A polygenic-score-based approach for identification of gene-drug interactions stratifying breast cancer risk.

An individual's genetics can dramatically influence breast cancer (BC) risk. Although clinical measures for prevention do exist, non-invasive personalized measures for reducing BC risk are limited. Commonly used medications are a promising set of modifiable factors, but no previous study has explored whether a range of widely taken approved drugs modulate BC genetics. In this study, we describe a quantitative framework for exploring the interaction between the genetic susceptibility of BC and medication usage among UK Biobank women. We computed BC polygenic scores (PGSs) that summarize BC genetic risk and find that the PGS explains nearly three-times greater variation in disease risk within corticosteroid users compared to non-users. We map 35 genes significantly interacting with corticosteroid use (FDR < 0.1), highlighting the transcription factor NRF2 as a common regulator of gene-corticosteroid interactions in BC. Finally, we discover a regulatory variant strongly stratifying BC risk according to corticosteroid use. Within risk allele carriers, 18.2% of women taking corticosteroids developed BC, compared to 5.1% of the non-users (with an HR = 3.41 per-allele within corticosteroid users). In comparison, there are no differences in BC risk within the reference allele homozygotes. Overall, this work highlights the clinical relevance of gene-drug interactions in disease risk and provides a roadmap for repurposing biobanks in drug repositioning and precision medicine.

Toxicity due to steroid treatment in ITP remains a concern.

Corticosteroids are the preferred first-line treatment in ITP in guidelines. The analyses by Wang et al. shows that hospital-registered steroid-related toxicity occurs frequently and emphasizes that exposure should be for a limited duration of time. Commentary on: Wang et al. Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: a population-based study. Br J Haematol 2024;204:1986-1993.

Use of inhaled corticosteroids and the risk of hospitalisation for pneumonia in children with asthma: a nationwide cohort study.

BACKGROUND: The potential association between the use of inhaled corticosteroids (ICS) and the risk of pneumonia among adults is disputed and paediatric-specific evidence is scarce. AIM: To assess the potential association between ICS, use and the risk of hospitalisation for pneumonia among children (age 2-17 years) with asthma. METHODS: This was a cohort study based on nationwide data from routine clinical practice in Sweden (January 2007 to November 2021). From 425 965 children with confirmed asthma, episodes of new ICS use and no use were identified using records of dispensed drugs. We adjusted for potential confounders with propensity score overlap weighting and the risk of a hospitalisation with pneumonia as primary diagnosis was estimated. Multiple subgroup and sensitivity analyses were also performed. RESULTS: We identified 249 351 ICS (mean follow-up of 0.9 years) and 214 840 no-use (mean follow-up of 0.7 years) episodes. During follow-up, 369 and 181 events of hospitalisation for pneumonia were observed in the ICS and no-use episodes, respectively. The weighted incidence rates of hospitalisation for pneumonia was 14.5 per 10 000 patient-years for ICS use episodes and 14.6 for no-use episodes. The weighted HR for hospitalisation for pneumonia associated with ICS use was 1.06 (95% CI 0.88 to 1.28) and the absolute rate difference was -0.06 (95% CI -2.83 to 2.72) events per 10 000 patient-years, compared with no use. CONCLUSIONS: In this nationwide cohort study, we found no evidence of an association between ICS use and the risk of hospitalisation for pneumonia among children with asthma, as compared with no use.

Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease.

Vaso-occlusive episodes (VOEs) are a major concern in patients with sickle cell disease (SCD). Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in case reports or series. No comparative study has been conducted to investigate this risk, which is still debated. Several clinical trials demonstrated the effectiveness of corticosteroids for the treatment of VOEs, but with increased rates of readmission. The aim of the study was to assess the risk of hospitalization for VOE associated with exposure to systemic corticosteroids in patients with SCD. We used a case-case-time-control design in a nationwide population-based cohort built in the French national health insurance database between 2010 and 2018. The population included all patients with SCD with at least 1 hospitalization for VOE. Corticosteroids were identified using out-of-hospital dispensing data. The outcome was the first hospitalization for VOE. The case-case-time-control design induces self-adjustment for time-invariant confounders, including genotype. Analyses were adjusted for time-dependent confounders (infections, red blood transfusions) and stratified by exposure to hydroxyurea. Overall, 5151 patients were included in the main analysis. Corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.4-5.6). In patients exposed to hydroxyurea, the adjusted odds ratio was 2.6 (95% CI, 1.1-6.4); it was 4.0 (95% CI, 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOEs and should be limited in patients with SCD.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

Higher risk of osteoporosis in adult-onset asthma than childhood-onset asthma: from genetic and prospective evidence.

