Steroid Withdrawal Research Articles

Pediatric Topical Steroid Withdrawal Syndrome: What Is Known, What Is Unknown.

Topical steroid withdrawal syndrome (TSW) is a debated condition marked by burning erythema, severe itching, and dry skin following the discontinuation of topical corticosteroids (TCS). This study reviewed reported pediatric TSW cases. With a total of 21 cases reported (inconsistent data provided), 60% (6/10) used TCS on the face; 69% (9/13) were associated with an escalation in potency of TCS and 75% (3/4) were the erythematoedematous variant. Overall, data on TSW in children is lacking and standardized diagnostic criteria are needed.

Profiles of peripheral regulatory T cells forecasts the feasibility of steroid withdrawal after liver transplantation based on cellular thermal modeling

After liver transplantation, steroid therapy is often used to prevent rejection. However, long-term steroid use can lead to serious side effects, therefore, this study aimed to evaluate the feasibility of peripheral regulatory T cell profiles for steroid discontinuation after liver transplantation through cellular thermal modeling and real-time monitoring of intracellular thermodynamics. In this study, cellular thermal modeling techniques were used to simulate the thermodynamic characteristics of peripheral TREgs under different conditions. The dynamic changes of peripheral Treg in liver transplantation animal models were monitored by flow cytometry and molecular biology. Significant changes in peripheral Treg profiles were observed after initiation of steroid therapy, especially in the discontinuation group, and these changes were strongly associated with the restoration of immune homeostasis. Real-time monitoring of the thermodynamic data revealed that peripheral Treg activity showed a specific temperature dependence in the cellular thermal model. Cell thermal modeling combined with real-time monitoring of intracellular thermodynamics provides a new perspective for evaluating the feasibility of peripheral regulatory T cell profiles for steroid discontinuation after liver transplantation. Strengthening the dynamic monitoring of peripheral Treg spectrum provides an important basis for the formulation of personalized immunosuppression strategies, and improves the therapeutic effect and quality of life of liver transplant patients.

A Case Report of Systemic Steroid Therapy for False Brain Tumors in Children

Study design: Case report. Purpose: to study the efficacy of systemic steroid in pediatric pseudotumor cerebri. Introduction: Pseudotumor cerebri is a condition caused by elevated intracranial pressure presenting most commonly with headache. It is a diagnosis of exculsion. Methods: A 15 year old girl presented in our OPD with headache since 3months, more in the posterior aspect, continuous type with severe intensity, non - radiating. On examination, her best corrected visual acuity in right eye was 6/9 and left eye was 6/6parts. She had normal anterior segment, normal IOP. Fundoscopy showed both optic discs edematous, pink in color with blurry disc margins, tortuous disc vessels, edematous peripapillary area. Rest of the retina was normal. Lumbar puncture showed elevated opening CSF pressure and normal CSF composition. Hence, she was diagnosed with IIH. She was started on oral prednisolone 1mg/kgbw once a day dosage, oral acetazolamide 250mg once a day, topical nepafenac 0.1% one drop thrice a day and timolol 0.5% eye drops twice a day. Discussion: The main goals of treatment are alleviation of symptoms, including headache, and preservation of vision. Steroids were commonly used for treating IIH in the past, but cause significant long - term side effects, such as weight gain, that are undesirable in IIH patients. Furthermore, withdrawal of steroids can cause rebound intracranial hypertension. Thus, steroids should not be used routinely for IIH treatment. Results: By the end of one month, patient was relieved of symptoms, best corrected visual acuity was 6/6 in both eyes with normal IOP, normal optic disc in both eyes. Conclusion: Steroids are an effective way of managing idiopathic intracranial hypertension in pediatric patients.

Assessing Long-Term Adverse Outcomes in Older Kidney Transplant Recipients: A Propensity Score-Matched Comparison of Early Steroid Withdrawal Versus Continuous Steroid Immunosuppression Using a Large Real-World Database.

Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2±3.7 years (ESW) and 69.2±3.4 years (SCI, p=0.96). The Kaplan-Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p=0.01) and 3 years (34.89% vs 44.29%, p=0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p=0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p=0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p<0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects.

