Steroid Consumption Research Articles

P553 Factors related to steroid consumption in IBD patients: Evidence from a multicenter Study

Abstract Background Steroids are frequently used to induce remission in inflammatory bowel disease (IBD) but should not be used as maintenance treatment. Understanding the factors related to steroid consumption is essential in order to avoid over prescription of these drugs. Methods A cross-sectional study was conducted between 2019 and 2020 in six medical centers in Israel. Data was collected using a structured self-administered tool containing the following: socio demographic and clinical characteristics, knowledge of side effects and complications of steroid treatment, self-care and compliance with medical instructions, Steroid Assessment Tool (SAT) and objective physiological measures. Results The study included 402 IBD patients; 262 patients with Crohn’s disease (CD) (66%) and 135 patients with ulcerative colitis (UC) (34%). Most of the patients reported being monitored in the IBD unit in the medical centers (87.7%). A quarter of the patients (n=88) had been prescribed systemic steroids over the previous year, and 20 (23%) received 3 or more prescriptions for systemic steroids over the preceding year. Likewise, over 20% of patients were on systemic steroid therapy for over 4 months in the preceding year. Those patients were mostly men and ultra-orthodox. Patients with UC were prescribed steroids more often than CD patients. Knowledge levels regarding appropriate steroid consumption were significantly higher among women (F=40.24, p<.001) and lower among ultra-orthodox patients (X2=6.43, p<.05). Although most of the patients (85.9%) were routinely treated by gastroenterologist, the majority (80%) choose to visit the general practitioner when their disease had flared up. Conclusion Several factors were found to be related to inappropriateness use of steroids in IBD patients. Thus, tailored intervention for specific population should be developed to ensure that steroids are used correctly and that their side effects are minimized. Also, infrastructure and alignment of an integrated health care delivery system, with multidisciplinary team may provide the optimal environment for care coordination, especially during disease flare.

Ocular and extra-ocular complications following long-term steroid consumption in children with idiopathic nephrotic syndrome

Background: High dose of corticosteroids are required by patients with idiopathic nephrotic syndrome for long duration due to repeated relapse. The aims of this study were to analyze the ocular and extra-ocular complications of steroids on children with nephrotic syndrome.
 Methods: This cross-sectional study was conducted at Dhaka Shishu (Children) Hospital from September 2017 to September 2019. Children with nephrotic syndrome between 1-16 years of age, who received steroid for at least three months, participated in this study. Total 70 children were enrolled. Detailed history was taken from parents regarding initial episode, drug history, visual problem, headache, hypertension, weight gain, psychosis, bone pain, epigastric pain and excessive growth of body hair. Comprehensive opthalmologic assessment including visual acquity, intraocular pressure and cataract were performed. Detail of renal histopathology and treatment regimen in each patient was noted.
 Results: A total of 70 patients were included, 61.4% were male and 38.6% were female. Median age at the time of examination was 60 months (range 17 to 216 months). The mean duration of disease was 33.71±21.12 months. The mean cumulative steroid dose at the time of examination was 8485.91±7326.83 mg. Fourteen (20%) patients had posterior subcapsular cataract. Among 70 patients, we could do visual acuity for 25 (35.7%) patients, intraocular pressure (IOP) in mm for 51 (72.85%) patients. Among them raised IOP was found in five (9.8%) patients. In right eye mean IOP was 14.16±3.57 and for left eye 14.77±3.55 mm. Renal biopsy was performed in 15 (21.43%) cases. Among the biopsy report, it was found that mesangial proliferative glomerulonephritis (MPGN) in 8 (53.33%), focal segmental glomerulonephritis (FSGS) in 2 (13.33%) and minimal change in 5 (33.34%) cases. Among all cases, 12 (17.14%) patients developed Cushingoid facies, 3 (4.2%) patients had hypertrichosis, 3 (4.2%) patients had central obesity and 4 (5.7%) patients had buffalo hump but none had hypertension, diabetes mellitus, epigastric pain, bone pain or psychosis.
 Conclusion: Cataract formation was the most frequent ocular complication after large dose of oral corticosteroid therapy. The present study emphasizes the need for regular eye screening. Cushingoid facies was the most frequent among extra-ocular complications.
 Birdem Med J 2021; 11(1): 7-10

Looking ‘acceptably’ feminine: A single case study of a female bodybuilder’s use of steroids

