Bothersome Condition Research Articles

(166) Surgical Excision and Grafting with Simultaneous Dorsal Plication for Ventral Plaque Accompanied by Urethral Tethering

Abstract Introduction Peyronie's disease, a condition characterized by penile curvature, approximately affects 9% of men. Surgical interventions are often employed to address this bothersome condition, and these can include techniques such as plication of the tunica albuginea, incision, or excision of the plaque with grafting procedures, and penile prosthesis implantation. The recommended treatment options vary depending on the specific constellation of symptoms and underlying conditions experienced by the patient. Objective We present a case of severe ventral curvature and penile shortening due to urethral tethering, resulting in residual curvature even after undergoing plaque excision and grafting. Methods The patient is a 65-year-old gentleman with a history of metastatic renal cell carcinoma, deep vein thrombosis status post inferior vena cava filter placement as well as anticoagulation with apixaban, and diabetes mellitus who presented with a complaint of progressive penile curvature over his past 12 months. His secondary complaints included difficulty and pain with intercourse. He noted a 90-degree ventral erection. He denies any history of penile trauma, surgery, or pelvic radiation, though he did report chest radiation for his metastatic kidney cancer. Penile doppler noted a large ventral mid penile plaque measuring 9.5x7.7x5 mm. Due to the severe, bothersome curvature, the patient was recommended excision and grafting (Tutoplast). Intraoperatively, a 2.5 cm x 3.0 cm plaque was excised and a Tutoplast pericardial allograft was used to cover the corporal defect. However, due to urethral tethering the patient still had residual curvature. We opted to perform a dorsal tunica albuginea plication using the Lue 16 dot technique. Results Penile plication remains a tool in the armamentarium of the reconstructive urologist and andrologist for penile curvature arising from Peyronie’s disease. However, in the setting of severe curvature, the penile length loss arising from plication alone can be prohibitive. Therefore incision, or excision with grafting has been implemented with significant sparing of penile length. On the other hand, there is a limit to which length can be maintained and occasionally the tethering of the corpus spongiosum can result in residual curvature. Contralateral tunical plication is therefore an option to be performed concomitantly with grafting procedures. This combination is uncommon but has been reported. In our approach, the patient’s severe curvature was improved with ventral plaque excision and grafting. However, his residual curvature at this stage was able to be corrected with minimal effect on his penile length by applying a dorsal plication technique with minimal additional risk. During the follow-up after the surgery, the patient reported a smooth recovery without any complications. There was no residual curvature, and the patient was able to achieve normal erections sufficient for intercourse without the need for additional measures. Conclusions The correction of severe ventral curvature deformity can be challenging, the surgeon should be prepared to perform additional correction procedures if penile straightening was limited by the tethering of the neurovascular bundle or urethra. Excision and grafting of ventral plaque with concomitant dorsal tunica plication for residual curvature in settings of urethral tethering is a safe viable and effective option with excellent functional results. Disclosure No.

(191) Excision and Grafting with Concomitant Dorsal Plication for Ventral Plaque with Urethral Tethering