Evaluating the Impact of Steroid Withdrawal on Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Evaluating the Impact of Steroid Withdrawal on Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

6409 Successful Treatment Of Severe Ectopic ACTH-dependent Cushing’s Syndrome With Osilodrostat

Abstract Disclosure: K.A. Lee: None. C. Mendes Pessoa: None. W. Huang: Consulting Fee; Self; WH, Honoraria from Consulting and Speaking received from Recordati Rare Disease. Background: Cushing’s syndrome due to ectopic ACTH secretion is rare and may progress rapidly, making treatment very challenging. Previous case reports have described therapeutic options including adrenal steroidogenesis inhibitors, bilateral adrenalectomy (BAL), and adrenal embolization with success. Clinical Case: A 27-year-old woman with metastatic neuroendocrine tumor presented with sudden onset and rapidly progressing symptoms of fatigue, muscle weakness, acne and weight gain within two weeks. Laboratory findings confirmed severe Cushing’s syndrome due to ectopic ACTH secretion: AM cortisol 173.4 µg/dL (5-25), ACTH 1425 pg/mL (7.2-63.3), 24 hour urine cortisol 29,498 mcg/24hr (4-50), DHEA-Sulfate 1314 µg/dL (65 - 380), and testosterone 133 ng/dL (0-100). She was also found to have severe hypokalemia, hypocalcemia and hyperglycemia (despite an HbA1C of 6.2 at 2 weeks before presentation). CT- scan showed diffuse thickening of the bilateral adrenal glands. Due to widely metastatic disease in the peritoneum, BAL was considered non-feasible. The patient was admitted to hospital and initiated on osilodrostat at 20mg twice daily (after correction of hypokalemia) with close monitoring of her electrolytes, cortisol, EKG and steroid withdrawal symptoms. There was a rapid improvement of cortisol levels in response to osilodrostat. During treatment, she developed steroid withdrawal symptoms for which she was started on medium dose hydrocortisone. Bilateral adrenal arterial embolization was attempted but ultimately needed to be converted to right only adrenal gland embolization due to a hypertensive urgency and difficulty with catheterization. Her symptoms of Cushing’s syndrome significantly improved with the treatment. During her hospitalization, her hypokalemia was managed with spironolactone and potassium supplement, hypocalcemia with calcium supplement, and hyperglycemia with basal and bolus insulins. With significant improvement of cortisol levels, her hypocalcemia and hyperglycemia resolved and required no further treatment. Her potassium levels normalized and spironolactone was stopped. She remains on potassium supplement to keep K level at upper half of normal range to avoid long QTc. After discharge, her morning cortisol levels (before morning dose of hydrocortisone) continued to decrease and her osilodrostat dose was gradually tapered to 5mg once daily at night. Hydrocortisone was continued as part of the block-and-replace regimen. Conclusion: This case described a unique sudden onset and rapid progression of ectopic ACTH dependent Cushing’s syndrome and successful utilization of a block-and-replace approach by using the steroidogenesis inhibitor osilodrostat in prompt control of the hypercortisolism and related comorbidities. We also explored the feasibility of adrenal embolization for definitive management in the context of unfeasible BAL. Presentation: 6/2/2024

