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1.
Management of acute severe ulcerative colitis in chile: Experience of a multidisciplinary team.
Pérez de Arce, E, Quera, R, Núñez, P, Simian, D, Ibáñez, P, Lubascher, J, Figueroa, C, Pizarro, G, Flores, L, Carrasco-Avino, G, et al
Gastroenterologia y hepatologia. 2022;(3):206-207
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Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.
Berke, K, Constantinescu, G, Masjkur, J, Kimpel, O, Dischinger, U, Peitzsch, M, Kwapiszewska, A, Dobrowolski, P, Nölting, S, Reincke, M, et al
The Journal of clinical endocrinology and metabolism. 2022;(3):e1181-e1192
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CONTEXT Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need. OBJECTIVE This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma. METHODS This retrospective cross-sectional study, which took place at 7 European tertiary-care centers, comprised 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma (PHEO), primary aldosteronism (PA), autonomous cortisol secretion (ACS), and nonfunctional adrenal incidentaloma (NFAI). Mesaures of diagnostic performance were assessed (with [95% CIs]) for discriminating different subgroups of patients with adrenal incidentaloma. RESULTS Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol, and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA, and PHEO at respective sensitivities of 83.3% (66.1%-100%), 90.8% (83.7%-97.8%), and 94.8% (89.8%-99.8%); and specificities of 98.0% (96.9%-99.2%), 92.0% (89.6%-94.3%), and 98.6% (97.6%-99.6%). With the addition of tumor size, discrimination improved further, particularly for ACC (100% [100%-100%] sensitivity, 99.5% [98.9%-100%] specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70%-71% sensitivity, 89%-90% specificity). CONCLUSION Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate the identification of almost all clinically relevant adrenal tumors.
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24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency.
Turcu, AF, Mallappa, A, Nella, AA, Chen, X, Zhao, L, Nanba, AT, Byrd, JB, Auchus, RJ, Merke, DP
Frontiers in endocrinology. 2021;:751191
Abstract
BACKGROUND Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking. OBJECTIVE To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling. PARTICIPANTS AND METHODS We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I-II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI. RESULTS In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men. CONCLUSION 11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.
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Extracorporeal photopheresis vs standard therapies for steroid-refractory chronic graft-vs-host disease: Pharmacoeconomic assessment of hospital resource use in Spain.
Boluda, B, Solana-Altabella, A, Cano, I, Acuña-Cruz, E, Rodríguez-Veiga, R, Ballesta-López, O, Megías-Vericat, JE, Martínez-Cuadrón, D, Gómez, I, Solves, P, et al
Journal of clinical apheresis. 2021;(4):612-620
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BACKGROUND This study assessed pharmacoeconomic costs associated with extracorporeal photopheresis (ECP) compared with other available second-line therapies for chronic graft-vs-host disease (cGvHD) in a tertiary Spanish institution. METHODS Patients (≥18 years) diagnosed with steroid-refractory cGvHD were eligible. Data were collected retrospectively from index date until 1 year or relapse. Patients were distributed in two cohorts (ECP vs non-ECP), matched by age (≤ or > 40), hematopoietic stem cell transplant (HLA-identical sibling donor or other) and number of previous immunosuppressive lines (1, 2, or ≥ 3). Costs were assigned using the 2016 diagnosis-related group (DRG) system: DRG 579 (€22 383) overnight stay due to major complication (ie, sepsis, pneumonia, parenteral nutrition, or respiratory failure), and DRG 875 (€5154) if no major complication. The primary endpoint was healthcare resource utilization per patient. RESULTS Forty patients (n = 20 per cohort) were included. Median age was 49, and 37.5% were female. Mean total cost per patient was €25 319 (95% CI: €17 049-€33 590) across the two cohorts, with a slightly lower mean cost per ECP-treated patient (€23 120) compared with the non-ECP cohort (€27 519; P = .597). Twenty-seven inpatient hospitalizations occurred among ECP-treated patients, vs 33 in the non-ECP cohort. Day hospital and external consultations were more frequent in the ECP cohort. However, fewer inpatient admissions included DRG 579 compared with the non-ECP cohort (44% vs 58%). Inpatient length of stay was slightly shorter in the ECP cohort (30 vs 49 days; P = .298). CONCLUSIONS ECP treatment may yield economic savings in Spain through resource savings and moving costs toward outpatient care.
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Use of Prophylactic Steroids to Prevent Hypocalcemia and Voice Dysfunction in Patients Undergoing Thyroidectomy: A Randomized Clinical Trial.
