Steroid Response Research Articles

Perturbations in the airway microbiome are associated with type 2 asthma phenotype and severity.

Airway microbiome has been linked to asthma heterogeneity, yet little is known about the associations between airway microbiota and type 2 (T2) asthma phenotype and severity. We aimed to determine the relationship of nasopharyngeal (NP) and induced sputum (IS) microbiota to the phenotypic features of T2 asthma. NP and IS samples from subjects with T2 mild-to-moderate asthma (n=23) and severe asthma (n=21) and healthy controls (n=16) were analyzed. Bacterial microbiota and functional profiles were compared. The correlation between microbial communities and clinical as well as inflammatory features was examined in asthmatics of two statuses. Differences in NP and IS microbiota were associated with T2 asthma phenotype. Alterations in NP microbiota were more reflective of T2 inflammation and severity, with additional stratification of a subgroup characterized by significant elevations in T2 inflammatory biomarkers and reductions in bacterial richness and diversity (P < .05). Burkholderia-Caballeronia-Paraburkholderia, Ralstonia and Rhodococcus were identified as hub taxa within NP microbial network in T2 severe asthma, which were prevalent in the entire airway and involved in bacterial functions including inflammatory and steroid responses (P < .05). The composition and diversity of IS microbiota were complex, with Veillonella as the most altered genus, showing an increase with increasing asthma severity. Our work revealed the significant associations of microbiota perturbations throughout the entire respiratory tract to the extent of T2 inflammation, phenotype and severity in T2 asthma. The specific taxa identified invite further mechanistic investigations to unravel their possibility as biomarkers and therapeutic targets for T2 severe asthma.

Risk factors of pediatric steroid-induced ocular hypertension.

Steroid-induced ocular hypertension (SIOH) is a significant ocular complication of pediatric steroid administration. In this study, we analyzed the risk factors associated with pediatric SIOH. We retrospectively collected data from 78 children under 20 years of age who received systemic steroids during hospitalization. The data included age, gender, primary disease, intraocular pressure (IOP) before and one month after administration, total monthly steroid dose adjusted for body weight (BW), and one-month changes in red blood cell, white blood cell, and platelet counts. A multivariate analysis was used to identify risk factors related to steroid responsiveness. Thirty patients (38.5%) were classified as steroid responders, and 48 as non-responders. The median IOP during the first month of steroid treatment was 24.0 mmHg (IQR; 23.0-28.3) for responders and 15.0 mmHg (IQR; 12.3-18.0) for non-responders. The Generalized Estimating Equations analysis revealed that younger age, male sex, primary disease, increase the amount of white blood cell (WBC) and total steroid dose per BW in one month were independently associated variables. The receiver operating characteristic analysis also revealed that the cutoff values for age, total monthly steroid dose, the increase amount of WBC were 11.0 years, 40.7mg/kg and 3.40 × 10²/µl respectively. High-dose steroid administration, especially in male, younger patients, necessitates careful monitoring for IOP changes during treatment. WBC count also needs to be monitored during IOP follow-ups. What is known Steroid-induced ocular hypertension (SIOH) is one of the essential complicationsduring steroid administration,but onlylimited analyses have been performed in children. What is new A comprehensive analysis of multiple factors was performed that are predicted to be associated with pediatric SIOH from previous literature. Younger age, male sex, primary disease, increase the amount of WBC, and highertotal monthly steroid dose were extracted as risk factors of SIOH. This study can contribute to the prediction of cases in which ophthalmologic examinations are particularly important during systemic steroid administration in children.

Rat Model of Menopausal/Andropausal Hypertension with Different Sensitivities to Non-Genomic Antihypertensive Responses of Female and Male Sex Steroids