7071 Cushing disease presenting with Dilated Cardiomyopathy

Abstract Disclosure: H. Majeed: None. C. Nguyen: None. R. Galagan: None. D. Lovre: None. Background: Hypercortisolism manifests with numerous ways due to the wide distribution of glucocorticoid receptors. Here we describe a case of Cushing’s disease presenting with reversible non-ischemic cardiomyopathy. Case Presentation: A 30-year-old male presented to ER with palpitations, dyspnea, and atypical chest pain. His exam was notable for a BMI of 30.26 kg/m2, HR 76 bpm and BP of 200/110 mm Hg. His EKG revealed Left ventricular hypertrophy. Echocardiogram (ECHO) showed an EF of 25-30% with diffuse hypokinesis. An angiogram demonstrated normal coronary anatomy. He was started on Lisinopril, Carvedilol, and Spironolactone for non-ischemic cardiomyopathy. He also complained of a 40 lb weight gain, loss of libido, hot flashes and breast tenderness. He was referred to endocrinology. Initial evaluation demonstrated total testosterone (TT) of 171 ng/dl (286-1511 ng/dl), FSH 3.8 IU/L (2-12 IU/L), LH 5.6 IU/L (2-9 IU/L) consistent with secondary hypogonadism. Further pituitary workup revealed AM cortisol level 31.22 mcg/dl (4.3-22.4mcg/dl), ACTH 79 pg/ml (7.2 - 63.3pg/ml), IGF-1 257 ng/mL (88-246 ng/mL), Prolactin 23.7 ng/dl (2.1- 17.7ng/dl), TSH 0.54 mIU/l (0.35-3.74mIU/l) and FT4 0.6 ng/dl (0.76-1.46 ng/dl). A 24hr urine cortisol was 167 ug(0-50ug/24h) and midnight salivary cortisol 0.160 ug/dl (&amp;lt;0.010-0.090 ug/dl). An overnight 1mg dexamethasone suppression test (DST) resulted in AM cortisol of 20.95 mcg/dl (&amp;lt;1.8mcg/dl) and 8mg DST cortisol fell from 34 mcg/dl to 4.16 mcg/dl. A pituitary MRI revealed a left 6 mm x 4 mm microadenoma. He was treated with levothyroxine pre-op for central hypothyroidism. He underwent transsphenoidal resection of the pituitary adenoma. Post-op AM cortisol was 1.1 mcg/dl. His steroid withdrawal syndrome was treated with a prolonged course of tapered hydrocortisone. Two months post-op ECHO showed EF of 55-60%. His BP normalized on carvedilol alone. Eighteen months post-op he no longer required any hormone replacement. Repeat ACTH 24.4 pg/ml, Total Testosterone 584ng/dl, TSH 0.57 mIU/l and FT4 0.93 and 24hr urine cortisol was 24ug/dl, MN salivary cortisol &amp;lt;0.10 ug/dl confirming remission of his cushing's disease and resolution of secondary hypogonadism and hypothyroidism. Conclusion: Prolonged hypercortisolism can cause abnormal cardiac remodeling resulting in cardiomyopathy. Surgical remission of Cushing’s disease reverses hypercortisolism which may restore normal cardiac function. Presentation: 6/2/2024

12343 Cardiac Function Recovery Following Left Adrenalectomy For A Pheochromocytoma With Ectopic ACTH Syndrome

Abstract Disclosure: T.D. Williams: None. D. Lovre: None. R.C. Galagan: None. Background: Pheochromocytoma and Cushing’s Syndrome are implicated in Non-ischemic Cardiomyopathy/Heart Failure with reduced Ejection Fraction (NICM/HfrEF) due to catecholamine induced hypertension and cardiomyocyte toxicity. Subsequent hypoxia and calcium overload in cardiomyocytes results in oxidative stress and cell death. Excess cortisol secretion increases angiotensin II, causing hypertrophy. Subsequent increases in atrogin I lead to myo-fibrinolysis and fibrosis. We present a patient with NICM/HFrEF due to both catecholamine excess and ectopic ACTH syndrome from an adrenal pheochromocytoma. Following adrenalectomy, systolic cardiac function returned to normal. Clinical Case A 42-year-old female was referred to endocrinology after a hypertensive emergency concurrent with NSTEMI, NICM, and HFrEF (EF 45%). Initial work up revealed: Troponin I 0.49 ng/ml; (0 - 0.04 ng/ml), Na+ 140 mmol/L; (136 - 144 mmol/L), K+ 2.3 mmol/L; ​​(3.7 - 5.2 mmol/L), CO2 41 mmol/L; (23 - 29 mmol/L), Glucose 53 mg/dL; (64 - 100 mg/dL), Cortisol 57.2 ug/dL; (5 - 25 ug/dL), ACTH 363.7 pg/mL; (7.2 - 63.3 pg/mL). She failed both 1 mg and 8 mg overnight dexamethasone suppression tests: 0800 cortisol 48.5 ug/dL (&amp;lt; 1.8 ug/dL) &amp; 56.8 ug/dL (&amp;gt; 50% decrease in baseline cortisol level of 57.2 ug/dL) consistent with ectopic ACTH syndrome. Elevated plasma normetanephrine 0.98 nmol/L; (0 - 0.89 nmol/L) and chromogranin A 250 ng/mL; (0 - 103 ng/mL) suggested a neuroendocrine tumor. Pituitary MRI revealed a normal pituitary gland. Abdominal MRI detected a 3.6 x 2.5 cm left adrenal nodule and PET/CT CU-64 showed increased activity (Krenning 4) consistent with a pheochromocytoma. Notwithstanding Ketoconazole (200 mg/day) for 7 months, her EF fell to a low of 15-20%. A left adrenalectomy was performed and post-op 0800 cortisol was 12.3 ug/dL (6.0 - 26.0 ug/dL). Oral hydrocortisone was initiated at 20 mg QAM/10 mg QPM for steroid withdrawal syndrome, tapered over 8 months and withdrawn when a cosyntropin stimulation test 60-min cortisol was 19.3 ug/dL; (&amp;gt;18.0 ug/dL). Eleven months post op, her 0800 cortisol was 8.8 ug/dL and ACTH 27.4 pg/mL. One month post-op, TTE showed EF: 15-20%, six months post-op EF: 25-30%, eight months post-op EF: 35-40% and 15 months post-op EF was normal at 50%. Her heart failure symptoms resolved, and her activity returned to normal. Conclusion This case illustrates a remarkable restoration of cardiac function following resection of a pheochromocytoma. Our patient's case is unique due to the restoration of cardiac function despite the dual impact of excessive catecholamines and cortisol. Our patient’s clinical course contributes to an evolving understanding of cardiomyopathy associated with pheochromocytoma and ectopic ACTH syndrome and highlights the potential for cardiomyopathy reversal with targeted endocrine surgical and medical interventions. Presentation: 6/1/2024

