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  1. Gupta G, S R, Singh Y, Thangavelu L, Singh SK, Dureja H, et al.
    Drug Dev Res, 2021 11;82(7):880-882.
    PMID: 34323298 DOI: 10.1002/ddr.21862
    COVID-19's second wave had a significant impact on India, on May 7, 2021, the largest daily recorded case count was a little more than 4 million, and it has since fallen. Although the number of new cases reported has dropped, during the third week of May 2021, India accounted for about 45% of new cases identified globally and around 34% of deaths. As India maintains its present level of stability, a new urgent threat has emerged in the form of coronavirus-associated mucormycosis. Mucormycosis, an acute and deadly fungal infection caused by Mucorales-related fungal species, is a fungal emergency with a particularly aggressive propensity for contiguous spread, associated with a poor prognosis if not properly and immediately identified, and treated. Mucormycosis, sometimes referred to as the "black fungus," has increased more rapidly in India during the second wave of COVID-19 than during the first wave, with at least 14,872 cases as of May 28, 2021. Uncontrolled diabetic mellitus (DM) and other immunosuppressive diseases such as neutropenia and corticosteroid treatment have traditionally been identified as risk factors for mucormycosis. Therefore, the use of glucocorticoids or high doses of glucocorticoids in mild COVID-19 cases (without hypoxemia) should be avoided. In addition, drugs that target the immune pathway, such as tocilizumab, are not recommended without clear benefits.
    Matched MeSH terms: Glucocorticoids/adverse effects
  2. Hamidah A, Thambidorai CR, Jamal R
    PMID: 16124452
    We describe a patient with Evans syndrome (autoimmune hemolytic anemia and autoimmune thrombocytopenia) who was refractory to steroids and intravenous immunoglobulin. She responded to splenectomy and has remained in clinical remission for 3 years. In the majority of cases, splenectomy rarely induces a durable remission but it may be beneficial in a small group of patients, hence should be considered as alternative therapy in the management of these patients.
    Matched MeSH terms: Glucocorticoids/adverse effects
  3. Ismail AM, Balakrishnan R, Rajakumar MK
    J Bone Joint Surg Br, 1969 Aug;51(3):503-5.
    PMID: 5820795
    A case of disruption of patellar ligament is described. An association with previous steroid infiltration is present in this case.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  4. Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al.
    Pediatr Nephrol, 2020 Aug;35(8):1529-1561.
    PMID: 32382828 DOI: 10.1007/s00467-020-04519-1
    Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  5. Chong YJ, Wong CK, Shatriah I
    Middle East Afr J Ophthalmol, 2015 Jan-Mar;22(1):125-8.
    PMID: 25624689 DOI: 10.4103/0974-9233.148364
    Conjunctival necrosis is a rare complication following periocular/intraocular triamcinolone acetonide injection and has been reported extensively in adults. We describe a child who developed conjunctival necrosis following subconjunctival injection of triamcinolone acetonide for severe chronic anterior uveitis. Prompt diagnosis and management of this uncommon condition is vital.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  6. Mohd Ramli ES, Suhaimi F, Ahmad F, Shuid AN, Mohamad N, Ima-Nirwana S
    Curr Drug Targets, 2013 Dec;14(14):1675-82.
    PMID: 24107234
