Steroid Regimen Research Articles

Symptoms: Sudden Hearing Loss and Aural Fullness

Symptoms: Sudden Hearing Loss and Aural Fullness

Evolution in IgA Nephropathy Treatment: How Will SGLT2 Inhibitors, Steroid Regimens, and Experiment Therapies Change the Treatment Landscape?

Evolution in IgA Nephropathy Treatment: How Will SGLT2 Inhibitors, Steroid Regimens, and Experiment Therapies Change the Treatment Landscape?

RF09 | PSAT83 Diagnosis of Adrenal Insufficiency Based on Peak Stimulated Cortisol Levels Between 14 and 18 mcg/dL on High Dose Cosyntropin Stimulation Testing

Abstract Background Traditionally, stimulated serum cortisol < 18 mcg/dL at 30 or 60 minutes has been used as the cutoff for diagnosis of adrenal insufficiency (AI) during high dose cosyntropin stimulation testing (CST). Recent studies suggest that a cutoff of 14-15 mcg/dL is more accurate when using more specific monoclonal immunoassays (IAs). In February 2017, our institution switched from a polyclonal IA to a monoclonal IA. Despite this change, providers were diagnosing AI based on the 18 mcg/dL cutoff. Long term glucocorticoid use has several unwanted pleiotropic effects such as impaired glucose tolerance or diabetes mellitus (DM), hypertension (HTN), and increased risk of infection. Our study aims to evaluate patients with peak stimulated cortisol levels between 14-18 mcg/dL diagnosed with AI and placed on steroids. Methods We retrospectively reviewed charts of patients with peak cortisol levels 14-18 mcg/dL at 30 or 60 minutes on high dose CST with 250 mcg cosyntropin between February 2017 and August 2021. Cortisol levels were assessed using the monoclonal IA Roche Elecsys Cortisol II. Data regarding type and etiology of AI as well as patient demographics, comorbidities, steroid regimen, and follow up cortisol testing was collected. Worsening HTN and DM were defined as increase in blood pressure and HgbA1c respectively and/or intensification of medications between baseline at time of CST and last follow up while on steroids. Results 41 patients met inclusion criteria. 29 (71%) patients were female and mean age at CST was 52 years (range 21-86). Most patients were diagnosed with secondary (71%) or partial secondary (19%) AI by provider. Most common etiologies were pituitary disease (45%), chronic steroid use (24%), and unilateral adrenalectomy (19%). Mean follow up was 23 months (range 0.5-57). 33 (80%) patients were started or continued on glucocorticoid replacement. Remaining patients who were never started on steroids had a peak cortisol ≥ 15.6 mcg/dL. 21/33 (64%) of patients started on steroids had repeat adrenal function testing a mean of 18 months (range 2-42) after the initial CST. Based on testing or clinical judgement, 19/33 (58%) were taken off steroids. In patients treated with steroids, 64% developed weight gain, 42% worsening HTN, and 6% worsening DM. Additionally, 48% developed an infection, 24% insomnia, and 15% psychiatric illness. Conclusions The majority of patients with peak stimulated cortisol between 14-18 mcg/dL on high dose CST had secondary AI. Over 50% of patients started on steroids were later able to stop. Steroid-related complications were observed, but this may not differ significantly from the general population. This study underscores the importance of interpreting CST results in the context of the cortisol assay used and evaluating patients with secondary AI for recovery of the hypothalamic-pituitary-adrenal axis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.

PSAT048 Management of a Unilateral Testicular Tumor in a Patient with Congenital Adrenal Hyperplasia – Malignancy or Testicular Adrenal Rest Tumor?

