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Long-term prednisone versus hydrocortisone treatment in children with classic Congenital Adrenal Hyperplasia (CAH) and a brief review of the literature.
Ahmed, SEAM, Soliman, AT, Ramadan, MA, Elawwa, A, Abugabal, AMS, Emam, MHA, De Sanctis, V
Acta bio-medica : Atenei Parmensis. 2019;(3):360-369
Abstract
BACKGROUND Debate still exist about the safety of long-term use of prednisone (PD) versus hydrocortisone (HC) for treating children with congenital adrenal hyperplasia -21OH D (CAH). Despite recent developments in congenital adrenal hyperplasia -21OH D (CAH), several issues related to patient growth and final height remain unsolved. Debate still exist about the safety of long-term use of PD versus HC for treating children with CAH. The mechanism by which glucocorticoid therapy interferes with growth is complex and multifactorial. Relatively slight supra-physiologic levels may be enough to blunt growth velocity. An increased risk of developing obesity is another possible consequence of hyper-cortisolism in children with CAH. OBJECTIVES OF THE STUDY To evaluate the anthropometric and biochemical effects of long-term PD versus HC treatment in children with CAH-21OHD. A brief review of the literature is also reported. PATIENTS AND METHODS This retrospective study evaluated linear growth and biochemical data of thirty children with classic CAH (19 females and 11 males), who were on PD (n=22) or HC (n=8) treatment, since their first diagnosis. Clinical data included age, gender, duration of therapy, dose of HC and or equivalent dose of HC in the PD group, blood pressure, height (Ht) and weight. Ht-SDS and BMI were also calculated. Biochemical data included measurement of 17- OH progesterone, cholesterol, triglycerides (TG), HDL, LDL, fasting glucose, and insulin concentrations. HOMA-IR was calculated. Carotid intima-media thickness (CIMT) was measured using high-resolution B-mode ultrasonography. Thirty normal age matched children were used as controls for the anthropometric and CIMT data. RESULTS The age of children and duration of treatment did not differ among the two treatment groups. After a mean of 6 years of treatment, the Ht-SDS and BMI did not differ between the three groups of children. The equivalent hydrocortisone dose of children on prednisone was significantly higher than the dose for the hydrocortisone group. Both systolic and diastolic blood pressures (BP) of children on PD was slightly higher compared to those on hydrocortisone group. However, the BP of the 2 treatment groups was not different compared to control children. Fasting blood glucose, homeostatic model assessment insulin resistance (HOMA-IR), plasma TG, HDL, and cholesterol did not differ among the two treatment groups. LDL levels were significantly higher in the PD group versus the HC group. The mean CIMT did not differ among the two treatment groups but was significantly higher in the treated groups versus controls. There was a significant linear correlation between BMI-SDS and CIMT (r=0.37, p=0.047). CONCLUSIONS Children with CAH-21OHD who were kept on PD therapy for 6.4±2.7 years, since the beginning of diagnosis, have maintained normal linear growth. No difference in BMI, HOMA-IR, or CIMT was detected among the two treated groups. The efficiency, safety and convenience of a single daily dose of PD could be a good and relatively safe alternative to HC for the continuing medical treatment of patients with CAH-21OHD. However, more prospective studies across childhood and adolescence are necessary to draw definitive conclusions.
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Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial.
Ebrahimi, F, Giaglis, S, Hahn, S, Blum, CA, Baumgartner, C, Kutz, A, van Breda, SV, Mueller, B, Schuetz, P, Christ-Crain, M, et al
The European respiratory journal. 2018;(4)
Abstract
Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia (CAP) is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomised controlled, multicentre trial. Patients with CAP were randomly assigned to either 50 mg prednisone or placebo for 7 days. The primary end-point was time to clinical stability; main secondary end-points were length of hospital stay and mortality.In total, 310 patients were included in the analysis. Levels of cell-free nucleosomes as surrogate markers of NETosis were significantly increased at admission and declined over 7 days. NETs were significantly associated with reduced hazards of clinical stability and hospital discharge in multivariate adjusted analyses. Moreover, NETs were associated with a 3.8-fold increased adjusted odds ratio of 30-day mortality. Prednisone treatment modified circulatory NET levels and was associated with beneficial outcome.CAP is accompanied by pronounced NET formation. Patients with elevated serum NET markers were at higher risk for clinical instability, prolonged length of hospital stay and 30-day all-cause mortality. NETs represent a novel marker for outcome and a possible target for adjunct treatments of pneumonia.