Abstract Introduction Peyronie's disease, a condition characterized by penile curvature, approximately affects 9% of men. Surgical interventions are often employed to address this bothersome condition, and these can include techniques such as plication of the tunica albuginea, incision or excision of the plaque with grafting procedures, and penile prosthesis implantation. The recommended treatment options vary depending on the specific constellation of symptoms and underlying conditions experienced by the patient. Objective We present a case of severe ventral curvature and penile shortening due to urethral tethering, resulting in residual curvature even after undergoing plaque excision and grafting. Methods The patient is a 65-year-old gentleman with a history of metastatic renal cell carcinoma, deep vein thrombosis status post inferior vena cava filter placement as well as anticoagulation with apixaban, and diabetes mellitus who presented with a complaint of progressive penile curvature over his past 12 months. His secondary complaints included difficulty and pain with intercourse. He noted a 90-degree ventral erection. He denies any history of penile trauma, surgery, or pelvic radiation, though he did report chest radiation for his metastatic kidney cancer. Penile doppler noted a large ventral mid penile plaque measuring 9.5x7.7x5 mm. Due to the severe, bothersome curvature, the patient was recommended excision and grafting (Tutoplast). Intraoperatively, a 2.5 cm x 3.0 cm plaque was excised and a Tutoplast pericardial allograft was used to cover the corporal defect. However, due to urethral tethering the patient still had residual curvature. We opted to perform a dorsal tunica albuginea plication using the Lue 16 dot technique. Results Penile plication remains a tool in the armamentarium of the reconstructive urologist and andrologist for penile curvature arising from Peyronie’s disease. However, in the setting of severe curvature, the penile length loss arising from plication alone can be prohibitive. Therefore incision, or excision with grafting has been implemented with significant sparing of penile length. On the other hand, there is a limit to which length can be maintained and occasionally the tethering of the corpus spongiosum can result in residual curvature. Contralateral tunical plication is therefore an option to be performed concomitantly with grafting procedures. This combination is uncommon but has been reported. In our approach, the patient’s severe curvature was improved with ventral plaque excision and grafting. However, his residual curvature at this stage was able to be corrected with minimal effect on his penile length by applying a dorsal plication technique with minimal additional risk. During the follow-up after the surgery, the patient reported a smooth recovery without any complications. There was no residual curvature, and the patient was able to achieve normal erections sufficient for intercourse without the need for additional measures. Conclusions The correction of severe ventral curvature deformity can be challenging, the surgeon should be prepared to perform additional correction procedures if penile straightening was limited by the tethering of the neurovascular bundle or urethra. Excision and grafting of ventral plaque with concomitant dorsal tunica plication for residual curvature in settings of urethral tethering is a safe viable and effective option with excellent functional results. Disclosure No.

A Pre-Voiding Alarm System Using Wearable Ultrasound and Machine Learning Algorithms for Children With Nocturnal Enuresis.

Nocturnal enuresis is a bothersome condition that affects many children and their caregivers. Post-voiding systems is of little value in training a child into a correct voiding routing while existing pre-voiding systems suffer from several practical limitations, such as cumbersome hardware, assuming individual bladder shapes being universal, and being sensitive to sensor placement error. Methods: A low-voltage ultrasound system with machine learning has been developed in estimating bladder filling status. A custom-made flexible 1D transducer array has been excited by low-voltage coded pulses with a pulse compression technique for an enhanced signal-to-noise ratio. In order to minimize the negative influence of possible transducer misplacement, a multiple-position training strategy using machine learning has been adopted in this work. Three popular classification methods, KNN, SVM and sparse coding, have been utilized to classify the acquired different volumes ranging from 100 ml to 300 ml into two categories: low volume and high volume. The low-volume category requires no further action while the high-volume category triggers an alarm to alert the child and caregiver. Results: When the sensor placement is ideal, i.e., the position of the practical sensor placement is on spot with the trained position, the precision and recall of the classification using sparse coding are [Formula: see text] and [Formula: see text], respectively. Even if the transducer array is misplaced by up to 4.5 mm away from the ideal location, the proposed system is able to maintain high classification accuracy (precision [Formula: see text] and recall [Formula: see text]). Category: Early/Pre-Clinical Research Clinical and Translational Impact: The proposed ultrasound sensor system for nocturnal enuresis is of significant clinical and translational value as it addresses two major issues that limit the wide adoption of similar devices. Firstly, it offers enhanced safety as the entire system has been implemented in the lowvoltage domain. Secondly, the system features ample tolerance to sensor misplacement while maintaining high classification accuracy. These features combined provide a much more user-friendly environment for children and their caregivers than existing devices.

Female sexual medicine: an assessment of medical school curricula in a major United States city.