This article aims to shed some light on the motivations for and methods of female steroid consumption apropos broader changes in female body image ideals. Moreover, the study attempts to explore the connections between the competitive logic of liberal-postmodern consumer capitalism, ‘competitive femininity’ and steroid use. There is a growing consensus that an increasing number of women are consuming steroids, yet this phenomenon remains relatively under-researched and as such not much is known about this particular group of users. Utilising a single in-depth case study, this paper offers some additional insight gleaned from an ethnographic interview with a female bodybuilder who uses steroids. Her narrative elucidates some of the risks, harms and motivations for steroid consumption alongside broader changes in female body image ideals. Among the central findings, this paper highlights that the female bodybuilder is not resisting cultural norms but rather hyper-conforming to them by over-identifying with a hyper-idealised form of what constitutes ‘acceptable femininity’. We conclude that steroid consumption retains a strong connection to the desire for aesthetic appeal and that both short and long-term motivations for using steroids are grounded in the drive for conformity. This has pertinent clinical implications for health professionals, particularly in relation to the efficacy of attempts to reduce steroid consumption by warning users of the potential adverse health effects.

Examining the Effects of Anabolic-Androgenic Steroids on Repetitive Mild Traumatic Brain Injury (RmTBI) Outcomes in Adolescent Rats.

Background: Repetitive mild traumatic brain injury (RmTBI) is increasingly common in adolescents. Anabolic–androgenic steroid (AAS) consumption among younger professional athletes is a significant risk factor for impaired neurodevelopment. Given the increased rates and overlapping symptomology of RmTBI and AAS use, we sought to investigate the behavioural and neuropathological outcomes associated with the AAS Metandienone (Met) and RmTBI on rats. Methods: Rats received either Met or placebo and were then administered RmTBIs or sham injuries, followed by a behavioural test battery. Post-mortem MRI was conducted to examine markers of brain integrity and qRT-PCR assessed mRNA expression of markers for neurodevelopment, neuroinflammation, stress responses, and repair processes. Results: Although AAS and RmTBI did not produce cumulative deficits, AAS use was associated with detrimental outcomes including changes to depression, aggression, and memory; prefrontal cortex (PFC) atrophy and amygdala (AMYG) enlargement; damaged white matter integrity in the corpus callosum; and altered mRNA expression in the PFC and AMYG. RmTBI affected general activity and contributed to PFC atrophy. Conclusions: Findings corroborate previous results indicating that RmTBI negatively impacts neurodevelopment but also demonstrates that AAS results in significant neuropathological insult to the developing brain.

A ‘messenger of sex’? Making testosterone matter in motivations for anabolic-androgenic steroid injecting

ABSTRACTAnabolic-androgenic steroids are synthetic derivatives of testosterone. They are thought to be the most commonly used performance and image-enhancing drugs (PIEDs) in Australia. However, the motivations for men’s use of steroids and other PIEDs are poorly understood. Established ways of understanding these motivations highlight men’s performance and/or image-related concerns, in the context of contemporary masculinities and gender norms. Researchers have paid little attention to how the social and political features of testosterone shape and transform steroid use. Instead, testosterone tends to be taken for granted as a ‘messenger of sex’ that acts on the body in predictable and routinised ways. This article takes a different approach. Drawing on feminist science studies and interviews conducted for an Australian research project, we investigate how the cultural and symbolic meanings assigned to testosterone shape the ontological politics of men’s steroid consumption. Approaching testosterone as an emergent social and biopolitical gathering rather than as a stable sex hormone allows us to better understand how men’s PIED consumption is mediated, particularly by pervasive ideas about sexual difference and the biology of gender. In concluding, we consider ways of better engaging men who consume steroids in health initiatives, in keeping with their concerns and perspectives.

Boosting bodily capital: Maintaining masculinity, aesthetic pleasure and instrumental utility through the consumption of steroids

Anabolic-androgenic steroid consumption is considered a significant public health issue in a number of countries but particularly in the northeast of England. Informed by ongoing ethnographic work on steroid use, this article aims to explore two particular dimensions of bodily capital within the overarching context of hyper-masculinity. Towards this end we focus on aesthetic pleasure as the ‘boosted’ body becomes a site of contemporary consumption before taking a look at the instrumental utility derived from a sufficiently primed and tuned body. Accordingly, and with a view towards the changing currency of bodily capital, we explore the contemporary importance attached to both attaining and maintaining both elements of a ‘boosted’ bodily capital. The significant role steroids play in facilitating this is then discussed; yet rather than locating its consumption in the realm of ‘deviancy’, we view it as a means of hyper-conforming to neoliberalism’s cultural norms and values. By drawing upon a range of perspectives, we hope to offer up new insights into the demand for steroids apropos the pursuit for an aesthetically pleasing and instrumentally effective body.

