History Of Glucocorticoid Use Research Articles

Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. Prognostic study, level III.

Risk factors and clinical presentation of rhino-orbital mucormycosis: Lesson learnt during Covid pandemic

ABSTRACT Aim: To analyze the potential predisposing factors and clinical presentation of mucormycosis in patients with COVID-19. Material and Methods: Medical records of 141 patients with COVID-19-associated mucormycosis (CAM) treated at a tertiary care center in Bihar were reviewed. The predisposing factors, clinical features, and imaging findings of mucormycosis were analyzed. Results: The median age was 48 years (IQR, 43-60). A total of 58 patients developed concurrent CAM and 83 post-CAM. The median interval between COVID-19 and onset of CAM symptoms was 15 days (IQR, 9–16). A total of 80 patients received at-home treatment for COVID-19, and 73 had mild-to-moderate disease. While 61 patients received in-hospital treatment, 57 had severe disease. At presentation, 131 patients had hyperglycemia: 64 type 2 diabetes mellitus (DM) and 67 new-onset DM. The history of glucocorticoid use for COVID-19 was present in 125 patients; 47% were administered at home without monitoring plasma glucose. The common presenting features were toothache, periocular or facial pain, and edema. Rhino-orbital mucormycosis was the most common. Imaging revealed rhinosinusitis in all patients, including pansinusitis (68%), pterygopalatine fossa involvement (21%), cavernous sinus thrombosis (38%), brain abscess (8%), and infarct (4%). All patients received intravenous liposomal amphotericin B, and surgical debridement was performed in 113. Conclusion: COVID-19 patients with hyperglycemia are at risk of developing CAM, irrespective of the severity. Timely recognition of symptoms and prompt initiation of therapy by primary healthcare physicians are imperative for enhancing outcomes. Additionally, glucocorticoid overuse should be avoided, and close monitoring for hyperglycemia development is warranted.

Cross-sectional studies of the causal link between asthma and osteoporosis: insights from Mendelian randomization and bioinformatics analysis.

Asthma and osteoporosis are prevalent health conditions with substantial public health implications. However, their potential interplay and the underlying mechanisms have not been fully elucidated. Previous research has primarily focused on the impact of glucocorticoids on osteoporosis, often overlooking the role of asthma itself. We conducted a multi-stage stratified random sampling in Chongqing, China and excluded individuals with a history of glucocorticoid use. Participants underwent comprehensive health examinations, and their clinical data, including asthma status, were recorded. Logistic regression and Mendelian randomization were employed to investigate the causal link between asthma and osteoporosis. Furthermore, bioinformatics analyses and serum biomarker assessments were conducted to explore potential mechanistic pathways. We found a significant association between asthma and osteoporosis, suggesting a potential causal link. Mendelian Randomization analysis provided further support for this causal link. Bioinformatics analyses revealed that several molecular pathways might mediate the impact of asthma on bone health. Serum alkaline phosphatase levels were significantly elevated in the asthma group, suggesting potential involvement in bone turnover. Our study confirms a causal link between asthma and osteoporosis and highlights the importance of considering asthma in osteoporosis prediction models. It also suggests that asthma may accelerate osteoporosis by increasing bone turnover through inflammatory factors, disrupting the coupling between osteoblasts and osteoclasts, ultimately leading to bone loss.

Performance of mNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Serial or compare bone mineral densitometry: how to do it step by step

Bone mineral densitometry (BMD) is the most valuable method for assessing bone and calculating fracture risk. Serial or comparative bone densitometry is important in rheumatologists' work on osteoporosis management. The response or lack of response to osteoporosis treatment based on densitometry scans is crucial. This paper examines the timing of scan requests concerning the history of glucocorticoid use, renal or other solid organ transplantation, malignancy, and other situations discussed. We encountered four types of compared scans based on the centers where BMD was performed and the precision of the devices used for this survey: Same Center, Same Device (SSSD), Same Center Different Devices (SCDD), Different Centers Same Devices (DCSD), and Different Centers Different Devices (DCDD). We discussed the principles of comparison and the key indicators.

Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an emerging global epidemic. The intention of this study was to explore the risk model and validation of CRKP infection in patients with cerebrovascular disease in the intensive care unit (ICU). The data of patients with cerebrovascular disease and Klebsiella pneumoniae infection were retrospectively collected. The patients were divided into the CRKP group and the carbapenem-susceptible Klebsiella pneumoniae (CSKP) group. There were significant differences (P < 0.05) between the CRKP group and the CSKP group for many variables. Multivariate binary logistic regression analysis showed that the number of types of antibiotics used, history of glucocorticoid use, and duration of mechanical ventilation before the occurrence of infectious bacteria are the independent risk factors for CRKP infection in patients with cerebrovascular disease in the ICU, and a nomogram risk model was constructed accordingly. The area under the ROC curve of the risk model was 0.868 (95% CI: 0.803-0.934).

Lumbar posterior group muscle degeneration: Influencing factors of adjacent vertebral body re-fracture after percutaneous vertebroplasty.

The purpose of the study was to explore the influencing factors of adjacent vertebral re-fracture after percutaneous vertebroplasty (PVP) for osteoporosis vertebral compression fractures (OVCFs). We retrospectively analyzed the clinical data of 55 patients with adjacent vertebral re-fracture after PVP operation for OVCFs in our hospital from January 2016 to June 2019, they were followed up for 1 year and included in the fracture group. According to the same inclusion and exclusion criteria, we collected the clinical data of 55 patients with OVCFs without adjacent vertebral re-fracture after PVP in the same period and included them in the non-fracture group. We performed univariate and multivariate logistic regression analysis on the influencing factors of adjacent vertebral re-fracture in patients with OVCFs after PVP. There were significant differences in body mass index (BMI), bone mineral density (BMD) T-value, amount of bone cement injected, bone cement leakage, history of glucocorticoid use, cross-sectional area (CSA), cross-sectional area asymmetry (CSAA), fat infiltration rate (FIR), and fat infiltration rate asymmetry (FIRA) of lumbar posterior group muscles [multifidus (MF) and erector spinae (ES)] between the two groups (p < 0.05). There was no significant difference in sex, age, or time from the first fracture to operation, the CAS, CSAA, FIR, and FIRA of psoas major (PS) between the two groups (p > 0.05). Multivariate logistic regression showed that a higher dose of bone cement, greater CSAA and FIR of multifidus, and higher CSAA of erector spinae were independent risk factors for recurrent fractures of adjacent vertebrae after PVP. There are many risk factors for recurrent vertebral fracture after PVP in patients with OVCFs, and degeneration of paraspinal muscles (especially posterior lumbar muscles) may be one of the risks.

Weakness After an Intraarticular Steroid Injection: A Case Report of Acute Steroid-Induced Myopathy

Introduction: Weakness is a common chief complaint in the emergency department, and the use of glucocorticoids is pervasive in medicine. Muscle weakness, or myopathy, is a well documented side effect of chronic glucocorticoid use. However, acute myopathy, with an onset shortly after initiation of glucocorticoids, is much rarer. Case Report: We present a case of acute steroid-induced myopathy after a single intra-articular dose of triamcinolone in a young, healthy, active male. To our knowledge, this is the first case described in the medical literature of acute steroid-induced myopathy following a single intra-articular injection. Conclusion: In a patient who presents with proximal muscle weakness and has a history of glucocorticoid use, the diagnosis of steroid-induced myopathy should be considered. Acute steroid-induced myopathy should be high on the differential in a patient who presents with typical symptoms and has been prescribed glucocorticoids for less than 14 days or, in rare cases, may have recently received a single dose of glucocorticoids. Treatment is supportive and outpatient management is typically indicated, as respiratory muscle involvement is rare.

Weakness After an Intra-articular Steroid Injection: A Case Report of Acute Steroid-induced Myopathy.

IntroductionWeakness is a common chief complaint in the emergency department, and the use of glucocorticoids is pervasive in medicine. Muscle weakness, or myopathy, is a well documented side effect of chronic glucocorticoid use. However, acute myopathy, with an onset shortly after initiation of glucocorticoids, is much rarer.Case ReportWe present a case of acute steroid-induced myopathy after a single intra-articular dose of triamcinolone in a young, healthy, active male. To our knowledge, this is the first case described in the medical literature of acute steroid-induced myopathy following a single intra-articular injection.ConclusionIn a patient who presents with proximal muscle weakness and has a history of glucocorticoid use, the diagnosis of steroid-induced myopathy should be considered. Acute steroid-induced myopathy should be high on the differential in a patient who presents with typical symptoms and has been prescribed glucocorticoids for less than 14 days or, in rare cases, may have recently received a single dose of glucocorticoids. Treatment is supportive and outpatient management is typically indicated, as respiratory muscle involvement is rare.

