Frequent Steroid Research Articles

Persistent hypoglycemia in patients with liver cancer.

Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon. Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.

Impact of steroids on the immune profiles of children with asthma living in the inner-city.

Background: Inner-city asthma is associated with high morbidity and systemic steroid use. Chronic steroid use impacts immune function; however, there is a lack of data with regard to the extent of immunosuppression in patients with asthma and who are receiving frequent systemic steroids. Objective: To identify the impact of frequent systemic steroid bursts on the immune function of children with asthma who live in the inner city. Methods: Children ages 3-18 years with asthma were divided into study (≥2 systemic steroid bursts/year) and control groups (0-1 systemic steroid bursts/year). Lymphocyte subsets; mitogen proliferation assay; total immunoglobulin G (IgG) value, and pneumococcal and diphtheria/tetanus IgG values were evaluated. Results: Ninety-one participants were enrolled (study group [n = 42] and control group [n = 49]). There was no difference in adequate pneumococcal IgG value, diphtheria/tetanus IgG value, mitogen proliferation assays, lymphocyte subsets, and IgG values between the two groups. Children who received ≥2 steroid bursts/year had a significantly lower median pneumococcal IgG serotype 7F value. Most of the immune laboratory results were normal except for the pneumococcal IgG value. Most of the participants (n/N = 72/91 [79%]) had an inadequate pneumococcal IgG level (<7/14 serotypes ≥1.3 µg/mL). The participants with inadequate pneumococcal IgG level and who received a pneumococcal polysaccharide vaccine 23 (PPSV23) boost had a robust response. There was no significant difference in infection, steroid exposure, asthma severity, or morbidities between those with adequate versus inadequate pneumococcal IgG values. Conclusion: Children with asthma who live in the inner city and receive ≥2 steroid bursts/year do not have a significantly different immune profile from those who receive ≤1 steroid bursts/year do not have a significantly different immune profile from those who do not. Although appropriately vaccinated, most participants had an inadequate pneumococcal IgG level, regardless of steroid exposure and asthma severity. These children may benefit from PPSV23.

Diagnosis and management of secondary adrenal crisis.

Adrenal crisis (AC) is a life threatening acute adrenal insufficiency (AI) episode which can occur in patients with primary AI but also secondary AI (SAI), tertiary AI (TAI) and iatrogenic AI (IAI). In SAI, TAI and IAI, AC may develop when the HPA axis is unable to mount an adequate glucocorticoid response to severe stress due to pituitary or hypothalamic disruption. It manifests as an acute deterioration in multi-organ homeostasis that, if untreated, leads to shock and death. Despite the availability of effective preventive strategies, its prevalence is increasing in patients with SAI, TAI and IAI due to more frequent exogenous steroid administration, pituitary immune-related effects of immune checkpoint inhibitors and opioid use in pain management. The delayed diagnosis of acute AI which remains infrequently suspected increases the risk of AC. Its main precipitating factors are infections, emotional distress, surgery, cessation or reduction in GC doses, pituitary infarction or surgical cure of endogenous Cushing's syndrome. In patients not known previously to have SAI/TAI/IAI, recognition of its symptoms, signs, and biochemical abnormalities can be challenging and cause delay in proper diagnosis and therapy. Effective therapy of AC is rapid intravenous administration of hydrocortisone (initial bolus of 100mg followed by 200mg/24h as continuous infusion or bolus of 50mg every 6h) and 0.9% saline. In diagnosed patients, preventive education in sick-day rules adjustment of glucocorticoid replacement and hydrocortisone parenteral self-administration must be performed repeatedly by trained health care providers. Strategies to improve the adequate preventive education in patients at risk for secondary AI should be promoted in collaboration with various medical specialist societies and patients support associations.

