Prednisone Group Research Articles

The Effects of Burst Steroid Therapy on Short-term Decongestion in Acute Heart Failure Patients With Pro-inflammatory Activation: A Post Hoc Analysis of the CORTAHF Randomized, Open-label, Pilot Trial

The effect of steroids on congestion in patients with acute heart failure (AHF) is not known. Patients with AHF, NT-proBNP levels > 1500 pg/mL and high-sensitivity C-reactive protein (hsCRP) levels > 20 mg/L were randomized to once-daily oral 40 mg prednisone for 7 days or usual care. In this post hoc analysis, congestion score was calculated on the basis of orthopnea, edema and rales (0 reflecting lack of congestion, and 9 maximal congestion) at each time point. Among 100 eligible patients randomized, those assigned to prednisone had a greater improvement in congestion score at day 31 (win odds for the prednisone group compared to usual care at day 31 was 1.77 (95% CI 1.17-2.84; P = 0.0066) in all patients and 2.41 (95% CI 1.37-5.05; P = 0.0016) in patients with IL-6 > 13 pg/mL at baseline. In patients with congestion scores ≥ 7 at baseline, the effects of prednisone therapy on the EQ-5D visual analog scale score were 4.30 (95% CI 0.77-7.83) points at day 7 and 5.40 (0.51-10.29) points at day 31, accompanied by lower heart rate and respiratory rate and higher oxygen saturation compared to usual care. In patients with AHF and inflammatory activation, 7-day steroid therapy was associated with reduction in signs of congestion up to day 31. These results need confirmation in larger studies examining potential effects of steroids on congestion, diuresis, fluid redistribution and vascular permeability as well as clinical effects in AHF.

Burst steroid therapy for acute heart failure: The CORTAHF randomized, open-label, pilot trial.

Burst steroid therapy, effective in acute respiratory diseases, may benefit patients with acute heart failure (AHF) in whom inflammatory activation is associated with adverse outcomes. CORTAHF assessed whether burst steroid therapy reduces inflammation and results in better quality of life and clinical outcomes in AHF. Patients with AHF, N-terminal pro-B-type natriuretic peptide >1500 pg/ml, and high-sensitivity C-reactive protein (hsCRP) >20 mg/L were randomized 1:1 to oral, once daily 40 mg prednisone for 7 days or usual care, without blinding. Patients were followed for 90 days. A total of 101 patients were randomized. At day 7 the primary endpoint, hsCRP decreased in both arms-adjusted geometric mean ratios (GMRs) were 0.30 and 0.40 in the prednisone and usual care arms (ratio of GMRs 0.75, 95% confidence interval [CI] 0.56-1.00, p = 0.0498). The 90-day risk of worsening heart failure (HF), HF readmission or death as reported by the unblinded investigators was significantly lower in the prednisone group (10.4%) than in usual care (30.8%) (hazard ratio 0.31, 95% CI 0.11-0.86, p = 0.016). The EQ-5D visual analogue scale score as reported by the unblinded patients increased more in the prednisone group on day 7 (least squares mean difference 2.57, 95% CI 0.12-5.01 points, p = 0.040). All effects were statistically significant in the pre-specified subgroup with centrally-measured interleukin-6 >13 pg/ml. Adverse events, particularly hyperglycaemia, occurred more in the prednisone group with no difference in infection rate. In this small open-label study of patients with AHF, burst steroid therapy was associated with reduced inflammation as measured by hsCRP levels at day 7 (primary endpoint). Secondary endpoints showed improved quality of life at day 7 and reduced 90-day risk of death or worsening HF. Large prospective studies are needed to evaluate these findings.

#777 Renal recovery for patients with ANCA-associated vasculitis and low eGFR in a Spanish cohort

