Management of acute severe ulcerative colitis-an update for generalist and specialist clinicians.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC. SOURCES OF DATA: The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials. AREAS OF AGREEMENT: Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery. AREAS OF CONTROVERSY: Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous. GROWING POINTS: The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC. AREAS TIMELY FOR DEVELOPING RESEARCH: Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research.

ZFP36 family expression is suppressed by Th2 cells in asthma, leading to enhanced synthesis of inflammatory cytokines and cell surface molecules.

Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of ZFP36 family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (https://www.ncbi.nlm.nih.gov/gds) showed significantly suppressed expression of ZFP36 family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with ZFP36 family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1ß, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of ZFP36 family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.

Treatment of Noninfectious Uveitic Macular Edema with Periocular and Intraocular Corticosteroid Therapies: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema. METHODS: A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients. RESULTS: This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation. CONCLUSIONS: The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The association between myasthenia gravis and risk of fracture: a systematic review and meta-analysis.

Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle-Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I2 = 93%; between-study variance [τ2] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro.

BACKGROUND: Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features. METHODS: We investigated the effects of passive sensitisation on IL-5, NF-κB, HDAC-2, ACh, and ChAT in human bronchial epithelial cells (HBEpCs) and the effects of fluticasone furoate (FF) and umeclidinium (UME) alone and in combination on these responses. RESULTS: IL-5 and NF-κB levels were increased, and that of HDAC-2 reduced in sensitised HEBpCs. Pretreatment with FF reversed the effects of passive sensitisation by concentration-dependent reduction of IL-5, resulting in decreased NF-κB levels and restored HDAC-2 activity. Addition of UME enhanced these effects. Sensitized HEBpCs also exhibited higher ACh and ChAT levels. Pretreatment with UME significantly reduced ACh levels, and addition of FF caused a further small reduction. CONCLUSION: This study confirmed that passive sensitisation of AECs results in an inflammatory response with increased levels of IL-5 and NF-κB, reduced levels of HDAC-2, and higher levels of ACh and ChAT compared to normal cells. Combining FF and UME was found to be more effective in reducing IL-5, NF-κB, and ACh and restoring HDAC-2 compared to the individual components. This finding supports adding a LAMA to established ICS/LABA treatment in asthma and suggests the possibility of using an ICS/LAMA combination when needed.

Efficacy of different doses of corticosteroids in treating severe COVID-19 pneumonia.

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.

A diagnostic dilemma: cytomegalovirus colitis as an uncommon comorbidity in inflammatory bowel disease: a case report.

BACKGROUND: The role of cytomegalovirus infection as an opportunistic pathogen in exacerbating ulcerative colitis and its response to treatment remain a topic of ongoing debate. Clinicians encounter numerous challenges, including the criteria for differentiating between an acute ulcerative colitis flare and true cytomegalovirus colitis, the diagnostic tests for identifying cytomegalovirus colitis, and determining the appropriate timing for initiating antiviral therapy. CASE PRESENTATION: A 28-year-old Syrian female with a seven-year history of pancolitis presented with worsening bloody diarrhea, abdominal pain, and tenesmus despite ongoing treatment with azathioprine, mesalazine, and prednisolone. She experienced a new flare of acute severe ulcerative colitis despite recently completing two induction doses of infliximab (5 mg/kg) initiated four weeks prior for moderate-to-severe ulcerative colitis. She had no prior surgical history. Her symptoms included watery, bloody diarrhea occurring nine to ten times per day, abdominal pain, and tenesmus. Initial laboratory tests indicated anemia, leukocytosis, elevated C-reactive protein (CRP) and fecal calprotectin levels, and positive CMV IgG. Stool cultures, Clostridium difficile toxin, testing for Escherichia coli and Cryptosporidium, and microscopy for ova and parasites were all negative. Sigmoidoscopy revealed numerous prominent erythematous area with spontaneous bleeding. Biopsies demonstrated CMV inclusions confirmed by immunohistochemistry, although prior biopsies were negative. We tapered prednisolone and azathioprine and initiated ganciclovir at 5 mg/kg for ten days, followed by valganciclovir at 450 mg twice daily for three weeks. After one month, she showed marked improvement, with CRP and fecal calprotectin levels returning to normal. She scored one point on the partial Mayo score. The third induction dose of infliximab was administered on schedule, and azathioprine was resumed. CONCLUSION: Concurrent cytomegalovirus infection in patients with inflammatory bowel disease presents a significant clinical challenge due to its associated morbidity and mortality. Diagnosing and managing this condition is particularly difficult, especially regarding the initiation or continuation of immunosuppressive therapies.