Dhahri, AA, Ahmad, R, Rao, A, Bhatti, D, Ahmad, SH, Ghufran, S, Kirmani, N
JAMA otolaryngology-- head & neck surgery. 2021;(10):866-870
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IMPORTANCE Total thyroidectomy is associated with risks related to temporary hypocalcemia and vocal quality dysfunction. Dexamethasone has been proposed to have a physiological effect on hypocalcemia and voice quality. OBJECTIVE To assess the effect of preoperative dexamethasone used to improve hypocalcemia and postthyroidectomy voice dysfunction. DESIGN, SETTING, AND PARTICIPANTS This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted from January 15, 2014, to December 31, 2019, at the Department of Surgery, Holy Family Hospital in Rawalpindi, Pakistan. All patients with a benign thyroid condition and no preoperative corrected hypocalcemia and voice or vocal quality dysfunction were included. Patients were excluded if they had previous thyroid or neck surgery, known vocal cord dysfunction on laryngoscopy, hearing or voice problems, a history of gastroesophageal reflux, stomach ulcer disease, or contraindications to steroid use. INTERVENTIONS Corrected serum calcium levels and Voice Analog Score defined and measured preoperatively. The dexamethasone group received a 2-mL intravenous dose of 8 mg of dexamethasone 60 minutes before the induction of anesthesia. In contrast, the placebo group received 2 mL of intravenous normal saline (0.9%) 60 minutes before the induction of anesthesia. MAIN OUTCOMES AND MEASURES Evidence of hypocalcemia and voice dysfunction. Voice dysfunction was defined as a subjective score of less than 50 on a Voice Analog Score scale of 0 to 100 points. RESULTS A total of 192 patients (mean [SD] age, 38.9 [12.4] years; 156 women [81.2%]) were included in the study, with 96 patients randomized to each study group (dexamethasone group, mean [SD] age, 39.2 [12.1] years; 75 women [78.1%]; placebo group, mean [SD] age, 38.5 [12.9] years; 81 women [84.5%]). In the first 24 hours after undergoing thyroidectomy, 47 patients (24.4%) developed hypocalcemia and 18 (9.4%) were symptomatic. At 3 days postthyroidectomy, 4 of 96 patients (4.2%) in the placebo group had hypocalcemia compared with no patients in the dexamethasone group. At 24 hours postthyroidectomy, 8 of 96 patients (8.3%) in the dexamethasone group had voice dysfunction compared with 32 of 96 patients (33.3%) in the placebo group. A total of 40 patients (20.8%) reported voice dysfunction. The absolute reduction in the rate of hypocalcemia at 24 hours was 24% (95% CI, 11.9%-35.2%) and at 3 days was 4.2% (-0.44% to 10.0%). The rate of symptomatic hypocalcemia was 19% lower in the dexamethasone group than in the placebo group (95% CI, 11.1%-27.7%). The rate of voice dysfunction was 25% lower in the dexamethasone group than in the placebo group (95% CI, 13.7%-35.7%). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, a single preoperative dose of dexamethasone was safe and effective in reducing postoperative hypocalcemia and voice dysfunction rates in patients undergoing thyroidectomy. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT04752852.
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Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.
Addison, AB, Wong, B, Ahmed, T, Macchi, A, Konstantinidis, I, Huart, C, Frasnelli, J, Fjaeldstad, AW, Ramakrishnan, VR, Rombaux, P, et al
The Journal of allergy and clinical immunology. 2021;(5):1704-1719
Abstract
BACKGROUND Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.
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Underestimated reactions and regulation patterns of adrenal cytochromes P450.
Bernhardt, R, Neunzig, J
Molecular and cellular endocrinology. 2021;:111237
Abstract
Although cytochrome P450 (CYP) systems including the adrenal ones are being investigated since many years, there are still reactions and regulation patterns that have been underestimated ever since. This review discusses neglected ones to bring them into the focus of investigators working in the field. Novel substrates and reactions described for adrenal CYPs recently point to the fact that different from what has been believed for many years, adrenal CYPs are less selective than previously thought. The conversion of steroid sulfates, intermediates of steroid biosynthesis as well as of exogenous compounds are being discussed here in more detail and consequences for further studies are drawn. Furthermore, it was shown that protein-protein interactions may have an important effect not only on the activity of adrenal CYPs, but also on the product pattern of the reactions. It was found that, as expected, the stoichiometry of CYP:redox partner plays an important role for tuning the activity. In addition, competition between different CYPs for the redox partner and for electrons and possible alterations by mutants in the efficiency of electron transfer play an important role for the activity and product pattern. Moreover, the influence of phosphorylation and small charged molecules like natural polyamines on the activity of adrenal systems has been demonstrated in-vitro indicating a possible regulation of adrenal CYP reactions by affecting redox partner recognition and binding affinity. Finally, an effect of the genetic background on the consequences of mutations in adrenal CYPs found in patients was suggested from corresponding in-vitro studies indicating that a different genetic background might be able to significantly affect the activity of a CYP mutant.