P833 Burden of steroid use in patients with moderate ulcerative colitis in Europe and the United States

Abstract Background Steroids are an effective short-term therapy option for induction of remission of ulcerative colitis (UC). However, long-term and frequent steroid use is common in clinical practice despite the risks of complications and adverse events.1 We aimed to describe disease burden in moderate UC patients (pts) based on their steroid use history. Methods Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their pts in France, Germany, Italy, Spain, the UK and US from Jan 2020–Mar 2021. GIs reported patient demographics, clinical characteristics, treatments and healthcare resource utilization (HCRU). Pts reported quality of life (QoL) via the EQ-5D, short inflammatory bowel disease questionnaire (SIBDQ), and work productivity and activity impairment (WPAI) questionnaire. Pts had received 5-ASA or immunomodulator with no biologic or Janus kinase inhibitor in the 90 days following treatment initiation, had a history of physician-assessed moderate disease severity or a Mayo endoscopic subscore of 2, and no history of colectomy. Pts were categorized as: no steroids (NS; never received steroids), short term/intermittent (ST/I; currently receiving intermittent steroids or received steroids within the last two years for &amp;lt;90 days), or long term/escalated (LT/E; received steroids for ≥90 days within the last two years or had undergone steroid dose escalation within their current course). Analyses were descriptive. Results Overall, 217NS, 88 ST/I and 172 LT/E pts were analysed (Table 1). Median (interquartile range) total steroid use duration was 4.1 (1.6–22.3) months for ST/I and 14.9 (5.8–36.7) months for LT/E. NS (24.4%), ST/I (25.0%) and LT/E (26.2%) pts experienced abdominal pain; 0.5%, 4.6% and 5.2% had severe/extremely severe pain, respectively. Non-bloody diarrhoea was reported by 16.6%, 14.8%, 20.9% of pts, respectively. In the last 12 months, mean (standard deviation; SD) number of health care visits for NS, ST/I and LT/E was 6.1 (6.2), 7.3 (4.8), 8.0 (7.1); mean (SD) number of tests was 20.8 (17.2), 23.3 (15.7), 25.2 (18.2), respectively. NS, ST/I and LT/E patients reported mean EQ-5D scores (0.85, 0.81, 0.79), SIBDQ total scores (54.6, 49.7, 48.3) and overall work impairment (19.4, 23.1, 27.7). Key comorbidities experienced by ST/I and LT/E were hypertension, depression and diabetes (Figure 1). Conclusion Patients with long-term or escalated steroid use had high symptom burden, frequent comorbidities, high HCRU, and poor QoL. This highlights the need for alternative treatment approaches for moderate UC patients to avoid long-term steroid use. 1. Cross R.K. Inflamm Bowel Dis. 2017;23(10):1689–1701

Chronic Lymphoproliferative Disorder of Natural Killer Cells: Patient Characteristics, Laboratory Features, and Clinical Outcomes