Efficacy and safety of corticosteroids and ACTH in epileptic syndromes beyond Infantile Epileptic Spasms Syndrome (IESS): A systematic review and meta-analysis.

We conducted a systematic review investigating the efficacy and tolerability of adrenocorticotropic hormone (ACTH) and corticosteroids in children with epilepsies other than infantile epileptic spasm syndrome (IESS) that are resistant to anti-seizure medication (ASM). We included retrospective and prospective studies reporting on more than five patients and with clear case definitions and descriptions of treatment and outcome measures. We searched multiple databases and registries, and we assessed the risk of bias in the selected studies using a questionnaire based on published templates. Results were summarized with meta-analyses that pooled logit-transformed proportions or rates. Subgroup analyses and univariable and multivariable meta-regressions were performed to examine the influence of covariates. We included 38 studies (2 controlled and 5 uncontrolled prospective; 31 retrospective) involving 1152 patients. Meta-analysis of aggregate data for the primary outcomes of seizure response and reduction of electroencephalography (EEG) spikes at the end of treatment yielded pooled proportions (PPs) of 0.60 (95% confidence interval [CI] 0.52-0.67) and 0.56 (95% CI 0.43-0.68). The relapse rate was high (PP 0.33, 95% CI 0.27-0.40). Group analyses and meta-regression showed a small benefit of ACTH and no difference between all other corticosteroids, a slightly better effect in electric status epilepticus in slow sleep (ESES) and a weaker effect in patients with cognitive impairment and "symptomatic" etiology. Obesity and Cushing's syndrome were the most common adverse effects, occurring more frequently in trials addressing continuous ACTH (PP 0.73, 95% CI 0.48-0.89) or corticosteroids (PP 0.72, 95% CI 0.54-0.85) than intermittent intravenous or oral corticosteroid administration (PP 0.05, 95% CI 0.02-0.10). The validity of these results is limited by the high risk of bias in most included studies and large heterogeneity among study results. This report was registered under International Prospective Register of Systematic Reviews (PROSPERO) number CRD42022313846. We received no financial support.

Prothrombin time predicts steroid response in severe alcohol-related hepatitis.

BACKGROUND AND AIMS: Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH). METHODS: Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7. RESULTS: A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954). CONCLUSIONS: BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.

Evaluation of Induction Immunosuppression and Risk of Incisional Hernia After Liver Transplantation.

INTRODUCTION: Liver transplantation (LT) is a technically complex operation and usually performed on ill patients. A major postoperative morbidity is incisional hernia, occurring in 9.5%-32.4% of cases. There are mixed results in transplant studies regarding potential risk factors. Additionally, the literature is lacking in the relationship between specific immunosuppressive induction agents administered during LT and postoperative incisional hernia. METHODS: A single center, retrospective cohort study of patients who underwent primary LT between 4/2011-1/2018 was conducted. Clinical variables including demographics and comorbidities were reviewed. The primary end point was the development of an incisional hernia following LT. Sub analysis was performed for secondary end points to determine potential risk factors, including immunosuppressive induction agent. RESULTS: Overall, 418 patients met inclusion criteria. At 5 y post-LT, there were 66/271 (24.4%) and 53/147 (36.1%) patients diagnosed with an incisional hernia in the methylprednisolone and basiliximab groups, respectively. After propensity score matching, there was no difference in incisional hernia development between induction agents, P = 0.19. For patients with body mass index ≥30 and postoperative seroma of the abdominal wall, the hazard ratios were 2.67 (95% CI = 1.7, 4.3) and 2.03 (95% CI = 1.1, 3.9), respectively. CONCLUSIONS: Incisional hernia rate after LT was 28.5% at 5 y. Our analysis found that immunosuppressive induction agent at LT was not associated with the development of postoperative incisional hernia. However, preoperative obesity (body mass index ≥30) and postoperative seroma of the abdominal wall were potential risk factors. Further studies are needed to delineate if these risk factors remain across institutions and in alternative settings.

