High-dose Corticosteroids Research Articles

Epidemiology and treatment trends for acute encephalopathy under the impact of SARS-CoV-2 pandemic based on a prospective multicenter consecutive case registry.

Acute encephalopathy is a severe condition predominantly affecting children with viral infections. The purpose of this study was to elucidate the epidemiology, treatment, and management of acute encephalopathy. The study also aimed to understand how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected epidemiological trends. This retrospective study used the database of the Febrile Acute Convulsion and Encephalopathy registry, a prospective multicenter consecutive case registry for acute encephalopathy and febrile convulsive status epilepticus. Pediatric patients aged 0-18years hospitalized and diagnosed with acute encephalopathy between January 2020 and August 2023 were included in this study. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) was the most common syndrome (36 cases, 27.5%). SARS-CoV-2 was the most common pathogen (19 cases, 14.5%), followed by influenza virus type A (15 cases, 11.5%). Targeted temperature management was performed for 25 (69.4%) of 36 patients with AESD; 5 (50.0%) of 10 patients with hemorrhagic shock and encephalopathy; and only 1 (5.9%) of 17 patients with mild encephalitis or encephalopathy with a reversible splenial lesion (MERS). High-dose corticosteroids were administered to 9 (90.0%) of 10 patients with hemorrhagic shock and encephalopathy and 11 (30.6%) of 36 patients with AESD. The primary causative pathogen of acute encephalopathy has changed to SARS-CoV-2. AESD remains the most common syndrome. Targeted temperature management is more, whereas high-dose corticosteroid therapy is less, frequently used. No specific treatment for mild encephalitis or encephalopathy with a reversible splenial lesion has been established.

Approach to Managing the Initial Presentation of Multiple Sclerosis: A Worldwide Practice Survey.

Available disease-modifying therapies (DMTs) for multiple sclerosis (MS) are rapidly expanding; although escalation approaches aim to balance safety and efficacy, emerging evidence suggests superior outcomes for people with MS who are exposed to early high-efficacy therapies. We aimed to explore practice differences in prevailing management strategies for relapsing-remitting MS. We used a worldwide electronic survey launched by the Practice Current section of Neurology® Clinical Practice. Questions pertained to a case of a 37-year-old woman presenting with optic neuritis. Respondents were asked to indicate their initial investigations, relapse management strategy, choice of disease-modifying therapy, and plan for follow-up imaging (contrast/noncontrast). Survey responses were stratified by key demographic variables along with 95% confidence intervals (95% CIs). We received 153 responses from 42 countries; 32.3% responders identified as MS specialists. There was a strong preference for intravenous delivery of high-dose corticosteroids (87.7%, 95% CI 80.7-92.5), and most of the responders (61.3%, 95% CI 52.6-69.4) indicated they would treat a nondisabling (mild sensory) MS relapse. When asked to select a single initial DMT, 56.6% (95% CI 47.6-65.1) selected a high-efficacy therapy (67.5% MS specialists vs 53.7% non-MS specialists). The most selected agents overall were fingolimod (14.7%), natalizumab (15.5%), and dimethyl fumarate (20.9%). Two-thirds of respondents indicated they would request contrast-enhanced surveillance MRI. Although there is a slight preference for initiating high-efficacy DMT at the time of initial MS diagnosis, opinions regarding the most appropriate treatment paradigm remain divided.

A multivariable prediction model for invasive pulmonary aspergillosis in immunocompromised patients with acute respiratory failure (IPA-GRRR-OH score).

