Long-term efficacy of the trans-obturator and retropubic mid-urethral slings for stress urinary incontinence: update from a randomized clinical trial

Purpose

To report the extended long-term results of the use of tension-free vaginal tape(TVT) and trans-obturator tape (TOT) for the treatment of female stress urinary incontinence (SUI).

Methods

A prospective, multicentre randomized clinical trial comparing the use of TVT and TOT was used to evaluate 87 patients. The inclusion criteria were stress or mixed UI associated with urethral hyper mobility (the stress component was clinically predominant), while the exclusion criteria were previous anti-incontinence surgery and/or pelvic organ prolapse. The objective cure criteria were a negative provocative stress test and a negative 1-h pad test, with no further treatment for SUI. The subjective cure criteria were a 3-day voiding diary, quality-of-life questionnaires (UDI6–IIQ7), and patient satisfaction on a scale from 0 to 10.

Results

Eighty-seven patients were evaluated (47 TOT and 40 TVT) at a median follow-up of 100 months. Subjective and objective cure rates were 59.6 and 70.2 % in the TOT group and 75 and 87.5 % in the TVT group. The mid-to-long-term trend was a decreasing continence rate in patients who underwent TOT, compared with a stable rate for TVT. The Kaplan–Meier survival curve showed that continence rate decreased for up to 25 months after surgery, with stabilization thereafter for the TVT group while continuing to drop in the TOT group, with no inter-group difference.

Conclusion

The patients in both groups were highly satisfied at long-term follow-up. The overall continence rate worsened for both groups within 25 months. While the results tend to stabilize in the TVT group, a further decline in the TOT was observed.

     

Endometrioid-like yolk sac and Sertoli-Leydig cell tumors in a carrier of a Y heterochromatin insertion into 1qh region: a causal association?

We describe the case of a young woman showing yolk sac tumors (YST) and a Sertoli-Leydig cell tumor (SLCT) in the right ovary, with recurrences in the right adnexum and with hepatic metastasis. To our knowledge, YST and SLCT have never been described as components of the same tumor or reported as associated in the same patient. The patient's karyotype showed the presence of Y chromosome inserted into the 1qh region; the inserted region corresponded to Yq12 heterochromatin. LOH analysis revealed 1p36 paternal allele loss in the proband tumor, thus supporting a germ cell origin for the tumor. The presence of Y heterochromatin in 1qh DNA might induce disturbances in the normal regulation of oncogenes located in 1q.     

Simultaneous occurrence of peripheral T-cell lymphoma unspecified and B-cell small lymphocytic lymphoma. Report of 2 cases

We report on 2 composite lymphomas occurring in elderly patients, morphologically characterized by the combination of peripheral T-cell lymphoma (PTCL) unspecified and B-cell small lymphocytic lymphoma. Immunohistochemistry provided objective confirmation of the coexistence of the 2 malignancies, as did molecular biology by revealing clonal T-cell receptor gamma and immunoglobulin heavy chain gene rearrangements. One of the patients had no history of indolent lymphoma either at the personal and family level, whereas the other showed a strong familial predisposition, his mother and sister having suffered from B-cell chronic lymphocytic leukemia. Epstein-Barr virus was detected in the PTCL component of 1 case, but was negative in the other. To the best of our knowledge, the simultaneous occurrence of PTCL unspecified and B-cell small lymphocytic lymphoma is an exceptional event; the possible pathogenetic correlations between the 2 neoplasms are discussed.     

Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings

Objective

To calculate the prevalence of common gain of function gene mutations in patients with different clinical manifestations of venous thromboembolism.

Design and setting

Case–control study in two hospitals in Italy.

Participants

387 patients with venous thromboembolism and 286 controls.

Main measures

Factor V (FV) Leiden, factor II (FII) A20210 and JAK2 V617F mutations.

Results

Among patients with deep vein thrombosis in one leg, 23 (20.9%) carried FV Leiden and FII A20210 mutations. Similar figures were observed in patients with cerebral vein thrombosis (CVT; n = 9; 20.0%) and in patients presenting with splanchnic vein thrombosis (SVT; n = 26; 18.7%). A lower prevalence was obtained in patients with retinal vein thrombosis (n = 11; 11.8%). The JAK2 F617 mutant allele was found in 27 (21.1%) patients with SVT, but in none of the patients presenting with a thrombotic event from different districts. 13 of the 27 JAK2 V617F‐positive subjects with SVT were previously known to have a myeloproliferative disease (MPD). Three other patients had a diagnosis of MPD after the occurrence of the thrombotic event.