Introduction: Hypertension is prevalent in older women and men, but the impact of sex differences is unclear. Methods: Blood pressure (BP) was evaluated weekly for 15 weeks using tail-cuff plethysmography in intact or gonadectomized female and male rats. Similarly, gonadectomized rats were subcutaneously treated daily for 15 weeks with estradiol in females or testosterone in males. Treatment with estrogen in males and androgen in females for BP was also examined. The non-genomic antihypertensive potency and efficacy of different sex steroids were determined; catheters were implanted in the carotid artery of hypertensive rats for BP recording with bolus injections in the jugular vein at cumulative doses (1 × 10−7−1 × 10−4M kg−1 min−1) of dehydroepiandrosterone (DHEA), estradiol, testosterone, or 5β-dihydrotestosterone (5β-DHT). Results: Data showed a time-dependent increase in BP after gonadectomy in female and male rats until hypertension values were reached. Males are more sensitive to the development of hypertension than females. The increases in BP in females and males were completely prevented by estradiol or testosterone, respectively. Testosterone completely prevented hypertension in females, whereas estradiol only partially in males. Antihypertensive potencies in conscious hypertensive rats were DHEA = 5β-DHT = testosterone >> estradiol, in females and DHEA = 5β-DHT >> testosterone >> estradiol in males. The efficacy was DHEA = 5β-DHT = testosterone >> estradiol in females and 5β-DHT = DHEA >> testosterone >> estradiol in males. Conclusion: Gonadectomized males developed hypertension faster than females, suggesting that androgen deficiency plays an important role in BP reduction. Antihypertensive responses of steroids are structure-dependent; estradiol demonstrated the lowest potency, whereas 5β-DHT was a potent antihypertensive without estrogenic and androgenic actions, suggesting it is as a therapeutic candidate for controlling hypertension in both sexes.

Steroid response in a rare case of vertebrae butterfly with spinal cord compression caused by chronic subdural hematoma

IntroductionSpinal subdural hematoma (SSH) is a rare entity. Clinical symptoms include motor, sensory and/or autonomic dysfunction due to compression of the spinal cord. There is no standard consensus in the management of SSH. Here, we report a rare case of SSH of sudden onset following trauma, successfully treated with conservative therapy.AimThis case highlights butterfly vertebrae as an incidental imaging finding before SSH diagnosis.Case studyA 30-year-old female presented with weakness in the lower extremities after trauma, accompanied by paresthesia, urinary retention, and impaired defecating function. The thermoregulatory sweat exam revealed sudomotor dysfunction. Multiple slice computed tomography (MSCT) examination of the whole spine revealed wedge deformity of vertebral corpus (VC) L4 on the right lateral side, and VC L5 butterfly vertebrae. Spine magnetic resonance imaging (MRI) revealed an extramedullary intradural lesion at the T7 to T10 level suggestive of subdural hematoma.Results and discussionThe administration of methylprednisolone pulse therapy, combined with physical rehabilitation, led to a rapid and significant improvement in the patient's motor function. The absence of the spinal pain possibly indicated that there was no more extension of the hematoma; motor recovery, even if slight, should be a predictor of successful conservative therapy, and physical rehabilitation.ConclusionsSSH is an uncommon condition, with varying clinical presentation, and progression. This case report highlights significant improvement following conservative steroid treatment of a SSH. It also highlights a unique incidental finding of butterfly vertebra in a patient with paraparesis following trauma.

7274 Assessing The Interactome Of Hexose-6-Phosphate Dehydrogenase In Breast Cancer Cells And Identifying Anterior Gradient Protein 2 As Interacting Partner By Using A BioID Method

Abstract Disclosure: G. Sakalauskaite: None. M. Weingartner: None. T. Bock: None. J. Birk: None. M. Tsachaki: None. A. Odermatt: None. Hexose-6-phosphate dehydrogenase (H6PD) catalyzes the first two steps of the pentose-phosphate pathway in the endoplasmic reticulum (ER). It is so far the only enzyme shown to generate NADPH in the ER. H6PD is involved in physiological processes such as glucose and steroid metabolism, redox regulation, and response to ER-stress. So far, only one H6PD interacting partner, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), has been reported. This enzyme uses NADPH for its well-reported role in glucocorticoid activation. However, H6PD has 11β-HSD1-independent functions, such as the recently described modulation of breast cancer cell properties. Here, we adapted the BioID approach to identify novel H6PD interacting partners in the ER. First, we generated a triple negative breast cancer cell line MDA-MB 231 stably expressing a H6PD-biotin ligase fusion protein. Then, we validated the method to confirm the known interaction between H6PD and 11β-HSD1. Next, we analyzed enriched biotinylated proteins by mass spectrometry and further assessed potential candidates by co-immunoprecipitation and functional assays. The resulting interactome revealed a potential hit cluster of protein disulfide isomerase (PDI) family members, different ER-resident chaperones and luminal calcium binding proteins. Due to its association with breast cancer, we further examined the PDI Anterior gradient protein 2 (AGR2) as H6PD interacting partner. Physical interaction between AGR2 and H6PD was confirmed by co-immunoprecipitation assay in MCF7 cells. Downregulation of AGR2 by siRNA resulted in elevated H6PD protein levels but decreased activity. Furthermore, increased H6PD activity was observed when this protein was co-expressed with AGR2 in HEK-293 cells. In conclusion, the results validated the use of the BioID approach to identify protein interactions within the ER and they revealed that AGR2 physically interacts with H6PD, thereby controlling its expression and enzyme activity. Presentation: 6/3/2024

Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15).