Although approximately 41% of women experience sexual dysfunction, limited education on female sexual medicine (FSM) in medical school results in underpreparedness among physicians when addressing these bothersome conditions. This study aims to evaluate the extent to which FSM is represented in medical education by examining current preclinical and clinical curricula. Preclinical curriculum materials on female sexual anatomy, physiology, and pathology, as well as obstetrics and gynecology clinical materials (syllabi, lecture materials, and supplemental resources), were collected from medical schools in the Chicago area. We utilized previous literature to identify specific components of medical school content to evaluate. Upon reviewing each institution's curricula, we evaluated materials for topic saturation and assessed goals of each syllabus in terms of required content. Curriculum materials were collected from 7 medical schools. In the preclinical assessment, 1 institution identified all anatomic components of the clitoris in our review, 4 discussed the physiology of the female orgasm, 3 highlighted the prevalence and epidemiology of female sexual dysfunction (FSD), 3 addressed treatments for FSD, and 1 instructed a genitourinary physical exam specific to assessing FSD. When assessing obstetrics and gynecology clinical materials, 5 institutions included topics related to FSM. Of these, only 1 institution had corresponding required synchronous clerkship time dedicated to these topics as a 1-hour lecture, in addition to an optional online training to third-year clinical students in comprehensive sexual history-taking practices, including screening for FSD. One other institution offered supplemental case-based gynecology modules including vulvovaginal diseases and chronic pelvic pain, though sexual pleasure, arousal, and libido were not included. The results of this study highlight the need for the inclusion of standardized curricula related to FSM in medical education to equip future physicians to treat patients with sexual dysfunction. The strengths of this study include that it is the first of its kind to complete a comprehensive review of FSM curricula at a cohort of undergraduate medical institutions. Its limitations include a small sample size of 7 medical schools limited to 1 geographical area. Our focused needs assessment of medical schools in the Chicago area reveals inconsistencies in outlined institution-specific course goals related to FSM and thus highlights the need for restructuring the curricula to prepare future physicians to recognize and treat patients with sexual dysfunction.

Intralesional Measles, Mumps and Rubella Vaccine versus Formic Acid Puncture in the Treatment of Common Warts: A Prospective Randomised Study.

Many therapeutic modalities have been reported for the treatment of warts: a common bothersome condition; however, no single treatment is completely effective. This study aimed to evaluate the efficacy and safety of intralesional injection of measles, mumps and rubella (MMR) vaccine and to compare its efficacy with 85% formic acid puncture for common warts. This was a prospective comparative study. A total of 60 patients, divided into two groups, were included in the study. Group A received an intralesional MMR vaccine of 0.3 ml per lesion, and group B received 85% formic acid puncture into each lesion with a maximum of 10 warts treated in each case. Five sessions were conducted every 2 weeks in each case with a follow-up period of 3 months to check for recurrence. The Chi-square test, Fisher's test and t-test were used for statistical analysis. A P-value <0.05 was considered statistically significant. In group A, the complete response was observed in 62.5%, partial response in 8% and no response in 4.1% of patients. In group B, the complete response was observed in 31.8%, partial response in 63.6% and no response in 4.5% of patients. The difference in cure rates was found to be statistically significant with a P value of 0.031. No recurrence was observed in both groups in the follow-up period. Immunotherapy by intralesional MMR vaccine is a simple, well-tolerated, effective and cost-benefit modality for the treatment of warts and showed a statistically significant cure rate than formic acid therapy.

Anatomical and functional outcomes after bilateral sacrospinous colposuspension (BSC) for the treatment of female genital prolapse