Abstract Background and Aims Renal failure secondary to ANCA-associated vasculitis (AAV) represents a clinical and therapeutic challenge [1]. Fifteen percent to 38% of the patients develop end-stage kidney disease within 5 years, and once patients need dialysis, 29% to 82% die or remain on dialysis 3 to 6 months after its initiation [2]. Therefore, effectively managing renal vasculitis and preventing patients from reaching dialysis have important consequences [2]. A post hoc analysis of ADVOCATE trial examined outcomes in a patient subgroup with severe renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) ≤20 ml/min per 1.73 m2) at enrollment into the trial, and observed an average eGFR increase of 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0,003) [2]. This study aimed to compare the average eGFR increase in our cohort of AAV with severely reduced GFR (<20 ml/min) treated with different induction treatment schemes. Method We performed a retrospective study which included 19 patients with the diagnosis of AAV and severe renal insufficiency at onset with eGFR between 15 to 20 ml/min per 1.73 m2. We analyzed the eGFR increase after 12 months of follow-up, according to the induction treatment scheme: cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other (prednisone alone, prednisone with plasma exchange or prednisone with mycophenolic acid). We compared our results to those obtained in the avacopan and prednisone groups in the ADVOCATE trial. Results In the subgroup of eGFR between 15 to 30 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 21 ± 5 ml/min per 1.73 m2 and after 12 months of follow-up the mean eGFR was 41 ± 23 ml/min per 1.73 m2 with an increase of 20 ± 23 ml/min per 1.73 m2. In the subgroup of eGFR between 15 to 20 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 17 ± 2 ml/min per 1.73 m2 and after 12 months of follow-up, the mean eGFR was 35 ± 20 ml/min per 1.73 m2 with an increase of 18 ± 21 ml/min per 1.73 m2. After 12 months of follow-up, the mean increase of eGFR was 18, 17, 10 and 23 ml/min per 1.73 m2 in the cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other groups, respectively. We compared our results with the post hoc analysis of the ADVOCATE trial in Table 1 and our results are similar to the avacopan group and better than the prednisone group (p < 0.05). Conclusion In our cohort of eGFR between 15 to 20 ml/min per 1.73 m2 at enrollment, the mean increase in eGFR after 12 months of follow-up was similar to the avacopan group and greater than the prednisone group in the ADVOCATE trial.

A randomised trial of oral prednisone for cystic fibrosis pulmonary exacerbation treatment.

Elevated markers of systemic and pulmonary inflammation are associated with failure to recover lung function following pulmonary exacerbations in people with cystic fibrosis (pwCF). Our aim was to determine whether adjuvant oral prednisone treatment would improve recovery of forced expiratory volume in 1 s (FEV1) % pred in CF pulmonary exacerbations not responding to antibiotic therapy. This was a randomised, double-blind, placebo-controlled trial in pwCF treated with intravenous antibiotics for a pulmonary exacerbation. At day 7, those who had not returned to >90% baseline FEV1 % pred were randomised to adjuvant prednisone 1 mg·kg-1 twice daily (maximum 60 mg·day-1) or placebo for 7 days. The primary outcome was the difference in proportion of subjects who recovered >90% baseline FEV1 % pred at day 14 of i.v. antibiotic therapy. 173 subjects were enrolled, with 76 randomised. 50% of subjects in the prednisone group recovered baseline FEV1 on day 14 compared with 39% of subjects in the placebo group (difference of 11%, 95% CI -11-34%; p=0.34). The mean±sd change in FEV1 % pred from day 7 to day 14 was 6.8±8.8% predicted in the prednisone group and 4.6±6.9% predicted in the placebo group (mean difference 2.2% predicted, 95% CI -1.5-5.9%; p=0.24). Time to subsequent exacerbation was not prolonged in prednisone-treated subjects (hazard ratio 0.83, 95% CI 0.45-1.53; p=0.54). This study failed to detect a difference in FEV1 % pred recovery between adjuvant oral prednisone and placebo treatment in pwCF not responding at day 7 of i.v. antibiotic therapy for pulmonary exacerbations.

Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury.

Purpose: To determine the impact of oral prednisone on the final visual acuity (VA) and prevention of proliferative vitreoretinopathy (PVR) in patients having pars plana vitrectomy (PPV) for globe injuries. Methods: A retrospective chart review was performed of all globe injuries with an initial repair and subsequent PPV between 2009 and 2018. Data included the initial VA, zones of injury, initial closure date, time to secondary intervention (PPV), oral prednisone (1 mg/kg/day) use, the final VA, and enucleation rate. Multivariable regression models were used to assess the impact of oral prednisone use on anatomic and functional outcomes. Results: The mean (±SD) patient age was 46.25 ±18.56 years (range, 13-92); 131 (83.9%) were men. Oral prednisone intake was recorded in 81 patients (52.3%). The prednisone group had significantly more zone 3 involvement (P = .001), worse initial VA (2.28 vs 1.92 logMAR; P = .003), and a greater mean number of surgeries (P = .020) than the no-steroids (control) group but an equivalent final logMAR VA (1.57 vs 1.52; P = .881). The prednisone group had significant VA improvement (P = .025); however, oral prednisone use did not predict the development of PVR (29.23% vs 12.90%; odds ratio [OR], 2.81; 95% CI, 0.89-8.85) or retinal detachment (27.27% vs 29.58%; OR, 0.59; 95% CI, 0.23-1.56). Conclusions: Despite a worse initial clinical presentation, patients who received oral prednisone had significant visual improvement compared with the control group. However, oral prednisone (1 mg/kg/day) use at the time of injury did not decrease the PVR rate.

