Indication, performance and outcomes of adrenal vein sampling in patients with primary hyperaldosteronism.

Primary hyperaldosteronism (PAH) is an important cause of secondary hypertension (HTN). The study of the same requires a high clinical suspicion in addition to a hormonal study that confirms hormonal hypersecretion. It is important to start the appropriate treatment once the diagnosis is confirmed, and for this is necessary to demonstrate whether the hormonal hypersecretion is unilateral (patients who could be candidates for surgical treatment) or bilateral (patients who are candidates for pharmacological treatment only). At the Hospital del Mar since 2016 there has been a multidisciplinary work team in which Nephrologists, Endocrinologists, Radiologists and Surgeons participate to evaluate cases with suspected hyperaldosteronism and agree on the best diagnostic-therapeutic approach for these patients, including the need for adrenal vein sampling, which is a technique that in recent years has become the gold standard for the study of PAH. In the present study we collect the experience of our centre in performing AVC and its usefulness for the management of these patients.

Follow-up care of 12 months of patients with bladder cancer in Spain: A multicenter prospective cohort study.

The therapeutic approach of bladder cancer strongly determines its prognosis. We describe the treatments and outcomes for a Spanish cohort of patients with bladder cancer for the first 12 months after diagnosis and identify the factors that influenced the decision to undergo the treatment received. We conducted a multicenter, prospective, cohort study including primary bladder cancer patients during the first 12 months after diagnosis. The clinical outcomes were performance status (ECOG), adverse events and any cause of mortality. We stratified the analysis by factors that might influence the treatments received. We conducted univariate and multivariable logistic regression models to assess which patient and tumor characteristics were associated with receiving adjuvant treatment in the subgroup of noninvasive bladder cancer patients. In total, 314 patients were included (85% men; 53.8% >70 years) in 7 tertiary Spanish hospitals; 82.2% had a noninvasive urothelial bladder cancer (NMIBC). Patients received mostly surgery plus adjuvant therapy (67.7%). BCG (32.8% patients) was the most frequently administered adjuvant therapy, followed by intravesical chemotherapy (17.8% patients) and radiotherapy (10.8%). The variability of administered treatments among hospitals was low. Patients with NMIBC were more likely to receive adjuvant therapy if they had a higher educational level, some comorbidities and a high-grade tumor. The number of fully active patients (ECOG 0) significantly decreased during the first year of follow-up from 58% to 36 % (OR: 2.41, 95%CI 1.82-3.20); at 12-month follow-up 10.8% patients had died from any cause. In conclusion, most of the patients had a NMIBC. Surgery alone or plus adjuvant therapy were the commonest curative options of bladder cancer. BCG therapy was the adjuvant therapy most frequently administered. Higher educational level, presence of comorbidities and a high-grade tumor were associated with adjuvant therapy. Patient performance status was worsening over time. Almost 1 of 10 patients died during the first year of follow-up.

Association between histological diaphragm atrophy and ultrasound diaphragm expiratory thickness in ventilated patients.

BACKGROUND: Diaphragm fiber atrophy has been evidenced after short periods of mechanical ventilation (MV) and related to critical illness-associated diaphragm weakness. Atrophy is described as a decrease in diaphragm fiber cross-sectional area (CSA) in human diaphragm biopsy, but human samples are still difficult to obtain in clinics. In recent years, ultrasound has become a useful tool in intensive care to evaluate diaphragm anatomy. The present study aimed to evaluate the ability of diaphragm expiratory thickness (Tdi) measured by ultrasound to predict diaphragm atrophy, defined by a decrease in diaphragm fiber CSA obtained through diaphragm biopsy (the gold standard technique) in ventilated patients. METHODS: Diaphragm biopsies and diaphragm ultrasound were performed in ventilated donors and in control subjects. Demographic variables, comorbidities, severity on admission, treatment, laboratory test results and evolution variables were evaluated. Immunohistochemical analysis to determine CSA and ultrasound measurements of Tdi at end-expiration were performed, and median values of the control group were used as thresholds to determine agreement between them in further analysis. Sensitivity, specificity, and positive and negative predictive values of an ultrasound Tdi cutoff for detecting histologic atrophy were calculated. Agreement between two ultrasound observers was also assessed. RESULTS: Thirty-five ventilated organ donors and 5 ventilated controls were included, without differences in basic characteristics. CSA and Tdi were lower in donors than in controls. All donors presented lower CSA, but only 74% lower Tdi regarding control group thresholds. The cut-off value for lower diaphragm expiratory thickness (Tdi < 1.7 mm) presented a sensitivity of 73%, a specificity of 67%, a positive predictive value of 96% and a negative predictive value of 17% for determining the presence of diaphragm atrophy (CSA < 2851 µm2). CONCLUSIONS: Diaphragm atrophy and thickness reduction is associated to MV. While a lower Tdi in diaphragm ultrasound is a good tool for diagnosing atrophy, normal or increased Tdi cannot rule atrophy out showing that both parameters should not be considered as synonymous.