Estimating the effect of diuretics and inhaled corticosteroids for evolving bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Off-label treatment of extremely preterm infants with diuretics and inhaled corticosteroids (ICS) for evolving bronchopulmonary dysplasia (BPD) is common. Their effectiveness in reducing mortality or BPD severity, and optimal treatment timing, are unclear. OBJECTIVES: To determine whether diuretic treatment or ICS administration for infants with early evolving (between 10-27 days postnatal) and progressively evolving (28th-day-36th-week postnatal) BPD are independently associated with reduced mortality and moderate or severe BPD at 36-weeks postmenstrual age (PMA). METHODS: We examined neonates born before 28 weeks' gestation and admitted to neonatal intensive care units on postnatal Day 0 between 2006 and 2016 using data collected during routine care recorded within the Paediatric Health Information System (PHIS). An early evolving BPD cohort consisted of infants treated with oxygen, positive pressure or mechanical ventilation at 10 days postnatal. The progressively evolving BPD cohort consisted of infants treated with these modalities at 28 days. In new users, we evaluated the effect of diuretic and ICS treatment on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding by respiratory status using marginal structural models. RESULTS: Early evolving BPD was present in 10,135 patients; progressively evolving BPD in 11,728. New diuretic exposure during early evolving BPD (adjusted risk ratio [aRR] 0.77, 95% confidence interval [CI] 0.65, 0.93) was associated with decreased mortality or moderate/severe BPD risk. New diuretics (aRR 0.86, 95% CI 0.75, 0.99) during progressively evolving BPD between 28-days-36-weeks PMA were less strongly associated with mortality or moderate/severe BPD reduction. There was no strong association for ICS in patients with early evolving (aRR: 1.40; 95% CI: 0.79, 2.51) or progressively evolving BPD (aRR 1.16, 95% CI 0.95, 1.49). CONCLUSION: Diuretics, but not ICS, for evolving BPD were associated with mortality and BPD risk reduction.

Local and Systemic Side Effects of Corticosteroid Injections for Musculoskeletal Indications.

Corticosteroid injections can be associated with a range of potential side effects, which may be classified as local or systemic and further stratified as immediate or delayed in onset. Radiologists performing image-guided musculoskeletal injections should recognize the potential side effects of corticosteroid medication when counseling patients before injection and consider such side effects in planning individual injections. This Review summarizes the available evidence regarding the local and systemic side effects of corticosteroid injections performed for musculoskeletal indications. Local side effects include postinjection flare, skin hypopigmentation and atrophy, infection, tendon rupture, accelerated progression of osteoarthritis, and osseous injury. Systemic side effects include adrenal suppression or insufficiency, facial flushing, hypertension, hyperglycemia, and osteoporosis. Additional targeted counseling is warranted regarding side effects that are specific to certain patient populations (i.e., premenopausal women, patients with diabetes, athletes, and pediatric patients). Corticosteroid injections are contraindicated in the presence of superficial or deep infection, fracture, or a prosthetic joint. Guidelines on the frequency, duration, and maximal lifetime use of corticosteroid injections are currently lacking. Further research is needed regarding the long-term complications of continuous corticosteroid use, particularly with regard to osseous effects.

Efgartigimod combined with steroids as a fast-acting therapy for myasthenic crisis: a case report.

