[Clinical path and life quality of women under 75 years with an urinary incontinence relevant to surgical treatment]. / Parcours de soins et qualité de vie des femmes de moins de 75 ans relevant d'une prise en charge chirurgicale pour incontinence urinaire.

OBJECTIVES: Urinary incontinence has a high prevalence and a significant impact on quality of life, especially for women. Surgery is possible after failure of lifestyle changes, physiotherapy. Analyzing the care pathway of women under 75 years of age who have undergone surgery for urinary incontinence in link with recommendation and suggest possible improvements. METHODS: Quantitative, multicentric, retrospective survey carried out between 10/09/2019 and 25/11/2019, based on anonymous self-report questionnaire, among women aged between 32 and 75 and operated in different hospitals in Loire (France). RESULTS: Ninety-three answers were exploited out of 204. Among the women, 49.5 % had stress, 50.5 % mixed incontinence. Before the intervention, it had evolved for 5 years on average and caused discomfort evaluated at an average 7.5/10. Eighty percent frequently used protective pads and bladder training. Lifestyle changes and the voiding diary were not used much. Eighty-six percent of women felt comfortable to speak to a physician. Seventy-three percent had performed a urodynamic test, 47 % an abdominal ultrasound and 40 % a urinalysis. Seventy-seven percent performed physiotherapy, 39 % self-administered physiotherapy, 7 % used medication. The postoperative quality of life was evaluated at 7.8/10; 58 % felt healed and 69 % considered their sex life had improved. CONCLUSIONS: The care pathway could be improved through systematic screening for urinary incontinence and its impact. The development of a care plan to coordinate and propose quick care could help patients to improve their life.

Socio-spatial inequalities in smoking among young adults: What a 'go-along' study says about local smoking practices.

Smoking prevalence in Canada has declined; yet, not among all segments of the population. Residents of high-deprivation neighbourhoods and young adults are over-represented among current smokers. There is a dearth of theoretically informed research focused on better understanding the connection between smoking, social inequalities, and place among young adults. To contribute to this understudied area, we undertook a qualitative study drawing upon the collective lifestyles framework. We conducted walking interviews (go-alongs) with 27 young adults (smokers and non-smokers) living in five diverse urban neighbourhoods in Montreal, Canada. We present the findings as neighbourhood portraits wherein participants' accounts revealed how local smoking practices shaped and were shaped by rules and regulations and the meaning and use of neighbourhood resources. In the discussion we reflect on the opportunities and constraints to smoking with a focus on young adults. We also consider the possible implications for socio-spatial inequalities in smoking and the relationship to tobacco control strategies.

Comparative analysis of outcomes after liver resection and liver transplantation for early stages hepatocellular carcinoma in HIV-infected patients. An intention-to-treat analysis.

BACKGROUND: To address the results of resection for hepatocellular carcinoma (HCC) in human immunodeficiency virus (HIV)-carriers, and to compare them against survival after liver transplantation (LT). METHODS: All patients with HIV and HCC listed for LT (candidates = LTc+) or resection (LR+) between 2000 and 2017 in our centre were analysed and compared for overall survival (OS) and disease-free survival (DFS). RESULTS: The LTc + group (n = 43) presented with higher MELD scores and more advanced portal hypertension and HCC stages than LR + group (n = 15). One-, 3- and 5-year intention-to-treat survival rates were: 81%, 60% and 44%, versus 86%, 58% and 58% in the LTc+ and LR + groups, respectively (p = 0.746). Eleven LTc + patients dropped out. After LT, OS was 81%, 68% and 59% (no difference with LR + group; p = 0.844). There tended to be better DFS after LT, reaching 78%, 68% and 56% versus 53%, 33% and 33% in the LR + group (p = 0.062). CONCLUSION: This was the largest series of resections for HCC in HIV + patients and the first intention-to-treat analysis. Although LT and resection do not always concern the same population, they enable equivalent survival. At the price of higher recurrence rate, resection could be integrated in the global armoury of liver surgeons.

Pharmacokinetics and biodistribution study of self-assembled Gd-micelles demonstrating blood-pool contrast enhancement for MRI.

