Low vitamin K1 intake in haemodialysis patients.

BACKGROUND & AIMS: Vitamin K acts as a coenzyme in the γ-carboxylation of vitamin K-dependent proteins, including coagulation factors, osteocalcin, matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6) protein. Osteocalcin is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification. GAS6 activity prevents the apoptosis of vascular smooth muscle cells. Few data on vitamin K intake in chronic kidney disease patients and no data in patients on a Mediterranean diet are available. In the present study, we evaluate the dietary intake of vitamin K1 in a cohort of patients undergoing haemodialysis. METHODS: In this multi-centre controlled observational study, data were collected from 91 patients aged >18 years on dialysis treatment for at least 12 months and from 85 age-matched control subjects with normal renal function. Participants completed a food journal of seven consecutive days for the estimation of dietary intakes of macro- and micro-nutrients (minerals and vitamins). RESULTS: Compared to controls, dialysis patients had a significant lower total energy intake, along with a lower dietary intake of proteins, fats, carbohydrates, fibres, and of all the examined minerals (Ca, P, Fe, Na, K, Zn, Cu, and Mg). With the exception of vitamin B12, vitamins intake followed a similar pattern, with a lower intake in vitamin A, B1, B2, C, D, E, folates, K1 and PP. These finding were confirmed also when normalized for total energy intake or for body weight. In respect to the adequate intakes recommended in the literature, the prevalence of a deficient vitamin K intake was very high (70-90%) and roughly double than in controls. Multivariate logistic model identified vitamin A and iron intake as predictors of vitamin K deficiency. CONCLUSIONS: Haemodialysis patients had a significantly low intake in vitamin K1, which could contribute to increase the risk of bone fractures and vascular calcifications. Since the deficiency of vitamin K intake seems to be remarkable, dietary counselling to HD patients should also address the adequacy of vitamin K dietary intake and bioavailability. Whether diets with higher amounts of vitamin K1 or vitamin K supplementation can improve clinical outcomes in dialysis patients remains to be demonstrated.

Margin and complication rates in clampless partial nephrectomy: a comparison of open, laparoscopic and robotic surgeries.

In performing partial nephrectomy (PN), surgeons focus on complete removal of tumor, preservation of renal function, the absence of major perioperative complications, expressed by the formula margin, ischemia and complication (MIC). The aim of current study was to perform a single-institution comparison of clampless open (OPN), laparoscopic (LPN) or robot-assisted (RAPN) PN as well as to evaluate pre-, intra- and postoperative factors that may influence achievement of ideal MIC. All consecutive clampless OPN, LPN or RAPN performed by experienced surgeons between 2006 and 2015 were included in the analysis. MIC was defined as negative surgical margin plus zero-ischemia plus absence of any grade ≥3 complications according to Clavien-Dindo classification. Bivariate and multivariate logistic regression models were fitted to predict the MIC. Odds ratios with 95 % confidence intervals were calculated. 80 patients underwent OPN, 66 LPN and 31 RAPN, and both groups had similar characteristics. The MIC rate was 67.5, 86.3 and 83.3 % in the OPN, LPN and RAPN groups, respectively (p = 0.016). At logistic regression analysis, surgical approach (p = 0.03) and operative time (p = 0.008) were independent predictors of the MIC rate. When stratified according to the surgical approach, preoperative aspects and dimensions used for an anatomical classification (PADUA) score, LPN, RAPN and operative time were independent predictors of MIC rate (p = 0.0488, p = 0.0494, p = 0.0479 and p = 0.0108, respectively). Clampless LPN and RAPN have an efficacy and safety profile that is on par with OPN, offering the additional benefits of a reduced operative time, blood loss, on demand ischemia and rate of high-grade complications.

Evaluation of electrospun bioresorbable scaffolds for tissue-engineered urinary bladder augmentation.

