Steroid-treated Group Research Articles

Antenatal steroids elicited neurodegenerative-associated transcriptional changes in the hippocampus of preterm fetal sheep independent of lung maturation

BackgroundAntenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function.MethodsDate-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection.ResultsPreterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration (“Prion Disease”, “Alzheimer’s Disease”, “Arachidonic Acid metabolism”). Adverse changes were independent of respiratory function during ventilation.ConclusionsOur data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Secondary infections in critically ill patients with COVID-19 receiving steroid therapy.

Secondary infections can occur during or after the treatment of an initial infection. Glucocorticoids may decrease mortality in patients with severe COVID-19; however, risk of secondary infection is not well described. Our primary objective was to investigate the risk of secondary infection among critically ill patients with COVID-19 treated with glucocorticoids. We examined patients with COVID-19 being treated in the intensive care unit at two academic medical centers from 1 to 7/2020. One hundred-seven patients were included. Of these, 31 received steroids and 76 patients did not. Analysis of the larger cohort was performed followed by a matched pairs analysis of 22 steroid and 22 non-steroid patients. Secondary infection was seen in 14 patients (45.2%) receiving steroids compared to 35(46.1%) not receiving steroids (p = 0.968). Secondary infections were most frequently encountered in the respiratory tract. Escherichia coli and Staphylococcus aureus were the most frequently identified organisms. Mortality was 16.1% in the steroid-treated group compared to 23.7% in the control group (p = 0.388). After performing matched pairs analysis and multivariable logistic regression there was no significant difference between secondary infection or mortality and steroid receipt. Secondary infections were common among critically ill patients with COVID-19, but the incidence of secondary infection was not significantly impacted by steroid treatment.

The Efficacy of Corticosteroids in the Management of Tietze Syndrome: A Randomized Controlled Trial

Abstract Background So far there are no clinical trials in the literature discussing the methods of treatment of Tietze‟s syndrome. Particularly, conservative methods of treatment are used, which include pain management using analgesics and nonsteroidal anti-inflammatory drugs. Oral corticosteroids offer a safe and effective treatment modality that is proven to be useful in a significant number of chest wall syndromes such as Sternoclavicular arthritis, Painful xiphoid syndrome, Costovertebral arthritis, and Slipping rib syndrome as well as conditions arising from ligament and tendon diathesis. Objective To use oral Corticosteroids in management of patients with Tietze syndrome at Ain shams university hospitals‟ cardiothoracic department and measuring the outcome randomly compared with the conventional NSAIDs to achieve the best outcome and quality of life. Methods This study included 40 patients who were diagnosed clinically as Tietze Syndrome at Ain Shams University Hospitals-cardiothoracic department in the duration between August 2020 till March 2022 with age ranging from 14 to 45 years and were sorted randomly. Two groups of patients were chosen and matched randomly as „Control arm‟ and „Interventional arm‟. The control group received the conventional NSAIDs (in the form of 50 mg of diclofenac potassium as „cataflam‟ twice daily) and the Interventional group received oral corticosteroids (in the form of 20 mg of prednisolone as „solupred‟ twice daily). Results Our study suggested that in patients with moderate to severe chondritis diagnosed clinically as Tietze syndrome, a 3 week course of oral 40 mg prednisolone is superior to the conventional oral NSAIDs in alleviating pain and improving the quality of life which is evidenced by the decline in EQ-5D total score of patients receiving oral steroids at the end of the treatment course as well as during each week throughout the trial timeframe. A highly significant reduction in pain score demonstrated via NRS was evident in the steroid-treated group compared to the NSAIDs-treated group at the same time point. Conclusion Oral corticosteroids are effective and safe in non-responding, obstinate Tietze syndrome. The results were unexpectedly good, obtaining significant relief and an outstanding refinement in quality of life reported by patients receiving oral steoids. There is no widely accepted protocol for oral steroid usage in Tietze syndrome and similar chest wall pain syndromes. Some other studies propose surgery in such patients. We think that surgery is a troublesome intervention for the patient and his doctor as well.

Paper 08: In Vitro Effects of Triamcinolone and Methylprednisolone on the Viability and Mechanics of Native Articular Cartilage

