The search for a biomarker in overactive bladder syndrome (OAB) is an emerging field of interest, as bladder dysfunction is a common complaint that causes significant morbidity. A biomarker may give us insight as a diagnostic tool, and also inform us about how severe the condition is, how it may progress and how it may best be treated. The protein of interest here is nerve growth factor (NGF) and it has been shown to be a dynamic molecule in the bladder of patients with OAB. Urinary levels have been seen to rise in patients with OAB and fall in those who respond to treatment. However, there have also been many studies that examine this trend in numerous other conditions, e.g. interstitial cystitis, bladder outflow obstruction, renal stone disease and patients with neurological impairment after stroke. As a result the specificity of this as a potential urinary biomarker for OAB is questioned. This is a review of published studies, which discusses the pros and cons of NGF as a potential urinary biomarker. The evidence is examined and the studies are summarised together in a Table. Questions remain about the reliability, practicality and specificity of NGF as a biomarker for OAB. These questions need to be addressed by further studies that could clarify the points raised. Objective• To review the current literature on the use of urinary nerve growth factor (NGF) as a potential biomarker for overactive bladder syndrome (OAB). Method• A comprehensive electronic literature search was conducted using the PubMed database to identify publications relating to urinary NGF. Results• There are a growing number of publications that have measured urinary NGF levels in different types of bladder dysfunction. These range from OAB, bladder pain syndrome, idiopathic and neurogenic detrusor overactivity, bladder oversensitivity and bladder outflow obstruction. Urinary NGF levels do appear to be raised in these pathological states when compared with healthy control samples.• In patients with OAB, these raised urinary NGF levels appear to also reduce after successful treatment with antimuscarinics and botulinum toxin A, which indicates a potential use in monitoring responses to treatment. • However, raised levels are not limited to OAB, which questions its specificity.• Urinary NGF measurements are performed with an enzyme-linked immunosorbent assay using polyclonal antibodies to NGF. The technique requires standardisation, and the different antibodies to NGF require validating.• Also a definition of what is the 'normal' range of NGF in urine is still required before it can be used as a diagnostic and prognostic tool. Conclusions• Whilst the evidence for an increased urinary NGF in OAB appears convincing, many questions about its validity remain including: specificity, sensitivity, cost-and time-effectiveness. • Many criteria for what constitutes a biomarker still need to be evaluated and met before this molecule can be considered for this role. 372
IntroductionIn 1809, Johann Friedrich Meckel described the embryology of a small bowel diverticulum, which now bears his name. Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract, with a prevalence ranging from 1% to 4% of the population. The majority are clinically silent and are incidentally identified at surgery or at autopsy. The lifetime risk of complications is estimated at 4%, with most of these complications occurring in adults. It is these cases that can cause problems for the clinician, as the diagnosis can be elusive and the consequences extremely serious.Case presentationWe present the case of a 68-year-old Caucasian man with axial torsion of a Meckel's diverticulum around its base, a rare complication. He presented with acute, severe abdominal pain, and a clinical diagnosis of perforated acute appendicitis was made. Laparotomy revealed a torted Meckel's diverticulum with distal necrosis and perforation, which was resected. His recovery was uncomplicated, and he was discharged to home six days post-operatively.ConclusionTorsion is an extremely rare complication of Meckel's diverticulum. Its presentation can be elusive, and it can mimic a number of different, more common intra-abdominal pathologies. Imaging appears to be an unreliable diagnostic tool, and the diagnosis is usually made intra-operatively. Factors pre-disposing these patients to axial torsion of Meckel's diverticulum include the presence of mesodiverticular bands, a narrow base, excessive length, and associated neoplastic growth or inflammation of the diverticulum. The importance of searching for a diseased Meckel's diverticulum at laparotomy in appropriate circumstances is highlighted. Once identified, prompt surgical excision generally leads to an uncomplicated recovery.
