans , Dose-Response Relationship, Drug , Double-Blind Method , Healthy Volunteers , Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors
19.
J Vasc Interv Radiol ; 34(11): 1997-2005.e3, 2023 11.
Article in English | MEDLINE | ID: mdl-37468093

ABSTRACT

PURPOSE: To compare secondary outcomes after ablation (AB), surgical resection (SR), and liver transplant (LT) for small hepatocellular carcinomas (HCCs), including resource utilization and adverse event (AE) rates. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results Program (SEER)-Medicare, HCCs <5 cm that were treated with AB, SR, or LT in 2009-2016 (n = 1,067) were identified using Healthcare Common Procedure Coding System codes through Medicare claims. Index procedure length of stay, need for intensive care unit (ICU) level care, readmission rates, and AE rates at 30 and 90 days were compared using chi-square tests or Fisher exact tests. Examined AEs included hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, liver failure, and anesthesia-related AEs, identified by International Classification of Diseases, Ninth/10th Revision, codes. RESULTS: The median length of stay for initial treatment was 1 day, 6 days, and 7 days for AB, SR, and LT, respectively (P < .001). During initial hospital stay, 5.0%, 40.8%, and 63.4% of AB, SR, and LT cohorts, respectively, received ICU-level care (P < .001). By 30 and 90 days, there were significant differences among the AB, SR, and LT cohorts in the rate of postprocedural hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, and anesthesia-related AEs (P < .05). By 90 days, the readmission rates after AB, SR, and LT were 18.6%, 28.2%, and 40.6% (P < .001), respectively. CONCLUSIONS: AB results in significantly less healthcare utilization during the initial 90 days after procedure compared with that after SR and LT due to shorter length of stay, lower intensity care, fewer readmissions, and fewer AEs.


Subject(s)
Liver Neoplasms , Pneumonia , Sepsis , Aged , Humans , United States , Abscess , Medicare , Liver Neoplasms/therapy , Hemorrhage , Pneumonia/epidemiology , Pneumonia/etiology , Sepsis/epidemiology , Sepsis/etiology , Retrospective Studies
20.
Ann Vasc Surg ; 97: 289-301, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37355014

ABSTRACT

BACKGROUND: With increasing regionalization of complex aortic surgery within fewer US centers, patients may face increased travel burden when accessing aortic surgery. Longer travel distances have been associated with inferior outcomes after major surgery; however, the impacts of distance on reinterventions and costs have not been described. This study aims to assess the association between patient travel distance and longer-term outcomes including costs and reinterventions after complex aortic surgery. METHODS: A retrospective review was conducted of all patients in the Vascular Implant Surveillance and Interventional Outcomes Network database undergoing complex endovascular aortic repair including internal iliac or visceral vessel involvement, complex thoracic endovascular aortic repair including Zone 0-2 proximal extent or branched devices, and complex open abdominal aortic aneurysm repair including suprarenal or higher clamp sites. Travel distance was stratified by Rural-Urban Commuting Area population-density category. Multinomial logistic regression models, negative-binomial models, and zero-inflated Poisson models were used to assess the association between travel distance and index procedural and comprehensive first-year costs, long-term imaging, and long-term reinterventions, respectively. RESULTS: Between 2011 and 2018, 8,782 patients underwent complex aortic surgery in the Vascular Implant Surveillance and Interventional Outcomes Network database, including 4,822 complex endovascular aortic repairs, 2,672 complex thoracic endovascular aortic repairs, and 1,288 complex open abdominal aortic aneurysm repairs. Median travel distance was 22.8 miles (interquartile range 8.6-54.8 miles, range 0-2,688.9 miles). Median age was 75 years for all distance quintiles. Patients traveling farther were more likely to be female (26.8% in quintile 5 [Q5] vs. 19.9% in Q1, P < 0.001) and to have had a prior aortic surgery (20.8% for Q5 vs. 5.9% for Q1, P < 0.001). Patients traveling farther had higher index procedural costs, with adjusted odds ratio (OR) 2.34 (95% confidence interval [CI] 1.86-2.94, P < 0.0001) of being in the highest cost tertile versus lowest for patients in Q5 vs. Q1. For patients with ≥ 1-year follow-up, those traveling farther had higher imaging costs, with adjusted Q5 OR 1.55 (95% CI 1.22-1.95, P = 0.0002), and comprehensive first-year costs, with adjusted Q5 OR 2.06 (95% CI 1.57-2.70, P < 0.0001). In contrast, patients traveling farther had similar numbers of reinterventions and imaging studies postoperatively. CONCLUSIONS: Patients traveling farther for complex aortic surgery have higher procedural costs, postoperative imaging costs, and comprehensive first-year costs. These patients should be targeted for increased care coordination for improved outcomes and healthcare system burden.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Female , Aged , Male , Blood Vessel Prosthesis Implantation/adverse effects , Postoperative Complications/etiology , Treatment Outcome , Retrospective Studies , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Risk Factors
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