Steroid Dose Research Articles

#3140 Investigating the impact of Anti-IL5 therapy in eosinophilic granulomatosis with polyangiitis (EGPA): a three year longitudinal perspective

Abstract Background and Aims In the randomized, placebo-controlled MIRRA trial [1] for relapsing and refractory eosinophilic granulomatosis with polyangiitis (EGPA), adjuvant therapy with 300 mg anti-IL5 mAB Mepolizumab [MEPO] for 12 months (M), accrued longer times in remission, reduced steroid exposure and reduced relapse rates [1]. The aim of this study is to analyze the outcome of 100 mg MEPO monthly s/c for a minimum of 36 months. Changes to adjuvant immunosuppression and indications for anti-IL5 class switch from MEPO 100 mg s/c to Benralizumab (BRZ) or Reslizumab (Res) were assessed. Method In this observational study, 20 EGPA patients received anti-IL5 therapy for a minimum of 36M (range 49-68M). All commenced on 100 mg s/c MEPO every four weeks. Anti-IL5 therapy switched to BRZ or Res due to partial response or intolerance. Assessment time points included MEPO commencement, 6, 12, 18, 24 and 36 months. Results Overall, there was a 50% reduction in steroid dose by 12 months. This continued to reduce to 24M, by which time 2 were off steroids and a further 10/20 (50%) on weaning dose ≤ prednisolone 5 mg/day. Mean steroid dose continued to decrease to 36 months. The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10/20 (50%) at M0 to 4/20 (20%) by M24. Clinical benefits included ANCA serology normalized in all four positive patients by 12 months. Mean eosinophil count reduced from 0.42 mg ± 0.33 × 109/L at M0 to 0.04 ± 0.03 × 109/L at 12 and 24M. BVAS reduced from median 5 [3-7], to 0 [0-1] by 24M. The change in mean FEV1 over 12 months was from (M0) 2.11 ± 0.66 to (M12) 2.39 ± 0.62 and FVC (M0) 3.42 ± 0.87 to (M12) 3.67 ± 0.93/105.60 ± 20.47 respectively. All 20 EGPA patients receiving anti -IL5 therapy, ranging from 49-68M remain on therapy. At 36M, 9 have remained on 100 mg s/c MEPO. 10 (50%) have switched to an alternative anti-IL5 agent—10 switched to benralizumab, 1 initially on benralizumab to reslizumab. 9/10 had achieved partial response prior to switch (reduction in steroids / relapse rate), 1/10 had no response.. During the duration of the study, 3 patients had a break of therapy, but all resumed anti-IL5 treatment with good response. Hence, all 20 remain on anti-IL5 beyond 24M. After 36M, one patient required cyclophosphamide along with anti-IL5 therapy for myocarditis. A further patient had Rituximab for EGPA/ Rheumatoid arthritis overlap between anti-IL5 agents. Conclusion In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 36M. By 24 months 2 are steroid free and a further 10 on weaning dose ≤5 mg. Furthermore, the number on adjuvant conventional immunosuppression reduced over the 24M (n = 4 at 24M). This study demonstrates that anti-IL5 therapy serves as a favorable model for steroid and conventional immunosuppressant minimization in EGPA. Clinical benefits of reduction in BVAS, improved pulmonary function tests and reduced serum eosinophilia were recorded. The relapsing nature of EGPA places a dependency of therapy on steroids and this study demonstrated sustained and ongoing improvement annually with continued anti-IL5 therapy. Some participants required a switch in anti-IL5 agent.

#2101 Beyond corticosteroids: rituximab in managing minimal change disease and glucocorticoid-related toxicity