ObjectivesTo assess the efficacy (defined as improvements in maximum urinary flow rate [Q max ] of ≥50%, post-void residual urine volume [PVR] and scores on the International Prostate Symptom Score [IPSS] questionnaire) and safety of urethral sphincter injections of onabotulinumtoxinA in women with a primary disorder of urethral sphincter relaxation, characterised by an elevated urethral pressure profile (UPP) and specific findings at urethral sphincter electromyography (EMG), i.e. Fowler's syndrome. Patients and MethodsIn this open-label pilot Institutional Review Board-approved study, 10 women with a primary disorder of urethral sphincter relaxation (elevated UPP, sphincter volume, and abnormal EMG) presenting with obstructed voiding (five) or in complete urinary retention (five) were recruited from a single tertiary referral centre. Baseline symptoms were assessed using the IPSS, and Q max and PVR were measured. After 2% lidocaine injection, 100 U of onabotulinumtoxinA was injected into the striated urethral sphincter, divided on either side, under EMG guidance. Patients were reviewed at 1, 4 and 10 weeks after injection, and assessed using the IPSS, Q max and PVR measurements. The UPP was repeated at week 4. ResultsThe mean (range) patient age was 40 (25-65) years, and the mean symptom scores on the IPSS improved from 25.6 to 14.1, and the mean 'bother' score reduced from 6.1 to 3.5 at week 10. As compared with a baseline mean Q max of 8.12 mL/s in the women who could void, the Q max improved to 15.8 mL/s at week 10. Four of the five women in complete retention could void spontaneously, with a mean Q max of 14.3 mL/s at week 10. The mean PVR decreased from 260 to 89 mL and the mean static UPP improved from 113 cmH 2 O at baseline to 90 cmH 2 O. No serious side-effects were reported. Three women with a history of recurrent urinary tract infections developed a urinary tract infection. There were no reports of stress urinary incontinence. Seven of the 10 women opted to return for repeat injections. ConclusionsThis pilot study shows an improvement in patient-reported lower urinary tract symptoms, and the objective parameters of Q max , PVR and UPP, at 10 weeks after urethral sphincter injections of onabotulinumtoxinA. No serious side-effects were reported. This treatment could represent a safe outpatient treatment for young women in retention due to a primary disorder of urethral sphincter relaxation. However, a larger study is required to confirm the findings of this pilot study.
BackgroundTo evaluate safety, acceptability and pilot efficacy of transcutaneous low-frequency tibial nerve stimulation (TNS) using a novel device as home-based neuromodulation.MethodsIn this single-centre pilot study, 48 patients with overactive bladder (OAB) (24 with neurogenic and 24 with idiopathic OAB) were randomized to use a self-applicating ambulatory skin-adhering device stimulating transcutaneously the tibial nerve at 1 Hz for 30 minutes, either once daily or once weekly, for 12 weeks. Changes in OAB symptoms and QoL were measured at baseline, weeks 4, 8, and 12 using validated scoring instruments (ICIQ-OAB and ICIQ-LUTSqol), 3-day bladder diary and a Global Response Assessment (GRA) at week 12.ResultsThirty-four patients completed the study (idiopathic n=15, neurogenic n=19). No significant adverse effects were noted. Patients found the device acceptable. Eighteen patients (53%) reported a moderate or marked improvement in symptoms from the GRA. Between baseline and week-12, ICIQ-OAB part A sub-scores improved from mean (SD) 9.3 (2.5) to 7.5 (3.1), and from 9.1 (1.9) to 5.9 (1.7) in the daily and the weekly arms, respectively. ICIQ-LUTSqol part A sub-scores improved from mean (SD) 51 (12.8) to 44.2 (13.1) and 44.9 (9.0) to 35.9 (8.8) in the daily and the weekly arms, respectively. Bladder diary mean 24-hour frequency episodes improved from 11.5 to 8.8 at week 12 for both arms.ConclusionsThis novel ambulatory transcutaneous TNS (TTNS) device is safe and acceptable for use in patients reporting OAB symptoms as a form of home-based neuromodulation. A larger study however is required to confirm clinical efficacy.
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