Prednisolone Research Articles

Pediatric frequent relapsing nephrotic syndrome with multiple cerebral infarctions accompanied by patent foramen ovale and cerebral venous sinus thrombosis: a case report

BackgroundIdiopathic nephrotic syndrome (NS) presents as a hypercoagulable state, of which thromboembolism (TE) is a well-known life-threatening complication. Although TE is more likely to occur in venous vessels than arterial vessels, arterial TE is important because it may cause after-effects, including tissue necrosis and cerebral infarction (CI); therefore, prompt diagnosis and appropriate treatment are required. We report a pediatric NS case with multiple CIs.Case presentationA 14-year-7-month-old Japanese girl was diagnosed with frequent relapsing NS, accompanied by headache and disturbance of consciousness during the second relapse. Brain magnetic resonance imaging (MRI) and four-dimensional computed tomography revealed multiple CIs, vasogenic edema, and cerebral venous sinus thrombosis (CVST). The patient had no underlying thrombophilia other than hypercoagulability due to NS and prednisolone (PSL), and no cardiac arrhythmia; however, a right-to-left shunt through the patent foramen ovale (PFO) was observed with the Valsalva maneuver by echocardiography. Therefore, we assumed that a potential cause of multiple CIs might be an embolic stroke, caused by thrombosis formed from a hypercoagulable state due to NS and PSL treatment and reached through PFO. Antiplatelet and anticoagulant therapies were administered for TE. She was treated with PSL and mycophenolate mofetil (MMF) for NS. Rituximab (RTX) was administered to prevent NS relapse after complete remission (CR). She underwent transcatheter PFO closure at age 14 years and 9 months because we considered that the right-to-left shunt through the PFO would be one of the risks for recurrent cerebral embolism when NS relapses. One year after the onset of CIs, an MRI indicated that the CVST had resolved, leaving no neurological sequelae due to CI; therefore, anticoagulant therapy was discontinued. And then she has been in CR for NS with only MMF therapy.ConclusionsCI is a serious complication in patients with NS. The pathogenesis of multiple CIs is various, including right-to-left shunt through PFO, in addition to the hypercoagulability due to NS. It is important to investigate and manage underlying risks such as PFO, besides preventing the relapses of NS by aggressive treatments using MMF and RTX, in patients with NS.

Reactivation of hepatitis C virus caused by steroid monotherapy for sudden deafness

Hepatitis C virus (HCV) reactivation has been reported to be caused due to several anticancer drugs and immunosuppressive agents; however, HCV reactivation after steroid monotherapy has rarely been reported. Here, we report the case of a 65-year-old Japanese man with HCV infection who developed HCV reactivation after the administration of prednisolone (PSL) for 6 days for sudden deafness. In the patient history, the positivity for anti-HCV antibody was observed, but serum level of HCV RNA was not measured. Two months after PSL administration, the patient experienced an alanine aminotransferase (ALT) flare and the serum level of HCV RNA was observed to be 6.2 log IU/mL; then, the patient was admitted to our hospital for hepatitis treatment. Based on the clinical course and laboratory findings, the patient was diagnosed with HCV reactivation. Although the ALT levels decreased spontaneously during follow-up, they did not drop to normal range; subsequently, sofosbuvir and ledipasvir treatments were started. A sustained virological response 24 weeks after the end of treatment was achieved. This case study suggests that HCV reactivation with hepatitis flare can occur even after a steroid monotherapy, and doctors should pay attention to HCV reactivation when administering PSL for patients with HCV infection.

Prednisone and prednisolone effects on development, blood, biochemical and histopathological markers of Aquarana catesbeianus tadpoles

Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.

Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study

BackgroundInterstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD.MethodsThis single centre, retrospective nested case–control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups’ patient characteristics.ResultsWe studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs.ConclusionsJAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients.

P996 Clinical Efficacy and Predictive Factors for the Effectiveness of Granulocyte and Monocyte Adsorption Apheresis Therapy for Ulcerative Colitis：A Retrospective Observational Single Center Study