BACKGROUND: Generalized myasthenia gravis (gMG) can be managed with acetylcholinesterase inhibitors (AChEis; e.g., pyridostigmine), corticosteroids, other immunosuppressive drugs (e.g., tacrolimus), and their combinations. Intravenous immunoglobulin (IVIg) or plasmapheresis (PLEX) may be administered if symptoms persist. PLEX and IVIg are also mainstays of treatment for myasthenic crisis. Recently, efgartigimod was approved in Japan for treating adults with gMG (irrespective of the antibody status) who do not have a sufficient response to corticosteroids and nonsteroidal immunosuppressive therapies. Efgartigimod is generally safe and well tolerated. However, since phase III trials of efgartigimod excluded those with myasthenic crisis, the efficacy of efgartigimod in treating myasthenic crisis is still unclear. Moreover, there are no reports that efgartigimod therapy can reduce the dose of corticosteroids needed to achieve a minimal manifestation status. CASE PRESENTATION: We report the case of a 70-yeat-old woman with gMG who developed a myasthenic crisis. After she was diagnosed with gMG, the patient had been treated with oral corticosteroids and tacrolimus for 1 year. However, she refused to continue taking the medication, and two weeks later, she developed ptosis, dysphagia and dyspnea. The patient was intubated and treated with efgartigimod in combination with steroid therapy, and she recovered without PLEX or IVIg. Afterward, when she experienced worsening of fatigue and increased levels of anti-acetylcholine receptor antibodies, efgartigimod therapy was effective. The patient achieved minimal manifestation status even after the reduction of corticosteroids and showed improvements in the Myasthenia Gravis Activities of Daily Living scales after 4 cycles of efgartigimod infusion. CONCLUSIONS: Our case suggests that efgartigimod can be an alternative drug for achieving minimal manifestation status in patients with myasthenic crisis. Considering its strong efficacy and safety, efgartigimod could be expanded to use as bridging therapy in the acute and chronic phases of gMG.

Real-world approaches to outpatient treatment of status migrainosus: A survey study.

OBJECTIVES: Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. BACKGROUND: SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72-h duration is required before the attack can be treated as SM. METHODS: The Refractory Headache Special Interest Group from AHS developed a four-question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. RESULTS: Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72-h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti-inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). CONCLUSIONS: Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management.

Safety of dermatologic medications in pregnancy and lactation: An Update - Part I: Pregnancy.

The breadth of therapeutic options for the management of dermatologic skin conditions continues to expand rapidly as exemplified by biologics and small molecule drug development. While dermatologists and healthcare providers are aware of the underlying mechanisms and indications for these therapeutics, there is a recognized practice gap due to an incomplete understanding of the safety of these medications in women of childbearing age during the prepartum, antepartum and postpartum phases. Although a two-part continuing medical education review was published regarding the prescribing practices and safety profiles of these new therapeutics in women of childbearing age while pregnant or lactating in 20141,2, many new medications have been approved since then. Herein, we will update the safety of dermatologic therapies during pregnancy and Part II will review the safety of medications during lactation.

Safety of dermatologic medications in pregnancy and lactation: An Update - Part II: Lactation.

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation.

Methylprednisolone dosing for pediatric critical asthma: a single-center cohort study.

OBJECTIVE: We aimed to characterize intravenous (IV) methylprednisolone (MP) dosing regimens and clinical outcomes for children hospitalized for critical asthma (CA). METHODS: A single-center, retrospective review was performed of children admitted to the pediatric intensive care unit (PICU) for CA between September 2015 and October 2019. Patients 5-to 17-year-olds, initiated on continuous nebulized albuterol, and prescribed at least one dose of IV MP were included. The primary outcome was to characterize PICU MP dosing. Cohorts were then compared by MP dosing: conservative-dose methylprednisolone (CDMP, ≤ 0.5 mg/kg/dose every 6 h) and standard-dose methylprednisolone (SDMP, > 0.5 mg/kg/dose every 6 h). Clinical efficacy endpoints were the duration of continuous nebulized albuterol and PICU length of stay (LOS). Safety endpoints included corticosteroid-related adverse events. RESULTS: Of 168 children studied, 50 (29.8%) were prescribed CDMP and 118 (70.2%) SDMP. The overall mean MP dose was 31.3 ± 19.6 mg (weight-adjusted: 0.77 ± 0.32 mg/kg/dose). Compared to those prescribed SDMP, those prescribed CDMP had a shorter median duration of continuous nebulized albuterol (12.8 [IQR: 10.5-20] versus 17.3 [IQR: 11.3-29.7] hours, p = 0.019) and median PICU LOS (0.9 [IQR: 0.7-1.4] versus 1.2 [IQR: 0.9-1.8] days, p = 0.012). No corticosteroid-related adverse events were observed. In adjusted models, weight-adjusted IV MP dose was not associated with PICU LOS or duration of continuous nebulized albuterol. CONCLUSIONS: Intravenous MP dosing for pediatric CA varied widely in our study sample. Prospective, controlled trials are required to validate our observations including clinical efficacy and safety endpoints.