Invasive pulmonary aspergillosis (IPA) is a life-threatening opportunistic infection in immunocompromised patients. The diagnosis is often made late, with mortality reaching 90% when mechanical ventilation is needed. We sought to develop and validate a risk prediction model for the diagnosis of IPA. We used two independent datasets of immunocompromised patients with acute respiratory failure admitted to 12 intensive care units (ICUs). The derivation dataset include 3262 patients. Factors associated with probable or proven IPA were identified, and a risk prediction model was developed. This model was then validated in a prospective dataset (776 patients). IPA prevalence was 4.5% (146/3262) and 3.3% (26/776), in the derivation and the validation cohorts, respectively. The final model included eight variables constitutive of the IPA-GRRR-OH score: type of immunosuppression, high-dose or long-term corticosteroids, neutropenia, the presence of structural lung disease, time from symptoms onset to ICU admission > 7 days, hemoptysis, focal alveolar pattern on the chest imaging, and viral co-infection. The median score [IQR] was 2 [1-3] in the derivation and 1 [0-3] in the validation cohort. The best cutoff score for IPA diagnosis was 4 (sensitivity 23.1%; specificity 90.5%; negative predictive value 91.4%). Discrimination and calibration were good in both the derivation (AUC 0.72 [0.68-0.76]) and the validation cohort (AUC 0.85 [0.76-0.93]). The IPA-GRRR-OH is a clinical score, easily available at ICU admission, which reliably predicts IPA in immunocompromised patients with acute respiratory failure. Studies to demonstrate benefits from the bedside implementation of this score are warranted.

VEXAS syndrome: is it more a matter of inflammation or hematopoietic clonality? A case series approach to diagnosis, therapeutic strategies and transplant management.

VEXAS syndrome is a complex hemato-inflammatory disorder, driven by somatic mutations in the UBA1 gene within hematopoietic precursor cells. It is characterized by systemic inflammation, rheumatological manifestations, and frequent association with myelodysplastic syndrome (MDS). We present a series of four VEXAS cases, all of which include concomitant MDS, each displaying distinct genetic signatures and clinical features at diagnosis, with a focus on their diagnostic and therapeutic implications. Our findings underscore the importance of extending UBA1 sequencing beyond exon 3 in cases with strong clinical suspicion. Given the rarity of non-canonical variants and the limited gene annotation, germline tissue control should be considered to differentiate somatic from germline mutations. Hematological management, including considerations for transplantation, was primarily guided by the Revised International Prognostic Scoring System (IPSS-R) for MDS due to the absence of a specific risk stratification system for VEXAS or therapy guidelines. A critical point of our discussion is the role of inflammation in the peri-transplant period; in one patient, the combination of disease-modifying antirheumatic drugs (DMARDs) and high-dose corticosteroids before transplant was crucial in controlling inflammation, resulting in a successful hematopoietic stem cell transplantation (HSCT). In contrast, uncontrolled inflammation contributed to the peri-transplant death of another patient. These cases highlight the importance of effective inflammation management in optimizing HSCT outcomes. Additionally, our study emphasizes the urgent need for specific management guidelines for VEXAS syndrome, including a comprehensive risk stratification system and optimal timing for transplantation.

The Use of Fresh Osteoarticular Allografts for Steroid-induced Osteonecrosis of the Femoral Condyle With Collapse in Childhood Cancer Patients: Single-institutional Experience

