History of urological malignancies before kidney transplantation, oncological outcome on the long term.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

History of urological malignancies before kidney transplantation, oncological outcome on the long term. / Antecedentes de neoplasias urológicas previos al trasplante renal. Resultados oncológicos a largo plazo.

INTRODUCTION: We aimed to report the oncological outcomes of ESRD patients with histories of urological malignancies who were subsequently submitted to kidney transplantation (KT). MATERIAL AND METHOD: Retrospective study lead in the Puigvert Foundation (Barcelona) registry of 1,200 KT performed from 1988 to 2018. Eighty-five urological malignancies that were treated before KT in 81 patients were identified: 15 (18%) prostate cancers, 49 (58%) RCC, 19 (22%) urothelial carcinomas and 2 (2%) testicular cancers. Baseline characteristics, cancer staging, treatment and follow-up were registered as well as the chronology of the start of dialysis, inscription on the waiting list and kidney transplantation. Endpoints included were cancer recurrence, metastatic progression, cancer-specific death and overall survival. RESULTS: In a median follow-up of 13.1 years (2.2-32), 16/85 (19%) cancer recurrences were reported, with 3 (4%) who progressed to metastasis and died of cancer. Median overall survival after cancer treatment was 25.3 years and cancer-specific survival was 95% at 25 years. Median time from cancer treatment to kidney transplantation was 4.8 years: 3.7 years in prostate cancer, 3.9 years in RCC and 8.8 years in bladder cancer. The median time from start of dialysis to kidney transplantation was 1.8 years in patients with histories of urological malignancy versus 0.5 year in the total cohort of 1,200 renal transplanted over the same period. CONCLUSIONS: Well-selected patients with histories of urological malignancies greatly benefit from kidney transplantation with infrequent and late cancer recurrence. Waiting time could be optimized in low-risk prostate cancer and RCC, but more robust data are needed.

Reference ranges for fetal cardiac, ventricular and atrial relative size, sphericity, ventricular dominance, wall asymmetry and relative wall thickness from 18 to 41 gestational weeks.

OBJECTIVE: To construct nomograms for fetal cardiac, ventricular and atrial relative size and geometry parameters from 18 to 41 weeks' gestation using a low-risk population of singleton pregnancies. METHODS: This was a prospective cohort study of 602 low-risk singleton pregnancies undergoing comprehensive fetal echocardiography, from 18 to 41 weeks of gestation, to assess fetal cardiac, atrial and ventricular relative size and sphericity, ventricular dominance, wall asymmetry and relative wall thickness. Intra- and interobserver measurement reproducibility was evaluated using intraclass correlation coefficients (ICC). In order to construct reference ranges across pregnancy, parametric regressions were tested to model each measurement against gestational age and estimated fetal weight. The measurements evaluated were: cardiothoracic ratio; atrial-to-heart area ratios; ventricular-to-heart area ratios; cardiac, ventricular and atrial sphericity indices; right-to-left basal and midventricular ratios; septal-to-free wall thickness ratios; and relative wall thickness. RESULTS: Fetal cardiac, ventricular and atrial morphometry for assessing relative size and geometry could be successfully performed in > 95% of the population, with moderate-to-excellent interobserver reproducibility (ICC, 0.623-0.907) and good-to-excellent intraobserver reproducibility (ICC, 0.787-0.938). Cardiothoracic ratio and ventricular right-to-left ratio showed a modest increase throughout gestation. Atrial-to-heart and ventricular-to-heart area ratios, atrial sphericity indices and septal-to-free wall thickness ratios were constant with gestational age. Left and right ventricular basal sphericity indices showed a tendency to decrease at the end of gestation, while left and right midventricular sphericity indices tended to decrease in the second trimester. The cardiac sphericity index and left and right relative wall thickness showed a modest decrease with gestational age. Nomograms across gestation were constructed for all echocardiographic parameters described. CONCLUSIONS: The assessment of cardiac, ventricular and atrial relative size and geometry is feasible and reproducible in the fetus. We provide standardized reference ranges for these parameters throughout gestation, enabling the accurate assessment of cardiac remodeling patterns during fetal life. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cardiac filling and ejection time fractions by pulsed-wave Doppler: reference ranges and potential clinical application.

