Teresa Martí

Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial

BackgroundTuberous sclerosis (TS) is a rare autosomal dominant systemic disease with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign tumour with high morbidity frequently present in TS. The aim of the study was to test the effect of rapamycin in reducing the volume of AML in TS.MethodsTwenty four-month prospective open-label, single arm, unicentre Phases II andIII study. The primary endpoint was to evaluate the effect of treatment on the reduction of at least 50% AML volume from baseline at 24 months. The secondary endpoints were: average tumour reduction, surgical complications, skin lesions and drug safety.The study population comprised 17 patients, aged >10 years who were diagnosed with TS and had ≥1 renal AML >2 cm of diameter and had a serum creatinine < 2mg/dl and urine protein/creatinine ratio < 22.6 mg/mmol. The trial was conducted at Fundació Puigvert. Rapamycin was given to achieve stable plasma levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal measurements by MRI at baseline, 6, 12 and 24 months.ResultsTen out of 17 patients were success responders for the main outcome −58.8%, 95%CI: 32.9% to 81.6%-. After 6 months of therapy, the mean volume decrease was 55.18% (5.01 standard error (SE); p<0.001) and 66.38% (4.41 SE; p<0.001) at year 1. There was no significant decrease between year 1 and 2. According to RECIST criteria, all patients achieved a partial response at year 1 and all but two had already achieved this partial response after 6 months.The main analysis was performed according to the intention-to-treat principle analysis. Tumour volume was analyzed over time by means of mixed models for repeated measurement analysis. We used the baseline tumour volume as a covariate for the absolute change and percentage change from baseline data. The analysis was performed using SAS version 9.2 software, and the level of significance was established at 0.05 (two-sided).ConclusionsThis study show that mTOR inhibitors are a relatively safe, efficacious and less aggressive alternative than currently available options in the management of AML in TS.Trial registrationEudraCT number: 2007-005978-30, ClinicalTrials.gov number: NCT0121712

CT Findings in Urinary Diversion after Radical Cystectomy: Postsurgical Anatomy and Complications

Numerous surgical procedures have been developed for urinary diversion in patients who have undergone a radical cystectomy for bladder cancer or, less frequently, a benign condition. Because urinary diversion procedures are complex, early and late postsurgical complications frequently occur. Possible complications include alterations in bowel motility, anastomotic leaks, fluid collections (abscess, urinoma, lymphocele, and hematoma), fistulas, peristomal herniation, ureteral strictures, calculi, and tumor recurrence. Computed tomography (CT) is an accurate method for evaluating such events. Multiplanar reformatting and three-dimensional volume rendering of multidetector CT image data are particularly useful for achieving an accurate and prompt diagnosis of complications and obtaining information that is essential for adequate surgical management. In addition, knowledge of urinary diversion procedures, normal postsurgical appearances, and optimal CT technique for postsurgical evaluations is essential for detecting complications and avoiding misdiagnosis.

Mixed Methods Research With Groups at Risk New Developments and Key Debates

The potential of social transformation embedded in mixed methods research is one of the longstanding and ongoing debates within the specialized literature (Hesse-Biber, 2010; Mertens, 2011). Manifold reflections have been provided in this regard, each of them shedding light on different perspectives, with arguments ranging from a strong support for this role for mixed methods research and others arguing against this position (Mertens & Hesse Biber 2012; Sandelowski, 2014). The transformative paradigm serves as one philosophical framework that supports the use of mixed methods research to address social justice issues, particularly considering the need to give voice to underprivileged populations (Mertens, 2009, 2014). The communicative paradigm also considers the importance of creating useful scientific knowledge by establishing an intersubjective dialogue with the researched groups (Gomez, Puigvert, & Flecha, 2011; Puigvert, 2012). Denzin (2012) argues that mixed methods research can promote a dialogic democracy as a way toward shaping real utopias. Postcolonial or indigenous researchers have also shed light on different aspects to counter the existing power relations with postcolonial societies (Chilisa, 2011; Smith, 1999). Social science researchers encounter stimulation to give greater consideration to addressing issues of social justice from a variety of sources. In a context of scarcity of resources, citizenry is demanding more public discussion and accountability in the decision-making processes about how to allocate public resources. In this context, European funding for social science research was questioned because of its dubious returns to society. While research in other sciences were clearly supporting the improvement of citizens’ lives, this was not that clear in the case of social sciences. The program Horizon 2020 defined research priorities in Europe for the next decade; however, in its initial proposal, social sciences were not included. The scientific community mobilized and submitted an open letter signed by thousands of researchers and major stakeholders to the Commissioner (see the open letter at http://www.eash.eu/openletter2011/) stating that in order to tackle large-scale transitions European societies are undergoing, there is a need to include social science research as part of the solution. Citizens and societies need to see in which ways social science research is contributing to improve their lives and communities. The usefulness claim also comes from the most at risk groups of society as the research community is asked to contribute to reduce inequalities and provide effective solutions for

Efectos de la rapamicina en los angiomiolipomas de pacientes con esclerosis tuberosa

BACKGROUND Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas). Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. MATERIAL AND METHODS At present, our study includes 17 patients with TS. All had at least one AML greater than 2cm in diameter diagnosed by MRI. They received rapamycin during 12 months. Plasma levels remained stable between 4-8ng/dl. The AML size was monitored every six months by abdominal MRI. RESULTS At 12 months of inclusion, MRI indicated a decrease in the size of AML in all patients showing at least a 50% reduction in 82.4% (14/17, 95% CI [56.57%, 96.20%]). The mean percent reduction was 66.3% (95% CI [56.9%, 75.6%], P<.0001). The major side effects observed were: oral aphthous ulcers (5/17); hypertriglyceridemia (3/17); microcytosis and hypochromia (3/17); diarrhea (2/17); acne (1/17); acute pyelonephritis (1/17); and proteinuria (1/17). CONCLUSIONS These preliminary clinical data suggest that rapamycin can play a beneficial role in the treatment of TS. Our experience in 17 patients treated for 12 months demonstrates safety and efficacy in reducing AML volume.