Factors associated with renal function compensation after donor nephrectomy. / Factores asociados a la compensación de la función renal tras la nefrectomía para donación.

INTRODUCTION: Kidney transplant donors lose 50% of their renal mass after nephrectomy. The remaining kidney compensates for this loss and it is estimated that 70% of the baseline renal function prior to donation is recovered. Factors associated with post-donation renal compensation are not well understood. METHODS: Retrospective study of 66 consecutive kidney donors (mean age 48.8 years, 74.2% women). We analysed the potential factors associated with the compensatory mechanisms of the remaining kidney by comparing donors according to their renal compensation rate (RCR) (Group A, infra-compensation [<70%]; Group B, normal compensation [>70%]). RESULTS: We compared Group A (n=38) and group B (n=28). Predictors for RCR>70% were higher baseline creatinine (A vs B: 0.73±0.14 vs 0.82±0.11; P=.03) and a lower baseline glomerular filtration rate (GFR), estimated both by MDRD-4 (A vs B: 97.7±18.8 vs 78.6±9.6ml/min; P<.001) and CKD-EPI (A vs B: 101.7±15 vs. 88.3±11.7ml/min; P≤.001). Age, gender, smoking, hypertension and GFR measured by Tc-DTPA did not show any correlation with the RCR. The multivariate analysis confirmed baseline estimated glomerular filtration rate (eGFR) to be a predictor of compensation: the higher the baseline eGFR, the lower the likelihood of >70% compensation (MDRD-4, OR=0.94 [95% CI 0.8-0.9], P=.01). The compensation rate decreased by 0.4% (P<.001) and 0.3% (P=.006) for every ml/min increase in baseline eGFR estimated by MDRD-4 and CKD-EPI, respectively. CONCLUSIONS: One year after living donor nephrectomy, the remaining kidney partially compensates baseline renal function. In our experience, baseline eGFR is inversely proportional to the one-year renal compensation rate.

Prediction of coronary disease incidence by biomarkers of inflammation, oxidation, and metabolism.

The effect of circulating biomarkers in predicting coronary artery disease (CAD) is not fully elucidated. This study aimed to determine the relationship with CAD and the predictive capacity of nine biomarkers of inflammation (TNF-α, IL-10, IL-6, MCP-1, CRP), oxidation (GHS-Px), and metabolism (adiponectin, leptin, and insulin). This was a case-cohort study, within the REGICOR population-cohorts (North-Eastern Spain), of 105 CAD cases and 638 individuals randomly selected from a cohort of 5,404 participants aged 35-74 years (mean follow-up = 6.1 years). Biomarkers' hazard ratio (HR)/standard deviation was estimated with Cox models adjusted for age, sex, and classical risk factors. Discrimination improvement and reclassification were analyzed with the c-index and the Net reclassification index (NRI). GHS-Px (adjusted HRs = 0.77; 95%CI:0.60-0.99), insulin (1.46; 1.08-1.98), leptin (1.40; 1.03-1.90), IL-6 (1.34; 1.03-1.74), and TNF-α (1.80; 1.26-2.57) were significantly associated with CAD incidence. In the model adjusted for all biomarkers, TNF-α (1.87;1.31-2.66) and insulin (1.59;1.16-2.19) were independently associated with CAD. This final model, compared to a model without biomarkers, showed a c-index difference of 1.3% (-0.7, 3.2) and a continuous NRI of 33.7% (2.6, 61.9). TNF-α and insulin are independently associated with CAD incidence and they improve reclassification when added to a model including classical risk factors.

MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney donors. / MDRD o CKD-EPI en la estimación del filtrado glomerular del donante renal vivo.

INTRODUCTION: The evaluation of the measured Glomerular Filtration Rate (mGFR) or estimated Glomerular Filtration Rate (eGFR) is key in the proper assessment of the renal function of potential kidney donors. We aim to study the correlation between glomerular filtration rate estimation equations and the measured methods for determining renal function. MATERIAL AND METHODS: We analysed the relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene-triamine-pentaacetate) and those estimated by the four-variable Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in a series of living donors at our institution. RESULTS: We included 64 donors (70.6% females; mean age 48.3±11 years). Baseline creatinine was 0.8±0.1 mg/dl and it was 1.1±0.2 mg/dl one year after donation. The equations underestimated GFR when measured by Tc99m-DTPA (MDRD4-9.4 ± 25ml/min, P<.05, and CKD-EPI-4.4 ± 21ml/min). The correlation between estimation equations and the measured method was superior for CKD-EPI (r=.41; P<.004) than for MDRD4 (r=.27; P<.05). eGFR decreased to 59.6±11 (MDRD4) and 66.2±14ml/min (CKD-EPI) one year after donation. This means a mean eGFR reduction of 28.2±16.7 ml/min (MDRD4) and 27.31±14.4 ml/min (CKD-EPI) at one year. CONCLUSIONS: In our experience, CKD-EPI is the equation that better correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening purposes.

Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

INTRODUCTION AND OBJECTIVES: To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. METHODS: Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. RESULTS: Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. CONCLUSIONS: All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Percutaneous coronary intervention reduces mortality in myocardial infarction patients with comorbidities: Implications for elderly patients with diabetes or kidney disease.

BACKGROUND: Percutaneous coronary intervention (PCI) reduces mortality in most myocardial infarction (MI) patients but the effect on elderly patients with comorbidities is unclear. Our aim was to analyse the effect of PCI on in-hospital mortality of MI patients, by age, sex, ST elevation on presentation, diabetes mellitus (DM) and chronic kidney disease (CKD). METHODS: Cohort study of 79,791 MI patients admitted at European hospitals during 2000-2014. The effect of PCI on in-hospital mortality was analysed by age group (18-74, ≥75years), sex, presence of ST elevation, DM and CKD, using propensity score matching. The number needed to treat (NNT) to prevent a fatal event was calculated. Sensitivity analyses were conducted. RESULTS: PCI was associated with lower in-hospital mortality in ST and non-ST elevation MI (STEMI and NSTEMI) patients. The effect was stronger in men [Odds ratio (95% confidence interval) 0.30 (0.25-0.35)] than in women [0.46 (0.39-0.54)] aged ≥75years, and in NSTEMI [0.22 (0.17-0.28)] than in STEMI patients [0.40 (0.31-0.5)] aged <75years. PCI reduced in-hospital mortality risk in patients with and without DM or CKD (54-72% and 52-73% reduction in DM and CKD patients, respectively). NNT was lower in patients with than without CKD [≥75years: STEMI=6(5-8) vs 9(8-10); NSTEMI=10(8-13) vs 16(14-20)]. Sensitivity analyses such as exclusion of hospital stays <2days yielded similar results. CONCLUSIONS: PCI decreased in-hospital mortality in MI patients regardless of age, sex, and presence of ST elevation, DM and CKD. This supports the recommendation for PCI in elderly patients with DM or CKD.

Validation of the Regicor Short Physical Activity Questionnaire for the Adult Population.