BackgroundPelvic organ prolapse is a bothersome condition affecting many women at advanced age, but also frequently observed in young women with certain risk factors. Various surgical techniques have been developed with the aim of providing effective surgical treatment for apical prolapse. The vaginal bilateral sacrospinous colposuspension surgery (BSC) with ultralight mesh and utilization of the i- stich is a relatively new minimal invasive technique with very promising outcomes. The technique offers apical suspension, in the presence or absence of the uterus. The objective of this study is to evaluate the anatomical and functional outcomes of bilateral sacrospinous colposuspension with ultralight mesh in 30 Patients treated with the vaginal single incision standardized technique.MethodsIn this retrospective study, 30 patients were treated by BSC for significant vaginal, uterovaginal or cervical prolapse. A simultaneous anterior colporrhaphy, posterior colporrhaphy or both were performed when indicated. Anatomical and functional outcomes were assessed 1 year postoperatively using the Pelvic Organ Prolapse Quantification system (POP-Q) and the standardised Prolapse Quality of Life (P-QOL) questionnair.ResultsThe POP-Q parameters were significantly improved at twelve months after surgery compared to baseline. The total score and all four subdomains of the P-QOL-questionnaire showed positive trends and improvement at twelve months after surgery when compared to preoperative values. All patients were asymptomatic and expressed high satisfaction one year after surgery. No intraoperative adverse events were recorded for all patients. Only minimal postoperative complications were recorded and they all resolved completely with conservative management.ConclusionThis study highlights the functional and anatomical outcomes of the minimally invasive vaginal bilateral sacrospinal colposuspension with ultralight mesh for the management of apical prolapse. The one year postoperative results of the proposed procedure reflect excellent outcomes with minimal complications. The data published here are very promising and warrant further investigations and more studies to evaluate the long-term outcomes of BSC in the surgical management of apical defects.Trial registrationThe study protocol was approved by the Ethics Committee at the University Hospital of Cologne, Germany (Date of registration: 08.02.2022) (Registration number: 21-1494-retro) (retrospectively registered).

EFFICACY OF TRISUGANDHA ARKA KAVALA IN THE MANAGEMENT OF MUKHADOURGANDHYA WITH REFERENCE TO HALITOSIS

Mukhadourgandhya is mentioned in many Ayurvedic diseases; likewise, halitosis can be seen in many diseases. Mukhadourgandhya (halitosis) is quite an embarrassing and bothersome condition. Causative factors for Mukhadourgandhya are oral unhygienic, dental causes, throat disorders and non-oral causes like gastritis, etc. Among 10 people, 7 of them show this condition. Using the chlorohexidine solution for gargling shows various side effects. In this present study, Trisugandha Arka, an Ayurvedic formulation mentioned in the Ayurvedic text on Mukhadourgandhya, was selected, and the Arka formulation was prepared as mentioned in the text. Kavala was selected as the mode of administration as this procedure is indicated in Mukhadourgandhya condition. 5 patients of mukhadourgandhya (halitosis) condition were given Trisugandha Arka for Kavala for 7 days. The assessment of the condition was done before and after treatment. The result of the study was assessed after comparing the condition before and after the completion of the study. The Trisugandha Arka has aromatic oil and antimicrobial action and Vata-Kapha Hara properties which prove effective in the condition of Mukhadourgandhya.

Bladder Wall Structure Alterations in Patients Treated With Botulinum Toxin for Detrusor Overactivity - A Morphological Study.

The overactive bladder syndrome (OAB) is a bothersome condition that affects up to 33% of the population. In up to 69% of the cases, the underlying condition is an overactive detrusor (DO). Treatment options rely on behavioral changes, medical treatment, neuromodulation, and invasive treatment, such as injecting botulinum toxin (BoNT) in the detrusor or augmentation cystoplasty. The aim of this study was to evaluate, by morphological assessment on cold-cup biopsies of the bladder, the effect of botulinum toxin injections on the bladder wall, focusing on the histological structure and signs of inflammation and fibrosis. We evaluated consecutive patients with DO that received BoNT intradetrusor injections. We analyzed inflammation and fibrosis in 36 patients, divided into two groups based on their history of BoNT treatment. Our patients underwent at least one round of injections and specimens were compared individually, before and after each injection. A decrease in inflammation was found in 26.3% of the cases, a reactive increase in 31.5%, and no change in 42.1%. No de novo or increase in preexisting fibrosis was found. In some cases, fibrosis diminished after a second round of BoNT. In most cases, BoNT intradetrusor injections in DO patients showed no effect on bladder wall inflammation and actually improved the inflammatory condition of the muscle in a significant number of samples.

Elevated Level of Serum Neurotrophin-4, but Not of Brain-Derived Neurotrophic Factor, in Patients with Chronic Kidney Disease-Associated Pruritus.

