Preliminary evaluation of an indwelling epidural catheter for repeat methylprednisolone administration in canine lumbosacral stenosis.

Objective: To determine the complications, outcomes, and patency of a permanent epidural catheter and subcutaneous access port system (ECAPS) as part of conservative management of degenerative lumbosacral stenosis in dogs. Animals and procedure: Medical records of 11 client-owned dogs that underwent an ECAPS insertion were evaluated retrospectively. Clinical signs, complications related to the procedure, and system patency are reported. Results: All dogs had lumbosacral pain at their initial neurological assessment, with comfort levels adequately controlled following epidural infiltrations. None suffered from complications related to the ECAPS procedure. In 10 dogs, there were no malfunctions for the duration of the study. However, in 1 dog, there was a suspected leak at Day 814. The longest duration of patency reported in this study was 870 d (at the time of writing). Conclusion: Placement of an ECAPS is a feasible technique and a viable option to permit repeated epidural injections of steroids in dogs with degenerative lumbosacral stenosis that is managed conservatively. Further studies are required to evaluate complication rates.

Évaluation préliminaire d'un cathéter épidural permanent (à demeure) pour l'administration répétée de méthylprednisolone lors de sténose lombosacrée dégénérative chez le chien. Objectif: Décrire la technique, les complications, les résultats et la perméabilité d'un système composé d'un cathéter épidural et d'un port d'injection sous-cutanée (ECAPS) pour le traitement médical de la sténose lombosacrée dégénérative chez le chien. Animaux et protocole: Les dossiers médicaux de 11 chiens appartenant à des clients ayant subi l'implantation d'un ECAPS ont été évalués de façon rétrospective. Cette étude décrit les signes cliniques, les complications reliées à la procédure et la perméabilité du système. Résultats: Tous les patients inclus présentaient de la douleur lombosacrée à l'examen initial. Le niveau de confort de tous les patients suite aux injections épidurales fut maitrisé de façon adéquate. Aucun des patients n'a subi de complications reliées à l'implantation du système. Le système n'a pas démontré de dysfonctionnement dans le cas de dix patients. Chez un des patients, une fuite fut suspectée au jour 814. La durée maximale de perméabilité enregistrée dans cette étude est de 870 jours (au moment de la rédaction). Conclusion: L'implantation d'un système ECAPS représente une option faisable et viable pour l'administration additionnelle de stéroïdes pour une gestion conservatrice de sténose lombosacrée dégénérative chez les chiens atteints. Des recherches supplémentaires sont requises pour l'évaluation des taux de complications.(Traduit par les auteurs).

A case of leptospirosis in transcarpathia complicated with Jarisch-Herxheimer reaction.

A case report of Jarisch-Herxheimer (JHR) reaction on a 10th day of Leptospirosis caused by Leptospira Pomona. JHR occurs as a complication of an antibiotic treatment of various spirochetes and may lead to respiratory distress syndrome, renal failure, hepatic insufficiency, and multiple organ failure. This case represents a skin and cardio-vascular form of JHR with no lung involvement. The patient was treated with benzylpenicillin and low dexamethasone doses for 5th day of the disease with a shift to ceftriaxone and high doses of methylprednisolone. The fastest diagnosis of a sporadic zoonotic disease, early start of antibiotic therapy, and adequate doses of corticosteroids are key to the successful treatment of leptospirosis.

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland.

OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.

[L-DEP regimen salvage therapy for refractory primary hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection in 4 children].

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

Comparison of local versus intramuscular steroid injection in patients with carpal tunnel syndrome: A prospective open label randomized clinical trial.