Objectives: The chondrotoxic effects of methylprednisolone acetate (MP) and triamcinolone acetonide (TA) have been well described. Prior studies have demonstrated a dose-dependent chondrotoxic effect of intra articular (IA) steroids starting at 7 mg for MP and 18 mg for TA. However, the effects of these steroids on the mechanical properties of articular cartilage are largely unknown. The purpose of this study was to investigate the in vitro effects of a single one-hour MP or TA exposure on the viability, mechanics, and biochemical content of native articular cartilage explants. Methods: Articular cartilage explants (n=6 per group) were harvested from the femoral condyle of the bovine stifle. Explants were exposed to chondrogenic medium containing a clinical dose of MP or TA for one hour, followed by fresh medium wash and exchange. Explants in the negative control group underwent the same treatment with chondrogenic medium alone. At t=24 hours post-treatment, samples were assessed for viability (live/dead), mechanical properties (creep indentation and Instron tensile testing), biochemical (collagen and glycosaminoglycan) content, and pyridinoline cross linking via mass spectrometry. Results: Mean cell viability was significantly decreased in native explants exposed to MP (35.5%) compared to control (49.8%, p &lt; 0.001) and TA (45.7%, p = 0.003) (Figure 1). There was significant weakening of mechanical properties of steroid-treated native explants when compared to control (Figure 2), with decreases in aggregate modulus (646.3 kPa vs 312.8 kPa [MP] and 257.0 kPa [TA), p &lt; 0.001), shear modulus (370.1 kPa vs 191.2 kPa [MP] and 157.4 kPa [TA], p &lt; 0.001), and ultimate tensile strength (UTS) (9.650 MPa vs 5.648 MPa [MP], p = 0.021 and 6.065 MPa [TA], p = 0.040). The Young’s modulus in TA-exposed native cartilage (7.924 MPa) was significantly lower than MP (12.35 MPa, p = 0.026) exposed explants but not significantly different compared to control (11.97 MPa, p =0.072). No significant differences in collagen and glycosaminoglycan content were found in the steroid-treated groups (Figure 3). Pyridinoline cross linking was significantly decreased in explants exposed to TA compared to control (p = 0.027). Conclusions: The results of this in vitro study suggest that a single clinical dose of MP is chondrotoxic and that a single clinical dose of MP or TA can lead to substantial early decreases in both the tensile and compressive properties of native articular cartilage. The shear modulus of steroid-exposed explants in this study dropped 48-57% compared to healthy control. In human knee cartilage, drops in shear modulus of this magnitude have been correlated with the progression from healthy knee cartilage to ICRS grade 1-2 osteoarthritis. Furthermore, decreases in Young’s modulus by 25-50% have been correlated with the same degree of osteoarthritis, and the Young’s modulus of steroid exposed cartilage dropped an average of 34% in this study. Although there were no detectable changes to the extracellular matrix composition or structure, a single one-hour steroid exposure was enough to cause chondrotoxicity and altered mechanics to native explants 24 hours after exposure, which raises the concern for risk of mechanical failure of the cartilage tissue. Clinicians should be judicious regarding use of intra-articular steroids, particularly in patients with intact healthy articular cartilage.

Triamcinolone acetonide with arthroscopic capsular release for frozen shoulder promotes early recovery of shoulder abduction

Current treatment options for frozen shoulder are not established as the standard-of-care. The condition may resolve without intervention, but symptoms may persist despite treatment. Frozen shoulder is associated with inflammatory reactions that can reduce quality of life. Our aim was to determine whether triamcinolone acetonide, an immunosuppressive steroid, improved functional recovery when administered after arthroscopic capsular release (ACR) for frozen shoulder. We selected participants using inclusion and exclusion criteria designed to reduce the impact of potential confounding factors. Under general anesthesia, we performed ACR followed by manipulation to ensure adequate range of motion (ROM) and wound closure. In the steroid treatment group, we injected triamcinolone acetonide into the glenohumeral joint immediately prior to wound closure. The follow-up period was six months. To determine the efficacy of steroids in improving overall post procedure functional recovery we statistically analyzed data from various qualitative and quantitative variables. Our study consisted of 22 patients with frozen shoulder, 11 in each of the surgery-only and surgery with steroid injection groups. There were no significant differences between groups in the demographic data of the study participants. We observed significantly greater improvements in abduction ROM in the steroid treatment group than in the surgery-only group, at three and six months post treatment. Improvements in other movement parameters were similar in both groups. The steroid-treated group had a significantly higher numerical rating scale score for night pain at three months post treatment than the surgery-only group. Postoperative steroid treatment led to early recovery of the abduction ROM in patients with frozen shoulder. Hence, the current standard-of-care protocol for frozen shoulder and other similar conditions requiring surgical intervention should include this type of treatment. Therapeutic reduction in the inflammatory response following ACR can significantly improve prognosis and quality of life.

