Maternal and fetal outcomes in phaeochromocytoma and pregnancy:a multicentre retrospective cohort study and systematic review of literature

Background Phaeochromocytoma or paraganglioma (collectively known as PPGL) in pregnant women can lead to severe complications and death due to associated catecholamine excess. We aimed to identify factors associated with maternal and fetal outcomes in women with PPGL during pregnancy.Methods We did a multicentre, retrospective study of patients with PPGL and pregnancy between Jan 1, 1980, and Dec 31, 2019, in the International Pheochromocytoma and Pregnancy Registry and a systematic review of studies published between Jan 1, 2005, and Dec 27, 2019 reporting on at least five cases. The inclusion criteria were pregnancy after 1980 and PPGL before or during pregnancy or within 12 months post partum. Eligible patients from the retrospective study and systematic review were included in the analysis. Outcomes of interest were maternal or fetal death and maternal severe cardiovascular complications of catecholamine excess. Potential variables associated with these outcomes were evaluated by logistic regression.Findings The systematic review identified seven studies (reporting on 63 pregnancies in 55 patients) that met the eligibility criteria and were of adequate quality. A further 197 pregnancies in 186 patients were identified in the International Pheochromocytoma and Pregnancy Registry. After excluding 11 pregnancies due to potential overlap, the final cohort included 249 pregnancies in 232 patients with PPGL. The diagnosis of PPGL was made before pregnancy in 37 (15%) pregnancies, during pregnancy in 134 (54%), and after delivery in 78 (31%). Of 144 patients evaluated for genetic predisposition for phaeochromocytoma, 95 (66%) were positive. Unrecognised PPGL during pregnancy (odds ratio 27.0; 95% CI 3.5-3473.1), abdominal or pelvic tumour location (11.3; 1.5-1440.5), and catecholamine excess at least ten-times the upper limit of the normal range (4.7; 1.8-13.8) were associated with adverse outcomes. For patients diagnosed during pregnancy, alpha-adrenergic blockade therapy was associated with fewer adverse outcomes (3.6; 1.1-13.2 for no alpha-adrenergic blockade vs alpha-adrenergic blockade), whereas surgery during pregnancy was not associated with better outcomes (0.9; 0.3-3.9 for no surgery vs surgery).Interpretation Unrecognised and untreated PPGL was associated with a substantially higher risk of either maternal or fetal complications. Appropriate case detection and counselling for premenopausal women at risk for PPGL could prevent adverse pregnancy-related outcomes. Copyright (C) 2020 Elsevier Ltd. All rights reserved

Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid

Pharmacolog

Genetic and Clinical Investigation of Pheochromocytoma: A 22-Year Experience, from Freiburg, Germany to International Effort

Although deceptively simple, the etio-pathogenesis of pheochromocytoma represents a clinical and molecular genetic investigative challenge. Here, we summarize, from a historical point of view, the 22-year-long studies initiated at the University of Freiburg, which developed from a local experience to a national and finally an international effort. All research activities are translational and clinical and hence, registry based and intended to improve the outcome of the patients, whether by improved detection, prevention, or treatment. Major clinical steps are the prospective study on hormone tests and imaging techniques for adrenal and extra-adrenal abdominal tumors as well as the concept of organ sparing and endoscopic tumor resection. Further, we introduced 18-fluoro-dopa positron emission tomography. Population-based registries were used in order to identify germline mutations in the susceptibility genes VHL, RET, SDHB, and SDHD in non-syndromic pheochromocytoma. We differentiated distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. Finally, we identified predictors and prevalence of paraganglioma syndromes associated with mutations of the SDHC gene

Methane Activation on a La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3) Perovsksite; Catalytic and Electrocatalytic Results

The catalytic and electrocatalytic behaviour of the La(0.6)Sr(0.4)Co(0.8)Fe(0.2)O(3) (LSCF) perovskite deposited on yttria stabilized zirconia (YSZ), was studied during the reaction of methane oxidation. Experiments were carried out at atmospheric pressure, and at temperatures between 600 and 900 degrees C. When, instead of cofeeding with methane in the gas phase, oxygen was electrochemically supplied as O(2), considerable changes in the methane conversion and product selectivity were observed. The non-faradaic effects (NEMCA) were also studied and compared to those observed with metal catalysts