Conclusion

Carriership of FV Leiden or FII A20210 mutations identifies an at‐risk condition for venous thrombosis in the lower extremities, SVT or CVT. In patients with SVT, screening for the JAK2 V617F mutation may be useful in recognising patients who should be carefully observed for the subsequent development of overt MPD. Thus, genetic tests may play a different role, various clinical manifestations of venous thromboembolism being associated with distinct risk profiles.Venous thrombosis is the third most common cardiovascular affliction after ischaemic heart disease and stroke.¹ It is common in Caucasians, affecting 1 in 1000 individuals every year, and is strongly associated with life‐threatening pulmonary embolism. The pathogenesis of venous thrombosis is multifactorial, involving acquired and genetic factors. In addition to circumstantial predisposing factors (eg, surgery, pregnancy, immobilisation and malignancy), genetic predisposition due to molecular abnormalities of components of the coagulation pathway have been found in subjects who had had thromboembolic disease.² Abnormalities within the gene loci encoding for natural anticoagulants (antithrombin, protein C and protein S) and for fibrinogen have been shown to be rather uncommon risk factors for venous thrombosis.³ In patients of European ancestry, common gain‐of‐function mutations within the gene of the coagulation factor V (FV Leiden mutation) and the factor II (FII) gene (a G→A transition at nucleotide position 20210) have been shown to account for a large number of cases of thromboembolism.^2,3 Recently, the JAK2 V617F mutation, an acquired somatic event occurring in most patients with polycythaemia vera (PV) and in about half of the patients with essential thrombocythaemia (ET) or myelofibrosis (MF),^4,5,6,7,8 has been found in a high proportion of patients with Budd–Chiari syndrome⁹ and in patients without cirrhosis with portal and mesenteric venous thrombosis, a heterogeneous group of disorders.¹⁰Thus, the high frequency of common mutations in patients presenting with venous thromboembolism raised the hypothesis that it can be considered as a feasible and practical approach for the identification of predisposing genetic risk factors. Genetic test results can better inform individuals about their risk of recurrence and appropriated tailored strategies for the prevention of venous thrombosis.However, depending on the different clinical manifestations of venous thromboembolism, the prevalence of inherited coagulation abnormalities varies, suggesting pathogenic differences.^11,12,13 These data support the hypothesis that mechanistic differences are involved in the pathogenesis of thrombosis in different clinical settings. Thus, before considering whether it is advisable to investigate a subject for inherited risk factors, we need to know the prevalence of these risk factors in different clinical settings.We, therefore, calculated the prevalence of inherited thrombophilic risk factors in a large cohort of patients referred for a thrombophilic investigation with different clinical manifestations of venous thromboembolism.     

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.     

The impact of social work environment, teamwork characteristics, burnout, and personal factors upon intent to leave among European nurses

OBJECTIVES: Europe's nursing shortage calls for more effective ways to recruit and retain nurses. This contribution aims to clarify whether and how social work environment, teamwork characteristics, burnout, and personal factors are associated with nurses' intent to leave (ITL). METHODS: Our sample comprises 28,561 hospital-based nurses from 10 European countries. Different occupational levels have been taken into account: qualified registered nurses (n = 18,594), specialized nurses (n = 3957), head nurses (n = 3256), and nursing aides and ancillary staff (n = 2754). RESULTS: Our outcomes indicate that ITL is quite prevalent across Europe, although we have found some differences across the countries depending on working conditions and economic situation. Quality of teamwork, interpersonal relationships, career development possibilities, uncertainty regarding treatment, and influence at work are associated with nurses' decision to leave the profession across Europe, notwithstanding some country-specific outcomes. A serious lack of quality of teamwork seems to be associated with a 5-fold risk of ITL in 7 countries. As far as personal factors are concerned, our data support the hypothesized importance of work-family conflicts, satisfaction with pay, and burnout. A high burnout score seems to be associated with 3 times the risk of ITL in 5 countries. CONCLUSIONS: To prevent premature leaving, it is important to expand nurses' expertise, to improve working processes through collaboration and multidisciplinary teamwork, and to develop team training approaches and ward design facilitating teamwork.     

Molar bite force and its correlation with signs of temporomandibular dysfunction in mixed and permanent dentition

The aim of the study was to evaluate molar bite force (BF) magnitude and its correlation to the signs of temporomandibular dysfunction (TMD), gender, weight, height and age in 101 students ranging in age from 6 to 18 years (32 boys/21 girls with mixed dentition and 23 boys/25 girls with permanent dentition). TMD clinical signs were evaluated using the Craniomandibular Index (CMI), and two subscales, the Dysfunction Index (DI) and the Palpation Index (PI). BF was determined with a pressurized tube connected to a sensor (MPX5700-Motorola SPS). anova, Tukey's test, and Pearson's and Spearman's coefficients were evaluated. BF was higher in the permanent dentition (P < 0.05). There was no difference in BF between genders within the groups, but boys with permanent dentition had higher values than children with mixed dentition (P < 0.05). The girls with permanent dentition presented negative correlation in BF with PI and CMI (P < 0.05). BF was positively correlated with weight, height and age in the permanent dentition group (P < 0.05). It was concluded that BF increased from mixed to permanent dentition, with an assumed enhancing influence of body variables and ageing. The TMD signs in older girls were correlated to decreasing BF, suggesting an influence of muscle tenderness preventing subjects from exerting maximum BF.     

Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction.

The influence of liposome composition, size, lamellarity and charge on the (trans)dermal delivery of tretinoin (TRA) was studied. For this purpose we studied both multilamellar (MLV) or unilamellar (UV) liposomes. Positively or negatively charged liposomes were obtained using either hydrogenated (Phospholipon90H) or non-hydrogenated soy phosphatidylcholine (Phospholipon90) and cholesterol, in combination with stearylamine or dicetylphosphate. Liposomal formulations were characterized by transmission electron microscopy (TEM) and optical and light polarized microscopy for vesicle formation and morphology, and by dynamic laser light scattering for size distribution. In order to obtain more information about the stability and the thermodynamic activity of the liposomal tretinoin, TRA diffusion through a lipophilic membrane was investigated. The effect of the vesicular incorporation of tretinoin on its accumulation into the newborn pig skin was also studied. The experiments were performed in vitro using Franz cells in occlusive conditions and were compared to three different controls. The tretinoin amount delivered through and accumulated in the several skin layers was detected by HPLC. Furthermore, TEM in combination with osmium tetroxide was used to visualize the skin structure after the liposomal administration. Overall obtained results showed that liposomes may be an interesting carrier for tretinoin in skin disease treatment, when appropriate formulations are used. In particular, negatively charged liposomes strongly improved newborn pig skin hydration and TRA retention, though no evidence of intact vesicle penetration was found.