Effects of Ziyin Liangxue Formula Combined with Prednisone on Immune Function and ST2/IL-33 Pathway in Mice with Immune Thrombocytopenia

To investigate the effects of Ziyin Liangxue formula combined with prednisone on immune function and the ST2/IL-33 pathway in mice with immune thrombocytopenia. In 40 BALB/c mice, 32 were constructed as immune thrombocytopenia mouse models by antiplatelet serum injection. After successful modeling, the mice were randomly divided into model group, Ziyin Liangxue formula group (0.2 ml/10 g), prednisone group (0.2 ml/10 g), and Ziyin Liangxue formula + prednisone group (0.2 ml/10 g), 8 mice in each group, and the other 8 mice were set as control group. The drugs were administered by gavage at the dose, and the model group and control group were given equal amounts of saline by gavage once a day for 2 weeks of continuous intervention. Blood samples and spleen tissues were collected, the peripheral platelet count was measured by automatic hematology analyzer, the pathological changes in spleen tissue was observed by HE staining, the levels of serum transforming growth factor (TGF)-β, interleukin (IL)-17, and peripheral blood thrombopoietin (TPO) were detected by enzyme-linked immunosorbent assay (ELISA), the expression of IL-33, sST2, and ST2 in spleen tissue was detected by Western blot, and the cell counts of peripheral blood Th17 and Treg were detected by flow cytometry. Compared with the control group, the number of platelets, the level of TPO, TGF-β, and Treg cells were significantly decreased (P <0.05), while the level of IL-17, Th17 cells, and the expression of IL-33, sST2, and ST2 protein were significantly increased in the model group (P <0.01). Compared with the model group, the number of platelets, the level of TPO, TGF-β, and Treg cells were significantly increased (P <0.05), while the level of IL-17, Th17 cells, and the expression of IL-33, sST2, and ST2 protein were significantly decreased in the Ziyin Liangxue formula + prednisone group (P <0.01). Ziyin Liangxue formula + prednisone can effectively regulate Th17/Treg balance, thus effectively improve immune thrombocytopenia, and the mechanism may be related to the regulation of ST2/IL-33 signaling pathway.

Improvement of idiopathic pulmonary fibrosis through a combination of Astragalus radix and Angelica sinensis radix via mammalian target of rapamycin signaling pathway-induced autophagy in rat.

There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF) in clinic. Astragalus radix (AR; Huangqi) and Angelica sinensis radix (AS; Danggui) have been frequently used in the treatment of IPF. This study aimed to reveal the pharmacological effects and the mechanisms of the action of an AR-AS combination in treating IPF. Sprague-Dawley rats were randomly divided into six groups (n=5): control, bleomycin (BLM) model, AR, AS, AR + AS, and prednisone (PDN) groups. A transforming growth factor-β1 (TGF-β1)-induced MRC-5 cell model were also used. Pulmonary fibrosis, inflammation, oxidative stress, and autophagy were evaluated by performing hematoxylin and eosin (H&E) staining, Masson staining, immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and hydroxyproline assay following the treatment of AR, AS, and the AR-AS herb pair. Rats administered the AR-AS herb pair had lower α-smooth muscle actin (α-SMA), collagen I, fibronectin, and vimentin levels in lung tissues, and lower inflammatory cytokine levels in rat serum. In addition, the AR-AS herb pair induced mammalian target of rapamycin (mTOR)-mediated autophagy and reduced oxidative stress in BLM-induced rats. The effects of the AR and AS combination were confirmed in MRC-5 cells treated with TGF-β1. Specifically, the combination of AR and AS attenuated MRC-5 cell fibrosis, inflammation, and oxidative stress while inducing autophagy. The combination of AR and AS protects against IPF by inducing autophagy via inhibiting the mTOR signaling pathway. The synergistic action of AR and AS is superior to that of either AR or AS alone.

