Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 2. The biological variability of the murine Local Lymph Node Assay (LLNA) for skin sensitisation

The Local Lymph Node Assay (LLNA) is the most common in vivo regulatory toxicology test for skin sensitisation, quantifying potency as the EC3, the concentration of chemical giving a threefold increase in thymidine uptake in the local lymph node. Existing LLNA data can, along with clinical data, provide useful comparator information on the potency of sensitisers. Understanding of the biological variability of data from LLNA studies is important for those developing non-animal based risk assessment approaches for skin allergy. Here an existing set of 94 EC3 values for 12 chemicals, all tested at least three times in the same vehicle have been analysed by calculating standard deviations (SD) for logEC3 values. The SDs range from 0.08 to 0.22. The overall SD for the 94 logEC3 values is 0.147. Thus the 95% confidence limits (2xSD) for LLNA EC3 values are within a factor of 2, comparable to those for physico-chemical measurements such as partition coefficients and solubility. The residual SDs of Quantitative Mechanistic Models (QMMs) based on physical organic chemistry parameters are similar to the overall SD of the LLNA, indicating that QMMs of this type are unlikely to be bettered for predictive accuracy.     

Intraoperative Practice Variability in Total Knee Arthroplasty

BackgroundConsiderable practice variability exists among orthopedic surgeons performing total knee arthroplasty (TKA). The purpose of this study is to understand what TKA surgical and perioperative techniques are standard among high-volume academic knee arthroplasty surgeons.MethodsA written survey with 59 questions regarding management preferences in TKA was distributed by the 2018 John N. Insall Traveling Fellows to all arthroplasty-trained attending physicians at 13 medical centers, with 45 responses recorded.ResultsSurveyed surgeons performed unicompartmental knee arthroplasty (88%) and bilateral TKA (87%). Most surveyed surgeons rarely or never performed outpatient primary TKA (71%). Conventional alignment guides and cemented implants were used by 80% of respondents. Most surgeons used posterior-stabilized implants (67%), followed by cruciate-retaining (20%), ultracongruent (20%), and medial congruent or medial pivot designs (17.8%). Surveyed surgeons frequently or always resurfaced the patella (73%), used a tourniquet for the entire case (73%), and used tranexamic acid for all TKAs (91%). The most common locations for intra-articular anesthetic injection were the arthrotomy (91%), the periosteum (84%), and the medial posterior capsule (82%). Saline (62%) and dilute iodine (47%) were the most common irrigation fluids. The arthrotomy was most commonly closed with running barbed suture (60%) followed by interrupted vicryl (40%). Skin closure was predominantly with running monocryl (60%) followed by staples (29%). Anticoagulation for TKA was primarily aspirin 81 mg BID (60%).ConclusionThere was considerable variability among surgeons polled although a strong preference for more conventional and less developmental techniques prevailed.     

Multicentric Analytical and Inter-observer Comparability of Four Clinically Developed Programmed Death-ligand 1 Immunohistochemistry Assays in Advanced Clear-cell Renal Cell Carcinoma

BackgroundPrevious studies have suggested increased clinical benefit with inhibition of programmed death-ligand 1 (PD-L1)/programmed death-1 in patients with PD-L1–positive locally advanced/metastatic renal cell carcinoma (RCC). We examined the analytical and inter-observer comparability of PD-L1–positivity across 4 clinically developed immunohistochemistry assays in clear-cell RCC (CCRCC).Materials and MethodsRandomly selected archived, formalin-fixed, paraffin-embedded nephrectomy specimens from 201 patients with locally advanced CCRCC were screened using VENTANA SP142. From these, 30 cases were selected based on their tumor-infiltrating immune cell (IC) PD-L1 status (PD-L1-IC–positivity of < 1%, 1%-5%, or > 5%; 10 cases each). These cases were stained for PD-L1 using VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, and scored for PD-L1 expression on IC and tumor cells (TC) by trained readers at 5 sites.ResultsAdjusted mean percentages of PD-L1-IC–positivity and PD-L1-TC–positivity varied from 4.0% to 4.9% and from 1.3% to 10.7%, respectively, between assays. Inter-assay differences in PD-L1-IC–positivity were small and non-significant (P = .1938 to .9963); for PD-L1-TC–positivity, significant differences were observed between VENTANA SP142 and the other assays (P ≤ .0001) and between VENTANA SP263 and DAKO 28-8 (P = .0248). Intra-class correlation values showed moderate-to-high inter-reader agreement for each assay for PD-L1-IC–positivity and for 3 assays for PD-L1-TC–positivity.ConclusionsIn this first multicenter analytical comparison study of PD-L1 assays in CCRCC, PD-L1–positivity could be assessed reproducibly using all 4 assays for IC and for 3 of the 4 assays for TC.     