    Osteoporosis is a major global health problem. Osteoporosis is characterized by the loss of bone mass and strength which leads to an increased risk of fracture. Glucocorticoid treatment is the leading cause of secondary osteoporosis. Glucocorticoid action in bone depends upon the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). The oestrogen deficient state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk) is commonly used in the local cuisine of South East Asia. It is also traditionally used to treat many diseases such as inflammation, dermatitis and joint pain. Studies have revealed antioxidant properties through its flavonoids compound naringenin which acts as a superoxide scavenger that may help in the endogenous antioxidant defence system to protect bone against osteoporosis. Recent studies found that Ps extract has the ability to inhibit the expression and activity of 11β-HSD1 in adipose tissue and bone which restored bone structure and strength. It also accelerates fracture healing in the oestrogen deficient state through its antioxidant properties. The cost of conventional treatment is high and together with the adverse effects it leads to noncompliance. Treatment modalities with herbal medicine, less side effects and is cheaper need to be explored.This review focused on the therapeutic effect of Ps extract on fracture healing in ovariectomized rats and its protective effects against glucocorticoid induced osteoporotic rats.
    Matched MeSH terms: Glucocorticoids/adverse effects
  7. Soga T, Dalpatadu SL, Wong DW, Parhar IS
    Neuroscience, 2012 Aug 30;218:56-64.
    PMID: 22626647 DOI: 10.1016/j.neuroscience.2012.05.023
    Synthetic glucocorticoid (dexamethasone; DEX) treatment during the neonatal stage is known to affect reproductive activity. However, it is still unknown whether neonatal stress activates gonadotropin-inhibitory hormone (GnIH) synthesizing cells in the dorsomedial hypothalamus (DMH), which could have pronounced suppressive action on gonadotropin-releasing hormone (GnRH) neurons, leading to delayed pubertal onset. This study was designed to determine the effect of neonatal DEX (1.0mg/kg) exposure on reproductive maturation. Therefore, GnRH, GnIH and GnIH receptors, G-protein coupled receptors (GPR) 147 and GPR74 mRNA levels were measured using quantitative real-time PCR in female mice at postnatal (P) days 21, 30 and in estrus stage mice, aged between P45-50. DEX-treated females of P45-50 had delayed vaginal opening, and irregular estrus cycles and lower GnRH expression in the preoptic area (POA) when compared with age-matched controls. The expression levels of GPR147 and GPR74 mRNA in the POA increased significantly in DEX-treated female mice of P21 and P45-50 compared to controls. In addition, GPR147 and GPR74 mRNA expression was observed in laser captured single GnRH neurons in the POA. Although there was no difference in GnIH mRNA expression in the DMH, immunostained GnIH cell numbers in the DMH increased in DEX-treated females of P45-50 compared to controls. Taken together, the results show that the delayed pubertal onset could be due to the inhibition of GnRH gene expression after neonatal DEX treatment, which may be accounted for in part by the inhibitory signals from the up-regulated GnIH-GnIH receptor pathway to the POA.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  8. Siddique MI, Katas H, Amin MCIM, Ng SF, Zulfakar MH, Buang F, et al.
    J Pharm Sci, 2015 Dec;104(12):4276-4286.
    PMID: 26447747 DOI: 10.1002/jps.24666
    Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  9. Tan TT, Lau IS, Kong NC, Zainal AG
    Malays J Pathol, 1997 Jun;19(1):27-33.
    PMID: 10879239
    Matched MeSH terms: Glucocorticoids/adverse effects*
  10. Md Din N, Tomkins-Netzer O, Talat L, Taylor SR, Isa H, Bar A, et al.
    J Glaucoma, 2016 07;25(7):598-604.
    PMID: 26900824 DOI: 10.1097/IJG.0000000000000379
    PURPOSE: To determine risk factors for intraocular pressure (IOP) elevation and glaucoma in children with nonjuvenile idiopathic arthritis-related uveitis and any IOP-related changes in the retinal nerve fiber layer (RNFL) thickness.