Abstract Male patients with Congenital Adrenal Hyperplasia (CAH) are at risk of developing testicular adrenal rest tumors (TART). Late presentations are rare and often misdiagnosed as primary testicular germ cell tumors or other more common benign testicular lesions. We describe the case of a patient with CAH and a unilateral testicular tumor with regression in size after initiation of dexamethasone. A 24-year-old male with salt-wasting form of 21-hydroxylase deficiency underwent testicular U/S for evaluation of TART. While aware of a painless firm nodule on the latero-posterior aspect of his left testicle, his main concern was new onset infertility as he had conceived previously. He denied personal or family history of malignancy. Testicular U/S showed a 1.1×0.7×0.8 cm ill-defined, heterogeneously hypoechoic lesion with scattered calcifications and internal vascularity. He was referred to urology to undergo evaluation for possible for testicular cancer. CT abdomen/pelvis showed no evidence of metastatic disease. AFP was less than 2.5 ng/mL (reference range < 9.0 ng/mL), hCG was less than 1.0 mIU/mL (reference range<5.0 mIU/mL), and LDH was 221 U/L (reference range 140-271 U/L). The patient declined surgical intervention at this point and requested medical management. After discussion with the patient, we opted to trial dexamethasone to help suppress the nocturnal surge of ACTH in addition to his physiological dose of prednisone and fludrocortisone for CAH. He was started on 0.25 mg of dexamethasone followed closely with serial imaging and labs. Prior to initiation of dexamethasone, ACTH was 90.3 pg/mL (reference range 7.2–63.3 pg/mL). Two months after initiation of dexamethasone, ACTH decreased to 10.0 pg/mL. LH after initiation of dexamethasone was 8.58 mIU/mL (reference range 1.24–8.62 mIU/mL), FSH was 11.90 (reference range 1.27–19.26 mIU/mL), and testosterone level was 177 ng/dL (reference range 259-818 ng/dL). Testicular U/S six months after starting dexamethasone showed a 50% reduction in size of the heterogeneous hypoechoic left testicular lesion measuring 0.5×0.5×0.4 cm consistent with TART. However, he continued to have concerns regarding infertility, with work-up currently underway. TARTs are thought to arise from aberrant adrenal cells that may descend with the testes during embryogenesis. High ACTH levels in CAH due to lack of negative feedback can cause proliferation of these undifferentiated adrenal cells. Infertility is a predominant symptom due to local mass effect on the testes. Treatment of TART to prevent infertility requires elucidating an optimal steroid regimen that suppresses ACTH production, without suppression of LH and FSH. Moreover, most of the TARTs (around 80%) are bilateral and never malignant. Our patient's testicular tumor poses a diagnostic challenge given the late and atypical presentation of a unilateral tumor. The response to dexamethasone is very reassuring but continued surveillance is warranted. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Impact of Dose Reduction of Topical Steroids to Manage Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis.

To evaluate the impact of type and dose of swallowed topical steroids (STS) and concurrent steroid therapy on the development and resolution of adrenal insufficiency (AI) in pediatric eosinophilic esophagitis (EoE). We performed a retrospective case-control study of pediatric EoE subjects in a single tertiary care center, who were treated with STS for at least 3 months and diagnosed with AI based on a peak stimulated cortisol level of <18 µg/dL (500 nmol/L). Steroid forms and doses, and endoscopy data were collected at the time of AI diagnosis and AI resolution or the last known evaluation. Steroid formulations were converted to a fluticasone-equivalent dose for analysis. Thirty-two EoE subjects with AI were identified, and 20 had AI resolution, including 12 who remained on lower dose STS. Eight of the 32 patients were also treated with extended-release budesonide (ER budesonide), which resulted in a 7-fold higher total daily steroid dose, and thus were analyzed separately. When the 24 cases that were not on ER budesonide were compared to the 81 controls, no difference was found in the STS dose nor total daily steroid dose, although the inhaled steroid dose had marginal significance. Peak eosinophil counts tended to increase when STS doses were decreased, except in subjects on ER budesonide at AI diagnosis. Altering the total daily steroid regimen can lead to resolution of AI in patients with EoE, though this may come at the expense of disease control.