AIM: This study compared the efficacy and safety of local corticosteroid injection (LCI) vs intramuscular (IM) corticosteroid injection in mild to moderate carpal tunnel syndrome (CTS). METHODS: This is an open labeled, randomized controlled trial conducted during December 2021 to August 2023. Eighty-six patients with CTS were randomized in 1:1 ratio to receive either single 40 mg methylprednisolone (MP) injection at the wrist (LCI arm), or single 40 mg MP intramuscular injection (IM arm) in the deltoid. Primary outcome was absolute Symptom Severity Scale (SSS) at 3 months. Secondary outcomes were SSS score at 1-month, Functional Status Scale (FSS) score at 1 and 3 months, and recurrence at 3 months and injection site pain assessed on visual analog (VAS) scale. RESULTS: Median age was 45 (range 22 - 80) years, and 86 % were females. Baseline characteristics were comparable between groups. Mean SSS score at 3 months was similar in two arms (1.72 ± 0.71 vs 2.0 ± 0.93) with mean difference (MD) -0.03 (-0.31 to 0.25, p = 0.83) after adjusting for baseline SSS scores. LCI, however, resulted in significantly better SSS (1.48 ± 0.51 vs 1.88 ± 0.69, adjusted p = 0.04), and FSS scores (1.57 ± 0.44 vs 1.80 ± 0.66, adjusted p = 0.03) at 1 month compared to IM arm. Response rate (67.4 % vs 55.8 %; p = 0.30) and recurrence rate (17.1 % vs 22.6 %, p = 0.74) at 3 months were similar. Injection site pain was severe in LCI arm[median 5 (range 3 - 8) vs median 3 (range 2 - 6)]. CONCLUSIONS: In patients with mild to moderate CTS, LCI resulted in better improvement in the BCTQ scores at 1 month compared to IM steroid. However, 3-month's outcome was similar. Intramuscular steroid injection was better tolerated.

Comparison of side effects of different steroids used in intratympanic injections.

OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Association between clinical characteristics, acute steroid treatment and oligoclonal bands result in multiple sclerosis: A retrospective study.

BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is important for diagnosis of multiple sclerosis (MS). Previous studies reported that treatment with intravenous methylprednisolone (IVMP) before lumber puncture (LP) could suppress OCBs production. The aim of this study was to assess whether IVMP initiation prior to CSF collection affects OCBs results in patients with an acute demyelinating event. Additionally, we examined which clinical characteristics are associated with the presence of OCBs in the CSF. METHODS: We retrospectively evaluated patients admitted to the neurology department at rabin medical center (RMC) between 2010 and 2022 who underwent LP with OCBs analysis as part of their demyelinating attack workup. Patients were divided into OCB-positive and OCB-negative groups and demographical and clinical characteristics (including timing and duration of acute steroid treatment and history of prior demyelinating attacks) were analyzed for association with OCBs results. RESULTS: A total of 342 patients were included with a median age of 35 years (IQR, 27-46). Two hundred thirty-eight (69.6 %) were OCB-positive. Initiation of IVMP before LP was not associated with negative OCBs (11.8 % Vs. 13.5 %, P = 0.721), nor was it correlated with OCBs positivity (OR=0.86, P = 0.66). CSF cell count was higher in OCB-positive patients (5 Vs. 3, P = 0.001), and a history of prior demyelinating attacks was associated with- (33.6 % Vs. 20.2 %, P = 0.014) and predictive of OCBs positivity (OR=2, P = 0.013). CONCLUSIONS: Timing of steroids was not associated with OCB positivity. However, pleocytosis and a prior attack were associated with OCB positivity in this cohort. Our results suggest that steroid treatment is unlikely to affect OCBs results. Ideally, larger prospective studies would be needed to confirm our observations.

Traumatic Spinal Cord Injury.