    PATIENTS AND METHODS: Clinical data were collected from children attending a tertiary referral uveitis clinic between May 2010 and October 2012. We assigned 206 eyes of 103 children into 32 normal eyes, 108 normotensive uveitics (NU), 41 hypertensive uveitics (HU: raised IOP without glaucomatous disc), and 25 glaucomatous uveitics (GU: raised IOP with glaucomatous disc). Risk factors for raised IOP, glaucoma and steroid response (SR) were evaluated and RNFL thickness across groups was compared with determine changes related to raised IOP.

    RESULTS: IOP elevation occurred in 40 patients (38.8%) or 66/174 eyes with uveitis (37.9%); and SR occurred in 35.1% of all corticosteroid-treated eyes. Chronic uveitis was a significant risk factor for raised IOP [odds ratio (OR)=9.28, P=0.001], glaucoma, and SR (OR=8.4, P<0.001). Higher peak IOP was also a risk factor for glaucoma (OR=1.4, P=0.003). About 70% of SR eyes were high responders (IOP increase >15 mm Hg from baseline), associated with younger age and corticosteroid injections. Although no significant RNFL thinning was detected between HU and NU eyes, significant thinning was detected in the inferior quadrant of GU (121.3±28.9 μm) compared with NU eyes (142.1±32.0 μm, P=0.043).

    CONCLUSIONS: Children with chronic uveitis are at higher risk of raised IOP and glaucoma. Thinning of the inferior RNFL quadrant may suggest glaucomatous changes in uveitic children with raised IOP.

    Study site: Moorfields Eye Hospital, London
    Matched MeSH terms: Glucocorticoids/adverse effects
  11. Hong JGS, Tan PC, Kamarudin M, Omar SZ
    BMC Pregnancy Childbirth, 2021 Feb 15;21(1):138.
    PMID: 33588801 DOI: 10.1186/s12884-021-03628-5
    BACKGROUND: Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration.

    METHODS: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids.

    RESULTS: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different.

    CONCLUSIONS: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect.

    TRIAL REGISTRATION: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .

    Matched MeSH terms: Glucocorticoids/adverse effects*
  12. Suhana MR, Farihah HS, Faizah O, Nazrun SA, Norazlina M, Norliza M, et al.
    Clin Ter, 2011;162(4):313-8.
    PMID: 21912818
    Osteoporosis is a proven complication of long-term glucocorticoid therapy. Concern on glucocorticoid induced osteoporosis has increased dramatically in recent years with the widespread use of synthetic glucocorticoids. Glucocorticoid action in bone depends upon the activity of 11βhydroxysteroid dehydrogenase type 1 enzyme (11βHSD1). This enzyme plays an important role in regulating corticosteroids by locally interconverting cortisone into active cortisol. This has been demonstrated in primary cultures of human, mouse or rat osteoblasts. Therefore, inhibition of this enzyme may reduce bone resorption markers. Piper sarmentosum (Ps) is a potent inhibitor of 11βHSD1 in liver and adipose tissue. In this study we determined the effect of Ps on 11βHSD1 activity in bones of glucocorticoid-induced osteoporotic rats.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  13. Ramli ES, Suhaimi F, Asri SF, Ahmad F, Soelaiman IN
    J. Bone Miner. Metab., 2013 May;31(3):262-73.
    PMID: 23274351 DOI: 10.1007/s00774-012-0413-x
    Rapid onset of bone loss is a frequent complication of systemic glucocorticoid therapy which may lead to fragility fractures. Glucocorticoid action in bone depends upon the activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). Regulations of 11β-HSD1 activity may protect the bone against bone loss due to excess glucocorticoids. Glycyrrhizic acid (GCA) is a potent inhibitor of 11β-HSD. Treatment with GCA led to significant reduction in bone resorption markers. In this study we determined the effect of GCA on 11β-HSD1 activity in bones of glucocorticoid-induced osteoporotic rats. Thirty-six male Sprague-Dawley rats (aged 3 months and weighing 250-300 g) were divided randomly into groups of ten. (1) G1, sham operated group; (2) G2, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral vehicle normal saline vehicle; and (3) G3, adrenalectomized rats administered with intramuscular dexamethasone 120 μg/kg/day and oral GCA 120 mg/kg/day The results showed that GCA reduced plasma corticosterone concentration. GCA also reduced serum concentration of the bone resorption marker, pyridinoline and induced 11β-HSD1 dehydrogenase activity in the bone. GCA improved bone structure, which contributed to stronger bone. Therefore, GCA has the potential to be used as an agent to protect the bone against glucocorticoid induced osteoporosis.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  14. Mohd Zain A, Md Noh UK, Hussein S, Che Hamzah J, Mohd Khialdin S, Md Din N
    J Glaucoma, 2019 04;28(4):321-324.
    PMID: 30585941 DOI: 10.1097/IJG.0000000000001164
    PURPOSE: The purpose of this study was to investigate the association between long-term intranasal steroid use and intraocular pressure (IOP) elevation.

