Appendix or Ileum-Which is the Best Material for Mitrofanoff Channel Formation in Adults?

PURPOSE: We report long-term data on a large cohort of adults who underwent formation of a continent catheterizable channel for various indications. We examined outcomes according to the tissue used for channel formation. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 176 consecutive adult patients in whom a continent catheterizable channel was created using the Mitrofanoff principle for a broad range of indications a median of 142 months (range 54 to 386) previously. We evaluated outcomes in terms of continued use and continence for each type of material used for channel formation. RESULTS: At the time of this review 165 of the 173 patients (95.4%) included in this study were alive. We included 114 women (65.9%) and 59 men (34.1%) who underwent surgery at a median age of 42 years (range 18 to 73) with a mean followup of 78.6 months (median 60, range 2 to 365). The rate of revision for all causes was higher in the ileal group than in the group with an appendiceal channel (channel stenosis rate 22.7% vs 17.2%, p = 0.39, and channel incontinence rate 36.0% vs 19.5%, p = 0.03). Although 38.7% of patients underwent major surgical revision of the channel at some point, 75.9% of channels continued to be used, of which 90.2% were continent. CONCLUSIONS: This study provides a pragmatic overview of the outcome of these challenging cases. Mitrofanoff channel formation represents a durable technique. Appendix and ileum are each a viable choice for tissue use. Tissue selection depends on availability and individual patient factors.

Subcutaneous C1-esterase inhibitor to prevent hereditary angioedema attacks: Safety findings from the COMPACT trial.

BACKGROUND: The first subcutaneous (SC) C1-esterase inhibitor concentrate (C1-INH) was approved by the U.S. Food and Drug Administration in June 2017 as routine prophylaxis to prevent hereditary angioedema attacks in adolescents and adults at a dose of 60 IU/kg twice weekly based on the phase III Clinical Study for Optimal Management of Preventing Angioedema With Low-volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT) trial. OBJECTIVE: This article aimed to evaluate the relationship of the C1-INH (SC) dose regimens tested in the COMPACT trial (40 IU/kg and 60 IU/kg twice weekly) and the occurrence of adverse events (AEs). METHODS: Patients were instructed to record any AEs in their e-diary daily. Safety and tolerability were assessed based on reported AEs, including injection-site reactions (ISRs); unsolicited AEs (AEs other than ISRs); serious AEs; thrombotic, thromboembolic, anaphylactic, hypersensitivity, sepsis, and bacteremia events; inhibitory antibodies to C1-INH; and clinically significant abnormalities in laboratory assessments. Information on ISRs was specifically solicited. RESULTS: No relationship between the dose of C1-INH (SC) and the incidence of ISRs or unsolicited AEs was observed. The proportion of injections followed by at least one ISR was 12% with C1-INH (SC) 40 IU/kg versus 5% with 60 IU/kg and 6% with placebo. No ISRs were serious or led to treatment discontinuation, and all resolved. There were no anaphylaxis, thromboembolic, sepsis, or bacteremia events reported during treatment with C1-INH (SC). All hypersensitivity AEs were nonserious, and the majority were assessed as being unrelated to treatment. No inhibitory antibodies to C1-INH were observed. CONCLUSION: C1-INH (SC) is safe and well tolerated with no dose-dependent safety concerns, as demonstrated in the COMPACT trial.Clinical trial NCT01912456, www.clinicaltrials.gov.

Clinical trials assessing ototopical agents in the treatment of pain associated with acute otitis media in children.

Otalgia (ear pain) is one of the characteristic symptoms and best predictor of acute otitis media (AOM) in children. Although oral pain medications are the current mainstay for the treatment of AOM-associated otalgia, ototopical agents have been investigated as an alternative treatment strategy. To permit review and assessment of this treatment modality, a systematic literature search was conducted to identify all randomized, controlled trials of ototopical agents. Four trials were identified, including those examining ototopical benzocaine in combination with antipyrine, lidocaine, tetracaine, and herbal extracts. Although the current available evidence suggests ototopical agents may be safe and effective, we conclude that further studies with more rigorous methodology are needed to conclusively demonstrate their utility in this setting.

Animal models in urinary diversion.

We set out to critically assess the value of animal experimentation in urinary diversion through intestinal segments, as some authors question the effectiveness of animal research, criticising the methodological quality, lack of standardization, inadequate reporting and the few systematic reviews in this field. Based on a comprehensive MEDLINE literature search (MeSH database; search terms: urinary diversion, urinary reservoirs, continent, rat, dog, animal models) we retrieved and evaluated all full-length papers published in English, German, French, and Spanish languages from 1966 to 2011 reporting the use of animal models in the setting of urinary diversion. Studies were stratified according to the addressed research question. Within each category species, gender, number of animals, age at procedure, type of diversion, mortality, length of follow-up, experimental procedure and outcome were recorded and tabulated. In all, 159 articles were judged to be relevant and while there are numerous animal models only a few have been used in more than one study. Animals were used for the systematic study of new surgical techniques (93 articles) or metabolic and functional consequences of urinary reconstruction (66 articles). For the latter purpose, the most often used animal is the rat, whereas the dog model is preferred for technical experimentation. In many studies, the validity of the model is at least questionable. Animal experiments have repeatedly been conducted addressing the same question, often with striking discrepancies in outcome. Animal studies were even performed after a surgical technique had been pioneered in humans. The use of animal models in urinary diversion is far from standardized rendering the results less than ideal for comparison across studies. Due to differences in anatomy and physiology, the applicability of findings in animal experiments to clinical urology is limited. Continued effort is needed to optimise the use of animal models in experimental urology.