Berberine Inhibits the Inflammatory Response Induced by Staphylococcus aureus Isolated from Atopic Eczema Patients via the TNF-α/Inflammation/RAGE Pathways.

Atopic eczema patients exhibit high levels of Staphylococcus aureus (S. aureus) skin colonization. S. aureus can stimulate macrophages and the expression of proinflammatory cytokines. Berberine (BBR), an alkaloid, attenuates S. aureus toxin production. This study investigated if BBR suppressed bacterial growth and inflammatory response induced by eczema-patient-derived S. aureus using murine macrophage (RAW 264.7) and human monocyte cell lines (U937). RAW 264.7 and U937 were treated with BBR at different concentrations and stimulated with heat-killed S. aureus (ATCC #33591) or S. aureus derived from severe eczema patients (EC01-EC10), who were undergoing topical steroid withdrawal, for 24 h. TNF-α protein levels were determined by ELISA, gene expression by qRT-PCR, cell cytotoxicity by trypan blue excursion, and reactive oxygen species (ROS) levels by fluorometric assay. BBR showed a bacteriostatic effect in S. aureus (ATCC strain #33591 and clinical isolates (EC01-EC10) and suppressed TNF-α production in RAW 264.7 and U937 cells exposed to heat-killed S. aureus (ATCC and clinical isolates) dose-dependently without any cell cytotoxicity. BBR (20 µg/mL) suppressed >90% of TNF-α production (p < 0.001), downregulated genes involved in inflammatory pathways, and inhibited S. aureus ROS production in U937 and RAW 264.7 cells (p < 0.01). BBR suppresses S. aureus-induced inflammation via inhibition of TNF-α release, ROS production, and expression of key genes involved in the inflammatory pathway.

Association of early steroid withdrawal with kidney transplant outcomes in first-transplant and retransplant recipients.

