Feasibility of primary aldosteronism diagnosis in initial evaluation without medication withdrawal or confirmatory tests.

PURPOSE: Primary aldosteronism (PA), a frequent cause of hypertension, is highly associated with cardiovascular risk and mortality. PA diagnosis is often difficult due to the need to discontinue antihypertensive medication interfering with the renin-angiotensin-aldosterone system (I-RAAS). Our objective was to ascertain diagnosis of PA through biochemical assessments during screening while maintaining I-RAAS medications. METHODS: Hypertensive patients assessed for PA were involved. Patients were grouped according to the use of I-RAAS drugs during screening and the presence of PA. The diagnostic accuracy of the aldosterone-to-renin ratio (ARR), and other biochemical features were evaluated. RESULTS: 265 patients included, 122/265 with PA, and 192/265 were on I-RAAS therapy. The area under ROC curve (AUROC) of ARR for PA in patients without I-RAAS was 0.769 (95%CI: 0.66-0.877), and was 0.877 (95%CI: 0.828-0.926) in those with I-RAAS drugs. Sensitivity, specificity, positive predictive value, and negative predictive value (PPV) of cut-off of ARR > 50 were: 76%, 81%, 77.5%, and 79.6%. ARR > 50 plus hypokalemia had a PPV of 92.6% for PA. AUROC values of ARR evaluated in each group of antihypertensive drugs were >0.850 in all cases. CONCLUSIONS: ARR during I-RAAS therapy demonstrates reliability and accuracy for PA diagnosis. An ARR > 50 combined with hypokalemia while on I-RAAS medication could be considered indicative of PA diagnosis.

Differences in the clinical and hormonal presentation of patients with familial and sporadic primary aldosteronism.

Purpose: To compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). Methods: A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group). Results: A total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels. Conclusion: In addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.

Renin as a Biomarker to Guide Medical Treatment in Primary Aldosteronism Patients. Findings from the SPAIN-ALDO Registry.

INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.

Is adrenal venous sampling always necessary to differentiate between unilateral and bilateral primary aldosteronism? Lesson from the SPAIN-ALDO register.

PURPOSE: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. METHODS: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. RESULTS: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). CONCLUSION: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes.

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.

The Benefit of Bariatric Surgery on Histological Features of Metabolic Associated Fatty Liver Disease Assessed Through Noninvasive Methods.

BACKGROUND: In patients with clinically severe obesity, metabolic associated fatty liver disease (MAFLD) and steatohepatitis are highly prevalent. There is a lack of prospective studies evaluating the impact of bariatric surgery (BS) on MAFLD using both noninvasive and histological criteria. The present study aims to assess the impact of BS on MAFLD using histological and biochemical criteria. METHODS: This is a prospective study of 52 patients subjected to BS. Noninvasive fibrosis risk scores (NIFRS) along with anthropometric, clinical, and biochemical parameters were recorded pre- and 12 months post-BS. Liver biopsy was obtained in all individuals at baseline (wedge biopsy) and was repeated at 12 months (percutaneous Tru-cut) in those diagnosed with steatohepatitis. The primary outcome was the change in the degree of steatohepatitis and fibrosis. The secondary outcome was the change in scores for hepatocellular ballooning, lobular inflammation, steatosis, and fibrosis. RESULTS: One year after BS, steatohepatitis resolved in core biopsies with no worsening of fibrosis in 95.7% of individuals (n = 21, 95% CI: 87.3-100), and 13 (56.5%) exhibited complete resolution. Of 15 patients with fibrosis at baseline, 13 (86.7%) showed improvement and 12 exhibited fibrosis resolution. The values of transaminases improved, but only gamma glutamyl transferase (GGT) showed statistical significance. Among the NIFRS, NAFLD fibrosis score (NFS) and Hepamet fibrosis score (HFS) showed significant improvement. CONCLUSIONS: In the setting it was studied, BS improved or resolved steatohepatitis and fibrosis in patients with obesity. NIFRS, especially NFS and HFS, and levels of GGT could be used as markers of recovery of liver function after BS.

A Degenerate Metal-Templated Catalytic System with Redundant Functional Groups for the Asymmetric Aldol Reaction.

A degenerate zinc-templated catalytic system containing two bipyridine ligands with redundant functional groups for either enamine or hydrogen bond formation was applied to the asymmetric aldol reaction. This concept led to both a higher probability of reaction and rate acceleration. Thus, the catalyst loading could be decreased to a remarkable 2 mol % in what we think is a general approach.

Prevalence and predictors of non-alcoholic steatohepatitis in patients with morbid obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.