DEPRESI INDUCED STEROID

Back Ground: Depression is a natural disturbance of feeling that is characterized by feelings of sadness, loss of interest and easily tired. Steroids are drugs that can reduce swelling, pain and heat due to inflammation through reducing the immune response. Steroids are often used in cases of systemic Lupus Erythematosus in the long term. Therefore management of the disease must be done well because steroids can cause depression. Case Report:Women, 37 years old, depressed mood, disappointment in life, loss of enthusiasm, fatigue, decreased appetite and difficulty sleeping for 1 year. 4 years ago I took steroids for 2 years at a dose of 20mg / day, because rheumatoid arthritis was stopped by os, and for the past 1 year, steroid consumption was due to Systemic Lupus Erythematosus around 60 mg / day. . Before the os consumes steroids, the OS has never experienced depression.BP: 110/70 mmHg , HR 88x/menit, RR 20x/menit, Temp 37°C. Skor BDI 21. Laboratorium Hb 11,8 g/dl, Leukosit 7500/mm3, trombosit 201.000/mm3,,Kalium 2,8, KGDad 99 mg/dlSGOT 29 ,SGPT32, Ureum 15,78 mg/dl, Creatinin 0,65 mg/dl. Tot Colesterol 198mg/dl, LDL 128 mg/dl, HDL 35 mg/dl Fototoraks : Jantung dan Parudalambatas normal, FotoLumbosakral : SpondilosisLumbalis. The patient is diagnosed with depression. Given psychotherapy, sandepril 2 x 25 mg for 3 months. Patients show clinical improvement marked by reduced sadness and can understand the disease. Conclusion :Steroid-induced depression has been reported after psychotherapy and sandepril 2 x 25 mg of the patient's condition showed improvement.

DEPRESI INDUCED STEROID: STUDI KASUS

Back Ground: Depression is a natural disturbance of feeling that is characterized by feelings of sadness, loss of interest and easily tired. Steroids are drugs that can reduce swelling, pain and heat due to inflammation through reducing the immune response. Steroids are often used in cases of systemic Lupus Erythematosus in the long term. Therefore management of the disease must be done well because steroids can cause depression. Case Report:Women, 37 years old, depressed mood, disappointment in life, loss of enthusiasm, fatigue, decreased appetite and difficulty sleeping for 1 year. 4 years ago I took steroids for 2 years at a dose of 20mg / day, because rheumatoid arthritis was stopped by os, and for the past 1 year, steroid consumption was due to Systemic Lupus Erythematosus around 60 mg / day. . Before the os consumes steroids, the OS has never experienced depression.BP: 110/70 mmHg , HR 88x/menit, RR 20x/menit, Temp 37°C. Skor BDI 21. Laboratorium Hb 11,8 g/dl, Leukosit 7500/mm3, trombosit 201.000/mm3,,Kalium 2,8, KGDad 99 mg/dlSGOT 29 ,SGPT32, Ureum 15,78 mg/dl, Creatinin 0,65 mg/dl. Tot Colesterol 198mg/dl, LDL 128 mg/dl, HDL 35 mg/dl Fototoraks : Jantung dan Parudalambatas normal, FotoLumbosakral : SpondilosisLumbalis. The patient is diagnosed with depression. Given psychotherapy, sandepril 2 x 25 mg for 3 months. Patients show clinical improvement marked by reduced sadness and can understand the disease. Conclusion :Steroid-induced depression has been reported after psychotherapy and sandepril 2 x 25 mg of the patient's condition showed improvement.

Osteo-necrosis of femoral head in North Indian population: Risk factors and clinico-radiological correlation

IntroductionOsteonecrosis of femoral head (ONFH) is a common cause of destruction of hip joint in young patients and is one of the commonest indications of total hip replacement in India and other Asian countries. Data on risk factors for avascular necrosis and their relation to clinical and radiological outcomes is scarce. This study will help to understand the epidemiology of the condition and quantitatively define risk of disease with exposure to various known risk factors. Materials and methods100 patients diagnosed to have ONFH and 100 matched controls were included in this prospective study. Details regarding alcohol consumption and steroid use were taken. Association between Harris hip score & Visual analogue scale for pain and Ficat staging and area of femoral head involvement on MRI was studied. Association between amounts of alcohol and steroid consumed (average and cumulative doses) and clinical and radiological variables was also studied. ResultsCorticosteroid exposure was present in 44%, alcohol in 30% patients and 22% cases were idiopathic. There was a statistically significant difference between average weekly alcohol consumption, drink-years, average daily dose of steroid and cumulative doses of steroids between the cases and the controls. Odds-ratio for steroid exposure in cases with ONFH was 134.5, 0.0006, and odds-ratio for alcohol exposure was 32.7, 0.0001. There was a significant correlation between the amount of alcohol (r = −0.348, p = 0.02) and steroid (r = −0.334, p = 0.001) consumption and HHS, and between amount of alcohol (r = 0.312, p = 0.035) and steroid (r = 0.546, p = 0.001) consumption and area of femoral head involvement. There was a strong positive correlation between clinical and radiological parameters (area of femoral head involved and HHS, r = −0.70, p = 0.000). ConclusionRisk factors such as steroid intake and alcohol intake are important and accounts for majority of the cases of ONFH. The quantity of these exposures is directly related to the severity of disease on clinico-radiological scales.