Abstract Background Granulocyte and Monocyte Adsorption Apheresis (GMA) is one of the valuable non-immunosuppressive therapies in the treatment of ulcerative colitis (UC). However, due to the limited number of facilities where GMA can be performed, there are few reports on the combined effects of GMA and prednisolone (PSL), the frequency of GMA implementation or predictive factors for the effectiveness. In this study, we examined the combined effect of GMA and PSL as a remission induction therapy, the frequency of GMA and predictive factors. Methods A retrospective observational study was conducted at Kushiro Rosai Hospital. We analyzed clinical data from UC patients who underwent GMA from February 2015 to May 2023. Results The study included 54 patients (30 males and 24 females), with a median age of 48 years and a median disease duration of 2 years. The median Lichtiger-CAI (L-CAI) was 8. There were 43 patients of pancolitis. There were 51 biologics-naïve patients and 3 biologics-experienced patients. Concomitant medications included 5-ASA agents in 21 patients, immunomodulators in 7 patients, and PSL in 31 patients. The median CRP was 1.19 mg/dl and the median albumin was 3.5 g/dl. Adverse events were observed in 3 patients (fatigue, dizziness, palpitations). The median number of GMA sessions was 10, with 33 patients undergoing twice weekly and 9 patients three times weekly. The clinical remission rate was 80% (43/54), and the clinical response rate was 89% (48/54), with a significant improvement in the median L-CAI from 8 to 3 before and after GMA (P<0.001). In the comparison between the PSL concomitant group and the non-PSL group, the clinical remission rate was 83.9% (26/31) in PSL group and 73.9% (17/23) in non-PSLgroup (P=0.369). The clinical response rate was significantly higher in the PSL group (87% (27/31)) than in non-PSL group (52.2% (12/23)) (P=0.004). There was no significant difference in the clinical remission/response rate between the group that underwent GMA twice a week (76.9% (30/39)/84.6% (33/39)) and three times a week (77.8% (7/9)/77.8% (7/9)). In univariate analysis, biologics-naïve was extracted as a contributing factor to clinical remission. The cumulative remission rate at 52 weeks was 72% overall. There was no significant difference in the cumulative remission rate between the PSL group (76.8%) and the non-PSL group (67.6%) (P=0.524). There was also no significant difference between the twice-weekly group (75%) and the three-times-weekly group (57.1%) (P=0.236). Conclusion GMA for UC was found to be useful and safely performed as a remission induction therapy. Concomitant use of PSL increased the clinical response rate. The frequency of GMA showed that three times per week was as effective as two times per week.

2,4'-Dihydroxybenzophenone Exerts Bone Formation and Antiosteoporotic Activity by Stimulating the β-Catenin Signaling Pathway.

2,4'-Dihydroxybenzophenone (DHP) is an organic compound derived from Garcinia xanthochymus, but there have been no reports on its biochemical functions and bioavailability. In this study, we evaluated whether DHP affects osteoblast differentiation and activation in MC3T3-E1 preosteoblast cells, as well as antiosteoporotic activity in zebrafish larvae. Nontoxic concentrations of DHP-treated MC3T3-E1 preosteoblast cells increased alkaline phosphatase (ALP) activation and mineralization in a concentration-dependent manner, accompanied by higher expression of osteoblast-specific markers, including Runt-related transcription factor 2 (RUNX2), osterix, and ALP. Consistent with the data in MC3T3-E1 preosteoblast cells, DHP upregulated osteoblast-specific marker genes in zebrafish larvae and simultaneously enhanced vertebral formation. We also revealed that DHP increased the phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 and the total expression of β-catenin in the cytosol and markedly increased the localization of β-catenin into the nucleus. Furthermore, DHP restored the prednisolone (PDS)-induced marked decrease in ALP activity and mineralization, as well as osteoblast-specific marker expression. In PDS-treated zebrafish, DHP also alleviated PDS-induced osteoporosis by restoring vertebral formation and osteoblast-related gene expression. Taken together, these results suggest that DHP is a potential osteoanabolic candidate for treating osteoporosis by stimulating osteoblast differentiation.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

BackgroundVacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme1 (UBA1) gene and characterised by an overlap between autoinflammatory and haematologic disorders.Case presentationWe reported a case of a 67-year-Japanese man receiving peritoneal dialysis (PD) who had recurrent aseptic peritonitis caused by the VEXAS syndrome. He presented with unexplained fevers, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed high serum C-reactive protein concentration and increased cell count in PD effluent. He was treated with antibiotics for PD-related peritonitis, but this was unsuccessful. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images demonstrated intense FDG uptake in his left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and he was treated with oral prednisolone (PSL) 15 mg daily with good response. However, he was unable to taper the dose to less than 10 mg daily because his symptoms flared up. Since Tocilizumab was initiated, he could taper PSL dose to 2 mg daily. Sanger sequencing of his peripheral blood sample showed a mutation of the UBA1 gene (c.122 T > C; p.Met41Thr). We made a final diagnosis of VEXAS syndrome. He suffered from flare of VEXAS syndrome at PSL of 1 mg daily with his cloudy PD effluent. PSL dose of 11 mg daily relieved the symptom within a few days.ConclusionsIt is crucial to recognise aseptic peritonitis as one of the symptoms of VEXAS syndrome and pay attention to the systemic findings in the patients.

