Continence and complications rates after male slings as primary surgery for post-prostatectomy incontinence: A systematic review

Objectives: to analyze continence and complications rates after male slings as first line surgical treatment, in order to improve patient counseling for the management of SUI postprostatectomy. Method: A MedLine search using specified search terms was done on January 23, 2012. This research rendered 160 records. Results: No controlled trial was available for analysis. The majority of papers dealing with out- come and complications came from a few centres. At a median follow-up of 15 months the pooled cure rates for all kinds of slings was 77.4; in the AdVance group the pooled cure rates was 72.5%; in the InVance group it was 74.2% while in the Remeex group it was 84.3%. Conclusions: Only a few number observational studies addressed review selection criteria. The pooled overall cure rates is high but there are no data concerning reliable pre- and postopera- tive prognostic factors affecting treatment failure and complications rates, thus it is not possi- ble to have suitable criteria for a better patient selection. The statistically pooled results obtained should be interpreted with caution because of several limitations due to several study selection limitations: observational study design, few number of analysed studies, heterogene- ity, lack of outcome definition and standardisation, between-study variability, high risk of bias

Theoretical Study on Highly Active Bifunctional Metalloporphyrin Catalysts for the Coupling Reaction of Epoxides with Carbon Dioxide

Highly active bifunctional metalloporphyrin catalysts were developed for the coupling reaction of epoxides with CO2 to produce cyclic carbonates. The bifunctional catalysts have both quaternary ammonium halide groups and a metal center. To elucidate the roles of these catalytic groups, DFT calculations were performed. Control reactions using tetrabutylammonium halide as a catalyst were also investigated for comparison. In the present article, the results of our computational studies are overviewed. The computational results are consistent with the experimental data and are useful for elucidating the structure-activity relationship. The key features responsible for the high catalytic activity of the bifunctional catalysts are as follows: 1) the cooperative action of the halide anion (nucleophile) and the metal center (Lewis acid); 2) the near-attack conformation, leading to the efficient opening of the epoxide ring in the rate-determining step; and 3) the conformational change of the quaternary ammonium cation to stabilize various anionic species generated during catalysis, in addition to the robustness (thermostability) of the catalysts

ROBOT-ASSISTED LAPAROSCOPIC HYSTEROSACROPEXY FOR PELVIC ORGAN PROLAPSE

Introduction Pelvic organ prolapse (POP) surgery can be performed either transperineally or transabdominally. The individual woman\u2019s surgical history and goals, as well as her individual risk for surgical complications, prolapse recurrence and de novo symptoms impact the selection of surgical route. Transabdominal repairs are the most common surgical procedures for POP and are associated to recurrence rates up to 10%, whereas transperineal approaches are reported to be a source of higher recurrence rates. Transabdominal procedures can be performed either by laparotomy or by laparoscopy. Recently several series have reported that laparoscopic approach to treat POP (with or without robotic assistance) is feasible and safe with good short and intermediate-term results, comparable to open approaches. This paper describes the technical aspects of robot-assisted laparoscopic hysterosacropexy (RALHSP) using the da Vinci surgical system. Design Since 2006, 10 consecutive patients with POP (mean age 54.5 years), who wished to preserve the uterus, underwent RALHSP as single reconstructive procedure. Two surgeons performed all procedures with the same technique. All complications were collected at a 90-day follow-up using the standardised Clavien classification system. The following outcomes were evaluated: operative time, blood loss, complications, in hospital stay, catheterization time, cure rate. The surgical steps were: bilateral dissection of the perimetrium; identification and extraperitonealization of the uterine cervix; incision of the peritoneum at presacral level and distal to the cervix; placement of a 20 x 2.5 cm polypropylene mesh, willing to embrace the cervix, secured to the anterior longitudinal sacral legament with 0 Tycron stitches; mesh extraperitonealization. Results Al procedures were performed successfully using the Robot-assisted approach. No additional reconstructive procedures were thought to be necessary at the end of surgery. The mean operative time was 103 minutes; the mean blood loss was 18 mL. Neither intra- nor major post-operative complications occurred. According to the Clavien classification system, 4 patients (40%) had grade 1 early complications (two nausea episodes, two electrolyte disturbance); and one patient (10%) had grade 2 complication (diarrhoea). At a mean follow-up of 9.3 months all patients declared themselves satisfied with the anatomical and functional results achieved. Conclusion RALHSP represents an effective option for the management of POP in selected women who wish to preserve the uterus. Moreover da Vinci robotic system allows performing similar procedures to those performed by standard laparoscopy or laparotomy without increasing the morbidity rate when compared to standard laparoscopy, and allows the same functional results