Background: Despite success in treating childhood acute lymphoblastic leukemia and lymphoma (ALL), modern multiagent chemotherapy regimens containing high-dose corticosteroids can result in osteonecrosis afflicting survivors, frequently involving the knee. Thus, we describe the usage of fresh osteoarticular allograft (FOAG) to treat steroid-induced osteonecrosis of the femoral condyle in pediatric cancer survivors. We assessed the efficacy of FOAGs to heal necrotic bone, provide long-term pain relief, while retrospectively reviewing quality of life and functional status. Methods: We recorded patient demographics, pain, and functional scores preoperatively, postoperatively, and at the most recent follow-up, additional surgical procedures, and radiographic outcomes at each timepoint. Anatomic locations and sizes of the grafts were noted using operative reports and intraoperative photographs. Function and pain scores were collected by direct patient communication or through survey, with data scored using the KOOS (Knee Injury and Osteoarthritis Outcome Score), PROMIS (Patient-Reported Outcomes Measurement Information System), and CTCAE (Common Terminology Criteria for Adverse Events) scoring tools. Results: Eighteen patients, (12 females) over a period of 8 years, underwent the procedure. One patient was excluded due to death before 12 months follow-up. The average age at diagnosis of femoral condyle osteonecrosis was 14.5 years. The average age at the time of surgery was 18.5 years (range, 13 to 25 y). All patients had at least 16 months follow-up (average 60 mo; range 16 to 99 mo). Grafts ranged in size from 18 to 27.5 mm. All patients reported a return to normal function of the knees with KOOS scores approaching normal, PROMIS scores averaging 46, and CTCAE outcomes improving at an average of 34 months post-surgery. Two patients experienced a partial graft failure, which was repaired with new allografts. Conclusions: Although historical reviews indicated unsatisfactory results, our experience highlights the successful usage of FOAG for the management of patients treated for childhood leukemia who develop steroid-induced osteonecrosis of the femoral condyle. This procedure proved effective in managing pain and improving function and quality of life, with good bone ingrowth despite large necrotic lesions. Levels of Evidence: Therapeutic Level IV.

Clinical features and factors associated with outcomes of antibody-negative autoimmune encephalitis in patients requiring intensive care

Background and objectivesAntibody-negative autoimmune encephalitis (AE) is a form of encephalitis characterized by the absence of detectable autoimmune antibodies, despite immunological evidence. However, data on management of patients with antibody-negative AE in the intensive care unit (ICU) are limited. This study aimed to explore the characteristics and subtypes of antibody-negative AE, assess the effects of immunotherapy, and identify factors independently associated with poor functional outcomes in patients requiring intensive care.MethodsThis retrospective, single-center study analyzed consecutive adult patients diagnosed with antibody-negative AE and admitted to the ICU of a large tertiary hospital between 2019 and 2023. Multivariate regression analysis was used to identify factors linked to poor functional outcomes six months after ICU admission, as defined by a modified Rankin Scale score of 3–6. Generalized linear mixed models were applied to evaluate the effect of immunotherapy on longitudinal changes in the Clinical Assessment Scale in Autoimmune Encephalitis and modified Rankin Scale scores.ResultsOf the 1220 patients with severe encephalitis admitted to the ICU, 107 were diagnosed with antibody-negative AE and included in the analysis. Six months after ICU admission, 67 patients (62.6%) had poor functional outcomes, including 28 deaths (26.2%). Factors independently associated with poor outcomes were high-dose corticosteroid therapy (odds ratio [OR] 8.734, 95% confidence interval [CI] 2.483–30.717), older age at onset (OR 1.063, 95% CI 1.028–1.099), acute respiratory failure at ICU admission (OR 10.931, 95% CI 2.062–57.751), and dyskinesia/dystonia (OR 14.109, 95% CI 1.336–148.957). The generalized linear mixed model also indicated that high-dose corticosteroid therapy was associated with poorer longitudinal outcomes.ConclusionsWhile high-dose corticosteroids are frequently used to treat AE, their risks may outweigh their benefits in severe antibody-negative AE cases. Older patients and those with dyskinesia/dystonia or respiratory failure, may require more careful monitoring and timely intervention for improved outcomes. However, prospective validation of these findings is necessary to confirm their applicability and guide future treatment strategies.

Recurrent Haemoptysis Revealing Hughes-Stovin Syndrome

Hughes-Stovin Syndrome (HSS) is a rare and severe disorder characterized by the combination of pulmonary artery aneurysms and deep vein thrombosis. We report the case of a 42-year-old male presenting with recurrent hemoptysis revealing HSS. Management consisted of high-dose corticosteroids and cyclophosphamide. The patient showed marked clinical and radiological improvement. HSS, as a rare form of Behçet’s disease, is associated with high morbidity and mortality due to thrombosis and potential rupture of aneurysms. Immunosuppression remains the cornerstone of management. Anticoagulation is controversial and requires careful consideration. Early diagnosis and prompt treatment are critical in managing HSS.