Abstract Background and Aims Minimal Change Disease (MCD) is the primary cause of Nephrotic Syndrome in children, accounting for 10 to 20% of cases in adults. Glucocorticoids (GC) remain the cornerstone of treatment. Despite a positive response in the majority of patients, up to 25% experience frequent relapses, and up to 30% are GC-dependent, exposing them to significant GC-related toxicity. Rituximab has been increasingly used in these patients, although 2021 KDIGO guidelines still points to cyclophosphamide as the preferred second-line therapy. This study aims to describe a single-centre experience with RTX, examining its effectiveness and assessing its potential to reduce GC exposure. Method A retrospective cohort study was conducted on 19 patients with MCD who were considered for RTX at adult age at a tertiary hospital centre between 2015 and 2023. Patients who refused treatment, those with MCD associated with other glomerular diseases, and those with less than 6 months of follow-up post-RTX were excluded from the study. Results Twelve patients met the inclusion criteria, including 5 diagnosed before the age of 18. The mean age at RTX initiation was 38.8 ± 14.8 years, with 75% being male. The median MCD duration pre-RTX was 140.5 [18.8–353.5] months, and the median follow-up post-RTX was 18.0 [12.5–41] months. All patients had preserved renal function and exhibited GC-dependency and/or frequent relapses, with 8 patients having received prior cyclophosphamide and/or cyclosporine A (CsA) treatment. At RTX initiation, all patients were on GC therapy (median 11.1 [10–50] mg/day), with 4 also on CsA. 10 patients were in complete remission, while 2 were in a relapse phase, subsequently achieving complete remission. Various induction regimens were employed: 6 patients received 1000 mg of RTX twice within 2 weeks, 1 received a single dose of 1000 mg, and 5 received a single dose of 500 mg. Out of the 12 patients, 5 did not receive RTX maintenance administrations, while 6 received 500 mg of RTX every 6 to 9 months and 1 patient received 1000 mg every 6 months. Only one adverse event was reported, one uncomplicated upper respiratory tract infection. Regardless of the induction regimen, all patients maintained a sustained response with complete remission for the following 6 months. All the 7 patients who underwent RTX maintenance did not experience disease relapse, although 2 continued GC therapy (one due to an associated autoimmune disease). Among the 5 patients who did not undergo RTX maintenance, 3 maintained complete remission throughout the follow-up, with a mean time free from any immunosuppression of 14.8 ± 10.6 months. The other 2 patients relapsed at a mean time of 27.5 ± 0.7 months. After relapse, 1 patient resumed GC therapy, and both started RTX maintenance with 500 mg every 6 to 9 months, subsequently achieving and maintaining complete remission. Among the 12 patients, 9 discontinued GC (1 continued CsA) after an average of 5.9 ± 4.2 months post-RTX, with a mean GC-free period of 16.6 ± 13.2 months during the follow-up period. Conclusion RTX proved to be safe and effective for steroid-dependent and/or frequently relapsing MCD, even with a low induction single dose of 500 mg. This low induction regimen may be an effective and potentially preferable option to minimize toxicity. RTX can significantly reduce relapse rate and steroid dose, avoiding complications associated with extended and high-dose GC administration. Notably, this outcome was not achieved previously with cyclophosphamide or CsA. RTX maintenance therapy may not be universally required for all patients with MCD, since a long period without relapse can be observed after induction therapy. Considering the current absence of a marker for disease activity, it should be taken into account individual patient characteristics and disease severity, particularly previous relapses after RTX induction. Considering the RTX effectiveness, ability to extend remission, safety, and GC sparing ability, it should be seriously considered as the preferred second-line treatment.

#1602 Lupus nephritis multidisciplinary consultation: a new strategy for increasingly complex patients