Development of a broad-spectrum one-step immunoassay for detection of glucocorticoids in milk using magnetosome-based immunomagnetic beads

Immunomagnetic beads provide novel tools for high-throughput immunoassay techniques. In this study, protein G (PG) was immobilized onto bacterial magentic particles (BMPs) using an additional cysteine residue at the C-terminus. A broad-spectrum monoclonal antibody against glucocorticoids (GCs) was attached to BMPs through PG-Fc interaction, generating BMP-PG-mIgG immunomagentic beads. A sensitive one-step immunoassay was developed for GCs based on combination of BMP-PG-mIgG and dexamethasone-horseradish peroxidase tracer (DMS-HRP). The developed assay exhibited half inhibitory concentrations (IC50) for dexamethasone (DMS), betamethasone (BMS), prednisolone (PNS), hydrocortisone (HCS), beclomethasone (BCMS), cortisone (CS), 6-α-methylprednisone (6-α-MPNS), fludrocortisone acetate (HFCS) of 0.98, 1.49, 2.42, 9.29, 1.63, 6.13, 7.3, and 4.89 ng/mL, respectively. The method showed recoveries ranging rates from 86.5 % to 117 % with a coefficient of variation less than 12.3 % in milk sample, which showed a good correlation with LC-MS/MS. Thus, the proposed assay offers a rapid and broad-spectrum screening tool for simultaneous detection of GCs in milk.

Structured organic frameworks as endocrine disruptor adsorbents suitable for Fenton regeneration and reuse

New porous materials, such as metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs), have been actively investigated due to their environmental applications. In this study, four of such structured materials, namely Fe3O4 @COF, MIL-53(Al), MIL-53(Al)-F127 and NH2-MIL-101(Fe) were synthetized. These materials have been tested for the first time for the adsorption in aqueous media of two endocrine disruptor pollutants, bisphenol A (BPA) and prednisolone (PDN). The adsorbents were characterized by the analysis of the point of zero charge (PZC), the functional groups (FTIR) and their physic-chemical structure (N2-isotherms, SEM, XRD and XPS). MIL-53-Al provided the highest uptake of both BPA (177.78 mg g−1) and PDN (280.70 mg g−1) even when using a real wastewater matrix. Additionally, this MOF resulted to be a so-called catalytic-adsorbent, maintaining an appropriate adsorbent capacity after five regenerations cycles via Fenton-like process, causing only 20% and 5% adsorption detriment for BPA and PDN, respectively. This avoids spent adsorbent disposal issues and make this new kind of adsorbent to have the potential to be used in real environmental application scenarios.

Autoimmune hepatitis developed after COVID-19 vaccination and ameliorated temporarily but relapsed or stopped improving, and finally resolved by steroid therapy:a report of three cases

The severe acute respiratory syndrome coronavirus 2 vaccine has contributed to infection control and the prevention of complications due to coronavirus disease 2019 (COVID-19). Conversely, the COVID-19 vaccine has been associated with adverse effects due to liver injury caused by autoimmunity or drugs. To date, Japanese journals have only published five reports of autoimmune liver damage associated with the COVID-19 vaccination. Although the pathogenic mechanism has not yet been fully elucidated, corticosteroids or azathioprine have shown effectiveness in certain patients. However, there have been cases of liver injury resulting in deaths. Here, we encountered three patients who developed autoimmune hepatitis (AIH) within 10 days following vaccination. All three patients were treated with prednisolone (PSL) and achieved remission. However, the serum alanine aminotransferase levels in all cases were observed to either increase or cease to improve during the therapeutic course before PSL administration. It is therefore imperative to closely monitor liver injury after the COVID-19 vaccination. In cases where AIH is suspected and a recurrence of liver dysfunction occurs, PSL may be administered. Future considerations should not only encompass the underlying mechanism by which autoimmunity contributes to the development of liver injury following COVID-19 vaccination but also the optimal treatment period for PSL and the long-term prognosis of AIH after COVID-19 vaccination.

Two-dimensional high performance liquid chromatography purification of underivatized urinary prednisone and prednisolone for compound-specific stable carbon isotope analysis.

