Nd:YAG/Er:YAG dual laser compared with topical steroid to treat vulvar lichen sclerosus: A randomised controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a novel non-ablative Nd:YAG/Er:YAG dual laser treatment for vulvar lichen sclerosus (LS) in comparison with the recommended first-line therapy with topical steroid. DESIGN: A randomised investigator-initiated active-controlled trial. SETTING: Single tertiary referral centre. POPULATION: Women with vulvar LS. METHODS: Randomisation (2:1) to Nd:YAG/Er:YAG laser therapy or topical clobetasol proprionate therapy. Four laser treatments at 0, 1, 2 and 4 months or decreasing doses of steroid for 6 months. MAIN OUTCOME MEASURES: The primary outcome was the change in objective validated clinical LS score in the laser arm between baseline and 6 months. Secondary outcomes were laser tolerability/safety, symptom scores and patient satisfaction. RESULTS: Sixty-six women were included, 44 in the laser group and 22 in the steroid group. The total LS score decreased by -2.34 ± 1.20 (95% CI -2.71 to -1.98) in women treated with laser compared with a decrease of -0.95 ± 0.90 (95% CI -1.35 to -0.56) in those receiving steroid applications (p < 0.001). Laser treatment was safe and well tolerated. Subjective severity scores (on visual analogue scale) and vulvovaginal symptoms questionnaire scores improved similarly for the laser and steroid arms without significant differences between the two treatments. Patient satisfaction was higher in the laser arm than in the steroid arm (p = 0.035). CONCLUSIONS: Non-ablative dual Nd:YAG/Er:YAG laser therapy was safe and significantly improved clinical outcome and subjective symptoms at the 6-month follow up. This suggests that laser may be a promising alternative to corticosteroid therapy. However, the authors caution regular follow ups because of the premalignant nature of the disease.

Nd:YAG/Er:YAG dual laser vs. topical steroid to treat vulvar lichen sclerosus: study protocol of a randomized controlled trial.

PURPOSE: Vulvar lichen sclerosus (LS) is a chronic debilitating inflammatory skin disease. Today, the gold standard is a life-long topical steroid treatment. Alternative options are highly desired. We present a study protocol of a prospective, randomized, active-controlled, investigator-initiated clinical trial comparing a novel non-invasive dual Nd:YAG/Er:YAG laser therapy with the gold standard for the management of LS. METHODS: We recruited 66 patients, 44 in the laser arm and 22 in the steroid arm. Patients with a physician-administered clinical LS score ≥ 4 were included. Participants received either four laser treatments 1-2 months apart, or 6 months of topical steroid application. Follow-ups were planned at 6, 12, and 24 months. The primary outcome looks at the efficacy of the laser treatment at the 6-month follow-up. Secondary outcomes look at comparisons between baseline and follow-ups within the laser or the steroid arm, and comparisons between laser vs. steroid arm. Objective (LS score, histopathology, photo documentation) and subjective (Vulvovaginal Symptoms Questionnaire, symptom VAS score, patient satisfaction) measurements, tolerability, and adverse events are evaluated. CONCLUSION: The findings of this trial have the potential to offer a novel treatment option for LS. The standardized Nd:YAG/Er:YAG laser settings and the treatment regime are presented in this paper. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT03926299.

Combination therapy with botulinum toxin and bulking agent-An efficient, sustainable, and safe method to treat elderly women with mixed urinary incontinence.

AIMS: To evaluate the efficacy, sustainability and safety of combined botulinum toxin and polyacrylamide hydrogel (PAHG) therapy to treat urgency and stress components of therapy-refractory mixed urinary incontinence (MUI) in an elderly study population. METHODS: Fifty-five women with therapy-refractory MUI were treated with botulinum toxin and PAHG in one surgical procedure. Urgency urinary incontinence (UUI) and stress urinary incontinence (SUI) outcomes were separately assessed after 4 and 12 months by objective UUI episodes/24 h and cough test, subjective impact of UUI and SUI on quality of life, and subjective International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). MUI outcome was calculated by combining UUI and SUI outcomes. Complications were monitored throughout the study. RESULTS: At 4 months, objective cure rates were 73%, 53%, and 42%, and subjective cure rates were 71%, 52%, and 50% for SUI, UUI, and MUI. At 12 months, objective cure rates were 73%, 56%, 50% and subjective cure rates were 78%, 42%, and 40% for SUI, UUI, and MUI. The ICIQ-UI SF score decreased by 9.0 and 8.7 points after 4 and 12 months. All complications were transient and included 22% clean intermittent catheterization immediately after surgery, 33% postvoid residual volumes >100 ml at 14 days, and 13% symptomatic urinary tract infection within the first postoperative month. CONCLUSIONS: The combination of botulinum toxin and PAHG is effective, sustainable and safe to treat therapy-refractory MUI, even in an elderly and frail study population. Patients benefit from the short surgical procedure without the need for general anaesthesia or discontinuation of anticoagulation.