Abstract Background and Aims Lupus nephritis (LN) is a major course of morbidity and mortality in patients with systemic lupus erythematosus (SLE), best managed by a multidisciplinary group. Recent management advances require greater collaboration between specialists and individualized treatments in severe cases. Method We conducted a retrospective, single-center study of a cohort of incident patients which were diagnosed with LN between 2015 and 2022 and began follow-up in the multidisciplinary rheumatology and nephrology consultation of our institution. Clinical and analytical characteristics at diagnosis and during follow-up were studied. The primary endpoint was complete remission rate at follow-up end, according to GLOSEN (Grupo de Estudio de Enfermedades Glomerulares de la SEN) [1] criteria. Changes in immunosuppression schemes over time were studied. Results 26 patients (92.3% women) were included. Median age at SLE diagnosis was 30.5 years [Interquartile range (IQR) 23.7 – 44.2]. Most patients were Hispanic (14 patients, 53.8%). Median time between SLE and LN diagnosis was 21 months (IQR 0-129 months). In 9 patients (34.6%), SLE and LN onset happened simultaneously. Most common renal manifestation was hematuria, which appeared in 19 patients (73.1%). Median proteinuria was 1.83 g/d (IQR 0.88-2.92) and serum creatinine level, 0.69 (IQR 0.51-1.18). Hypocomplementemia (88.5%) and positivity to anti-DNA (69.2%) were common. Most frequent classes found in renal biopsies were IV (30.8%) and V (23.1%). At LN debut, SLEDAI score, which assesses SLE manifestations, had a median value of 16 (IQR 12-20). Mycophenolate mofetil (96.2%) was the main induction agent. Intravenous steroids were administered in 14 patients (53.8%) and the rest received steroids at a dose of 0.5 mg/kg/day. Addition of another therapy, mainly tacrolimus (6 patients, 23.1%) and belimumab (4 patients, 15.4%), was needed to achieve remission in 12 patients (46.2%). In 8 of them (66.6%), treatments were added within the first 6 months. These 12 patients had less chronicity in the biopsy (median chronicity index: 0 vs. 2; p 0.004) and had higher proteinuria (median 1.41 g/day vs. 0.4 g/day; p 0.001). Likewise, SLEDAI score at 3 months was significantly higher in these 12 patients than in the standard of care group (median SLEDAI score 13 vs. 8; p 0.016). No differences were found in 3 month serum creatinine (p 0.181) or 3 month hematuria (p 0.496) After a median follow-up of 47 months, 15 (57.7%) and 9 patients (34.6%) achieved complete and partial remission, respectively. No differences in percentages of remission were observed between the 2 groups. Steroids were withdrawn in 12 patients (46.2%). Median steroid dose at the end of follow-up was 5 mg (IQR 3-5). Conclusion In our LN cohort, higher SLEDAI and proteinuria indicated the need for an individualized approach. Collaboration between Rheumatology and Nephrology specialists is essential to identify patients with these needs.

#2475 Glomerulonephritis associated with anti -TNF-α therapy

Abstract Background and Aims Biologic agents like tumor necrosis factor α inhibitors/ anti-TNF-α/, IL6 and CD80/26 are widely used in many rheumatologic diseases but these may also elicit effects on renal function. These drugs, as well as rheumatic diseases themselves, can cause autoimmune renal disorders. Though effective on the main inflammatory process the incidence of kidney injury associated with their administration is increasing. Various forms of glomerulopathies have been described in connection with biological therapy - proliferative lupus nephritis, oligo immune necrotizing crescentic glomerulonephritis, membranous glomerulonephritis, IgA nephropathy and others. Method We report the clinical and pathologic findings in two patients with Rheumatoid arthritis and Ankylosing spondylitis on biologic therapy with an anti-TNF-α agent. During the treatment they presented with nephritic syndrome requiring kidney histology. Results Case 1: The first patient is a 52-year-old man diagnosed with ankylosing spondylitis, HLA-B27 positive, 15 years before admission. Four years before admission treatment with Golimumab /anti-TNF-α/ has been initiated. During the follow-up period urine tests revealed proteinuria and hematuria, which required more detailed tests. The patient presented with clinical features of nephritic syndrome, marked lower extremity edema, hematuria, nephrotic range proteinuria, impaired hypertension control. Kidney biopsy revealed membranoproliferative glomerulonephritis. It was assumed that kidney injury was most likely associated with Golimumab therapy. Its administration was discontinued, and therapy was started with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Mycophenolate Mofetil 1500 mg was started from the third month. General condition and laboratory results improved considerably. The occurrence of stiffness and pain in the sacroiliac joints several months after stopping biologic treatment necessitated the inclusion of Sulfasalazine to the therapy. Initiation of therapy with another class of biologic agent, Anti-IL-17 monoclonal antibody, was discussed with the follow-up rheumatologists. Case 2: The second patient is a 66-year-old woman, with a history of hypertension and essential thrombocythemia, who was diagnosed with seropositive rheumatoid arthritis 3 years before admission, treated with Adalimumab /anti-TNF-α/. Follow-up examinations revealed low-grade proteinuria, hematuria and impaired renal function. Kidney biopsy revealed IgA nephropathy. Following the discontinuation of Adalimumab, the patient was treated with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Kidney function significantly improved at the third month of treatment and proteinuria was gradually reduced. Initiation of Rituximab /antiCD20/ treatment was discussed with rheumatologists. Conclusion Treatment with biological drugs can cause immune-mediated glomerular disorder/IGD/. These events are rare, and the causative effects of a specific drug is hard to establish. When a patient is suspected of having an IGD, kidney biopsy should be performed for the exact diagnosis. The drug should be discontinued, and the treatment for the new-onset renal disorder should be promptly started. A rechallenge test of the same or a similar drug should be avoided, whereas switching to a different therapy is a reasonable option.