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy

ImportanceThe Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available.ObjectiveTo assess the long-term efficacy and safety of the Ritux 3 treatment regimen.Design, Setting, and ParticipantsThis 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015.ExposurePatients were initially randomized in the rituximab plus prednisone group or prednisone-alone group.Main outcomes and measuresThe primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse.ResultsOf the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse.Conclusions and RelevanceIn this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.

In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs?

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (&gt; 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Hematologic Response to Steroid Use in Patients with Primary Immune Thrombocytopenia: A Research Study in a Salvadoran Population

Introduction. Thrombocytopenia Immune (ITP) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. It is one of the more common causes of thrombocytopenia in otherwise asymptomatic adults. The use of high-doses dexamethasone has proven efficacy and safety in previously untreated patients with immune thrombocytopenia even though these findings are not entirely clear yet. AIM. The primary goal to assess the global response (platelets &amp;gt;30 x 109/L) and complete response (platelets &amp;gt;100 x 109/L) within the different implemented regimes in previously untreated adult with primary immune thrombocytopenia. Further goals aimed to describe the clinical characteristic of patients with primary immune thrombocytopenia and the most frequent adverse events in the use of steroids. Results. A total of 44 patients were treated with steroids, 16 patients in the high-dose dexamethasone (HD-DXM) group, 23 patients received methylprednisolone (MTP) and 5 patients with prednisone (PDN). The female gender was the most affected in all the groups with 61.3% (n=27) presenting more cases than the female sex in the methylprednisolone group 65.2% (n=15), although without significant statistical difference (P = 0.384). The mean age of onset was 38, 44, and 40 years, respectively (P = 0.352). The most frequent clinical manifestations were purpura sicca (petechiae and bruising) with 75%, 91.3% and 60.0%, for the dexamethasone, methylprednisolone and prednisone groups, respectively. The mean platelet count in the groups was around the mean of 26 x 109/L, with the methylprednisolone group presenting the lowest values (3 x 109/L). The overall response was different for the three groups (87.5% vs 95.6% vs 100%, P = 0.43) with a complete response of 56.2% vs 60.8% vs 80.0% (P = 0.85). Early response was achieved in the methylprednisolone group with 3.5 days, versus dexamethasone with 4.0 days and prednisone with 7 days. The sustained response at 6 months was lower in the prednisone group 80.0%. The most frequent adverse events occurred in the HD-DXM group with fatigue in 31.2% (n = 5) followed by edema, hyperglycemia and insomnia with 18.7% (n = 3). Conclusions. Our study demonstrated that PDN provides greater overall responses as initial treatment in ITP. MTP provides the fastest responses followed by HD-DXM. The sustained response was maintained in the HD-DXM Group. The HD-DXM group presented 68.7% cases with at least one adverse event associated with the use of the steroid. The findings suggest continuing to perform more studies in our population.

Prednisone Plus Ivig Compared with Prednisone for Immune Thrombocytopenia during Pregnancy

