Low-dose Steroids Research Articles

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Clinical spectrum in microbiologically proven Demodex blepharokeratoconjunctivitis: An observational study.

To study the demographic, clinical, and microbiological profile of Demodex-related blepharokeratoconjunctivitis (BKC) at a tertiary eye care hospital. This retrospective observational study was conducted from January 2016 to September 2022. It included 83 patients with microbiologically proven Demodex BKC who presented to the cornea department of our tertiary care eye center. The clinical, microbiological, and demographic data of the 83 cases were analyzed. Of the 83 cases, 57 (68.67%) were younger than 40 years, and 25 (30.12%) were below 20. Most patients presented with a good visual acuity of 20/40 or better (93 eyes; 84.55%). The disease was unilateral in 55 patients and bilateral in 28. Cylindrical dandruff was the predominant presentation noted in 61 eyes (54.95%), followed by corneal scarring in 47 eyes (42.34%) and corneal vascularization in 40 eyes (36.04%). On light microscopy, 87.95% of the positive samples were identified as Demodex folliculorum , 7.23% as Demodex brevis , and 6.02% remained unidentified. Tea tree oil and lid scrubs eradicated the disease in most patients clinically (75/83, 90.36%). The spectrum of BKC includes both lid signs and corneal involvement. It can be a cause of recurrent BKC and detection of the mite by microscopic evaluation of the lashes can confirm the diagnosis. In most cases, the tea tree oil can effectively manage this condition. However, low doses of topical steroids are needed to control the inflammation in patients with corneal involvement.

Coexistence of Sickle Cell Thalassaemia with Overlapping Syndrome: A Case Report of Systemic Lupus Erythematosus and Autoimmune Hepatitis

This case report highlights a rare and unique occurrence: the simultaneous presence of sickle cell thalassaemia and overlapping syndrome, which involves systemic lupus erythematosus and autoimmune hepatitis. The coexistence of sickle cell disease with overlapping syndrome is exceptionally rare, with only a few documented cases in the literature, one of which involves sickle cell β-thalassaemia. Significantly, this case enhances understanding of the intricate relationship among these conditions, and offers valuable perspectives on how to clinically manage them. The authors present the case of a young male in his early 20s, who presented with haemolytic anaemia, jaundice, joint pain, and hepatomegaly. Extensive laboratory investigations, including serological markers, haemoglobin electrophoresis, and liver function tests, confirmed the coexistence of sickle cell thalassaemia, systemic lupus erythematosus, and autoimmune hepatitis. The treatment included O2 therapy, hydration, hydroxyurea, and antibiotics. After 4–5 days, the patient showed improvement, and at discharge, hydroxyurea and folic acid were continued. Significantly, considering the complex medical history of the patient, a decision was made to include a carefully considered, low-dose steroid regimen. The choice of a maintenance dose over an induction therapy was specifically made to mitigate potential complications, particularly the risk of vaso-occlusive crises in patients with sickle cell disease. This case report contributes to the understanding of concurrent manifestation of these complex conditions, and emphasises the importance of a comprehensive approach, early diagnosis, and timely management, to optimise patient outcomes in such intricate overlapping syndromes.

AN OBSERVATIONAL STUDY OF EFFECT ON LIPID PROFILE BY SHORT TERM USE OF LOW DOSE STEROID THERAPY IN COMMON ORTHOPAEDIC CONDITIONS