Effect of steroid treatment on the diagnostic yield of baseline 18f-fluorodeoxyglucose positron emission tomography in aggressive B cell lymphoma

Aggressive B cell lymphoma often requires prompt steroid treatment, even before baseline 18f-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and definitive treatment, to alleviate symptoms or prevent organ damage. Since lymphoma is a steroid-sensitive malignancy, there are concerns that steroids might affect the results of FDG PET/CT and decrease its diagnostic yield. The aim of the current study was to evaluate the effect of steroids administered before baseline PET/CT on the maximum standardized uptake value (SUVmax) and additional PET/CT parameters. Retrospective review of the database in a tertiary medical center yielded 178 patients newly diagnosed with aggressive B cell lymphoma between January 2017 and May 2020 who had an available baseline FDG PET/CT scan. The cohort was divided into patients who received steroids before PET/CT (n = 47) and those who did not (n = 131), and the groups were compared for SUVmax and additional PET/CT parameters. The steroid-treated group had a higher disease stage and lactate dehydrogenase level compared to the steroid-naïve group, with a trend toward a higher international prognostic index. There was no significant between-group difference in SUVmax (P = 0.61). This finding remained consistent across steroid treatment durations and dosage regimens. Further evaluation revealed a significantly larger mean tumor volume and a trend toward a higher tumor metabolic burden in the steroid-treated group, yet no between-group difference in SUV mean or other PET/CT parameters. In this retrospective analysis of patients with aggressive B cell lymphoma, steroid prophase prior to baseline PET/CT did not decrease the diagnostic yield of the scan. However, further studies are required to fully appreciate the impact of steroids on PET CT parameters.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy

The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold. This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes. Following ethical review and approval, date-mated ewes with single fetuses received intramuscular injections of either (1) four 6-mg maternal intramuscular injections of dexamethasone phosphate every 12 hours (n=22), (2) 4 2-mg maternal intramuscular injections of betamethasone phosphate every 12 hours (n=21), or (3) 4 2-mL maternal intramuscular injections of saline every 12 hours (n=16). Of note, 48 hours after first injection, (124±1 day), lambs were delivered, ventilated for 30 minutes, and euthanized for sampling. Arterial blood gas, respiratory, hematological, and biochemical data were analyzed for between-group differences with analysis of variance according to distribution and variance, with P<.05 taken as significant. After 30 minutes of ventilation, lambs from both steroid-treated groups had significant and equivalent improvements in lung function relative to saline control (P<.05). There was no significant difference in arterial blood pH, pO2, pCO2, lung compliance, ventilator efficiency index, or lung volume at necropsy with a static pressure of 40 cmH2O. The messenger RNA expression of surfactant protein (Sp)a, Spb, Spc, Spd, aquaporin (Aqp)1, Aqp5, and sodium channel epithelial 1 subunit beta (Scnn1b) was equivalent between both steroid groups. Maternal and fetal plasma neutrophil, glucose, and fetal plasma C-peptide levels were significantly elevated in the dexamethasone group, relative to the betamethasone group. Fetal plasma insulin-like growth factor 1 was significantly reduced in the dexamethasone group compared with the betamethasone group (P<0.05). Fetal adrenocorticotropic hormone (r=0.53), maternal glucose value (r=-0.52), and fetal glucose values (r=-0.42) were correlated with maternal weight in the betamethasone group (P<.05), whereas fetal pCO2 and pO2 were not correlated. There was no significant difference between male and female lamb outcomes in any groups for any of the items evaluated. This study reported that in preterm lambs, a low-dose treatment regimen of 8 mg betamethasone achieves lung maturation equivalent to that of a 24-mg dexamethasone-based regimen, but with smaller perturbations to the maternofetal hypothalamic-pituitary-adrenal axis. These data suggested that given steroid pharmacokinetic differences between sheep and humans, a betamethasone dose of 2 mg may remain above the minimum dose necessary for robust maturation of the preterm lung. Maternal weight-adjusted betamethasone doses might also be a key to reducing perturbations to the maternofetal hypothalamic-pituitary-adrenal axis.

Prophylactic Anti-Osteoporotic Effect of Matricaria chamomilla L. Flower Using Steroid-Induced Osteoporosis in Rat Model and Molecular Modelling Approaches.

The anti-osteoporotic activity of ethanol extract from the Matricaria chamomilla L. flower was evaluated using steroid-induced osteoporosis in a rat model for the first time. Biochemical parameters such as serum calcium, phosphate, magnesium, creatinine, and alkaline phosphatase were assessed. At a 400 mg/kg body weight dose, the extract showed 54.01% and 27.73% reduction in serum calcium and phosphate ions serum levels, respectively. Meanwhile, it showed a 20% elevation in serum magnesium level, compared to the steroid-treated group. It also showed a significant decrease in creatinine and alkaline phosphatase levels, by 29.41% and 27.83%, respectively. The obtained results were further supported by biomechanical analyses, which revealed that a 400 mg/kg body weight dose of the flower extract increased bone strength and thickness. At the same time, it does not affect the bone length, compared to the diseased group. Histopathological examination revealed that the extract showed a significant increase in trabecular thickness, and it had restored the architecture of the cortical and trabecular structure with well-organized bone matrix. The possible inhibitory effect of the major phenolic compounds identified from the plant extract on cathepsin K was investigated using molecular docking. Rutin (4) had the best-fitting score within the active site, as evidenced by the free binding energy, (∆G = −54.19 Kcal/mol). ADMET/TOPKAT revealed that the examined compounds had variable pharmacodynamics and pharmacokinetic properties that could be improved to enhance the bioavailability during incorporation in various dosage forms. Thus, it can be concluded that this plant extract showed potential therapeutic benefits for osteoporosis.

