Recommendation for the collection and analysis of endometrial biopsies for hormone therapies

The assessment of endometrial safety is one of the key requirements for the clinical development of new products for hormone therapy (HT) to treat menopausal symptoms in women who have a uterus. Both the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) provide detailed guidance on the requirements for the evaluation of biopsies to prove endometrial safety. However, there are some discrepancies between the European and the US requirements, making it difficult to fulfil both guidelines simultaneously. In order to facilitate multinational clinical trials performed within clinical programs to develop novel HT products, we developed an approach considering both guidance documents as far as possible and proposed solutions for issues that are inconsistently described in these guidelines. A table with the required sample sizes is given. Our recommendation for a unified approach for the estimation of the hyperplasia rate for hormone therapies fulfils the intent of the recommendations of both the FDA and the EMA and thus leads to a globally harmonized drug development for hormone therapies.     

Effects of some adenosine analogs on morphine-induced analgesia and tolerance

1. The analogs of adenosine D- and L-phenylisopropyladenosine (D- and L-PIA) and chloroadenosine (CADO) induced analgesia in mice (hot-plate test). 2. The antinociceptive effects of the three adenosine agonists were antagonized by caffeine but were unaffected by naloxone. 3. Morphine-induced antinociception was increased by pretreatment with adenosine agonists. 4. Whereas CADO significantly attenuated the induction of morphine tolerance, D- and L-PIA did not affect the process.     

Grande prématurité : évolution de 1994 à 2006

ObjectiveEvaluate the incidence of births before 33 weeks of amenorrhea over a 12-year period and the place of prematurity induced among them. Determine the evolution of various causes of birth prior to that and draw up a detailed inventory.Patients and methodsThis is a retrospective study from 1994 to 2006, concerning mothers who gave birth in the Network Users Association of computerized records in Pediatrics, Obstetrics and Gynecology (AUDIPOG) between 22 and 32 + 6 days of maternity. A total of 3781 deliveries were included. The statistical significance of links between the degree of prematurity (high prematurity/extreme prematurity) and the type of prematurity (induced/spontaneous) or mode of early work in the event of induced prematurity (trigger/prior cesarean work) was determined. The evolution of different etiologies was also studied with a complete inventory in 2006.ResultsWe observed a significant increase in the rate of births before 33SA: it was multiplied by 3 in 12 years and stood at 1.7% of births in 2006. No increase in prematurity induced was observed, but in case of preterm labor induced the number of births by caesarean section increased significantly. Concerning the evolution of etiologies, vaginal and urinary infections decreased the most, followed by fetal malformations. Only multiple pregnancies increased significantly. The principle cause of preterm birth was hypertension. Prior to 28SA, premature births were caused by metrorrhagia and infections at greater levels than 28–32SA.Discussion and conclusionThe growing number of births before 33SA is a serious phenomenon that must be monitored as they are increasingly common in France.     

Hospitalization deficit of in‐ and outpatient cases with cardiovascular diseases and utilization of cardiological interventions during the COVID‐19 pandemic: Insights from the German‐wide helios hospital network

BackgroundTreatment numbers of various cardiovascular diseases were reduced throughout the early phase of the ongoing COVID‐19 pandemic. Aim of this study was to (a) expand previous study periods to examine the long‐term course of hospital admission numbers, (b) provide data for in‐ and outpatient care pathways, and (c) illustrate changes of numbers of cardiovascular procedures.Methods and ResultsAdministrative data of patients with ICD‐10‐encoded primary diagnoses of cardiovascular diseases (heart failure, cardiac arrhythmias, ischemic heart disease, valvular heart disease, hypertension, peripheral vascular disease) and in‐ or outpatient treatment between March, 13th 2020 and September, 10th 2020 were analyzed and compared with 2019 data. Numbers of cardiovascular procedures were calculated using OPS‐codes. The cumulative hospital admission deficit (CumAD) was computed as the difference between expected and observed admissions for every week in 2020. In total, 80 hospitals contributed 294 361 patient cases to the database without relevant differences in baseline characteristics between the studied periods. There was a CumAD of −10% to −16% at the end of the study interval in 2020 for all disease groups driven to varying degrees by both reductions of in‐ and outpatient case numbers. The number of performed interventions was significantly reduced for all examined procedures (catheter ablations: −10%; cardiac electronic device implantations: −7%; percutaneous cardiovascular interventions: −9%; cardiovascular surgery: −15%).ConclusionsThis study provides data on the long‐term development of cardiovascular patient care during the COVID‐19 pandemic demonstrating a significant CumAD for several cardiovascular diseases and a concomitant performance deficit of cardiovascular interventions.     