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition.

Clinical profile and short-term outcomes of acute severe ulcerative colitis in Vietnam: insights from a resource-limited setting.

Acute severe ulcerative colitis (ASUC) is a significant complication of ulcerative colitis, affecting roughly 25% of patients and increasing the risk of colectomy and hospital mortality. While intravenous steroids are a primary treatment, only 67% of patients respond, necessitating rescue therapy for non-responders. Data on ASUC in the Vietnamese population are scarce. This study aims to provide insights into the clinical characteristics and short-term outcomes of Vietnamese patients with ASUC. We conducted a prospective case series on ASUC patients admitted to the University Medical Center in Ho Chi Minh City from January 2021 to June 2023. Steroid response was assessed using the Travis Oxford criteria. We evaluated clinical features, in-hospital steroid response rates, endoscopic remission, and colectomy rates 12 months post-hospitalization. Seventeen patients with a median age of 42 years (70.6% male) were included. The median time from symptom onset to diagnosis was six weeks, and 47.1% had a history of ulcerative colitis. Median CRP value was 75.8 mg/L, and 76.5% had fecal calprotectin concentrations above 800 µg/g. All patients had a Mayo endoscopic subscore of ≥2, with 12.5% showing deep ulcers. Eleven patients (64.7%) responded to in-hospital steroid treatment, while 6 (35.3%) required rescue therapy with infliximab or tofacitinib. After one year, 10 of 11 (90.1%) achieved mucosal healing, and no patients underwent colectomy. Corticosteroids remain the cornerstone for initial ASUC therapy, though many patients do not respond. Anti-TNF agents and tofacitinib show potential benefits for those unresponsive to steroids. This study highlights the effectiveness of corticosteroids and biologics in managing ASUC in Vietnam.

Minimal change glomerular disease associated with solid neoplasms: a systematic review.

Paraneoplastic minimal change disease (MCD) has been associated with hematological malignancies, whereas solid malignancies are commonly associated with membranous glomerulonephritis. In this systematic review of the literature, we describe the clinical features, treatment and outcome of MCD associated with solid neoplasms. We performed a systematic review of the MEDLINE, COCHRANE, EMBASE and SCOPUS databases, including case reports of adult patients with biopsy-proven MCD and solid malignancy, without language or time restrictions. Sixty-seven papers were included, presenting 86 cases with a mean age of 57.8 ± 14.7years; 41.0% were women. Nephrotic syndrome was the initial presentation in 96.2% of patients; 67.2% had kidney function impairment, and 21.2% required kidney replacement therapy. The most frequent malignancies were malignant thymoma (34.9%), kidney (14.0%), lung (12.8%), and gastrointestinal tumors (12.8%). In 40.7% of cases, the neoplasm diagnosis preceded MCD by 33.8 ± 46.1months, while in 31.4%, it followed diagnosis ofMCD by 12.4 ± 22.6months. In 27.9%, the neoplasm and kidney disease were diagnosed simultaneously. Immunosuppressive therapy was started in 79.1% of cases and tumor-specific treatment in 83.7%. Remission of MCD was achieved in 80.2% of patients: 38.2% responded to immunosuppressive treatment alone and 29.6% to oncological treatment alone. The association between MCD and solid neoplasms is well-documented. Immunosuppressive therapy alone induced nephrotic syndrome remission in over one-third of cases; most others responded to tumor-specific treatment. Solid tumor screening should be considered in MCD independently of the steroid response, though more data on solid tumor-associated MCD prevalence are needed for a definitive statement. CRD42024521854.