Cardiotoxicity and peri-operative considerations in immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy: a narrative review.

Immunotherapy has transformed cancer treatment, particularly with immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. Despite their efficacy, these therapies can induce cardiotoxicity, presenting significant clinical challenges. Immune checkpoint inhibitors can cause myocarditis; pericarditis; arrhythmias; and myocardial infarction through immune-mediated inflammation. Chimeric antigen receptor T-cell therapy may result in cardiovascular complications due to cytokine release syndrome, including myocardial dysfunction, endothelial damage and arrhythmias. We used PubMed, Embase and Google Scholar to search for peer-reviewed articles in September 2024 without setting any date limits. Our selection criteria encompassed studies focusing on cardiotoxicity related to immune checkpoint inhibitors or chimeric antigen receptor T-cell therapy, comprising original research, meta-analyses, clinical trials and review articles. The findings were reported narratively. Early diagnosis of cardiotoxicity is critical but challenging due to non-specific symptoms. Diagnostic tools include ECG; cardiac biomarkers; echocardiography; cardiac magnetic resonance imaging; and endomyocardial biopsy. However, no single tool is definitive. High-dose corticosteroids are the first-line treatment for immune checkpoint inhibitor-induced myocarditis, with additional immunosuppressive therapies for refractory cases. Standard heart failure management protocols should be followed in cases of heart failure. Tocilizumab and corticosteroids are utilised for chimeric antigen receptor T-cell therapy-induced cytokine release syndrome, alongside supportive care, including fluid resuscitation and vasopressors for severe cases. As the use of immunotherapy expands, understanding the mechanisms, risk factors and management strategies for cardiotoxicity is increasingly important. Collaborative efforts among oncologists, cardiologists and anaesthetists are essential to mitigate these risks, especially in peri-operative settings. Ongoing research is vital to improve the safe and effective use of immunotherapeutic drugs while minimising cardiovascular adverse effects.

Identifying subgroup of severe community-acquired pneumonia based on clinical metagenomics, a multicenter retrospective cohort study.

Severe community-acquired pneumonia (sCAP) is one of the major diseases within the ICU. We hypothesize that subtyping sCAP based on simple inflammatory markers, organ dysfunction, and clinical metagenomics results is feasible. In this study, we retrospectively enrolled immunocompetent sCAP patients requiring invasive mechanical ventilation, who underwent clinical metagenomics from 17 medical centers. We collected data on potentially pathogenic species reported by clinical metagenomics and clinical information for all patients. Latent class analysis (LCA) was applied to routine clinical parameters such as gender, age, white blood cell (WBC), lymphocytes, C-reactive protein (CRP), and Procalcitonin (PCT), identifying two optimally fitting models. A total of 569 patients were enrolled. Compared to class B, class A was characterized by a younger age, higher CRP and PCT levels, and a higher incidence of coagulation dysfunction, liver failure, circulatory failure, and renal failure. However, the mortality rates were similar between the two groups. In class A, more cases of Streptococcus spp. and fewer cases of HSV-1 and Candida spp. were detected. Among the patients in the two phenotypes, 48.7% and 57.5% received corticosteroid treatment, respectively. In the class A, corticosteroid treatment was not associated with patient mortality (unadjusted hazard ratio (HR)=0.988; 95% confidence interval (CI), 0.634-1.541; p=0.959). In contrast, in the class B group, the use of corticosteroids was associated with a reduced mortality rate (adjusted HR=0.719; 95% CI, 0.525-0.986; p=0.04). Additional analysis showed that in class B, methylprednisolone was associated with reduced mortality (adjusted HR=0.61; 95% CI, 0.44-0.86; p=0.005), while dexamethasone was not associated with mortality (adjusted HR=1.4; 95% CI, 0.89-2.22; p=0.148). In addition, after dose conversion, the results showed that higher doses of corticosteroids in class B were associated with increased mortality (adjusted HR=1.01; 95% CI, 1.00-1.01; p=0.005). We identified two classes based on clinical metagenomics and clinical features. Class B exhibited a better response to corticosteroid compared to class A. The rapid identification of these phenotypes could facilitate the screening of sCAP patients responsive to corticosteroid in future prospective clinical trials.

Acute visual field loss as first presentation of cancer associated retinopathy

Aims/Purpose: To describe a case of cancer‐associated retinopathy (CAR) due to advanced bilateral ovarian cancer presenting with visual field loss, photopsia and nyctalopia.Methods: A case report of a 53‐year‐old female with bilateral serous surface papillary ovarian cancer stage IIIC with one week history of visual field defect, photopsia and nyctalopia. Patient has undergone multiple surgical interventions and chemotherapy cycles plus bevacizumab in the last 7 years.Results: At the presentation, best‐corrected visual acuity (BCVA) was 20/20 in both eyes, normal pupils with no relative afferent pupillary defect and no dyscromatopsia. She denied pain with ocular movements. Examination of anterior and posterior segment was unremarkable. Humphrey visual field test showed a bilateral concentric peripheral field loss. Macular spectral domain optic coherence tomography (SD‐OCT) was normal, however peripheral SD‐OCT revealed marked thinning of the outer retinal layers. Fundus Autofluorescence (FAF) exhibited hyperfluorescence in mid‐peripheral retina more notorious in perivascular areas. Full‐field electroretinogram showed asimmetrical cone and rod dysfunction. Given these clinical findings and the history of ovarian cancer, CAR diagnosis was made. Treatment was started with high dose corticosteroids, immunoglobulins and Rituximab achieving improvement of visual phenomena, stabilization of visual acuity and interruption of retinal damage on OCT and FAF after 3 months of follow‐up.Conclusions: CAR is a paraneoplastic syndrome with poor visual prognosis. A cross reaction occurs between tumor and retinal antigens triggering an autoimmune response leading to a retinal degeneration, being alpha enolase and anti recoverin the most common. More than fifty percent of cases test positive to these antibodies. Despite negative results, treatment is important because patients with visual improvement are described in literature.

Refractory Idiopathic Hypereosinophilic Syndrome Presenting with Myocarditis and Responding to Imatinib: A Case Report

Abstract Idiopathic hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent hypereosinophilia leading to multi-organ dysfunction. Its clinical manifestations vary widely; however, cardiac and neurological involvement are the leading causes of morbidity and mortality. Corticosteroids are the initial treatment of choice, but in idiopathic HES resistant to corticosteroids, second-line therapy should be considered. Imatinib is usually reserved for patients with a positive platelet-derived growth factor receptor A (PDGFR-A) mutation; however, its use in idiopathic HES with a negative PDGFR mutation is debatable given that such patients usually respond well to high doses of corticosteroids. Here, we present a case of a young male with corticosteroid-refractory idiopathic HES successfully treated with imatinib. The patient presented with features suggestive of acute coronary syndrome and confusion. A coronary angiogram was normal. Echocardiography showed an ejection fraction of 37%, and brain imaging showed evidence of multifocal cerebral thromboembolic infarcts. During the hospital stay, the patient developed diffuse alveolar hemorrhage. Biochemically, it was noted that the patient had hypereosinophilia. Through thorough workup, a diagnosis of idiopathic HES was established. The patient was started on high-dose corticosteroid (500 mg intravenous methylprednisolone daily) followed by a maintenance dose of prednisolone (0.5 mg/kg/day), but had no response. Second-line therapy with imatinib (400 mg per oral daily for 4 days and then down-titrated to 100 mg daily) was initiated, which resulted in drastic biochemical and clinical improvements. This case report supports the efficacy of imatinib as a second-line agent in corticosteroid-resistant idiopathic HES with a negative PDGFR mutation.