RAPIDLY PROGRESSIVE MICROSCOPIC POLYANGIITIS WITH DIFFUSE ALVEOLAR HEMORRHAGE

RAPIDLY PROGRESSIVE MICROSCOPIC POLYANGIITIS WITH DIFFUSE ALVEOLAR HEMORRHAGE

S2754 New-Onset Inflammatory Bowel Disease After Ixekizumab Initiation for Psoriatic Arthritis

Introduction: Monoclonal antibodies have become common practice for treatment of psoriatic arthritis (PsA), inflammatory bowel disease (IBD), and many autoimmune diseases. IL-17 inhibitors (IL-17i), such as Ixekizumab (IXE), are suspected to paradoxically exacerbate subclinical IBD or induce new-onset IBD in psoriatic arthritis patients. Case Description/Methods: A 50-year-old male presented with worsening upper abdominal pain, intermittent fevers, and diarrhea for 3-weeks. Patient began IXE 2-months prior for PsA. One-week before admission, computed tomography (CT) showed changes consistent with proximal and transverse colitis, autoimmune panel found ASCA IgG 27.7. Colonoscopy 3-years prior for hemorrhoidal banding showed diverticulosis in the sigmoid colon. On arrival, patient was hypotensive with labs: fecal calprotectin 3424 mcg/g, ESR 40 mm/hr, CRP 227 mg/L, and C. difficile negative. IXE was held and colonoscopy revealed severe rectal proctitis, sparing of sigmoid and distal descending colon, with inflamed ulcerations in the transverse colon preventing advancement of the scope, leading to initial diagnosis of indeterminate IBD (A,B). While on IV methylprednisolone 20 mg every 8 hours for 1-week, symptoms persisted with repeat labs: fecal calprotectin 725 mcg/g, ESR 11 mm/hr, CRP 1.72 mg/L. Repeat colonoscopy showed improved inflammation in a continuous circumferential pattern from transverse colon to the cecum, with sparing of the rectum and descending colon (C). Days later, he improved and was discharged with outpatient follow-up on oral prednisone 40 mg. One-month later, patient worsened with fecal calprotectin 2990 mcg/g. After another month, colonoscopy revealed pancolitis from rectum to cecum (D), with biopsies, diagnosis of ulcerative colitis was confirmed. Patient was initiated on Adalimumab shortly after and is now feeling significantly better as he tapers off his steroid regimen. (Figure) Discussion: IL-17i's ability to affect cell dysregulation and gut dysbiosis can explain the suspected risk of IBD in PsA. Recent literature has found rare cases and low incidence rates of new-onset IBD when treating diseases like PsA with IL-17i (2.4 per 1000 patient-years). Despite the rarity, there are practical recommendations prior to initiating IL-17i: discuss adverse risks, screen IBD history, obtain fecal calprotectin, and if > 250 mcg/g with further testing confirming inflammation (colonoscopy, CT), IL-17i are contraindicated and alternative immunosuppressive agents are recommended.Figure 1.: (A) Colonoscope view of transverse colon; inflammation characterized by congestion, erythema, and friability in a continuous and circumferential pattern from descending colon to the transverse colon, graded as Mayo Score 3 (severe, with spontaneous bleeding, ulcerations) preventing colonoscope from advancing past the transverse colon. (B) Rectal biopsy found severe chronic active proctitis, crypt abscesses, and mucosal erosions/ulceration; negative for dysplasia or granulomas. (C) Repeat colonoscope view of transverse colon; colitis with altered vascularity, congestion and pseudopolyps in a continuous circumferential pattern from transverse colon to the cecum. (D) Final colonoscope view of transverse colon; mild to severe pancolitis from rectum to cecum, with superficial ulcerations and friability of mucosa, Mayo Score 3.