Introduction Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by an isolated low platelet count and is the most common cause of thrombocytopenia during pregnancy, accounting for 1%-4% of thrombocytopenia in pregnant women. Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications. However, management of ITP during pregnancy can be challenging because treatment choices are limited. Corticosteroids or intravenous immunoglobulin (IVIg) are recommended as first-line treatments for pregnant women with ITP, but the response to initial treatment is approximately 39% and 38%, respectively, lower than that in nonpregnant patients with ITP. Therefore, in-depth studies investigating new solutions for the first-line treatment of ITP during pregnancy are urgently needed. Our previous retrospective study revealed an advantage of prednisone combined with IVIg compared to prednisone monotherapy for pregnant patients with ITP. Therefore, the aim of this prospective, randomized, open-label study was to further assess the efficacy and safety of prednisone plus IVIg compared to prednisone monotherapy in pregnant women with ITP. The study has been registered at clinicaltrials.gov. NCT05333744 Methods Eligible treatment-naive ITP patients during pregnancy with a platelet count &amp;lt; 30 × 10^9/L, accompanied by or without bleeding symptoms, were randomly assigned 1:1 to receive prednisone 20 mg per day for 4 weeks plus IVIg 400 mg/kg (total dose ≤20 g per day) for 5 days or prednisone 20 mg monotherapy per day for 4 weeks. Prednisone was gradually tapered to the maintenance dose of 5-10 mg per day until 6 weeks after delivery if there was a response to treatment; otherwise, prednisone was gradually tapered to withdrawal. The primary outcome was overall response (OR), defined as a platelet count ≥ 30 × 10^9/L, a doubling of the baseline platelet count and the absence of bleeding. Secondary endpoints included complete response (CR), time to response, platelet counts at delivery, platelet counts of newborns, and adverse events in parturients. CR was defined as platelet count ≥100×10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding. Results A total of 100 treatment-naive ITP patients during pregnancy were randomly assigned to either the prednisone plus IVIg (n=50) or prednisone monotherapy (n=50) groups. All the baseline characteristics were comparable between the two groups. The median ages of patients in the prednisone plus IVIg group and prednisone monotherapy group were 30.32 years (range, 22-43) and 30 years (range, 28-46), respectively. For patients in the combination and monotherapy groups, the mean estational ages at intervention start were 28.3 weeks and 30.9 weeks, respectively. All patients were followed up for more than 2 months. OR was observed in 23 (46.0%) patients in the combination group and 22 (44%) in the monotherapy group, and no significant difference was observed between the two groups (p=0.91). A significant difference was observed in the time to response between the prednisone plus IVIg group and prednisone monotherapy group (6.14 days vs. 9.84 days, p=0.001). However, the predelivery platelet transfusion of the prednisone plus IVIg group was greater than that of the prednisone monotherapy group. There were no significant differences in the delivery mode between the combined group and monotherapy group. No significant differences were found between the two groups in neonatal outcomes, particularly concerning the neonatal platelet counts. Conclusion Prednisone plus IVIg was an effective and safe treatment for ITP in pregnancy, and this therapy may be a new first-line treatment option for pregnant patients with ITP.

Feasibility of apalutamide combined with androgen deprivation therapy and short-course low-dose prednisone in treating metastatic hormone-sensitive prostate cancer: a pilot randomized controlled trial.

The role of prednisone in the prevention of androgen receptor antagonist-related rash and treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This pilot trial (ChiCTR2200060388) aimed to investigate the feasibility of apalutamide combined with androgen deprivation therapy (ADT) and short-course low-dose prednisone in the treatment of mHSPC. All patients received apalutamide and ADT and were randomly divided into two groups based on the administration of oral prednisone or not (control group). The primary endpoint was the incidence of rash. The secondary endpoint included the proportions of patients with a decline in PSA ≥50% from baseline, PSA ≥90% from baseline, and decreased to PSA ≤0.2 ng/mL. Between June 2021 and March 2022, a total of 83 patients were enrolled (41 in the prednisone group and 42 in the control group). During the 6-month follow-up, the incidence of rash was significantly lower in the prednisone group compared with the control group (17.1% vs. 38.1%, P=0.049). There were no significant differences in the incidence of other adverse events, the number of patients who required dose adjustment (reduction, interruption, or discontinuation) of apalutamide due to rash, the number of patients with prostate-specific antigen (PSA) decreased by ≥50%, the number of patients with PSA decrease ≥90%, and the number of patients with PSA ≤0.2 ng/mL between the two groups. All patients with diabetes had stable glycemic control with no glucose-related adverse events. In patients with mHSPC, the addition of short-course low-dose prednisolone to apalutamide plus ADT can reduce the incidence of rash without risk of other adverse events.

In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p&lt;0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p&lt;0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis

IntroductionGiant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. MethodsWe conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. ResultsOne hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs –0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference –0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DiscussionOur data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.

Impact of Asian Race on Prognosis in De Novo Metastatic Prostate Cancer.