SACRAL NEUROMODULATION FOR THE TREATMENT OF REFRACTORY LOWER URINARY TRACT DYSFUNCTION: RESULTS FROM A MULTICENTER STUDY

Hypothesis / aims of study Sacral neuromodulation (SNM) has been used as a safe, effective treatment option for patients with lower urinary tract dysfunction (LUTD). Several clinical studies demonstrated its positive effects on refractory urge incontinence, non-obstructive urinary retention, urgency frequency syndrome, as well as on other non urological disorders, such as faecal incontinence and chronic constipation. The aim of this research project was to evaluate the efficacy and safety of sacral neuromodulation on the management of LUTD refractory to the standardised first line treatment options. Study design, materials and methods We retrospectively collected and evaluated data from patients undergoing SNM between September 2001 and November 2010 in 4 Urological Centres of Northeast Italy. The patients were affected by Overactive Bladder Syndrome (OAB) and non-obstructive Urinary Retention (UR). All the patients were evaluated with voiding diaries, before and after implantation. Patients included in the present evaluation were followed in a network of 4 Italian urological centres which participate to the Italian Clinical Service project - a national urological database and medical care project aiming at describing and improving the use of implantable urological devices in the Italian clinical practice. To evaluate the patient reported outcome (PRO) of the impact of SNM on refractory OAB, we retrospective revised files from all implanted patients who completed pre and post-operatively the King\u2019s Health Questionnaire (KHQ). KHQ is a specific assessment instrument of the heath related quality of life (HRQoL) for patients with OAB, and incontinence symptoms. It consists of 21 items distributed in nine dimensions: general health (GH), incontinence impact (II), role limitations (RLs), personal limitations (PLs), social limitations (SLs), personal relationship (PR), emotions (Em), sleep/energy (Slp/En), and severity measures (SMs). The score of each dimension ranges from 0 (lower OAB symptoms impact; better HRQoL) to 100 (higher OAB symptoms impact; worse HRQoL). Continuous normally distributed variables were reported as the mean value \ub1 standard deviation (SD). Continuous non-normally distributed variables were presented as the median values and an interquartile range (IQR). The t-test, the Mann-Whitney and Wilcoxon tests were used to compare continuous variables, as appropriate. A two-sided p < 0.05 was considered statistically significant. Results Overall, 135 patients underwent implantation of SNM during the period under review. Eighty-three out of 135 (61.5%) patients complained of OAB, and 52 (38.5%) of UR. In patients treated for OAB, we documented a statistically significant reduction in the mean number of: incontinence episodes/die, pads/die, daily micturitions, nocturnal micturitions and global micturitions (see table I). In patients treated for UR, we observed a statistically significant reduction in the mean post voiding residual volume and in the number of self catheterization (see table II). Concerning the impact of SNM on HRQOL from patients complaining of refractory OAB, only nineteen patients (17 female and 2 male), from a single centre, filled-in the KHQ pre- and/or postoperatively The median patients\u2019 age was 70 years (range 65-74) with a median follow-up of 42 months (range 17.5-48). Median and range of quality of life KHQ of general health and personal relationship pre- and post-operatively were reported in table III. Table I. SNM clinical outcomes in patients with refractory OAB Variable N Baseline FU P-value Incontinence episode/die, mean\ub1SD 48 4.1\ub12.7 1.5\ub12.1 <0.001\ub0 Pads/die, mean\ub1SD 44 3.4\ub12.4 1.3\ub11.4 <0.001\ub0 Voided volume, mean\ub1SD 45 143.6\ub169.9 206.7\ub188.5 <0.001* Daily micturition, mean\ub1SD 48 10.4\ub14.2 7.4\ub12.5 <0.001\ub0 Nightly micturition, mean\ub1SD 48 2.6\ub11.8 0.8\ub10.9 <0.001\ub0 Global micturition, mean\ub1SD 48 13.0\ub15.3 8.1\ub12.7 <0.001\ub0 *T-Test; \ub0 Wilcoxon test Table II. SNM clinical outcomes in patients with non-obstructive urinary retention Variabile N Baseline FU P-value Post void reisdual urine, mean\ub1SD 30 321.4\ub1153.5 87.2\ub196.9 <0.001\ub0 Catheterism/die, mean\ub1SD 30 3.8\ub11.4 1.3\ub11.3 <0.001\ub0 Daily micturition, mean\ub1SD 29 4.7\ub13.8 5.4\ub12.0 0.159\ub0 Nightly micturition, mean\ub1SD 29 0.7\ub11.3 0.7\ub11.1 0.886\ub0 Global micturition, ,mean\ub1SD 29 5.4\ub14.6 6.1\ub12.5 0.328\ub0 *T-Test; \ub0 Wilcoxon test Table III. Median and range of HRQoL assessed pre- and postoperatively by King\u2019s Health Questionnaire* of general health and personal relationship of patients underwent SNM for refractory OAB. Dimension pre-SNM median (rance) post-SNM median (range) p-Value Wilcoxon matched pairs test GH 50 (37.5-50) 50 (25-62.5) 1 II 100 (100-100) 100 (50-100) 0.063 RLs 83.3 (50-100) 50 (33.3-100) 0.102 PLs 83.3 (66.7-100) 33.3 (16.7-83.3) 0.026 SLs 77.8 (50-94.4) 0 (0-50) 0.017 PR 0 (0-25) 0 (0-33.3) 0.785 Em 77.8 (22.2-88.9) 33.3 (11.1-44.4) 0.14 Slp/En 50 (33.3-75) 50 (16.7-66.7) 0.109 SMs 58.3 (33.3-79.2) 66.7 (25-75) 0.671 *The score ranges from 0 (lower OAB symptoms, better HRQoL) to 100 (higher OAB symptoms, worse HRQoL). In comparison of the preoperative setting, patients after the implant showed a better scores in many KHQ dimensions. In particular for personal limitations (p=0.026), and social limitations (p=0.017). The length of follow-up did not significantly impact on HRQoL scores. Interpretation of results SNM offers objective benefits for people with refractory OAB and for those with urinary retention without structural obstruction. Concerning the PRO, because OAB symptoms in general may have a serious impact on a person\u2019s daily activities and social life, the effect of treatment on disease-specific HRQoL also reflects its efficacy. In our series we observe a significant improvement of HRQoL for the following KHQ items: personal limitations and social limitations. We observe a better, although not significant, HRQoL also for the following items: Incontinence Impact, Role Limitations, and Emotions. We did not found any correlation between the follow-up length and HRQoL. We should take great caution in interpreting these results because all the measures of the impact of SNM on the HRQOL comes from a small number of patients\u2019 perspective. Concluding message This multicenter research project confirmed the midterm safety and effectiveness of sacral neuromodulation in the treatment of refractory overactive bladder syndrome and non-obstructive urinary retention, showing high cure rates and low complication rates

