Laparoscopic uterosacral ligament colpopexy for apical support in addition to hysterectomy for pelvic organ prolapse.

AIM: To evaluate the perioperative complications and the anatomical outcomes of our laparoscopic uterosacral ligament (USL) colpopexy, which is a novel laparoscopic technique for the management of uterine prolapse. The objective was to report on outcome after 2 years of a technique using laparoscopic USL colpopexy. METHODS: A total of 152 uterine prolapse patients underwent laparoscopic USL colpopexy from May 2013 to April 2015. We described the surgical technique and performed a retrospective analysis of this laparoscopic technique. Patients underwent standardized assessment and examination using pelvic organ prolapse quantification (POP-Q) score. The dependent values of Ba point (bladder), C point (vaginal cuff) and Bp point (rectum) were recorded preoperatively, and at 1, 3, 6, 12 and 24 months of postoperative examination. Pre/postoperative data were compared using the Kaplan-Meier method. RESULTS: Mean age, operative time and amount of hemorrhage were 68.2 ± 7.5 years, 118.3 ± 36.4 min and 60.5 ± 73.3 mL, respectively. Overall recurrent prolapse, which was defined as POP-Q stage II or higher, was noted in 29 patients (19%). However, only 2 patients presented recurrent rectocele among 51 patients with preoperative POP-Q stage II of uterine prolapse alone (recurrence rate; 3.9%). The pre/postoperative average POP-Q scores were -0.2/-2.7 cm (P < 0.05) at Ba point, -1.9/-5.1 cm (P < 0.05) at C point and -2.4/-2.3 cm (P = 0.06) at Bp point. CONCLUSION: Laparoscopic visualization of uterosacral ligaments may result in safe colpopexy. Our results show this will be a useful procedure for apical support as native tissue repair.

The Arabidopsis USL1 controls multiple aspects of development by affecting late endosome morphology.

The polar transport of auxin controls many aspects of plant development. However, the molecular mechanisms underlying auxin tranport regulation remain to be further elucidated. We identified a mutant named as usl1 (unflattened and small leaves) in a genetic screen in Arabidopsis thaliana. The usl1 displayed multiple aspects of developmental defects in leaves, embryogenesis, cotyledons, silique phyllotaxy and lateral roots in addition to abnormal leaves. USL1 encodes a protein orthologous to the yeast vacuolar protein sorting (Vps) 38p and human UV RADIATION RESISTANCE-ASSOCIATED GENE (UVRAG). Cell biology, Co-IP/MS and yeast two-hybrid were used to identify the function of USL1. USL1 colocalizes at the subcellular level with VPS29, a key factor of the retromer complex that controls auxin transport. The morphology of the VPS29-associated late endosomes (LE) is altered from small dots in the wild-type to aberrant enlarged circles in the usl1 mutants. The usl1 mutant synergistically interacts with vps29. We also found that USL1 forms a complex with AtVPS30 and AtVPS34. We propose that USL1 controls multiple aspects of plant development by affecting late endosome morphology and by regulating the PIN1 polarity. Our findings provide a new layer of the understanding on the mechanisms of plant development regulation.

MRI classification of uterosacral ligament involvement in endometriosis: the Hôtel-Dieu classification.

OBJECTIVE: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep infiltrating endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis. METHODS: Twenty-two women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analysed retrospectively, blinded to histopathology, and a classification of the preoperative aspect of USLs linked to PPVs was designed. RESULTS: According to their aspects, 6 radiological types of USL were identified. The "L-category" corresponded to linear types with regular or irregular margins, including types 1, 2, 3A, and 3B. The "N-category" corresponded to haemorrhagic or nodular types, including types 4, 5A, 5B, and 6. For the L-category, PPVs ranged from 75% to 88%, depending on the USL radiological type. For the N-category, PPVs were 100% for each type. In women with endometriosis symptoms, MRI underestimated USL involvement, especially for type 1. Among the 6 uteri with lateral deviation, only one false-positive result concerning the stretched USL was induced. CONCLUSIONS: In women with endometriosis symptoms, our MRI classification identified 2 USL categories, corresponding to 2 kinds of PPV; in these symptomatic patients, a normal MRI does not rule out a DIE diagnosis. ADVANCES IN KNOWLEDGE: Our MRI classification of USL involvement in endometriosis may be used as a non-invasive staging of the disease, making it much clearer for clinicians and patients. Hence, we are able to propose a suitable diagnostic and therapeutic procedure for each radiological type.

Comparative steady-state pharmacokinetic evaluation of immediate-release topiramate and USL255, a once-daily extended-release topiramate formulation.

PURPOSE: Compare the pharmacokinetic (PK) profiles of immediate- and extended-release formulations of topiramate (TPM) in healthy subjects following multiple dosing, and evaluate maintenance of topiramate exposures after switching formulations. METHODS: A randomized, open-label, single-center, two-way crossover, multiple-dose study comparing the steady-state PK profile of once-daily extended-release topiramate (USL255) to immediate-release topiramate (TPM-IR) administered twice-daily. The TPM PK profile was evaluated using standard PK parameters (e.g., AUC0-24 , Cmax , Cmin ) as well as less common PK criteria such as fluctuation index (FI), peak occupancy time (POT), and percent coefficient of variation (%CV). In addition, partial AUC (AUCp ) analyses provided comparisons of the AUC profiles over predetermined time intervals between TPM-IR and USL255. Pharmacokinetic equivalence between formulations was defined as containment of the 90% confidence intervals (CIs) of the USL255/TPM-IR geometric least-squares mean (GLSM) ratio within the equivalence limits of 80-125%. The effect of switching between treatments was assessed by evaluating equivalence of PK parameters between the day prior to formulation switch and the day immediately following formulation switch. Maintenance of steady state after switching formulations was also evaluated by comparing the slope between Cmin values at formulation switch and 24 h postswitch. Tolerability was evaluated through adverse event monitoring, vital sign measurements, and clinical laboratory evaluations. KEY FINDINGS: USL255 was well tolerated and provided TPM plasma exposure equivalent to TPM-IR at various time intervals. USL255 also demonstrated a significantly lower Cmax (p < 0.001) and higher Cmin (p < 0.001), longer tmax , lower %CV, and 26% decreased FI, as compared with TPM-IR. Further, switching between TPM-IR and USL255 did not affect TPM concentrations, including Cmin , immediately after transitioning and at steady state. SIGNIFICANCE: As compared with TPM-IR, USL255 provided equivalent plasma exposure with an extended absorption profile. Therefore, USL255 offers a once-daily alternative to twice-daily TPM-IR, with reduced TPM fluctuations.