OBJECTIVES: Fetal cardiac function can be evaluated using a variety of parameters. Among these, cardiac cycle time-related parameters, such as filling time fraction (FTF) and ejection time fraction (ETF), are promising but rarely studied. We aimed to report the feasibility and reproducibility of fetal FTF and ETF measurements using pulsed-wave Doppler, to provide reference ranges for fetal FTF and ETF, after evaluating their relationship with heart rate (HR), gestational age (GA) and estimated fetal weight (EFW), and to evaluate their potential clinical utility in selected fetal conditions. METHODS: This study included a low-risk prospective cohort of singleton pregnancies and a high-risk population of fetuses with severe twin-twin transfusion syndrome (TTTS), aortic stenosis (AoS) or aortic coarctation (CoA), from 18 to 41 weeks' gestation. Left ventricular (LV) and right ventricular inflow and outflow pulsed-wave Doppler signals were analyzed, using valve clicks as landmarks. FTF was calculated as: (filling time/cycle time) × 100. ETF was calculated as: (ejection time/cycle time) × 100. Intraclass correlation coefficients (ICC) were used to evaluate the intra- and interobserver reproducibility of FTF and ETF measurements in low-risk fetuses. The relationships of FTF and ETF with HR, GA and EFW were evaluated using multivariate regression analysis. Reference ranges for FTF and ETF were then constructed using the low-risk population. Z-scores of FTF and ETF in the high-risk fetuses were calculated and analyzed. RESULTS: In total, 602 low-risk singleton pregnancies and 54 high-risk fetuses (nine pairs of monochorionic twins with severe TTTS, 16 fetuses with AoS and 20 fetuses with CoA) were included. Adequate Doppler traces for FTF and ETF could be obtained in 95% of low-risk cases. Intraobserver reproducibility was good to excellent (ICC, 0.831-0.905) and interobserver reproducibility was good (ICC, 0.801-0.837) for measurements of all timing parameters analyzed. Multivariate analysis of FTF and ETF in relation to HR, GA and EFW in low-risk fetuses identified HR as the only variable predictive of FTF, while ETF was dependent on both HR and GA. FTF increased with decreasing HR in low-risk fetuses, while ETF showed the opposite behavior, decreasing with decreasing HR. Most recipient twins with severe TTTS showed reduced FTF and preserved ETF. AoS was associated with decreased FTF and increased ETF in the LV, with seemingly different patterns associated with univentricular vs biventricular postnatal outcome. The majority of fetuses with CoA had FTF and ETF within the normal range in both ventricles. CONCLUSIONS: Measurement of FTF and ETF using pulsed-wave Doppler is feasible and reproducible in the fetus. The presented reference ranges account for associations of FTF with HR and of ETF with HR and GA. These time fractions are potentially useful for clinical monitoring of cardiac function in severe TTTS, AoS and other fetal conditions overloading the heart. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo / A clinical management protocol for COVID-19 infection in pregnant women

La infección causada por el nuevo coronavirus SARS-CoV-2 (COVID-19) representa actualmente una de las mayores emergencias sanitarias a nivel mundial. La aparición de una nueva infección potencialmente grave y la situación de pandemia actual ha implicado importantes ajustes en la práctica clínica en medicina materno-fetal. Aunque no parece existir una mayor afectación o susceptibilidad al virus de las mujeres embarazadas respecto la población general, existen aspectos específicos ligados a la gestación que deben tenerse en cuenta de cara al diagnóstico y manejo de la COVID-19 en pacientes embarazadas. En el siguiente documento se exponen las recomendaciones y el protocolo de actuación ante la infección por COVID-19 durante el embarazo desarrollado en nuestro centro, basado en la evidencia científica disponible hasta la fecha y las principales recomendaciones internacionales

The severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy

[A clinical management protocol for COVID-19 infection in pregnant women]. / Guía de actuación para el manejo de la infección por COVID-19 durante en el embarazo.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused a large global outbreak and has had a major impact on health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. Very few studies have reported on the effects of the infection on maternal health, since its onset. The mother and foetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-foetal medicine practice have made profound changes in order to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists. In this review an evidenced-based protocol is presented for the management of COVID-19 in pregnancy.

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment.