Both COA and AOA have a genetically causal effect on osteoporosis. COA and AOA were independently associated with incident osteoporosis, and the risk was greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications. PURPOSE/INTRODUCTION: Childhood-onset asthma (COA) differs with adult-onset asthma (AOA) on genetic susceptibility, severity, and co-morbidities. Whether COA or AOA is independently associated with osteoporosis is unexplored. We aimed to determine the effects of COA and AOA on osteoporosis at genetic and individual level. METHODS: We used two-sample Mendelian randomization analysis to explore the causal effects of COA and AOA on osteoporosis. In the UK Biobank cohort, we included 478,289 osteoporosis-free participants at baseline (2006-2010). Participants were classified as non-asthma, COA, and AOA at recruitment. Multivariate Cox regression analysis was used to evaluate the effects of COA, AOA, and multiple asthma medications on incident osteoporosis risk. RESULTS: COA and AOA were causally related to osteoporosis, with odds ratio of 1.007 (95% confidence interval (CI), 1.0003-1.0132) and 1.012 (95% CI, 1.002-1.023), respectively. Multivariate Cox regression analysis suggested that COA (hazard ratio (HR), 1.46; 95% CI, 1.32-1.61) and AOA (HR, 1.70; 95% CI, 1.61-1.80) were independently associated with incident osteoporosis, and the risk was greatly higher in AOA (HR, 1.51; 95% CI, 1.34-1.70). In addition to corticosteroids, monotherapy with leukotriene modifiers (HR, 1.70; 95% CI, 1.20-2.42), long-acting beta agonists (HR, 1.49; 95% CI, 1.18-1.87), and short-acting beta agonists (HR, 1.72; 95% CI1.01-2.93) were independently associated with a higher risk of osteoporosis. CONCLUSIONS: Both COA and AOA have a genetically causal effect on osteoporosis, and the risk of osteoporosis is greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications.

Effects of Early Short-Course Corticosteroids on Immune-Related Adverse Events in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. METHODS: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. RESULTS: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35-1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12-0.85; p = 0.013). CONCLUSION: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs.

The effect of inhaler prescription on the development of lung cancer in COPD: a nationwide population-based study.

BACKGROUND: COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD. METHODS: A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded. RESULTS: Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86-3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01-1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01-1.39), along with older age and male sex, were independently associated with the development of lung cancer. CONCLUSION: Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta-analysis.

We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52-0.67) and 0.56 (95% CI 0.43-0.68). The relapse rate was high (PP 0.33, 95% CI 0.27-0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and "symptomatic" etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48-0.89) or corticosteroids (PP 0.72, 95% CI 0.54-0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02-0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.

Outcomes of Preoperative Medical Therapy for Thyroidectomy in Autoimmune Thyroid Disease.

INTRODUCTION: Thyroidectomy provides definitive treatment for autoimmune thyroid disease (AITD) often resulting in improved quality of life. Historically, patients with AITD undergoing thyroidectomy have increased rates of postoperative hypoparathyroidism and recurrent laryngeal nerve palsy. We investigated the outcomes of preoperative medications in patients with AITD undergoing thyroidectomy. METHODS: We performed a retrospective analysis of patients who underwent thyroidectomy for AITD at a single institution from 2015 to 2021. Surgical outcomes and perioperative laboratory values were analyzed by type of AITD and type of preoperative medical treatment: none, saturated solution of potassium iodide (SSKI), corticosteroids, or both SSKI and corticosteroids. RESULTS: A total of 123 patients underwent thyroidectomy for AITD and were included in analysis: 50 received no preoperative medications, 40 received SSKI, 20 received corticosteroids, and 13 received both. Seventy-six patients had Graves' disease and 47 had Hashimoto's thyroiditis. There were no significant differences in blood loss, operative time, wound complications, hematoma, or recurrent laryngeal nerve injury for patients treated with preoperative corticosteroids compared to those who were not. Patients who received corticosteroids and patients with Graves' disease more commonly had at least one instance of hypocalcemia postoperatively (P < 0.01, P = 0.01), although only on postoperative day 1 was mean calcium < 8.5 mg/dL. There was no difference in rate of transient or permanent hypoparathyroidism. CONCLUSIONS: Patients who received corticosteroids preoperatively had no increased risk of complications. They did have mildly lower calcium levels in the early postoperative period, although no difference in hypoparathyroidism. Further exploration is warranted to investigate the impact of preoperative corticosteroids on operative difficulty, quality of life, and autoantibody clearance.