Tissue engineering represents a potential and valuable approach for the treatment of urologic pathologies. Bioresorbable polymeric scaffolds can be regarded as effective platforms to surgically treat bladder diseases and subsequently guide the formation of novel tissue after implantation. To this aim, the evaluation of electrospun scaffolds made up of poly(ε-caprolactone) blended with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) is presented here. Firstly, the microstructure and the viscoelastic/mechanical properties of the electrospun fabrics were investigated. Then, the in vivo response was assessed by performing a urinary bladder augmentation using female Wistar rats as an animal model. 15 days after the surgical procedure, the scaffolds were covered by regenerative urothelium up to 50%, which increased to 50-100% after 30 days. These encouraging results, collected in the 90-day follow-up, clearly showed the potential applications of tissue engineering in the urologic field. A longer in vivo evaluation is currently underway.

Efficacy of venom immunotherapy given every 3 or 4 months: a prospective comparison with the conventional regimen.

BACKGROUND: Standard venom immunotherapy involves the administration of the maintenance dose every 4 to 6 weeks. This regimen may have adherence problems, especially in the long term; thus, extended intervals have been proposed. OBJECTIVE: We prospectively compared the efficacy of 3- or 4-month extended maintenance dose vs the conventional regimen. METHODS: Patients receiving immunotherapy with a single venom were offered the extended maintenance dose (EMD) and were then followed up for field re-stings. Only the re-stings by the insect for which the patients received immunotherapy were considered. A comparable group of patients receiving the conventional maintenance dose (CMD) was used for comparison by logistic regression analysis. RESULTS: Seventy-six patients (60 male; mean age, 48 years) receiving the EMD were re-stung on 247 occasions by the insect for which they were receiving immunotherapy. The group receiving CMD included 110 patients (82 male; mean age, 44 years) certainly re-stung on 167 occasions by the specific insect. The percentage of re-sting without reaction was 93.5% in the EMD group and 81.5% in the CMD group, with a significant difference in favor of the former (P=.001). At logistic regression analysis, only age, but not maintenance dose protocol, was predictive of subsequent systemic reactions. CONCLUSION: The EMD is as effective and safe as the CMD. An increased maintenance seems to be the best option in term of convenience and economic savings.

Onabotulinumtoxin-A intradetrusorial injections modulate bladder expression of NGF, TrkA, p75 and TRPV1 in patients with detrusor overactivity.

How onabotulinumtoxinA (onab/A) injected in the detrusor muscle improves detrusor overactivity (DO) is still a matter of debate. Nerve growth factor (NGF) seems to play a role in determining urgency and DO. Recent studies showed that NGF decreases in patients with DO who respond to onab/A treatment. We investigated onab/A-induced changes on gene expression of NGF, TRPV1, TrkA and p75 in bladder wall tissue of patients affected by neurogenic and idiopathic DO. Twenty-five patients (18 with neurogenic DO and 7 with idiopathic DO) received onab/A injections into the detrusor muscle. Urodynamic studies and cystoscopies with sampling of the bladder wall were performed before and 1 month after onab/A injections. Onab/A-induced changes in urodynamic variables (first volume and maximum pressure of uninhibited detrusor contractions and maximum cystometric capacity) and NGF, TRPV1, TRKA, p75 gene expression by means of quantitative Real Time-Polymerase Chain Reaction. NGF protein levels were assessed in tissue homogenates by enzyme-linked immunosorbent assay. Onab/A significantly improved urodynamic findings (as shown by the increase in maximum cystometric capacity), decreased the bladder tissue levels of NGF protein and significantly increased NGF, TrkA, p75 and TRPV1 gene expression independently from the etiology of DO. No significant correlation has been found between NGF down-regulation and the increase in MCC. Correlations between NGF gene expression and NGF receptors' gene expression were influenced by onab/A dosages. In the short time follow-up, onab/A decreases NGF protein levels and increases NGF and associated receptors' gene expression possibly by inhibiting NGF release. Further studies with longer follow-up will clarify time course of onab/A-induced modifications in NGF expression.