Magnetic resonance angiography (MRA) requires the use of contrast agents (CAs) to enable accurate diagnosis. There are currently no CAs on the market with appropriate pharmacokinetic (PK) parameters, namely long persistence in the blood, that can be easily used for MRA. We have recently synthesized amphiphilic building blocks loaded with gadolinium (Gd), which self-assemble into Gd-micelles in aqueous media, and have evaluated their potential as a blood-pool contrast agent (BPCA) in vivo. To assess the short and long term PK of Gd-micelles, the blood and organs of the mice were analyzed at t = 30 min, 1, 2, 3 h, 7, 14 and 21 days. Gd-DOTA was used as a control because it is the gold-standard CA for MRA despite its rapid clearance from the blood compartment. Gd-micelles circulated in the blood for more than 3 h postinjection whereas Gd-DOTA was eliminated less than half an hour postinjection. No side effects were observed in the mice up to the end of the study at 21 days and no accumulation of Gd was observed in the brain or bones. The Magnetic Resonance Imaging (MRI) parameters and the results of this in vivo study indicate the true BCPA properties of Gd-micelles and warrant further development.

Added Value of Spectroscopy to Perfusion MRI in the Differential Diagnostic Performance of Common Malignant Brain Tumors.

BACKGROUND AND PURPOSE: Perfusion and spectroscopic MR imaging provide noninvasive physiologic and metabolic characterization of tissues, which can help in differentiating brain tumors. We investigated the diagnostic role of perfusion and spectroscopic MR imaging using individual and combined classifiers of these modalities and assessed the added performance value that spectroscopy can provide to perfusion using optimal combined classifiers that have the highest differential diagnostic performance to discriminate lymphomas, glioblastomas, and metastases. MATERIALS AND METHODS: From January 2013 to January 2016, fifty-five consecutive patients with histopathologically proved lymphomas, glioblastomas, and metastases were included after undergoing MR imaging. The perfusion parameters (maximum relative CBV, maximum percentage of signal intensity recovery) and spectroscopic concentration ratios (lactate/Cr, Cho/NAA, Cho/Cr, and lipids/Cr) were analyzed individually and in optimal combinations. Differences among tumor groups, differential diagnostic performance, and differences in discriminatory performance of models with quantification of the added performance value of spectroscopy to perfusion were tested using 1-way ANOVA models, receiver operating characteristic analysis, and comparisons between receiver operating characteristic analysis curves using a bivariate χ2, respectively. RESULTS: The highest differential diagnostic performance was obtained with the following combined classifiers: maximum percentage of signal intensity recovery-Cho/NAA to discriminate lymphomas from glioblastomas and metastases, significantly increasing the sensitivity from 82.1% to 95.7%; relative CBV-Cho/NAA to discriminate glioblastomas from lymphomas and metastases, significantly increasing the specificity from 92.7% to 100%; and maximum percentage of signal intensity recovery-lactate/Cr and maximum percentage of signal intensity recovery-Cho/Cr to discriminate metastases from lymphomas and glioblastomas, significantly increasing the specificity from 83.3% to 97.0% and 100%, respectively. CONCLUSIONS: Spectroscopy yielded an added performance value to perfusion using optimal combined classifiers of these modalities, significantly increasing the differential diagnostic performances for these common brain tumors.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries.

New Magnetic Resonance Imaging Index for Renal Fibrosis Assessment: A Comparison between Diffusion-Weighted Imaging and T1 Mapping with Histological Validation.

A need exists to noninvasively assess renal interstitial fibrosis, a common process to all kidney diseases and predictive of renal prognosis. In this translational study, Magnetic Resonance Imaging (MRI) T1 mapping and a new segmented Diffusion-Weighted Imaging (DWI) technique, for Apparent Diffusion Coefficient (ADC), were first compared to renal fibrosis in two well-controlled animal models to assess detection limits. Validation against biopsy was then performed in 33 kidney allograft recipients (KARs). Predictive MRI indices, ΔT1 and ΔADC (defined as the cortico-medullary differences), were compared to histology. In rats, both T1 and ADC correlated well with fibrosis and inflammation showing a difference between normal and diseased kidneys. In KARs, MRI indices were not sensitive to interstitial inflammation. By contrast, ΔADC outperformed ΔT1 with a stronger negative correlation to fibrosis (R(2) = 0.64 against R(2) = 0.29 p < 0.001). ΔADC tends to negative values in KARs harboring cortical fibrosis of more than 40%. Using a discriminant analysis method, the ΔADC, as a marker to detect such level of fibrosis or higher, led to a specificity and sensitivity of 100% and 71%, respectively. This new index has potential for noninvasive assessment of fibrosis in the clinical setting.

