Sensitive approach and future perspectives in microscopic patterns of mycorrhizal roots.

The harmonization of methodologies for the assessment of radicular endophytic colonization is a current necessity, especially for the arbuscular mycorrhizas. The functionality of mycorrhizal symbionts for plants can be described only by indicators obtained based on microscopic analysis. That is the reason for which a unifying methodology will lead to the achievement of highly correlated indicators comparable from one research to another. Our proposed methodology can further digitize the microscopic observations of colonization. The MycoPatt system is developed as a methodological framework for obtaining objective and comparable microscopic observations. The horizontal, vertical and transversal indicators are highly adaptable and allow the tracking of mycorrhizal colonization in root length. All structures developed by symbionts can be traced and the obtained metadata can be compared without any transformation. Mycorrhizal maps have a high degree of applicability in evaluating soil inoculum efficiency. In the future, the application of this method will lead to digital maps with a high degree of accuracy. MycoPatt allows the mathematical expression of colonization patterns, being a complex model that converts biological data into statistically comparable indicators. This will further allow obtaining inferences with applicative importance and similarity spectra for the colonizing fungi and host plants.

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks.

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor.

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).

Quality of labour neuraxial analgesia and maternal satisfaction at a tertiary care teaching hospital: a prospective observational study.

PURPOSE: Current labour analgesia practices are evidence-based; however, such evidence often originates in controlled trials, the results of which may not be readily applicable in the context of day-to-day clinical practice. The objective of this study was to evaluate the effectiveness of and maternal satisfaction with the neuraxial labour analgesia regimen provided at a tertiary care teaching hospital. METHODS: All women with a viable pregnancy who requested neuraxial analgesia for labour during November 2011 at our institution were approached to participate in this prospective study. Patients were managed as per departmental routine based on a patient-controlled epidural analgesia regimen with a maintenance solution of 0.0625% bupivacaine and fentanyl 2 µg·mL(-1). Demographic and obstetric data, characteristics of the neuraxial analgesia, pain scores, side effects, and complications were recorded. After delivery, patients completed a satisfaction questionnaire. RESULTS: All 332 eligible women were approached, and 294 completed the study. Most women received epidural analgesia and considered its placement comfortable. A large number of women reported having experienced pain during the first or second stages of labour (38% and 26%, respectively). Although 24.4% of women required top-ups both by nurses and physicians, adjustment in the local anesthetic maintenance concentration was made in only 7.8% of the cases. Most women (92%) were satisfied with the quality of analgesia. Unintentional dural puncture occurred in three (1%) cases, and there were no cases of intravascular catheter insertion or systemic local anesthetic toxicity. Overweight women (body mass index 25-30 kg·m(-2)) (adjusted odds ratio [AOR] = 2.56; 95% confidence interval [CI]: 1.1 to 5.97), those undergoing induced labour (AOR = 2.4; 95% CI: 1.2 to 5.2), and those requiring top-ups by the anesthesiologist (AOR = 5.08; 95% CI: 2.31 to 11.11) were associated with more dissatisfaction with pain control during the first stage of labour. CONCLUSION: Although our technique with dilute local anesthetic-opioid infusion was considered effective in previous randomized clinical trials, it did not provide sufficient labour analgesia for a large proportion of women. Nevertheless, most women were satisfied with their pain management and childbirth experience. Strategies to individualize care for labour and delivery should be readily available while providing labour analgesia.