#2623 Homeostatic Model Assessment (HOMA) in pediatric patients with nephrotic syndrome receiving tacrolimus

Abstract Background and Aims Children with nephrotic syndrome (NS) receive diabetogenic drugs like tacrolimus (TAC) and steroids. TAC is toxic to pancreatic β-cells and suppresses insulin production in a time and dose dependent manner. This is well documented in renal transplant patients who develop post-transplant diabetes mellitus (PTDM). Although overt diabetes is uncommon in children receiving TAC for NS, the subclinical effect on β cell function has not been studied. Our aim was to study pancreatic beta cell function as assessed by homeostasis model assessment (HOMA) indices in children with NS who received TAC therapy for at least 1 year duration. Method We performed a prospective descriptive study where we followed children (1-18 years) with NS who received TAC therapy for at least 1 year. We noted patient demographics, clinical and histologic pattern of NS, cumulative steroid dose (mg/kg/day) received 90 days prior and TAC C0 levels. Fasting insulin, blood sugar to calculate HOMA indices for IR (insulin resistance), HOMA % β for beta cell function, HOMA-IS (insulin sensitivity), C-peptide and HbA1C were done once at study inclusion and yearly intervals when required. Statistical analysis included Pearson's correlation, paired t test and regression analysis. Results We performed HOMA indices in 37 children (19 males, 18 females) between September 2021-February 2023. Six patients had 2 measurements during the study period. The mean age of onset of NS was 28 months (95% CI [20; 36]) and mean age at HOMA indices measurement was 69 months (95% CI [59; 79]). Of the 37 patients, 54% (20/37) had late steroid resistance, 32% (12/37) had early steroid resistance, 8% (3/37) had steroid dependent NS, 6% (2/37) had frequently relapsing NS. Kidney biopsy performed in 36 children showed minimal change disease in 55.5% (20/36) and focal segmental glomerulosclerosis in 44.5% (16/36). The mean TAC duration, TAC Co level and mean cumulative steroid dose received in last 90 days were 27 months (95% CI [22;32]), 4.54 ng/ml (95% CI [4.12;4.97]) and 0.36 mg/kg/d (95% CI [0.28;0.44]) respectively. Eleven (30%) patients had cutaneous signs of insulin resistance like acanthosis nigricans and 9 (24%) patients had fasting blood sugar of >100 mg/dl. In Pearson's correlation analysis we found positive correlation between TAC Co level, HOMA IR (r = 0.4, P = 0.008) and TAC Co, HOMA %β (r = 0.44, P = 0.003) and cumulative steroid dose, fasting blood glucose (r = 0.3, P = 0.46). There was negative correlation between TAC Co level, HOMA IS (r = −0.4, P = 0.007). In regression analysis, only TAC Co level significantly influenced all HOMA indices including insulin resistance, insulin sensitivity and beta cell function. A HbA1C of > 5.7 (pre-diabetes range) was found in 32.4% (12/37) patients which warrants further monitoring. C-peptide levels were significantly higher after 12 months of TAC therapy in 6 patients who had two measurements (p = 0.032). Conclusion Tacrolimus therapy for nephrotic syndrome in children can affect pancreatic beta cell function as assessed by HOMA indices. Long term monitoring of pancreatic beta cell function in children with NS on TAC is needed to assess the full extent of these subclinical alterations.