Effect of ischaemic preconditioning on recurrence of hepatocellular carcinoma in an experimental model of liver steatosis.

BACKGROUND: Livers with parenchymal abnormalities tolerate ischaemia-reperfusion (IR) injury poorly. IR injury is a risk factor for hepatocellular carcinoma (HCC) recurrence. This study assessed the link between liver parenchymal abnormalities and HCC recurrence, and evaluated the protective effect of ischaemic preconditioning. METHODS: C57BL/6 mice were fed a choline-deficient diet for 6 and 12 weeks, or standard chow. Hepatic IR and ischaemic preconditioning were achieved by clamping liver blood inflow. Hepa 1-6 HCC cells were inoculated through the spleen. Thereafter, tumour burden, serum α-fetoprotein and cancer cell aggressiveness were compared among groups. RESULTS: Hepatocellular damage and expression of inflammatory genes (encoding interleukin 6, tumour necrosis factor α, hypoxia inducible factor 1α and E-selectin) were exacerbated after IR injury in mice with severe steatosis. Compared with control livers or those with minimal steatosis, livers exposed to a prolonged choline-deficient diet developed larger tumour nodules and had higher serum α-fetoprotein levels. Non-ischaemic liver lobes from mice with steatosis were not protected from accelerated tumour growth mediated by IR injury. This remote effect was linked to promotion of the aggressiveness of HCC cells. Ischaemic preconditioning before IR injury reduced the tumour burden to the level of that in non-ischaemic steatotic controls. This protective effect was associated with decreased cancer cell motility. CONCLUSION: Livers with steatosis tolerated IR poorly, contributing to more severe HCC recurrence patterns in mice with increasingly severe steatosis. IR injury also had a remote effect on cancer cell aggressiveness. Ischaemic preconditioning before IR injury reduced tumour load and serum α-fetoprotein levels. SURGICAL RELEVANCE: Liver ischaemia-reperfusion (IR) injury is associated with organ dysfunction and surgical morbidity. Livers with steatosis tolerate IR injury poorly in the setting of both liver resection and liver transplantation. Ischaemic preconditioning is a simple method to mitigate IR injury. This study shows that ischaemic preconditioning of mouse livers with steatosis reduces ischaemia-mediated tumour growth acceleration. Liver parenchymal abnormalities such as warm IR injury and liver steatosis should be taken into account to predict accurately the risk of liver cancer recurrence after surgical management. Ischaemic preconditioning strategies may hold therapeutic potential not only to mitigate surgical morbidity but also to reduce postoperative recurrence of liver cancer.

Occupation-dependent loading increases bone strength in men.

SUMMARY: Ex vivo analyses of humeri and radii from an anthropological collection and in vivo analyses of the distal radius of retired men indicate that occupation-dependent loading positively influences bone strength by an increase of bone size when young followed by a slowdown of the age-related endocortical and trabecular bone alteration. INTRODUCTION: Skeleton responds to mechanical stimuli, but it is not established whether chronic loading in the context of occupational activities (OA) influences bone properties. We assessed the impact of occupation-dependent loading on upper limb bone strength. METHODS: Individuals were classified according to the intensity of physical loading associated with their OA in two models. Ex vivo, computed tomography scans of the humeri and radii of 219 male skeletons (age of death, 20-93 years) from an anthropological collection of the 20th century (Simon collection) were used to determine estimates of bone strength and cross-sectional geometry. In vivo, distal radius were analysed in 180 men enrolled in the Geneva Retirees Cohort study using high-resolution peripheral quantitative computed tomography and finite element analysis. RESULTS: Heavy-loading OA was associated with higher bone strength in both models. This benefit was associated with higher total area (Tt.Ar), medullary area (Me.Ar) and cortical area (Ct.Ar) in young adult skeletons, but the difference decreased in older age. In older men, the humerus supporting heavy loading had a lower Me.Ar. This effect resulted in greater asymmetries of the Me.Ar and the Ct.Ar/Tt.Ar ratio between the humeri of men with unilateral versus bilateral heavy-loading OA. In vivo, an additional benefit of heavy-loading OA was observed on the distal radius trabecular density and microstructure. CONCLUSION: Repeated occupation-dependent loading positively influences bone strength by an increase of bone size when young followed by a slowdown of the age-related endocortical and trabecular bone alteration. These data supports the necessity to promote bone health in the context of sedentary occupation.

