Response of lower esophageal contractility to changing concentrations of halothane or isoflurane: A multicenter study

A multiple-center study was performed to determine the relationship between lower esophageal contractility, clinical signs, and anesthetic concentration as expressed by minimum alveolar concentration (MAC). One hundred four American Society of Anesthesiologists Class I through III patients were exposed to isoflurane (with and without nitrous oxide) or halothane in concentrations of 0.5, 1.0, and 1.5 MAC. Heart rate and systolic blood pressure were continuously monitored. Both the amplitude and frequency of spontaneous and provoked lower esophageal contractions were measured in situ by using a 24-F probe equipped with provoking and measuring balloons. Combined results demonstrated statistically significant correlations (P<0.001) between lower esophageal contractility and MAC. Spontaneous lower esophageal contractions decreased from 1.10±0.12 (SEM) contractions per minute (0.5 MAC) to 0.42±0.05 (1 MAC) to 0.18±0.05 (1.5 MAC). Provoked lower esophageal contractility values decreased from 45±4 mm Hg (0.5 MAC) to 29±3 (1 MAC) to 19±2 (1.5 MAC). Heart rate changes did not correlate with MAC, and systolic blood pressure correlated in only one of three centers. Intracenter and intercenter analyses failed to demonstrate a significant relationship between lower esophageal contractility and heart rate or systolic blood pressure. No intracenter differences in either amplitude or frequency of lower esophageal contractions were observed, despite differences in volatile agents, induction techniques and agents, patient populations, and duration of anesthesia. Our studies indicate that lower esophageal contractility may be an indicator of anesthetic depth as reflected by MAC, but further studies are needed to quantify the effects of surgical stimulus, intravenous anesthetics, vasodilators, anticholinergics, calcium channel blockers, beta-adrenergic agonists, and the presence of a nasogastric tube.     

Comparing the Approach to Radical Prostatectomy Using the Multiport da Vinci Xi and da Vinci SP Robots: A Propensity Score Analysis of Perioperative Outcomes

BackgroundUse of the single-port da Vinci SP robotic platform for various urological procedures has been described by several groups. However, the comparative performance of the SP robot in relation to earlier models such as the da Vinci Xi is still unclear.ObjectiveTo compare intraoperative and short-term postoperative outcomes between the da Vinci Xi and SP robots for patients undergoing radical prostatectomy (RP) in a referral center.Design, setting, and participantsData were prospectively collected for patients undergoing RP from June 2019 to April 2020 in a single center. The da Vinci SP was used for 71 patients and the da Vinci Xi for 875 patients. After propensity score (PS) matching, two groups of 71 patients were selected for the comparative study.InterventionRP via a transperitoneal approach using the same technique steps and anatomy access with both robot consoles.Outcome measurements and statistical analysisA PS analysis was performed using the covariates age, body mass index, Charlson comorbidity index, Sexual Health Inventory for Men score, American Urological Association symptom score, prostate size, prostate-specific antigen levels, Gleason score, D’Amico risk group, and degree of nerve-sparing. Intraoperative performance and short-term functional (continence and potency) and oncological outcomes were compared between the groups.Results and limitationsMedian follow-up was 4.4 mo (interquartile range [IQR] 1.6–7.2) for the SP group and 3.2 mo (IQR 1.6–4.8) for the Xi group (p = 0.2). The median total operative time and median console time were both significantly higher in the SP group, with median differences of 14 min (95% confidence interval [CI] 9–19) and 5 min (95% CI 0–5), respectively. The proportion of patients with blood loss of >100 ml was significantly lower in the SP group (difference of 27%, 95% CI 12–42%). No intra- or postoperative complications were reported in either group. There were no significant differences in pain scores at 6, 12, and 18 h or in positive surgical margin rates between the groups. The SP group had a significantly higher percentage of extraprostatic extension than the Xi group (difference of 16%, 95% CI 4.6–27%). None of the patients experienced biochemical recurrence during follow-up. The difference in continence rates at 45 d between the SP and Xi groups was 11% (95% CI ?5.6% to 28%) and the difference in potency rates at 45 d was ?7.3% (95% CI ?21% to 6.2%). The short-term follow-up for comparison of functional and oncological outcomes is a limitation.ConclusionsDespite differences in trocar placement and technology between the two da Vinci consoles, the SP has satisfactory intraoperative performance compared to the Xi. SP surgery can be performed safely and effectively during the initial learning phase. However, longer-term follow-up is needed to provide further evidence on the impact of SP implementation on functional and oncological outcomes.Patient summaryWe compared intraoperative and short-term postoperative outcomes for patients who underwent radical prostatectomy using two different robots, the da Vinci Xi and the single-port da Vinci SP. We found that operative time was longer for the Single Port console. Studies with long-term follow-up are needed to compare the functional and oncological outcomes.     

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in...     

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.     

微生物法测定力达霉素的效价

建立力达葛素效价测定的微生物检定法，检定菌为枯草芽孢杆菌。当力达葛素的浓度为1.85～13.51μg／ml时，其抑菌圈直径与反应剂量呈线性关系，并与HPLC法进行比较，测定结果基本一致。     

抗生素效价测定中EXCEL表的多碟兼容性

提高EXCEL表格在抗生素效价测定统计中的多碟兼容性。方法：对Excel统计表格进行重新编写与优化。结果：运用新Compatible表格模板即可完成任意碟数为一个试验组的统计分析。讨论：新的Compatible表格能有效减轻数据处理时的工作强度，使实用性变得更强，应用范围变得更广。     

Oncologic,Functional, and Complications Outcomes of Robot-assisted Radical Cystectomy with Totally Intracorporeal Neobladder Diversion

Background

Robot-assisted radical cystectomy (RARC) with totally intracorporeal neobladder diversion is a complex procedure that has been reported with good outcomes in small series.