The gas chromatography-combustion isotope ratio mass spectrometry (GC/C/IRMS) confirmation procedure for prednisone (PS) and prednisolone (PSL) is still a great challenge for the doping control laboratory due to the many structurally similar steroids present in urinary matrices. This study aims to establish an innovative online two-dimensional high performance liquid chromatography (2D-HPLC) purification method for measuring the carbon isotope ratios (CIRs) and achieving the identification of the synthetic forms of these two endogenous anabolic androgenic steroids (EAASs). Initially, the one-dimensional chromatographic column was used to separate and purify endogenous reference compounds (ERCs), and the co-elution fluids containing PS and PSL were switched to a two-dimensional chromatographic column for further purification through an online transfer system. Then the purified compounds were analyzed using GC/C/IRMS after sample pretreatments. The results showed that the minimum detection concentration of PS and PSL reached 30 ng mL-1, and no isotope fractionation occurred during the entire collection and preparation process. This method has been validated with the WADA technical document and showed good sensitivity and selectivity, demonstrating its practical applicability for urine samples in doping control laboratories.

Optimal treatment targets for lupus nephritis using per-protocol repeat kidney biopsy findings at 2 years and clinical data up to 5 years: a single-center observational study.

The criteria for remission in both clinical and pathological contexts for lupus nephritis (LN) remain controversial. To identify optimal short-term goals (remission criteria) for LN predicting long-term success at 5 years, using repeat kidney biopsy (Biopsy 2) and clinical data. Single-center observational study. Twenty-three consecutive LN patients undergoing Biopsy 2 2 years post-induction therapy were evaluated. Two ideal long-term goals at 5 years were defined as: "A," Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and prednisolone (PSL) ⩽5 mg/day, and "B," proteinuria ⩽0.2 g/day with a normal serum creatinine level and PSL ⩽5 mg/day. Histologically, the electron-dense deposit (EDD) score grades immune deposits based on their intensity, amount, and location. A score of ⩽1 was defined as "electron microscopy remission (ER)." Conventional renal indices failed to predict long-term goals. The short-term goals with an accuracy (area under the curve: 95% confidence interval) of ⩾0.8 predicted long-term goals: "A at 5 years" (A-5y), A-2y (0.91: 0.79-1.00), DORIS-R-2y (0.87: 0.72-1.00), EDD score (0.85: 0.70-1.00), B-2y (0.83: 0.66-0.99), and SLEDAI-R-2y (0.82: 0.66-0.98) as well as "B at 5 years" (B-5y), A-2y (0.87: 0.73-1.00), B-2y (0.87: 0.73-1.00), EDD score (0.85: 0.69-1.00), and DORIS-R-2y (0.83: 0.67-0.99). EDD scores predicted A-5y, B-5y, and PSL dose at 5 years in proportion to the score. The clinical and histological goals aligned. The best predictive short-term goal was A-2y. Concordance between clinical remission (A-2y, B-2y, and DORIS-R-2y) and histological remission (ER) at 2 years suggests optimal short-term goals for LN.

A unique profile of serum cytokines in type 1 autoimmune pancreatitis and chronic rhinosinusitis.

Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease (IgG4-RD). Although AIP and IgG4-RD are characterized by multiple organ involvement including salivary glands, lung, and kidney, co-occurrence of chronic rhinosinusitis (CRS) and AIP/IgG4-RD has been poorly defined. We explored molecular mechanism accounting for the co-occurrence of CRS and AIP/IgG4-RD. Serum concentrations of IFN-α and IL-33 were measured by enzyme-linked immune-sorbent assay. We encountered a patient with concurrent type 1 AIP/IgG4-RD and CRS. Induction of remission by prednisolone (PSL) for type 1 AIP/IgG4-RD led to a marked improvement of CRS. Serum cytokine analysis after PSL treatment revealed a marked reduction in serum concentrations of IFN-α and IL-33, both of which are candidate pathogenic cytokines for AIP/IgG4-RD. Given that IL-33 is shared as one of pathogenic cytokines by type 1 AIP/IgG4-RD and CRS, enhanced IL33 responses may cause concurrent type 1 AIP/IgG4-RD and CRS.

Supercritical Antisolvent Precipitation of Corticosteroids/β-Cyclodextrin Inclusion Complexes.