Assessing mental health and the relation with variables of demographic and clinical in Crohn's disease patients; 2016-2017.

Background:Crohn's disease is a group of special diseases that are considered in psychiatric studies because there is a contrast between the physical and psychological diseases among the affected patients.Aim:The aim of this study was assessing mental health and the relation with variables of demographic and clinical in Crohn's disease patients.Methods:In this epidemiological study, 96 patients with Crohn's disease who referred to educational hospitals in Ahvaz during 2016--2017 were evaluated by demographic and clinical questionnaires and SCL-90 questionnaires for mental health, and the information was analyzed by SPSS software version 22.Results:The mean physical complaints in subjects was 24.63 ± 4.08 and the mean mental health was calculated to be 187.75 ± 25.17. Multivariate analysis of mental health showed that steroid consumption (P value < 0.001) and nonsmoking (P value = 0.038) were associated with higher mental health in the individuals.Conclusions:Crohn's patients suffered from decreased mental parameters in dimensions such as physical complaints, obsession--compulsion behavior, sensitivity to interactions, depression, anxiety, aggression, phobia, psychosis, and paranoid thoughts.

Neutrophilia as a biomarker for overall survival in newly diagnosed high-grade glioma patients undergoing chemoradiation

ObjectiveTo study the prognostic value of neutrophil disorders in a retrospective cohort of high-grade glioma patients receiving definitive concurrent temozolomide and radiation. Materials and methodsClinical records of consecutive patients treated in our Institution between January 2005 and December 2010 with concurrent temozolomide (75 mg/m2 daily) and radiation were collected. The prognostic value of pretreatment neutrophilia on survival, defined as a neutrophil count exceeding 7 G/L, was examined. ResultsWe identified 164 patients, all treated with concurrent temozolomide-based chemoradiotherapy. Initial surgery was achieved in most (75%), with resection > 90% in 55 patients (34%). Total 151 patients (92%) had glioblastoma, and 13 patients (8%) had WHO grade III glioma. Eighty-two patients (50%) displayed pretreatment neutrophilia. Neutrophilia was not associated with concurrent or adjuvant temodal discontinuation (p > 0.3). The 2-year actuarial overall survival was 45%. Steroid consumption, i.e. 60 mg or more of daily prednisolone, increased pretreatment neutrophil count (p = 0.005). In univariate analysis, neutrophilia was associated with worse overall survival (p = 0.019), as well as age ≥ 65 years (p = 0.009), surgical resection < 90% (p = 0.003) and prednisolone consumption ≥ 60 mg/day (p = 0.016). In multivariate analysis, neutrophilia (p = 0.013), age ≥ 65 (p = 0.001), and surgical tumor resection < 90% (p = 0.010) independently decreased overall survival, while, steroid consumption was not (p = 0.088). ConclusionIn high-grade gliomas treated with concurrent temozolomide and radiation, pretreatment neutrophilia may be a significant prognosis factor for overall survival. In addition with previously available markers, this independent cost-effective biomarker could help identifying patients with worsened prognosis.

Results of lipid lowering with statins in patients following acute coronary syndrome (ACS) in a tertiary centre

Pemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity. Therefore, the removal of autoantibodies by immunoadsorption is a targeted therapeutic intervention for patients with pemphigus vulgaris.A total of 9 patients with pemphigus vulgaris resistant to the standard treatment regimen were treated by immunoadsorption using the TheraSorb™-Ig adsorber system and analyzed retrospectively. Patients received immunoadsorption on two or four consecutive days. Cycles were repeated every two or four weeks, respectively. Treatment was performed for a mean period of 17.5 months (range 6–26). Outcome was measured as improvement in clinical disease analyzed by the investigators global assessment and the reduction of autoantibodies in serum measured by indirect immunofluorescence and ELISA. Tolerability of treatment by patients was evaluated using a visual analog scale.Retrospective analysis of 9 patients consecutively treated by immunoadsorption revealed an 80% reduction of the autoantibody concentration in serum after 6 months of treatment, led to a clinical improvement of disease in combination with classical immunosuppression. Steroid consumption could be reduced by 50% after 30 and 75% after 90 days. Therapy resulted in a total response rate of 89%, with 56% of patients reaching partial and 33% complete remission. The bi-weekly treatment regimen resulted in effective improvement of disease and was in favor to the 4-weekly regimen by the subjective judgment of tolerability by the patients.Immunoadsorption for the treatment of pemphigus vulgaris is safe and effective. The good tolerability of a bi-weekly treatment regimen shown here might be a valuable therapeutic option in further studies defining the optimal frequency of immunoadsorption required in treatment of pemphigus.

Successful and well-tolerated bi-weekly immunoadsorption regimen in pemphigus vulgaris

BackgroundPemphigus vulgaris is a chronic autoimmune disease characterized by blisters and erosions forming in the mucous membranes and the skin. Many patients are severely impaired by pain, weight loss and increased risk of infections. The disease is mediated by specific autoantibodies directed against desmogleins that contribute to connect keratinocytes in the epidermis. Autoantibody deposition in the skin causes inflammation and intraepidermal akantholysis. The concentration of autoantibodies in serum correlates with disease activity. Therefore, the removal of autoantibodies by immunoadsorption is a targeted therapeutic intervention for patients with pemphigus vulgaris. Patients and methodsA total of 9 patients with pemphigus vulgaris resistant to the standard treatment regimen were treated by immunoadsorption using the TheraSorb™-Ig adsorber system and analyzed retrospectively. Patients received immunoadsorption on two or four consecutive days. Cycles were repeated every two or four weeks, respectively. Treatment was performed for a mean period of 17.5 months (range 6–26). Outcome was measured as improvement in clinical disease analyzed by the investigators global assessment and the reduction of autoantibodies in serum measured by indirect immunofluorescence and ELISA. Tolerability of treatment by patients was evaluated using a visual analog scale. ResultsRetrospective analysis of 9 patients consecutively treated by immunoadsorption revealed an 80% reduction of the autoantibody concentration in serum after 6 months of treatment, led to a clinical improvement of disease in combination with classical immunosuppression. Steroid consumption could be reduced by 50% after 30 and 75% after 90 days. Therapy resulted in a total response rate of 89%, with 56% of patients reaching partial and 33% complete remission. The bi-weekly treatment regimen resulted in effective improvement of disease and was in favor to the 4-weekly regimen by the subjective judgment of tolerability by the patients. ConclusionImmunoadsorption for the treatment of pemphigus vulgaris is safe and effective. The good tolerability of a bi-weekly treatment regimen shown here might be a valuable therapeutic option in further studies defining the optimal frequency of immunoadsorption required in treatment of pemphigus.

Predominance of Comorbidities in the Detriment of Daily Activity in Sarcoidosis Patients.

Sarcoidosis may affect lung function, working ability, overall mobility, and daily activity. In the present study we performed an analysis of clinical settings in patients with sarcoidosis to disentangle its influence on daily physical activity (PA). PA assessment (number of steps per day, daily energy expenditure) was performed by accelerometry during consecutive 7days after discharge from hospital. Thirty patients with sarcoidosis, aged 46.4±10.5, were enrolled in the study. Clinical data (age, gender, steroid consumption, weight, and comorbidities), lung function tests (forced expiratory volume in one second - FEV1, forced vital capacity - FVC, and lung diffusion for carbon monoxide - DLCO), mobility (6-minute walk test - 6 MWT) and physical performance (oxygen consumption at anaerobic threshold - VO2/AT) were estimated. The mean daily PA (5214±2699 steps/day) and VO2max (22.3±7.0ml/kg/min) were lower when referenced to the age-group predicted values. A significant greater daily PA was observed in sarcoidosis patients without comorbidities compared with those having more than two comorbidities (p=0.046). No association was found between steroid use, lung function, and 6MWT. Daily PA was associated with patients aerobic efficacy and VO2max (r=0.38, p<0.04). The findings demonstrate a significant influence of comorbidities on sarcoidosis patients' exercise tolerance and daily PA. Special treatment considerations, including the potential impact of comorbidities, may help optimize exercise regimes, link physical activity with health, and prevent sarcoidosis complications.