OBJECTIVES: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: This was a prospective observational case-control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age-matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA-affected heart specimen, using synchrotron radiation-based X-ray phase-contrast microcomputed tomography and histology, respectively. RESULTS: We included 30 fetuses with CoA and 60 gestational age-matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left-to-right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0-2.7) vs 1.8 (1.7-2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1-84.9) vs 47.0 (43.0-55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume-loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Renal Artery Dissection in a Young Woman: Diagnoses Beyond Fibromuscular Dysplasia.

A 31-year-old woman presented at the emergency room after experiencing colic pain in the right iliac fossa for 5 days. She had previously consulted another center, where deterioration of renal function had been identified and abdominal computed tomography (CT) angiography had shown a dissection of the right renal artery, with areas suggestive of infarction in the right kidney, as well as an aneurysm in the left renal artery and a smaller left kidney. The patient had no relevant family or personal history except posttraumatic carotid-cavernous fistula in 2014, which had been treated with embolization. In our hospital, the patient was hypertensive and acute renal failure was confirmed, accompanied by an increase in lactate dehydrogenase and isomorphic microhematuria. After a new CT Scan, in addition to the lesions described in the renal arteries, another aneurysm in the splenic artery and an aneurysm of the right femoral artery were identified. Antihypertensive treatment was initiated with calcium antagonists and anticoagulation. Subsequent renal arteriography confirmed the dissection of the right renal artery, which could not be repaired, and a coated stent was placed in the left renal artery to exclude the aneurysm. The splenic artery lesion was treated 2 months later. The etiological diagnosis in this young woman was challenging. The presence of visceral aneurysms suggested a differential diagnosis comprising fibromuscular dysplasia, vasculitis, and collagenopathies. Using a multidisciplinary approach and directed anamnesis, the presence of frequent sprains, joint hypermobility, and skin fragility was confirmed. Blood immunology and CT angiography including the thoracic and cervical territories were normal. Echocardiography revealed tricuspid insufficiency. All these data suggested the presence of a collagen-like Ehlers-Danlos syndrome (vascular form). The diagnosis was confirmed by the genetic study, which showed a pathogenic mutation in the COL3A1 gene. Currently, the patient is asymptomatic with recovered renal function following treatment with a beta-blocker and antiplatelet therapy.

Altered nitrogen metabolism in biocontrol strains of Penicillium rubens.

The importance of the metabolic route of nitrogen in the fungus Penicillium rubens (strain PO212) is studied in relation to its biocontrol activity (BA). PO212 can resist a high concentration of chlorate anion and displays a classical nitrate-deficiency (nit-) phenotype resulting in poor colonial growth when nitrate is used as the main source of nitrogen. Analyses of genes implicated in nitrate assimilation evidenced the strong sequence conservation of PO212 and CH8 genome with penicillin producers such as reference strain P. rubens Wisconsin 54-1255, P2niaD18 and Pc3, however also revealed the presence of mutations. PO212 carries a mutation in the gene coding for zinc-binuclear cluster transcription factor NirA that specifically mediates the regulation of genes involved in nitrate assimilation. The nirA1 mutation causes an early stop of NirA factor, losing 66% of its sequence. The NirA1 mutant form is unable to mediate a nitrate-dependent regulation of nitrate and nitrite reductase coding genes. In this study, we study another isolate, CH8, with potential BA and nit- phenotype. A mutation in the nitrate permease coding gene crnA was found in CH8. An insertion of a guanine in the coding sequence cause a frameshift in CrnA with the loss of the last two transmembrane domains. Analysis of PO212 and CH8 isolates and complementation strains show the importance of NirA regulator in maintaining correct transcriptional levels of nitrate and nitrite reductases and suggest CrnA as the main nitrate transporter. the presence of alternative transporter for chlorate and the existence of a mechanism for preventing nitrite derived toxicity in Penicillum. BA of PO212 is partially altered when nirA1 mutation was complemented. This result and the finding of CH8, a novel biocontrol P. rubens strain with a nit- phenotype, suggest that nitrogen metabolism is a component of biocontrol capacity.

Biventricular impact of mild to moderate fetal pulmonary valve stenosis.