Impact of new technologies on diabetes care

Technologies for diabetes management, such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems, have improved remarkably over the last decades. These developments are impacting the capacity to achieve recommended hemoglobin A1c levels and assisting in preventing the development and progression of micro- and macro vascular complications. While improvements in metabolic control and decreases in risk of severe and moderate hypoglycemia have been described with use of these technologies, large epidemiological international studies show that many patients are still unable to meet their glycemic goals, even when these technologies are used. This editorial will review the impact of technology on glycemic control, hypoglycemia and quality of life in children and youth with type 1 diabetes. Technologies reviewed include CSII, CGM systems and sensor-augmented insulin pumps. In addition, the usefulness of advanced functions such as bolus profiles, bolus calculators and threshold-suspend features will be also discussed. Moreover, the current editorial will explore the challenges of using these technologies. Indeed, despite the evidence currently available of the potential benefits of using advanced technologies in diabetes management, many patients still report barriers to using them. Finally this article will highlight the importance of future studies tailored toward overcome these barriers to optimizing glycemic control and avoiding severe hypoglycemia.     

100例高血压病患者短程心率变异性分析

目的:评价自主神经活动在高血压病中的调节作用。方法:观测100例高血压病(Ⅰ组)和54例正常人(Ⅱ组)及高血压病伴心电图改变(ⅠA组)和不伴心电图改变(ⅠB组)心率变异性(以下称HRV)时域参数SDNN、rMSSD、PNN50、Bottom4项指标。结果:Ⅰ组与Ⅱ组差异有显著性(P<0.05);ⅠA组与ⅠB组组差异无显著性(P>0.05)。结论:在高血压病中,交感神经张力增高,副交感神经活动减弱及损伤可能是HRV降低的重要因素。     

Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students

Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.     

老年男性心肌缺血患者心率变异分析（附67例报告）

采用正常搏动ＲＲ间期的标准差（ＳＤ）及心率变异指数（ＨＲＶ ｉｎｄｅｘ）作为指标，分析６７例老年男性心肌缺血患者的心率变异，并与正常老年男性组及正常青壮年男性组进行了对比，发现前组的ＲＲ间期ＳＤ、ＨＲＶｉｎｄｅｘ均明显低于后两组，其结果有显著性差异（Ｐ均〈０．０１）。提示心肌缺血可破坏交感与迷走神经的均衡性，造成心率变异降低。     

Inter- and intra-individual variability of non-invasive tear break-up time in Hong Kong Chinese

Non-invasive tear break-up time (NITBUT) has been proposed as a measure of tear film integrity which is superior to the more commonly used tear break-up time (TBUT), since it does not alter the volume or the physicochemical properties of the tear layer by the addition of fluorescein. We measured NITBUT by measuring the time taken for distortions or discontinuities to appear in the reflected image of a grid pattern which covered about 80 per cent of the corneal surface. NITBUT measures were made 100 times on seven Hong Kong Chinese subjects with up to 20 consecutive measures being made on a single day. We also measured NITBUT on one occasion on an unselected population of 52 Hong Kong Chinese subjects. NITBUT shows a skewed distribution in all subjects, with many shorter values and some extremely long values. There are statistically significant variations in NITBUT from day to day, and from subject to subject. The group of 52 subjects also had a skewed NITBUT distribution with many short values and some very long values. The arithmetic mean does not adequately represent NITBUT data, either for individual subjects or for this group of subjects. As many as five to eight measures may be necessary to gain a stable estimate of the NITBUT and stability of the measure is improved if extreme values are omitted. We recommend the use of nonparametric statistics to compare NITBUT values from day to day in or between subjects.