Early steroid withdrawal (ESW) is often preferred over conventional steroid maintenance (CSM) therapy for kidney transplant recipients with low immunological risks because it may minimize immunosuppression-related adverse events while achieving similar transplant outcomes. However, the risk-benefit balance of ESW could be less favorable in retransplant recipients given their unique immunological risk profile. We hypothesized that the association of ESW with transplant outcomes would differ between first-transplant and retransplant recipients. To assess whether the impact of ESW differs between first and retransplant recipients, we studied 210 086 adult deceased-donor kidney transplant recipients using the Scientific Registry of Transplant Recipients. Recipients who discontinued maintenance steroids before discharge from transplant admission were classified with ESW; all others were classified with CSM. We quantified the association of ESW (vs. CSM) with acute rejection, death-censored graft failure, and death, addressing retransplant as an effect modifier, using logistic/Cox regression with inverse probability weights to control for confounders. In our cohort, 26 248 (12%) were retransplant recipients. ESW was used in 30% of first-transplant and 20% of retransplant recipients. Among first-transplant recipients, ESW was associated with no significant difference in acute rejection (aOR=1.04 [95% CI=1.00-1.09]), slightly higher hazard of graft failure (HR=1.09 [95% CI=1.05-1.12]), and slightly lower mortality (HR=0.93 [95% CI=0.91-0.95]) compared to CSM. Nonetheless, among retransplant recipients, ESW was associated with notably higher risk of acute rejection (OR=1.42 [95% CI=1.29-1.57]; interaction p<0.001) and graft failure (HR=1.24 [95% CI=1.14-1.34]; interaction p=0.003), and similar mortality (HR=1.01 [95% CI=0.94-1.08]; interaction p=0.04). In retransplant recipients, the negative impacts of ESW on transplant outcomes appear to be non-negligible. A more conservatively tailored approach to ESW might be necessary for retransplant recipients.

53268 Analysis of Google Search Trends on Topical Steroid Withdrawal Syndrome

53268 Analysis of Google Search Trends on Topical Steroid Withdrawal Syndrome

Real-Life Clinical Outcomes of Benralizumab Treatment in Patients with Uncontrolled Severe Asthma and Coexisting Chronic Rhinosinusitis with Nasal Polyposis.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p < 0.001), steroid cycles by 84% (p < 0.001), emergencies visit by 83% p < 0.001) and admissions by 76% (p < 0.001), improving all the scales for asthma control, (p < 0.001). In terms of lung function, differences were observed in FVC% (p < 0.001), FEV1% (p < 0.001), and FEV1/FVC% (69.5 ± 10 vs. 74 ± 10, p < 0.001). In relation to CRSwNP, differences were observed in SNOT-22 (54.66 ± 17 vs. 20.24 ± 9, p < 0.001), VAS obstruction (7.91 ± 1 vs. 1.36 ± 1, p < 0. 001), VAS drip (7.76 ± 1 vs. 1.38 ± 1, p < 0.001), VAS anosmia (7.66 ± 1 vs. 1.38 ± 1, p < 0.001) and VAS facial pressure (7.91 ± 1 vs. 1.22 ± 1, p < 0.001). The mean FEOS score after treatment was 73 ± 14. A complete response/super response was achieved in 33 patients (57%), good response in 16 (28%) and partial response in 9 (15%). Conclusions: The administration of benralizumab to patients with uncontrolled severe asthma associated with CRSwNP has been demonstrated to improve nasal symptoms, asthma control and lung function. This resulted in a reduction in the need for oral steroids, maintenance and rescue medication, emergency room visits, and hospital admissions, with 57% of patients achieving the clinical remission criteria.

A Histological Study of the Effects of Administration and Withdrawal of Anabolic Androgenic Steroid (Nandrolone Decanoate) on the Hippocampus and the Prefrontal Cortex in Adult Male Albino Rats

Abstract Background The PFC and the hippocampus are parts of the limbic systems and have a major role in emotion regulation, memory and learning. Anabolic androgenic steroids (AASs) are large groups of synthetic derivatives of testosterone, prescribed for the treatment of male hypogonadism. Common abuse of AASs has spread among the general population and Aim of the Work The aim of the current work was to study the effects of AASs on the PFC and the hippocampus histologically and statistically and to evaluate the reversibility of these effects in these regions after AASs withdrawal. Material and Methods 24 adult male albino rats (3 – 6) months old (weighing 200-225 gm) were used in the current study and divided into 3 groups; according to the procedure and treatment type: control group (I) (12 rats) and AASs treated group (II) (6 rats) and Withdrawal group (III) (6 rats). Fixation for the brain using bouin solution was done first in situ followed by its removal and transfer to a glass bottle containing bouin solution for 24 hours to ensure complete fixation. The PFC and the hippocampi were obtained through parasagittal section. Specimens were processed for preparation of paraffin blocks then stained with H&amp;E stain and immunohistochemically stained for GFAP antibody. Image analysis &amp;morphometry were performed on stained sections for; number of surviving pyramidal neurons and the mean area percentage of GFAP staining. Results On examination of H&amp;E-stained sections of control groups, the PFC was formed of the six- layers, the molecular layer, outer granular layer, outer pyramidal layer, inner granular layer, inner pyramidal layer and the multiform layer. The Hippocampus was formed of two components: the dentate gyrus (DG), the hippocampus proper (Cornu Ammonis, with its four regions: CA1, CA2, CA3 and CA4). The cells forming the hippocampus proper were arranged in three layers; the molecular, the pyramidal and the polymorphic layers. In immunohistochemically stained section, the present work showed minimal apparent immune-reaction in the cytoplasm and processes of astrocytes in the PFC and CA1 region of the hippocampus in the control group. On examination of H&amp;E-stained sections of the AASs treated groups, signs of neuronal damage were observed. The inner pyramidal layer of the PFC and the pyramidal layer of CA1 region of the hippocampus revealed abnormal shrunken pyramidal cells having deeply stained nuclei, peri-cellular spaces and flame like appearance with pointed end. Moreover, these layers demonstrated also normal pyramidal cells showing also large rounded open vesicular nuclei and prominent nucleoli. Immunohistochemically stained sections of the treated group in both regions showed apparent extensive brownish immunostaining of the astrocytes with ramifying processes along the layer. Examination of H&amp;E-stained sections of the withdrawal group revealed the inner pyramidal layer of the PFC and the pyramidal layer of CA1 region of the hippocampus showing normal pyramidal cells having large rounded open vesicular nuclei, prominent nucleoli and apical dendrites. It also showed dark irregular cells having deeply stained nuclei, peri- cellular spaces and flame like appearance with pointed end. Immunohistochemically stained section of the treated group in both regions showed apparent minimal brownish immunostaining of the astrocytes. Conclusion Results of the present experimental study demonstrated that AASs (in the form of ND) administration affecting the PFC and the hippocampus resulted in several histopathological and morphometric harmful effects which regressed to a lesser extent through its withdrawal after 2 weeks.

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: AUNOS database study.

The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p<0.001), 3-year (6.0 vs. 4.3%, p<0.001) and 5-year follow-up (7.7 vs. 6.4%, p=0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p=0.0005), 3-year (7.6 vs. 5.5%, p<0.001) and 5-year follow-up (11.5 vs. 8.8%, p<0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p=0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p=0.53) or 5-year follow-up (7.2 vs. 8.1%, p=0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p=0.98) and at 3 years (5.5 vs. 5.4%, p=0.45), respectively. Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

The successful use of rituximab in IgA nephropathy patients with podocytopathy: a case series.

Immunoglobulin A nephropathy (IgAN) with podocytopathy is a rare pathological type of glomerular disease. The use of rituximab (RTX) in the treatment of glomerular diseases has increased in recent decades, but the efficacy of RTX in the treatment of patients with IgAN and podocytopathy has rarely been reported. This was a single-centre retrospective study of IgAN patients with podocytopathy who were treated with RTX as second-line therapy was conducted at our centre from 2019 to 2022. The aim of this study was to investigate the efficacy and safety of RTX in IgAN patients with podocytopathy. Seven out of eight patients met the criteria for complete remission following RTX therapy. Only one patient experienced adverse events (infectious diarrhoea and pulmonary infection) and experienced relapse 6 months after RTX therapy. The maximum relapse-free time after RTX therapy was 20 months, while the maximum relapse-free time before RTX therapy was only 6 months. The number of relapses before RTX therapy (per year) was one to four; moreover, seven patients did not relapse and maintained remission at the last follow-up despite steroid withdrawal after RTX therapy. Overall, RTX effectively reduced proteinuria, increased the maximum relapse-free time, reduced the number of relapses per year and helped patients stop steroid use as soon as possible. RTX also helped most patients achieve clinical remission. RTX appears to be an effective and safe alternative for treating IgAN patients with podocytopathy with steroid dependence or frequent relapse.