Infectious complications after liver transplantation in human immunodeficiency virus-infected recipients.

BACKGROUND: Few studies have investigated infections in human immunodeficiency virus (HIV)-infected liver transplant patients. The aim of this study was to describe the prevalence, time of onset, mortality of infectious complications, other than hepatitis C virus (HCV), and to identify risk factors for their development in a large single-center cohort of HIV-infected liver transplant patients. METHODS: We studied 109 consecutive HIV-infected patients who underwent liver transplantation (LT) between 1999 and 2010 and followed until December 2012. RESULTS: The median age was 44 years (interquartile range [IQR] 41-49), 82.6% were male, and the median follow-up was 45.7 months (IQR 14-65). The major indications for LT were HCV cirrhosis (61%) and hepatocellular carcinoma (19%). Forty patients (37%) developed at least 1 infection during the first year after LT. Twenty-eight (26%) patients had an episode of bacteremia. Five (4.6%) patients developed a cytomegalovirus infection. Fungal infections occurred in 5 (4.5%) patients. Four (3.6%) patients developed an HIV-related opportunistic infection. A total of 43 (39.4%) patients died during follow-up. Mortality related to infection occurred in 9 (7%) cases, and 20 (42.5%) patients died because of HCV recurrence. No patients died from opportunistic infections. Model for end-stage liver disease (MELD) score >17 was associated with a 2-fold higher risk (hazard ratio 1.96; 95% confidence interval 1.01-3.80) of developing infectious complications. CONCLUSIONS: Infections are not a major cause of mortality after LT in HIV patients and opportunistic infections of acquired immunodeficiency syndrome are infrequent. A MELD score >17 increased the risk of developing post-LT infectious complications. Recurrence of HCV infection remains a major cause of mortality.

Low immunogenicity of quadrivalent meningococcal vaccines in solid organ transplant recipients.

Immunization against meningococcal disease is recommended for solid organ transplant (SOT) recipients at high risk for meningococcal disease or travelling to an endemic country. However, the immunogenicity of meningococcal vaccines has not been studied in this population. We analyzed the immune response of quadrivalent (against Neisseria meningitidis serogroups A, C, Y, and W) polysaccharidic non-conjugate and conjugate meningococcal vaccines in kidney- and liver-transplant patients using bactericidal assays against the targeted serogroups. Upon vaccination with a non-conjugate (n = 5) or a conjugate vaccine (n = 10), respectively, 40% and 50% of patients were able to mount an immune response, achieving at least the threshold correlated with protection defined as human serum bactericidal antibody titers of ≥4. Responders showed only partial and low responses (titers ≤64), thus predicting a rapid decline in bactericidal response. Only 1 patient developed a booster response to preexisting immunity. Our data argue for the need of additional measures for SOT recipients, when they are at risk of meningococcal disease.

Postmortem magnetic resonance imaging of the heart ex situ: development of technical protocols.

Postmortem MRI (PMMR) examinations are seldom performed in legal medicine due to long examination times, unfamiliarity with the technique, and high costs. Furthermore, it is difficult to obtain access to an MRI device used for patients in clinical settings to image an entire human body. An alternative is available: ex situ organ examination. To our knowledge, there is no standardized protocol that includes ex situ organ preparation and scanning parameters for postmortem MRI. Thus, our objective was to develop a standard procedure for ex situ heart PMMR examinations. We also tested the oily contrast agent Angiofil® commonly used for PMCT angiography, for its applicability in MRI. We worked with a 3 Tesla MRI device and 32-channel head coils. Twelve porcine hearts were used to test different materials to find the best way to prepare and place organs in the device and to test scanning parameters. For coronary MR angiography, we tested different mixtures of Angiofil® and different injection materials. In a second step, 17 human hearts were examined to test the procedure and its applicability to human organs. We established two standardized protocols: one for preparation of the heart and another for scanning parameters based on experience in clinical practice. The established protocols enabled a standardized technical procedure with comparable radiological images, allowing for easy radiological reading. The performance of coronary MR angiography enabled detailed coronary assessment and revealed the utility of Angiofil® as a contrast agent for PMMR. Our simple, reproducible method for performing heart examinations ex situ yields high quality images and visualization of the coronary arteries.