27777 Examining the risk of postoperative Mohs surgery complications in patients with history of glucocorticoid use

Background: Glucocorticoids are strong anti-inflammatory agents with pleiotropic effects and are used to treat a wide variety of conditions. Long term steroid use has been associated with an increased risk of nonmelanoma skin cancer and impaired wound healing. The risk of postoperative complications after Mohs micrographic surgery (MMS) in patients with a recent history of glucocorticoid use compared with those with no history of use is unknown.

The clinical characteristics of severe influenza virus pneumonia complicated with invasive pulmonary aspergillosis: a retrospective study of 15 cases

Objective: To explore the clinical characteristics, risk factors and possible inflammatory response mechanisms in critically ill patients with influenza and invasive pulmonary aspergillosis co-infection. Methods: Sixty-four patients with severe influenza virus pneumonia were included in the RICU of the China-Japanese Friendship Hospital from November 1(st), 2017 to March 31(th), 2018. There were 33 males and 31 females, with an average age of (55±14) years. T-tests or χ(2) test were applied for comparisons between the two groups. Fifteen patients were complicated with IPA and were classified as the IPA group, while the other 49 served as the control group. The clinical characteristics, laboratory examinations, and endoscopic manifestations were compared between the two groups and the risk factors for severe influenza virus pneumonia with IPA were analyzed by multivariate logistic regression. The possible mechanisms of inflammatory response were explored by comparing the differences of plasma inflammatory factors between the two groups. Results: Seven patients (7/15, 47.7%) in the IPA group died. The percentage of wheezing in the IPA group (n=13) was significantly higher than that in the control group (n=25) (P<0.05). The values of WBC [(11.0±2.7)×10(9)/L], and the levels of blood GM [(2.46±0.80) μg/L] and BALF GM [(5.30±0.98) μg/L] in the IPA group were significantly higher than those in the control group, while PCT was lower than that in the control group[(6.1±3.3)×10(9)/L, (0.33±0.07) μg/L and (0.73±0.17) μg/L, respectively] (P<0.01). Compared with the control group, the chest CT of the IPA group showed more nodules along the bronchial bundle (n=11), massive consolidation shadow (n=9), halo sign (n=3) and cavity/air crescent sign (n=5) (control group: 8, 11, 0 and 4, respectively) (P<0.05). Airway mucosal pseudomembrane formation (n=12) and airway stenosis (n=10) were significantly higher in the IPA group than in the control group (2 and 17) (P<0.05). Multivariate logistic regression analysis suggested that the history of glucocorticoid use after ICU admission, normal PCT, multiple nodules, halo signs and pseudomembrane formation under endoscopy were risk factors for severe influenza virus pneumonia with IPA. The plasma pro-inflammatory factors IFN-γ [IPA group: 34.9 (20.6-64.0) μg/L] and IL-2 [16.2 (8.9-20.7) μg/L] were significantly lower than in patients without IPA [control group: 65.2 (43.8-124.5) μg/L and 20.4 (14.6-28.8) μg/L, respectively] (P<0.05); while the inflammatory inhibitors IL-4 [51.6 (32.7-69.7) μg/L) and IL-10 [15.7 (11.8-92.5) μg/L] were higher in IPA group [control group 8.9 (6.1-15.0) μg/L and 7.8 (3.6-21.8) μg/L] (P<0.05). SOFA scores showed a negative correlation with IFN-γ (r=-0.658, P=0.02) and IL-6 (r=-0.602, P=0.038), but a positive correlation with IL-10 (r=0.641, P=0.025) by Spearman correlation analysis. Conclusions: Some relatively specific clinical characteristics could be found in severe influenza pneumonia complicated with IPA. IPA should be highly suspected when a patient had a history of glucocorticoid use after ICU admission, high WBCs in the course of treatment without significant increase of PCT,multiple nodules along the airway distribution and the characteristic pseudomembrane formation under bronchoscopy. Influenza virus caused imbalance of immune responses, leading to a weakened pro-inflammatory response and a strengthened inflammatory suppression, which might be a possible mechanism for IPA development.