Introduction:Corticosteroids, potent anti-inflammatory drugs used for decades, provide symptomatic relief but carry risks like infection and chronic conditions. Despite complications, theyre prescribed for orthopedic issues. Glucocorticoids influence lipid levels, with conflicting effects. Steroids are termed a double-edged sword. This study aims to assess lipid profile effects of short-term, low-dose steroid therapy in Orthopedics and Rheumatology, evaluating glucocorticoid therapy impact and investigating other effects on musculoskeletal patients. Materials and Methods:This prospective, non-randomized observational study was conducted, focusing on patients with orthopedic and rheumatological issues. Over 150 patients were included, selected through convenient sampling. Inclusion criteria involved patients aged 18-65 without dyslipidemia or cardiovascular conditions, while exclusion criteria included those with specific medical conditions or high BMI. Patients provided written informed consent before undergoing blood tests for lipid profile and blood sugar levels, with vital signs measured. They received Medrol 4 mg thrice daily for ten days, after which outcomes including lipid levels, blood sugar, and blood pressure were assessed. Results:At baseline, 88.67% had desirable cholesterol levels and 11.33% had borderline levels. At follow-up, 20.67% had borderline levels and 79.33% had desirable levels, a statistically significant difference. Mean cholesterol levels decreased from 169.16 ± 19.70 mg/dl to 161.11 ± 27.60 mg/dl, also significant. For triglycerides, 92.67% had normal levels at baseline, decreasing to 65.33% at follow-up, with mean levels increasing from 131.33 ± 6.97 mg/dl to 139.12 ± 23.88 mg/dl. HDL levels showed improvement, with 84.67% having desirable levels at baseline compared to 43.33% at follow-up, with mean levels increasing from 41.09 ± 5.13 mg/dl to 50.71 ± 4.21 mg/dl. LDL levels decreased from 132.43 ± 16.86 mg/dl to 122.59 ± 16.93 mg/dl, with significant changes in distribution. Conclusions:Short-term steroid use for orthopedic conditions affects lipid profiles: Total cholesterol, LDL, and TG rise significantly, countered by increased HDL, offering protection. Long-term effects on lipid profiles and cardiovascular risk require further study. Risk of avascular necrosis due to subtle lipid profile changes also warrants investigation.

Comparison between Tab Tofacitinib and Low-Dose Oral Steroid in Patients Having Vitiligo Over 6 Months

Background: Vitiligo is a chronic autoimmune condition characterized by depigmented patches on the skin, presenting significant treatment challenges. Recent studies have focused on the immunomodulatory effects of tofacitinib, a Janus kinase inhibitor, and the anti-inflammatory properties of low-dose oral steroids, yet comparative data on their efficacy and safety are scarce. Objective: The aim of this study was to compare the efficacy and safety of tofacitinib tablets with low-dose oral steroids in the treatment of vitiligo over a six-month period. Methods: This descriptive comparative study involved 42 patients with vitiligo, recruited from the Department of Dermatology at the Combined Military Hospital Abbottabad between November 15, 2022, and November 15, 2023. Participants were randomly assigned to receive either tofacitinib tablets (Group A) or low-dose oral steroids (Group B), with adherence monitored through routine follow-ups. The primary outcome measured was the proportion of repigmentation, assessed using standardized photography and Image software, alongside lesion size reduction and the incidence of adverse events. Statistical analyses were performed using SPSS version 25, with p-values ≤0.05 considered significant. Results: Both groups demonstrated comparable efficacy in terms of repigmentation and lesion size reduction, with no significant difference observed between the tofacitinib (55.8% ± 15.2 repigmentation; 100% lesion size reduction) and low-dose steroid groups (50.2% ± 13.5 repigmentation; 85.71% lesion size reduction) at the 6-month follow-up. The incidence of adverse events was similarly low and statistically non-significant between the two groups. Conclusion: Tofacitinib and low-dose oral steroids are both effective and safe for the treatment of vitiligo, offering valuable options for patient management. Further research with larger sample sizes and longer follow-up is necessary to confirm these findings and evaluate the long-term outcomes of these treatments.