In this study, corticosteroid-β-cyclodextrin (β-CD) inclusion complexes were prepared by using supercritical antisolvent (SAS) precipitation to enhance the dissolution rate of dexamethasone (DEX) and prednisolone (PRED), which are poorly water soluble drugs. The processing of the active principles in the absence of a carrier led to their almost complete extraction (the small amount of obtained material precipitates in the form of crystals). The coprecipitation of the ingredients in the presence of β-CD was investigated at different concentrations, pressures, and molar ratios. For both the corticosteroids, the optimized operating conditions were 40 °C, 120 bar, an equimolar ratio, and a concentration in DMSO of 20 mg/mL; these conditions led to the attainment of microparticles with mean diameters equal to 0.197 ± 0.180 μm and 0.131 ± 0.070 μm in the case of DEX and PRED, respectively. Job's method confirmed the formation of inclusion complexes with a 1/1 mol/mol ratio. Compared to the pure ingredients, the obtained powders have an improved release rate, which is about three times faster in both cases. The release curves obtained under the best operating conditions were fitted using different models. The best fitting was obtained using the Weibull model, whose parameters are compatible with a combined release mechanism involving Fickian diffusion and controlled release.

Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial

Introduction Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. Patients and methods This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. Results The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. Conclusions The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain. KEY MESSAGES Low initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis. Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

Efficacy and safety of 5-aminolevulinic acid in adult-onset Still's disease: A preclinical study in mice and a pilot study in humans

The study aimed to investigate the therapeutic effects of 5-aminolevulinic acid/sodium ferrous citrate (5-ALA/SFC) on adult-onset Still's disease (AOSD), specifically focusing on arthritis and macrophage activation syndrome (MAS). We used mouse models to assess the impact of 5-ALA/SFC on collagen-induced arthritis (CIA) and MAS induced by synthetic oligonucleotides containing CpG motifs (CpG-S-ODN). Additionally, we conducted a pilot study with AOSD patients receiving prednisolone (PSL) treatment and 5-ALA/SFC administration to evaluate its efficacy and safety. The 5-ALA/SFC group exhibited significantly lower joint scores in CIA mice. In CpG-S-ODN-treated mice, 5-ALA/SFC administration led to reduced hemophagocytosis and splenomegaly. The anti-inflammatory properties of 5-ALA/SFC were attributed to the suppression of CCL4 and CXCL10 production in monocytes and the induction of M2 macrophages. AOSD patients treated with 5-ALA/SFC demonstrated successful PSL tapering without adverse events. Collectively, the administration of 5-ALA/SFC showed promising potential in ameliorating arthritis and MAS in AOSD patients.

Immune thrombocytopenia secondary to primary cytomegalovirus infection after renal transplantation treated with a thrombopoietin receptor agonist: a case report

BackgroundImmune thrombocytopenia (ITP) is an acquired disorder characterised by a low platelet count due to immune-mediated destruction and impaired platelet production. Here we report a rare case of primary cytomegalovirus (CMV) infection followed by thrombocytopenia after renal transplantation (RT).Case presentationA 24-year-old male patient with end-stage kidney disease secondary to hereditary focal segmental glomerulosclerosis was treated with peritoneal dialysis and received ABO-compatible living-related RT from his aunt. Nine months after the RT, the patient was diagnosed with primary CMV infection. After initiating treatment for primary CMV infection, the patient developed thrombocytopenia. After excluding other diseases or drugs that may cause thrombocytopenia, the patient was finally diagnosed with ITP, administered prednisolone (PSL), and started on Helicobacter pylori eradication therapy. Tapering the PSL dose was difficult, but thrombopoietin receptor agonists (TPO-RAs) were effective.ConclusionsIn this case, the patient was diagnosed with ITP, and other causes of thrombocytopenia after RT were successfully ruled out. This case report demonstrates that RT recipients can develop ITP after CMV infection, and, in such cases, TPO-RAs may be an attractive option as a second-line therapy.

Abstract 13584: Prognostic Value of Combined Assessment of Cardiac Magnetic Resonance and Fluorodeoxyglucose Positron Emission Tomography in Patients With Cardiac Sarcoidosis