Objective

To present complications and oncologic and functional outcomes of this procedure.

Design, setting, and participants

Between 2003 and 2012 in a tertiary referral center, 70 patients were operated on by two experienced robotic surgeons. Data were collected prospectively and reviewed retrospectively.

Intervention

RARC with totally intracorporeal modified Studer ileal neobladder formation.

Outcome measurements and statistical analysis

The overall outcome of RARC with a totally intracorporeal neobladder was presented by assessing (1) surgical margins, (2) recurrence or cancer-specific death at 24 mo, (3) 30-d and 90-d complications graded according to the modified Clavien-Dindo system, (4) daytime and nighttime continence (no or one pad per day) at 6 and 12 mo, and (5) satisfactory sexual activity or potency at 6 mo and 12 mo. Survival rates were estimated by Kaplan-Meier plots.

Results and limitations

Median follow-up of the cohort was 30.3 mo (interquartile range: 12.7–35.6). We recorded negative margins in 69 of 70 patients (98.6%). Clavien 3–5 complications occurred in 22 of 70 patients (31.4%) at 30 d and 13 of 70 (18.6%) at >30 d. At 90 d, the overall complication rate was 58.5%. Clavien <3 and Clavien ≥3 complications were recorded in 15 of 70 patients (21.4%) and 26 of 70 (37.1%), respectively. Kaplan-Meier estimates for recurrence-free, cancer-specific, and overall survival at 24 mo were 80.7%, 88.9%, and 88.9%, respectively. Daytime continence and satisfactory sexual function or potency at 12 mo ranged between 70% and 90% in both men and women. Limitations of this study include its retrospective design, selection bias due to the learning curve phase, and missing data.

Conclusions

In this expert center for RARC, outcomes after RARC with totally intracorporeal neobladder diversion appear satisfactory and in line with contemporary open series.     

STATISTICAL INFERENCE FOR RELATIVE POTENCY IN BIVARIATE DOSE-RESPONSE ASSAYS WITH CORRELATED RESPONSES

ABSTRACT

The analysis of dose-response assays measuring two correlated responses is considered. Attention is given to statistical inference for the potency ratio. Results from a simulation study suggest that a post hoc adjustment for the correlation in parameter estimates obtained from univariate fits provides nearly as much power to detect differences in potency as a bivariate response model fit.     

VaxArray assessment of influenza split vaccine potency and stability

Vaccine manufacturers require more rapid and accurate tools to characterize the potency and stability of their products. Currently, the gold standard for influenza vaccine potency is the single radial immunodiffusion (SRD) assay, which has inherent disadvantages. The primary objective of this study was to investigate the ability of the VaxArray Influenza (VXI) seasonal hemagglutinin (sHA) potency assay to accurately quantify potency and stability in finished vaccines as well as to quantify hemagglutinin protein (HA) within crude in-process samples. Monobulk intermediates and mono- and multivalent vaccines were tested using VXI. Quantification of HA in crude samples was evaluated by spiking known concentrations of HA into allantoic fluid. VXI generated SRD equivalent potency measurements with high accuracy (within ±10%) and precision (CV 10 ± 4%) for antigen components of monobulk intermediates and multivalent split vaccines. For these vaccines and vaccine intermediates, the VXI linear dynamic range was ∼0.01–0.6 μg/mL, which is 12× greater than the linear range of SRD. The measured sample limit of detection (LOD) for VXI varied from 0.005 to 0.01 μg/mL for the different subtypes, which in general is ≥600× lower than the LOD for SRD. VXI was able to quantify HA in crude samples where HA only accounts for 0.02% of the total protein content. Stability indication was investigated by tracking measured potency as a function of time at elevated temperature by both SRD and VXI. After 20 h at 56 °C, the ratio of VXI to SRD measured potency in a quadrivalent vaccine was 76%, 125%, 60%, and 98% for H1/California, H3/Switzerland, B/Phuket and B/Brisbane, respectively. Based on the study results, it is concluded that VXI is a rapid, multiplexed immunoassay that can be used to accurately determine flu vaccine potency and stability in finished product and in crude samples from upstream processes.     

Validation of alternative potency assays for influenza vaccines requires clinical studies

Readers of this Special Issue of Vaccine are likely unified by a desire to enhance vaccine efficacy and improve vaccine manufacturing efficiency. For influenza vaccines, challenges to achieving those goals are many, and range from improved surveillance to less cumbersome production platforms and more reliable performance verification. Specifically, demand is growing for an alternative vaccine potency assay. Assuming that a replacement potency assay is found to be promising, one question will be: how will it be judged to be accurate? It is generally agreed that any potential replacement for SRID will have to exhibit good correlation with SRID and yield a value within ±20% of the SRID determined potency. In my opinion, SRID itself has enough limitations that judging alternatives relative to that particular standard will not ensure that the industry as a whole transitions to an improved method. In fact, it could blind us to an assay that may ultimately provide a better predictive measure of vaccine efficacy (or immunogenicity). There is only one way to verify that measured potency is correlated with, and predictive of, measured immunogenicity – test the relationship in clinical studies.