S2722 Cytomegalovirus Colitis in an Immunocompetent Patient Presenting With New Onset Ulcerative Colitis: A Clinical Vignette

Introduction: Cytomegalovirus (CMV) colitis is a rare disease among immunocompetent patients presenting with inflammatory bowel disease (IBD). CMV can cause steroid-refractory IBD, which may require antiviral and infliximab (IFX) combination therapy. Case Description/Methods: A 23-year-old woman was admitted for dehydration and poor oral intake in the setting of eight bloody bowel movements per day, tenesmus, and weight loss. She presented to an outside hospital 5-weeks prior with abdominal cramps and bright red blood per rectum. The CT scan showed bowel wall thickening and mucosal enhancement in the rectosigmoid and descending colon. A colonoscopy 2-weeks prior to admission was suggestive of severe ulcerative colitis (UC) and she was started on mesalamine/budesonide. Due to poor clinical response, she was switched to prednisone 40 mg for 5 days. Outpatient medical management failed and, upon admission, she was converted to methylprednisolone 20 mg every eight hours. Serum CMV PCR was positive at 1,758 IU/mL and colonic biopsies showed scattered CMV inclusions by immunohistochemical staining. She was started on ganciclovir 5mg/kg/dose IV in addition to the steroid regimen and IFX infusions were deferred. By day 2 of ganciclovir IV and day 7 of methylprednisolone IV, IBD symptoms began to resolve. On discharge at hospital day 12, patient was transitioned to twice daily oral valganciclovir 900 mg for a 3-week course and an oral prednisone taper. CMV PCR was 1,185 IU/mL on discharge and < 100 IU/mL at one week follow up. IFX therapy was initiated 45 days post discharge with improved symptoms, as characterized by a 17-lb weight gain at 3-month follow-up. (Figure) Discussion: CMV colitis is a rare diagnosis in immunocompetent patients with early, steroid naïve IBD. Serum PCR positive infection has been reported more commonly after 2-3 weeks of steroid therapy. CMV infection is a recognized complication and marker of poor prognosis in moderate to severe UC, especially those who present with steroid refractory disease. It is believed that the inflammatory mediators associated with UC play a synergistic role in CMV reactivation and subsequent disease. In addition, local corticosteroid induced immunosuppression may further facilitate CMV gene transcription, resulting in disease progression and poor steroid response. There remains no consensus for management of UC with concomitant CMV colitis however, in our patient the use of antiviral and biologic therapy (IFX) promoted disease regression and clinical improvement.Figure 1.: H&E Stain (20x) demonstrating active chronic colitis (left). Immunohistochemical staining (40x) showing CMV immunoreactivity (right).

A RARE CASE OF WERNICKE'S ENCEPHALOPATHY INDUCED BY HYPEREMESIS GRAVIDARUM: A DIAGNOSTIC DILEMMA

A RARE CASE OF WERNICKE'S ENCEPHALOPATHY INDUCED BY HYPEREMESIS GRAVIDARUM: A DIAGNOSTIC DILEMMA

Macrolide versus Non-Macrolide in Combination with Steroids for the Treatment of Lobar or Segmental Mycoplasma pneumoniae Pneumonia Unresponsive to Initial Macrolide Monotherapy.

In the last few decades, macrolide-resistant Mycoplasma pneumoniae (MRMP) has been increasing in proportion. This study aimed to evaluate the treatment outcomes of children with lobar or segmental MP pneumonia unresponsive to the initial 3–5-day macrolide therapy, who then switched to either a non-macrolide, macrolide + steroid, or a non-macrolide + steroid regimen, according to the 2019 KSPID and KAPARD guideline during the 2019–2020 Mycoplasma epidemic in South Korea. A total of 190 patients <18 years old were admitted during the study period for MP lobar or segmental pneumonia, and 16.8% (n = 32/190) were responsive to the initial macrolide monotherapy, whereas 83.2% (158/190) were refractory. The median age of the patients was 7 (interquartile range [IQR], 5–9) years old and 46.2% (n = 73/158) were male. The overall treatment success rates of non-macrolide, macrolide + steroid, and non-macrolide + steroid groups were 46.2%, 80.8%, and 100.0%, respectively. Patients in the non-macrolide + steroid group had the shortest fever duration after a regimen change of 1 (IQR, 0–3) day compared with patients in the non-macrolide group and macrolide + steroid group; 2 (IQR, 1–4) days and 2 (IQR, 1–3.3) days (p = 0.004), respectively. Follow-up CRP (ß, 0.169; CI, 0.050–0.287; p = 0.006), macrolide + steroid therapy (ß, −1.694; CI, −2.463–−0.925; p < 0.001), and non-macrolide+ steroid therapy (ß, −2.224; CI, −3.321–−1.127; p < 0.001) were shown to be significantly associated with the duration of fever after admission. To conclude, in patients with severe MP pneumonia that failed to respond to the initial macrolide therapy, a non-macrolide + steroid had the highest treatment success rate and a shorter duration of fever.