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Testicular vs adrenal sources of hydroxy-androgens in prostate cancer.
Zang, T, Taplin, ME, Tamae, D, Xie, W, Mesaros, C, Zhang, Z, Bubley, G, Montgomery, B, Balk, SP, Mostaghel, EA, et al
Endocrine-related cancer. 2017;(8):393-404
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Abstract
Neoadjuvant androgen deprivation therapy (NADT) is one strategy for the treatment of early-stage prostate cancer; however, the long-term outcomes of NADT with radical prostatectomy including biochemical failure-free survival are not promising. One proposed mechanism is incomplete androgen ablation. In this study, we aimed to evaluate the efficiency of serum hydroxy-androgen suppression in patients with localized high-risk prostate cancer under NADT (leuprolide acetate plus abiraterone acetate and prednisone) and interrogate the primary sources of circulating hydroxy-androgens using our recently described stable isotope dilution liquid chromatography mass spectrometric method. For the first time, three androgen diols including 5-androstene-3β,17β-diol (5-adiol), 5α-androstane-3α,17β-diol (3α-adiol), 5α-androstane-3β,17β-diol (3β-adiol), the glucuronide or sulfate conjugate of 5-adiol and 3α-adiol were measured and observed to be dramatically reduced after NADT. By comparing patients that took leuprolide acetate alone vs leuprolide acetate plus abiraterone acetate and prednisone, we were able to distinguish the primary sources of these androgens and their conjugates as being of either testicular or adrenal in origin. We find that testosterone, 5α-dihydrotestosterone (DHT), 3α-adiol and 3β-adiol were predominately of testicular origin. By contrast, dehydroepiandrosterone (DHEA), epi-androsterone (epi-AST) and their conjugates, 5-adiol sulfate and glucuronide were predominately of adrenal origin. Our findings also show that NADT failed to completely suppress DHEA-sulfate levels and that two unappreciated sources of intratumoral androgens that were not suppressed by leuprolide acetate alone were 5-adiol-sulfate and epi-AST-sulfate of adrenal origin.
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Five years experience on 3,4-diaminopyridine phosphate in Lambert-Eaton syndrome: Case reports.
Portaro, S, Brizzi, T, Sinicropi, S, Cacciola, A, De Cola, MC, Bramanti, A, Milardi, D, Lupica, A, Bramanti, P, Toscano, A, et al
Medicine. 2017;(38):e7839
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Abstract
RATIONALE To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation. OUTCOMES Five out of 7 patients presented a clinical improvement persisting at last 5-year follow-up; 2 out of them improved taking only 3,4-DAPP at the maximal dosage, whereas the remaining received concomitant medications, such as prednisone and azathioprine. However, the clinical amelioration was not statistically significant. No one of the patients reported severe adverse events, except one, complaining of transient chin and perioral paresthesias. A significant association between QMG and the type of pharmacological drugs therapy (P = .028) emerged. Indeed, we observed an improvement of the clinical condition in all 3 subjects treated with 3,4-DAPP and prednisone. CONCLUSIONS In this study, we confirm 3,4-DAPP treatment efficacy on muscle strength, but minor evidence of drug effectiveness have been demonstrated on the autonomic nervous system involvement and on the deep tendon reflexes reappearance, a part from patients who received 3,4-DAPP associated to prednisone.
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Serum metabolomic response of myasthenia gravis patients to chronic prednisone treatment.