Introduction: Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is a rare form of large granular lymphocytic leukemia. The clinical characteristics and outcomes of patients (pts) with CLPD-NK in the literature are limited. We aim to describe the patient characteristics, laboratory features, and clinical outcomes of CLPD-NK by reporting on, to our knowledge, the largest single-center cohort of CLPD-NK in the United States. Methods: We retrospectively identified Mayo Clinic pts with CLPD-NK, defined per the WHO 5 th edition and 2022 International Consensus Classification. We conducted chart review to collect clinical and laboratory data. Overall survival (OS) was plotted using Kaplan-Meier. Time to first treatment (TTFT) was displayed using cumulative incidence methodology accounting for competing risk of death. Univariable Cox regression models investigated associations between patient characteristics and outcomes (OS and TTFT). Results: We identified 45 pts who were diagnosed with CLPD-NK between 1997 and 2022. The median age at diagnosis was 69 years (range: 25-90) and 32 pts (71%) were male. At the time of diagnosis, 10 pts (22%) had a concomitant autoimmune disorder and 9 (20%) had laboratory evidence of a serologic abnormality (monoclonal gammopathy, rheumatoid factor, etc.). In addition, 10 pts (22%) had a prior diagnosis of a hematologic malignancy and 12 (27%) had a prior diagnosis of a solid tumor. Clinically, 4 pts (9%) had B symptoms, 15 (33%) had splenomegaly, and 13 (29%) were transfusion dependent. At diagnosis, median hemoglobin (hgb) was 10.2 g/dL, with 25 pts (56%) showing a hgb &amp;lt;11g/dL and 8 (18%) demonstrating a hgb &amp;lt;8 g/dL. The median platelet count was 202x10^9/L, with 12 pts (27%) demonstrating a platelet count &amp;lt;150x10^9/L. The median white blood cell count was 5.8x10^9/L. The median absolute neutrophil count (ANC) was 1.2x10^9/L, with 29 pts (64%) demonstrating an ANC &amp;lt;1.5x10^9/L. The median absolute lymphocyte count (ALC) was 3.8x10^9/L, with 20 pts (44%) demonstrating an ALC &amp;gt;4x10^9/L. The median absolute abnormal NK cell count per flow cytometry was 2.2x10^9/L. Flow cytometry revealed killer cell immunoglobulin-like receptor (KIR) restriction in all pts, with 27 (61%) lacking KIR expression and 17 (39%) demonstrating KIR restriction in CD158a, CD158b, and/or CD158e. CD7 expression was present in 42 pts (93%; 31% dim/partial), CD8 expression was present in 22 (49%; 42% d/p), CD56 expression was present in 17 (39%; 23% d/p), CD57 expression was present in 26 (59%; 46% d/p), CD94 expression was present in 33 (77%; 7% d/p), and NKG2A expression was present in 21 (50%; 5% d/p). Bone marrow examination (n=30) revealed that the median number of NK infiltrate was 11% (range: 5-40%) of cellularity, with 20 demonstrating an intrasinusoidal infiltrative pattern. The median follow-up was 41 months (mo), and 23 pts required at least one line of treatment. Treatment indications included anemia (39%), neutropenia (4%), bi/pancytopenia (39%), lymphocytosis (4%), or other (13%). The median TTFT was 32 mo (95% CI 2-93 mo). Hgb &amp;lt;11g/dL was associated with a shorter TTFT (9.7 vs 187 mo); however, neutropenia and thrombocytopenia were not associated with TTFT. For first-line treatment, in addition to frequent steroid use, 16 pts (70%) received a methotrexate-based regimen, 6 (26%) received a cyclophosphamide-based regimen, and 1 (4%) received a cyclosporine-based regimen. The median TTFT was not reached. Of those who required systemic treatment, 9 pts required a second-line therapy. The median OS from diagnosis was 162 mo (95% CI: 84-not estimable, NE), with 33 pts alive at last follow-up (Figure 1a). Increasing age (HR 1.2, 95% CI 1.1-1.3, p=0.002) and lack of CD94 expression (HR 5.6, 95% 1.3-25.0, p=0.02) were associated with worse OS. In the 23 pts who required treatment, the median OS from treatment initiation was 84 mo (95% CI: 52-NE) (Figure 1b). Conclusions: In this large cohort of 45 pts, the majority had neutropenia and anemia, and approximately half required systemic treatment. Estimated median OS from diagnosis exceeded a decade for the entire cohort and was seven years after treatment initiation. Anemia was associated with a shorter TTFT, while increasing age and lack of CD94 expression were associated with worse OS. This rare disease warrants additional investigations to understand optimal management and improve outcomes, especially for those requiring treatment.

Frequency of posterior cataract in steroid-dependent or frequent relapse nephrotic syndrome in children.

Objective: To determine the frequency of posterior cataract in steroid-dependent or frequent relapse nephrotic syndrome (NS) in children presenting to National Institute of Child Health (NICH), Karachi. Study Design: Cross Sectional study. Setting: Department of Pediatrics, NICH, Karachi. Period: September 2022 to February 2023. Material &amp; Methods: We enrolled children of both genders aged between 2 to 15 years with NS (frequent relapsing or steroid dependent) who were taking steroid for at least 6 months. Baseline demographic information of patients including age and gender along with duration of NS, duration of steroid treatment, present doses of steroid, and total cumulative dose of steroid were noted. Ophthalmological examination was carried out from ophthalmology department by slit lamp examination and the frequency of posterior cataract was noted. Results: In a total of 154 children, 84 (54.5%) were girls. The mean age was 3.41±1.33 years. The most common presenting features/complaints were periorbital edema, fever and pedal edema reported in 112 (72.7%), 56 (36.4%) and 36 (23.4%) children respectively. The posterior cataract was found to be present among 23 (14.9%) children. Age (p&lt;0.001), frequent relapse (p=0.001), increased duration of NS (p&lt;0.001), duration of steroid treatment (p&lt;0.001), number of relapses (p&lt;0.001) and total cumulative dose of steroids (p&lt;0.001) were significantly associated with posterior cataract. Conclusion: The frequency of posterior cataract among children having frequent relapse or steroid dependent nephrotic syndrome was 14.9%. Duration of nephrotic syndrome, duration of steroid treatment, number of relapses and cumulative steroid treatment dose were significantly linked with posterior cataract.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P= .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Clinical presentation and prognosis in children over 10-year-old with primary nephrotic syndrome