COVID-19 Associated Mucormycosis and Risk Factors: A Case-Control Study from Turkey

Background: Mucormycosis, a fatal fungal infection, has increased during the COVID-19 pandemic and posed significant challenges for clinicians. Objectives: Our research focused on identifying the clinical traits of patients with COVID-19-associated mucormycosis (CAM), comparing them with a control group, and identifying risk factors for the development of CAM. Methods: Our study was conducted on 39 CAM patients and 78 control patients from September 2020 to October 2022 at a tertiary education center and regional hospital. The control group was selected blindly in a 1:2 ratio among patients who did not develop mucormycosis, were hospitalized due to COVID-19, and were either discharged or deceased. The control group was matched to the case group regarding age and hospitalization date. To test potential risk factors for CAM, we performed a binary logistic regression analysis. The variables included in the multivariate binary logistic regression model were gender, diabetes, cumulative steroid dose (dexamethasone equivalent), duration of steroid treatment, and tocilizumab/anakinra treatment. Results: In our study, 39 patients were diagnosed with CAM. The average age of the patients was 66 ± 11.5 years. Of the patients, 54.7% (n = 64) were male, with a statistically significantly higher proportion of men in the CAM group (74.4% vs. 44.9%, P = 0.003). The diabetes rate was 51.3% (n = 60) among all patients, and it was higher in the CAM group (69.2% vs. 42.3%, P = 0.006). Regarding in-hospital mortality, the rate was higher in the CAM group (56.4% vs. 14.1%, P < 0.001). The median length of stay in the hospital was 37 days for the CAM group and 10 days for the control group (P < 0.001). The cumulative steroid dose was elevated in the CAM group compared to the control group (191 ± 61.4 mg vs. 117 ± 69.8 mg, P < 0.001). The duration of steroid treatment was 16.5 ± 6.2 days in the CAM group, compared to 9.8 ± 4.7 days in the control group (P < 0.001). Among CAM cases, paranasal involvement was the most common (56.4%), followed by rhino-orbital involvement (33.3%). In binary logistic regression analysis, male gender (OR, 3.9; 95% CI, 1.4 – 11.3), diabetes mellitus (OR, 4.4; 95% CI, 1.5 – 12.4), more than ten days of steroid use (OR, 5.5; 95% CI, 1.3 – 22.4), and tocilizumab/anakinra use (OR, 0.23; 95% CI, 0.06 – 0.8) were identified as risk factors for the development of CAM (p values 0.011, 0.005, 0.019, and 0.020, respectively). Conclusions: Male gender, diabetes mellitus, and steroid use for more than ten days were identified as positive risk factors, while tocilizumab/anakinra use was identified as a negative risk factor for the development of CAM.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study

PurposeRadiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. MethodsIn Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. ResultsResponse rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. ConclusionsThis Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.

Patients with Steroid Sensitive Nephrotic Syndrome: A Case Series

Nephrotic syndrome (NS) is one of the most common kidney diseases found in childhood. The prevalence of nephrotic syndrome worldwide is approximately 16 cases per 100,000 children with an incidence of two to seven per 100,000 children. Nephrotic syndrome may affect adults and children of both genders and any race. Nephrotic syndrome in children can be classified into three groups; secondary, congenital, infantile, and idiopathic. In first case, a 3-year-old male patient was presented with complaints of fever, cough for 6 days and swelling all over the body, decreased urine output, oral intake for 2 days, edema of face, body and tiredness for 3 days. Laboratory investigations showed elevated ESR, ferritin and lipid profile. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis conveyed right basal pleural effusion. In second case, a 4-year-old male patient was presented with complaints of facial puffiness, fever, breathing difficulty, abdominal distension and pain but no edema. He had history of right inguinal hernia and atrial septal defect. Cholesterol level was found to be elevated. Urine routine examination showed elevated urine albumin levels (+++). USG abdomen and pelvis showed mild ascites and right pleural effusion. Presenting third case, a 12-year-old female patient was presented with complaints of edema and decreased urine output. Patient had history of recurrent episodes of edema and decreased urine output for 11 months. Laboratory investigations showed elevated total cholesterol, declined LFT test and RFT test was found to be normal. Urine routine examination showed elevated urine albumin levels (+++), pus cells, RBC, granular cast and bacteria present. USG abdomen and pelvis indicate acute glomerulo nephritis and acute to moderate ascites. Here case series with 3 cases showed the sequence of nephrotic syndrome which is treated with corticosteroid with its side effects and cumulative dose of steroid in children. Keywords: Nephrotic syndrome, Hypocholesteremia, Hypoproteinuria, Hyponatremia, pediatric

Protocol for the systematic review of the Pneumocystis jirovecii-associated pneumonia in non-HIV immunocompromised patients.

Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy. Despite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine. The protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review of literature published between January 2010 and July 2023, using the databases PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies. It is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research. Here, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients.

The most effective corticosteroid dose in the treatment of glenohumeral osteoarthritis: Feasibility pilot and protocol for double blinded randomized controlled trial

ObjectiveOsteoarthritis affects over 5.4 million people in the United States. A common treatment is to perform intra-articular corticosteroid injections. However, the ideal steroid dose is unknown. This study aimed to pilot a corticosteroid injection protocol for primary glenohumeral OA. MethodsWe conducted a double blinded randomized feasibility pilot study. Patients with primary osteoarthritis of the glenohumeral joint were recruited and randomized to receive 20 ​mg, 40 ​mg, or 80 ​mg of triamcinolone. The primary outcome was the feasibility of the protocol and change in the Shoulder Pain and Disability Index (SPADI) 6 months following injection. Results300 patients were screened for participation with 78 meeting inclusion criteria. 19 subjects completed the study. The most common reason for not participating was concern they would receive a smaller dose than previous injections. There was a 26% dropout rate, with 2 patients undergoing a total shoulder arthroplasty. There was no clinically significant difference (p ​= ​0.090) between the groups at 6-months for the SPADI although all treatment groups showed a reduction of SPADI from baseline at 6 months. There was one adverse event in the 20 ​mg group, with a patient experiencing facial flushing after the injection. ConclusionWe were successful in developing a feasible protocol. In the future excluding those who have received previous injections would be helpful for a higher enrollment rate. This patient concern highlights the need to complete clinical trials to guide medical decisions surrounding corticosteroid administration. NCT03586687.

Laparoscopic excision of accessory spleen for recurrent autoimmune hemolytic anemia after splenectomy: a case report

BackgroundSplenectomy is indicated in cases of autoimmune hemolytic anemia (AIHA), which are refractory to medical management. In post-splenectomy, there exists a theoretical risk of AIHA recurrence, especially if an accessory spleen undergoes compensatory hypertrophy. In this context, we present a unique case of recurrent AIHA managed through laparoscopic excision of the accessory spleen (LEAS).Case presentationA 60-year-old male underwent laparoscopic splenectomy (LS) for AIHA refractory to standard medical therapies. Following the surgery, there was a marked improvement in hemolytic anemia symptoms, and oral steroid therapy was terminated 7 months post-LS. Nonetheless, a year after the LS, the patient exhibited a marked decline in hemoglobin levels, dropping to a concerning 5.8 g/dl, necessitating the reintroduction of oral steroids. A subsequent contrast-enhanced computed tomography (CT) scan unveiled an enlarged accessory spleen. The patient then underwent LEAS, during which the accessory spleen, obscured within adipose tissue, proved challenging to visualize laparoscopically. This obstacle was surmounted utilizing intraoperative ultrasonography (US), enabling successful excision of the accessory spleen. The post-surgical period progressed without complications, and the steroid dosage was reduced to one-twelfth of its initial preoperative quantity.ConclusionsRecurrent AIHA can be instigated by post-splenectomy compensatory hypertrophy of the accessory spleen. Ensuring comprehensive splenic tissue excision is crucial in AIHA management to obviate recurrent stemming from hypertrophic remnants. In scenarios of AIHA recurrence tied to an enlarged accessory spleen, LEAS stands as a viable and effective therapeutic modality.

