Tunneled Tunica Vaginalis Flap for Recurrent Urethrocutaneous Fistulae

The tubularized incised plate (TIP) hypospadias repair is currently the most widely used urethroplasty technique. The most significant post-TIP complication is urethrocutaneous fistula (UCF) development. Tunneled tunica vaginalis flap (TVF) is a well-described technique for the repair of UCF. We retrospectively reviewed all patients undergoing repeat repair of UCF after TIP repair from 2001 to 2005. Twelve boys underwent TVF repair at our institution for recurrent UCF. Fistulae ranged from distal penile to penoscrotal in location. Median surgical time was 45 minutes and no postoperative complications occurred. After a median follow-up of 32 months (range 16–48 months), no patient has yet had a recurrence of UCF. In conclusion, TVF repair is a successful technique for the treatment of UCF after previous failed repair. TVF is technically simple to perform and should be considered for treating UCF following TIP urethroplasty, particularly in a repeat surgical setting

Myofascial urinary frequency syndrome is a novel syndrome of bothersome lower urinary tract symptoms associated with myofascial pelvic floor dysfunction

This study describes a novel, distinct phenotype of urinary symptoms named myofascial urinary frequency syndrome (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit persistency : a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of persistency in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex

The Persistency Index: A novel screening tool for identifying myofascial pelvic floor dysfunction in patients seeking care for lower urinary tract symptoms

BACKGROUND: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome. Despite a high influence on quality of life, low awareness of this condition combined with no objective diagnostic testing leads to the frequent misdiagnosis or underdiagnosis of myofascial urinary frequency syndrome. OBJECTIVE: This study aimed to develop a screening measure to identify patients with myofascial urinary frequency syndrome (bothersome lower urinary tract symptoms secondary to myofascial pelvic floor dysfunction) from patient-reported symptoms. STUDY DESIGN: A population of patients with isolated myofascial urinary frequency syndrome was identified by provider diagnosis from a tertiary urology practice and verified by standardized pelvic floor myofascial examination and perineal surface pelvic floor electromyography. Least Angle Shrinkage and Selection Operator was used to identify candidate features from the Overactive Bladder Questionnaire, Female Genitourinary Pain Index, and Pelvic Floor Distress Index predictive of myofascial urinary frequency syndrome in a pooled population also containing subjects with overactive bladder (n=42), interstitial cystitis/bladder pain syndrome (n=51), and asymptomatic controls (n=54) (derivation cohort). A simple, summated score of the most discriminatory questions using the original scaling of the Pelvic Floor Distress Index 5 (0-4) and Genitourinary Pain Index 5 (0-5) and modified scaling of Female Genitourinary Pain Index 2b (0-3) had an area under the curve of 0.75. As myofascial urinary frequency syndrome was more prevalent in younger subjects, the inclusion of an age penalty (3 points added if under the age of 50 years) improved the area under the curve to 0.8. This score was defined as the Persistency Index (possible score of 0-15). The Youden Index was used to identify the optimal cut point Persistency Index score for maximizing sensitivity and specificity. RESULTS: Using a development cohort of 215 subjects, the severity (Pelvic Floor Distress Index 5) and persistent nature (Female Genitourinary Pain Index 5) of the sensation of incomplete bladder emptying and dyspareunia (Female Genitourinary Pain Index 2b) were the most discriminatory characteristics of the myofascial urinary frequency syndrome group, which were combined with age to create the Persistency Index. The Persistency Index performed well in a validation cohort of 719 patients with various lower urinary tract symptoms, including overactive bladder (n=285), interstitial cystitis/bladder pain syndrome (n=53), myofascial urinary frequency syndrome (n=111), controls (n=209), and unknown diagnoses (n=61), exhibiting an area under the curve of 0.74. A Persistency Index score ≥7 accurately identified patients with myofascial urinary frequency syndrome from an unselected population of individuals with lower urinary tract symptoms with 80% sensitivity and 61% specificity. A combination of the Persistency Index with the previously defined Bladder Pain Composite Index and Urge Incontinence Composite Index separated a population of women seeking care for lower urinary tract symptoms into groups consistent with overactive bladder, interstitial cystitis/bladder pain syndrome, and myofascial urinary frequency syndrome phenotypes with an overall diagnostic accuracy of 82%. CONCLUSION: Our study recommends a novel screening method for patients presenting with lower urinary tract symptoms to identify patients with myofascial urinary frequency syndrome. As telemedicine becomes more common, this index provides a way of screening for myofascial urinary frequency syndrome and initiating pelvic floor physical therapy even before a confirmatory pelvic examination

Activation and Involvement of Ral GTPases in Colorectal Cancer

Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the anti-tumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. While AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional anti-tumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC

Rare variants in tenascin genes in a cohort of children with primary vesicoureteric reflux

Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in tenascin XB (TNXB) as a cause of PVUR with joint hypermobility

A Six-Gene Signature Predicts Survival of Patients with Localized Pancreatic Ductal Adenocarcinoma

Jen Jen Yeh and colleagues developed and validated a six-gene signature in patients with pancreatic ductal adenocarcinoma that may be used to better stage the disease in these patients and assist in treatment decisions

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1. Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1 . Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets