Marco Torella

Tension-free Vaginal Tape for the Treatment of Urodynamic Stress Incontinence: Efficacy and Adverse Effects at 10-Year Follow-Up

BACKGROUND One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings. OBJECTIVE To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. INTERVENTION Standard retropubic TVT. MEASUREMENTS Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes. RESULTS AND LIMITATIONS A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p>0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9cm H(2)O (hazard ratio [HR]: 16.2; p=0.01) and maximum detrusor pressure during the voiding phase ≤29cm H(2)O (HR: 8.0; p=0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p=0.01) and of USI (HR: 8.9; p=0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred. CONCLUSIONS The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.

The endovanilloid/endocannabinoid system in human osteoclasts: Possible involvement in bone formation and resorption

Recent studies suggest a role for the endocannabinoid/endovanilloid anandamide in the regulation of bone resorption/formation balance in mice. Here, we examined the co-expression of the transient receptor potential vanilloid type 1 (TRPV1) and the cannabinoid CB1/CB2 receptors together with N-acylphosphatidylethanolamine-hydrolizing phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), the two enzymes responsible of the synthesis and catabolism of anandamide respectively, in human osteoclasts. Co-expression of TRPV1, CB1/CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Moreover, agonist-evoked calcium entry indicated that the TRPV1 receptor is functionally active in vitro. Consistently, biomolecular and functional experiments showed that resiniferatoxin (RTX), a selective TRPV1 receptor agonist, increased the expression and the activity of TRAP and cathepsin K, two specific osteoclast biomarkers. The evidence that cannabinoid and vanilloid receptors are co-expressed in human osteoclasts suggests that they might cross-talk to modulate the intrinsic balance of bone mineralization and resorption by different actions of anandamide through TRPV1 and cannabinoid receptors. The presence of the endocannabinoid/endovanilloid proteins in human osteoclasts will likely have implications for the management of bone demineralization associated syndrome (i. e. osteoporosis).

Urinary tract infections in women

Urinary tract infections (UTIs) are conditions frequently complained by women both in the general population and in the hospital setting. Indeed it has been estimated that one woman out of three will experience at least an episode of UTI during lifetime. A comprehensive literature review of published experimental and clinical studies of UTI was carried out at the University of Insubria electronic library (SFX Bicocca-Insubria) with cross-search of seven different medical databases (AMED, BIOSIS Previews on Web of Knowledge, Cochrane Library, Embase and Medline on Web of Knowledge, OvidSP and PubMed). We aimed to draw a clinical guideline addressed to the management of UTI, based on the most recent evidence.

The impact of urinary stress incontinence in young and middle-age women practising recreational sports activity: an epidemiological study

Objectives: To evaluate the prevalence of urinary stress incontinence (USI) in menstruating women practising recreational sports activity, to detect specific sports with a stronger association with urinary incontinence (UI) and to evaluate risk factors possibly related to this condition. Design: Epidemiological study. Setting: Non-competitive sports organisations in the province of Varese, Italy. Participants: 679 women of fertile age, practising recreational sports activity. Intervention: Anonymous questionnaire on UI. Main outcome measurements: The questionnaire included questions about patients’ general characteristics, occurrence of UI in relation to sport or daily general activities, time of onset of this condition, frequency of leakage episodes, correlation of incontinence with types of movements or sports, subjective impression of being limited on such occasions and/or necessity to modify the type of sport. Results: UI was reported by 101 women (14.9%). Of these, 32 (31.7%) complained of UI only during sports activity, 48 (47.5%) only during daily life and 21 (20.8%) in both circumstances. Body mass index and parity were significantly associated with the risk of UI. Looking at the different sports activities, a higher rate of incontinence was found in women participating in basketball (16.6%), athletics (15%), and tennis or squash (11%). 10.4% of women abandoned their favourite sport, because of USI, and a further 20% limited the way they practised their favourite sport to reduce leakage episodes. Conclusions: Female UI affects a significant proportion of young women practising non-competitive sports activity; it can cause abandonment of the sport or limitation of its practice.

TVT-O for the Treatment of Pure Urodynamic Stress Incontinence: Efficacy, Adverse Effects, and Prognostic Factors at 5-Year Follow-up

BACKGROUND Inside-out tension-free vaginal transobturator tape (TVT-O) is currently one of the most effective and popular procedures for the surgical treatment of female stress urinary incontinence (SUI), but data reporting long-term outcomes are scarce. OBJECTIVE To evaluate the efficacy and safety of TVT-O 5-yr implantation for management of pure SUI in women. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was conducted in four tertiary reference centers. Consecutive women presenting with urodynamically proven, pure SUI treated by TVT-O were included. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. INTERVENTION TVT-O implantation without any associated procedure. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Data regarding subjective outcomes (International Consultation on Incontinence-Short Form [ICIQ-SF], Patient Global Impression of Improvement, patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow-up. Multivariable analyses were performed to investigate outcomes. RESULTS AND LIMITATIONS Of the 191 women included, 21 (11.0%) had previously undergone a failed anti-incontinence surgical procedure. Six (3.1%) patients were lost to follow-up. The 5-yr subjective and objective cure rates were 90.3% and 90.8%, respectively. De novo overactive bladder (OAB) was reported by 24.3% of patients at 5-yr follow-up. Median ICIQ-SF score significantly improved from 17 (interquartile range [IQR]:16-17) preoperatively to 0 (IQR: 0-2) (p<0.0001). Failure of a previous anti-incontinence procedure was the only independent predictor of subjective recurrence of SUI (hazard ratio [HR]: 4.4; p = 0.009) or objective (HR: 3.7; p = 0.02). No predictive factor of de novo OAB was identified. CONCLUSIONS TVT-O implantation is a highly effective option for the treatment of women with pure SUI, showing a very high cure rate and a low incidence of complications after 5-yr follow-up.

Distribution of Notch protein members in normal and preeclampsia-complicated placentas

Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry. In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21Cip1 in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology.

The endovanilloid/endocannabinoid system: A new potential target for osteoporosis therapy

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis. We report that in osteoclasts from osteoporotic patients, TRPV1 channels are upregulated and, if persistently stimulated with resiniferatoxin, become clustered to the plasma membrane while inducing a massive over-expression of CB2 receptors. By providing new evidence for a critical functional cross-talk between CB2 and TRPV1 receptors in osteoporosis, we speculate that TRPV1 desensitization, or its enhanced trafficking, together with TRPV1 agonist-induced CB2 receptor overexpression, might be critical to minimize calcium entry in osteoclasts, which could be in turn responsible of cell over-activation and higher bone resorption. Our data pave the way to the use of TRPV1 agonist together with CB2 agonists or CB1 antagonists in osteoporosis.

Effectiveness of the association micronized N-Palmitoylethanolamine (PEA)–transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study

OBJECTIVE Aim of our study was to evaluate the effectiveness of the association between N-Palmitoylethanolamine and transpolydatin in the management of chronic pelvic pain related to EMS. STUDY DESIGN This was a randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 61 subjects, submitted to a first line laparoscopic conservative surgery, who were randomized into 3 groups receiving: group A (n=21) the association N-Palmitoylethanolamine-transpolydatin 400 mg + 40 mg twice a day for 3 months; group B (n=20) the placebo for 3 months; group C (n=20) a single course of Celecoxib 200mg twice a day for 7 consecutive days. Assessments of the severity of pelvic endometriosis (pelvic pain, dysmenorrhoea and dyspareunia) were recorded before and after treatment on a questionnaire and a 10-point VAS. Differences between groups were verified with Kruskal-Wallis ANOVA for non-parametric multiple comparisons. RESULTS A marked decrease in dysmenorrhoea, dyspareunia and pelvic pain was observed in all groups, and the association between N-Palmitoylethanolamine and transpolydatin resulted to be more effective than placebo (P<.001). Additionally, the treatment with Celecoxib resulted in a decrease in pelvic pain more effective either than the association N-Palmitoylethanolamine and transpolydatin or placebo. CONCLUSION These preliminary results show that the association between micronized N-Palmitoylethanolamine and transpolydatin is effective in the management of pelvic pain related to endometriosis after laparoscopy. Additionally, this association seems to be safe, shows an optimal control of pain and can be used in patients who are unable to receive other therapies.

Raloxifene slows down the progression of intima-media thickness in postmenopausal women.

Objective:To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women. Design:In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor &agr;, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined. Results:The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857 mm/18 months in the placebo group (P < 0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P < 0.02), low-density lipoprotein cholesterol (P < 0.02), soluble forms of intercellular adhesion molecule-1 (P < 0.005) and vascular cell adhesion molecule-1 (P < 0.04), E-selectin (P < 0.02), interleukin-6 (P < 0.005), tumor necrosis factor &agr; (P < 0.005) levels, and homeostatic model assessment index (P < 0.005) and a significant increase in plasma adiponectin levels (P < 0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio = 0.41; 95% CI: 0.32-0.70). Conclusion:Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.

Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels

The pathogenesis of bone resorption in β-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with β-thalassemia major and its relationship with iron overload and iron chelation therapy. This study demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting tartrate-resistant acid phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both tartrate-resistant acid phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that transient receptor potential vanilloid type 1 activation/desensitization influences tartrate-resistant acid phosphatase expression and activity, and this effect is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in patients with thalassemia major. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-thalassemia major –preventing iron-overload and alleviating associated osteoporotic changes – is exciting.