The Outcome of Tapered Steroid Regimen When Used to Treat Acute Borderline Cellular Rejection After Kidney Transplant: A Single-Center Experience.

BackgroundTreatment of acute borderline cellular rejection (BCR) after kidney transplant has shown mixed results with no consensus on the necessity and modality of interventions.MethodsThe emphasis of our study was to assess the histopathologic response when BCR of kidney transplant is being treated with rapid steroid regimen. We analyzed all diagnosed acute BCR between 2018 and 2020. Patients were divided to a treatment responder group (RG) and non-responder group (NRG). All diagnosed BCR were treated with rapid steroid regimen and followed by a biopsy to assess response. Demographic data, recipients’ comorbidities and clinical data, donor type, and induction immunosuppression regimen data were collected.ResultsNinety-one patients had acute BCR and were treated with rapid steroid followed by a repeat biopsy. Sixty-three (69%) patients showed persistence BCR and were considered NRG. Age, gender, and race were similar between the two groups. Class I and II calculated panel reactive antibodies were similar between the groups. No significant difference in the median serum creatinine (SCr) was noted between the groups. RG and NRG had a median SCr of 1.6 mg/dL (1.2 - 2.1) and 1.5 mg/dL (1.4 - 2.0), respectively (P < 0.79). The median SCr at the time of the follow-up biopsy was not different between the groups: SCr of 1.6 mg/dL (1.2 - 2.0) vs. 1.4 mg/dL (1.2 - 2.2) for the RG and NRG, respectively (P < 0.93).ConclusionWhen rapid steroid regimen was used to treat acute BCR after kidney transplant, only smaller number of patients showed response based on the histology evaluation of the follow-up post-treatment biopsies.

Comparison of the effect of three steroid regimens on cardiac function in Duchenne muscular dystrophy

BackgroundSteroid therapy of patients with Duchenne muscular dystrophy (DMD) delays the onset of cardiac dysfunction. ObjectiveThe aim of this study was to compare the effects of 3 different steroid regimens on cardiac function assessed by echocardiography. MethodsPatients diagnosed with DMD, between 8 and 23 years of age were reviewed between January 2000 and September 2018. Participants were classified into four groups. Control group (no steroid treatment), Prednisone 10 mg/kg/weekend day, Prednisone 0.40 mg - 0.75 mg/kg/day and Deflazacort 0.9 mg/kg/day.Demographic data, echocardiographic measurements of shortening fraction (FS) and left ventricular end diastolic diameter z-score were collected and compared between cohorts. ResultsDevelopment of cardiac dysfunction in groups receiving prednisone daily or 3 day prednisone was less common in comparison to the control group (p = 0.005). No patient on the Deflazacort group had abnormal left ventricular FS. There was no difference in the age of initiation of steroid therapy among groups (p = 0.08). Age of development of systolic dysfunction by echocardiography between daily prednisone and weekend prednisone was not significantly different (p = 0.07). There was no difference in the number of patients developing of cardiac dysfunction between patients receiving prednisone daily or 3 day prednisone (p = 0.4). The entire cohort (77 patients) demonstrated a decline in the cardiac function over time. ConclusionsOur study confirms the delay in development of left ventricular dysfunction related to steroid therapy. Deflazacort seems to show a significant beneficial effect on cardiac function, compared to daily and weekend prednisone therapies.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study

BackgroundCorticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. MethodsThis observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. ResultsData of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). ConclusionPulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound.