Salvage surgery for pouch-related complication after ileal pouch–anal anastomosis: a report of two cases

BackgroundPouch-related complications (PRCs), such as pelvic abscesses and perianal complex fistulas, can occur after ileal pouch–anal anastomosis (IPAA) in ulcerative colitis (UC). They are often difficult to treat and require salvage surgery. We report two cases of PRC associated with fistulas.Case presentationFirst case: A 38-year-old man was diagnosed with UC at age 26 years. Four months after the diagnosis of UC, the patient underwent hand-assisted laparoscopic restorative proctocolectomy, IPAA, and ileostomy for acute fulminant UC. Two years after the closure of the ileostomy, the patient developed a perianal abscess and underwent ileostomy reconstruction. He was referred to our department at 35 years of age, because his symptoms did not improve despite repeated seton drainage of a complicated perineal fistula. We diagnosed PRC with a pelvic abscess and complicated pouch fistula and performed salvage surgery. This diagnosis was revised to Crohn’s disease. Second case: A 50-year-old man was diagnosed with UC at age 18 years and was administered high doses of steroids; however, his symptoms did not improve. He underwent restorative proctocolectomy, IPAA, and ileostomy at another hospital. The ileostomy was closed, and his condition stabilized thereafter. At 35 years of age, perianal pain developed, and he was diagnosed with a complicated pouch–perineal fistula. A fistula was observed near the staple line of the ileal end closure on the head side of the pouch. Reconstruction of the ileostomy and seton drainage were performed; however, his symptoms did not improve, and he was referred to our hospital. We diagnosed PRC with a pelvic abscess and a complicated pouch fistula and performed salvage surgery. The resected specimen showed strictures in two locations: at the oral site of the afferent limb (at the pouch) and at the IPAA. Both patients returned to society and are currently outpatients.ConclusionsWe encountered two cases of PRC after IPAA that did not improve with seton drainage or ileostomy. Pouch resection was performed after considering the patient’s quality of life and reintegration into society.

Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group

ObjectiveTo develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.MethodsA systematic literature review using Cochrane guidance was carried...

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.

Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer.

Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti-spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

Would hyperbaric oxygen therapy be a supportive treatment method for refractory idiopathic granulomatous mastitis?

BackgroundRefractory IGM causes patients to use antibiotics, steroid therapy, immunosuppressive agents for a very long time and even leads to surgical procedures resulting in the loss of breast tissue. Hyperbaric Oxygen Therapy (HBOT) is a frequently used method in the treatment of wounds that are difficult to heal. We thought that HBOT would be an alternative treatment method for refractory IGM patients. MethodsIt is a retrospective cohort study on refractory IGM patients conducted at three tertiary care treatment centers between January 2021 and July 2023. The patients were evaluated in two groups: those who only took steroid treatment and those who received HBOT and steroid treatment. The demographic and clinical characteristics of the patients, the types of treatment applied and their responses to treatment were evaluated. ResultsThere were no significant differences generally in the demographic and clinical features in both groups. The incidence of multicentric GM was found to be higher in the HBOT group (66.67%; p = 0.044). Although the recovery results were similar in both groups, the average daily steroid dose and duration of drug use were found to be higher in the group receiving only steroid treatment (16 mg vs. 4 mg and 270 days vs. 30 days) (p<0.001). ConclusionIn our study, we showed for the first time in the literature that HBOT is effective in the treatment of refractory IGM patients. Our study needs to be supported by prospective studies evaluating cost effectiveness and possible long term complications..

Pulmonary Cavitation as a Complication of COVID-19: Case Series and a Brief Review of the Literature

The COVID-19 pandemic has led to an unprecedented surge in respiratory illness cases worldwide. Although uncommon, pulmonary cavitation has been reported as a potential complication of COVID-19. This case series report describes four cases of COVID-19 patients with lung cavities, highlighting the various causes and clinical manifestations of this complication, and a review of the literature on the presence of lung cavities in COVID-19 patients. In two cases, the cavities were most likely due to secondary bacterial superinfections, with one case being complicated by multi-drug-resistant bacteria. Another case developed cavities secondary to a fungal infection, while the third case was directly caused by SARS-CoV-2 invasion in the lungs. The presence of cavities with or without air-fluid level or pneumothorax in COVID-19 patients should be considered as a potential complication of this infection, especially in those with respiratory symptoms. Physicians should remain vigilant for the development of pulmonary cavitation in COVID-19 patients, particularly those receiving high doses of steroids. Additionally, spontaneous pneumothorax should be considered an alarming sign in COVID-19 patients.