Sengupta, M, Cheema, A, Kaminski, HJ, Kusner, LL, ,
PloS one. 2014;(7):e102635
Abstract
Prednisone is often used for the treatment of autoimmune and inflammatory diseases but they suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction resulting in weakness. The patients with myasthenia gravis are primarily treated with prednisone. We analyzed the metabolomic profile of serum collected from patients prior to and after 12 weeks of prednisone treatment during a clinical trial. Our aim was to identify metabolites that may be treatment responsive and be evaluated in future studies as potential biomarkers of efficacy or adverse effects. Ultra-performance liquid chromatography coupled with electro-spray quadrupole time of flight mass spectrometry was used to obtain comparative metabolomic and lipidomic profile. Untargeted metabolic profiling of serum showed a clear distinction between pre- and post-treatment groups. Chronic prednisone treatment caused upregulation of membrane associated glycerophospholipids: phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, 1, 2-diacyl-sn glycerol 3 phosphate and 1-Acyl-sn-glycero-3-phosphocholine. Arachidonic acid (AA) and AA derived pro-inflammatory eicosanoids such as 18-carboxy dinor leukotriene B4 and 15 hydroxyeicosatetraenoic acids were reduced. Perturbations in amino acid, carbohydrate, vitamin and lipid metabolism were observed. Chronic prednisone treatment caused increase in membrane associated glycerophospholipids, which may be associated with certain adverse effects. Decrease of AA and AA derived pro-inflammatory eicosanoids demonstrate that immunosuppression by corticosteroid is via suppression of pro-inflammatory pathways. The study identified metabolomic fingerprints that can now be validated as prednisone responsive biomarkers for the improvement in diagnostic accuracy and prediction of therapeutic outcome.
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Treatment with metadoxine and its impact on early mortality in patients with severe alcoholic hepatitis.
Higuera-de la Tijera, F, Servín-Caamaño, AI, Cruz-Herrera, J, Serralde-Zúñiga, AE, Abdo-Francis, JM, Gutiérrez-Reyes, G, Pérez-Hernández, JL
Annals of hepatology. 2014;(3):343-52
Abstract
BACKGROUND & AIM: Despite treatment with glucocorticoids, mortality remains high in patients with severe alcoholic hepatitis. Oxidative stress and depletion of mitochondrial glutathione are implicated factors in liver injury. The aim of this study was to evaluate the impact of the addition of metadoxine, a drug which possesses a multifactorial mechanism of action, including antioxidant properties, to standard treatment with glucocorticoids in patients with severe alcoholic hepatitis. MATERIAL AND METHODS This randomized open label clinical trial was performed in Mexico's General Hospital (Registry Key DIC/10/107/03/043). We randomized 70 patients with severe alcoholic hepatitis. The first group received prednisone (40 mg/day), and the second group received prednisone (40 mg/day) plus metadoxine tablets (500 mg three times daily). The duration of treatment in both groups was 30 days. Survival at 30 and 90 days, development of complications, adverse events and response to treatment (Lille model) were assessed. RESULTS In the group receiving metadoxine, significant improvements were observed, as follows: survival at 30 days (74.3 vs. 45.7%, P = 0.02); survival at 90 days (68.6 vs. 20.0%, P = 0.0001). There was less development or progression of encephalopathy (28.6 vs. 60.0%, P = 0.008) and hepatorenal syndrome (31.4 vs. 54.3%, P = 0.05), and the response to treatment (Lille model) was higher in the metadoxine group (0.38 vs. 0.63, P = 0.001; 95% CI 0.11 to 0.40). There were no differences between groups regarding the development or progression of variceal hemorrhage or infection. The incidence of adverse events, mainly gastrointestinal, was similar in both groups. CONCLUSIONS Addition of metadoxine to glucocorticoid treatment improves the short-term survival of patients with severe alcoholic hepatitis and diminishes the development or progression of encephalopathy and hepatorenal syndrome.
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Oral etoposide and oral prednisone for the treatment of castration resistant prostate cancer.