Immigrant and Native Romani Women in Spain: Building Alliances and Developing Shared Strategies

Romani women, both immigrant and native, face a greater risk of social exclusion because of the prejudices that mainstream society has about the Roma, and especially because they are women and some of them immigrants as well. This paper analyses how Romani immigrant and native women are building pan-ethnic identities, sharing alliances and developing common strategies in Spain. Previous studies on Romani women have tended to see them as passive and not active agents. Thus, very few have focused on the specific case of Romani immigrant women and on their modes of incorporation in their new contexts of reception. Drawing on data from two qualitative studies of Roma immigrant women and Gitanas in Spain, the authors demonstrate how everyday-life interactions and shared interests at informal and formal encounters lead to building solidarity alliances and sharing transnational narratives, thus overcoming subgroup ethnic boundaries and stereotypes. The analysis is carried out from the ‘other women’ approach, taking into account the voices of all types of Romani women, illiterate and literate, in the whole research process.

Use of Multidetector CT in Presurgical Evaluation of Potential Kidney Transplant Recipients

Kidney transplantation is the treatment of choice for end-stage renal disease. Optimal presurgical evaluation of the potential kidney transplant recipient is important for the success of the transplantation. Multidetector computed tomography (CT) allows assessment of the feasibility of kidney transplantation; detection of coexisting illnesses that may affect survival of the graft and that must be treated before transplantation; and evaluation of possible peripheral vascular disease, which is present in a significant number of potential kidney transplant recipients. Multidetector CT provides a wide range of information in these patients. Vascular and extravascular systems can be evaluated, allowing one to determine whether kidney transplantation is possible, whether presurgical procedures are necessary, and which is the best surgical technique for each candidate. Knowledge of the surgical techniques, use of an optimal multidetector CT technique, and the ability to identify common and uncommon radiologic findings are essential for correct evaluation of potential kidney transplant recipients.

Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated

BackgroundMutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), while mutations in PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 lays immediately adjacent to TSC2 and deletions involving both genes, the PKD1/TSC2 contiguous gene syndrome (CGS), are characterized by severe ADPKD, plus TSC. mTOR inhibitors have proven effective in reducing angiomyolipoma (AML) in TSC and total kidney volume in ADPKD but without a positive effect on renal function.Methods and resultsWe describe a patient with independent truncating PKD1 and TSC2 mutations who has the expected phenotype for both diseases independently instead of the severe one described in PKD1/TSC2-CGS. Treatment with mTOR inhibitors reduced the AML and kidney volume for 2 years but thereafter they resumed growth; no positive effect on renal function was seen throughout. This is the first case addressing the response to mTOR treatment when independent truncating mutations in PKD1 and TSC2 are present.ConclusionsThis case reveals that although PKD1 and TSC2 are adjacent genes and there is likely cross-talk between the PKD1 and TSC2 signalling pathways regulating mTOR, having independent TSC2 and PKD1 mutations can give rise to a milder kidney phenotype than is typical in PKD1/TSC2-CGS cases. A short-term beneficial effect of mTOR inhibition on AML and total kidney volume was not reflected in improved renal function.

A Review of the Imaging Techniques for Measuring Kidney and Cyst Volume in Establishing Autosomal Dominant Polycystic Kidney Disease Progression

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder; it is defined by progressive renal cyst formation and subsequent renal enlargement that leads to end-stage renal disease. Until recently, only symptomatic treatments for ADPKD existed. However, therapies that address the underlying pathophysiology of ADPKD are now available and accurate identification of the rate of disease progression is essential. Summary: Published data on the different imaging modalities for measuring kidney and cyst volumes in ADPKD are reviewed. The advantages and drawbacks of the different techniques for calculating kidney volume from renal imaging are also examined, including the use of manual planimetry, stereology, and the ellipsoid equation, as well as the prospect of semi- and fully automatic techniques. The translation of these approaches into clinical practice and their role in informing treatment decisions is discussed. Key Messages: These new therapies require the accurate monitoring of disease progression, which along with diagnosis and prognosis, relies on the effective use of renal imaging techniques. There is growing support for the use of total kidney volume as a measure of cyst burden and as a prognostic predictor of renal function in ADPKD, showing promise as a marker of disease progression.

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression

Background: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. Methods: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m2). Results: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31–55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. Conclusions: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

Carcinoma urotelial renal en una paciente con enfermedad renal poliquística autosómico dominante: Presentación de un caso y revisión de la literatura

We describe a case of urothelial carcinoma of renal pelvis in a 48 years old woman affected of autosomal dominant polycystic kidney disease (ADPKD). We discuss the difficulty of the radiological diagnostic and we revise the incidence of renal tumors in this entity. Association between urothelial carcinoma and ADPKD is highly infrequent and without apparently causal relation.