Background: Although the combined assessment of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) and 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) was useful for the detection of cardiac sarcoidosis (CS), its prognostic value remains unclear. Methods: We examined 90 consecutive CS patients diagnosed by both CMR and FDG-PET before prednisolone (PSL) therapy between September 2008 and April 2023 in our hospital. We calculated the overlap rate of FDG uptake area in the LGE-positive area to evaluate the association between concordance of FDG/LGE areas and adverse events. Patients were divided into two groups according to the median concordance ratio (overlap rate) between FDG and LGE areas (70 %). The primary outcome was a composite of sustained ventricular tachycardia/fibrillation (VT/VF), worsening heart failure, and sudden cardiac death. Results: Median interval between CMR and FDG-PET was 6.5 (IQR 3.0-24.0) days. There are no significant differences on age, sex, left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) level, and extent of LGE between the groups. During a median follow-up period of 3.2 (IQR 1.0-6.2) years, the primary outcome occurred in 25 (28%) patients. Patients with lower concordance showed a higher incidence of the primary outcome (Figure A), and lower improvement in LVEF after PSL therapy (Figure B) compared to those with higher concordance. In multivariable Cox regressions, lower concordance was significantly associated with the primary outcome adjusted for history of VT/VF (HR 7.37, P = 0.001), LVEF (HR 7.75, P = 0.001), log BNP (HR 5.62, P = 0.006), and extent of LGE (HR 11.75, P = 0.017). Conclusions: Lower concordance ratio of FDG/LGE before PSL therapy was associated with higher incidence of adverse events and lower improvement of LVEF. Assessment of active inflammation in the extent of LGE might be useful for risk stratification and prediction of the response to PSL in patients with CS.

A case of tubulointerstitial nephritis and uveitis syndrome accompanied by subclinical choroiditis

BackgroundTubulointerstitial nephritis and uveitis (TINU) syndrome is an uveits characterized by complications of idiopathic acute tubulointerstitial nephritis, and most cases present only anterior uveitis. We report a case of TINU syndrome in which the presence of choroiditis was revealed by multimodal imaging.Case presentationA 12-year-old male visited our hospital with a 6-day history of ocular pain and hyperemia. Conjunctival and ciliary injections, 1 + flare and 3 + cells of anterior chamber inflammation with mutton fat keratic precipitates were observed in both eyes (OU), together with redness and swelling of the optic disc OU. Laboratory tests showed slightly high levels of soluble IL-2R and serum β2 microglobulin and markedly high levels of urinary β2 microglobulin. The diagnosis of probable TINU syndrome was established on the basis of bilateral uveitis and urinalysis results in accordance with a clinical criteria of tubulointerstitial nephritis. With treatment with oral prednisolone (PSL) at 20 mg/day, ocular findings improved, and the dose of PSL was gradually reduced and withdrawn 6 months later. However, 1 month later from the withdrawal, ocular inflammation recurred with the presence of retinal exudates and snowball vitreous opacities in the peripheral retina OU. Fluorescein angiography showed leakages from peripheral retinal vessels and staining corresponding to retinal exudates. Indocyanine green angiography showed hypofluorescent dots scattered over the ocular fundus. Optical coherence tomography revealed the presence of choroidal thickening. Laser speckle flowgraphy color map showed a relatively cooler color. Findings from these multimodal images indicated the presence of subclinical choroiditis; therefore, oral PSL was administered again, and ocular inflammatory findings were improved.ConclusionsTINU syndrome can exhibit subclinical choroiditis detected with multimodal imaging. Further studies are necessary to determine the frequency of subclinical choroiditis in TINU syndrome.

Pharmacokinetics of immunosuppressive agents during hemoperfusion in a sheep model

IntroductionHemoadsorption shows promising signals in organ preservation and post lung transplantation. However, its potential impact on the pharmacokinetics of immunosuppressant drugs (ID) is still unknown.MethodsIn this interventional study, CytoSorb® hemoperfusion was tested in healthy sheep (n = 5) against a sham extracorporeal circuit (n = 3). Seven different ID (tacrolimus (TAC), cyclosporin A (CYA), mycophenolate mofetil (MMF), everolimus (EVER), basiliximab (BAS), methylprednisolone (MP) and prednisolone (PRED)) were administered in clinically relevant doses and combinations. Their levels were measured repeatedly in blood samples from the extracorporeal circulation over 6 h following administration. Population pharmacokinetic modeling analysis (NONMEM® 7.5) was performed.ResultsNegligible clearance was observed for PRED and BAS. For all other substances, a saturable adsorption sub-model with linear decrease of the adsorption effect over the adsorbed amount best described the measured concentrations. The maximum absolute adsorbed amounts (95% CI) for TAC, CYA, MMF, EVER, and MP were 0.040 (0.028–0.053), 1.15 (0.39–1.91), 4.17 (2.00–6.35), 0.0163 (0.007–0.026), and 53.4 mg (20.9–85.9), respectively, indicating an adsorption of less than 5% of the daily administered dosages for all investigated substances.DiscussionIn this large animal model, CytoSorb® hemoperfusion appears to have a limited effect on the clearance of tested ID.