Prevalence and predictors of non-alcoholic steatohepatitis in patients with morbid obesity.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in morbid obesity (MO). A considerable proportion of patients with MO have non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is the only procedure that reliably differentiates NASH from other stages of NAFLD, but its invasive nature prevents it from being generalisable. Hence, non-invasive assessment is critical in this group of patients. OBJECTIVES: To report NAFLD/NASH prevalence in a cohort of patients with MO and to identify predictors of NASH. METHODS: Fifty-two consecutive patients subjected to bariatric surgery in a University hospital in Spain underwent LB. Anthropometric, clinical and biochemical variables were registered. According of the results of the LB, individuals were classified by whether they had NASH or not. Multiple logistic regression analysis was performed to identify independent factors associated with NASH. RESULTS: NAFLD was reported in 94.2% of the patients, simple steatosis was present in 51.92% and NASH in 42.31%. Meanwhile, 17.3% of patients exhibited significant fibrosis (≥F2). HIGHT score for NASH risk was established using five independent predictors: systemic Hypertension, Insulin resistance, Gamma-glutamyl transferase, High density lipoprotein cholesterol and alanine Transaminase. This score ranges from 0 to 7 and was used to predict NASH in our cohort (area under the receiver operator characteristic curve 0.846). A score of 4 or greater implied high risk (sensitivity 77.3%, specificity 73.3%, positive predictive value 68%, negative predictive value 81.5%, accuracy 75%). CONCLUSIONS: NAFLD is practically a constant in MO with a considerable proportion of patients presenting NASH. The combination of five independent predictors in a scoring system may help the clinician optimise the selection of patients with MO for LB.

The Effect of the Dose of Isotonic Saline on the Correction of Serum Sodium in the Treatment of Hypovolemic Hyponatremia.

BACKGROUND: Overcorrection of serum sodium (SNa) during therapy of hyponatremia can result in osmotic demyelination syndrome. Our aim was to determine the relationship between the isotonic saline solution dose (ISSD) administered and the 24-h SNa increase (24SNa) in patients with hypovolemic hyponatremia (HH). METHODS: Retrospective study of HH patients treated with ISS in a tertiary hospital of Madrid, Spain, between 1 January-30 May 2019. The 24-h ISSD received and corresponding 24SNa were calculated. The latter was classified as 3 groups: ≥8 mmol/L, ≥6 mmol/L, or <4 mmol/L. Multivariate regression analyses were performed and ROC curves calculated to study the relationship between ISSD and 24SNa. RESULTS: Thirty patients were included, age 72 years (60-80), 50% were women. 24SNa was ≥8 mmol/L/24 h in 33%, ≥6 mmol/L/24 h in 50%, and <4 mmol/L/24 h in 30%. Median ISSD in each group was: 32 mL/kg/24 h (29-37), 31 mL/kg/24 h (25-33), and 20 mL/kg/24 h (14-22), respectively. An ISSD ≥ 30 mL/kg/24 h had an odds ratio (OR) of 16 (95% CI: 2.5-95.1; p = 0.004) for a 24SNa ≥8 mmol/L, with a sensitivity and specificity of 80%. CONCLUSIONS: The 24SNa depends on ISSD. An ISSD between 23-30 mL/kg/24 h seems to be safe and effective.

Fungal biosynthesis of lignin-modifying enzymes from pulp wash and Luffa cylindrica for azo dye RB5 biodecolorization using modeling by response surface methodology and artificial neural network.

This study demonstrates the evaluation between the artificial neural network technique coupled to the genetic algorithm (ANN-GA) and the response surface methodology (RSM) for prediction of Reactive Black 5 (RB5) decolorization by crude enzyme from Pleurotus. sajor-caju. Fungal lignin-modifying enzymes (FLME) were synthesized using pulp wash (PW) as an inducing substrate, and L. cylindrica (L.C) for cell immobilization. When grown in PW, the fungus showed higher Lac activity (126.5 IU. mL-1), whereas when immobilized a higher MnP activity was achieved (22.79 IU. mL-1), but both methods were capable of decolorizing the dye in about 89.4 % and 75 %, respectively. This indicates applicability of PW as an alternative substrate for FLME induction and viability of immobilization for MnP synthesis. For RB5 decolorization, the action of the crude enzyme extract was considered as a function of pH, dye concentration, temperature, and reaction time. The models are well adjusted to predict the efficiency of biodecolorization, with no statistical difference between ANN-GA and RSM, which indicates potential for green enzymes prospecting application in bioprocess industry.