Pseudophakic macular edema in a steroid responder treated successfully with intravitreal methotrexate: A case report

Pseudophakic macular edema (PME) is typically treated with nonsteroidal anti-inflammatory drugs (NSAIDs) initially, followed by steroids. Treatment with steroids becomes challenging in steroid responders. We report a case of PME treated with intravitreal methotrexate (Mtx) in a steroid responder. A 54-year-old-male underwent anterior vitrectomy with secondary intraocular-lens implantation following an eventful cataract surgery. Topical steroids given as a postoperative regimen led to severe steroid response and therefore were replaced by NSAIDs. Intraocular pressure was controlled by antiglaucoma drugs. Furthermore, he developed cystoid macular edema (CME). Since steroids were contraindicated, he was administered two intravitreal injections of Mtx 15 days apart, resulting in resolution of CME and restoration of vision.

Peripheral Blood Cell DNA Methylation Can Predict Steroid Response in Nephrotic Syndrome

Peripheral Blood Cell DNA Methylation Can Predict Steroid Response in Nephrotic Syndrome

Managing RS3PE: Diagnostic approach, initial steroid response, and long-term management with DMARDs

Background. RS3PE, or Remitting Seronegative Symmetrical Synovitis with Pitting Edema, is a unique and relatively rare form of inflammatory arthritis that predominantly affects older adults. It is distinguished by its hallmark features: symmetrical swelling of the joints, significant pitting edema in the extremities, and a negative serological profile for common markers associated with rheumatoid arthritis, such as rheumatoid factor (RA factor) and anti-citrullinated protein antibodies (anti-CCP). This condition is often characterized by a remitting course, meaning that symptoms may improve or resolve over time, particularly with appropriate treatment. The condition usually affects older adults and can sometimes be associated with other underlying health issues, such as malignancies or infections. The “remitting” aspect of RS3PE refers to the fact that the symptoms often improve or resolve over time, particularly with appropriate treatment, which usually involves corticosteroids or other anti-inflammatory medications. Case report. This case study details the clinical presentation, diagnosis, and management of a 56-year-old female patient with known hypertension who presented with bilateral dorsal hand swelling, pain, and early morning stiffness over a 15-day period. The patient’s initial examination revealed bilateral pitting edema and active arthritis in the proximal interphalangeal joints, with significant warmth and tenderness. Laboratory tests showed elevated ESR and CRP, normocytic normochromic anemia, and negative rheumatoid factor and anti-CCP antibodies. Imaging studies, including X-ray, ultrasound, and mammogram, showed no erosive changes or malignancy, while a Pap smear and serum CA-125 levels were within normal limits. The clinical picture, combined with the exclusion of other conditions, supported the diagnosis of RS3PE. Treatment commenced with intravenous low-dose dexamethasone, which led to significant symptomatic improvement. This was followed by a transition to oral prednisolone, and the patient initially showed complete resolution of symptoms. However, recurrence of symptoms occurred upon discharge, prompting the introduction of steroid-sparing agents: methotrexate and hydroxychloroquine, alongside continued oral steroid treatment. Over a two-month follow-up period, the patient experienced no signs of relapse. This case fits the clinical and investigative criteria for RS3PE. The patient showed symptomatic improvement after treatment with low-dose steroids.

Incidence of Steroid-Related Ocular Hypertension and Cataract Formation After Subtenon Triamcinolone in Non-Uveitic Pediatric Patients.

To describe intraocular pressure (IOP) changes after injection of subtenon triamcinolone (STT) during examination under anesthesia (EUA) for pediatric patients. Multicenter, retrospective case series of pediatric patients STT from three tertiary care ophthalmic services between November 2018 and October 2023. Of 392 patients identified, 59 eyes of 41 patients (10.5%) were included. Laser was administered in 95.1% of the cases. STT dose ranged from 4 to 20 mg. The most common diagnosis was retinopathy of prematurity (43.9%). Two eyes (3.4%) of 2 patients (4.9%) were mild steroid responders. One eye (1.7%) of 1 patient (2.4%) was a moderate responder. There were no high steroid responders, and all eyes with steroid response showed a return of IOP to normal range at next visit without needing any IOP-lowering medications. No patients were diagnosed with glaucoma or required glaucoma surgery. Only 1 eye (1.7%) developed trace posterior subcapsular cataract, while no optic disc cupping or inflammation were noted. Subtenon triamcinolone injection is commonly used to prevent inflammation at the time of retinal photocoagulation treatment in pediatric patients. It has a favorable safety profile in relation to IOP elevation and cataract formation. There was no requirement for IOP lowering medications or surgical interventions.