MON-183 Adrenal Androgen Control and Steroidal Side Effects in Adolescents and Adults with Congenital Adrenal Hyperplasia Treated with Glucocorticoids

Introduction: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive disorder that results in little or no cortisol biosynthesis, increased production of precursor steroids, and excess production of adrenal androgens. Glucocorticoid (GC) treatment, the current standard of care for CAH, is used to correct cortisol deficiency and reduce excessive androgens. Elevated 17-hydroxyprogesterone (17OHP) is used for diagnosis and management. GC titration to achieve 17OHP <1000 ng/dL may be targeted for adrenal androgen control; however, patients with 17OHP <1000 ng/dL might be at risk for complications of long-term GC excess. This real-world study evaluated adrenal androgen levels and potential GC complications in adolescents and adults with CAH. Methods: TriNetX, a research network that includes electronic medical records from >37 million U.S. patients, was searched on 30Aug2019 for patients who met the following criteria: diagnosis code of E25.0 (ICD-10) or 255.2 (ICD-9); history of GC use; available 17OHP laboratory result; and ≥15 years of age (“grown”) at the most recent 17OHP assessment. Patients were categorized as “adequately controlled” (17OHP <1000 ng/dL) or “poorly controlled” (17OHP ≥1000 ng/dL). Assessments included: demographics; laboratory results for 17OHP, adrenocorticotropic hormone (ACTH), and androstenedione (A4); and low-density lipoprotein (LDL). Adequately vs. poorly controlled groups were compared using Chi-square tests and t-tests. Results: Of 511 grown CAH patients, 352 were adequately controlled and 159 were poorly controlled. Mean concentrations for 17OHP were 244 and 5939 ng/dL in the adequately and poorly controlled cohorts, respectively (p<0.01). Adequately controlled patients also had lower ACTH and A4 than poorly controlled patients: ACTH (72 vs 389 pg/mL, p<0.01); A4 (82 vs 256 ng/dL, p<0.01). Compared to poorly controlled patients, adequately controlled patients were more likely to be female (81% vs 57%, p<0.01) and older (mean birth year: 1981 vs 1986, p<0.01). Adequately controlled patients also had evidence of more metabolic and infection complications, including higher mean LDL (105 vs 94.3 mg/dL, p=0.02), more type 2 diabetes mellitus (9% vs 4%, p=0.08), and more respiratory tract infections (21% vs 11%, p=0.01). Conclusions: In this retrospective analysis, patients with adequately controlled CAH (17OHP <1000 ng/dL) had better adrenal androgen control (lower A4) but also higher rates of complications potentially related to excessive GC exposure. These findings highlight the current challenges of managing CAH with GC regimens alone.

Risk factors of parastomal hernia in patients undergoing laparoscope radical cystectomy and ileal conduit diversion