Role of Steroids in Sickle Cell Patients With Acute Chest Syndrome.

BackgroundThe role of corticosteroids to treat acute chest syndrome (ACS) in patients with sickle cell disease (SCD) has always been a matter of debate. In clinical practice, systemic steroids were given for ACS with more severe disease. With the lack of standard treatment guidelines, their use to treat ACS is highly physician-dependent and varies widely across different hospitals. The utility of corticosteroids in ACS remains unclear. The objective of our study was to describe the differences between SCD patients treated with corticosteroids for ACS and those who were not and to evaluate the association between corticosteroid use, length of stay, and readmission rates.MethodologyWe performed a retrospective chart review of patients with SCD ≤18 years of age hospitalized for ACS at Brookdale University Hospital Medical Center between January 2016 and May 2021.ResultsWe identified 43 patients with 60 episodes of ACS (median age was 11 years and 55% were males). In total, 32 such episodes were treated with corticosteroids. The use of bronchodilators (p = 0.23), hydroxyurea (p = 0.13), and the presence of fever (p = 0.86) showed no significant difference between the two groups. The need for blood transfusions (p = 0.005), intensive care unit admission (p = 0.031), respiratory support (p = 0.011), and chest X-ray finding with more than one lobe involvement (p = 0.003) all point to moderate or severe ACS, which has been linked to steroid use. The length of hospital stay (p = 0.07) and the readmission rate (p = 0.31) were not statistically significant between the groups. Even in the subgroup with asthma, the length of stay was not different between the groups (p = 0.44).ConclusionsOur results show that treatment with systemic steroids for ACS is associated with more severe disease. The length of hospital stay was not different between the steroid-treated and untreated groups. Corticosteroids were not associated with a higher readmission rate in our study population, even in ACS patients with comorbid asthma. Further adequately powered prospective trials are needed to investigate the efficacy of corticosteroids in ACS.

Effect of Steroid Treatment on the Diagnostic Yield of Baseline PET CT in Aggressive B Cell Lymphoma

Aggressive B cell lymphomas often require prompt steroid treatment prior to baseline 18f-fluorodeoxyglucose positron-emission tomography (PET CT) scan and definitive treatment in order to alleviate symptoms and/or prevent organ damage. Since lymphomas are a steroid sensitive malignancy, there is a concern that steroid prophase might affect PET CT results and diagnostic yield.We conducted a retrospective cohort study to evaluate the effect of steroid treatment prior to baseline PET CT scan on the standardized uptake value (SUV) max and additional PET CT parameters by examining two groups of patients: steroid-naïve and steroid-treated patients. The effect of steroid administration on SUV max was examined across different daily and weekly steroid doses and durations of treatment.Between January of 2017 and May 2020, 187 newly diagnosed patients with aggressive B cell lymphoma who had a pre-treatment PET CT scan were evaluated. 160 patients (85.5%) had Diffuse large B-cell lymphoma (DLBCL)/ High-grade B-cell lymphoma, 13 patients (7%) had primary mediastinal (thymic) large B-cell lymphoma, 9 patients (4.8%) had primary DLBCL of the central nervous system and 5 patients (2.7%) had Burkitt lymphoma.132 patients (70.6%) were included in the steroid-naïve group and 55 patients (29.4%) in the steroid-treated group. In the steroid-treated group, the mean duration of steroid treatment was 10.49 (±9.28) days. Average daily dose of steroid treatment was equivalent to 72.27 (±36) mg of prednisone and the mean cumulative prednisone dose during the week prior to PET CT scan was equivalent to 367.95 (±239.9) mg of prednisone.There was no statistical significant difference between the groups in age, gender or KI67. However, patients in the steroid treated group had a significantly higher stage of disease compared to the steroid-naïve group (mean 3.44 compared to 2.99, respectively, p=0.01). The steroid-treated group also had a trend towards a higher IPI score (mean 2.45 versus 2.08, p=0.08) and a trend towards a higher LDH level (mean 2309.89 U/L, range 250-81374 versus mean 877.65 U/L, range 272-22036, p= 0.07), as depicted in table 1.There was no statistical difference in SUV max between the steroid-naïve and steroid-treated groups (p=0.97). This was consistent across various steroid treatment durations and dosage regimes. Patients in the steroid-treated group had a trend towards a higher tumor burden and a larger tumor volume compared to the steroid-naïve group, however it did not reach statistical significance. Mean tumor volume was 179.04 cm 3 in the steroid naïve group and 337.06 cm 3 in the steroid treated group (p=0.17). Mean tumor burden was 1944.84 in the steroid-naïve group and 3016.94 in the steroid-treated group (p=0.09).There was no difference in additional PET CT parameters including SUV mean, SUV max and SUV mean of liver and mediastinum between the groups as depicted in table 2.In conclusion, in aggressive B cell lymphoma, pre-treatment with steroids prior to initial PET CT scan does not affect SUV max or other PET CT parameters and does not reduce PET CT diagnostic yield. [Display omitted] DisclosuresGurion: Medison: Consultancy; Gilead Sciences: Consultancy; Takeda Pharmaceuticals: Consultancy; JC Health Care: Honoraria; Roche: Honoraria.