The effect of nandrolone treatment with and without enforced swimming on histological and biochemical changes in the heart and coronary artery of male rats

Objective:Chronic anabolic androgenic steroid (AAS) consumption increases incidence of cardiovascular abnormalities in athletes and mechanisms underlying those abnormalities continue to be investigated. This study examines whether nandrolone consumption induced cardiac and coronary artery wall abnormalities via oxidative stress. It was also designed to determine whether enforced swimming augmented possible cardiotoxic effects of nandrolone in rat heart.Methods:Twenty-four male Wistar rats were divided into 3 groups: control, nandrolone, and nandrolone with enforced swimming. Nandrolone group received 10 mg/kg body weight nandrolone 3 times a week for 6 weeks. Nandrolone group with enforced swimming received the same amount of nandrolone and was forced to swim with excess weight of 20% body weight.Results:After 6 weeks of treatment, results indicated proliferation of heart muscle and coronary smooth muscle cells and lipid peroxidation; significant rise in levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate oxidase, homocysteine (Hcy), apolipoprotein B, low-density lipoprotein, and cholesterol, as well as severe fibrosis in heart tissue and around coronary arteries of nandrolone and nandrolone with enforced swimming groups compared with control group.Conclusion:These findings strongly support idea that nandrolone intake by sedentary rats and exercised rats induced heart abnormality mediated by oxidative stress, which was manifest in increased lipid peroxidation, Hcy, and 8-OHdG in heart tissue.

Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease.

The results from controlled clinical trials investigating the efficacy of azathioprine and 6-mercaptopurine for the treatment of active Crohn's disease have been conflicting and controversial. An updated meta-analysis was performed to assess the effectiveness of these drugs for the induction of remission in active Crohn's disease. The primary objective was to determine the efficacy and safety of azathioprine and 6-mercaptopurine for induction of remission in active Crohn's disease. We searched MEDLINE, EMBASE and the Cochrane Library from inception to 30 October 2015. Review articles and conference proceedings were also searched to identify additional studies. Randomized controlled trials (RCTs) of oral azathioprine or 6-mercaptopurine compared to placebo or active therapy involving adult patients with active Crohn's disease were selected for inclusion. Data were extracted by two independent observers based on the intention-to-treat principle. Outcomes of interest included: clinical remission, clinical improvement, fistula improvement or healing, steroid sparing, adverse events, withdrawals due to adverse events and serious adverse events. We calculated the pooled relative risk (RR) and 95% confidence intervals (95% CI) for each outcome. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting each outcome was assessed using the GRADE criteria. Thirteen RCTs (n = 1211 patients) of azathioprine and 6-mercaptopurine therapy in adult patients were identified: nine included placebo comparators and six included active comparators. The majority of included studies were rated as low risk of bias. There was no statistically significant difference in clinical remission rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (95/197) of patients receiving antimetabolites achieved remission compared to 37% (68/183) of placebo patients (5 studies, 380 patients; RR 1.23, 95% CI 0.97 to 1.55). There was no statistically significant difference in clinical improvement rates between azathioprine or 6-mercaptopurine and placebo. Forty-eight per cent (107/225) of patients receiving antimetabolites achieved clinical improvement or remission compared to 36% (75/209) of placebo patients (8 studies, 434 patients; RR 1.26, 95% CI 0.98 to 1.62). There was a statistically significant difference in steroid sparing (defined as prednisone dose < 10 mg/day while maintaining remission) between azathioprine and placebo. Sixty-four per cent (47/163) of azathioprine patients were able to reduce their prednisone dose to < 10 mg/day compared to 46% (32/70) of placebo patients (RR 1.34, 95% CI 1.02 to 1.77). GRADE analyses rated the overall quality of the evidence for the outcomes clinical remission, clinical improvement and steroid sparing as moderate due to sparse data. There was no statistically significant difference in withdrawals due to adverse events or serious adverse events between antimetabolites and placebo. Ten percent of patients in the antimetabolite group withdrew due to adverse events compared to 5% of placebo patients (8 studies, 510 patients; RR 1.70, 95% CI 0.94 to 3.08). Serious adverse events were reported in 14% of patients receiving azathioprine compared to 4% of placebo patients (2 studies, 216 patients; RR 2.57, 95% CI 0.92 to 7.13). Common adverse events reported in the placebo controlled studies included: allergic reactions. leukopenia, pancreatitis and nausea. Azathioprine was significantly inferior to infliximab for induction of steroid-free clinical remission. Thirty per cent (51/170) of azathioprine patients achieved steroid-free remission compared to 44% (75/169) of infliximab patients (1 study, 339 patients; RR 0.68, 95% CI 0.51 to 0.90). The combination of azathioprine and infliximab was significantly superior to infliximab alone for induction of steroid-free clinical remission. Sixty per cent (116/194) of patients in the combined azathioprine and infliximab group achieved steroid-free remission compared to 48% (91/189) of infliximab patients (2 studies, 383 patients; RR 1.23, 95% CI 1.02 to 1.47). Azathioprine or 6-mercaptopurine therapy was found to be no better at inducing steroid free clinical remission compared to methotrexate (RR 1.13, 95% CI 0.85 to 1.49) and 5-aminosalicylate or sulfasalazine (RR 1.24, 95% CI 0.80 to 1.91). There were no statistically significant differences in withdrawals due to adverse events between azathioprine or 6-mercaptopurine and methotrexate (RR 0.78, 95% CI 0.23 to 2.71); between azathioprine or 6-mercaptopurine and 5-aminosalicylate or sulfasalazine (RR 0.98, 95% CI 0.38 to 2.54); between azathioprine and infliximab (RR 1.47, 95% CI 0.96 to 2.23); or between the combination of azathioprine and infliximab and infliximab (RR 1.16, 95% CI 0.75 to 1.80). Common adverse events in the active comparator trials included nausea, abdominal pain, pyrexia and headache. Azathioprine and 6-mercaptopurine offer no advantage over placebo for induction of remission or clinical improvement in active Crohn's disease. Antimetaboilte therapy may allow patients to reduce steroid consumption. Adverse events were more common in patients receiving antimetabolites although differences with placebo were not statistically significant. Azathioprine therapy is inferior to infliximab for induction of steroid-free remission. However, the combination of azathioprine and infliximab was superior to infliximab alone for induction of steroid-free remission.