    PATIENTS AND METHODS: In total, 100 eyes from 50 patients on long-term intranasal steroids (>2 y) for allergic rhinitis and 90 eyes from 45 controls were included in this study. Patients on other forms of steroids and risk factors for glaucoma were excluded. IOP was measured and nonmydriatic stereoscopic optic disc photos were taken for each eye. The vertical cup-to-disc ratio and the status of the optic disc were evaluated.

    RESULTS: The mean IOP for intranasal steroids group was significantly higher (15.24±2.31 mm Hg) compared to the control group (13.91±1.86 mm Hg; P=0.000). However, there were no significant differences in the vertical cup-to-disc ratio and the status of glaucomatous optic disc changes between the groups.

    CONCLUSIONS: Prolonged use of intranasal steroids cause statistical significant increase in IOP in patients with allergic rhinitis although no significant glaucomatous disc changes were seen. We suggest patients on long-term use of intranasal steroid have a yearly eye examination to be monitored for IOP elevation and those with additional risk factors for glaucoma is closely monitored for glaucoma.

    Matched MeSH terms: Glucocorticoids/adverse effects*
  15. Mohamad Asri SF, Mohd Ramli ES, Soelaiman IN, Mat Noh MA, Abdul Rashid AH, Suhaimi F
    Molecules, 2016 Nov 15;21(11).
    PMID: 27854305
    Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum (Ps) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration (p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.
    Matched MeSH terms: Glucocorticoids/adverse effects*
  16. Mohd-Tahir NA, Thomas P, Mohamed-Said MS, Makmor-Bakry M, Li SC
    Int J Rheum Dis, 2018 Mar;21(3):647-655.
    PMID: 29105349 DOI: 10.1111/1756-185X.13206
    INTRODUCTION: Glucocorticoid therapy is associated with an appreciable risk of bone loss leading to fractures that require expensive treatments. This study aimed to evaluate the cost-effectiveness of bisphosphonates for prevention of hip fracture in glucocorticoid-induced osteoporosis (GIOP) in Malaysia.

    METHOD: Retrospective data were collected from GIOP patients referred to the Universiti Kebangsaan Malaysia Medical Centre. Fracture events and direct medical costs were compared between bisphosphonates and calcium/vitamin D combination.

    RESULTS: Fracture events were reported in 28 out of 93 included patients, with hip and vertebral fractures representing 42.9% and 35.7%, respectively. Overall, the use of bisphosphonates could not be considered cost-effective for treatment of all GIOP patients. The presence of certain fracture risk factors was able to modify the cost-effectiveness of bisphosphonates. Bisphosphonates was considered cost-effective if started in patients more than 60 years old. However, the use of bisphosphonates was not cost-effective in GIOP patients with secondary osteoporosis. The incremental cost-effectiveness ratios (ICER) of bisphosphonates in patients with risk factors of previous fracture or rheumatoid arthritis were Malaysian Ringgits (MYR) 108 603.40 and MYR 25 699.21, respectively.

    CONCLUSION: Fracture risk factors of age, previous fracture, rheumatoid arthritis and secondary osteoporosis may modify the cost-effectiveness outcomes of bisphosphonates. Bisphosphonates would be considered cost-effective in patients more than 60 years old as compared to calcium/vitamin D treatments. Further evaluation of the impact of fracture risk factors in larger populations would provide more precise information to better assist rational and economical use of anti-osteoporosis treatment in GIOP patients.
    Matched MeSH terms: Glucocorticoids/adverse effects*
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