Little is known about the impact of Asian race on the long-term survival outcomes of males with de novo metastatic prostate cancer (PCa). Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. This multiple-cohort study included individual patient-level data for males with de novo metastatic PCa from the following 3 cohorts: LATITUDE clinical trial data (n=1,199), the SEER program (n=15,476), and the National Cancer Database (NCDB; n=10,366). Primary outcomes were overall survival (OS) in LATITUDE and NCDB and OS and cancer-specific survival in SEER. Across all 3 cohorts, Asian patients diagnosed with de novo metastatic PCa had better survival than white patients. In LATITUDE, median OS was significantly longer in Asian versus white patients in the androgen deprivation therapy (ADT) + abiraterone + prednisone group (not reached vs 43.8 months; hazard ratio [HR], 0.45; 95% CI, 0.28-0.73; P=.001) as well as in the ADT + placebo group (57.6 vs 32.7 months; HR, 0.51; 95% CI, 0.33-0.78; P=.002). In SEER, among all patients diagnosed with de novo metastatic PCa, median OS was significantly longer in Asian versus white males (49 vs 39 months; HR, 0.76; 95% CI, 0.68-0.84; P<.001). Among those who received chemotherapy, Asian patients again had longer OS (52 vs 42 months; HR, 0.71; 95% CI, 0.52-0.96; P=.025). Using data on cancer-specific survival in SEER resulted in similar conclusions. In NCDB, Asian patients also had longer OS than white patients in aggregate and in subgroups of males treated with ADT or chemotherapy (aggregate: 38 vs 26 months; HR, 0.72; 95% CI, 0.62-0.83; P<.001; ADT subgroup: 41 vs 26 months; HR, 0.71; 95% CI, 0.60-0.84; P<.001; chemotherapy subgroup: 34 vs 25 months; HR, 0.67; 95% CI, 0.57-0.78; P<.001). Asian males have better OS and cancer-specific survival than white males with metastatic PCa across different treatment regimens. This should be considered when assessing prognosis and in designing multinational clinical trials.

Efficacy and safety of oral corticosteroids to treat outpatients with acute exacerbations of COPD in primary care: a multicentre pragmatic randomised controlled study.

To compare prednisone and placebo for the treatment of outpatients treated for acute exacerbations of chronic obstructive pulmonary disease (COPD) in a primary care setting. A multicentre, parallel, double-blind, pragmatic randomised controlled trial was performed in France. A total of 66 general practitioners included patients aged ≥40 years with cumulative smoking of ≥10 pack-years and a diagnosis of certain or likely acute exacerbation of COPD. Oral prednisone (40 mg) or placebo were administered daily for 5 days. The main outcome was treatment failure at 8 weeks, defined as a composite criterion based on the occurrence of at least one of the following: unplanned visit to an emergency department or to a practitioner in the ambulatory setting, hospital admission or death. The planned sample size was 202 patients per group. 175 patients were included from February 2015 to May 2017 (43% of the planned sample). All-cause 8-week treatment failure rate was 42.0% in the prednisone group and 34.5% in the placebo group (relative risk 1.22, 95% CI 0.87-1.69, p=0.25). Respiratory-related 8-week treatment failure rate was 27.6% in the prednisone group and 13.6% in the placebo group (relative risk 2.00, 95% CI 1.15-3.57, p=0.015). Although the planned sample size was not achieved, the study does not suggest that oral corticosteroids are more effective than placebo for the treatment of an acute exacerbation of COPD in a primary care setting.

Long-term prednisone treatment causes fungal microbiota dysbiosis and alters the ecological interaction between gut mycobiome and bacteriome in rats.

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats.

Yue-bi-tang attenuates adriamycin-induced nephropathy edema through decreasing renal microvascular permeability via inhibition of the Cav-1/ eNOS pathway.

Edema is one of the most typical symptoms of nephrotic syndrome. Increased vascular permeability makes a significant contribution to the progression of edema. Yue-bi-tang (YBT) is a traditional formula with excellent clinical efficacy in the treatment of edema. This study investigated the effect of YBT on renal microvascular hyperpermeability-induced edema in nephrotic syndrome and its mechanism. In our study, the content of target chemical components of YBT was identified using UHPLC-Q-Orbitrap HRMS analysis. A nephrotic syndrome model was replicated based on male Sprague-Dawley rats with Adriamycin (6.5mg/kg) by tail vein injection. The rats were randomly divided into control, model, prednisone, and YBT (22.2g/kg, 11.1g/kg, and 6.6g/kg) groups. After 14d of treatment, the severity of renal microvascular permeability, edema, the degree of renal injury, and changes in the Cav-1/eNOS pathway were assessed. We found that YBT could regulate renal microvascular permeability, alleviate edema, and reduce renal function impairment. In the model group, the protein expression of Cav-1 was upregulated, whereas VE-cadherin was downregulated, accompanied by the suppression of p-eNOS expression and activation of the PI3K pathway. Meanwhile, an increased NO level in both serum and kidney tissues was observed, and the above situations were improved with YBT intervention. It thus indicates YBT exerts therapeutic effects on the edema of nephrotic syndrome, as it improves the hyperpermeability of renal microvasculature, and that YBT is engaged in the regulation of Cav-1/eNOS pathway-mediated endothelial function.

Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization

Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate. To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure. A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021). Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy. The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life. Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights. Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure. Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.

PD21-07 RACIAL IMPACT (ASIAN VS. WHITE) ON THE PROGNOSIS OF PATIENTS WITH DE NOVO MCSPC: AN ANALYSIS ON LATITUDE, SEER AND NCDB

You have accessJournal of UrologyCME1 Apr 2023PD21-07 RACIAL IMPACT (ASIAN VS. WHITE) ON THE PROGNOSIS OF PATIENTS WITH DE NOVO MCSPC: AN ANALYSIS ON LATITUDE, SEER AND NCDB XuDong Ni, Michael Luu, Weiwei Ma, Stephen Freedland, Timothy J. Daskivich, and Yao Zhu XuDong NiXuDong Ni More articles by this author , Michael LuuMichael Luu More articles by this author , Weiwei MaWeiwei Ma More articles by this author , Stephen FreedlandStephen Freedland More articles by this author , Timothy J. DaskivichTimothy J. Daskivich More articles by this author , and Yao ZhuYao Zhu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Little is known about the impact of race (Asian or White) on the long-term survival outcomes of men with de novo mCSPC treated with different methods. Understanding racial disparities in survival is critical for accurate prognostic risk stratification and for informing the design of multiregional clinical trials. METHODS: This multiple-cohort study included individual patient-level data of men with de novo mCSPC from the following 3 cohorts: LATITUDE clinical trial data (LATITUDE [n = 1199]); Surveillance, Epidemiology, and End Results (SEER [n = 5496]); and the National Cancer Database (NCDB [n = 10366]). Key efficacy outcomes were overall survival (OS) in LATTITUDE and NCDB as well as OS and cancer-specific survival (CSS) in SEER. Kaplan-Meier analysis with propensity score matching (PSM) was used for survival analysis. Hazard ratios were calculated using a multivariate Cox proportional-hazard model. RESULTS: Across all three cohorts, Asian patients diagnosed with de novo mCSPC had better OS and CSS than White patients. In LATITUDE, median OS was significantly longer in Asian than in White men in the ADT+Abiraterone+Prednisone group (not reached vs. 43.8 months, HR0.47, 95% CI 0.28–0.77, P = 0.003 for cox analysis) as well as in the ADT+placebo group (57.6 months vs. 32.7 months, HR0.49, 95% CI 0.32–0.75, P = 0.001 for cox analysis). In SEER, among all patients diagnosed with de novo mCSPC, median OS was significantly longer in Asian than in White men (53 months vs. 42 months, HR0.76, 95% CI 0.68–0.85, p<0.001 for cox analysis). When analyses were restricted to patients who received chemotherapy, Asian men again had longer OS (67 months vs. 41 months, HR0.70 95% CI 0.51–0.95, p=0.02 for cox analysis). Using CSS data in SEER resulted in similar conclusions as OS. In NCDB, Asians also had longer OS than White men (whole cohort: 38 months vs. 26 months, HR0.73, 95%CI 0.63–0.84, P = 0.02 for cox analysis; ADT subgroup: 41 months vs. 26 months, HR0.75, 95% CI 0.63–0.89, p<0.001 for cox analysis; Chemotherapy subgroup: 34 months vs. 27 months, HR0.80, 95% CI 0.69–0.94, p=0.005 for cox analysis). CONCLUSIONS: Asian men had better OS and CSS than White men with mCSPC across different treatment regimens in all datasets examined and should be considered as an independent prognostic factor. This racial difference should also be considered when designing multiregional clinical trials. Further studies including biological analyses are needed to understand the etiology of the apparent survival advantage for Asian men. Source of Funding: NSFC 81972375, 81802528 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e592 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information XuDong Ni More articles by this author Michael Luu More articles by this author Weiwei Ma More articles by this author Stephen Freedland More articles by this author Timothy J. Daskivich More articles by this author Yao Zhu More articles by this author Expand All Advertisement PDF downloadLoading ...