Treatment strategies in MDA5-positive clinically amyopathic dermatomyositis: a single-center retrospective analysis

Melanoma differentiation-associated protein 5 (MDA5) antibody positive amyopathic dermatomyositis (DM) is a rare inflammatory disease. So far, there is no official treatment guideline in MDA5 amyopathic dermatomyositis, but early and aggressive immunosuppressive combination treatment can induce a stable remission. We retrospectively analyzed a cohort of eight patients (male n = 5) that were diagnosed with MDA5-positive amyopathic DM. Patient data comprised demographics, CT-guided diagnosis of pulmonary involvement, pulmonary function testing including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) data on baseline and mean long-term follow-up of 51 months (24–92 months) to evaluate treatment strategies. Depending on severity of organ involvement treatments were individualized including cyclophosphamide, immunoglobulins and plasmapheresis. Simultaneously, oral treatment with tacrolimus was commenced in four of the eight patients. Most patients received remission maintenance therapy with a combination of tacrolimus, rituximab and low dose steroids. In all patients, improvement in FVC was recorded and five patients achieved an improvement in DLCO. An improvement in the CT imaging morphological findings was observed in four patients. Awareness for the entirety of all clinical and disease-related findings of amyopathic DM is crucial, and remission maintenance is often achieved with a combination of tacrolimus and rituximab.

Reducing agalsidase beta infusion time in Fabry patients: low incidence of antibody formation and infusion-associated reactions in an Italian multicenter study

BackgroundFabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking. This study investigated a new and specific protocol for reducing agalsidase beta infusion time in which a stable dosage of 15 mg/h is infused for the first four months, and the infusion rate is increased progressively from 15 to 35 mg/h for the subsequent four infusions. The shortest infusion time is reached after six months and maintained thereafter. The incidence of infusion-associated reactions (IARs) and the development of anti-drug antibodies were analyzed, and the disease burden and the clinical evolution of the disease at 12 months were evaluated.ResultsTwenty-five of the 31 patients were naïve to enzyme or chaperone treatment at baseline and six patients had been switched from agalsidase alfa. The reduced infusion time protocol was well tolerated. Only one patient exhibited an IAR, with mild symptoms that resolved with low-dose steroids. Six patients globally seroconverted during treatment (4 with a classic phenotype and 2 with late-onset disease). All but three patients were seronegative at month 12. All patients were stable at the study’s end (FAbry STabilization indEX value < 20%); reducing infusion time did not negatively impact clinical outcomes in any patient. The perceived medical assessment showed that the quality of life of all patients improved.ConclusionsThe study demonstrates that reducing agalsidase beta infusion time is possible and safe from both an immunogenic and clinical point of view. The use of a low infusion rate in the first months when the probability of onset of the development of antibodies is higher contributed to very limited seroconversion to antibody-positive status.

Late Presentation of Early-onset Sarcoidosis: A Case Report

Background: Early-onset sarcoidosis is a rare systemic inflammatory granulomatous disease, distinguished by onset before the age of 4 and notably lacking pulmonary involvement. Unfortunately, the condition often shows clinical features similar to juvenile idiopathic arthritis, resulting in the misdiagnosis of numerous patients. This case report delves into the challenges associated with the delayed diagnosis of early-onset sarcoidosis, with a particular focus on the diagnostic methods employed to address this delayed recognition. Case presentation: A 15-year-old girl presented with a history of recurrent fever since infancy, accompanied by rash, arthritis, and joint deformity. Previously misdiagnosed with juvenile idiopathic arthritis, she underwent management with steroids and methotrexate, yielding no improvement. The diagnosis of early-onset sarcoidosis was made during adolescence based on serial examinations, comprehensive laboratory and radiological evaluations, and subsequent histopathology findings. Presently, the patient is receiving treatment with low-dose steroids and biologic therapy (Tocilizumab) and experiencing no disease progression. Conclusion: This case report underscores the importance of considering early-onset sarcoidosis in the differential diagnosis of pediatric patients exhibiting persistent arthritis from an early age. Early detection and treatment are crucial in averting complications and enhancing the overall quality of life.