Cushing in a Leaf: Endocrine Disruption From a Natural Remedy

Information regarding the safety of herbal drugs is often not reported. We describe the case of a 65-year-old woman referred to us for a iatrogenic hypercortisolism, who denied any previous steroid consumption. She reported only a chronic application of a phytocosmetic cream, containing ethanol extract of the Cardiospermum halicacabum (CH) plant. Adrenal insufficiency occurred after the cream application was stopped. CH is used in traditional and Western medicine for its documented anti-inflammatory properties. Once the presence of synthetic glucocorticoids was ruled out in the phytocosmetic product, we investigated whether and how its chronic application could have caused the iatrogenic hypercortisolism. Liquid chromatography high-resolution mass spectrometry (LC-HRMS) was performed to exclude the presence of known glucocorticoids in the cream. ELISA assay and Western blot analysis were employed to assess ACTH secretion and the glucocorticoid receptor expression respectively in murine ACTH-secreting pituitary adenoma cells AtT-20/D16v-F2, treated with dexamethasone, CH tincture, and mifepristone alone or in combination. To detect specific interaction of CH extract with the glucocorticoid receptor, we performed a dual-luciferase reporter assay in HEK293 cells. In AtT-20/D16v-F2 cells, CH extract showed to significantly reduce basal and CRH-induced ACTH secretion and the glucocorticoid receptor expression, similarly to dexamethasone; these effects were counteracted by mifepristone. In HEK293 cells, dexamethasone significantly induced luciferase activity after 24- and 36-hour treatment and CH tincture only after 36 hours; these effects were antagonized by mifepristone. CH extract displays a glucocorticoid-like activity, by means of a direct binding to the glucocorticoid receptor.

The mechanism underlying alpinetin-mediated alleviation of pancreatitis-associated lung injury through upregulating aquaporin-1.

Characterized by its acute onset, critical condition, poor prognosis, and high mortality rate, severe acute pancreatitis (SAP) can cause multiple organ failure at its early stage, particularly acute lung injury (ALI). The pathogenesis of ALI is diffuse alveolar damage, including an increase in pulmonary microvascular permeability, a decrease in compliance, and invasion of many inflammatory cells. Corticosteroids are the main treatment method for ALI; however, the associated high toxicity and side effects induce pain in patients. Recent studies show that the effective components in many traditional Chinese medicines can effectively inhibit inflammation with few side effects, which can decrease the complications caused by steroid consumption. Based on these observations, the main objective of the current study is to investigate the effect of alpinetin, which is a flavonoid extracted from Alpinia katsumadai Hayata, on treating lung injury induced by SAP and to explore the mechanism underlying the alpinetin-mediated decrease in the extent of ALI. In this study, we have shown through in vitro experiments that a therapeutic dose of alpinetin can promote human pulmonary microvascular endothelial cell proliferation. We have also shown via in vitro and in vivo experiments that alpinetin upregulates aquaporin-1 and, thereby, inhibits tumor necrosis factor-α expression as well as reduces the degree of lung injury. Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated aquaporin expression, which inhibits tumor necrosis factor-α and, thus, alleviates SAP-induced ALI.