Objective To investigate the incidence rate of parastomal hernia(PH) among patients who have received laparoscope radical cystectomy and ileal conduit diversion and to discover the risk factors for PH. Methods Data of 162 patients who underwent surgery of laparoscope radical cystectomy and ileal conduit diversion for bladder cancer between Jan 2012 and Dec 2017 were studied. The patients who had suffered other tumors before surgery or without follow-up data were excluded. At last, 148 patients were enrolled in this retrospective study. According to the occurrence of PH, the patients were divided into two groups: PH group and non-PH group. There were 21 patients (12 males and 9 females) in PH group. The mean age was (66.5±8.6) years old, and mean body mass index (BMI) was (33.4±5.2) kg/m2. 11 patients with synchronous disease and 10 patients without synchronous disease before operation in PH group. Postoperative T stage <T3 in 17 cases, ≥T3 in 4 cases. 4 Cases received neoadjuvant chemotherapy and 5 cases received adjuvant chemotherapy. Tumor recurrence was found in 6 cases. 16 cases had hypoproteinemia. Ileal conduit was made through abdominal incision in 9 cases, and 12 cases was made with laparoscopy. After the surgery, there was severe cough in 7 cases and abdominal distension in 7 cases. 3 cases had previous abdominal operation, and 5 cases had history of glucocorticoid use. The mean size of the stoma was (3.0±0.6) cm. The mean length of the outflow tract was (11.2 ±1.3) cm. We did trans-rectus stoma in 4 cases, and para-rectus stoma in 17 cases. There were 127 patients (82 males and 45 females) in non-PH group. The mean age was (71.4 ±7.4) years, and the mean BMI was (28.8±4.1)kg/m2. 60 patients with synchronous disease and 67 patients without. Postoperative T stage <T3 in 96 cases, ≥T3 in 31 cases. 29 patients received neoadjuvant chemotherapy and 39 cases received adjuvant chemotherapy. Tumor recurrence was found in 38 cases. 66 cases had hypoproteinemia. Ileal conduit was made through abdominal incision in 55 cases, under laparoscopy in 72 cases. There was severe cough in 34 cases and abdominal distension in 38 cases. 21 cases had previous abdominal operation, and 35 cases had history of glucocorticoid use. The mean size of the stoma was (2.3±0.4) cm. The mean length of the outflow tract was (12.2±1.6) cm. 4 cases had trans-rectus stoma, and 17 cases had para-rectus stoma. Postoperative rate of PH was estimated using the Kaplan-Meier methods. Chi-square test were used for the univariate analysis between group of PH and the normal one. Multivariate Logistic regression analysis was used to judge the independent risk factors of PH. Results Patients were followed up for 24 months. PH occurred in 21 cases, the 1, 2, 5 year cumulative incidence of PH was 9.9%, 5.4% and 16.7% respectively. Clinical characteristics, including age at surgery(χ2=4.018, P=0.045), obesity(χ2=3.949, P=0.047), perioperative hypoproteinemia(χ2=4.279, P=0.039), chronic constipation(χ2=5.416, P=0.020), stoma location(χ2=6.464, P=0.011), stoma size(χ2=3.915, P=0.048), were significantly different between the PH group and the normal group(P<0.05). Multivariate Logistic regression analysis shows that obesity(OR=1.326, 95%CI=1.102-1.548, P=0.043), stoma location(OR=0.892, 95%CI=0.854-0.931, P=0.028), stoma size(OR=1.365, 95%CI=1.089-1.631, P=0.028) were the independent risk factors for PH. Conclusion We demonstrated that most of PH usually develop in 2 years after undergoing radical cystectomy with ileal conduit diversion. Obesity, stoma location and stoma size are independent risk factors. Preoperative counseling and preventative measures regarding PH formation should be emphasized, particularly in those patients with risk factors. Key words: Urinary bladder neoplasms; Radical cystectomy; Urinary diversion; Hernia

The changes of serum cortisol, pro-B-type natriuretic peptide and interleukin-6 in critically ill children with stress

Objective To understand the changes of the levels of serum cortisol, pro-B-type natriuretic peptide(Pro-BNP) and interleukin-6(IL-6) in the critical stress children. Methods The experimental group enrolled the children with severe infection, polytrauma and cardiopulmonary resuscitation admitted in PICU of Children′s Hospital of Fudan University from May 2015 to December 2015.The children admitted to the surgical ward during the same period without trauma, infection, heart, kidney and adrenal diseases or dysfunction, and without a long history of glucocorticoid use were selected as the control group.According to the pediatric critical illness score(PCIS), the experimental group was divided into 3 subgroups: severe critically ill group(PCIS≤70, n=17), critically ill group(PCIS 71-89, n=26), and non-critically ill group(PCIS≥90, n=15). What′s more, the experimental cases were divided into survival group (n=39)and death group(n=19) according to the prognosis.On the day of admission and during the period with stable condition, the peripheral blood sample were collected to detect serum cortisol, Pro-BNP and IL-6.While the control cases were detected the same items on the day of admission or pre-operation. Results The concentrations of serum cortisol, Pro-BNP and IL-6 on the day of admission in severe critically ill group, critically ill group and non-critically ill group were higher than those in the period with stable condition (P 0.05). The concentrations of Pro-BNP and IL-6 in death group were significantly higher than those in survival group(P 0.05). PCIS was negatively correlated with serum cortisol, Pro-BNP and IL-6 (r=-0.571, -0.661 and -0.504, P<0.05, respectively). Conclusion The levels of serum cortisol, Pro-BNP and IL-6 in critically ill children all significantly increase in acute critically ill period, which are all negatively correlated with PCIS.They can be used as the indicators of severity of illness.Pro-BNP and IL-6 also can be used as the indicators of the prognosis of disease. Key words: Critically ill children; Stress; Cortisol; Pro-B-type natriuretic peptide; Interleukin-6

Effect of preadmission glucocorticoid therapy on 30-day mortality in critically ill patients: a retrospective study of a mixed ICU population in a tertiary hospital