Objective: To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers. Methods: The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types. Results: There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-old with the onset age of 4.5 (3.2, 6.8) years. The proportion of SRNS was significantly higher in patients >10-year-old than those ≤10-year-old (24.6% (29/118) vs. 15.9% (65/408), χ2=4.66, P=0.031). There was no statistical difference in the pathological types between >10-year-old and ≤10-year-old (P>0.05), with minimal change disease the most common type (56.0% (14/25) vs. 60.5% (26/43)). The percentage of cases with renal tubulointerstitial lesions was significantly higher in children >10-year-old compared to those ≤10-year-old (60.0% (15/25) vs. 23.3% (10/43), χ2=9.18, P=0.002). There were 29 cases presented with SRNS in PNS over 10-year-old, including 19 initial non-responders and 10 late non-responders. Analyzed by Kaplan-Meier curve, it was shown that the percentage of persistent proteinuria after 6 months of immunosuppressive treatments was significantly higher in initial non-responders than those of the late non-responders ((22±10)% vs. 0, χ2=14.68, P<0.001); the percentage of minimal change disease was significantly higher in patients of late non-responders than those of the initial non-responders (5/6 vs. 3/13, P=0.041). Of the 63 >10-year-old with steroid-sensitive nephrotic syndrome followed up more than one year, 38 cases (60.3%) had relapse, and 14 cases (22.2%) were frequent relapse nephrotic syndrome and steroid dependent nephrotic syndrome. Among the 45 patients followed up over 18-year-old, 22 cases (48.9%) had recurrent proteinuria continued to adulthood, 3 cases of SRNS progressed to kidney insufficiency, and one of them developed into end stage kidney disease and was administrated with hemodialysis. Conclusions: Cases over 10-year-old with PNS tend to present with SRNS and renal tubulointerstitial lesions. They have a favorable prognosis, but are liable to relapse in adulthood.

Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms

BackgroundChildren with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA.MethodsOPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI).ResultsPatients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children.ConclusionsEgyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

Can Oral Zinc Supplementation Reduce Relapses in Childhood Steroid-Sensitive Nephrotic Syndrome? A Systematic Review.

Frequent relapses and steroid dependence are common treatment challenges of steroid-sensitive nephrotic syndrome (SSNS) in children. Acute respiratory infection (ARI) is the most frequently reported trigger of relapse. Given the role of zinc supplementation in preventing ARI, some studies show that this targeted intervention may reduce relapses in childhood SSNS. This systematic review aimed to determine if oral zinc supplementation can significantly reduce relapses in this disease. We searched the PubMed and Google Scholar electronic databases for interventional and observational analytical studies without limiting their year or language of publication. We selected studies with primary data that met our inclusion criteria, screened their titles and abstracts, and removed duplicates. We used a preconceived structured form to extract data items from selected studies and conducted a quality assessment of randomized controlled trials (RCTs) and non-randomized studies with the Cochrane collaboration tool and the Newcastle Ottawa Scale, respectively. We qualitatively synthesized the extracted data to validate the review's objective. Eight full-text articles were selected, comprising four RCTs and four observational analytical studies. Two of the RCTs had a high risk of bias in three parameters of the Cochrane collaboration tool, while three non-randomized studies had low methodological quality. A total of 621 pediatric patients with SSNS were investigated in the eight studies: six participants dropped out in one study. Three RCTs indicate that zinc supplementation may lead to sustained remission or reduction in relapse rate. Similarly, three observational analytical studies suggest a significant relationship between reduced serum zinc levels and disease severity. Despite the association of zinc deficiency with increased morbidity in SSNS and the reduction of relapse rates with zinc supplementation, there is no robust evidence to recommend its use as a therapeutic adjunct. We recommend more adequately-powered RCTs to strengthen the current evidence.