OBJECTIVES: To define the pattern of fetal echocardiographic changes associated with isolated pulmonary valve stenosis (PS) and to correlate the echocardiographic findings with neonatal outcome and the need for postnatal pulmonary valvuloplasty within the first 12 months postpartum. METHODS: This was a prospective cohort study between January 2009 and October 2015 of 16 fetuses with isolated PS and 48 controls matched by gestational age at ultrasound examination (± 2 weeks) evaluated at the Fetal Cardiology Unit at BCNatal (Barcelona). Standard fetal ultrasound and comprehensive echocardiography, which included cardiovascular morphometric parameters, and systolic and diastolic functional and timing measurements, were performed in all cases. Baseline characteristics and perinatal outcome were retrieved from clinical records. Cases were followed up until 12 months of age, and admission to intensive care unit, days of hospitalization, need for prostaglandins and requirement for postnatal surgery were reviewed. Fetal PS cases were analyzed according to the need for postnatal pulmonary valvuloplasty. RESULTS: The study groups were similar in terms of baseline, fetal ultrasound and perinatal characteristics. Median gestational age at diagnosis of PS was 33.4 (range, 20.0-36.5) weeks. Most cases corresponded to mild or moderate PS; only three fetuses had reversed flow in the ductus arteriosus before delivery. Six (37.5%) newborns, including all three with reversed flow in the ductus arteriosus prenatally, required postnatal pulmonary valvuloplasty. Fetuses with PS presented with larger and more globular hearts, with increased myocardial wall thickness in the third trimester. Despite preserved right ventricular (RV) ejection fraction and systolic longitudinal motion, PS cases showed increased right cardiac output and signs of diastolic dysfunction, with higher ductus venosus pulsatility index (0.72 ± 0.32 vs 0.53 ± 0.16, P = 0.004) and tricuspid E/E' ratio (7.52 ± 3.07 vs 5.76 ± 1.79, P = 0.022). In addition, fetuses with PS displayed a compensatory increase in left ventricular (LV) radial and longitudinal motion, as shown by a higher ejection fraction (79.3 ± 8.23% vs 67.6 ± 11.3%, P = 0.003) and mitral annular-plane systolic excursion (5.94 ± 1.38 vs 5.0 ± 1.22 mm, P = 0.035). Finally, fetuses requiring postnatal pulmonary valvuloplasty showed a different pattern of echocardiographic findings from those not requiring valvuloplasty, with a significantly smaller RV and pulmonary valve diameter, reduced tricuspid annular-plane systolic excursion (5.08 ± 1.59 vs 8.07 ± 1.93 mm, P = 0.028), increased LV cardiac output (340 ± 16 vs 176 ± 44 mL/min/kg, P = 0.003) and more pronounced signs of LV diastolic dysfunction (mitral E' velocity, 5.78 ± 0.90 vs 8.16 ± 1.58 cm/s, P = 0.008). CONCLUSIONS: Fetuses with PS present with more hypertrophic, larger and more globular hearts in the third trimester of pregnancy, associated with a higher right cardiac output and impaired biventricular relaxation. In addition, signs of increased LV contraction were observed. Our data suggest that RV and LV functional parameters could be useful for predicting the need for postnatal pulmonary valvuloplasty. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Opciones terapéuticas y factores predictivos de recurrencia y mortalidad cáncer-específica en pacients con tumor vesical después de traspante renal: análisis multiinstitucional / Treatment options and predictive factors for recurrence and cancer-specific mortality in bladder cancer after renal transplantation: A multi-institutional analysis