ROLE OF SYMPTOMS DURATION AS PROGNOSTICATOR FOR SACRAL NEUROMODULATION IN REFRACTORY OVERACTIVE BLADDER

Hypothesis / aims of study Sacral neuromodulation (SNM) offers a well-tolerated treatment option for patients with overactive bladder syndrome (OAB) refractory to conservative treatment. The advantageous effect of SNM depends on the accurate identification of suitable candidates during pre-implant percutaneous nerve evaluation. In the Literature there are conflicting data regarding the role of age, duration of complaints and neurogenic bladder dysfunction in predicting the effect of SNM, and up to-date no specific urological pre-treatment factors have been associated with response to SNM. The aim of this multicentric study was to investigate data from 103 patients with refractoy OAB who underwent SNM implant in order to evaluate the role of symptoms duration as possible pre-treatment prognosticator. Study design, materials and methods From September 2001 to November 2010 a total of 103 patients attending four different urological centres with refractory OAB underwent a temporary SNM implant. Patient data (demographics, medical history,urologic investigations, and diagnosis) were collected. Temporary implant results were evaluated from a voiding diary and patient history. More than 50% improvement of voiding parameters was considered a successful SNM and those patients were selected for implantation. We test the duration of complaints as prognosticator for predicting SNM result. We performed the Pearson correlation analysis. For comparison between groups either Student's t test or Mann-Whitney test were used, as appropriate. Results Eighty patients (77%) underwent a definitive implant. At a mean follow-up of 25.2 \uf0b1 22.9 months we observed a significant decrease (p<0.001) in the mean number of incontinence episodes/die (1.3\ub1 1.9 versus 4.6\ub12.4), number of pads/die (1.2 \ub1 1.4 versus 3.7 \ub1 2.2), daily urinary frequency (8.7 \ub1 2.8 micturitions/die versus 12.7 \ub1 4.8). Stratifying patients according to the lower urinary tract dysfunction aetiology (idiopathic, neurogenic, iatrogenic), we did not find any significant correlation between symptoms duration (neither as continuous nor categorical variables) and the improvement rates of incontinence episodes (figures 1-2), and micturition frequency (figures 3-4), although we observed better results mainly in neurogenic patients with < 4- year history of urinary symptoms (figure 5). Interpretation of results Patients with urgency and urge urinary incontinence due to neurogenic lower urinary tract dysfunction for a relatively long period of time may have a lower chance of a positive test compared with patients with neurogenic dysfunction for a relatively short period. Concluding message Duration of complaints was not found to be significant predictive factor for the success of SNM. Disclosure

Mass and metallicity scaling relations of high-redshift star-forming galaxies selected by GRBs