My experience on taeniasis and neurocysticercosis.

Taeniasis and neurocysticercosis (NCC) are major public health problems in developing countries. NCC is the leading cause of community-acquired active epilepsy. NCC may present as a medical emergency, especially when there is cysticercotic encephalitis or raised intracranial hypertension. Systematic community-based studies on taeniasis and NCC are lacking. We studied taeniasis and NCC-related active epilepsy disease burden in the pig farming community of Lucknow district, Uttar Pradesh, India. Based on the 30 cluster sampling approach as recommended by the World Health Organization, we estimated the prevalence of taeniasis, NCC-related active epilepsy, and silent NCC in the community. We also estimated the prevalence of swine cysticercosis. Taeniasis was detected in 18.6% of populations. Expulsions of tapeworm segments in stool, consumption of undercooked pork, age above 15 years, and handwash with clay or plain water after defecation were associated with taeniasis. On molecular analyses of positive stool samples, T. solium was identified in 40% and Taenia asiatica in 60% of cases. Active epilepsy was identified in 5.8% of subjects; 48% of them had NCC. On neuroimaging, NCC was detected in 15% of asymptomatic individuals. We observed that host genetic factors such as toll-like receptor-4, matrix metalloproteinase-9, intercellular adhesion molecule-1, and glutathione-S transferase gene polymorphisms were associated with seizure in NCC. When peripheral blood mononuclear cells (PBMCs) from NCC subjects were exposed to cysticerci fluid antigens in-vitro, PBMCs from symptomatic and asymptomatic subjects showed significantly higher Th 1 and Th 2 cytokines response respectively, symptomatic patients had significant Th-1 cytokines response, while asymptomatic individuals showed Th-2 response. Porcine cysticercosis was detected in 26% of swine; 38% of them had cysticerci in the brain. Swine with brain involvement showed clinical signs such as excessive salivation, excessive blinking and tearing, and subconjunctival nodule. On molecular analysis, 15% of cysticerci in swine were identified as T. asiatica. Infected swine when treated with albendazole plus/minus steroid, the response rate of cysticerci (either dead or resolved lesion) was 100% in albendazole-treated group and 71% in albendazole plus steroid-treated group. The above studies suggest that taeniasis and NCC are alarmingly high in the pig farming community of North India. Taeniasis in human and cysticercosis in swine due to T. asiatica call for further studies on this parasite.

Real-world clinical course of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan

BackgroundAs human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare chronic neurological disease, large scale studies to collect continuous clinical data have been difficult to conduct. Therefore, the incidence of comorbidities and drug utilization data remain unknown. When conducting trials to develop new drugs in rare disease such as HAM/TSP, historical control data obtained from registry studies would be useful, as cohorts in rare disease tend to be small. Long-term follow-up of patients with a chronic disease can also be challenging. In this study, we addressed the following two goals using registry data on patients (n = 486) enrolled in the Japanese HAM/TSP patient registry “HAM-net” from 2012 to 2016: 1) to clarify the epidemiological information of HAM/TSP such as the incidence of comorbidities and drug utilization and 2) to provide the real-world data on changes in lower limb motor dysfunction.ResultsIn HAM-net-registered patients, common comorbidities were fractures, herpes zoster, and uveitis, with incidences of 55.5, 10.4, and 6.5, respectively, per 1000 person-years. Every year, oral steroid treatment was administered in 48.2–50.7% of the HAM-net-registered patients and interferon-α treatment was used in 2.6–3.5% of patients. The median dose of oral prednisolone was low at 5.0 mg/day. The incidence of fractures and herpes zoster tended to be higher in the steroid-treated group than in the untreated group (fractures: 61.0 vs. 48.3, herpes zoster: 12.7 vs. 8.8, per 1000 person-years). The analysis of chronological change in Osame motor disability score (OMDS) indicated that the mean change in OMDS was + 0.20 [95% confidence intervals (CI): 0.14–0.25] per year in the one-year observation group (n = 346) and + 0.57 (95% CI: 0.42–0.73) over four years in the four-year observation group (n = 148). Significant deterioration of OMDS was noted in all subgroups with varying steroid use status.ConclusionsThis study revealed the incidence of comorbidities and drug utilization data in patients with HAM/TSP using registry data. Furthermore, this study provided real-world data on chronological changes in lower limb motor dysfunction in patients with HAM/TSP, indicating the utility of these data as historical controls.