Erbium:YAG laser treatment of female stress urinary incontinence: midterm data.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is treated using intravaginal laser therapy. We wanted to find out how incontinence severity at baseline and the number of laser interventions affect success rate, and whether the effect of laser therapy was obvious 6 months and 2 years after the last laser intervention. METHODS: Fifty-nine women, 32 with SUI I, 16 with SUI II, and 11 with SUI III were treated using an erbium-doped yttrium aluminium garnet (Er:YAG) laser following the IncontiLase® protocol. Therapy included five laser sessions with a 1-month interval between sessions. Objective (1-h pad test) and subjective data (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form [ICIQ-UI SF], Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire [PISQ-12]) were assessed at baseline, after two and four laser sessions and 6 months and 2 years after the fifth laser session. RESULTS: Objective cure/improve rates for mild SUI I were 69%, 78%, 91%, and 78% after two, four, and five laser sessions at the 6-month and 2-year follow-ups. Subjective cure rates (ICIQ-UI SF) were 53%, 69%, 72%, and 66%, and sexual function (PISQ-12) also improved. For SUI II, objective cure/improve rates were 31%, 63%, 69%, and 50%. Subjective cure rate was 13% at the 2-year follow-up. For SUI III, only one patient had an objective improvement after two and four laser sessions. CONCLUSIONS: Intravaginal laser therapy led to cure/improvement for SUI I and SUI II, but not for severe SUI III. Outcome was better after four to five laser sessions than after two laser sessions. Follow-up data 6 months and 2 years after laser intervention showed sustainability of the treatment.

[Acute and recurrent urinary tract infections in women presenting in primary practice]. / Akute und rezidivierende Harnwegsinfekte der Frau in der allgemeinmedizinischen Praxis.

Acute and recurrent urinary tract infections in women presenting in primary practice Abstract. Acute and recurrent urinary tract infections in women of all age groups are becoming an increasing problem in primary care and medical practice. Symptoms can be relieved by a guideline-oriented acute therapy and a multimodal infection prophylaxis. The restoration of the body's natural defence mechanisms plays a central role. This article informs about the causes, the basic diagnostic examinations and the practical use of therapeutic and prophylactic measures.

Current Treatment Concepts for Stress Urinary Incontinence.

Initially, stress urinary incontinence should be treated by conservative measures, such as weight reduction, hormonal substitution, physiotherapy, pelvic floor exercise and/or the use of pessaries. Incontinence surgeries are only recommended in case of unsuccessful conservative therapy. Today, tension-free suburethral sling insertions represent the gold standard of incontinence surgery yielding very good outcomes (cure rates of 80­90 %). Pelvic-floor sonography provides important information on decision of surgical methods and the management of complications. Furthermore, intra- or paraurethral injection of bulking agents is a promising, minimally invasive surgical alternative. This article discusses treatment concepts, pre-, intra- and post-operative examinations, decision on surgical methods, operational details for surgical success, and the prevention and management of complications.

Role of intrinsic sphincter deficiency with and without urethral hypomobility on the outcome of tape insertion.