OBJECTIVE: To develop and validate a short questionnaire to estimate physical activity (PA) practice and sedentary behavior for the adult population. METHODS: The short questionnaire was developed using data from a cross-sectional population-based survey (n = 6352) that included the Minnesota leisure-time PA questionnaire. Activities that explained a significant proportion of the variability of population PA practice were identified. Validation of the short questionnaire included a cross-sectional component to assess validity with respect to the data collected by accelerometers and a longitudinal component to assess reliability and sensitivity to detect changes (n = 114, aged 35 to 74 years). RESULTS: Six types of activities that accounted for 87% of population variability in PA estimated with the Minnesota questionnaire were selected. The short questionnaire estimates energy expenditure in total PA and by intensity (light, moderate, vigorous), and includes 2 questions about sedentary behavior and a question about occupational PA. The short questionnaire showed high reliability, with intraclass correlation coefficients ranging between 0.79 to 0.95. The Spearman correlation coefficients between estimated energy expenditure obtained with the questionnaire and the number of steps detected by the accelerometer were as follows: 0.36 for total PA, 0.40 for moderate intensity, and 0.26 for vigorous intensity. The questionnaire was sensitive to detect changes in moderate and vigorous PA (correlation coefficients ranging from 0.26 to 0.34). CONCLUSION: The REGICOR short questionnaire is reliable, valid, and sensitive to detect changes in moderate and vigorous PA. This questionnaire could be used in daily clinical practice and epidemiological studies.

FOXO1 down-regulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression.

Nuclear FOXOs mediate cell cycle arrest and promote apoptosis. FOXOs and p53 could have similar effects as tumor suppressor genes. In spite of extensive literature, little is known about the role of FOXO1 and its relationship with p53 status in bladder cancer. Expression of FOXO1 and p53 were analyzed by immunohistochemistry in 162 urothelial carcinomas (UC). Decreased FOXO1 expression, p53 overexpression and the combination FOXO1 down-regulation/p53 overexpression were strongly associated with high grade (P=.030; P=.017; P=.004, respectively), high stage (P=.0001; P<.0001; P<.0001, respectively) or both (P=.0004; P<.0001; P<.0001, respectively). In the overall series of cases, p53 overexpression was associated with tumor progression (hazard ratio [HR]=3.18, 95% confidence interval [CI] 1.19-8.48, P=.02), but this association was even stronger if having any alteration in any of the 2 genes was considered (HR=3.51, 95% CI 1.34-9.21, P=.01). Having both FOXO1 down-regulation and p53 overexpression was associated with disease recurrence (HR=2.75, 95% CI 1.06-7.13, P=.03). In the analysis of the different subgroups, having any alteration in any of the 2 genes was associated with progression in low-grade (P=.005) and pTa (P=.006) tumors. Finally, the combined FOXO1 down-regulation/p53 overexpression was associated with disease recurrence specifically in high-grade (P=.04) and in pT1 stage tumors (P=.007). Adding FOXO1 expression to the immunohistochemical analysis of p53 can provide relevant prognostic information on progression and recurrence of bladder cancer. It may be particularly informative on the risk of progression in the more indolent and on the risk of recurrence in the more aggressive tumors.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

Quality of life in patients with non-muscle-invasive bladder cancer: one-year results of a multicentre prospective cohort study.

