213 research outputs found
Beta-blocker bashing and downgrading in hypertension management: a fashionable trend representing a matter of concern
A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.
In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR â„20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR â„25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis â„70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD
Does Glycemic Control Offer Similar Benefits Among Patients With Diabetes in Different Regions of the World? Results from the ADVANCE trial
OBJECTIVE Participants in ADVANCE were drawn from many countries. We examined whether the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia, established market economies (EMEs), and eastern Europe.
RESEARCH DESIGN AND METHODS ADVANCE was a clinical trial of 11,140 patients with type 2 diabetes, lasting a median of 5 years. Demographic and clinical characteristics were compared across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified releaseâbased intensive glucose control regimen, targeting an HbAlc of â€6.5%, were compared across regions using Cox proportional hazards models.
RESULTS When differences in baseline variables were allowed for, the risks of primary outcomes (major macrovascular or microvascular disease) were highest in Asia (joint hazard ratio 1.33 [95% CI 1.17â1.50]), whereas macrovascular disease was more common (1.19 [1.00â1.42]) and microvascular disease less common (0.77 [0.62â0.94]) in eastern Europe than in EMEs. Risks of death and cardiovascular death were highest in eastern Europe, and the mean difference in glycosylated hemoglobin between the intensive and standard groups was lowest in EMEs. Despite these and other differences, the effects of intensive glycemic control were not significantly different (P â„ 0.23) between regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes.
CONCLUSIONS Irrespective of absolute risk, the effects of intensive glycemic control with the gliclazide MR-based regimen used in ADVANCE were similar across Asia, EMEs, and eastern Europe. This regimen can safely be recommended for patients with type 2 diabetes in all of these regions
Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism
Importance: Most patients with primary aldosteronism, a major cause of secondary hypertension, are not identified or appropriately treated because of difficulties in diagnosis and subtype classification. Applications of artificial intelligence combined with mass spectrometryâbased steroid profiling could address this problem.
Objective: To assess whether plasma steroid profiling combined with machine learning might facilitate diagnosis and treatment stratification of primary aldosteronism, particularly for patients with unilateral adenomas due to pathogenic KCNJ5 sequence variants.
Design, Setting, and Participants: This diagnostic study was conducted at multiple tertiary care referral centers. Steroid profiles were measured from June 2013 to March 2017 in 462 patients tested for primary aldosteronism and 201 patients with hypertension. Data analyses were performed from September 2018 to August 2019.
Main Outcomes and Measures: The aldosterone to renin ratio and saline infusion tests were used to diagnose primary aldosteronism. Subtyping was done by adrenal venous sampling and follow-up of patients who underwent adrenalectomy. Statistical tests and machine-learning algorithms were applied to plasma steroid profiles. Areas under receiver operating characteristic curves, sensitivity, specificity, and other diagnostic performance measures were calculated.
Results: Primary aldosteronism was confirmed in 273 patients (165 men [60%]; mean [SD] age, 51 [10] years), including 134 with bilateral disease and 139 with unilateral adenomas (58 with and 81 without somatic KCNJ5 sequence variants). Plasma steroid profiles varied according to disease subtype and were particularly distinctive in patients with adenomas due to KCNJ5 variants, who showed better rates of biochemical cure after adrenalectomy than other patients. Among patients tested for primary aldosteronism, a selection of 8 steroids in combination with the aldosterone to renin ratio showed improved effectiveness for diagnosis over either strategy alone. In contrast, the steroid profile alone showed superior performance over the aldosterone to renin ratio for identifying unilateral disease, particularly adenomas due to KCNJ5 variants. Among 632 patients included in the analysis, machine learningâdesigned combinatorial marker profiles of 7 steroids alone both predicted primary aldosteronism in 1 step and subtyped patients with unilateral adenomas due to KCNJ5 variants at diagnostic sensitivities of 69% (95% CI, 68%-71%) and 85% (95% CI, 81%-88%), respectively, and at specificities of 94% (95% CI, 93%-94%) and 97% (95% CI, 97%-98%), respectively. The validation series yielded comparable diagnostic performance.