Comparison of Lipid Profile in Different Types of Steroid Sensitive Idiopathic Relapsing Nephrotic Syndrome in Children during Active Disease and Remission

Introduction: Nephrotic syndrome is a disease of relapse and remission. Relapse rate is more than 80%. Hyperlipidemia and hypoalbuminemia are important characteristic of nephrotic syndrome. Hyperlipidemia persist even after remission of disease in frequent relapse nephrotic syndrome possibly due to frequent attack of disease and frequent use of steroid. Hyperlipidemia causes premature atherosclerosis, progressive renal injury leading to chronic renal failure, cardiac complications (myocardial infarction, hypertension), cerebrovascular disease and frequent relapse of nephrotic syndrome. Objectives: The aim of study was to see the lipid profile and comparison of lipid profile among different types of steroid sensitive idiopathic relapsing nephrotic syndrome during active disease and in remission. Materials and Methods: A cross sectional study included 120 ( 40 in each group) children aged 2-16 years with steroid sensitive idiopathic relapsing nephrotic syndrome patients who were admitted or attended in out patients department (OPD) in paediatric nephrology department Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, during December 2014 to December 2015. They were clinically examined and fasting lipid profile was done in each case during active disease and after one month of urinary remission. The study population were divided into three groups- Infrequent relapse nephrotic syndrome (IFRNS), frequent relapse nephrotic syndrome ( FRNS ) and steroid dependent nephrotic syndrome (SDNS) based on clinical response. Results: Total patients were 120 (40 in each group). The study showed a male predominance with a male to female ratio 2.24:1, male patients were 69%, female 31%. In all cases, there were increased mean total cholesterol, low density lipoprotein ( LDL ) , triglyceride (TG) and high density lipoprotein (HDL) was normal during active disease, more raised in FRNS and SDNS.There was significant decrease in the mean level of total cholesterol, LDL and triglyceride during remission ( p &lt;0.001). Cholesterol became normal but triglyceride and LDL remained elevated even after one month of urinary remission in FRNS and SDNS. Conclusion: Hyperlipidemia persist during remission of steroid sensitive relapsing nephrotic syndrome. Children with FRNS and SDNS should be addressed with lipid lowering medication, healthy foods and healthy life style. Multicenter prospective studies with larger sample are needed for validating the findings of the present study. Medicine Today 2022 Vol.34(2): 111-116

Subclinical hypothyroidism in children with idiopathic childhood nephrotic syndrome at a tertiary institution in South-West Nigeria.

Hypothyroidism in children with nephrotic syndrome (NS) is often attributed to prolonged loss of thyroxine binding globulin and thyroid hormones alongside protein in the urine. It has been historically associated with steroid-resistant NS alone. However, recent evidence supports the fact that subclinical hypothyroidism (SCH) does occur even in children with steroid responsive NS. Complications such as weight gain, hypercholesterolemia, delayed growth, delayed puberty, and depression could result from hypothyroidism and be erroneously attributed to NS, or the effect of steroid used in treatment. Incidentally salt intake, the major form of dietary iodine is often restricted in children with NS, possibly exacerbating any underlying hypothyroid state. The study aimed to determine the burden of SCH among our cohort of NS patients. A comparative cross-sectional study was designed to assess SCH [defined by high TSH (>6.0 mU/L and normal free T4 (0.8-2.0 ng/dl)] in hundred children with NS aged between one and fifteen years compared with hundred age and gender matched comparison group without NS. Blood and urine samples were collected to analyze thyroid function, serum albumin, serum protein and urinary protein. The prevalence of SCH was significantly higher in subjects with NS than their age, sex matched comparison group (12% vs. 2%, P = 0.006). The highest proportion (24.1%) of the children with NS who had SCH was found in the age range of 11-15 years and majority were females (19.4% vs. 7.8%, respectively, P = 0.086). The proportion of children with SCH were higher in those with steroid-resistant NS than those responsive to steroids (26.3% vs. 8.6% P = 0.033). The average values of serum albumin and protein were also significantly lower in children with SCH than those without (2.91 mg/dl ± 0.8 vs. 3.78 mg/dl ± 0.9 and 3.99 mg/dl ± 1.3 vs. 5.02 mg/dl ± 1.3, respectively, P < 0.005). Also, the average value of urinary protein was significantly higher in those with SCH than those without [94.29 mg/dl (42.3-101.0) vs. 69.19 mg/dL (31.2-108.2), respectively, P = 0.023]. Participants with steroid-resistant NS have almost three-folds odd of developing SCH compared to steroid sensitive subjects (AOR 2.901; 95% CI 1.831-4.012; P = 0.038). Screening of children for SCH with NS especially steroid-resistant NS and frequent relapsing steroid sensitive NS for hypothyroidism before complications arise is pertinent to their holistic management. This becomes even more imperative in our environment as iodine deficiency hypothyroidism is still prevalent in some parts of the country.