We present a comprehensive study of the relations between gas kinematics, metallicity and stellar mass in a sample of 82 gamma-ray burst (GRB)-selected galaxies using absorption and emission methods. We find the velocity widths of both emission and absorption profiles to be a proxy of stellar mass. We also investigate the velocity–metallicity correlation and its evolution with redshift. Using 33 GRB hosts with measured stellar mass and metallicity, we study the mass–metallicity relation for GRB host galaxies in a stellar mass range of 108.2–1011.1 M⊙ and a redshift range of z ∼ 0.3–3.4. The GRB-selected galaxies appear to track the mass–metallicity relation of star-forming galaxies but with an offset of 0.15 towards lower metallicities. This offset is comparable with the average error bar on the metallicity measurements of the GRB sample and also the scatter on the mass–metallicity relation of the general population. It is hard to decide whether this relatively small offset is due to systematic effects or the intrinsic nature of GRB hosts. We also investigate the possibility of using absorption-line metallicity measurements of GRB hosts to study the mass–metallicity relation at high redshifts. Our analysis shows that the metallicity measurements from absorption methods can significantly differ from emission metallicities and assuming identical measurements from the two methods may result in erroneous conclusions

Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

We have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues. CONCLUSIONS/SIGNIFICANCE: These findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises

Are we there yet? Australian road safety targets and road traffic crash fatalities

Background: Road safety targets are widely used and provide a basis for evaluating progress in road safety outcomes against a quantified goal. In Australia, a reduction in fatalities from road traffic crashes (RTCs) is a public policy objective: a national target of no more than 5.6 fatalities per 100,000 population by 2010 was set in 2001. The purpose of this paper is to examine the progress Australia and its states and territories have made in reducing RTC fatalities, and to estimate when the 2010 target may be reached by the jurisdictions. Methods. Following a descriptive analysis, univariate time-series models estimate past trends in fatality rates over recent decades. Data for differing time periods are analysed and different trend specifications estimated. Preferred models were selected on the basis of statistical criteria and the period covered by the data. The results of preferred regressions are used to determine out-of-sample forecasts of when the national target may be attained by the jurisdictions. Though there are limitations with the time series approach used, inadequate data precluded the estimation of a full causal/structural model. Results: Statistically significant reductions in fatality rates since 1971 were found for all jurisdictions with the national rate decreasing on average, 3% per year since 1992. However the gains have varied across time and space, with percent changes in fatality rates ranging from an 8% increase in New South Wales 1972-1981 to a 46% decrease in Queensland 1982-1991. Based on an estimate of past trends, it is possible that the target set for 2010 may not be reached nationally, until 2016. Unsurprisingly, the analysis indicated a range of outcomes for the respective state/territory jurisdictions though these results should be interpreted with caution due to different assumptions and length of data. Conclusions: Results indicate that while Australia has been successful over recent decades in reducing RTC mortality, an important gap between aspirations and achievements remains. Moreover, unless there are fairly radical ("trend-breaking") changes in the factors that affect the incidence of RTC fatalities, deaths from RTCs are likely to remain above the national target in some areas of Australia, for years to come

New understandings of the genetic basis of isolated idiopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone (GnRH) action. Because reduced or normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) levels may be observed in the affected patients, the term idiopathic central hypogonadism (ICH) appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and is fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome (KS). KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH (nICH), justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network

Genomes of the Most Dangerous Epidemic Bacteria Have a Virulence Repertoire Characterized by Fewer Genes but More Toxin-Antitoxin Modules

We conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. We also determined whether virulence is dictated by rules, or if it is the result of individual evolutionary histories. We systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans ("bad bugs") to their closest non-epidemic related species ("controls").We found several significantly different features in the "bad bugs", one of which was a smaller genome that likely resulted from a degraded recombination and repair system. The 10 Cluster of Orthologous Group (COG) functional categories revealed a significantly smaller number of genes in the "bad bugs", which lacked mostly transcription, signal transduction mechanisms, cell motility, energy production and conversion, and metabolic and regulatory functions. A few genes were identified as virulence factors, including secretion system proteins. Five "bad bugs" showed a greater number of poly (A) tails compared to the controls, whereas an elevated number of poly (A) tails was found to be strongly correlated to a low GC% content. The "bad bugs" had fewer tandem repeat sequences compared to controls. Moreover, the results obtained from a principal component analysis (PCA) showed that the "bad bugs" had surprisingly more toxin-antitoxin modules than did the controls.We conclude that pathogenic capacity is not the result of "virulence factors" but is the outcome of a virulent gene repertoire resulting from reduced genome repertoires. Toxin-antitoxin systems could participate in the virulence repertoire, but they may have developed independently of selfish evolution