Chronic kidney disease-associated pruritus (CKD-aP) is a bothersome condition that occurs in patients with advanced chronic kidney disease (CKD) and severely reduces their quality of life. Recently, much research has focused on the search for markers that are involved in the pathogenesis of CKD-aP and may become a therapeutic target. One of the suggested hypotheses is the increased activation of sensory neurons by molecules such as neurotrophins (NTs). An increased serum concentration of NTs has been demonstrated in pruritic patients, which may suggest their involvement in the pathogenesis of itch. The purpose of this study is to assess the serum concentration of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) in hemodialysis patients. The study enrolled 126 patients undergoing dialysis. Participants were divided into 2 groups: with and without CKD-aP. NRS scale was used to evaluate itch severity. Serum levels of NT-4 and BDNF have been assessed using ELISA. The results showed a significantly higher level of NT-4 in the group with pruritus. No significant difference was reported in the serum level of BDNF between the two groups of patients. There was also no correlation between serum NT-4 nor BDNF levels and the severity of pruritus. In summary, NT-4 may play an important role in the pathophysiology of pruritus in dialysis patients. More research is needed to understand the exact mechanism by which NTs influence the pathogenesis of CKD-aP.

Mining of unmapped remedies for allergic rhinitis within homoeopathy

Homeopathy treatment is well known for the holistic approach in treating all the patients. There are conditions stated in Organon of medicine by Dr Samuel Hahnemann about certain peculiarities and chronic disease due to the acute miasms which were mentioned in the aphorism 117 and 73 correspondingly. Allergic rhinitis is one of the utmost commonly met condition in which the change of weather in harvest season for which we must understand it quickly and prescribe to the patient for their relief. Its exhaustive bothersome condition which has a major impact in the day to day life of the person. Homoeopathic medicines have a great role in dropping the frequency and the intensity of the acute episodes of the allergic rhinitis accomplished by acute prescription, well along with a holistic and individualized approach must be chosen. Repertory also helps us in individuating and choosing the exact medicine.

The relative importance of different consequences of nocturnal enuresis among older women: A conjoint analysis experiment.

Adult nocturnal enuresis (NE) is an understudied and bothersome condition. Our objective was to conduct a conjoint analysis experiment to better understand the relative importance of NE consequences in older women. We developed a conjoint analysis survey that included four attributes related to NE (awakening at night, feeling rested in the morning, restricting fluid before bed, and wet perineal skin). We performed a prospective cross-sectional online study of women >62 years of age with NE using Sawtooth Software. Patients completed baseline questions, the International Consultation on Incontinence Questionnaire-nocturia Quality of Life(ICIQ-NqoL), and the conjoint analysis experiment. Hierarchical Bayes random effects regression analysis was used to determine the relative importance of the four attributes. A total of 200 women with a mean age of 71 years completed the study. The most common management of NE was diapers/pads (132/200). Approximately half of the participants experienced NE several times a week or nightly (101/200). The most important attribute was the frequency of being awakened at night (34, standard deviation [SD]: 16) and the frequency of feeling rested in the morning (32, SD: 15). Limiting drinking before bed (18, SD: 12) and wet groin skin (16, SD: 10) had significantly lower importance scores (p < 0.05). Age, sleeping with a partner in bed, body mass index, NE severity score, and the ICIQ-NqOL score were not significantly associated with any of the importance scores. Older women with NE place significantly more importance on the frequency of awakening at night, and feeling rested in the morning and lesser importance on associated lifestyle or physical manifestations of NE.

Treatment with the soluble guanylate cyclase activator BAY 60–2770 normalizes bladder function in an in vivo rat model of chronic prostatitis