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. STUDY: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. RESULTS: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. CONCLUSIONS: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Measuring neurobehavioral side effects of corticosteroids in pediatric acute lymphoblastic leukemia: A scoping review.

Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. We conducted a scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to describe the existing measurement tools used to evaluate neurobehavioral side effects of corticosteroids in pediatric ALL. From various databases and registers, 4047 studies were identified. Twenty-four articles met inclusion criteria. Clinical assessment was most used to evaluate these symptoms. Twelve validated measures were identified. Existing data about neuropsychiatric side effects of corticosteroids in pediatric ALL are extremely heterogeneous, creating challenges for standardized assessment and management.

Local and Systemic Side Effects of Corticosteroid Injections for Musculoskeletal Indications.

Corticosteroid injections can be associated with a range of potential side effects, which may be classified as local or systemic and further stratified as immediate or delayed in onset. Radiologists performing image-guided musculoskeletal injections should recognize the potential side effects of corticosteroid medication when counseling patients before injection and consider such side effects in planning individual injections. This Review summarizes the available evidence regarding the local and systemic side effects of corticosteroid injections performed for musculoskeletal indications. Local side effects include postinjection flare, skin hypopigmentation and atrophy, infection, tendon rupture, accelerated progression of osteoarthritis, and osseous injury. Systemic side effects include adrenal suppression or insufficiency, facial flushing, hypertension, hyperglycemia, and osteoporosis. Additional targeted counseling is warranted regarding side effects that are specific to certain patient populations (i.e., premenopausal women, patients with diabetes, athletes, and pediatric patients). Corticosteroid injections are contraindicated in the presence of superficial or deep infection, fracture, or a prosthetic joint. Guidelines on the frequency, duration, and maximal lifetime use of corticosteroid injections are currently lacking. Further research is needed regarding the long-term complications of continuous corticosteroid use, particularly with regard to osseous effects.

Antenatal corticosteroids and newborn respiratory outcomes in twins: A regression discontinuity study.

OBJECTIVE: To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. DESIGN: Regression discontinuity applied to population-based birth registry data. SETTING: British Columbia, Canada, 2008-2018. POPULATION: Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. METHODS: During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut-point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). MAIN OUTCOME MEASURES: Our primary outcome was a composite of newborn respiratory distress or in-hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in-hospital death. RESULTS: Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut-point were exposed. The risk of newborn respiratory distress or in-hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53-0.90; risk difference [RD] -12 cases per 100 births, 95% CI -20 to -4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in-hospital death (RR 0.89, 95% CI 0.70-1.13; RD -4.2 per 100, 95% CI -13 to +4.2). CONCLUSIONS: Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins.

Prophylactic corticosteroids for cardiopulmonary bypass in adult cardiac surgery.