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Steroid use during COVID-19 infection and hyperglycemia - What a physician should know.
Sosale, A, Sosale, B, Kesavadev, J, Chawla, M, Reddy, S, Saboo, B, Misra, A
Diabetes & metabolic syndrome. 2021;(4):102167
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BACKGROUND AND AIMS The COVID-19 pandemic continues to challenge us. Despite several strides in management, steroids remain the mainstay for treating moderate to severe disease and with it arises challenges such as hyperglycemia. The review aims to enhance awareness amongst physicians on steroid use and hyperglycemia. METHODS An advisory document describing various strategies for hyperglycemia management was prepared in the public interest by DiabetesIndia. RESULTS The review provides awareness on steroids and hyperglycemia, adverse outcomes of elevated blood glucose levels and, advice at the time of discharge. CONCLUSIONS The article emphasizes enhancing awareness on effective management of hyperglycemia during COVID-19.
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Urine Steroid Metabolomics as a Novel Tool for Detection of Recurrent Adrenocortical Carcinoma.
Chortis, V, Bancos, I, Nijman, T, Gilligan, LC, Taylor, AE, Ronchi, CL, O'Reilly, MW, Schreiner, J, Asia, M, Riester, A, et al
The Journal of clinical endocrinology and metabolism. 2020;(3):e307-18
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CONTEXT Urine steroid metabolomics, combining mass spectrometry-based steroid profiling and machine learning, has been described as a novel diagnostic tool for detection of adrenocortical carcinoma (ACC). OBJECTIVE, DESIGN, SETTING This proof-of-concept study evaluated the performance of urine steroid metabolomics as a tool for postoperative recurrence detection after microscopically complete (R0) resection of ACC. PATIENTS AND METHODS 135 patients from 14 clinical centers provided postoperative urine samples, which were analyzed by gas chromatography-mass spectrometry. We assessed the utility of these urine steroid profiles in detecting ACC recurrence, either when interpreted by expert clinicians or when analyzed by random forest, a machine learning-based classifier. Radiological recurrence detection served as the reference standard. RESULTS Imaging detected recurrent disease in 42 of 135 patients; 32 had provided pre- and post-recurrence urine samples. 39 patients remained disease-free for ≥3 years. The urine "steroid fingerprint" at recurrence resembled that observed before R0 resection in the majority of cases. Review of longitudinally collected urine steroid profiles by 3 blinded experts detected recurrence by the time of radiological diagnosis in 50% to 72% of cases, improving to 69% to 92%, if a preoperative urine steroid result was available. Recurrence detection by steroid profiling preceded detection by imaging by more than 2 months in 22% to 39% of patients. Specificities varied considerably, ranging from 61% to 97%. The computational classifier detected ACC recurrence with superior accuracy (sensitivity = specificity = 81%). CONCLUSION Urine steroid metabolomics is a promising tool for postoperative recurrence detection in ACC; availability of a preoperative urine considerably improves the ability to detect ACC recurrence.
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Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives.
Achilles, SL, Meyn, LA, Mhlanga, FG, Matubu, AT, Stoner, KA, Beamer, MA, Chirenje, ZM, Hillier, SL
American journal of reproductive immunology (New York, N.Y. : 1989). 2020;(3):e13287
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PROBLEM Contraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods. METHOD OF STUDY We collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge. RESULTS Compared to baseline, the number of cervical HIV target cells (#CD4 cells P < .04 and #CD11c cells P < .04), the concentration of the inflammatory cytokine IL-1β (P < .01), and the innate in vitro anti-HIV activity (P < .001) significantly decreased following DMPA initiation. In Cu-IUD users, genital HIV target cells increased (#CD4 cells P < .001, #CD4CCR5 cells P = .02, #CD4CD69 cells P < .001, #CD8CD69 P = .01, and #CD11c cells P = .003) at day 30 and resolved by day 180. IFN-γ (P < .001), IL-1β (P < .001), IL-6 (P < .001), IL-8 (P < .001), IL-10 (P < .01), and RANTES (P < .001) were also significantly increased at day 30. Minimal alterations were observed following initiation of subdermal implantable contraceptives. CONCLUSIONS This head-to-head study compared six contraceptives and found increased HIV target cells and cervical inflammation temporally associated with Cu-IUD initiation. Use of hormonal contraception, including DMPA, did not increase cervical HIV target cells or inflammation. Clinical Trial Number: NCT02038335.