CO138 Impact of Steroid Withdrawal at Various Time Points After Liver Transplantation on Diabetes Mellitus: A Population-Based Cohort Study in South Korea

CO138 Impact of Steroid Withdrawal at Various Time Points After Liver Transplantation on Diabetes Mellitus: A Population-Based Cohort Study in South Korea

Risk of topical steroid withdrawal reactions

Risk of topical steroid withdrawal reactions

#2205 Varying practice patterns in prevention, screening and treatment of diabetes early after kidney transplantation: a European survey

Abstract Background and Aims Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there is no consensus on preventive measures, nor on the optimal screening and treatment strategy. Method The European Renal Association—DESCARTES working group—distributed a web-based survey to transplant centers across Europe to gather information on the risk assessment, screening procedures and management practices for the prevention and treatment of PTDM in kidney-transplant recipients. Results Answers were obtained from 121 transplant centers across 15 European countries. Screening practices for pre-existing diabetes during the transplant work-up varied considerably, with only 13% of centers using the recommended oral glucose tolerance test (OGTT), while 14% did not screen at all. At transplantation, 19% (n = 23) of centers tailored the immunosuppressive regimen based on perceived PTDM risk, employing strategies like cyclosporin use (12/23), or early steroid withdrawal (2/23). Fifty-two percent adopted strict glycemic control with long-acting insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days—six months), mostly based on fasting glycemia and/or HbA1c, while only 8/82 incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycemia (&amp;lt;45 days) and by 58% in established PTDM (&amp;gt;45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycemia (&amp;lt;45 days) and PTDM (&amp;gt;45 days). Conclusion This European survey underscores significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for clearer guidance in approaching this complication.

Changes in thoracic radio density after living donor liver transplantation.

The outcomes after liver transplantation have greatly improved, which has resulted in greater focus on improving non-hepatic outcomes of liver transplantation. The present study aimed to evaluate thoracic spine radio density in children and adolescents after liver transplantation. A total of 116 patients who underwent living donor liver transplantation were retrospectively analyzed. The radio density at the eleventh thoracic vertebra was measured using computed tomography scan performed preoperatively then annually for 5 years postoperatively and subsequently every 2 or 3 years. The mean thoracic radio density of male recipients of male grafts had the lowest values during the study. The radio density of patients receiving a graft from a female donor was higher than in recipients with grafts from males. Total mean radio density decreased for first 5 years postoperatively and then increased. Changes in radio density were equally distributed in both steroid withdrawal and no steroid withdrawal groups for 5 years, after which patients with steroid withdrawal had a greater increase. Changes in radio density were equally distributed in both the steroid withdrawal and no steroid withdrawal groups up to age 20, after which patients in the steroid withdrawal group had a greater increase. Gender differences may affect the outcome of radio density changes after transplantation. Given the moderate association between thoracic radio density and bone mineral density in skeletally mature adults and further studies are needed to validate this relationship between thoracic radio density and bone mineral density changes in pediatric liver transplantation.

Steroid as a Saviour and Culprit in Pemphigus Vulgaris Therapy: A Rare Case Series

Introduction: Pemphigus is a group of autoimmune dermatological life-threatening diseases of which Pemphigus Vulgaris (PV) is the most common (1-5 cases/million/year) with a mortality rate of 60-90%. PV is generally characterized by painful oral erosions, along with or without cutaneous lesions, as blisters are often misdiagnosed. The management strategy of PV includes steroids along with adjuvant therapy. Case Presentation: We report the case of three female patients with a mean age of 30.67 years who were diagnosed with pemphigus vulgaris and was on steroid therapy for a long duration. The longterm steroid therapy in all these three patients resulted in adverse drug reactions such as Cushing syndrome, oral and vaginal candidiasis. Although the steroid was found to cause ADR among these patients, the treatment with steroids and rituximab was continued. The withdrawal of steroids results in flare-up conditions, whereas the addition of rituximab serves as a steroid sparring partner in the management of PV. However, premedication was administered before the infusion of rituximab to prevent potential toxicity associated with rituximab. Further, administration of pulse therapy over oral dosing of steroids lowers the risks of ADR and long-term complications associated with steroids. Conclusion: As PV requires the management with high doses of steroids along with the immunosuppressant, patients are more prone to developing drug-related problems. Hence, the rigorous monitoring of the therapy is vital to prevent adverse effects of long-term therapy. Clinical pharmacists and pharmacologists are the most suitable pillar of the healthcare system for drug therapy management.