BACKGROUND: Cardiac surgery triggers a strong inflammatory reaction, which carries significant clinical consequences. Corticosteroids have been suggested as a potential perioperative strategy to reduce inflammation and help prevent postoperative complications. However, the safety and effectiveness of perioperative corticosteroid use in adult cardiac surgery is uncertain. This is an update of the 2011 review with 18 studies added. OBJECTIVES: Primary objective: to estimate the effects of prophylactic corticosteroid use in adults undergoing cardiac surgery with cardiopulmonary bypass on the: - co-primary endpoints of mortality, myocardial complications, and pulmonary complications; and - secondary outcomes including atrial fibrillation, infection, organ injury, known complications of steroid therapy, prolonged mechanical ventilation, prolonged postoperative stay, and cost-effectiveness. SECONDARY OBJECTIVE: to explore the role of characteristics of the study cohort and specific features of the intervention in determining the treatment effects via a series of prespecified subgroup analyses. SEARCH METHODS: We used standard, extensive Cochrane search methods to identify randomised studies assessing the effect of corticosteroids in adult cardiac surgery. The latest searches were performed on 14 October 2022. SELECTION CRITERIA: We included randomised controlled trials in adults (over 18 years, either with a diagnosis of coronary artery disease or cardiac valve disease, or who were candidates for cardiac surgery with the use of cardiopulmonary bypass), comparing corticosteroids with no treatments. There were no restrictions with respect to length of the follow-up period. All selected studies qualified for pooling of results for one or more endpoints. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, and cardiac and pulmonary complications. Secondary outcomes were infectious complications, gastrointestinal bleeding, occurrence of new post-surgery atrial fibrillation, re-thoracotomy for bleeding, neurological complications, renal failure, inotropic support, postoperative bleeding, mechanical ventilation time, length of stays in the intensive care unit (ICU) and hospital, patient quality of life, and cost-effectiveness. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: This updated review includes 72 randomised trials with 17,282 participants (all 72 trials with 16,962 participants were included in data synthesis). Four trials (6%) were considered at low risk of bias in all the domains. The median age of participants included in the studies was 62.9 years. Study populations consisted mainly (89%) of low-risk, first-time coronary artery bypass grafting (CABG) or valve surgery. The use of perioperative corticosteroids may result in little to no difference in all-cause mortality (risk with corticosteroids: 25 to 36 per 1000 versus 33 per 1000 with placebo or no treatment; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.75 to 1.07; 25 studies, 14,940 participants; low-certainty evidence). Corticosteroids may increase the risk of myocardial complications (68 to 86 per 1000) compared with placebo or no treatment (66 per 1000; RR 1.16, 95% CI 1.04 to 1.31; 25 studies, 14,766 participants; low-certainty evidence), and may reduce the risk of pulmonary complications (risk with corticosteroids: 61 to 77 per 1000 versus 78 per 1000 with placebo/no treatment; RR 0.88, 0.78 to 0.99; 18 studies, 13,549 participants; low-certainty evidence). Analyses of secondary endpoints showed that corticosteroids may reduce the incidence of infectious complications (risk with corticosteroids: 94 to 113 per 1000 versus 123 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.76 to 0.92; 28 studies, 14,771 participants; low-certainty evidence). Corticosteroids may result in little to no difference in incidence of gastrointestinal bleeding (risk with corticosteroids: 9 to 17 per 1000 versus 10 per 1000 with placebo/no treatment; RR 1.21, 95% CI 0.87 to 1.67; 6 studies, 12,533 participants; low-certainty evidence) and renal failure (risk with corticosteroids: 23 to 35 per 1000 versus 34 per 1000 with placebo/no treatment; RR 0.84, 95% CI 0.69 to 1.02; 13 studies, 12,799; low-certainty evidence). Corticosteroids may reduce the length of hospital stay, but the evidence is very uncertain (-0.5 days, 0.97 to 0.04 fewer days of length of hospital stay compared with placebo/no treatment; 25 studies, 1841 participants; very low-certainty evidence). The results from the two largest trials included in the review possibly skew the overall findings from the meta-analysis. AUTHORS' CONCLUSIONS: A systematic review of trials evaluating the organ protective effects of corticosteroids in cardiac surgery demonstrated little or no treatment effect on mortality, gastrointestinal bleeding, and renal failure. There were opposing treatment effects on cardiac and pulmonary complications, with evidence that corticosteroids may increase cardiac complications but reduce pulmonary complications; however, the level of certainty for these estimates was low. There were minor benefits from corticosteroid therapy for infectious complications, but the evidence on hospital length of stay was very uncertain. The inconsistent treatment effects across different outcomes and the limited data on high-risk groups reduced the applicability of the findings. Further research should explore the role of these drugs in specific, vulnerable cohorts.

Practice variation in timing of antenatal corticosteroid administration in early-onset fetal growth restriction: A secondary analysis of the Dutch STRIDER study.

INTRODUCTION: In early-onset fetal growth restriction the fetus fails to thrive in utero due to unmet fetal metabolic demands. This condition is linked to perinatal mortality and severe neonatal morbidity. Maternal administration of corticosteroids in high-risk pregnancies for preterm birth at a gestational age between 24 and 34 weeks has been shown to reduce perinatal mortality and morbidity. Practice variation exists in the timing of the administration of corticosteroids based on umbilical artery monitoring findings in early-onset fetal growth restriction. The aim of this study was to examine differences in neonatal outcomes when comparing different corticosteroid timing strategies. MATERIAL AND METHODS: This was a post-hoc analysis of the Dutch STRIDER trial. We examined neonatal outcomes when comparing institutional strategies of early (umbilical artery pulsatility index >95th centile) and late (umbilical artery shows absent or reversed end-diastolic flow) administration of corticosteroids. The primary outcomes were neonatal mortality and a composite of neonatal mortality and neonatal morbidity, defined as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis or retinopathy of prematurity. We also analyzed predictors for adverse neonatal outcomes, including gestational age at delivery, birthweight, maternal hypertensive disorders, and time interval between corticosteroids and birth. RESULTS: A total of 120 patients matched our inclusion criteria. In 69 (57.5%) the early strategy was applied and in 51 (42.5%) patients the late strategy. Median gestational age at delivery was 28 4/7 (± 3, 3/7) weeks. Median birthweight was 708 (± 304) g. Composite primary outcome was found in 57 (47.5%) neonates. No significant differences were observed in the primary outcome between the two strategies (neonatal mortality adjusted odds ratio [OR] 1.22, 95% CI 0.44-3.38; composite primary outcome adjusted OR 1.05, 95% CI 0.42-2.64). Only gestational age at delivery was a significant predictor for improved neonatal outcome (adjusted OR 0.91, 95% CI 0.86-0.96). CONCLUSIONS: No significant differences in neonatal outcomes were observed when comparing early and late strategy of antenatal corticosteroid administration on neonatal outcomes in pregnancies complicated by early-onset fetal growth restriction. We found no apparent risk contribution of interval between corticosteroid administration and delivery in multivariate analysis. Gestational age at delivery was found to be an important predictor of neonatal outcome.