Objetivos: El tumor vesical (TV) en la población trasplantada representa un desafío debido al estado de inmunosupresión de los pacientes y a la mayor tasa de comorbilidades. El objetivo de este estudio fue analizar el tratamiento del TV tras el trasplante renal (TR), centrándose en el modo de presentación, diagnóstico, opciones de tratamiento, factores predictivos de recurrencia y mortalidad cáncer-específica. Material y métodos: Se realizó un estudio observacional prospectivo con un análisis retrospectivo de 88 pacientes con TV después de TR en 10 centros europeos. Se recogieron datos clínicos y oncológicos y se revisaron las indicaciones y los resultados del tratamiento adyuvante. Se aplicó el método de Kaplan-Meier para el análisis de la supervivencia y regresión de Cox uni- y multivariante para identificar los factores de riesgo. Resultados: En la revisión se incluyeron un total de 10.000 TR, identificando 87 pacientes con TV de novo, tras una mediana de seguimiento de 126 meses. La mediana del tiempo al diagnóstico fue 73 meses posterior al TR. Setenta y un pacientes (81,6%) fueron diagnosticados de TV no músculo-invasivo, de los cuales 29 (40,8%) recibieron tratamiento adyuvante: 6 de ellos (20,6%) recibieron el bacilo Calmette-Guérin (BCG) y 20 (68,9%) mitomicina C. En el análisis univariado los pacientes que recibieron BCG presentaron una tasa de recurrencia del TV significativamente menor (p = 0,043). En el análisis multivariante, el cambio de la inmunosupresión a inhibidores de mTOR redujo significativamente el riesgo de recurrencia (HR: 0,24; IC del 95%: 0,053-0,997; p = 0,049), mientras que la presencia de múltiples tumores lo aumentó (HR: 6,31; IC del 95%: 1,78-22,3; p = 0,004). Globalmente, 26 pacientes (29,88%) se sometieron a cistectomía, sin registrarse complicaciones mayores. La mortalidad global fue del 32,2% (28 pacientes) y la mortalidad cáncer-específica del 13,8%. Conclusiones: El tratamiento con bacilo Calmette-Guérin adyuvante y el cambio a inhibidores de mTOR reduce significativamente el riesgo de recurrencia de TV en TR, mientras que la presencia de tumores múltiples aumenta el riesgo

Objectives: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence. Material and methods:We conducted an observational prospective study with a retrospective analysis f 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed. Results: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P = .043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P = .049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P = .004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%. Conclusions: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk

Treatment options and predictive factors for recurrence and cancer-specific mortality in bladder cancer after renal transplantation: A multi-institutional analysis. / Opciones terapéuticas y factores predictivos de recurrencia y mortalidad cáncer-específica en pacientes con tumor vesical después de trasplante renal: análisis multiinstitucional.

OBJECTIVES: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence. MATERIAL AND METHODS: We conducted an observational prospective study with a retrospective analysis of 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed. RESULTS: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P=.043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P=.049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P=.004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%. CONCLUSIONS: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk.

Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function.

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-ß1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-ß1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome.

Robotic-assisted kidney transplantation: our first case.

PURPOSE: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. In order to reduce the morbidity of the open surgery, a robotic-assisted approach has been recently introduced. According to the published literature, the robotic surgery allows the performance of kidney transplantation under optimal operative conditions while maintaining the safety and the functional results of the open approach. METHODS: We present the case of a mother donating to her daughter affected by end-stage renal disease (ESRD) due to Alport disease (creatinine: 353 umol/l; GFR: 13 ml/min per 1.73 m(2)). RESULTS: A robotic-assisted kidney transplant (RAKT) was successfully performed. Surgical time was 120 min with 53 min for vascular suture. The estimated blood loss was <50 cc. The kidney started to produce urine intra-operatively with a rate of 250 cc/h, which remained constant over the next hours. During the first postoperative day, the patient was ambulating and started oral intake. Pain was minimal, and no analgesia was required after 48 h. Serum creatinine improved progressively to 89 umol/l on postoperative day 3. No surgical complications were recorded, and the patient was sent home on postoperative day 5. CONCLUSION: We present the first Spanish transperitoneal pure RAKT from a living-related donor. We believe this is the second pure robotic-assisted kidney transplantation case performed in Europe. We believe that the potential advantages of RAKT are related to the quality of the vascular anastomosis, the possible lower complication rate and the shorter recovery of the recipients.

Ovarian mature teratoma: a ten year experience in our institution.

PURPOSE OF INVESTIGATION: To describe the surgical management and diagnoses of mature ovarian teratomas and ovarian strumas in the present centre. MATERIALS AND METHODS: Descriptive retrospective analysis of cases of mature ovarian teratoma at the present university-associated hospital over ten years. RESULTS: The mean age was 29 years and in 17 patients the diagnosis was made during other surgery. When surgery was planned, the approach was 80.2% laparoscopic and 16.1% laparotomic. In the laparoscopy group more cases had been diagnosed previously as dermoid cyst by ultrasound and fewer days of hospital admission. In the laparotomy group the authors found higher ultrasound size and the size in the gross pathology description. With regards to treatment, 45.3% of cases underwent ovariectomy and 49.3% a cystectomy. Comparing these two groups, the authors found larger pelvic mass size in the group of ovariectomies. Healthy ovarian tissue in the removed specimen was found more frequently in the ovariectomies group (29.1%) but also in some cystectomies (7.5%). CONCLUSIONS: The surgical treatment of the ovarian mature teratoma in the present center was directed on the basis of ultrasound diagnosis, ultrasound tumor size, and the existence of associated gynecologic pathology. The authors strongly recommend a laparoscopic approach and a cystectomy in order to preserve fertility especially in young women.