Effects of steroid treatment on growth, nutrient partitioning, and expression of genes related to growth and nutrient metabolism in adult triploid rainbow trout (Oncorhynchus mykiss)

The contribution of sex steroids to nutrient partitioning and energy balance during gonad development was studied in rainbow trout. Specifically, 19-mo old triploid (3N) female rainbow trout were fed treatment diets supplemented with estradiol-17β (E2), testosterone (T), or dihydrotestosterone at 30-mg steroid/kg diet for a 1-mo period. Growth performance, nutrient partitioning, and expression of genes central to growth and nutrient metabolism were compared with 3N and age-matched diploid (2N) female fish consuming a control diet not supplemented with steroids. Only 2 N fish exhibited active gonad development, with gonad weights increasing from 3.7% to 5.5% of body weight throughout the study, whereas gonad weights in 3N fish remained at 0.03%. Triploid fish consuming dihydrotestosterone exhibited faster specific growth rates than 3N-controls (P < 0.05). Consumption of E2 in 3N fish reduced fillet growth and caused lower fillet yield compared with all other treatment groups (P < 0.05). In contrast, viscera fat gain was not affected by steroid consumption (P > 0.05). Gene transcripts associated with physiological pathways were identified in maturing 2N and E2-treated 3N fish that differed in abundance from 3N-control fish (P < 0.05). In liver these mechanisms included the growth hormone/insulin-like growth factor (IGF) axis (igf1, igf2), IGF binding proteins (igfbp1b1, igfbp2b1, igfbp5b1, igfbp6b1), and genes associated with lipid binding and transport (fabp3, fabp4, lpl, cd36), fatty acid oxidation (cpt1a), and the pparg transcription factor. In muscle, these mechanisms included reductions in myogenic gene expression (fst, myog) and the proteolysis-related gene, cathepsin-L, suggesting an E2-induced reduction in the capacity for muscle growth. These findings suggest that increased E2 signaling in the sexually maturing female rainbow trout alters physiological pathways in liver, particularly those related to IGF signaling and lipid metabolism, to partition nutrients away from muscle growth toward support of maturation-related processes. In contrast, the mobilization of viscera lipid stores appear to be mediated less by E2 and more by energy demands associated with gonad development. These findings improve the understanding of how steroids regulate nutrient metabolism to meet the high energy demands associated with gonad development during sexual maturation.

BMET-11SURGICAL RESECTION OF CEREBRAL METASTASES LEADS TO FASTER RESOLUTION OF PERI-TUMORAL EDEMA: A QUANTITATIVE ANALYSIS

BACKGROUND: Surgical resection and stereotactic-radiosurgery (SRS) are valid treatment options for selected patients with brain-metastases. The desired rate of resolution of the tumor-associated edema may play a role in the decision making process. However, the dynamics of edema resolution with each modality has not been well characterized. METHODS: Of 646 patients treated at our center for brain metastases between 2010-2014, we retrospectively identified 70 patients (100 metastases) who underwent either surgery or SRS for brain metastasis, and had sufficient clinical data, and radiological follow-up to be included in this study. Individual volumetric measurement of the tumor and edema before, and three months after treatment, was performed. RESULTS: Forty-six surgical cases were compared to 54 cases treated with SRS. As expected, the volume of the tumor and surrounding edema were significantly higher in the surgical group compared to SRS. However, resolution of edema was significantly superior in the surgical group (p < 0.0001). After a matching process based on the propensity of a patient to receive SRS, a nested cohort of 40 patients was analyzed (mean-maximal diameter:21.5mm vs. 18.8mm for surgery and SRS, respectively). At diagnosis, edema volume, but not tumor volume was significantly higher in the surgical group. Three months after treatment, the resolution of edema tended to be much more prominent in the surgical group (74.2% vs.18.8% improvement, p = 0.1). Steroid consumption was significantly higher in the SRS group (p = 0.02). No difference in the incidence of new neurological deficits after treatment was found between the groups. CONCLUSIONS: Resolution of tumor-associated edema in medium sized brain metastases tended to be more prominent after surgical resection compared to SRS. Irradiated patients required a significantly higher dose of steroids. Accordingly, when both treatment options are suitable, surgery appears to induce a faster resolution of edema and perhaps may alleviate edema-induced deficits faster in patients with brain metastases.