Uterine cyclin A2-deficient mice as a model of female early pregnancy loss.

Proper action of the female sex steroids 17β-estradiol (E2) and progesterone (P4) on the endometrium is essential for fertility. Beyond its role in regulating the cell cycle, cyclin A2 (CCNA2) also mediates E2 and P4 signaling in vitro, but a potential role in modulating steroid action for proper endometrial tissue development and function is unknown. To fill this gap in our knowledge, we examined human endometrial tissue from fertile and infertile cisgender women for CCNA2 expression and correlated this with pregnancy outcome. Functional assessment of CCNA2 was validated in vivo using a conditional Ccna2 uterine-deficient mouse model, while in vitro function was assessed using human cell culture models. We found that CCNA2 expression was significantly reduced in endometrial tissue, specifically the stromal cells, from women undergoing in vitro fertilization who failed to achieve pregnancy. Conditional deletion of Ccna2 from mouse uterine tissue resulted in an inability to achieve pregnancy, which appeared to be due to alterations in the process of decidualization, which was confirmed using in vitro models. From these studies, we conclude that CCNA2 expression during the proliferative/regenerative stage of the menstrual cycle allows for proper steroid responsiveness, decidualization, and pregnancy. When CCNA2 expression levels are insufficient, there is impaired endometrial responsiveness, aberrant decidualization, and loss of pregnancy.

Effect of intravenous methylprednisolone on serum antibody levels in thyroid eye disease

Background/aimsWe evaluated longitudinal autoantibody changes after intravenous methylprednisolone (IVMP), compared them with those in untreated patients and identified prognostic factors for treatment response.MethodsIn this single-centre, retrospective, observational study, a total...

Peripheral Blood Neutrophil Nadir and Time to Platelet Recovery during Induction Chemotherapy: Predictors of Clinical Outcomes and Markers for Optimizing Induction Treatment Intensity in Acute Lymphoblastic Leukemia.

To study the kinetics of blood count nadir and time to recovery and find its association with clinical outcomes in a cohort of Acute Lymphoblastic Leukemia (ALL). Data from 243 cases treated between January 2018 to December 2020 was retrospectively analysed. Along with baseline data, serial measures of peripheral blood counts, nadir, and time to partial and complete recovery of counts during course of induction chemotherapy were recorded. Post-induction Complete Remission (CR) status, Event-Free Survival (EFS) , and Overall Survival (OS) were recorded as clinical outcomes for analysis. Median age was 15 (range,1-62) years. Immunophenotype was B-ALL in 71% (n=172), and T-ALL in 27% (n=66). Good steroid response (D8) was seen in 89%(n=216), CR in 79% (n=192), and induction mortality in 12% (n=29). Median neutrophil nadir was 0.06(0-0.49) *10⁹/L and median day to nadir was D17. Median time to partial and complete platelet recovery was D18 and D25. Late neutrophil nadir (>D15) was independent predictor of refractory disease post-induction [OR=5.43 (95%CI 1.06-27.75)]. Late partial platelet recovery (>D22) was independent predictor of poorer EFS and OS [HR = 1.63 (95%CI 1.07-2.47)] and [HR = 1.5 (95% CI 1-2.4)] respectively. We found that a longer time to neutrophil nadir independently predicts refractory disease post-induction and late partial platelet recovery is an independent factor for poorer EFS and OS. Thus, Blood count kinetics as independent predictors of induction outcomes can provide a simple, easy-to-use tool for balancing toxicity-efficacy during induction therapy for ALL.

Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma.