Effect of steroids and relevant cytokine analysis in acute tubulointerstitial nephritis

BackgroundAcute tubulointerstitial nephritis (ATIN) is an important cause of acute kidney injury and often a potentially reversible disease. However, the role of steroids in ATIN remains controversial and the underlying mechanisms remain unresolved.MethodsA total of 113 adult patients with biopsy-proven ATIN were recruited from three tertiary referral centers. Of 102 patients with idiopathic or drug-induced ATIN, outcomes such as renal recovery, end-stage renal disease, and all-cause mortality were compared between the steroid-treated and non-treated groups. Plasma and urine inflammatory cytokine levels at the time of biopsy were analyzed in patients (n = 33) using a bead-based multiplex assay and compared with those of healthy individuals (n = 40).ResultsSteroids were used in 92 (81.4%) of the total patients and in 82 (80.3%) patients with idiopathic or drug-induced ATIN. The rate of renal recovery and the risks of end-stage renal disease and mortality were not different between the steroid-treated and non-treated groups. Despite using a propensity score matching method (n = 20 in each group), none of the outcomes were different between the two groups. Several cytokines, such as monocyte chemotactic protein-1, interferon-α, and interleukin-6 and interleukin-8 levels, were markedly elevated in plasma and urine of patients compared with those in healthy individuals. However, cytokines related to Th2 response, such as IL-10, IL-33, were not different between the two groups.ConclusionsSteroid use does not affect the overall outcome of ATIN. Based on the fact that targeting therapy should be investigated to improve outcomes, the present cytokine results will be helpful for developing a novel therapy for ATIN.

The Impact of Local Steroid Administration on the Incidence of Neuritis following Lumbar Facet Radiofrequency Neurotomy

Background: Pain arising from the lumbar facet joints is a common cause of axial back pain in adults. Radiofrequency neurotomy (RFN) of the medial branches of the spinal dorsal rami has been used as a treatment option. The most common side effect is transient, localized, burning, neuritic-type pain, termed post-neurotomy neuritis (PNN). Corticosteroids have been administered through the radiofrequency cannula after neurotomy to prevent PNN, but no study has examined the effects of this on PNN. Objectives: We investigated the incidence of PNN in patients who received corticosteroids after RFN and in those patients who did not receive corticosteroids. Study Design: Retrospective evaluation. Setting: Single-site interventional pain management practice in an urban tertiary academic medical center. Methods: One hundred and sixty-four patients were included in this study and were categorized into non-steroid (n = 87) and steroid (n = 77) groups. Patient’s age, gender, body mass index (BMI), laterality of procedure, use of neuropathic pain medications, baseline pain, and duration of pain were all recorded. PNN was determined if the patient self-reported transient burning or neuropathic pain at the site prior to or at the 6-week routine follow-up encounter. Results: There was no significant difference in demographic characteristics between the 2 groups in age, gender, baseline pain, and duration of pain. The proportion of patients in the steroid treated group with PNN was 5 out of 77 (6.4%) and the non-steroid group was 6 out of 87 (6.9%). There was no statistically significant difference between the groups. There was no statistically significant difference in the incidence in neuritis between individuals taking neuropathic agents and individuals not taking neuropathic agents. Limitations: This study has several limitations including small sample size, patients’ self-reported neuropathic symptoms, and inability to draw strong conclusions due to the retrospective study design. A single interventionalist performed all the procedures in this retrospective study and variations in technique amongst others are inevitable. Conclusion: Administration of steroids after RFN does not reduce the incidence of postneurotomy neuritis. Concurrently administering neuropathic medications does not protect against neuritis. Key Words: Radiofrequency neurotomy, radiofrequency ablation, neuritis, corticosteroid, lumbar facet pain, post neurotomy neuritis.

Steroid treatment in patients with acute-on-chronic liver failure precipitated by hepatitis B: A 10-year cohort study in a university hospital in East China.

To investigate retrospectively the efficacy of steroids in patients with acute-on-chronic liver failure (ACLF) precipitated by hepatitis B. Patients with ACLF precipitated by hepatitis B were included and categorized according to treatment modalities (steroid vs. control). Survival and clinical characteristics, including patients' age, baseline ACLF grade, the model for end-stage liver disease (MELD) score, and occurrence of infection were compared between the two groups. Survival analyses of subgroups classified by their age, ACLF grade and MELD score were performed. Cox regression analyses were conducted to identify factors associated with 60-day cumulative and transplant-free mortality. From 2007 to 2016, 293 patients with hepatitis B-precipitated ACLF were recruited, among whom 162 received at least five consecutive doses of corticosteroids. By day 60 transplant-free survival was 62.6% in the control group compared with 53.7% in the steroid group (P = 0.126). Steroid treatment failed to show a survival benefit in the survival analysis among the subgroup. Within 60 days, pulmonary and overall infections occurred with higher frequency in the steroid-treated group than in the controls (P = 0.003 and < 0.001, respectively). In the univariate analysis, age, baseline MELD score >20, CLIF consortium (CLIF-C) ACLF grade 2-3, pulmonary infection and overall infection were associated with 60-day mortality. In the multivariate analysis, older age, baseline MELD score >20 and CLIF-C ACLF grade 2-3 were independent risk factors of 60-day mortality. Steroid treatment did not improve transplant-free survival in patients with ACLF precipitated by hepatitis B.