植入携带有治疗性腺病毒的包裹支架对猪冠状动脉再狭窄的预防作用

目的寻找一种有效转送治疗基因到所扩张冠状动扩脉的靶部位的方法,以预防冠状动脉损伤后再狭窄。方法大白猪14只,随机分治疗组(包裹支架)和对照组(非包裹支架),每组7只,治疗组用高分子聚合物phosphorylocholine包裹不锈钢丝的包裹支架,对照组用非包裹支架,经复制缺陷的重组腺病毒RadTIMP-3处理后,植入猪的冠状动脉,4周后,行冠状动脉造影,取新鲜的心脏用福尔马林固定,进行组织形态分析。结果治疗组的血管腔内径平均值为(2.32±0.185) mm, 而非包裹支架的对照组平均直径为(1.79±0.31) mm,治疗组显著高于对照组,P=0.014。TiMP-3治疗组冠状动脉内膜的厚度为(0.34±0.17) mm,对照组为(0.81±0.32) mm,显著高于治疗组,P= 0.0059。结论经PC包裹支架输送含有TIMP-3基因的腺病毒到冠状动脉,可有效地抑制内膜平滑肌细胞的增生,减轻再狭窄。     

Changes in Intrathoracic Impedance are Associated With Subsequent Risk of Hospitalizations for Acute Decompensated Heart Failure: Clinical Utility of Implanted Device Monitoring Without a Patient Alert

BackgroundAcute decreases in intrathoracic impedance monitoring have been shown to precede heart failure hospitalization in a limited population of heart failure patients. We evaluated the relationship between changes in intrathoracic impedance with hospitalizations associated with acute decompensated heart failure (ADHF) in patients with cardiac resynchronization therapy plus defibrillator (CRT-D) devices.Methods and ResultsThe study enrolled 326 heart failure patients who had received CRT-D with impedance-monitoring capabilities (InSync Sentry, Medtronic). The date and duration of ADHF hospitalizations were retrospectively identified before device interrogation to obtain device diagnostic information. During 333 ± 96 days of device monitoring, 228 patients experienced 540 intrathoracic impedance fluid index threshold crossings events (TCE) at the nominal threshold value (60 Ω. days). During the initial 4-month evaluation period, 17 subjects experienced 22 ADHF hospitalizations. In the subsequent monitoring period (206 ± 95 days), 18 patients experienced 24 hospitalizations. The occurrence of TCEs during the monitoring period was independently correlated with the subsequent rate of ADHF hospitalization such that each TCE event during the risk stratification period was associated with a 35% increased risk for ADHF hospitalization in the remaining study period (P = .001). Poisson regression indicated that the subgroup of patients with an annual average rate of more than 3 threshold crossings per year during the monitoring period were significantly more likely to be hospitalized for ADHF than those patients with no TCE during the monitoring period (0.76 [0.20–1.325] vs. 0.14 [0.05–0.23] hospitalizations/subject/y [95%CI]; P = .02). Likewise, Kaplan-Meier analysis revealed that subsets of patients with more than 3 TCEs per year or with more than 30 days per year above threshold during the risk stratification period had significantly higher rates of ADHF hospitalization during the post risk stratification period than subjects with no TCE events, respectively.ConclusionsIn this multicenter retrospective cohort study, serial decreases in intrathoracic impedance sufficient to generate a fluid index threshold crossing as well as the net duration that the index remained above threshold during a 4-month monitoring period were associated with subsequent risk of ADHF hospitalization.     

小腿3.0 T MRA:非增强心电门控流动依赖MRA、连续移床MRA和时间分辨MRA的对比研究

目的对一组临床病人行小腿3.0TMRA检查分析,旨在比较3D非增强心电门控流动依赖型MRA(NE-MRA)、连续移床(CTM)MRA和时间分辨TWIST-MRA的应用价值。方法 36例外周动脉硬化闭塞症(PAOD)病人(Ⅱ～Ⅳ     

利用双能量CT单能外推法减少金属伪影

目的本研究目的旨在探讨利用双能量CT减少金属置入物引起的金属伪影的临床应用价值。方法本研究共有31例病人对金属置入的部位进行了双能量CT扫描     

Effect of Safety Measures on Bacterial Contamination Rates of Blood Components in Germany

SUMMARY: Requirements for bacterial testing of blood components on a defined quantity as part of routine quality control were introduced in Germany by the National Advisory Committee Blood of the German Federal Ministry of Health in 1997. The philosophy was to establish standardized methods for bacterial testing. Numerous measures to reduce the risk of bacterial contamination were implemented into the blood donation and manufacturing processes between 1999 and 2002. German Blood establishments performed culture-based bacterial testing on random samples of platelet concentrates (PCs), red blood cells (RBCs) and fresh frozen plasma (FFP) and reported data out of the production periods 1998, 2001 and 2005/2006. While the bacterial contamination rate of apheresis PCs remained nearly unchanged, it decreased by 70% for pooled PCs to a rate of 0.158% in the last observation period. Leukocyte-depleted RBCs with diversion of the initial blood volume showed a contamination rate of 0.029% which is significantly lower than that of RBCs without leukocyte depletion and diversion (0.157%). The contamination rate of plasma decreased by 80%. Preventive measures resulted in a significant reduction of bacterial contamination of blood components. Long-term monitoring with standardized methods for bacteria testing supports evaluation of the cumulative effect of contamination reducing measures.