Mid-term clinical efficacy of a volumetric magnetic resonance-guided high-intensity focused ultrasound technique for treatment of symptomatic uterine fibroids

Objective

To assess the mid-term efficacy of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) using a volumetric ablation technique for treating uterine fibroids.

Methods

Forty-six premenopausal women with 58 symptomatic uterine fibroids were prospectively included for MR-HIFU. After treatment, CE-MRI allowed measurement of the non-perfused volume (NPV) ratio, defined as the non-enhancing part of the fibroid divided by fibroid volume. Clinical symptoms and fibroid size on T2W-MRI were quantified at 3 and 6 months’ follow-up. The primary endpoint was a clinically relevant improvement in the transformed Symptom Severity Score (tSSS) of the Uterine Fibroid Symptom and Quality of Life questionnaire, defined as a 10-point reduction.

Results

Volumetric ablation resulted in a mean NPV ratio of 0.40 ± 0.22, with a mean NPV of 141 ± 135 cm³. Mean fibroid volume was 353 ± 269 cm³ at baseline, which decreased to 271 ± 225 cm³ at 6 months (P?<?0.001), corresponding to a mean volume reduction of 29 % ± 20 %. Clinical follow-up showed that 54 % (25/46) of the patients reported a more than 10-point reduction in the tSSS. Mean tSSS improved from 50.9 ± 18.4 at baseline to 34.7 ± 20.2 after 6 months (P?<?0.001).

Conclusion

Volumetric MR-HIFU is effective for patients with symptomatic uterine fibroids. At 6 months, significant symptom improvement was observed in 54 % of patients.

Key Points

? Volumetric MR-guided high-intensity focused ultrasound is a novel ablation technique for leiomyomatosis. ? We prospectively evaluated the outcome of volumetric MR-HIFU ablation for symptomatic fibroids. ? This study showed that volumetric MR-HIFU results in an effective treatment. ? A randomised controlled trial would set this technique in an appropriate context.     

Pars plana vitrectomy for disturbing primary vitreous floaters: clinical outcome and patient satisfaction

Background

Primary vitreous floaters can be highly bothersome in some patients. In the case of persistently bothersome floaters, pars plana vitrectomy may be the most effective treatment. The aim of this study is to evaluate the incidence of complications, and patient satisfaction, after pars plana vitrectomy for disabling primary vitreous opacities.

Methods

We included a total of 110 eyes that underwent pars plana vitrectomy between February 1998 and August 2010. Fifty-seven eyes (51.8 %) underwent 20-gauge vitrectomy, whereas 53 eyes (48.2 %) underwent 23-gauge vitrectomy. In a retrospective manner, we assessed intraoperative and postoperative complications. There was a considerable range of time between surgery and questionnaire (range: 4–136 months). Patient satisfaction was assessed by a questionnaire based on a modified NEI VFQ-25 questionnaire.

Results

A retinal detachment occurred in 10.9 % of cases, and the incidence did not differ significantly between the 20-gauge and 23-gauge vitrectomy groups. In 4.5 % of the eyes, a retinal detachment developed within the first 3 months, and 6.4 % occurred later in the postoperative period. Cystoid macular edema occurred in 5.5 %, and an epiretinal membrane was seen postoperatively in 3.6 % of cases. Development of glaucoma requiring glaucoma surgery, a macular hole, and postoperative scotoma, each occurred in 0.9 % of cases. No cases of endophthalmitis occurred. Eighty-five percent of patients were satisfied or very satisfied with the results of the vitrectomy. Eighty-four percent of all patients were completely cured from their troublesome vitreous floaters, and an additional 9.3 % of patients were less troubled by vitreous floaters. Ten patients (9.3 %) were dissatisfied, and six of these patients (5.6 %) had a serious complication that resulted in permanent visual loss.

Conclusions

Pars plana vitrectomy is an effective approach to treat primary vitreous floaters, resulting in a high rate of patient satisfaction. Postoperative complications may be more frequent than previously reported, so patients should be well-informed about the complication rate before reaching informed consent about this surgical intervention. Additional preventive measures should be considered to reduce this complication rate.     