Rituximab treatment in children with difficult-to-treat nephrotic syndrome

Purpose: Rituximab (RTX) has been offered as rescue therapy for patients with difficult-to-treat nephrotic syndrome (frequent relapsing, steroid-dependent and steroid resistant). We aimed to assess the efficacy and long-term outcomes of RTX treatment in children with difficult nephrotic syndrome and shared our experiences&#x0D; Materials and Methods: Medical records of children with difficult nephrotic syndrome who were treated with RTX were retrospectively evaluated. The relapse-free survival rate at 12 month and monitoring of B-cell depletion were assessed.&#x0D; Results: In the study included 20 children of which 8 had steroid-dependent (SDNS), 6 had frequent relapsing (FRNS), and 6 had steroid-resistant nephrotic syndrome (SRNS). The median number of relapses at 1 year before and after treatment in FRNS/SDNS patients receiving RTX treatment were compared. The median number of relapses decreased from 2 (1-4) to 0 (0-1) times/year. The mean duration of the follow-up period after RTX treatment was 23 (12-59) months, and 8 patients developed relapse. Repeated doses of RTX were administered to 5 patients who relapsed after RTX treatment. In these patients, CD19+B cells re-emerged during remission, while depletion of memory B-cells remained. &#x0D; Conclusion: The RTX treatment prolonged the remission time in FRNS/SDNS patients, but it was ineffective in SRNS patients. It was determined that the RTX doses can be repeated to maintain remission in these patients, and the best memory B-cell counts can help in timing the repeat doses.

Health-Related Quality of Life, Financial and Psychosocial Impact on Parents Having Children with Nephrotic Syndrome

Background &amp; objective: Childhood nephrotic syndrome (NS) follows a chronic course in most children. However, little has been studied about the burden of NS on the caregivers despite evidence that caregiver burden or impairment in their well-being may alter the outcome of chronic childhood illnesses. We aimed to study the multi-dimensional impact on the quality of life (QOL) of families of children with the NS to determine the significant predictors of caregiver burden and psychological distress among caregivers of children with NS in terms of Parents HRQOL (health related quality of life), Pediatrics Health-related quality of life Family Impact Module (PedsQLTM FIM) and Family Functioning Summary Score (FaF-SS).&#x0D; Methods: This cross-sectional analytical study was conducted over a period 6 months from October 2019 to March 2020. Parents of children with diagnosed nephrotic syndrome (frequent relapsers, steroid dependent and steroid resistant), on treatment for at least one year, attending at the Outpatient and In-patient Units of Pediatric Neprology, Dhaka Medical College &amp; Hospital (DMCH) and Dhaka Shishu Hospital were taken as cases. A total of 40 cases and 64 controls were consecutively included in the study. The control group consisted of parents of healthy age-sex matched children attending at the immunization clinic to have their children immunized. Data were collected by face-to-face interview of the parents using questionnaire of Pediatric Quality of Life Inventory 4 (PedsQLTM), Family Impact Module (FIM). PedsQL FIM is a multi-item scale comprising of 36 questions grouped under eight domains related to physical functioning, emotional functioning, social functioning, cognitive functioning, communication, worry, daily activities and family relationships.&#x0D; Results: Parents HRQOL-SS was compromised with certain aspect of their demographic characteristics. Parents with debt and widows had compromised HRQOL than the parents without debt and both of the spouses are living together (p = 0.174 and p=0.027 respectively). Parents whose children responding well to treatment had a better HRQOL than those whose children were not responding to treatment (p = 0.102). As PedsQLFIM-SS was compared between the demographic characteristics of the parents, again widows and parents with debt had significantly worse PedsQLFIM-SS (p = 0.007 and p = 0.038 respectively). Parents with debt also had impact on family functioning as evidenced by commendably reduced FaF-SS (family functioning summary score) in parents with debt than those in parents without debt (p = 0.029). There was no difference between case and control groups in terms of Parents HRQOL-SS and FaF-SS (956.8 ± 195.9 vs. 970.9 ± 287.7, p = 0.786 and 404.5 ± 87.8 vs. 391.4 ± 119.1, p = 0.549 respectively) and each of the six individual domains, except emotional functioning which was significantly poor in the case group than that in the control group (p = 0.005) Physical functioning was also considerably worse in the case group than that in the control group, although the difference was not statistically significant (p = 0.130).&#x0D; Conclusion: The study concluded that parents of the children with NS suffer from immense financial, physical and psychological burden. Burden is significantly greater for widows or when the families are in debt due to continued effort to cope with the stresses resulting from caregiving of their compromised children. Early diagnosis and treatment of parents’ burden is of utmost need to help improve parents’ health-related quality of life.&#x0D; Ibrahim Card Med J 2021; 11 (1): 28-34