BackgroundThis study aimed to investigate the association between preadmission glucocorticoid (GC) therapy and 30-day mortality in critically ill patients following admission to an intensive care unit (ICU). We aimed to determine whether this association differed according to daily GC dosage and type. We conducted a retrospective cohort study of adult patients admitted to a single tertiary academic hospital ICU from January 2012 to December 2017. We classified the patients regularly undergoing oral GC therapy as preadmission GC users, and those with no history of GC use were classified as non-GC users.ResultsThe study included 24,929 patients, of whom 816 (3.3%) were preadmission GC users. Thirty-day mortality in preadmission GC users (173 of 816 patients) was 21.2% compared to 8.8% (2113 of 24,113 patients) in non-GC users. Multivariate Cox regression analysis showed that preadmission GC users had a 1.62-fold increase in 30-day mortality compared to non-GC users [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.29–2.03, P < 0.001]. When comparing preadmission GC users with diabetes mellitus to non-GC users, a 2.29-fold increase in 30-day mortality was noted (HR 2.29, 95% CI 1.08–4.86, P = 0.031). In the sensitivity analysis, compared to non-GC users, daily dosages of ≤ 5 and > 5 mg of prednisolone in preadmission GC users showed 1.45-fold (HR 1.45, 95% CI 1.03–2.03, P = 0.033) and 1.67-fold (HR 1.67, 95% CI 1.25–2.24, P = 0.001) increases, respectively, in 30-day mortality after ICU admission. Moreover, prednisolone, methylprednisolone, and dexamethasone users in the preadmission GC users group showed 1.56-fold (HR 1.56, 95% CI 1.21–2.01, P = 0.001), 1.90-fold (HR 1.90, 95% CI 1.12–3.25, P = 0.018), and 1.30-fold (HR 1.30, 95% CI 1.05–1.50, P = 0.042) increases, respectively, in 30-day mortality compared to non-GC users.ConclusionPreadmission GC use among critically ill patients was associated with an increased 30-day mortality after ICU admission compared to non-GC use. This association was more prevalent in preadmission GC users with diabetes mellitus and in preadmission GC users who took > 5 mg/day of prednisolone and methylprednisolone.

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis

BackgroundGlucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. MethodsIn June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. ResultsThe consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. ConclusionAssociation Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study

Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid use (odds ratio 0·47, 95% CI 0·22-1·00; p=0·0501). In patients with Duchenne muscular dystrophy, glucocorticoid treatment is associated with reduced risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death. US Department of Education/National Institute on Disability and Rehabilitation Research; US Department of Defense; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Parent Project Muscular Dystrophy.

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.

Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

SUSTAINED ELEVATION OF INTRAOCULAR PRESSURE AFTER INTRAVITREAL ANTI-VEGF AGENTS: What Is the Evidence?

To summarize the literature addressing sustained and delayed elevation of intraocular pressure (IOP) in patients with neovascular age-related macular degeneration being treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. Analysis of current literature evaluating sustained and delayed elevation of IOP in patients receiving intravitreal anti-VEGF therapy for neovascular age-related macular degeneration. Studies have demonstrated that patients undergoing treatment with intravitreal anti-VEGF agents may experience sustained and delayed elevation of IOP. The incidence of sustained elevation of IOP in patients with neovascular age-related macular degeneration varied from 3.45% to 11.6%, and few patients required surgical management to control IOP. Possible risk factors associated with sustained and delayed elevation of IOP include, but are not limited to, history of glaucoma, phakia, history of glucocorticoid use, and/or extended treatment duration. There are multiple theories explaining the pathogenesis of sustained elevation of IOP, including microparticle obstruction of the trabecular meshwork, intraocular inflammation, and transient elevation of IOP. Sustained and delayed elevation of IOP in patients undergoing treatment of neovascular age-related macular degeneration with intravitreal anti-VEGF agents is likely a multifactorial process. Further studies to prospectively investigate sustained elevation of IOP in large, randomized, controlled trials might lead to a better understanding of the long-term adverse events associated with intravitreal anti-VEGF therapy.

PTH-128 The Frax Algorithm is of Limited Utility in Predicting Osteoporosis in Coeliac Disease

IntroductionOsteoporosis is the commonest complication of coeliac disease yet no reliable scoring system exists to guide patient selection for bone density measurement. The FRAX tool has been developed by the...