The Possible Protective Role of Barley Seeds on the Spleen after Administration of Glucocorticoids in Adult Albino Rats: A Histological and Immunohistochemical Study.

Background:Glucocorticoids (GCs) are the main treatment strategy in many autoimmune disease and inflammatory diseases; however, they have immunosuppressive effect on many organs. The barley seeds contain many antioxidant compounds, which may improve the antioxidant status and related physiological functions. Our aim in this work is to evaluate the possible protective role of barley seeds on some immune cells in the spleen against immunosuppressive effect of GCs in adult albino rats.Materials and Methods:Forty-five adult albino rats were equally divided into 3 groups. Group I: normal vehicle control (n = 15), Group II: steroid-treated animals (n = 15), and Group III: steroid/barley-treated group (n = 15). Specimens from spleen were processed for light and electron microscopy.Results:In steroid-treated group, the histological changes in white and red pulp were in the form of loss of architecture and wide empty spaces among the cells. Most of the cells showed degenerative change, dilatation of blood sinusoids, and deposition of fibrinoid material among the cells of the RP. However, multiple lysosomal bodies were observed in both dendritic and macrophage cells. These changes are improved in steroid/barley-treated group in the form of increasing the number and size of the lymphatic follicles. Most of the splenic cells regained normal structure. Dendritic cell marker CD86 and macrophage marker CD68 expression are increased.Conclusion:Barley protects the spleen tissues from steroid-induced structural changes; this could be mediated through its antioxidant effects, so barely is recommended as a healthy diet in patients consuming steroids.

Hepcidin Predicts Decrease in Erythroid Expansion in Sickle Cell Disease Patients Treated with Inhaled Steroids

Sickle cell disease (SCD) is a recessively inherited hemoglobin disorder; the most common and severe form is a consequence of homozygous βS mutation. High concentration of hemoglobin S damages RBC membranes, leading to hemolysis, vaso-occlusion, and inflammation, which together result in anemia, recurrent painful crises, and multiple end-organ damage (i.e. brain, kidney, lung, and bone). Anemia in SCD is multi-factorial. Causes include hemolysis, ineffective erythropoiesis, impaired iron utilization, insufficient erythropoietin responsiveness, and low oxygen affinity [Sherwood Blood 1986]. RBC transfusions are used to ameliorate symptoms and complications but indications are not clearly defined for adults. We postulate that impaired iron utilization in SCD is a consequence of complex regulation of hepcidin, the main hormone regulating circulating and systemic iron. We aim to explore correlation between hepcidin, inflammation and erythropoiesis to enhance our understanding of iron metabolism, hepcidin regulation, and pathophysiology of anemia in SCD. Ultimately this may yield more specific indications for RBC transfusion, and pave the way for novel therapeutic approaches.High hepcidin results in the sequestration of iron within macrophages and prevents further iron absorption in the gastrointestinal tract. Hepcidin expression is enhanced by iron and inflammation and suppressed by hypoxia and erythropoiesis. Distinguishing the relative contribution of these competing effects on hepcidin in SCD is complicated. For example, adult SCD patients in steady state have significantly lower hepcidin relative to heterozygous controls and do not correlate with markers of inflammation and erythropoiesis [Kroot Haematologica 2009]. In a randomized, placebo-controlled trial, inhaled steroids (mometasone) were administered to non-asthmatic SCD patients [Glassberg Am J Hematol 2017]. The results demonstrate improved pain scores and reduced hemolysis in the treated group although the mechanism of this effect is not known. In a subsequent analysis, markers of inflammation are suppressed in the treated group, correlating with macrophage activation. We thus evaluate hepcidin expression in stored serum samples from this trial of SCD patients treated with inhaled steroids or placebo. Samples before and after treatment were analyzed. Serum hepcidin quantification was performed with Hepcidin-25 ELISA kit (Intrinsic Lifesciences LLC). In addition, we evaluate if and how hepcidin levels correlate with pro-inflammatory markers measured with olink inflammation assay.Serum hepcidin concentration is not different in steroid- vs. placebo-treated SCD patients before or after treatment and no significant difference is observed in the hepcidin ratio after:before treatment between the two groups (Fig 1a). However, in the steroid group, hepcidin concentrations are increased in a higher proportion of patients although the difference does not reach statistical significance (Fig 1b). We thus hypothesize that hepcidin levels may be a marker of increased erythropoiesis relative to inflammation in SCD. Both IL-6 (Fig 2a) and IL-10 (Fig 2b), cytokines known to induce hepcidin expression during inflammation, decrease after treatment with steroids relative to placebo, and neither correlates with hepcidin concentration after treatment (Table I). Hepcidin is however inversely correlated with adenosine deaminase (ADA) and hemoglobin S and directly correlative with fibroblast growth factor 23 (FGF23), monocyte chemoattractant protein 1 (MCP1), and hemoglobin F in both placebo- and steroid-treated groups (Table I), potentially suggesting that hepcidin inversely correlates with expanded erythropoiesis. We thus use the newly available human ELISA kit for erythroferrone (ERFE) (Intrinsic Lifesciences LLC), a recently identified erythroid regulator of hepcidin [Kautz Nat Gen 2014], to evaluate correlation with hepcidin. Our results demonstrate that serum ERFE concentration decreases in steroid- (Fig 3a) but not placebo-treated SCD patients (Fig 3b), and no correlation with hepcidin is observed. Taken together, these data for the first time demonstrate a decrease in erythropoiesis and erythroid-regulation-induced hepcidin suppression in inhaled-steroid-treated SCD patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Correlation between serum periostin biomarker, spirometric airflow limitation, and airway dimensions by multidetector computed tomography in bronchial asthma