Infections in solid organ transplant HIV-infected patients.

Solid organ transplantation (SOT) is an appropriate therapeutic option for HIV-infected patients with end-stage organ disease. Recent experience in North America and Europe indicates that 3- to 5-year survival in HIV/HCV-coinfected liver recipients is lower than that of HCV-monoinfected recipients. Conversely, 3- to 5-year survival of non-HCV-coinfected transplant patients (liver, kidney and heart) was similar to that of non-HIV-infected patients. Preliminary experience with lung transplantation and combined kidney and pancreas transplantation is also satisfactory. Infections in HIV-infected recipients during the post-transplant period are similar to those seen in non-HIV-infected patients, although the incidence rates of tuberculosis and fungal infections seem to be higher. HIV-infected patients who are being evaluated for SOT should follow the same recommendations as those used for non-HIV-infected patients in order to prevent infections during the pre-transplant period. After transplantation, HIV-infected SOT recipients must follow recommendations on post-SOT and anti-HIV immunization and on antimicrobial prophylaxis. The recommended antiretroviral regimen is one based on raltegravir or dolutegravir plus two nucleos(t)ide reverse transcriptase inhibitors (tenofovir + emtricitabine or abacavir + lamivudine), because it can prevent pharmacokinetic interactions between antiretroviral drugs, immunosuppressive drugs and some of the antimicrobial agents used to treat or prevent post-transplant infections. In this manuscript, we review current recommendations for preventing infections both before and after transplantation. We also analyse the incidence, aetiology and clinical characteristics of opportunistic and non-opportunistic bacterial, mycobacterial, fungal and viral infections in HIV-infected SOT recipients during the post-transplant period.

Bone status and fractures in 85 adults with Wilson's disease.

UNLABELLED: Wilson's disease is characterized by copper deposition, especially in the liver and central nervous system. We assessed the prevalent fractures and bone mineral density (BMD) and related risk factors in 85 patients. BMD was normal, but patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk for fractures. INTRODUCTION: Wilson's disease (WD) is characterized by copper deposition, especially in the liver and central nervous system. Two studies showed a high prevalence of osteoporosis in WD patients. We wanted to assess the prevalent fractures and bone mineral density (BMD) and to identify risk factors for bone loss and fractures in a large group of WD patients. METHODS: In this prospective cross-sectional survey at National center of reference for WD, we included 85 patients, 47 women, and 38 men, with a mean age of 35 ± 10 years, and mean time from diagnosis to study of 21 ± 9 years; 57 (67%) patients had neurological signs. Peripheral fractures, prevalent radiological vertebral fractures (VFx), and dual-energy X-ray absorptiometry BMD measurements at the femoral neck (FN) and lumbar spine (LS) were studied. RESULTS: Mean LS and FN Z-score was normal (-0.37 ± 1.20 at LS and -0.06 ± 1.20 at FN). BMI <19 kg/m(2) and amenorrhea were associated with low BMD. Prevalent peripheral fractures were noted in 43 (51%) and VF in 7 (8%) patients. Severity of neurological involvement and male sex was associated with peripheral fractures, whereas older age, severe neurological involvement, and low BMD and Z-score values were associated with VF. CONCLUSION: Our data showing normal BMD overall do not support routine bone status evaluation in adults with WD. However, patients with severe neurological involvement, low BMI, and/or amenorrhea are at risk factors for fractures and may require specific monitoring.

Very prolonged liposomal amphotericin B use leading to a lysosomal storage disease.

Amphotericin B is a powerful polyene antifungal drug used for treating systemic fungal infections and is usually administered for a short period. Side effects after prolonged use are unknown in humans. Here we report the case of a 28-year-old man suffering from chronic granulomatous disease (CGD), treated for invasive cerebral aspergillosis with liposomal amphotericin B (L-AmB) for a very long time (8 consecutive years). We describe the efficacy and safety of this treatment in the long term. Aspergillosis was kept under control as long as L-AmB therapy was maintained, but relapsed when the dose was reduced. No overt renal toxicity was noted. The patient gradually developed hepatosplenomegaly and pancytopenia. Abnormalities of bone marrow were similar to the sea-blue histiocyte syndrome. Liver biopsy showed images of nodular regenerative hyperplasia related to CGD as well as a histiocytic storage disease. We discuss the very prolonged use of L-AmB leading to the development of a lysosomal storage disease.