Comparative study on outcome of intralesional steroid and combination of intralesional steroid with 5-fluorouracil in keloid treatment

Background: Though the definitive management of keloids are not yet established, many treatment modalities have been described which are being used alone or in combination all over the world with some promise. This study aims to assess the effect of intralesional steroids and 5-fluorouracil (5-FU) in the treatment of keloids. Methods: The study included 40 patients with keloids, out of which 20 received 6 doses of intralesional steroid and the other 20 received alternating three doses of intralesional steroid and three doses of 5-FU. The size of the keloid and the POSAS (Patient observer scar assessment scale) score were marked on the proforma and the patient was reassessed after 6 months. The decrease in volume and POSAS score was statistically analysed using paired and unpaired t tests. Results: There is a statistically significant decrease in POSAS score after intervention in both the steroid and steroid+5 FU groups. However, the decrease in POSAS score is significantly more in the group that received steroids alone. The group that received steroids had a greater decrease in volume (50% reduction) compared to the group that received the steroid-5FU combination (27% reduction). Conclusions: There is a statistically significant decrease in POSAS score after intervention in both the steroid and steroid+5 FU groups. However, the decrease in POSAS score is significantly more in the group that received steroids than the group that received steroid-5 FU combination.

Managing Infection Complications in the Setting of Chimeric Antigen Receptor T cell (CAR-T) Therapy.

Chimeric antigen receptor T-cell (CAR T-cell) therapy has changed the paradigm of management of non-Hodgkin's lymphoma (NHL) and Multiple Myeloma. Infection complications have emerged as a concern that can arise in the setting of therapy and lead to morbidity and mortality. In this review, we classified infection complications into three categories, pre-infusion phase from the time pre- lymphodepletion (LD) up to day zero, early phase from day of infusion to day 30 post-infusion, and late phase after day 30 onwards. Infections arising in the pre-infusion phase are closely related to previous chemotherapy and bridging therapy. Infections arising in the early phase are more likely related to LD chemo and the expected brief period of grade 3-4 neutropenia. Infections arising in the late phase are particularly worrisome because they are associated with adverse risk features including prolonged neutropenia, dysregulation of humoral and adaptive immunity with lymphopenia, hypogammaglobinemia, and B cell aplasia. Bacterial, respiratory and other viral infections, protozoal and fungal infections can occur during this time . We recommend enhanced supportive care including prompt recognition and treatment of neutropenia with growth factor support, surveillance testing for specific viruses in the appropriate instance, management of hypogammaglobulinemia with repletion as appropriate and extended antimicrobial prophylaxis in those at higher risk (e.g.high dose steroid use and prolonged cytopenia). Finally, we recommend re-immunizing patients post CAR-T based on CDC and transplant guidelines.

Comparison of Hyperglycemic Effects of Antenatal Administration of Dexamethasone in Gestational Diabetes: A Study of Recommended Versus Predicted Split Doses Regimens

Objective: To compare three consecutive days of hyperglycemic response following antenatal Dexamethasone regimens of 12mg or 6mg in diet-controlled gestational diabetes, administered for fetal lung maturity. Study Design: Quasi-experimental study Place and Duration of Study: Department of Obstetrics and Gynaecology, Combined Military Hospital, Kharian Pakistan, from Oct 2020 to Mar 2021. Methodology: Forty women who met inclusion criteria were selected and assigned to two Groups. Group-A was administered quartered 24 mg steroids 6 hours daily, and Group-B was administered halved 24mg 12 hours daily. Blood sugar levels (BSL) were recorded before and after meals, thrice a day for three consecutive days, and on proforma. Results: Among the selected patients, the mean age was 25.5±2.9 years, and the mean gestational age (duration of pregnancy) was 30.3±2.0 weeks. Out of six blood sugar levels recorded daily for three consecutive days, the episodes of hyperglycemia in the (Group-B) 12-hourly steroid dose were found to be less significant than those in the (Group-A) split 6-hourly dose. Conclusion: The recommended 12 mg, twice-a-day regimen of antenatal corticosteroids was better than the proposed 6mg, four times a day regimen as it caused fewer hyperglycemic episodes in gestational diabetics.