Background and purposeChronic pelvic pain syndrome (CPPS) is a common and bothersome condition for which no pharmacological treatment options with acceptable efficacy exist. The aim of this study was to investigate the effects of the soluble guanylate cyclase (sGC) activator BAY 60–2770 and the COX-2 inhibitor celecoxib on bladder function in a rat model of CPPS. Experimental approachForty-eight male Sprague-Dawley rats were intraprostatically injected with either saline, serving as control, or zymosan, to induce prostatitis. On days 8–20, the rats were treated with either dimethylsulphoxide (DMSO; vehicle), celecoxib, BAY 60–2770 or a combination of celecoxib and BAY 60–2770. Thereafter, micturition parameters were assessed in a metabolic cage and urine samples were collected. The following day, cystometry was performed. Subsequently, the urinary bladder and prostate were removed and examined histopathologically. Key resultsInduction of prostatitis led to a significant increase of micturition frequency and corresponding decrease of volume per micturition. These alterations were ameliorated by celecoxib, and completely normalized by BAY 60–2770. Induction of prostatitis led to a significantly increased number of non-voiding contractions, decreased bladder compliance and increased voiding time. These parameters were normalized by treatment with BAY 60–2770, either alone or in combination with celecoxib. The immunohistochemical analysis showed signs of prostate inflammation, but not bladder inflammation. Conclusion and implicationsInduction of prostatitis led to significant impairment in bladder function. These alterations could be prevented by BAY 60–2770, alone or in combination with celecoxib. This is the first study to show that sGC activators could be a promising option for the treatment of CPPS.

Insight on the intracrinology of menopause: androgen production within the human vagina

ABSTRACT Introduction The human vagina is extremely sensitive to hormonal changes occurring during the woman's lifetime, in particular the decline in estrogens that characterizes the menopause is known to induce a range of genital and sexual symptoms (dryness, burning, irritation, lack of lubrication, discomfort, pain), known as “genitourinary syndrome of menopause” (GSM). However, this reduction in estrogen levels is also accompanied by a progressive ageing-dependent decline in androgens for which the role of androgens in the development and treatment of GSM has received more attention. It is known that peripheral tissues compensate for circulating hormonal imbalances through the in-situ production of small quantities of sex hormones deriving from inactive precursors metabolized by specific cellular enzymes. This non-classical production and local activity of hormones is defined as “intracrinology”. Objective The aim of the study was to investigate whether the human vagina possesses the specific enzymatic machinery to convert weak androgen precursors, such as DHEA, into active androgens [Δ4-androstenedione (A), testosterone (T) and dihydrotestosterone (DHT)] as already described in other species. Methods In this study, a well established model of human smooth muscle cells (hSMCs), isolated from vagina tissues of women undergoing surgery for benign gynecological diseases, was used. Semi-quantitative RT-PCR was employed in order to evaluate the mRNA expression of the steroidogenic markers in hSMCs and corrispective tissue. The production of androgens was quantified in hSMCs medium by liquid chromatography tandem-mass spectrometry (LC-MS/MS). Results In vaginal tissues, AR mRNA was significantly less expressed than estrogen receptor α (ERα), whereas in hvSMCs, its mRNA expression was higher than progestin and both estrogen receptors. In hvSMCs and in vaginal tissue, when compared to ovaries, the mRNA expression of pro-androgenic steroidogenic enzymes (HSD3β1/β2, HSD17β3/β5), along with 5α-reductase isoforms and sulfo-transferase, resulted as being more abundant. In addition, enzymes involved in androgen inactivation were less expressed than in the ovaries. The LC-MS/MS analysis revealed that, in hvSMCs, short term DHEA supplementation increased Δ4-androstenedione levels in spent medium, while increasing testosterone (T) and dihydrotestosterone (DHT) secretion after longer incubation. Finally, androgenic signaling activation was evaluated through AR-dependent marker mRNA expression, after DHEA and T stimulation. Conclusions This study provides evidence for the presence of steroidogenic machinery in the human vagina, supporting, for the first time, the construct of intracrinology in this organ, emphasizing that the vagina is an androgen-dependent organ. These observations suggest the potential mechanism and resulting action of intravaginally administered DHEA, recently indicated for the treatment of GSM and open new perspectives for the treatment of this common and bothersome condition. Disclosure Work supported by industry: no.

Recent advances in the treatment of uremic pruritus.