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Low-dose antenatal betamethasone treatment achieves preterm lung maturation equivalent to that of the World Health Organization dexamethasone regimen but with reduced endocrine disruption in a sheep model of pregnancy

The intramuscular administration of antenatal steroids to women at risk of preterm delivery achieves high maternal and fetal plasma steroid concentrations, which are associated with adverse effects and may reduce treatment efficacy. We have demonstrated that antenatal steroid efficacy is independent of peak maternofetal steroid levels once exposure is maintained above a low threshold. This study aimed to test, using a sheep model of pregnancy, whether the low-dose antenatal steroid regimen proposed as part of the Antenatal Corticosteroids for Improving Outcomes in Preterm Newborns trial would achieve preterm lung maturation equivalent to that of the existing World Health Organization dexamethasone treatment regimen, but with reduced risk of adverse outcomes. Following ethical review and approval, date-mated ewes with single fetuses received intramuscular injections of either (1) four 6-mg maternal intramuscular injections of dexamethasone phosphate every 12 hours (n=22), (2) 4 2-mg maternal intramuscular injections of betamethasone phosphate every 12 hours (n=21), or (3) 4 2-mL maternal intramuscular injections of saline every 12 hours (n=16). Of note, 48 hours after first injection, (124±1 day), lambs were delivered, ventilated for 30 minutes, and euthanized for sampling. Arterial blood gas, respiratory, hematological, and biochemical data were analyzed for between-group differences with analysis of variance according to distribution and variance, with P<.05 taken as significant. After 30 minutes of ventilation, lambs from both steroid-treated groups had significant and equivalent improvements in lung function relative to saline control (P<.05). There was no significant difference in arterial blood pH, pO2, pCO2, lung compliance, ventilator efficiency index, or lung volume at necropsy with a static pressure of 40 cmH2O. The messenger RNA expression of surfactant protein (Sp)a, Spb, Spc, Spd, aquaporin (Aqp)1, Aqp5, and sodium channel epithelial 1 subunit beta (Scnn1b) was equivalent between both steroid groups. Maternal and fetal plasma neutrophil, glucose, and fetal plasma C-peptide levels were significantly elevated in the dexamethasone group, relative to the betamethasone group. Fetal plasma insulin-like growth factor 1 was significantly reduced in the dexamethasone group compared with the betamethasone group (P<0.05). Fetal adrenocorticotropic hormone (r=0.53), maternal glucose value (r=-0.52), and fetal glucose values (r=-0.42) were correlated with maternal weight in the betamethasone group (P<.05), whereas fetal pCO2 and pO2 were not correlated. There was no significant difference between male and female lamb outcomes in any groups for any of the items evaluated. This study reported that in preterm lambs, a low-dose treatment regimen of 8 mg betamethasone achieves lung maturation equivalent to that of a 24-mg dexamethasone-based regimen, but with smaller perturbations to the maternofetal hypothalamic-pituitary-adrenal axis. These data suggested that given steroid pharmacokinetic differences between sheep and humans, a betamethasone dose of 2 mg may remain above the minimum dose necessary for robust maturation of the preterm lung. Maternal weight-adjusted betamethasone doses might also be a key to reducing perturbations to the maternofetal hypothalamic-pituitary-adrenal axis.

Long-term efficacy of dexamethasone intravitreal implant in the treatment of Vogt-Koyanagi-Harada disease relapsing posterior uveitis.