AIMS: Intrinsic sphincter deficiency (ISD) is a known risk factor for therapy failure after tension-free vaginal tape (TVT) insertion. The purpose of this study was to investigate if the severity of ISD alone or other factors such as urethral mobility and tape localization influence outcomes. METHODS: One hundred and nine women with urodynamically determined ISD, a TVT insertion, and a 6-month follow-up visit were included. Urethral length, mobility, and tape localization were evaluated by pelvic floor sonography. Patients were classified into three urethral mobility groups (hypomobile, normomobile, hypermobile). Surgical outcome was assessed by a combination of objective and subjective criteria. RESULTS: Therapeutic success rate after TVT insertion was 81.6%. The severity of ISD did not associate with therapy failure. But urethral mobility (P < 0.0001), relative tape position (P = 0.0003), and tape-urethra distance (P < 0.0001) differed between cured and not cured patient groups. Patients with a relative tape position toward 1/2 of urethral length had a higher cure rate. Significantly different cure rates (P = 0.0003) were found for hypomobile (67%), normomobile (76%), and hypermobile (100%) urethras. For ISD patients with a hypomobile urethra, highest cure rates were obtained for tape-urethra distances between 2.5 and 3.5 mm. CONCLUSIONS: The reduced cure rate for ISD patients was due to the subgroup with a hypomobile urethra. A prospective study is needed to confirm that slightly shorter tape-urethra distances and a relative tape position more toward the mid-urethra will lead to better outcomes for this patient group.

Urethral bulking for recurrent stress urinary incontinence after midurethral sling failure.

AIMS: To assess the effectiveness of a polyacrylamide hydrogel (PAHG; Bulkamid®) in treating recurrent stress urinary incontinence (SUI) following a previous midurethral sling (MUS) implant. METHODS: This observational study, conducted since 2009, included 60 patients with recurrent SUI or mixed urinary incontinence (MUI) after a previous MUS and who chose to be treated with PAHG. Objective and subjective outcomes were assessed at 1, 6, and 12 months after the initial injection. Patients were classified as cured based on a negative cough test (supine and standing) and <2 g urine on 1-hr pad test and a VAS score improved by ≥90%. Improved were those with the loss of only a few drops of urine during the cough test and 2-10 g urine on 1-hr pad test or a reduction >50% compared with preoperative urine loss and a VAS score improved by ≥75%. RESULTS: The volume of PAHG injected in the current study ranged from 1-3 ml. Cured/improved rates were 93.3% (56/60), 88.3% (53/60), and 83.6% (46/55) at 1, 6, and 12 months, respectively. Patients with MUI had a cured urgency urinary incontinence rate of 36.8%, 47.4%, and 38.9%, respectively. Voiding dysfunction rates were 13.3% (8/60), 8.3% (5/60), and 1.8% (1/55) at 1, 6, and 12 months and urinary tract infection rates were 5% (3/60), 11.7% (7/60), and 3.6% (2/55), respectively. Other adverse events were short-term and/or observed in <4% of patients. CONCLUSIONS: PAHG can be used to treat recurrent SUI after MUS failure with good outcome and low complication rates. Neurourol. Urodynam. 36:722-726, 2017. © 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

Transcript clearance during the maternal-to-zygotic transition.

In all animals, a key event in the transition from maternal control of development to control by products of the zygotic genome is the elimination of a significant fraction of the mRNAs loaded into the egg by the mother. Clearance of these maternal mRNAs is accomplished by two activities: the first is maternally encoded while the second requires zygotic transcription. Recent advances include identification of RNA-binding proteins that function as specificity factors to direct the maternal degradation machinery to its target mRNAs; small RNAs-most notably microRNAs-that function as components of the zygotically encoded activity; signaling pathways that trigger production and/or activation of the clearance mechanism in early embryos; and mechanisms for spatial control of transcript clearance.

Distinct roles of the Pumilio and FBF translational repressors during C. elegans vulval development.

The C. elegans PUF and FBF proteins regulate various aspects of germline development by selectively binding to the 3' untranslated region of their target mRNAs and repressing translation. Here, we show that puf-8, fbf-1 and fbf-2 also act in the soma where they negatively regulate vulvaI development. Loss-of-function mutations in puf-8 cause ectopic vulval differentiation when combined with mutations in negative regulators of the EGFR/RAS/MAPK pathway and suppress the vulvaless phenotype caused by mutations that reduce EGFR/RAS/MAPK signalling. PUF-8 acts cell-autonomously in the vulval cells to limit their temporal competence to respond to the extrinsic patterning signals. fbf-1 and fbf-2, however, redundantly inhibit primary vulval cell fate specification in two distinct pathways acting in the soma and in the germline. The FBFs thereby ensure that the inductive signal selects only one vulval precursor cell for the primary cell fate. Thus, translational repressors regulate various aspects of vulval cell fate specification, and they may play a conserved role in modulating signal transduction during animal development.