Repeated white light transurethral resection of the bladder in nonmuscle-invasive urothelial bladder cancers: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transurethral resection of the bladder (TURB), the first step in treatment of patients with urothelial bladder cancers, is limited by technicalities, surgeon skill, and random chance. When high-risk superficial diseases are discovered, a repeated TURB is indicated. We reviewed current literature and performed a meta-analysis of the role of repeated TURB in the management of nonmuscle-invasive bladder cancers. METHODS: PubMed, MEDLINE, ISI Web of Knowledge, EBSCO, EMBASE, and Biomed Central databases were searched for reports in English from 1980 to June 2010. The end point was prevalence of persistent urothelial bladder cancer of any stage and grade at repeated TURB, assessed separately for T(a) and T(1) lesions at TURB. Persistence was presence at repeated TURB of same or lower stage cancer as at TURB; upstaging was presence of higher stage. RESULTS: There were 2327 original articles and 562 reviews retrieved. Data from 15 studies were pooled and analyzed. Prevalence of T(1) was reported in all and of T(a) in 8. Persistence rate prevalence at repeated TURB was 0.39 (95% confidence interval [CI]=0.26 to 0.54) for T(a) and 0.47 (95% CI=0.41 to 0.53) for T(1). Persistence was 19.4% to 56% and 15.2% to 55%, and upstaging occurred in 0% to 14.3% of T(a) and 0% to 24.4% of T(1) at repeated TURB, respectively. CONCLUSION: High percentages of persistence and upstaging confirm a repeated TURB is needed in patients with high-risk nonmuscle-invasive bladder cancer. Further investigation is encouraged taking risk stratification into consideration to evaluate the role of repeated TURB in low- and mid- risk diseases.

Managing mesh erosion after abdominal pelvic organ prolapse repair: ten years' experience in a single center.

OBJECTIVE: To report conservative and surgical strategies for treatment of mesh erosion after pelvic organ prolapse (POP) repair. METHODS: Between 1998 and 2008, 179 patients underwent integral pelvic floor reconstruction for advanced POP in our tertiary urogynecological unit. Patients' charts and follow-up data were entered into a computerized database and data analysis performed to search for mesh erosion/complications/surgery. RESULTS: 12 patients were diagnosed and treated for mesh erosion: in 10 of 179, surgery was performed in our department and the mesh used was polypropylene (PP): 3 after colposacropexy (CSP) (5.5%), 5 after CSP + hysterectomy (Hys) (6.5%), and 2 after hysterosacropexy (HSP) (3.9%); in 1 case, Gore-tex mesh was used, and another case had undergone CSP in another hospital using PP mesh. Time to mesh erosion ranged from 2 to 66 months (mean 22.9), with 4 erosions (33%) within 6 months of POP repair. In 4 asymptomatic patients (33%) erosion was incidentally discovered during clinical check-ups at 4, 31, 36 and 66 months. Five cases (41%) presented with occasional vaginal bleeding, associated with dyspareunia in 2. Treatments were individualized but in all cases conservative treatment was unable to resolve the complications and surgery was needed. At a mean follow-up of 57 months (range 18-120) after surgical treatment all patients were asymptomatic and free from erosions. CONCLUSIONS: The surgeon who approaches management of complications after abdominal/laparoscopic sacropexy should possess a comprehensive understanding of pelvic floor anatomy and surgical skills in order to individualize the management of such complications.

Vascular therapy for radiation cystitis.

PURPOSE: The underlying pathology of radiation cystitis is cellular and vascular damage followed by increased fibrosis and inflammation. This study was to determine if neovascular-promoting therapy could reduce the pathological changes in the bladder wall associated with pelvic irradiation. METHODS: Adult female Lewis inbred rats were irradiated with a single dose of 20 Gy directed at their bladder. Four weeks later, 30 rats were divided equally into one of three treatment groups for bladder wall injection of: (1) PBS (Control); (2) PBS containing 50 ng vascular endothelial growth factor (VEGF (165)); or (3) PBS containing 1 × 10(6) rat endothelial cells (EC). Age-matched non-irradiated rats (n = 10) served as untreated controls. At either 1.5 or 3 months following radiation, bladders were analyzed for collagen deposition using Masson's Trichrome staining of collagen and muscle and vascularization using Von Willebrand factor staining of ECs. Quantitative-PCR was used to examine markers of angiogenesis, hypoxia, and fibrosis. RESULTS: The collagen/muscle ratio was doubled in the control group 3 months post-irradiation (P < 0.05 vs. non-irradiated bladders). Both ECs and VEGF inhibited increases in collagen content (P < 0.05 vs. control). Similarly, irradiation reduced bladder wall vessel counts compared to non-irradiated controls (P < 0.05) and both ECs and VEGF maintained vessel counts similar to that of non-irradiated controls (P < 0.05). PCR analysis showed a higher expression of neovascular markers (CD31, KDR) in the EC and VEGF groups compared to non-irradiated controls (P < 0.05). CONCLUSIONS: Angiogenesis therapy may be useful in the prevention and/or treatment of the underlying pathology of radiation cystitis.