Purpose:To investigate the efficacy and safety of dexamethasone intravitreal implant in the treatment of relapsing posterior uveitis in patients with chronic recurrent Vogt–Koyanagi–Harada (VKH) disease.Methods: This was a prospective study of 29 eyes of 16 patients with posterior uveitis in chronic recurrent VKH disease. All patients received previous systemic steroid and immunosuppressive regimens. All patients underwent a comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), Indocyanine green angiography (ICGA), fundus fluorescein angiography (FFA), and spectral-domain optical coherence tomography (SD-OCT). All patients underwent intravitreal injection with sustained-release dexamethasone 0.7 mg implant (Ozurdex®). Primary outcome measures included mean change in BCVA and central foveal thickness (CFT) at 24 months of follow-up compared to the baseline.Results: At 24 month of follow-up, the mean BCVA improved from 0.82 ± 0.13 to 0.38 ± 0.06 logMAR (P < 0.0001). The mean CFT reduced from 505 ± 29 to 244 ± 23 um (P < 0.0001). The mean intraocular pressure (IOP) changed from 15.1 ± 2.2 to 16.9 ± 3.1 mmHg with no significant value (P-value = 0.0955). Twenty-one eyes (72.4%) received one injection, whereas eight eyes (27.6%) required two injections. The mean number of injections was 1.2 ± 0.60. The mean follow-up time was 24.75 ± 0.9 months. No serious ocular or systemic adverse events were noted during the follow-up period. Ocular hypertension was recorded in three (10.3%) eyes and controlled by IOP lowering medications. Cataract progression occurred in 11 (37.9%) eyes.Conclusion: Our cohort highlights the beneficial effects of the dexamethasone implant of 0.7 mg in the treatment of VKH disease relapsing posterior uveitis improving visual acuity, reducing macular edema, and minimizing the burden of systemic steroids in this sample study.

COVID-19 vaccination: a possible trigger for Addisonian crisis in a patient with Addison’s disease

Infection with COVID-19 disease is caused by the SARS-CoV-2 virus. Following its identification, the pursuit of the rapid development of effective vaccines became a pandemic-period international public health priority. This report describes the case of an older woman with Addison’s disease who developed acute clinical symptoms and signs indicative of an Addisonian crisis following each of two consecutive doses of the Pfizer BioNTech Covid-19 vaccines. Both presentations (with nausea, vomiting, hypotension, tachycardia, and transient hypoglycaemia) occurred within 24 hours of receipt of the vaccines. In each instance, she responded well to treatment with intravenous fluids, and temporarily changing her maintenance oral steroid regimen to higher dose intravenous steroids. She successfully completed a period of rehabilitation and was discharged home. Some pharmacokinetic and pharmacodynamic considerations of the Pfizer BioNTech COVID-19 vaccines are discussed. An overview is presented of Addison’s disease and Addisonian crisis. The discussion also applies two causality assessment systems to derive a classification of ‘probable’ adverse drug reactions for the index case report.

Selective laser trabeculoplasty for steroid-induced ocular hypertension following endothelial keratoplasty.

Purpose: To examine the safety and efficacy of selective laser trabeculoplasty (SLT) in patients responding to topical steroids with elevated intraocular pressure following endothelial keratoplasty. Methods: Patients that underwent Descemet Membrane Endothelial Keratoplasty (DMEK) or Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) were offered SLT as first-line therapy if they presented with steroid response and met inclusion criteria. Patient demographics, best-corrected visual acuity (BCVA), steroid and glaucoma regimens were recorded before and after SLT. Results: Twelve eyes of 8 patients were recruited to the study. All patients demonstrated a reduction in IOP and only one patient remained on anti-glaucoma drops after SLT. The mean (±SD) reduction in IOP following SLT was 8.8 (±4.9) mmHg (p < 0.0001). BCVA remained stable and no adverse events following treatment were observed. Conclusions: SLT may be a safe and effective treatment option that reduces topical antihypertensive burden while allowing continuance of corticosteroids in steroid-responsive eyes at high risk of rejection following endothelial keratoplasty. Larger randomized studies are needed to compare SLT efficacy with topical medication in this patient group and to review any impact on graft survival and glaucoma progression.