OBJECTIVE: Few studies describe the effect of non-muscle-invasive bladder cancer (NMIBC) on health-related quality of life (HRQL), although patients are mostly diagnosed at this stage of the disease. Taking into account this current evidence gap and the high incidence rates in Spain, we aimed to describe the evolution over time of HRQL in Spanish patients with NMIBC and to examine the clinical and treatment-related factors associated with HRQL change during the first year of management. METHODS AND MATERIALS: Observational multicenter prospective inception cohort study conducted in urology departments of 7 Spanish hospitals. A consecutive sample of 244 patients with anatomopathologically confirmed NMIBC, recruited from October 2010 to September 2011, was followed during the diagnostic process, and 6 and 12 months later. HRQL was assessed by generic and disease-specific instruments: the Short Form-36 (covering physical and mental health) and the Bladder Cancer Index, measuring urinary, bowel, and sexual domains (summary scores: 0-100). Bivariate analysis was performed and generalized estimating equation models were constructed to assess HRQL score change. RESULTS: Almost 52% of the patients were diagnosed at stage I, and 84% were men. The number of patients treated only with transurethral resection (TUR) was 144, and 82 also received intravesical therapy with bacillus Calmette-Guérin (BCG) or mitomycin C. Mental health was significantly worse than Short Form-36 reference norms at diagnosis (mean of 49.7 vs. 53.3, 95% CI: 52.5-54.2). Urinary domain improved significantly from diagnosis (85.2, 95% CI: 82.9-87.4) to 12-month evaluation (90.2, 95% CI: 87.7-92.8), whereas sexual domain showed deterioration from 56.4 (95% CI: 52.8-59.9) to 53.7 (95% CI: 50.0-57.4). Adjusted HRQL score changes from baseline to 12-month follow-up estimated with generalized estimating equation models showed improvement on the following parameters: urinary domain after TUR with or without intravesical therapy (+3.9, 95% CI: 0.1-7.7), bowel domain among patients treated with TUR and BCG (+7.0, 95% CI: 2.4-11.5), and sexual domain among those treated with TUR and mitomycin C (+13.1, 95% CI: 5.9-20.2). CONCLUSIONS: For the first time, a distinctive HRQL pattern of bladder cancer treatment benefits emerges for TUR alone, and in combination with BCG or mitomycin C, which deserves further research. Treatment differences cannot be interpreted in terms of efficacy but can be useful to generate hypotheses to test in future studies.

Bladder cancer index: cross-cultural adaptation into Spanish and psychometric evaluation.

BACKGROUND: The Bladder Cancer Index (BCI) is so far the only instrument applicable across all bladder cancer patients, independent of tumor infiltration or treatment applied. We developed a Spanish version of the BCI, and assessed its acceptability and metric properties. METHODS: For the adaptation into Spanish we used the forward and back-translation method, expert panels, and cognitive debriefing patient interviews. For the assessment of metric properties we used data from 197 bladder cancer patients from a multi-center prospective study. The Spanish BCI and the SF-36 Health Survey were self-administered before and 12 months after treatment. Reliability was estimated by Cronbach's alpha. Construct validity was assessed through the multi-trait multi-method matrix. The magnitude of change was quantified by effect sizes to assess responsiveness. RESULTS: Reliability coefficients ranged 0.75-0.97. The validity analysis confirmed moderate associations between the BCI function and bother subscales for urinary (r = 0.61) and bowel (r = 0.53) domains; conceptual independence among all BCI domains (r ≤ 0.3); and low correlation coefficients with the SF-36 scores, ranging 0.14-0.48. Among patients reporting global improvement at follow-up, pre-post treatment changes were statistically significant for the urinary domain and urinary bother subscale, with effect sizes of 0.38 and 0.53. CONCLUSIONS: The Spanish BCI is well accepted, reliable, valid, responsive, and similar in performance compared to the original instrument. These findings support its use, both in Spanish and international studies, as a valuable and comprehensive tool for assessing quality of life across a wide range of bladder cancer patients.

Experience in the treatment of rectourethral fistulae after radical prostatectomy.

OBJECTIVES: To report the clinical characteristics of rectourethral fistula (RUF) after radical prostatectomy (RP) as well as our experience managing them. METHODS: We present our experience in the treatment of RUF based on their clinical characteristics and the presence of associated complexity factors. After medical history and physical examination, the diagnostic work up was completed in all cases with urethrograms, cystoscopy and barium enema. From January 2000 to July 2010 we treated 12 patients with RUF. Mean age was 64 years(range 56-74 years). The etiology was open surgery in two cases and laparoscopic surgery in ten. Clinical presentation varied from 4 to 60 days after surgery. RESULTS: In our experience, endoscopic and radiological findings were well correlated. Two fistulae were small-less than 5 mm- on the urethral side of the anastomosis allowing spontaneous closure after conservative treatment. Ten patients had larger fistulas on the bladder side of the anastomosis and/or were associated with complexity factors that required a posterior transsphincteric York-Mason approach for resolution, with good recovery of urinary and fecal continence. CONCLUSION: The RUF is a significant complication after RP and it is difficult to solve. We propose early reconstructive surgery in large or complex RUF. The posterior transsphincteric York-Mason approach has allowed the repair in all cases.