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1.
Drugs to Prevent Bronchopulmonary Dysplasia: Effect of Baseline Risk on the Number Needed to Treat.
Jensen, EA, Roberts, RS, Schmidt, B
The Journal of pediatrics. 2020;:244-247
Abstract
Infants born very preterm have a variable baseline risk of bronchopulmonary dysplasia (BPD). Using the example of evidence-based drug therapies to prevent BPD, we designed a visual aid that displays the "number needed to treat" with CIs for caffeine, vitamin A, and hydrocortisone over a range of baseline risks.
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2.
Treating sepsis with vitamin C, thiamine, and hydrocortisone: Exploring the quest for the magic elixir.
Obi, J, Pastores, SM, Ramanathan, LV, Yang, J, Halpern, NA
Journal of critical care. 2020;:231-239
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Abstract
The administration of ascorbic acid (vitamin C) alone or in combination with thiamine (vitamin B1) and corticosteroids (VCTS) has recently been hypothesized to improve hemodynamics, end-organ function, and may even increase survival in critically ill patients. There are several clinical studies that have investigated the use of vitamin C alone or VCTS in patients with sepsis and septic shock or are ongoing. Some of these studies have demonstrated its safety and potential benefit in septic patients. However, many questions remain regarding the optimal dosing regimens and plasma concentrations, timing of administration, and adverse effects of vitamin C and thiamine. These questions exist because the bulk of research regarding the efficacy of vitamin C alone or in combination with thiamine and corticosteroids in sepsis is limited to a few randomized controlled trials, retrospective before-and-after studies, and case reports. Thus, although the underlying rationale and mechanistic pathways of vitamin C and thiamine in sepsis have been well described, the clinical impact of the VCTS regimen is complex and remains to be determined. This review aims to explore the current evidence and potential benefits and adverse effects of the VCTS regimen for the treatment of sepsis.
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3.
Classic and Nonclassic Apparent Mineralocorticoid Excess Syndrome.
Carvajal, CA, Tapia-Castillo, A, Vecchiola, A, Baudrand, R, Fardella, CE
The Journal of clinical endocrinology and metabolism. 2020;(4)
Abstract
CONTEXT Arterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low renin levels allowed the identification of 2 different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation. EVIDENCE ACQUISITION This review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism. EVIDENCE SYNTHESIS The spectrum of cortisol-mediated MR activation includes the classic AME syndrome to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. Nonclassic AME (NC-AME) is mainly related to partial 11βHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (ie, glycyrrhetinic acid-like factors [GALFS]) and other factors (ie, age, high sodium intake) (second hit). Subjects with NC-AME are characterized by a high F/E ratio, low E levels, normal to elevated blood pressure, low plasma renin and increased urinary potassium excretion. NC-AME condition should benefit from low-sodium and potassium diet recommendations and monotherapy with MR antagonists. CONCLUSION NC-AME has a higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene and epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage, and modulate the renin levels.
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4.
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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5.
Medical Management of Cushing's Syndrome: Current and Emerging Treatments.
Hinojosa-Amaya, JM, Cuevas-Ramos, D, Fleseriu, M
Drugs. 2019;(9):935-956
Abstract
Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, and long-term medical treatment is used to decrease cortisol levels and risk of metabolic comorbidities. Medical treatment is also often required while waiting for radiation effects to take place. In some cases, severe or life-threatening hypercortisolism must be urgently and medically treated, via intravenous medications or with combination therapy, before patients can undergo surgery. In the last decade, medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer side effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing's disease, and glucocorticoid receptor antagonists that block cortisol's action. Understanding the pathophysiology of Cushing's syndrome has also led to the identification of potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess, and/or decrease tumor cell proliferation, and induce senescence or apoptosis. We provide here a review of current and near-future medical options to treat Cushing's syndrome, and discuss updates on clinical trials and the efficacy and safety of novel or in-development drugs, as well as future potential targets.
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6.
HPA axis responses to psychological challenge linking stress and disease: What do we know on sources of intra- and interindividual variability?