Impact of a discharge prescription for dexamethasone on outcomes of children treated in the emergency department for acute asthma exacerbations.

OBJECTIVE: To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED). STUDY DESIGN: Prospective study of children 2-18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7-10 days after discharge. RESULTS: 564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes. CONCLUSIONS: Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations.

Searching for a "Window of Opportunity" in the Treatment of Vulvar Lichen Sclerosus: Evidence for Therapeutic Benefits of an Early Corticosteroid Treatment.

INTRODUCTION: Vulvar lichen sclerosus (VLS) is characterized by progressive anatomical changes which become increasingly severe and irreversible. The objective of this study was to investigate if a "window of opportunity" exists in VLS, i.e., to assess if an early treatment may prevent disease progression and facilitate clearance of symptoms and/or signs. METHODS: This retrospective, cohort study included VLS patients treated for the first time with a topical corticosteroid, namely with mometasone furoate 0.1% ointment, for 12 weeks (2016-2021). Scoring of subjective symptoms (global subjective score, GSS, and dyspareunia) and clinical features (global objective score [GOS] and sclerosis-scarring-atrophy) was performed at baseline (T0) and at the control visit (T1). We assessed if the achievement of clearance in GSS, GOS, sclerosis-scarring-atrophy, or dyspareunia depended on the time elapsed between VLS onset and treatment initiation. RESULTS: Among the 168 patients (59.2 ± 13.2 years) included, the median time between VLS onset and first treatment was 14.0 months. At T1, 48.8% of patients achieved clearance of GSS, 28% of GOS and 11.9% of both GSS and GOS, 57.9% of dyspareunia, and 19.2% of sclerosis-scarring-atrophy. The logistic regression model showed that each 10-month increase in treatment initiation adversely affected the clearance of GSS while starting treatment within 6 months of disease onset was significantly associated with clearance of GOS and sclerosis-scarring-atrophy. CONCLUSION: Early treatment is crucial in determining a complete healing of VLS-related symptoms and signs, especially of tissue sclerosis-scarring-atrophy, which appear poorly responsive, or even unresponsive, after the earliest stages of the disease. Thus our findings provide evidence for a "window of opportunity" in VLS treatment.

Successful treatment of concurrent cold agglutinin disease and myelodysplastic syndrome.

Herein, we describe a case of severe anemia presenting with myelodysplastic syndrome with cold agglutinin disease that was successfully treated by a moderate dose of steroids followed by cyclosporine. In patients with myelodysplastic syndrome, autoimmunity in erythroid cells is occasionally demonstrated, and autoimmune hemolytic anemia is seen in some patients. However, hemolytic anemia with cold agglutinin in patients with myelodysplastic syndrome is less common, and the effect of corticosteroids for autoimmune hemolytic anemia caused by cold agglutinin is thought to be limited. Although the elevated levels of reticulocytes and LDH are usually caused by ineffective hematopoiesis in myelodysplastic syndrome, clinicians should be aware of latent cold agglutinin disease. In the present case, in addition to the improvement of erythroid dysplasia, the corticosteroid-sparing effect on cold agglutinin disease may have played a role in the mechanism underlying the effectiveness of cyclosporine.