Calprotectin, a calcium-binding protein, plays a crucial role in inflammation and has been associated with various inflammatory diseases, including asthma. However, its regulation and impact on steroid hyporesponsiveness, especially in severe asthma, remain poorly understood. This study investigated the regulation of calprotectin proteins (S100A8 and S100A9) by IL-17 and its role in steroid hyporesponsiveness using in vitro and in vivo models. Calprotectin expression was assessed in primary bronchial fibroblasts from healthy controls and severe asthmatic patients, as well as in mouse models of steroid hyporesponsive lung inflammation induced by house dust mite (HDM) allergen and cyclic-di-GMP (cdiGMP) adjuvant. The effects of IL-17A stimulation on calprotectin expression and steroid response markers in bronchial epithelial and fibroblast cells were examined. Additionally, the therapeutic potential of paquinimod, a calprotectin inhibitor, in mitigating airway inflammation and restoring steroid response signatures in the mouse model was evaluated. The results demonstrated upregulation of calprotectin expression in asthmatic bronchial fibroblasts compared to healthy controls, as well as in refractory asthma samples compared to non-refractory asthma. IL-17 stimulation induced calprotectin expression and dysregulated glucocorticoid response signatures in lung epithelial and fibroblast cells. Treatment with paquinimod reversed IL-17-induced dysregulation of steroid signatures, indicating the involvement of calprotectin in this process. In the HDM/cdiGMP mouse model, paquinimod significantly attenuated airway inflammation and hyperresponsiveness, and restored steroid response signatures, whereas dexamethasone showed limited efficacy. Mechanistically, paquinimod inhibited MAPK/ERK and NF-κB pathways downstream of calprotectin, leading to reduced lung inflammation. These findings highlight calprotectin as a potential therapeutic target regulated by IL-17 in steroid hyporesponsive asthma. Targeting calprotectin may offer a promising approach to alleviate airway inflammation and restore steroid responsiveness in severe asthma. Further investigations are warranted to explore its therapeutic potential in clinical settings and elucidate its broader implications in steroid mechanisms of action.

Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study

BackgroundTreatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.MethodsCancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed.ResultsFifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8–26.9) months.ConclusionTofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.

Urinary Vitamin D Binding Protein as a Biomarker to Assess Steroid Responsiveness in Childhood Idiopathic Nephrotic Syndrome

Urinary Vitamin D Binding Protein as a Biomarker to Assess Steroid Responsiveness in Childhood Idiopathic Nephrotic Syndrome

Granulocyte Colony-Stimulating Factor Improves Prednisolone Responsiveness and 90-Day Survival in Steroid-Eligible Severe Alcohol-Associated Hepatitis: The GPreAH Study a Randomized Trial.

Severe alcohol-associated hepatitis (SAH) carries high 1-month mortality. Corticosteroids provide a modest 28-day but not 90-day survival benefit, due to development of infections and organ failures. Granulocyte colony-stimulating factor (GCSF) has shown promise in patients with SAH by its immunomodulatory and regenerative capabilities. We studied the safety and efficacy of combination (GCSF + prednisolone, GPred) therapy in management of steroid-eligible patients with SAH. Steroid eligible patients with SAH (discriminant function scores 32-90) were randomized to receive prednisolone (GrA, n = 42), GPred (GrB, n = 42), or GCSF alone (GrC, n = 42). GCSF was given as 150-300 mcg/d for 7 days followed by every third day for a maximum of 12 doses in 1 month. Prednisolone 40 mg/d was given for 7 days and continued for 28 days in responders (Lille score <0.45). Baseline characteristics of patient groups were comparable. On intention-to-treat analysis, the primary endpoint of 90-day survival was achieved in 64.3% (27/42) in prednisolone, 88.1% (37/42) in GPred, and 78.6%(33/42) in GCSF groups, respectively ( P = 0.03, prednisolone vs GPred). The 28-day survival was not different between the groups (85.7%, 95.2%, and 85.7%, respectively [ P = 0.27]). The GPred group had more responders by day 7 (71.4% vs 92.9% vs 76.2%, P = 0.037) and had greater reduction in discriminant function (-7.33 ± 4.78, -24.59 ± 3.7, -14.59 ± 3.41, P = 0.011) and MELDNa (-1.69 ± 1.26, -7.02 ± 1.24, -3.05 ± 0.83, P = 0.002) by day 90. The prednisolone-only group had higher incidence of new infections (35.7%, 19%, 7.1%, respectively, P < 0.002). Acute kidney injury (33.3%, 7.1%, 11.9%, P = 0.002), hepatic encephalopathy (35.7%, 9.5%, 26.2%, P = <0.001), and rehospitalizations (59.5%, 14.3%, 30.9%, P =<0.01) were lower in the GPred group. Addition of GCSF to prednisolone improves steroid responsiveness and 90-day survival with fewer infections and new onset complications in patients with SAH.

SURFASA Score for prediction of steroid response in children and adolescents with severe autoimmune hepatitis

SURFASA Score for prediction of steroid response in children and adolescents with severe autoimmune hepatitis