Immune Profiles in Inner-city Asthmatic Children Receiving Frequent Systemic Steroids

Immune Profiles in Inner-city Asthmatic Children Receiving Frequent Systemic Steroids

Incisional Hernia Repaired Using Thigh Muscle Fascia After Kidney Transplantation: A Case Report

Although monofilament mesh-based repair is a safe and effective procedure for incisional hernia (IH) in organ transplant patients, there is no definite evidence of IH treatment for patients with graft rejection and enhanced immunosuppressive therapy. We report a successful case of large IH repair using an autologous thigh muscle fascia sheet in a kidney transplant patient. A 69-year-old man had IH from the incision of kidney transplantation, which was performed 6 years ago. He had a large right lower abdominal distension hanging down to the inguinal portion. A computed tomography scan revealed a large IH with a maximum abdominal defect diameter of 15 cm. The hernia sac contained the intestine, colon, and transplanted kidney, which had pulled out along with the retroperitoneum and protruded into the abdominal wall. He had chronic active acute antibody-mediated rejection, which required frequent steroid pulse therapy and additional or adjusted immunosuppressive drugs. After total circumferential exposure of the hernia sac and abdominal fascia, the abdominal wall defect was closed using a horizontal mattress suture. The sutured line was covered with a thigh muscle fascia sheet harvested from the patient's right femur and attached to the closed fascia. He was discharged on postoperative day 13 without any complications, and no IH recurrence was observed 10 months after surgery. Hernia repair using autologous tissue could be a treatment option for post-transplant IH with a higher risk of infection.

Association Between the Number of Intratympanic Steroid Injections and Hearing Recovery in Sudden Sensorineural Hearing Loss.

The frequency of intratympanic (IT) steroid injection varies from once daily to once weekly or less among studies and does not reach a uniform standard. This study investigated the potential association between the number of IT steroid injections and hearing recovery to determine the optimal number in sudden sensorineural hearing loss (SSNHL) patients. A retrospective study involving 233 SSNHL patients receiving IT steroids plus batroxobin within 7 days of onset was performed. Patients were followed up for 3 months. More than 15 dB of HL improvement in the pretreatment pure tone average (PTA) was defined as effective. The effective group had a higher IT injection numbers than the ineffective group (≥ 6 times: 84.6 vs. 61.1, p < 0.001). Regardless of the unadjusted model or adjusted model, patients who received more frequent IT steroid injections seemed more likely to recover hearing (unadjusted model, OR, 95% CI: 1.25, 1.06–1.48; p = 0.007; adjusted model, OR, 95% CI: 1.21, 1.01–1.45; p = 0.044). Six IT injections had the highest rate of hearing recovery (79.1%). In conclusion, IT injection number was an independent factor that was positively associated with hearing recovery, and the optimal number of IT steroid injections was 6. Batroxobin plus higher number of IT steroid injections showed more effective for treating SSNHL.