Conclusions and Relevance: Machine learningâdesigned combinatorial plasma steroid profiles may facilitate both screening for primary aldosteronism and identification of patients with unilateral adenomas due to pathogenic KCNJ5 variants, who are most likely to show benefit from surgical intervention
Determinants of disease-specific survival in patients with and without metastatic pheochromocytoma and paraganglioma
BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) have a heterogeneous prognosis, the basis of which remains unclear. We, therefore, assessed disease-specific survival (DSS) and potential predictors of progressive disease in patients with PPGLs and head/neck paragangliomas (HNPGLs) according to the presence or absence of metastases. METHODS: This retrospective study included 582 patients with PPGLs and 57 with HNPGLs. DSS was assessed according to age, location and size of tumours, recurrent/metastatic disease, genetics, plasma metanephrines and methoxytyramine. RESULTS: Among all patients with PPGLs, multivariable analysis indicated that apart from older age (HR = 5.4, CI = 2.93-10.29, P < 0.0001) and presence of metastases (HR = 4.8, CI = 2.41-9.94, P < 0.0001), shorter DSS was also associated with extra-adrenal tumour location (HR = 2.6, CI = 1.32-5.23, P = 0.0007) and higher plasma methoxytyramine (HR = 1.8, CI = 1.11-2.85, P = 0.0170) and normetanephrine (HR = 1.8, CI = 1.12-2.91, P = 0.0160). Among patients with HNPGLs, those with metastases presented with longer DSS compared to patients with metastatic PPGLs (33.4 versus 20.2 years, P < 0.0001) and only plasma methoxytyramine (HR = 13, CI = 1.35-148, P = 0.0380) was an independent predictor of DSS. For patients with metastatic PPGLs, multivariable analysis revealed that apart from older age (HR = 6.2, CI = 3.20-12.20, P < 0.0001), shorter DSS was associated with the presence of synchronous metastases (HR = 4.9, CI = 2.78-8.80, P < 0.0001), higher plasma methoxytyramine (HR = 2.4, CI = 1.44-4.14, P = 0.0010) and extensive metastatic burden (HR = 2.1, CI = 1.07-3.79, P = 0.0290). CONCLUSIONS: DSS among patients with PPGLs/HNPGLs relates to several presentations of the disease that may provide prognostic markers. In particular, the independent associations of higher methoxytyramine with shorter DSS in patients with HNPGLs and metastatic PPGLs suggest the utility of this biomarker to guide individualized management and follow-up strategies in affected patients
Missed clinical clues in patients with pheochromocytoma/paraganglioma discovered by imaging
CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. OBJECTIVE: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). DESIGN: Prospective study protocol, which has enrolled patients from 6 European centers with confirmed PPGLs. SETTING AND PATIENTS: Data were analyzed from 235 patients (37% iPPGLs, 36% sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. RESULTS: iPPGL patients were diagnosed at a significantly higher age than fPPGLs (p<0.001), found to have larger tumors (p=0.003) and higher metanephrine and normetanephrine levels at diagnosis (p=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs. 4.3 symptoms, p<0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than in fPPGL (60.9%) and sPPGL (21.5%). CONCLUSIONS: Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients the PPGL diagnosis had been delayed. PrĂ©cis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.The research leading to these results has received funding from the following sources: The Seventh Framework Programme (FP7/2007â2013) under grant agreement n° 259735 awarded to F B, H T and G E. The study has further been supported by the Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio 205/1 âThe Adrenal: Central Relay in Health and Diseaseâ to M F, M R, J L, G E, and F B.
The authors are grateful to all patients who participated in this research and to Christina Brugger, Katharina Langton and Denise Kaden for excellent technical assistance.S
Pheochromocytoma and paraganglioma: Clinical feature based disease probability in relation to catecholamine biochemistry and reason for disease suspicion
OBJECTIVE
Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease.
DESIGN AND METHODS
Patients were tested for PPGLs because of signs and symptoms, an incidental mass on imaging or routine surveillance due to previous history or hereditary risk. Patients with (n=245) compared to without (n=1820) PPGLs were identified on follow-up. Differences in presenting features were then examined to assess probability of disease and relationships to catecholamine excess.
RESULTS
Hyperhidrosis, palpitations, pallor, tremor and nausea were 30-90% more prevalent (P<0.001) among patients with than without PPGLs, whereas headache, flushing and other symptoms showed little or no differences. Although heart rates were higher (P<0.0001) in patients with than without PPGLs, blood pressures were not higher and were positively correlated to body mass index (BMI), which was lower (P<0.0001) in patients with than without PPGLs. From these differences in clinical features, a score system was established that indicated a 5.8-fold higher probability of PPGLs in patients with high than low scores. Higher scores among patients with PPGLs were associated, independently of tumor size, with higher biochemical indices of catecholamine excess.
CONCLUSIONS
This study identifies a complex of five signs and symptoms combined with lower BMI and elevated heart rate as key features in patients with PPGLs. Prevalences of these features, which reflect variable tumoral catecholamine production, may be used to triage patients according to likelihood of disease
Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations
Additional file 1. Complementary data on primer sequences, SKI amplification and survival analyses
Prediction of metastatic pheochromocytoma and paraganglioma: a machine learning modelling study using data from a cross-sectional cohort
BACKGROUND
Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features, and how machine learning-based predictions compare with predictions made by specialists in the field.
METHODS
In this machine learning modelling study, we used cross-sectional cohort data from the PMT trial, based in Germany, Poland, and the Netherlands, to prospectively examine the utility of methoxytyramine to predict metastatic disease in 267 patients with pheochromocytoma or paraganglioma and positive biochemical test results at initial screening. Another retrospective dataset of 493 patients with these tumors enrolled under clinical protocols at National Institutes of Health (00-CH-0093) and the Netherlands (PRESCRIPT trial) was used to train and validate machine learning models according to selections of additional features. The best performing machine learning models were then externally validated using data for all patients in the PMT trial. For comparison, 12 specialists provided predictions of metastatic disease using data from the training and external validation datasets.
FINDINGS
Prospective predictions indicated that plasma methoxytyramine could identify metastatic disease at sensitivities of 52% and specificities of 85%. The best performing machine learning model was based on an ensemble tree classifier algorithm that used nine features: plasma methoxytyramine, metanephrine, normetanephrine, age, sex, previous history of pheochromocytoma or paraganglioma, location and size of primary tumours, and presence of multifocal disease. This model had an area under the receiver operating characteristic curve of 0·942 (95% CI 0·894-0·969) that was larger (p<0·0001) than that of the best performing specialist before (0·815, 0·778-0·853) and after (0·812, 0·781-0·854) provision of SDHB variant data. Sensitivity for prediction of metastatic disease in the external validation cohort reached 83% at a specificity of 92%.
INTERPRETATION
Although methoxytyramine has some utility for prediction of metastatic pheochromocytomas and paragangliomas, sensitivity is limited. Predictive value is considerably enhanced with machine learning models that incorporate our nine recommended features. Our final model provides a preoperative approach to predict metastases in patients with pheochromocytomas and paragangliomas, and thereby guide individualised patient management and follow-up.
FUNDING
Deutsche Forschungsgemeinschaft
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