This article provides a focused update on uremic pruritus, highlighting the latest evidence concerning the epidemiology, pathophysiology, and treatment options for this common and bothersome condition. Half of dialysis patients and a quarter of those with nondialysis chronic kidney disease experience bothersome itch that reduces quality of life and is increasingly recognized to be associated with poor outcomes including mortality. The KALM-1 trial, which reported effective symptomatic relief with difelikefalin, has bolstered support for the role of an imbalance of μ and κ-opioid receptor activity in pruritogenesis. The role of a chronic inflammatory state, increased cytokine levels and altered immune signaling in pruritogenic nerve activation continues to be elucidated with basic science, which paves the wave for future novel therapeutics. In the meantime, gabapentin appears to be the most evidence-based widely available uremic pruritus treatment, as long as care is taken with dosing and monitoring of side-effects. Uremic pruritus remains a top research priority. Patients with uremic pruritus may be able to look forward to a new decade of understanding, knowledge, and novel treatment options for this burdensome condition. As difelikefalin and other potential agents come to market, cost-effectiveness assessments of these interventions will help determine if the widespread use of them is feasible amongst renal programs.

BMMSC-sEV-derived miR-328a-3p promotes ECM remodeling of damaged urethral sphincters via the Sirt7/TGF\u03b2 signaling pathway

BackgroundStress urinary incontinence (SUI) is a common and bothersome condition. Invasive surgery will always be considered after conservative treatment fails, but the rates of postoperative complications and long-term recurrence are high. Thus, a new treatment strategy is still needed. In recent years, bone marrow mesenchymal stem cells (BMMSC) have shown great promise for SUI treatment. The therapeutic effects of BMMSC on SUI are achieved mainly by paracrine pathway signaling molecules, such as small extracellular vesicles (sEV). sEV are recognized as essential mediators of cell-to-cell communication. However, the therapeutic effects and detailed mechanisms of BMMSC-derived sEV in SUI remain mostly unexplored.MethodsThe effects of BMMSC-sEV on extracellular matrix (ECM) metabolism were assessed in vitro and in vivo. In a SUI rat model, TGF-β1 signaling was examined with or without BMMSC-sEV stimulation. sEV miRNAs were deeply sequenced, and the most likely miRNAs were evaluated as mediators of the TGF-β1 signaling pathway.ResultsBMMSC-sEV enhanced the synthesis of ECM components, including elastin, collagen I, and collagen III, and improved urethral function. Furthermore, BMMSC-sEV activated TGF-β1 signaling in primary fibroblast cells and in rat urethras. Several differentially expressed miRNAs were identified in the BMMSC-sEV. Bioinformatics analysis and in vitro studies showed that BMMSC-sEV miR-328a-3p can be transferred from BMMSC to fibroblasts and can regulate the Sirt7/TGF-β1 signaling pathway.ConclusionBMMSC-sEV promote ECM remodeling of damaged urethral sphincters by transferring miR-328a-3p to regulate the Sirt7/TGF-β1 signaling pathway.

Botulinum toxin A injection in the treatment of chronic pelvic pain with hypertonic pelvic floor in women: Treatment techniques and results.

Chronic pelvic pain (CPP) is an extremely bothersome condition which leads to major effects in women's everyday life. In addition to visceral sources of pain, pelvic floor dysfunction including myofascial pain and spasm on the pelvic floor muscles causing hypertonicity are causes often overlooked. Injecting botulinum toxin type A (BoNT-A) into hypertonic pelvic floor muscles may aid the relaxation of pelvic floor musculature. The muscles that are injected in CPP treatment include the obturator internus, levator ani (pubococcygeus, iliococcygeus, and puborectalis), and coccygeus. Generally, injections can be performed tolerably with safety under conscious sedation combined with local anesthesia. Most practitioners perform BoNT-A injection of pelvic floor muscles using anatomical landmarks identified by manual palpation only. For the precise location of injection sites, some needle guidance techniques were proposed, including electromyography, electrical stimulation, ultrasound, fluoroscopy, and/or computed tomography. Side effects of BoNT-A injection in CPP are rare and self-limiting. Because of the reversible nature of BoNT-A, reinjection appears to be necessary. Increasing proof points out that BoNT-A is a promising treatment option for CPP in women. We conducted a review of published literature in Pubmed, using chronic pelvic pain in women, hypertonic pelvic floor, and botulinum toxin as the keywords. This article aims to summarize the treatment techniques and results of BoNT-A injection for hypertonic pelvic floor in women with chronic pelvic pain.

