Comparative pharmacokinetics and tissue distribution of cryptotanshinone,tanshinone IIA,dihydrotanshinone I,and tanshinone I after oral administration of pure tanshinones and liposoluble extract of Salvia miltiorrhiza to rats

Salvia miltiorrhiza is one of the most commonly used traditional Chinese medicines in the treatment of cardiovascular and cerebrovascular diseases. Cryptotanshinone (CTS), tanshinone IIA (Tan IIA), dihydrotanshinone I (diTan I), and tanshinone I (Tan I) are the main active compounds in the liposoluble extract of Salvia miltiorrhiza. The differences in the pharmacokinetic and tissue distribution behaviors of the four tanshinones after oral administration of the liposoluble extract of Salvia miltiorrhiza and pure compounds are not clear. This study aims to compare the pharmacokinetics and tissue distribution of the four tanshinones after oral administration of pure tanshinone monomers and the liposoluble extract of Salvia miltiorrhiza. An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis method was developed for the determination of the four tanshinones. The results showed that the AUC and C_max of tanshinones in rats receiving the extract of Salvia miltiorrhiza were significantly increased compared with those receiving the pure tanshinones. In the tissue distribution experiments, the AUC of the four tanshinones in the extract was much greater than the AUC of the monomers in the lung, heart, kidney, liver, and brain, and the coexisting constituents particularly promoted the distribution of tanshinones into tissues that the drug cannot sufficiently penetrate. These findings suggested that the coexisting constituents in the liposoluble extract of Salvia miltiorrhiza play an important role in the alteration of plasma concentration and tissue distribution of the four tanshinones. Understanding these differences could be of significance for the development and application of Salvia miltiorrhiza extract and tanshinone components.     

COPD患者相关炎性因子水平与其病情严重程度的相关性研究

探讨慢性阻塞性肺病(COPD)患者的可溶性髓系细胞触发受体-1(sTREM-1)、结缔组织生长因子(CTGF)、亲环素-A(CyPA)水平与其病情严重程度的相关性。ELISA检测COPD患者与健康人血清sTREM-1、CTGF、CyPA水平。结果显示,COPD患者sTREM-1、CTGF、CyPA水平高于健康人。随着肺功能分级的增加,COPD患者血清中sTREM-1、CTGF、CyPA水平也随之增加。sTREM-1、CTGF、CyPA水平与FEV1/FVC呈现显著负相关性(P＜0.05)。Logistic回归分析显示,sTREM-1、CTGF、CyPA水平是严重COPD的影响因素。结果说明,COPD患者血清sTREM-1、CTGF、CyPA水平显著升高,并且与患者肺功能指标显著相关,可用于判断COPD患者的病情严重程度。     

套管式长针深层软组织松解术的临床特点与应用

套管式长针属古代“九针”中“长针”的范畴,可祛深邪久痹,通过松解神经根,刺激相应区域的肌肉,以调节机体生理功能。套管式长针深层软组织松解术依据中医学经筋理论和以痛为腧理论,属于古代针刺中的“经刺”“报刺”“恢刺”及“合谷刺”等范畴。通过针刺疏散瘀滞之气血,以通治痛。套管式长针弥补普通毫针刺激量小及松解类针具风险较大的不足,兼具针刺调衡、提插松解的双重作用。套管式长针深层软组织松解术对深层肌纤维紧张所导致的各类难治性疼痛类疾病疗效明显,为临床医生提供了新的治疗方式,具有较高的推广及应用价值。     

Idarucizumab for Intravenous Thrombolysis and Endovascular Thrombectomy in Acute Stroke: A Case Report

BackgroundNon–vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, are widely used to prevent ischemic stroke in patients with nonvalvular atrial fibrillation. Nonetheless, stroke occurs in 1–2% of patients, and the use of NOACs may increase the bleeding risk for patients who are receiving acute treatment of intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT). Idarucizumab, a monoclonal antibody developed to bind dabigatran, has been proven safe and effective for patients with uncontrolled bleeding or for patients planning to receive emergent procedures. It is now accepted that patients taking dabigatran with recurrent stroke may benefit from IVT after idarucizumab. However, there are limited data regarding idarucizumab use in patients planning to have EVT.Case ReportWe present the case of a male patient taking dabigatran who had a stroke and who was treated with idarucizumab followed by combined IVT and EVT. The patient had immediate recanalization of the occluded vessel and near total recovery of function after 3 months.Why Should an Emergency Physician be Aware of This?Our case report supports the evidence that patients presenting with acute ischemic stroke (AIS) despite being under dabigatran therapy should be evaluated for reversal by idarucizumab which can contribute to the eligibility for IVT as well as EVT. It has also been proved to provide better outcomes for patients with AIS. The availabilities of specific reversal agents for NOACs will probably alter the current management of patients with AIS.     

Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer

We have investigated the prognostic value of two novel interim ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus ∆SUV_NTO). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and ∆SUV_NTO) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and ∆SUV_NTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and ∆SUV_NTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters ∆SUV_NTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.     

Brain tissue oxygenation during transnasal endoscopic skull base procedures

PurposeWe aimed to study brain tissue oxygenation during the period of controlled reduction of arterial blood pressure – a maneuver often used in extended endoscopic skull base surgery for bloodless operative field.MethodsIntracranial pressure, arterial blood pressure and the resultant cerebral perfusion pressure were measured during extended endoscopic skull base surgery in 5 patients with diagnosed tumors of the skull base and arterial hypertension. Simultaneously, in those patients, we measured partial pressure of oxygen in the brain parenchyma (PbtO₂).ResultsValues of PbtO₂ lower than 15 mm Hg (risk of brain ischemia) were observed in 3 patients for periods of 40 min, 110 min and 123 min, respectively. In 2 of these patients, no hypotension (mean arterial pressure <65 mm Hg) was necessary for bloodless operative field. Another 2 patients had PbtO₂ above 30 mm Hg at the time when their mean arterial pressure was below 65 mm Hg. The time course of PbtO₂ followed that of cerebral perfusion pressure with a time lag of 40–60 s in all patients.ConclusionModerate reduction of arterial pressure, often used to obtain bloodless operative field during extended endoscopic skull base surgery, may in patients with the medical history of arterial hypertension be associated with critically low values of partial oxygen pressure in brain tissue.     

Large-Bore Aspiration Thrombectomy versus Catheter-Directed Thrombolysis for Acute Pulmonary Embolism: A Propensity Score–Matched Comparison

PurposeTo compare effectiveness and safety of large-bore aspiration thrombectomy (LBAT) with catheter-directed thrombolysis (CDT) for treatment of acute massive and submassive pulmonary embolism (PE).Materials and MethodsThis retrospective review included patients with acute PE treated with LBAT or CDT using tissue plasminogen activator (tPA) between December 2009 and May 2020. A propensity score based on Pulmonary Embolism Severity Index class and PE severity (massive vs submassive) was calculated, and 26 LBAT cases (age 60.2 y ± 17.1, 14/26 women) were matched with 26 CDT cases (age 59.7 y ± 14.2, 14/26 women).ResultsThe CDT group had 22.1 mg ± 8.1 tPA infused over 21.2 h ± 6.6. Both groups demonstrated similar initial and final systolic pulmonary artery pressure (PAP) (LBAT: 54.5 mm Hg ± 12.9 vs CDT: 54.5 mm Hg ± 16.3, P = .8, and LBAT: 42.5 mm Hg ± 14.1 vs CDT: 42.6 mm Hg ± 12.1, P = .8, respectively) and similar reductions in heart rate (LBAT: −5.4 beats/min ± 19.2 vs CDT: −9.6 beats/min ± 15.8, P = .4). CDT demonstrated a higher reduction in Miller score (−10.1 ± 3.9 vs −7.5 ± 3.8, P = .02). LBAT resulted in 1 minor hemorrhagic complication and 2 procedure-related mortalities, and CDT resulted in 1 minor and 1 major hemorrhagic complication.ConclusionsLBAT and CDT resulted in similar reductions of PAP and heart rate when used to treat acute PE. CDT reduced thrombus burden to a greater degree. Although hemorrhagic complications rates were not significantly different, the LBAT group demonstrated a higher rate of procedure-related mortality. Larger studies are needed to compare the safety of these techniques.