O02 Cancer, Covid and control of RA – a toxic combination?

Case report - IntroductionThis case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises.During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with high-dose steroids. Risks of infection (common and atypical) need to be considered.Case report - Case descriptionA is a 67-year-old female non-smoker diagnosed with seropositive rheumatoid arthritis (RF, anti –CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016.In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen.Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018.Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5—10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime.Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment.Case report - DiscussionCancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancerWhilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression.Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theoretical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters.Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life.Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations.Case report - Key learning pointsPrimary peritoneal cancer is uncommon and can present as an incidental findingWhilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of lifeMorbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers – lack of “named” providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult

Vaccines and Disease Relapses in Children with Nephrotic Syndrome.

More than half of children with idiopathic nephrotic syndrome develop frequent relapses or steroid dependence and require chronic use of immune suppressants, such as cyclosporin, mycophenolate mofetil, or B cell–depleting therapies, to maintain disease in remission ([1][1]). Loss of endogenous

POS-455 RITUXIMAB IN MANAGEMENT OF PEDIATRIC NEPHROTIC SYNDROME

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1–3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Many studies in the past decade have reported the effectiveness of rituximab for complicated FRNS/SDNS and refractory SRNS. Prospective study 1) To evaluate the efficacy of rituximab in glomerular diseases. 2) To evaluate response of rituximab by complete or partial remission of nephrotic syndrome after two to four doses of rituximab 375mg/m2, during the follow up period of 12 months and the outcome had been assessed using blood and urine biochemistry values (UPCR/24hr urine protein,serum albumin) i.e., Complete remission (UPCR < 0.2), Partial remission (> 50% decrease in proteinuria from base line), CD 19 cells (< 5%) 3)To look for safety of rituximab. The patients included in the study will be given the dosage of rituximab as per body surface area (BSA) i.e., 375 mg/m2 two to four doses and followed up for a period of 12 months.REGIMEN: 375 mg/m2 Rituximab (2 doses for SDNS, 4 doses for SRNS) after premedication. Inclusion criteria: Patients of age groups <18 yrs were included in the study. Patients with nephrotic syndrome who had received a trial of steroids, alkylating agent and at least 6 months therapy of calcineurin inhibitor had received the novel drug Rituximab. Exclusion criteria: Patients with active focus of infection (Acute/Chronic). Serological evidence of current or past HIV/Hepatitis B/Hepatitis C infection. Known allergic reaction to rituximab. Patients/Parents not willing to give informed consent. Out of 33 patients who received rituximab 18 patients were in SRNS group and 11 were SDNS. The mean age of the patients who used rituximab in SDNS was 13.7+- 9.1 and in SRNS was 10.7+-2.9. In SDNS, FSGS contributed 61% (n=11); MCD33% (n=3) while in SDNS, MCD 72% (n=8); FSGS 27% (n=3). The mean duration of the CNI therapy for SRNS was 20.7=-17.1 months while for SDNS was 18.7+-10.2 months. In SRNS group; Complete remission (CR) was seen in 50.0% while in FSGS 18.1%; partial remission (PR) attained in 33.3% in MCD and in FSGS 27.2% and no remission for 16.6% in MCD and 54.4% in FSGS. In SDNS group, CR was seen in 75.0% in MCD and 33.3% in FSGS; PR obtained in 12.5% in MCD and 66.6% in FSGS; no remission in 12.5% in MCD.The CD19 counts at baseline were 12.6 ± 3.4% of the leukocyte count. After rituximab therapy, CD19 levels were 0.2 ± 0.1 and 0.3 ± 0.2% after two and four doses in patients with SDNS and SRNS, respectively. This study confirm the efficacy of rituximab in patients with difficult nephrotic syndrome; remission was achieved in 50.0% patients with SRNS and a 72.72% patients achieved remission in patients with SDNS. There was a trend toward better response rates in patients with steroid-resistant MCD (83.3%) compared with FSGS (45.45%).