BackgroundPeriostin has shown to be involved in the many aspects of allergic inflammation, such as acceleration of allergen-induced eosinophil recruitment, development of a Th2 phenotype, increased expression of inflammatory mediators, and airway remodeling and fibrosis in bronchial asthma and that fibrosis is one factor that causes steroid resistance or hyporesponsiveness in bronchial asthma.AimThis study aimed to evaluate the possible role of serum periostin as a biomarker for airway inflammation, for predicting the patient’s possible response to inhaled corticosteroids (ICS) after its regular use and its correlation with disease severity and control compared with functional and radiological findings.Patients and methodsSixty nonsmoker, asthmatic patients of at least 20 years of age and 20 control healthy nonsmokers with matched age and sex were included. Patients were then subclassified into two: first, according to the asthma severity into mild, moderate, and severe and then according to asthma control (controlled, poorly controlled, and uncontrolled). Serum periostin, spirometry, and multidetector computed tomography were performed for all included populations.ResultsThere was significant statistical direct relation with increased serum periostin level and wall area and bronchial wall thickening (BWT) with asthma severity and all showed high significant increase among patients with uncontrolled than those with controlled asthma. Highly significant statistical direct correlation was found between BWT and serum periostin level. There was highly statistically significant decreased serum periostin level and BWT among the steroid-treated group of patients than in steroid-naive asthma (nonsteroid treated group of patients) which were significantly decreased after regular daily use of ICS for 6 months and also among uncontrolled patients after being adequately controlled than their baseline states.ConclusionSerum periostin marker and BWT had a significant, sensitive, accurate clinically relevant indicative value (especially when combined) as regards asthma control and severity and probable adequate response to ICS. Serum periostin not only could be a reliable biomarker for eosinophilic inflammation but also may contribute to the development of airway remodeling as assessed by multidetector computed tomography.

Nefropatías tubulointersticiales no obstructivas biopsiadas en Uruguay

IntroductionInterstitial nephropathies include a wide spectrum of acute and chronic renal diseases. The aims of this study were to evaluate frequency, clinical onset, histological damage, treatment and outcomes of patients with non-obstructive tubulointerstitial nephropathies (TIN) in Uruguay (defined by clinical diagnosis and/or renal biopsy). MethodsA retrospective analysis was performed on the complete clinical records of 124 patients. They were classified into two groups: Group 1: 66 patients with a clinical diagnosis of TIN and chronic kidney disease from the Uruguayan Renal Healthcare Program (PSR), and Group 2: 58 patients from the national Registry of Kidney biopsies (RUG/RUB). ResultsIn both cohorts, being female doubled the risk of TIN vs men (OR 2.3 in the PSR and 1.9 in the RUB, P<.05), mainly due to by drugs. The most frequent clinical presentation in the biopsied group was as acute renal failure/rapidly progressive renal failure (Table 1). A higher degree of interstitial infiltration of inflammatory cells was associated with more frequent steroid treatment (OR 6.3, 95% CI; 1.6–24.3, P<.05). In the steroid-treated group, a lower level of interstitial fibrosis was associated with glomerular filtration rate improvement (OR 0.143, 95% CI; 0.028-0.720, P<.05) ConclusionsThe results were similar to those found in international reports on the clinical presentation of TIN, and highlight the importance of renal histology in treatment decisions and to predict outcomes.