Withdrawal of immunosuppressants and low-dose steroids in patients with stable IgG4-RD (WInS IgG4-RD): an investigator-initiated, multicentre, open-label, randomised controlled trial

ObjectivesIgG4-related disease (IgG4-RD) is an immune-mediated, fibroinflammatory disease. Induction treatment with glucocorticoid (GC) is usually effective, but its tendency of relapse makes the strategy for maintenance treatment a challenge. The...

Approach to the Peripubertal Patient With Short Stature.

The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)-insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth. Extensive literature review through PubMed and other search engines. Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments. The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized.

Relapse treatment with low-dose steroids in steroid-sensitive minimal change disease.

The treatment of minimal change disease (MCD) consists of a high dose of steroids for several months, implying significant drug toxicity. Nevertheless, relapses of steroid-sensitive MCD usually respond to lower doses of steroids. The objective of this study was to analyze whether a low dose of steroids (LDS) is effective for the treatment of MCD relapses. Since 2018, new relapses of steroid-sensitive adult patients with MCD in three Spanish centers have been treated with LDS. The cumulative dose of steroids, the time to remission, and the relapse-free time were compared between relapses treated with LDS and previous relapses of the same patients treated with a standard dose of steroids (SDS). A total of 51 relapses in 31 patients were treated with LDS and compared with 48 historical relapses of the same patients treated with SDS. The mean doses of prednisone adjusted by weight for the initial treatment were 0.45 mg/kg (0.40-0.51 mg/kg) in the relapses treated with LDS and 0.88 mg/kg (0.81-1.00 mg/kg) in those treated with SDS. The mean cumulative doses of prednisone in LDS- and SDS-treated relapses were 1,191 mg (801-1,890 mg) and 3,700 mg (2,755-5,800 mg), respectively. The duration of treatment was 63 days (42-117 days) in the LDS group and was 140 days (65-195 days) in the SDS group. All patients achieved complete remission within 1 month after steroid therapy in both groups. The times to remission of the LDS and SDS groups were 19.10 ± 12.80 and 18.93 ± 12.98 days, respectively (p = 0.95). Among the steroid-sensitive patients with MCD, relapse therapy with LDS (0.5 mg/kg) appears effective and allows minimization of the steroid cumulative dose.

A prospective observational study on efficacy and tolerability of the drugs used in treating rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is an autoimmune disorder requiring long-term combination therapy with disease-modifying antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory agents (NSAIDS), low-dose steroids, proton pump inhibitors, calcium, and folic acid and these drugs cause multitude of side effects. This study on the efficacy and tolerability of drugs used in RA among South Indian patients can guide in tailoring a treatment regimen more suited for South Indian population. Aims and Objectives: The main objective of this study was to evaluate the efficacy and tolerability of drugs used in the treatment of RA among South Indian patients. Materials and Methods: In this prospective observational study, 120 newly diagnosed RA patients attending rheumatology outpatient department in a tertiary care center in South India were recruited after obtaining Institutional Ethics Committee approval and informed consent. Sociodemographic details and baseline investigations were done. Each patient was followed up for a period of 6 months wherein, response to treatment was evaluated and adverse drug reactions (ADRs) reported were collected, analyzed and appropriate treatment was instituted. Data analysis was done using SPSS software. Results: One hundred patients completed the study. There was female preponderance (85%) and 38% were rheumatoid factor positive. Efficacy of combination therapy was evidenced falling erythrocyte sedimentation rate (P &lt; 0.001), modified health assessment questionnaire,and disease activity score 28 scorings after 1st, 3rd, and 6th month of therapy (P &lt; 0.001) and improvement in hemoglobin count (P &lt; 0.001). The number of swollen joints was also significantly reduced (P &lt; 0.001). Common ADRs reported were gastritis (29%), mucosal ulcers (10%), macrocytic anemia (3%), chloroquine-related ocular toxicity (2%). Conclusion: NSAIDS and steroids helped to achieve early remission and caused most of adverse effects. Methotrexate and chloroquine had good tolerability and were preferred DMARDs in our center. Thus, we conclude that the combination therapy used in our center is efficacious and well tolerated by South Indian population.