OBJECTIVE: This article provides a review of the initial clinical and radiologic evaluation and treatment of patients with traumatic spinal cord injuries. It specifically highlights essential knowledge for neurologists who encounter patients with these complex injuries. LATEST DEVELOPMENTS: There has been improvement in the care of patients with traumatic spinal cord injuries, particularly in the prehospital evaluation, approach for immediate immobilization, standardized spinal clearance, efficient triage, and transportation of appropriate patients to traumatic spinal cord injury specialized centers. Advancements in spinal instrumentation have improved the surgical management of spinal fractures and the ability to manage patients with spinal mechanical instability. The clinical evidence favors performing early surgical decompression and spine stabilization within 24 hours of traumatic spinal cord injuries, regardless of the severity or location of the injury. There is no evidence that supports the use of neuroprotective treatments to improve outcomes in patients with traumatic spinal cord injuries. The administration of high-dose methylprednisolone, which is associated with significant systemic adverse effects, is strongly discouraged. Early and delayed mortality rates continue to be high in patients with traumatic spinal cord injuries, and survivors often confront substantial long-term physical and functional impairments. Whereas the exploration of neuroregenerative approaches, such as stem cell transplantation, is underway, these methods remain largely investigational. Further research is still necessary to advance the functional recovery of patients with traumatic spinal cord injuries. ESSENTIAL POINTS: Traumatic spinal cord injury is a complex and devastating condition that leads to long-term neurologic deficits with profound physical, social, and vocational implications, resulting in a diminished quality of life, particularly for severely affected patients. The initial management of traumatic spinal cord injuries demands comprehensive interdisciplinary care to address the potentially catastrophic multisystem effects. Ongoing endeavors are focused on optimizing and customizing initial management approaches and developing effective therapies for neuroprotection and neuroregeneration to enhance long-term functional recovery.

Drug resistant epilepsies: A multicentre case series of steroid therapy.

PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).

Bilateral retrobulbar optic neuritis combined with optic perineuritis associated with atezolizumab treatment for small cell lung carcinoma.

INTRODUCTION: Ocular immune-related adverse events (OirAEs) associated with novel cancer therapies of immune checkpoint inhibitors (ICIs) are emerging. Retrobulbar optic neuritis (ON) combined with optic perineuritis (OPN), associated with atezolizumab, has been rarely reported and has a unique clinical manifestation. CASE DESCRIPTION: A 67-year-old woman was diagnosed with small-cell lung cancer. As maintenance therapy, atezolizumab was administered continuously for 10 cycles for approximately 14 months. One week after the administration of the tenth dose of atezolizumab, the patient experienced a bilateral, successive painless visual decline. The fundus and the retinal nerve fiber layer revealed no abnormalities, but the ganglion cell of the macula disappeared loss. The concentric shrinking of the peripheral visual field of the left eye was noticed. Orbital MRI revealed bilateral optic nerve thickening and peripheral optic nerve sheath enhancement ("tram-track" and "doughnut" signs). Serology, cerebrospinal fluid results, and image examination ruled out common causes of vision decline, and the condition was identified as bilateral retrobulbar ON combined with OPN as a probable atezolizumab-related immune adverse event. Thereafter, atezolizumab was discontinued, and intravenous methylprednisolone pulse (IVMP) (160 mg/day for 5 days) plus intravenous immunoglobulin (20 g/day for 3 days) was administered. The patient's visual function considerably improved after three weeks. CONCLUSIONS: Retrobulbar ON and OPN associated with atezolizumab are rare side effects that are easily overlooked. Immune-related ON has unique features and requires early identification. The primary treatment for optic nerve irAEs is corticosteroids, but this is not standardized and should be used with caution.

Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial.

Objective: To study the efficacy of pulse methylprednisolone (MPS) therapy in patients with malaria-associated acute respiratory distress syndrome (ARDS). Materials and methods: The study was a randomized, single-blind, placebo-controlled trial with a total sample size of 44 patients. The total random number table was used on a computer for randomization. The sample size was divided into either the study group that received pulse MPS therapy along with the standard therapy to manage acute lung injury (ALI)/ARDS or the control group that received a placebo in the form of 100 mL of normal saline with the standard therapy to manage ALI/ARDS. The primary outcome was defined as either death of the patient or discharge from the hospital. The sequential organ failure assessment (SOFA) score, the lung injury score (LIS), duration of stay in the medical intensive care unit (MICU), number of days for which mechanical ventilation was required, and the rate of secondary infections between the study and the control groups were also calculated. Statistically significant differences among continuous variables were analyzed by t-test, and differences between categorical variables were assessed by Chi-squared test. Results: A total of 30 patients passed initial screening, out of which 60% were males and 40% were females. About 73.3% of the patients fell between the age groups of 36-45 years. A total of 20 patients (66.7%) were discharged from the hospital, while the remaining 10 patients succumbed to death in the intensive care unit (ICU) (33.3%). The outcome of death or discharge was found to be independent of the use of pulse MPS therapy (p = 0.44). No statistically significant difference was found between the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, SOFA score, and LIS between the two groups. Furthermore, the differences between the mean duration of stay in the MICU, the mean duration for the provision of mechanical ventilation (p = 0.41), and the rate of secondary infections (p = 0.46) remained unaffected with the use of pulse MPS therapy. Conclusion: Pulse MPS therapy has not shown any clear-cut benefit in the management of malaria-associated ARDS, and in fact, the continuous use of this treatment in hospitals may lead to worsened outcomes. A novel, effective therapy for this grave complication needs to be developed to reduce the morbidity and mortality in such patients, which is frequently encountered. The development of a robust surveillance system is required for adequate monitoring and early diagnosis of this complication, along with larger multicentric randomized clinical trials. Disclosures: Approval was granted by the Institutional Ethics Committee (IEC). All participants were only selected after taking their written informed consent. The authors have no conflicts of interest or acknowledgments to report. How to cite this article: Tiwari S, Kursange S, Goyal A, et al. Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial. J Assoc Physicians India 2023;71(11):36-39.

Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.

Importance: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. Objective: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. Design, Setting, and Participants: An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Interventions: Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). Main Outcomes And Measures: The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Results: Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]). Conclusions and Relevance: Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01560052.

A Case Report for Using Methylprednisolone for Severe ARDS Caused by SARS-CoV-2 Delta Variant in a Pediatric Patient With Lennox-Gastaut Syndrome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 can result in fatal comorbidities, including acute respiratory distress syndrome (ARDS). Several reports suggest that children have milder illness, though severe cases have still been reported. We report a 9-year-old boy with ARDS caused by the SARS-CoV-2 delta (B.1.617.2) variant. He was admitted to our hospital and carefully observed due to underlying Lennox-Gastaut syndrome. He developed intractable seizures with a high fever. Although the seizures were controlled, his respiratory condition deteriorated to severe ARDS. High-dose methylprednisolone was administered with high positive end-expiratory pressure and low tidal volume. After ARDS treatment, oxygenation improved sufficiently to permit extubation. This case suggests that close observation is required in pediatric patients with neurologic comorbidities because of an increased risk for severe COVID-19.

Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature.

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.

An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination: A Case Report.

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scar tissue formation. An acute exacerbation of IPF (AE-IPF) is a clinically significant respiratory decompensation that accounts for a significant proportion of IPF-related morbidity and mortality. AE-IPF can be idiopathic or associated with pulmonary embolism, infection, aspiration, surgery, and drug toxicity. In this novel case report, we describe a potential association between AE-IPF and BNT162b2 mRNA COVID-19 vaccination that was successfully treated with a short course of glucocorticoids. While our aim is to raise awareness for this yet-to-be-described adverse event, immunization against vaccine-preventable disease remains widely recommended in vulnerable patients with chronic lung disease such as IPF.

Clinical observation of low-dose combination chemotherapy in refractory/recurrent paroxysmal nocturnal hemoglobinuria patients: A single-center retrospective analysis.

BACKGROUND: We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of 20 refractory/recurrent PNH patients, including the clinical efficacy of chemotherapy treatment, safety, and survival. METHODS: The clinical data of 20 classic PNH patients who were refractory/recurrent or had glucocorticoid dependence in our hospital were analyzed, including clinical manifestations, laboratory examinations, treatment efficacy, and survival. RESULTS: Seventeen patients had a marked improvement in anemia after chemotherapy, 14 patients acquired blood transfusion independence, and the Hb of 3 patients increased to normal levels. Although 6 patients still needed blood transfusion, the transfusion interval was significantly prolonged. The percentages of LDH, TBIL, and RET, which are indicators of hemolysis, were significantly lower than those before chemotherapy. The dosage of adrenal glucocorticoids was reduced by more than half compared with that before chemotherapy. CONCLUSIONS: Chemotherapy can reduce PNH clones, promote normal hematopoiesis, and control hemolytic attack. It is a promising and widely used therapeutic method.