Assessment of Rhinostomy Parameters in Endonasal Dacryocystorhinostomy.

Epiphora is a bothersome condition seen in chronic dacryocystitis. The mainstay of treatment is surgical, that is creating an opening to establish a drainage pathway. With the advent of endoscope, endonasal DCR has gained popularity. Use of silicone stent in endonasal DCR has added advantage in improving the surgical outcome. And the use of DOS system in improving the success rates of endonasal DCR: (Mohammad et al. in Clin Ophthalmol 8:2491-2499, 2014) a total of 35 patients with chronic dacryocystitis were subjected for endonasal DCR with silicone bicanalicular stent. Patients were followed up at an interval of 1week, 3weeks, 6weeks and 6months post surgery. DCR ostium parameters were evaluated using DOS system. Silicone stent removal was done at sixth week and evaluated for success. The success rate in our study was 89%. The DOS score of the patient with successful surgery had a score of more than 30 and in the failed cases the score was between 22 and 28. The success rate of the procedure primarily depends on the ostium parameters and the position of the silicone stent. The DOS scoring system can be suitable tool in evaluating the same.

Is vaginal flatus related to pelvic floor functional anatomy?

Vaginal flatus is an embarrassing condition that can impair women's quality of life. The underlying pathophysiology is unclear. We aimed to evaluate the association between vaginal flatus and pelvic floor anatomy. Retrospective observational study on women seen in a tertiary urogynaecological service. All had undergone a standardised interview, clinical examination and four-dimensional transperineal ultrasound. Offline analysis of volume data was performed blinded against clinical data. Datasets of 570 women were analysed. Five hundred twelve (90%) were vaginally parous. Vaginal flatus was reported by 190 (33%). Mean bother score was 4.2 (SD 3.4, range 0-10). One hundred eighty-five reported frequency of vaginal flatus: it occurred < once a month in 25 (14%), once a month in 70 (38%), once a week in 47 (25%), once daily in 28 (15%) and > once daily in 15 (8%). One hundred two women identified the following precipitating factors: intercourse in 72 (71%), postural change in 22 (22%) and physical activities in 9 (9%). Vaginal birth, central and posterior compartment prolapse, anal incontinence, higher levator resting tone and younger age were associated with vaginal flatus. The latter was moderately correlated with symptom bother (correlation coefficient - 0.21). Vaginal flatus is a prevalent and bothersome condition affecting one-third of our study population. The condition is associated with pelvic floor functional anatomy. A higher resting tone may confer a higher resistance against which trapped air is expelled during physical activities. Younger age was moderately correlated with symptom bother.

PRImary care Management of lower Urinary tract Symptoms in men: protocol for development and validation of a diagnostic and clinical decision support tool (the PriMUS study).

IntroductionLower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care.Methods and analysisPRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool.Ethics and disseminationEthics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders.Trial registration numberISRCTN10327305.

Regenerative medicine and injection therapies in stress urinary incontinence

Stress urinary incontinence (SUI) is a common and bothersome condition. Anti-incontinence surgery has high cure rates, but concerns about mesh tapes have resulted in the resurgence of surgical procedures that involve increased abdominopelvic dissection and morbidity. Injection therapy with urethral bulking agents or stem cell formulations have been developed as minimally invasive alternatives. Many synthetic and biological bulking agents havebeen trialled, but several have been discontinued owing to safety concerns. The use of Macroplastique and Contigen has the largest evidence base, but, overall, success rates seem to be similar between the various agents and positive outcomes are poorly sustained for more than 6 months. Furthermore, subjective cure rates, although initially high, also deteriorate over time. The available data consistently demonstrate manifestly poorer outcomes for injection therapies than for surgery. Stem cell treatments are thought to functionally regenerate the urethral sphincter in patients with suspected intrinsic sphincter deficiency. Autologous adipose and muscle-derived stem cells seem to be the intuitive cell source, as they are comparatively abundant, can be harvested and cause minimal donor site morbidity. To date, only a few small clinical studies have been reported and most data are derived from animal models. The success rates of stem cell injection therapies seem to be comparable with those of bulking agents.