Preoperative Valsalva leak point pressure may not predict outcome of mid-urethral slings. Analysis from a randomized controlled trial of retropubic versus transobturator mid-urethral slings.

OBJECTIVE: To test the hypothesis that preoperative Valsalva leak point pressure (VLPP) predicts long-term outcome of mid-urethra slings for female stress urinary incontinence (SUI). MATERIALS AND METHODS: One hundred and forty-five patients with SUI were prospectively randomized to two mid-urethra sling treatments: Tension free vaginal tape (TVT) or transobturator tape (TOT). They were followed-up at 3, 6, 12 months post-operatively and then annually for the primary outcome variable, i.e. dry or wet and secondary outcome variables such as scores on the urogenital distress inventory (UDI-6) and the impact of incontinence on quality of life (IIQ-7) questionnaire as well as patient satisfaction as scored on a visual analogue scale (VAS). Preoperative VLPP was correlated with primary and secondary outcome variables. RESULTS: Mean follow-ups were 32 +/- 12 months (range 12-55) for TVT and 31 +/- 15 months (range 12-61) for TOT. When patients were analyzed according to VLPP stratification, 95 (65.5%) patients showed a VLPP > 60 cm H2O and 50 (34.5%) patients had a VLPP < or = 60 cm H2O. The overall objective cure rates were 75.8% for patients with VLPP > 60 cm H2O and 72% for those with VLPP < or = 60 cm H2O (p < 0.619). No significant differences in objective cure rates emerged when patients were stratified for pre-operative VLPP and matched for TOT or TVT procedures: VLPP > 60 cm H2O (82% vs. 68.9% p < 0.172); VLPP < or = 60 cm H2O (68% vs. 76% p < 0.528). CONCLUSIONS: When patients were stratified for preoperative VLPP (< or = or > of 60 cm H2O), preoperative VLPP was not linked to outcome after TVT or TOT procedures.

Preoperative Valsava leak point pressure may not predict outcome of mid-urethral slings: analysis from a randomized controlled trial of retropubic versus transobturator mid-urethral slings

OBJECTIVE: To test the hypothesis that preoperative Valsalva leak point pressure (VLPP) predicts long-term outcome of mid-urethra slings for female stress urinary incontinence (SUI). MATERIALS AND METHODS: One hundred and forty-five patients with SUI were prospectively randomized to two mid-urethra sling treatments: Tension free vaginal tape (TVT) or transobturator tape (TOT). They were followed-up at 3, 6, 12 months post-operatively and then annually for the primary outcome variable, i.e. dry or wet and secondary outcome variables such as scores on the urogenital distress inventory (UDI-6) and the impact of incontinence on quality of life (IIQ-7) questionnaire as well as patient satisfaction as scored on a visual analogue scale (VAS). Preoperative VLPP was correlated with primary and secondary outcome variables. RESULTS: Mean follow-ups were 32 + 12 months (range 12-55) for TVT and 31 + 15 months (range 12-61) for TOT. When patients were analyzed according to VLPP stratification, 95 (65.5 percent) patients showed a VLPP > 60 cm H2O and 50 (34.5 percent) patients had a VLPP < 60 cm H2O. The overall objective cure rates were 75.8 percent for patients with VLPP > 60 cm H2O and 72 percent for those with VLPP < 60 cm H2O (p < 0.619). No significant differences in objective cure rates emerged when patients were stratified for pre-operative VLPP and matched for TOT or TVT procedures: VLPP > 60 cm H2O (82 percent vs. 68.9 percent p < 0.172); VLPP < 60 cm H2O (68 percent vs. 76 percent p < 0.528). CONCLUSIONS: When patients were stratified for preoperative VLPP (< or > of 60 cm H2O), preoperative VLPP was not linked to outcome after TVT or TOT procedures.