Behçet's disease: recurrent ischemic stroke as an initial presentation - a case based review.

Behçet's disease (BD) is a rare systemic vasculitis that is characterized by recurrent oral and genital ulcers, uveitis, and skin lesions. Although neurological involvement is a known complication, ischemic stroke remains uncommon. Herein, we report a 37-year-old Kuwaiti woman who experienced recurrent ischemic stroke with no traditional risk factors. Imaging studies, including magnetic resonance imaging and angiography, confirmed the diagnosis of recurrent ischemic stroke and identified the underlying vasculitic changes. A detailed examination revealed a history of recurrent orogenital ulcers, leading to a diagnosis of BD. High-dose corticosteroids, azathioprine, and antiplatelet treatment were effectively used to manage her acute strokes and underlying vasculitis, thus preventing further thrombotic events. Our case report underscores the difficulties of diagnosing BD with ischemic stroke as the initial manifestation and emphasizes the importance of a multidisciplinary approach that involves rheumatologists, neurologists, and radiologists to create an effective treatment plan. Our findings also underscore the need for medical practitioners to be more knowledgeable about ischemic stroke in young patients without risk factors from endemic areas of BD, and to develop effective therapy plans. Our review of the English literature indicates that this is only the fifth report of stroke as the first presentation of BD.

Establishment and Validation of a Machine-Learning Prediction Nomogram Based on Lymphocyte Subtyping for Intra-Abdominal Candidiasis in Septic Patients.

This study aimed to develop and validate a nomogram based on lymphocyte subtyping and clinical factors for the early and rapid prediction of Intra-abdominal candidiasis (IAC) in septic patients. A prospective cohort study of 633 consecutive patients diagnosed with sepsis and intra-abdominal infection (IAI) was performed. We assessed the clinical characteristics and lymphocyte subsets at the onset of IAI. A machine-learning random forest model was used to select important variables, and multivariate logistic regression was used to analyze the factors influencing IAC. A nomogram model was constructed, and the discrimination, calibration, and clinical effectiveness of the model were verified. High-dose corticosteroids receipt, the CD4+T/CD8+ T ratio, total parenteral nutrition, gastrointestinal perforation, (1,3)-β-D-glucan (BDG) positivity and broad-spectrum antibiotics receipt were independent predictors of IAC. Using the above parameters to establish a nomogram, the area under the curve (AUC) values of the nomogram in the derivation and validation cohorts were 0.822 (95% CI 0.777-0.868) and 0.808 (95% CI 0.739-0.876), respectively. The AUC in the derivation cohort was greater than the Candida score [0.822 (95% CI 0.777-0.868) vs. 0.521 (95% CI 0.478-0.563), p < 0.001]. The calibration curve showed good predictive values and observed values of the nomogram; the Decision Curve Analysis (DCA) results showed that the nomogram had high clinical value. In conclusion, we established a nomogram based on the CD4+/CD8+ T-cell ratio and clinical risk factors that can help clinical physicians quickly rule out IAC or identify patients at greater risk for IAC at the onset of infection.

A case report of pulmonary paragonimiasis diagnosed via the deterioration of pulmonary cavities during high-dose corticosteroid therapy for chronic eosinophilic pneumonia

A 32-year-old Chinese woman with a cough and bloody sputum was diagnosed with chronic eosinophilic pneumonia. After starting corticosteroid therapy, chest radiography showed improvement in the bilateral infiltrative shadow. However, chest image findings showed worsening of the bilateral infiltrative shadow and pulmonary cavities during the 20 mg/day of oral prednisolone therapy. Transbronchial lung biopsy and bronchoalveolar lavage were repeated, and the patient was diagnosed with pulmonary paragonimiasis. After starting praziquantel treatment, chest radiography findings and clinical symptoms improved. Careful follow-up during corticosteroid therapy is important to judge whether transient improvement and true deterioration of radiological findings.