The role of protein plasticity in computational rationalization studies on regioselectivity in testosterone hydroxylation by cytochrome P450 BM3 mutants

Recently, it was found that mutations in the binding cavity of drug-metabolizing Cytochrome P450 BM3 mutants can result in major changes in regioselectivity in testosterone (TES) hydroxylation. In the current work, we report the intrinsic reactivity of TES' C-H bonds and our attempts to rationalize experimentally observed changes in TES hydroxylation using a protein structure-based in silico approach, by setting up and employing a combined Molecular Dynamics (MD) and ligand docking approach to account for the flexibility and plasticity of BM3 mutants. Using this approach, about 100,000 TES binding poses were obtained per mutant. The predicted regioselectivity in TES hydroxylation by the mutants was found to be in disagreement with experiment. As revealed in a detailed structural analysis of the obtained docking poses, this disagreement is due to limitations in correctly scoring hydrogen-bonding and steric interactions with specific active-site residues, which could explain the experimentally observed trends in regioselectivity in TES hydroxylation.     

Sensitivity of Spontaneous Baroreflex Control of the Heart and Hemodynamic Parameters are Not Influenced by the Menstrual Cycle

Objective: The purpose of this study was to evaluate if hemodynamic parameters and sympathetic activity vary between the follicular and luteal phase of the menstrual cycle before using sympathetic activity in pre-pregnancy risk assessment for preeclampsia. Methods: We studied 39 healthy women at days 5 to 10 and days 18 to 25 of the menstrual cycle. Blood pressure, heart rate, cardiac output, and total peripheral resistance were measured continuously using noninvasive finger arterial pressure waveform registration (Portapres Model 2, BMI, The Netherlands). Baroreflex sensitivity (BRS) and sympathetic activity by phase angle difference were studied using spectral analysis and xBRS. Results: There were no differences in hemodynamic parameters, BRS, and phase angle difference. Conclusion: There is no difference in blood pressure, BRS, and sympathetic activity between the first and second half of the menstrual period. We recommend using the first half of the cycle to be certain that no pregnancy exists, as the influence of very early pregnancy is unknown.     

Development of a microarray for Enchytraeus albidus (Oligochaeta): preliminary tool with diverse applications

Standard bioassays allow hazard assessment at the population level, but much remains to be learned about the molecular level response of organisms to stressors. The main aim of this study was the development of a DNA microarray for Enchytraeus albidus, a common soil worm species. Further, this microarray was tested using worms exposed to Cu, phenmedipham, and different soil types. Hybridization onto the developed microarray revealed several genes with homology to known sequences. Genes of interest were confirmed through real-time polymerase chain reaction. It was possible to discriminate between natural and chemical stressors and chemical concentrations. Gene responses were detected under conditions known to have effects in the reproduction of individuals. It was confirmed that the integration of different endpoints improves the assessment process and enhances the understanding of the modes of action of stressors. The chemical stress-induced genes were related to factors such as immune response, stress response, metabolic processes, and/or signal transduction. The present study represents the first step of a gene-level study in the ecologically relevant and standard test species E. albidus. It demonstrates the usefulness of cDNA normalization in the production of cDNA libraries of ecotoxicological standard organisms that are not genome models like E. albidus.     

Physical environmental correlates of self-reported and objectively assessed physical activity in Belgian type 2 diabetes patients

Despite the well-known beneficial effects of physical activity (PA) on the long-term outcomes of type 2 diabetes patients, the majority of this patient group remains inactive. Therefore, it is necessary to understand the most important PA determinants in type 2 diabetes patients in order to develop efficacious interventions to increase PA participation. The main aim of this study was to investigate the associations of physical environmental factors with objectively assessed and self-reported PA in type 2 diabetes patients. A total of 133 type 2 diabetes patients participated in this cross-sectional study (response rate: 43.3%). All participants completed the long International PA Questionnaire and two validated questionnaires to measure physical environmental perceptions and psychosocial factors. They also wore an accelerometer and a pedometer to measure PA objectively. Selection criteria were age 35-80, BMI 25-35 kg m(-2), treated for type 2 diabetes and no PA limitations. Data were collected in 2007. Physical environmental factors contributed significantly to the explained variance of all objective and self-reported PA measures (explained variance from 4% to 18%) after controlling for sociodemographic variables. Home PA equipment, walkability, aesthetics and convenience of PA facilities were the most consistent environmental correlates. The contribution of physical environmental factors remained significant for most PA measures after taking into account the variance explained by psychosocial factors (explained variance from 4% to 10%), except for step counts and recreational walking. Physical environmental factors could be important correlates of PA in type 2 diabetes patients, even beyond the contribution of sociodemographic and psychosocial variables, but additional research is needed. Nevertheless, sociodemographic and psychosocial factors remain very important and when developing future interventions, all these multidimensional correlates should be kept in mind.