Steroid-responsive Multifocal Motor Neuropathy with Cranial Manifestations

The typical presentation of multifocal motor neuropathy (MMN) is progressive asymmetric limb weakness. Cranial neuropathy is rare. We report a 28-year-old woman with cranial and bulbar palsies but with typical electrophysiological features of MMN by multifocal motor conduction blocks and serological markers of anti-ganglioside GM1 antibodies. The previous consensus on the treatment of MMN is intravenous immunoglobulins, but our patient responded to oral steroids and had clinical and electrophysiological improvement under continuous low-dose prednisolone treatment. In summary, MMN is a treatable chronic inflammatory disease of peripheral nerves. Cranial neuropathies can be its initial presentation. Electromyography studies are crucial for MMN diagnosis and helpful in monitoring disease activity and treatment responses. Although the previous guideline did not suggest using steroids for MMN, with careful patient selection, low-dose oral steroids can be an effective treatment in patients with relatively minor symptoms.

Treatment of Juvenile Myasthenia Gravis

The pathogenesis of juvenile myasthenia gravis is similar to that of adult-onset cases, but does differ significantly in that it is predominantly ocular type, has a low antibody-positive rate, a low thymoma complication rate, and a high remission rate. The evidence for the adult treatment strategy of low-dose steroids and fast-acting treatment is insufficient in children, and the safety of immunosuppressive drugs has not been established. Steroid use in children in particular requires caution due to the risk of growth retardation, and while lower doses are desirable, the efficacy of lower doses has not been as fully investigated as in adults. Conversely, experience has shown that the use of adequate doses of steroids results in high remission rates, and there is currently no rationale for recommending lower doses.

Thyroid Eye Disease: Epidemiology, Natural History, and Risk Factors.

Thyroid eye disease (TED) is an autoimmune disorder of the orbit and the most frequent extrathyroidal manifestation of Graves' disease but it may rarely occur in euthyroid/hypothyroid patients with chronic autoimmune thyroiditis. TED is a relatively infrequent disorder, particularly in its severe forms. Men tend to have more severe TED at an older age. The prevalence of TED is lower than in the past among patients with recent onset Graves' hyperthyroidism, and moderate-to-severe forms requiring aggressive treatments are no more than 5% to 6% of all cases. After an initial inflammatory (active) phase and a plateau phase, TED stabilizes and eventually inactivates (inactive or burnt-out phase) after an estimated period of 18-24 months. Minimal-to-mild TED often remits spontaneously, but complete restitutio ad integrum almost never occurs when TED is more than mild. Several risk factors contribute to its development on a yet undefined genetic background. Cigarette smoking is the most important of them, but thyroid dysfunction (both hyper- and hypothyroidism), radioactive iodine therapy (if not accompanied by low-dose steroid prophylaxis), elevated thyrotropin receptor antibodies, and, probably, hypercholesterolemia represent relevant modifiable risk factors. Early diagnosis, control and removal of modifiable risk factors, and early treatment of mild forms of GO (local treatment and selenium) may effectively limit the risk of progression to more severe forms.

Bilateral Glaucoma Drainage Device (GDD) Implantation in Steroid Induced Glaucoma