Role of anakinra in the management of icans after CAR T-cell therapy for lymphoma.

e19506 Background: Chimeric antigen receptor (CAR) T-cell immunotherapy is a revolutionary treatment modality which has gained attention for its potential in treating multiple refractory hematological malignancies. Significant toxicities associated with CAR T- cell therapy remain a major concern. Cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are seen early on post CAR-T cell therapy. To date, the treatment of ICANS has largely been limited to supportive care and corticosteroids. More recently, some early clinical data investigated the use of Anakinra as a promising agent in prevention and treatment of severe ICANS. Methods: We analyze three cases in which Anakinra was used to treat high-grade ICANS concurrently with high dose steroids. Results: A 51-year-old woman with high grade DLBCL and secondary CNS involvement was treated with Tisagenlecleucel CAR-T therapy. On day 2, patient became altered and was diagnosed with ICANS Grade II. High dose steroids were started leading to resolution of ICANS. However, patient’s mentation worsened by day 7, progressing to ICANS Grade IV by day 8, and Anakinra 100 mg IV was added to the steroid regimen. By day 11, after 4 doses of Anakinra, patient’s neurotoxicity completely resolved. Patient achieved a PR by day 30 after CAR-T cell infusion. In the second case, a 65-year-old man with DLBCL and leptomeningeal involvement developed ICANS Grade II on day 1 after Tisagenlecleucel CAR-T therapy and was started on high dose steroids. By day 4, neurotoxicity worsened and progressed to ICANS Grade IV. On day 5 patient was transferred to ICU for a mechanical ventilation, and Anakinra 100 mg IV was added and continued daily for 7 days. By day 12, neurotoxicity improved to ICANS grade II and patient was extubated. Meanwhile, high dose steroids were tapered. His condition acutely worsened by day 19, prompting transfer to the ICU and re-initiation of Anakinra concurrently with steroids. His family decided against further escalation of care on day 22. Patient was transitioned to comfort care and died 23 days post CAR-T cell infusion. In the third case, a 65-year-old man with mantle cell lymphoma was treated with Brexucabtagene autoleucel CAR-T therapy. On day 8, patient developed ICANS Grade I which rapidly progressed to Grade IV. High dose steroids were started and ICANS improved to Grade II on Day 9. However, on Day 10 patient’s mentation again worsened and one dose of Anakinra 100mg IV was added to the steroid regimen. By day 11, ICANS completely resolved, and patient was ultimately discharged home on day 15. Patient was able to achieve interval CR by day 30 after CAR-T cell infusion. Conclusions: In the reported cases, ICANS improved following administration of Anakinra, adding support to the idea that Anakinra may be beneficial in treatment of high-grade ICANS. Future studies are needed to better understand the overall efficacy and the ideal timeline for administration.

Pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: A systematic review and meta-analysis.

Systemic steroids are associated with reduced mortality in hypoxic patients with coronavirus disease 2019 (COVID‐19). However, there is no consensus on the doses of steroid therapy in these patients. Several studies showed that pulse dose steroids (PDS) could reduce the progression of COVID‐19 pneumonia. However, data regarding the role of PDS in COVID‐19 is still unclear. Therefore, we performed this meta‐analysis to evaluate the role of PDS in COVID‐19 patients compared to nonpulse steroids (NPDS). Comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases from inception through February 10, 2022 was performed for all published studies comparing PDS to NPDS therapy to manage hypoxic patients with COVID‐19. Primary outcome was mortality. Secondary outcomes were the need for endotracheal intubation, hospital length of stay (LOS), and adverse events in the form of superimposed infections. A total of 10 observational studies involving 3065 patients (1289 patients received PDS and 1776 received NPDS) were included. The mortality rate was similar between PDS and NPDS groups (risk ratio [RR]: 1.23, 95% confidence interval [CI]: 0.92–1.65, p = 0.16). There were no differences in the need for endotracheal intubation (RR: 0.71, 95%: CI 0.37–1.137, p = 0.31), LOS (mean difference: 1.93 days; 95% CI: −1.46–5.33; p = 0.26), or adverse events (RR: 0.93, 95% CI: 0.56–1.57, p = 0.80) between the two groups. Compared to NPDS, PDS was associated with similar mortality rates, need for endotracheal intubation, LOS, and adverse events. Given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings.