中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

Incidence of pressure ulcers in intensive care units and direct costs of treatment: Evidence from Iran

Background and objective

Pressure ulcer (PU) is one of the important and frequent complications of hospitalization, associated with high treatment costs. The present study was conducted to determine the incidence of PU and its direct treatment costs for patients in intensive care unit (ICU) in Iran.

Packed red blood cell transfusion (PRBC) attenuates intestinal blood flow responses to feedings in pre-term neonates with normalization at 24 hours

Objective: To determine whether packed red blood cell (PRBC) transfusion affects post-prandial superior mesenteric artery blood flow velocities (SMA BFVs) in very-low birth weight (VLBW) neonates and if so, at what time point after transfusion restoration of previous SMA BFV patterns occurs.

Design/Methods: VLBW pre-term neonates, older than 14 days and tolerating bolus enteral feedings administered every 3?h were enrolled in this prospective observational study. Pulsed Doppler ultrasound was used to measure pre- and post-prandial (at 45?min) time-averaged mean, peak and end diastolic velocities (TAMV, PSV, EDV) immediately before and after 15?ml/kg of PRBC transfusion was given over 3?h; patent ductus arteriosus (PDA) status was also evaluated. Subsequent pre- and post-prandial SMA BFVs were recorded 24 and 48?h after the transfusion.

Results: Pre- and post-prandial measurements were obtained for 21 out of 25 enrolled infants. Post-prandial SMA BFVs were attenuated during the feedings immediately after transfusion; at 24 and 48?h after transfusion, changes in post-prandial SMA BFVs were similar to those measured prior to transfusion; the presence of the PDA did not affect results.

Conclusions: PRBC transfusion blunted SMA BFV responses to feedings immediately after the transfusion with normalization observed 24?h post-transfusion.     

Optimal combination of antiangiogenic therapy for hepatocellular carcinoma

The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide.     

Similarities between interstitial cystitis/bladder pain syndrome and vulvodynia: implications for patient management

Interstitial cystitis/bladder pain syndrome (IC/BPS) and vulvodynia are chronic pain syndromes that appear to be intertwined from the perspectives of embryology, pathology and epidemiology. These associations may account for similar responses to various therapies.     

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.     

Prostatic Artery Embolization—Anatomic Predictors of Technical Outcomes

PurposeTo determine if cone-beam CT and digital subtraction angiography analysis of pelvic arterial anatomy has predictive value for radiation exposure and technical success of prostatic artery embolization (PAE).Materials and MethodsThis prospective, nonrandomized, single-center study included 104 consecutive patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Cone-beam CT was performed in 160/208 (76.9%) hemipelves to determine prostatic artery (PA) origin. Classification of pelvic arterial tortuosity was possible in 73/104 (70.2%) patients. Learning curves of 2 interventionalists who performed 86.5% of PAEs were analyzed.ResultsTortuosity of pelvic arteries was classified as mild in 25 (34.2%) patients median age 64 years, moderate in 40 (54.8%) patients median age 69 years, and severe in 8 (11.0%) patients median age 70 years (mild vs moderate, P = .002; mild vs severe, P = .019); median fluoroscopy times were 24, 36, and 46 minutes (P = .008, P = .023); median contrast volumes were 105, 122.5, and 142 mL (P = .029, P = .064); and bilateral PAE rates were 84.0%, 77.5%, and 62.5% (P = .437), respectively. PA origin from superior vesical artery was most frequent (27.5%) and showed higher dose area product (median 402.4 vs 218 Gy ∙ cm², P = .033) and fluoroscopy time (median 42.5 vs 27 min, P = .01) compared with PA origin from obturator artery, which was least frequent. Interventionalist experience revealed significant impact on procedure times (median 159 vs 130 min, P = .006).ConclusionsTortuosity of pelvic arteries was more frequent in older patients and predicted worse technical outcomes of PAE. PA origin from obturator artery was associated with lower dose area product and fluoroscopy time, especially compared with PA origin from superior vesical artery. Interventionalist experience showed significant influence on technical outcome.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Perfusion pressure flow study in the upper urinary tract

Hydronephrosis with an undetermined pathology is a common condition detected in imaging studies. In urological clinical practice, it is a persistent dilemma to predict whether this condition will progress to result in the deterioration of renal function. Perfusion pressure flow study of the upper urinary tract, known as the Whitaker test, provides an alternative diagnostic tool for solving this condition. Perfusion pressure flow study has been criticized for its invasiveness, nonphysiological approach, and inconsistency in predicting outcomes. However, it continues to be used to evaluate difficult or equivocal cases and to provide an objective assessment of the upper urinary tract.