Voiding dysfunction after radical retropubic prostatectomy: more than external urethral sphincter deficiency.

OBJECTIVES: To analyse the relationship between RRP and urodynamic bladder dysfunction, and compare preoperative and postoperative functional status over long-term follow-up. Hypothesis on the pathophysiologic mechanism underlying urodynamic dysfunction has been reported. METHODS: PubMed databank search for original articles followed by review of urodynamic parameters: bladder filling sensation, detrusor overactivity, bladder compliance, cystometric bladder capacity, impaired detrusor contractility, bladder outlet obstruction, urinary incontinence. RESULTS: Detrusor dysfunction was rarely present as the sole diagnosis and was usually coupled with intrinsic sphincter deficiency. Data on bladder filling sensation, cystometric capacity, detrusor overactivity, impaired detrusor contractility, and bladder outlet obstruction were limited and contradictory. Detrusor overactivity was a de novo dysfunction in 2%-77% of patients. Impaired bladder compliance was present in 8%-39% of patients and was de novo in about 50%. Impaired detrusor contractility was found in 29%-61% of patients, was de novo in 47%, and recovered in about 50% of patients. The role of these dysfunctions as etiologic agents of urinary incontinence or voiding symptoms was unevenly assessed. CONCLUSIONS: Postoperative decentralization of the bladder, inflammation and/or infection, and geometric bladder wall alteration associated with preexisting hypoxemia with/without neuroplasticity have been posited as causes of detrusor dysfunction. Nevertheless, the lack of consistent preoperative urodynamic investigation makes it difficult to assess the operation's exact role in causing these dysfunctions. Thus, urodynamics performed, at least in selected cases, preoperatively and during follow-up could help arrive at a precise diagnosis of the underlying dysfunction, indicate the appropriate treatment, and prevent the incidence and onset of postoperative urinary incontinence.

Are the baseline chances of survival comparable between the candidates for kidney transplantation who actually receive a graft and those who never get one?

BACKGROUND: The superiority of kidney transplantation over dialysis for patient survival often is assessed by comparing the survival rate of candidates who get a graft to that of those on the waiting list who do not. This study tries to ascertain if the two groups are comparable in terms of their chances of surviving. METHODS: Of the 187 non-diabetic patients who entered our waiting list during 1998 and 1999 for first cadaveric kidney transplants, 81 received a graft and 106 did not. We compared the two groups for factors which could affect survival and that were present at the moment of acceptance on the list. As one of those factors was the clinical score quantifying health status, as given by the transplant team and rated from 1 (high risk) to 4 (very good), we assessed its reliability by evaluating the survival of the patients we transplanted between 1988 and 1996, grouped according to that score. RESULTS: Transplanted patients had been immunized less frequently (2 vs 13%; P=0.02), had a lower dialytic age (16.9+/-2.1 vs 22.9+/-2.1 months; P<0.05), and better clinical scores (2.9+/-0.1 vs 2.6+/-0.1; P<0.05). The two groups did not differ in age, gender, or the presence of single specific diseases. Logistic regression analysis confirmed the results of univariate analysis. The clinical score was a very strong predictor of patient survival, as the survival of patients transplanted from 1988 to 1996 progressively improved with better scores (P<0.0001). CONCLUSIONS: Transplanted patients actually differ from non-transplanted candidates with respect to various factors potentially affecting survival. The difference is highly relevant clinically, yet it is not easily detected when considering mainly the presence or absence of specific diseases. A global quantitative clinical parameter based on a thorough medical evaluation is required to identify differences.