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Pheochromocytoma and paraganglioma: clinical feature-based disease probability in relation to catecholamine biochemistry and reason for disease suspicion.
Geroula, A, Deutschbein, T, Langton, K, Masjkur, J, Pamporaki, C, Peitzsch, M, Fliedner, S, Timmers, HJLM, Bornstein, SR, Beuschlein, F, et al
European journal of endocrinology. 2019;(4):409-420
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Abstract
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 the 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 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.
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Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2).
Brisard, L, Le Gouge, A, Lascarrou, JB, Dupont, H, Asfar, P, Sirodot, M, Piton, G, Bui, HN, Gontier, O, Hssain, AA, et al
Trials. 2014;:507
Abstract
BACKGROUND Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).
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Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT).
Lüscher, TF, Enseleit, F, Pacher, R, Mitrovic, V, Schulze, MR, Willenbrock, R, Dietz, R, Rousson, V, Hürlimann, D, Philipp, S, et al
Circulation. 2002;(21):2666-72
Abstract
BACKGROUND The endothelin (ET-1) system is activated in chronic heart failure (CHF). Whether, what type, and what degree of selective ET blockade is clinically beneficial is unknown. We investigated hemodynamic and neurohumoral effects of 3 weeks of treatment with various dosages of the orally available ET(A) antagonist darusentan in addition to modern standard therapy in patients with CHF. METHODS AND RESULTS A total of 157 patients with CHF (present or recent NYHA class III of at least 3 months duration), pulmonary capillary wedge pressure > or =12 mm Hg, and a cardiac index < or =2.6 L x min(-1) x m(-2) were randomly assigned to double-blind treatment with placebo or darusentan (30, 100, or 300 mg/d) in addition to standard therapy. Short-term administration of darusentan increased the cardiac index, but this did not reach statistical significance compared with placebo. The increase in cardiac index was significantly more pronounced after 3 weeks of treatment (P<0.0001 versus placebo). Pulmonary capillary wedge pressure, pulmonary arterial pressure, pulmonary vascular resistance, and right atrial pressure remained unchanged. Heart rate, mean artery pressure, and plasma catecholamines remained unaltered, but systemic vascular resistance decreased significantly (P=0.0001). Higher dosages were associated with a trend to more adverse events (including death), particularly early exacerbation of CHF without further benefit on hemodynamics compared with moderate dosages. CONCLUSIONS This study demonstrates for the first time in a large patient population that 3 weeks of selective ET(A) receptor blockade improves cardiac index in patients with CHF. However, long-term studies are needed to determine whether ET(A) blockade is beneficial in CHF.