Relationship between smoking, HPV infection, and risk of Cervical cancer.

PURPOSE OF INVESTIGATION: To document the relationship between smoking and HPV infection, and the risk of developing preinvasive lesions and cervical carcinoma. MATERIALS AND METHODS: Prospective, cross-sectional descriptive study. A total of 1,007 patients were recruited among women seen at the cervical pathology clinic of Sant Joan de Déu University Hospital in Barcelona (Spain) between January 2003 and March 2011. Patients were asked specifically about their smoking habits. Statistical analyses were done with SPSS v.19 software. Differences between groups were considered statistically significant at p < 0.05. RESULTS: In patients studied, 48.7% were smokers. The average number of cigarettes per day among smoking patients was 7.07 (1-40). In the of patients with HPV infection, 53% were smokers versus 37% of patients without HPV infection (p < 0.05). The average number of cigarettes per day among patients with HPV infection was 7.64 cigarettes/day versus 5.55 cigarettes/day among patients without HPV infection (p < 0.05). In the patients with high-risk HPV genotypes infection, 54.5% were smokers versus 43.2% of patients without high-risk HPV infection (p < 0.05). Risk of HPV infection increases 1.905 times among smoking patients versus no smoking patients (OR = 1.905, CI 95% (1.426-2.545), p < 0.05). Among patients with changes associated to HPV and atypical cells, there were 29.2% and 14.4% of smokers, respectively, versus 45.5%, 55.6%, and 48.6% of smokers among patients with grade 1 cervical intraepithelial neoplasia (CIN 1), CIN 2-3, and carcinoma, respectively (p < 0.05). Risk of CIN 2-3 or cervical carcinoma cervical increases 1.642 times among smoking patients versus no smoking ones (OR = 1.642, CI 95% (1.325-1.884), p < 0.05). CONCLUSIONS: Smoking interferes in the increase of HPV infection prevalence and in an increased risk of CIN and cervical carcinoma. Risk also increases with more cigars smoked per day.

Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study.

Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ(+) in CD4(+)CD69(+) and in CD8(+)CD69(+) and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2(+) in CD8(+)CD69(+) also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.

Monocyte implication in renal allograft dysfunction.

Macrophages are involved in the development and progression of kidney fibrosis. The aim of this study was to analyse the phenotype of circulating monocytes and their ability to predict kidney allograft dysfunction in living kidney transplant recipients. Whole blood samples from 25 kidney recipients and 17 donors were collected at five time-points. Monocyte phenotype was analysed by flow cytometry, and interleukin (IL)-10 and soluble CD163 by enzyme-linked immunosorbent assay. One week after transplantation, surface CD163 and IL-10 levels increased significantly from baseline [2·99 ± 1·38 mean fluorescence intensity (MFI) to 5·18 ± 2·42 MFI for CD163; 4·5 ± 1·46 pg/ml to 6·7 ± 2·5 pg/ml for IL-10]. This CD163 increase correlated with 4-month creatinine levels (r = 0·4394, P = 0·04). However, soluble CD163 decreased significantly from baseline at 1 week (797·11 ± 340·45 ng/ml to 576·50 ± 293·60 ng/ml). CD14(+) CD16(-) monocytes increased at 4 months and correlated positively with creatinine levels at 12 and 24 months (r = 0·6348, P = 0·002 and r = 0·467, P = 0·028, respectively) and negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r = 0·6056, P = 0·003). At 4 months, IL-10 decreased significantly (P = 0·008) and correlated positively with creatinine at 2 years (r = 0·68, P = 0·010) and with CD14(+) CD16(-) monocytes at 4 months (r = 0·732, P = 0·004). At 24 h, levels of human leucocyte antigen D-related declined from 12·12 ± 5·99 to 5·21 ± 3·84 and CD86 expression decreased from 2·76 ± 1·08 to 1·87 ± 0·95. Both markers recovered progressively until 12 months, when they decreased again. These results indicate that monitoring monocytes could be a promising new prognostic tool of graft dysfunction in renal transplant patients.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.