Zänkert, S, Bellingrath, S, Wüst, S, Kudielka, BM
Psychoneuroendocrinology. 2019;:86-97
Abstract
Stress is an ubiquitous phenomenon with significant impact on human physiology when it lasts too long, when it is too intense, or when it hits vulnerable individuals. Examining the mechanisms linking stress exposure with health and disease is an important endeavor in psychoneuroendocrine research. Empirical evidence so far revealed large intra- as well as inter-individual variability in hypothalamic-pituitary-adrenal (HPA) axis responses to acute psychosocial stress, showing that the HPA axis is a highly adaptive system. Thus, the characterization of intra- und inter-individual patterns of HPA axis reactivity is of high scientific interest and forms the basis on which mechanistic links between stress response (dys)regulation and health impairments can be examined. To date, basic knowledge has been, and still is, accumulated on demographic, biological (including genetic and epigenetic) factors, lifestyle behavioral variables, consumption of substances and medication, psychological and personality factors, as well as on methodological aspects. Besides this, there is also very recent progress in respect to the development of laboratory stress paradigms that can be applied in virtual reality or inside an MRI-scanner. In sum, the present review updates our current knowledge on moderating and intervening factors as sources of intra- und inter-individual variability in human cortisol stress responses and offers recommendations for future research designs.
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7.
Association Between Cortisol, Insulin Resistance and Zinc in Obesity: a Mini-Review.
Morais, JBS, Severo, JS, Beserra, JB, de Oiveira, ARS, Cruz, KJC, de Sousa Melo, SR, do Nascimento, GVR, de Macedo, GFS, do Nascimento Marreiro, D
Biological trace element research. 2019;(2):323-330
Abstract
Adipose tissue is considered an endocrine organ and its excess compromises the immune response and the metabolism of hormones and nutrients. Furthermore, visceral fat accumulation contributes to increased cortisol synthesis, which in turn induces metallothionein and Zip14 expression, which are proteins that contribute to reducing plasma zinc levels. Zinc plays a critical role in the secretion and signaling of insulin. Changes in the biochemical parameters of zinc, as observed in individuals who are obese, contribute to the manifestation of related disorders such as insulin resistance. Thus, the purpose of this review is to provide an update on the current information on the relationship between cortisol, zinc, and insulin resistance in obesity. The data in the literature provide evidence that cortisol affects zinc metabolism, and indicate possible repercussions on insulin signaling that might contribute to the development of resistance to the actions of insulin in obesity.
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8.
Children's cortisol response to the transition from preschool to formal schooling: A review.
Parent, S, Lupien, S, Herba, CM, Dupéré, V, Gunnar, MR, Séguin, JR
Psychoneuroendocrinology. 2019;:196-205
Abstract
This review examines the current state of knowledge regarding children's biological stress response during the transition from preschool to compulsory formal schooling, focusing on longitudinal studies that include repeated measures of cortisol concentrations in saliva or scalp hair. In all, eight independent studies (ten publications) were found and their results support the hypothesis that the transition from preschool to formal schooling coincides with an increase in cortisol concentration in both saliva and hair. Evidence of recovery (i.e. decrease in stress response over time) is more limited and suggests that it could take as many as 3-6 months before kindergarten children's cortisol concentration returns to baseline levels. However, important individual differences are observed. Potential predictors that have received some empirical support include child temperament (fearfulness/inhibition or surgency/extroversion) and prenatal maternal stress or anxiety. Very few studies, however, have examined whether there are actual functional consequences of individual differences in children's cortisol response associated with this transition. Finally, current methodological limitations and avenues for future studies are discussed.
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9.
The cortisol stress response induced by surgery: A systematic review and meta-analysis.
Prete, A, Yan, Q, Al-Tarrah, K, Akturk, HK, Prokop, LJ, Alahdab, F, Foster, MA, Lord, JM, Karavitaki, N, Wass, JA, et al
Clinical endocrinology. 2018;(5):554-567
Abstract
OBJECTIVE Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. DESIGN We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. METHODS We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time. RESULTS We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. CONCLUSIONS The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.
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10.
Patterns of Death in Patients with Sepsis and the Use of Hydrocortisone, Ascorbic Acid, and Thiamine to Prevent These Deaths.
Marik, PE
Surgical infections. 2018;(8):812-820
Abstract
Background: In general, patients with sepsis die from the host response to the infecting pathogen rather than from the infecting pathogen itself. Four patterns of death have been identified in sepsis, namely vasoplegic shock, single-organ respiratory failure (acute respiratory distress syndrome [ARDS]), multi-system organ failure (MSOF), and persistent MSOF with ongoing inflammation and immunosuppression with recurrent infections (persistent inflammation-immunosuppression and catabolism syndrome [PICS]). To improve the outcome of sepsis adjunctive therapies that modulate the immune system have been tested; these therapies that have targeted specific molecules or pathways have universally failed. Conclusion: We propose that the combination of hydrocortisone, intravenous ascorbic acid, and thiamine (HAT therapy), which synergistically targets multiple pathways, restores the dysregulated immune system and organ injury, and reduces the risk of death and organ failure following sepsis.