Objective: This study aims to report a case of Bilateral Glaucoma Drainage Device (GDD) implantation surgery in a patient with Steroid Induced Glaucoma. Case Presentation: A 18-year-old male patient with steroid-induced glaucoma and allergic conjunctivitis. The patient also complained about red eyes and itchy in both eyes and had been using steroid eye drops for 5 years. The patient also complained about headaches and blurry vision. The patient had undergone trabeculectomy surgery 5 months ago on the left eye. The visual acuity was 6/6 on the right eye and 6/7.5 on the left eye. His intraocular pressure (IOP) on the right eye was 24 mmHg, and his left eye was 23 mmHg with conjunctival left eye bleb, flat, and fibrosis. The patient then underwent a non-valve Virna’s GDD implant surgery on the right eye. On day two post-GDD, the IOP was 4 mmHg, and the COA was shallow, so reform the COA. At the first month follow-up, the patient's right eye pressure was still in normal condition with no complications, and then the plan was for left eye Virna’s GDD implantation surgery. At the first month follow-up after left eye GDD implantation, the visual acuity was 6/9 on the right eye and 6/24 on the left eye, with IOP RE 11mmHg and LE 16mmHg, from anterior segment deep anterior chamber, no plate exposed, no leakage, and tube not attached to the corneal endothelium. The patient's intraocular pressure was still in normal condition in both eyes, and no complications was found, although the patient was still using low-dose topical steroid eye drops. Conclusion: In steroid-induced glaucoma, after trabeculectomy failure, the implantation of GDD is the most effective option in controlling high IOP and slowing down glaucoma progressivity.

Single-Centre Experience With Low-Volume Plasma Exchange and Low-Dose Steroid to Treat Patients With Idiosyncratic Drug-Induced Acute Liver Failure

BackgroundIdiosyncratic drug induced liver injury (iDILI) causing acute liver failure (ALF) carries high short-term mortality and patients who meet King’s College hospital criteria for liver transplantation have 1-month survival of 34% without liver transplantation (PMID: 20949552). We present our experience with low volume plasma exchange (PLEX-LV, 50% of estimated plasma volume exchanged per session) and low dose steroid to treat iDILI ALF. MethodsWe retrospectively analyzed data of patients with iDILI (diagnosed as per RUCAM score), treated with PLEX-LV and low dose steroid (Prednisolone: 10 mg OD, with rapid taper) in our department from 2016 to 2022. Baseline and dynamic parameters (post-PLEX) were assessed as predictors of 1-month liver transplantation free survival. ResultsTwenty-two iDILI patients [probable: possible iDILI: 20:2, males: 9, age: 30 (14-84) years, median (range); MELD score: 30.5 (19-43)] underwent PLEX-LV for ALF during the study period.Causative agents were complementary and alternative medications (36%), antiepileptics (18%) antimicrobials (14%), antitubercular drugs (14%), antifungal drugs(9%)and others (9%). All patients had jaundice and encephalopathy; 9 patients also had ascites. None of the patients underwent liver transplantation. Study patients underwent 3 (1-7) PLEX sessions and 1.4 (0.6-1.6) litres of plasma was exchanged per session.One-month transplant free survival was 59% (13/22) in the study population and 63% (12/19) among patients who fulfilled Kings College Hospital Criteria for liver transplantation. Reduction of ≥25% in plasma Von Willebrand factor (VWF) levels after PLEX-LV predicted improved survival (HR: 0.09, 95%CI: 0.01-0.65; AUROC: 0.81; 95% CI: 0.6-1.0). ConclusionLow volume PLEX and low dose steroid appears a promising treatment option in patients with iDILI induced ALF not opting for liver transplantation. Dynamic changes in VWF level after PLEX predict 1 month survival in these patients.

Neither Conditioning Chemotherapy Nor GvHD-Prophylaxis: CD7 CAR-T Treatment Bridging to Haplo-HSCT