Zhu, YP, Yao, XD, Zhang, SL, Dai, B, Zhang, HL, Shen, YJ, Zhu, Y, Shi, GH, Lin, GW, Ye, DW
The Kaohsiung journal of medical sciences. 2014;(2):82-5
Abstract
Treatment options for patients with castration-resistant prostate cancer (CRPC) are limited. The purpose of our study was to investigate the safety and efficacy in terms of prostate-specific antigen (PSA) response of a low-dose oral combination of etoposide and prednisone in patients with CRPC. Thirty-nine patients with prostate cancer (median age, 77.9 years) with progressive disease after standard hormonal therapy were enrolled. Etoposide (25 mg, twice daily) and prednisone (5 mg, twice daily) were administered orally. Each cycle comprised 21 consecutive days of treatment followed by a 7-day drug holiday. All patients previously treated with an antiandrogen were required to undergo antiandrogen withdrawal prior to entry into the study. A total of 226 cycles were administered with a median of 6.7 cycles per patient (range, 1-18 cycles). Sixteen of 39 patients (41%) with elevated PSA levels at baseline achieved at least a 50% reduction in PSA levels. Median progression-free survival for all patients was 5.9 months (range, 1-17 months). No Grade 4 toxicities were observed. The predominant toxicities were mucositis, nausea, fatigue, and anemia in twelve, nine, eight, and seven patients, respectively. Hematologic toxicity was infrequent, with no episodes of febrile neutropenia. The combination of low-dose etoposide and prednisone is an efficacious and reasonably well-tolerated oral regimen in the treatment of elderly patients with CRPC. This regimen can be easily administered in an outpatient setting and does not require frequent patient visits.
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[Reversal of acute liver failure with N-acetylcysteine and prednisone in a patient with DRESS syndrome: a case report and literature review].
Pérez-Reyes, E, Casanova-Lara, A, Pérez-Torres, E, Córdova, J
Revista de gastroenterologia de Mexico. 2014;(3):208-10
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Central serous retinopathy.
Tarabishy, AB, Ahn, E, Mandell, BF, Lowder, CY
Arthritis care & research. 2011;(8):1075-82
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The influence of thiamazole, lithium carbonate, or prednisone administration on the efficacy of radioiodine treatment ((131)I) in hyperthyroid patients.
Oszukowska, L, Knapska-Kucharska, M, Makarewicz, J, Lewiński, A
Endokrynologia Polska. 2010;(1):56-61
Abstract
INTRODUCTION The effects of selected drugs (see below) on the efficacy of ((131)I) radioiodine therapy were examined. MATERIAL AND METHODS The study involved 200 hyperthyroid patients, treated with radioactive iodine. They were divided into five groups (40 persons in each). In Group I - patients were administered (131)I and thiamazole; in Group II they were given - (131)I and lithium carbonate; in Group III they were given - (131)I only (the assumed absorbed dose - 150-200 Gy, the same as in Groups I and II, for which Group III was a control group); in Group IV they were given - (131)I and prednisone; and in Group V they were given - (131)I only (250-350 Gy, the same as in Group IV, for which Group V was a control group). Therapeutic results were analyzed after six months based on clinical and hormonal status. The evaluation also included effects of the initial hormonal status on the outcome of (131)I therapy in Groups II and IV (v. respective controls, i.e. Groups III and V); such analysis was not performed in Group I because all the patients in that group were initially hyperthyroid. RESULTS In 145 patients (72.5%) the therapy with (131)I was effective. In 55 patients (27.5%) the therapy was ineffective. The application of thiamazole during the peritherapeutic period in patients treated with 131I reduced the effectiveness of radioiodine, while lithium carbonate had no effect on the therapy outcome. Prednisone increased the effectiveness of the therapy with (131)I. Normalisation of the initial concentration of TSH was advantageous for the (131)I therapeutic outcome only when the assumed absorbed doses of 150-200 Gy were applied, while being of no avail for doses above 250 Gy. CONCLUSIONS The present results indicate the necessity of careful analysis of administered drugs in hyperthyroid patients while qualifying them to (131)I therapy. The initial concentration of TSH has no effect on the efficacy of radioiodine therapy in cases where absorbed doses are regarded to be ablative. (Pol J Endocrinol 2010; 61 (1): 56-61).