A Case Report of MOG Antibody-Associated Disease (MOGAD) with Isolated Brainstem and Spinal Cord Involvement

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a central nervous system demyelinating disorder with diverse clinical presentations, including optic neuritis, myelitis, and acute disseminated encephalomyelitis. Specific radiological features, such as diffuse T2 hyperintense lesions in the brainstem, involvement of the cerebellar peduncles, and longitudinally extensive spinal cord lesions, are key to differentiating MOGAD from other demyelinating conditions. Here, we present two rare cases of MOGAD with isolated brainstem and spinal cord involvement, diagnosed through clinical evaluation, serologic testing, and magnetic resonance imaging findings. Both cases were successfully treated with high-dose corticosteroids, underscoring the critical importance of early recognition and prompt intervention to optimize patient outcomes.

Advancements of aquaporin 1 in ultrafiltration failure secondary to peritoneal dialysis.

For patients undergoing long-term peritoneal dialysis (PD), exposure to biologically incompatible PD solutions and the consequent peritoneal structure change can lead to progressive angiogenesis and fibrosis, and ultimately result in ultrafiltration failure (UFF). Peritoneal transport studies in aquaporin 1 (AQP1) knockout mice indicate that water transport across the peritoneum is mediated by AQP1, which accounts for up to 50% of ultrafiltration. Another recent study on a large cohort of PD patients with kidney failure further substantiated the impact of AQP1 genotype variation on water channel expression in the peritoneal membrane, influencing water transport, ultrafiltration, and patient prognosis. High-dose corticosteroid therapy in both patients and mice seems to be effective in regulating AQP1 to improve ultrafiltration. At present, increasing evidence suggests that AQP1 is relevant for the process of PD water osmotic transport and ultrafiltration. Despite a great deal of research having been done on the structure and function of aquaporin proteins, many fundamental issues remain unresolved.

Corticosteroid therapy for treating acute exacerbation of interstitial lung diseases: a systematic review.

Acute exacerbation of interstitial lung disease (AE-ILD) often results in death and poses significant challenges in clinical management. While corticosteroids are frequently employed, the optimal regimen and their clinical efficacy remain uncertain. To address this knowledge gap, we undertook a systematic review to evaluate the impact of steroid therapy on clinical outcomes in patients experiencing AE-ILD. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we systematically searched multiple databases, identifying 12 454 articles. After removing duplicates and screening titles and abstracts, 447 articles were selected for full-text review. Ultimately, nine studies met inclusion criteria, comparing high-dose corticosteroids with low-dose or non-steroidal interventions in treating AE-ILD. Key outcomes included in-hospital and long-term mortality, as well as AE recurrence. Analysis of nine studies (total n=18 509) revealed differential treatment effects based on the ILD subtype. In non-idiopathic pulmonary fibrosis (IPF) ILD, high-dose corticosteroid therapy (>1.0 mg/kg prednisolone) demonstrated improved survival (adjusted HR 0.221, 95% CI 0.102 to 0.480, p<0.001) and reduced 90-day mortality. Early tapering of high-dose corticosteroids (>10% reduction within 2 weeks) reduced in-hospital mortality (adjusted HR 0.37, 95% CI 0.14 to 0.99). Higher cumulative doses in the first 30 days (5185±2414 mg/month vs 3133±1990 mg/month) were associated with lower recurrence rates (adjusted HR 0.61, 95% CI 0.41 to 0.90, p=0.02). In IPF patients, however, high-dose therapy showed inconsistent benefits, with some studies reporting increased mortality risk (OR 1.075, 95% CI 1.044 to 1.107, p<0.001). This review emphasises the potential benefits of individualised treatment approaches for AE-ILD but highlights the need for caution in making definitive recommendations. Although high-dose corticosteroids may show promise, particularly in non-IPF cases, the current evidence is inconsistent, and the lack of robust supporting literature makes it difficult to draw firm conclusions. Further research through randomised controlled trials is necessary to refine and optimise therapeutic strategies for AE-ILD.

Influenza Virus-Associated Acute Necrotizing Encephalopathy in Two Young Children: Case Report

Background and Clinical Significance: Acute necrotizing encephalopathy (ANE) represents a severe complication, mainly described in children, of influenza virus infection. We report the cases of two young girls with ANE associated with influenza virus infection who were diagnosed by MRI cerebral scan. Case Presentation: A 7-year-old girl with a history of a previous episode of ANE presented with a worsening drowsy state and seizures. In the second case, an otherwise healthy 5-year-old girl presented with fever, seizures, and marked neurological deterioration. In both cases, nasopharyngeal swab testing was positive for influenza virus A, while cerebral MRI indicated ANE. Despite aggressive treatment with high-dose corticosteroids and a five-day course ofimmunoglobulins, the ultimate prognosis was poor in both patients. ANE is a serious complication of viral infections in children, with a high mortality rate and a broad spectrum of neurological sequelae. To date, the pathophysiology and management of influenza virus-induced ANE remain uncertain. Although ANE is usually sporadic, familial and recurrent cases have been reported, and anRAN-binding protein (RANBP2) mutation has occasionally been associated with its occurrence.Conclusions: Rapid recognition of neurological symptoms and suspicion of a viral trigger, especially in influenza-like illnesses, are both essential for the timely administration of effective therapy. Further research is needed to clarify the pathophysiology of ANE and establish the best therapeutic strategies to fight such a deadly disease.

Granulomatosis with polyangiitis with rapidly progressive glomerulonephritis treated with a multipronged approach-a case based review.

Granulomatosis with polyangiitis is an ANCA-associated vasculitis that involves small to medium-sized vessels. The extent of renal involvement varies, which is also associated with disease prognosis, with aggressive renal involvement having worse outcomes. Rapidly progressive glomerulonephritis with severe inflammatory features and extensive crescent formation can be challenging to treat. Usually, induction regimes utilize a combination of pulse dose methylprednisolone followed by rituximab or cyclophosphamide. Resistant diseases pose additional treatment challenges, and individualized treatment regimens have been described without accumulated outcome data. Cyclophosphamide, rituximab, azathioprine, methotrexate, and mycophenolate with or without plasmapheresis have been variably used, but there is a lack of consensus on a standardized regime in literature. Our case adds to the existing literature on the treatment-refractory granulomatosis with polyangiitis, which was treated with high-dose corticosteroid in combination with rituximab, low-dose cyclophosphamide, plasmapheresis, and brief use of hemodialysis. It also reiterates that the use of a variety of low-dose cyclophosphamide with rituximab could be beneficial for treatment-refractory cases or patients with severe renal involvement, in addition to better tolerance with low dose cyclophosphamide in comparison with full-dose cyclophosphamide.

Severe Disease Activation after Fingolimod Discontinuation in a Pediatric Multiple Sclerosis Patient: A Case Report and Literature Review.

Adult reports of unexpected severe disease worsening, often termed "rebound," shortly after discontinuing fingolimod in a subset of patients with multiple sclerosis (MS), have grown over the last decade. This phenomenon, however, remains poorly described in pediatric MS patients. We present findings of a 15-year-old who experienced a debilitating relapse 4 weeks after stopping fingolimod to switch to ocrelizumab. Imaging revealed multiple large new lesions far exceeding any previously observed activity level in the patient. Despite prompt high-dose corticosteroids, plasma exchange, and prolonged rehabilitation therapy, significant residual deficits involving cognition, balance, and vision remain from the attack. This case underscores that pediatric MS patients are also at risk of severe disease deterioration after fingolimod withdrawal and require close monitoring when switching therapies.