BACKGROUND: Relapsed/refractory (R/R) acute leukemia patients ineligible for allo-HSCT have poor prognosis. CAR-T therapy has shown promising therapeutic outcomes for these patients, but simultaneously confers the risk of pancytopenia and potential tumor relapse. Bridging CAR-T therapy with allo-HSCT has the potential to restore hematopoiesis and consolidate long-term efficacy. However, GvHD remains a major impediment, and the myeloablative conditioning regimen eradicates residual CAR-T cells and compromises CAR-mediated antitumor function. Furthermore, the implementation of conditioning regimen and GvHD-prophylaxis could lead to severe toxicities. Novel strategies are therefore warranted to preserve CAR-T cells, enhance antitumor potency and minimize complications. METHODS: In this study, we presented 10 patients (enrolled between November 2021 and June 2023) with R/R CD7-positive acute leukemia who proceeded directly to haploidentical HSCT (haplo-HSCT) after CAR-T therapy. All patients received allogeneic CD7 CAR-T therapy, manufactured from either haploidentical donors (n=8) in a phase I clinical trial of donor-derived CAR-T cells (NCT04599556) or (n=1) universal CD7 CAR-T cells (RD13-02) therapy (NCT05716113) or as a compassionate use program after the end of a phase I clinical trial of universal CD7 CAR-T cells (RD13-01) (NCT04538599). CAR-T cell doses were at 2´10 6(haploidentical donor, n=8), 4´10 6 (RD13-02, n=1) or 5´10 6 (RD13-01, n=1) cells/kg. After achieving complete remission with incomplete hematological recovery (CRi), all patients underwent haplo-HSCT without conditioning regimen or GvHD prophylaxis. The primary end point was efficacy, safety, hematopoiesis recovery, and donor chimerism. RESULTS: All patients relapsed from multiple lines of chemotherapy or immunotherapy (median, 7; range, 4-13), were ineligible for allo-HSCT and received palliative care. After CAR-T infusion, 9 patients achieved MRD-negative CRi, and 1 achieved MRD-positive CRi, on day 15 after CD7 CAR-T therapy. 9 patients developed grade 1-2 cytokine release syndrome, and no neurological toxicity was reported. All patients exhibited grade 4 pancytopenia and bone marrow hypocellularity and were directly bridging to haplo-HSCT. The median time from CAR-T infusion to haplo-HSCT was 19 (range, 15-89) days. One patient died of HHV6 infection in central nervous system on day 13 after haplo-HSCT and was not evaluable for the following safety and efficacy. 3 patients experienced short-term grade II acute GvHD, which was resolved completely after low dose steroid, anti-TNF-α or ruxolitinib therapy. One patient developed PTLD at 2.1 months post-HSCT. In 9 evaluable patients, 8 showed full donor chimerism at 1-month post-HSCT, and 1 showed autologous hematopoiesis recovery. At a median follow-up of 10.2 (range, 2.2-20.7) months after CAR-T therapy, 6 patients remained in MRD-negative CR with normal hematopoiesis (including the patient with autologous hematopoietic recovery), 1 had CD7-negative relapse at 5.6 months, 1 developed CD7-negative relapse at 4.3 months and died at 4.8 months, and 1 died from septic shocks at 3.7 months. OS, PFS, NRM, and CIR at 1 year were 64.3% (95% CI, 38.5%-100%), 51.4% (95% CI, 26.2%-100%), 22.9% and 25.7%, respectively. Peripheral normal T cells in 8/10 of patients remained CD7-negative at the last follow-up, illustrating a well-maintained CAR-T function post-HSCT. CONCLUSIONS: Our findings demonstrate a novel strategy to simultaneously achieve CAR-T persistence and complete HSC engraftment, while reducing the risks of GvHD, providing valuable insights into combining cellular therapy with allo-HSCT for the treatment of R/R acute leukemia patients ineligible for conventional allo-HSCT.

Treatments and Severe Outcomes for Patients Diagnosed With MIS-C at Four Children's Hospitals in the United States, March 16, 2020-March 10, 2021.