Gliptin-induced bullous pemphigoid.

OBJECTIVES: Bullous pemphigoid (BP) is a rare, autoimmune, blistering disease in elderly patients that can be triggered by external factors including drugs. Drug-induced bullous pemphigoid (DIBP) does not always follow a self-limiting course after the withdrawal of the offending drug. Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins seem to be associated with a significant risk of inducing BP. CASE PRESENTATION: We report 2 cases of BP attributed to the DPP-4 inhibitor linagliptin. In both cases, the clinical manifestation was strongly suggestive of BP. The diagnosis was verified by histology and direct immunofluorescence (DIF). Linagliptin and all other possible drug triggers of BP were discontinued after consultation with an endocrinologist and a cardiologist. Systemic treatment of BP consisted of methylprednisolone and tetracycline. During the follow-up period, one of the patients suffered a fatal brain stroke while the other was managed with reduced doses of corticosteroids. CONCLUSION: The proper management of autoimmune bullous skin disorders in elderly patients includes a scrupulous assessment of plausible drug triggers. Systemic corticosteroids for treating severe cases of DIBP can worsen concomitant diseases which often necessitates multidisciplinary care.

Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

Do people with eczema and their carers understand topical steroid potency? Results of two surveys.

Topical corticosteroids (TCSs) are classified into four potencies: mild, moderate, potent and very potent. Confusion arises from the wide range of products available, none of which have the potency level printed on the tubes or packaging. An online survey of patients and carers of people with eczema showed that only 17% of 984 respondents knew how many potencies there are. In a second survey, 315 respondents provided 1520 assignments of the potency of commonly used TCSs: 55.5% were correct, 21% were underestimates and 23.5% overestimates. Some errors were extreme: 12 (8%) of those using a very potent TCS considered it mild while 9 (27%) using a mild TCS considered it potent or very potent. Other themes expressed in free-text comments included inadequate and conflicting advice about using TCSs and lack of warnings about long-term adverse effects, particularly topical steroid withdrawal. Ninety-five per cent of respondents wanted TCSs to be clearly labelled with potency.

Higher cumulative dose of topical corticosteroids is associated with osteoporosis and major osteoporotic fracture: A nationwide case-control study.

BACKGROUND: Connections between long-term use of topical corticosteroids (TCSs) of varying potency and osteoporosis and major osteoporotic fracture (MOF) are unclear. Susceptibility to adverse bone effects of TCSs in different sex, age and ethnic groups is unknown too. OBJECTIVES: To demonstrate the association between cumulative dose of TCSs of varying potency and osteoporosis and MOF in Taiwanese population, with stratified analysis of sex and age. METHODS: We conducted a nationwide case-control study and obtained data from Taiwan National Health Insurance Research Database. Cumulative TCS doses in different exposure periods were calculated, and the potency of TCSs was converted to prednisolone equivalent. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for osteoporosis and MOF associated with TCS use. RESULTS: From 2017 to 2020, 129,682 osteoporosis cases and 34,999 MOF cases were selected and randomly matched with 518,728 and 139,996 controls by sex and age. We found clear dose-response relationships between long-term TCS exposure and osteoporosis and MOF. For example, compared to no TCS use, adjusted ORs of osteoporosis were 1.216 (95% CI 1.189-1.243), 1.260 (95% CI, 1.241-1.280) and 1.341 (95% CI, 1.314-1.369) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Adjusted ORs of MOF were 1.118 (95% CI 1.069-1.170), 1.191 (95% CI, 1.156-1.227) and 1.288 (95% CI, 1.238-1.340) for exposure to low, medium and high cumulative TCS doses, respectively, over 5 years. Stratified analysis showed women had higher ORs of osteoporosis and MOF compared to men. Younger people (<50 years) had highest OR of osteoporosis compared to other age groups. CONCLUSIONS: Higher cumulative TCS dose was associated with increased risk of osteoporosis and MOF. Long-term use of TCSs should be cautious, especially in susceptible populations such as women and young people.