Generation of metabolically diverse strains of Streptococcus pyogenes during survival in stationary phase.

Streptococcus pyogenes, in addition to causing fulminant disease, can be carried asymptomatically and may survive in the host without causing disease. Long-term stationary-phase cultures were used to characterize the metabolism of cultures surviving after glucose depletion. Survival of stationary-phase cultures in glucose-depleted rich medium was truncated by switching the cells to phosphate-buffered saline or by the addition of antibiotics, suggesting that survival depended on the presence of nutrients and metabolic activity. The metabolites of the pyruvate-to-acetate (PA) pathway (acetate and formate) and amino acid catabolic pathways (ammonia) accumulated throughout long-term stationary phase (12 weeks). Acid and ammonia production was balanced so that the culture pH was maintained above pH 5.6. Strains isolated from long-term stationary-phase cultures accumulated mutations that resulted in unique exponential-phase metabolisms, with some strains expressing the PA pathway, some strains producing ammonia, and some strains expressing both in the presence of glucose. Strains expressing high levels of PA pathway activity during exponential growth were unable to survive when regrown in pure culture due to the production of excess acid. These data suggest that S. pyogenes diversifies during survival in stationary phase into distinct strains with different metabolisms and that complementary metabolism is required to control the pH in stationary-phase cultures. One of three survivor strains isolated from tonsillar discard material from patients expressed high levels of the PA pathway during exponential growth. Sequencing of multiple group A streptococcus regulators revealed two different mutations in two different strains, suggesting that random mutation occurs during survival.

Stabilization of renal deterioration caused by bladder volume dependent obstruction.

PURPOSE: Previously published data from our unit show the detrimental effect of excessive bladder filling at normal pressure on renal function in chronically dilated renal units. Synchronous cystometry and dynamic renography identified a critical volume of filling that prevents upper tract drainage. In this followup study we determined whether maintaining bladder volume below this critical level would halt renal deterioration. MATERIALS AND METHODS: Followup data were collected on 20 patients in the original study. All had progressive renal function deterioration for which no other cause was identified. Creatinine measured nearest to the time of the study renogram served as a baseline and subsequent values were used to monitor renal function. Data were analyzed by the paired Student t test. RESULTS: Complete data were obtained on 14 patients with a mean age of 34.4 years (range 22 to 70). The mean glomerular filtration rate at entry to this part of the study was 42 ml per minute per 1.73 m(2) (range 18 to 69). Four patients had a neuropathic bladder, 4 had posterior urethral valves, 4 had bladder exstrophy, 1 had radiation cystitis, 1 had a solitary pelvic kidney and detrusor failure, 5 had a native bladder and 9 underwent cystoplasty. Drainage was via the native urethra and a Mitrofanoff channel in 7 cases each. Mean followup was 27 months (range 3 to 39). There was no significant difference in mean +/- SD creatinine at baseline vs latest followup (168 +/- 72 vs 185 +/- 90 micromol/l, p >0.05). CONCLUSIONS: In patients with bladder volume dependent renal obstruction function can be stabilized by consistently maintaining bladder volume below the critical level.

Persistence of Streptococcus pyogenes in stationary-phase cultures.

In addition to causing fulminant disease, Streptococcus pyogenes may be asymptomatically carried between recurrent episodes of pharyngitis. To better understand streptococcal carriage, we characterized in vitro long-term stationary-phase survival (>4 weeks) of S. pyogenes. When grown in sugar-limited Todd-Hewitt broth, S. pyogenes cells remained culturable for more than 1 year. Both Todd-Hewitt supplemented with excess glucose and chemically defined medium allowed survival for less than 1 week. After 4 weeks of survival in sugar-limited Todd-Hewitt broth, at least 10(3) CFU per ml remained. When stained with fluorescent live-dead viability stain, there were a number of cells with intact membranes that were nonculturable. Under conditions that did not support persistence, these cells disappeared 2 weeks after loss of culturability. In persistent cultures, these may be cells that are dying during cell turnover. After more than 4 weeks in stationary phase, the culturable cells formed two alternative colony phenotypes: atypical large colonies and microcolonies. Protein expression in two independently isolated microcolony strains, from 14-week cultures, was examined by use of two-dimensional electrophoresis. The proteomes of these two strains exhibited extensive changes compared to the parental strain. While some of these changes were common to the two strains, many of the changes were unique to a single strain. Some of the common changes were in metabolic pathways, suggesting a possible alternate metabolism for the persisters. Overall, these data suggest that under certain in vitro conditions, S. pyogenes cells can persist for greater than 1 year as a dynamic population.