Clinical management of multisystem inflammatory syndrome in children (MIS-C) has varied over time and by medical institution. Data on patients with MIS-C were collected from 4 children's hospitals between March 16, 2020 and March 10, 2021. Relationships between MIS-C treatments and patient demographics, clinical characteristics, and outcomes were described. Propensity score matching was utilized to assess the relative risk of outcomes dependent on early treatment with intravenous immunoglobulin (IVIG) or low-dose steroids, controlling for potential confounding variables. Of 233 patients diagnosed with MIS-C, the most commonly administered treatments were steroids (88.4%), aspirin (81.1%), IVIG (77.7%) and anticoagulants (71.2%). Compared with those patients without respiratory features, patients with respiratory features were less likely to receive IVIG and steroids on the same day (combination treatment) (44.1%). Controlling for confounding variables, patients receiving IVIG within 1 day of hospitalization were less likely to have hospital length of stay ≥8 days (RR = 0.53, 95% CI: 0.31-0.88). Patients receiving low-dose steroids within 1 day of hospitalization were less likely to develop ventricular dysfunction (RR = 0.45, 95% CI: 0.26-0.77), have increasingly elevated troponin levels (RR = 0.55, 95% CI: 0.40-0.75) or have hospital length of stay ≥8 days (RR = 0.46, 95% CI: 0.29-0.74). Treatments for MIS-C differed by hospital, patient characteristics and illness severity. When IVIG and low-dose steroids were administered in combination or low-dose steroids were administered alone within 1 day of hospitalization, the risk of subsequent severe outcomes was decreased.

FRI634 Diagnostic Delay Of Diabetic Amyotrophy Is Associated With Complicated Disease Leading To Mental, Physical, And Financial Debilitation- A Case Report

Abstract Disclosure: A.J. Zaidi: None. W. Staehle: None. Introduction: Delay in diagnosis is a major problem impacting medicine, especially if pathology is not very common, like Diabetic amyotrophy. It typically presents with unilateral proximal muscle weakness and pain affecting thighs, hips and buttocks. It is relatively a rare neurological complication of Diabetes Mellitus and prediabetes, affecting approximately 1 percent of the patients. It is commonly underrecognized leading to long course to diagnosis. Case presentation: A 58 year old female presented to clinic with 5 year history of Lower back and left hip pain, slowly progressive leg weakness, with weight loss 25 pounds. Her past medical history included Type 2 diabetes mellitus with A1C 6.9, controlled by Metformin alone. She had multiple previous presentations to local primary care physicians, with unclear clinical diagnosis. She underwent several tests and imaging, was seen by neurologist, orthopedist and spine physician. Her treatments included pain regimens with N-acetylcysteine, Ibuprofen, gabapentin, tizanidine, lidocaine patch, low dose steroids, physical therapy and chiropractor visits. These provided only partial symptomatic relief. She had no other significant history, She lost her job due to being limited by her pain. Exam revealed discomfort to palpation on lower lumbar, generalized atrophy of left thigh muscles, asymmetric proximal weakness, normal sensation and reflexes. Blood work showed normal ESR, CRP, CPK, ANA, myomarker panel, Vit D levels. CSF evaluation was deferred by the patient. Imaging from previous records included Hip X-ray with mild degenerative disease, Lumbar CT with mild arthropathy on the Left L5- S1. Unremarkable lumbar and Sacral MRI. EMG revealed L4 radiculopathy with denervation of L vastus medialis and tibialis anterior, Irritation in S1 nerve root, without denervation. Based on overall investigations, and lack of evidence of alternative diagnosis, it was determined that the patient had Diabetic Amyotrophy. She refused IVIG, treated with prednisone 5mg PO oral for a month, Duloxetine and gabapentin, with significant improvement in pain and weakness. Patient was also connected with appropriate social services, physical and occupational therapy. Conclusion: Diagnostic delay of diabetic amyotrophy can lead to mental, physical, and financial debilitation. Due to low prevalence and broad differential of proximal muscle wasting, it is a challenging to diagnose and remains the diagnosis of exclusion. EMG studies with polyradiculopathy in proximal leg musculature is suggestive. Physicians should have a high clinical suspicion for diabetic amyotrophy to prevent long clinical course leading to harm to the patient. The emphasis is on creating awareness of the disease, and improving communication among clinicians and with patients, which are relatively minor investments to prevent delayed diagnosis of underrecognized complication. Presentation: Friday, June 16, 2023