Performance of Noninvasive Liver Fibrosis Scores in the Morbid Obese Patient, Same Scores but Different Thresholds.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is a spectrum of progressive alterations, with the final step in liver fibrosis which carries a high burden of long-term mortality. The scores used to predict liver fibrosis are not properly validated in morbid obesity (MO). Our aim was to evaluate the performance of seven risk scores in bariatric surgery (BS) patients. METHODS: Cross-sectional analysis in a cohort of 60 patients with MO undergoing BS. Liver biopsy (LB) was taken and compared with fibrosis risk assessed by noninvasive scores: APRI, FIB-4, Forns, NFS (NAFLD fibrosis score), BARD, BAAT, and Hepamet. The area under the receiver operator characteristic curve (AUROC) and measures of diagnostic accuracy were calculated; performance of fibrosis scores was evaluated at standard threshold vs those suggested by ROC analysis. RESULTS: LB was available in 50 patients; 9 (18%) had significant fibrosis (F2-F4). The BARD and Forns scores best predicted the absence of fibrosis, both with negative predictive value (NPV) of 95.5%, with AUROC of 0.761 and 0.667, respectively. Modification of standard thresholds (2 for BARD and 6.9 for Forns) to those suggested by ROC analysis (3 and 3.6, respectively) improved performance of scores. Basal glucose, glycated hemoglobin (HbA1c), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were identified by logistic regression analysis as independent predictor of fibrosis. CONCLUSIONS: Existing scoring systems are unable to stratify fibrosis risk in MO using established thresholds; its performance is improved if these cutoffs are modified.

[Costs associated to disease-related malnutrition and treatment: a literature review]. / Costes asociados a la desnutrición relacionada con la enfermedad y su tratamiento: revisión de la literatura.

INTRODUCTION: disease-related malnutrition has a high prevalence, with clinical consequences potentially severe for the patient, and of high economic impact for the healthcare system. OBJECTIVE: to perform a review of the literature regarding the economic burden of disease-related malnutrition, to assess complications, and to determine the usefulness of enteral or oral nutritional supplementation from a cost analysis perspective. METHODS: a review of the literature up to June 2016 was carried out regarding economic costs of disease-related malnutrition and cost analysis of nutritional treatment, with special focus on retrieval of systematic reviews, meta-analysis, and randomized clinical trials. RESULTS: a total of 31 publications were selected, 15 on costs of disease-related malnutrition and 16 on costs of treatment. Disease-related malnutrition increases health care costs in relation to a longer hospital stay, higher incidence of infectious and non-infectious complications, greater need of treatment, increase in readmissions, more prolonged stay in the intensive care unit and/or the need of referral to continuing care centers at discharge. Publications regarding treatment with oral nutritional supplements suggest that these oral supplements are cost-effective and cost-beneficial both in ambulatory and hospitalized patients. CONCLUSIONS: disease-related malnutrition causes an increase in health care costs that could be minimized, among other approaches, by an early diagnosis and treatment for which oral nutritional supplements are cost-effective and cost-beneficial.

Optimal Gestational Weight Gain for Women with Gestational Diabetes and Morbid Obesity.

OBJECTIVES: Our aim was to investigate the greatest gestational weight gain (GWG) without adverse pregnancy complications in women with gestational diabetes mellitus (GDM) and morbid obesity. METHODS: An observational retrospective study including 3284 patients with single pregnancies and GDM was completed. Of the patients, 131 (4.0%) were classified as having pre-pregnancy morbid obesity (BMI ≥ 35 kg/m2). Perinatal complications were compared among BMI groups. In the group with morbid obesity, GWG threshold values to predict outcomes were examined based on sensitivity and specificity values under the receiver operating characteristic curve. RESULTS: GWG was higher in mothers with morbid obesity and macrosomic neonates: 11.3 (4.4-15.7) versus 4.8 (1.5-8.2) kg (p = 0.033). The GWG and neonatal ponderal index were positively correlated (r = 0.305, p = 0.001). The GWG was 7.0 (2.9-11.6) kg in women with hypertensive disorder versus 4.5 (1.0-7.5) kg in normotensive women (p = 0.017). A GWG above 5 kg was a risk factor for macrosomia (87.8% sensitivity, 54.7% specificity) and hypertensive disorder (70.0% sensitivity, 48.4% specificity). GWG associations were maintained after controlling for glycemic control, maternal and gestational age, parity, smoking and neonatal sex. CONCLUSIONS FOR PRACTICE: A GWG below 5 kg is recommended for women with GDM and morbid obesity. In these women, adequate GWG may prevent macrosomia, fetal overgrowth and hypertensive disorder.