Received Steroid Therapy Research Articles

The effect of COVID-19 pandemic on idiopathic inflammatory myositis patients: a single centre experience.

Pandemic caused by coronavirus disease (COVID-19) determines the life of clinicians and patients since 2 years. We have a lot of information about disease course, treatment and protection against virus, but less on the prognosis of infection in patients with idiopathic inflammatory myopathies (IIM). Also few data are available on triggered humoral response and side effects after vaccination. Our goal was to assess by a retrospective cross-sectional study the above data in our cohort (176 IIM patients) by identifying COVID-19 positive patients and follow disease course. Incidence and complications of vaccination were determined by questionnaires. 101 patients volunteered for complex blood test. By June 1st, 2021 significantly higher incidence of COVID 19 infections (34.7%) were identified comparing to the national prevalence (8.2%). A third of these infections occurred asymptomatically or mild. Patients requiring hospitalisation had a significantly longer disease duration and a higher incidence of anti-Jo-1 antibody. All patients infected by COVID-19 became seropositive regardless the immunosuppressive therapy or symptoms severity. 54.3% of the patients received anti-COVID-19 vaccine. 72.3% of patients became seropositive after vaccination. Higher antibody titer against spike protein was detected after Pfizer-BioNTech vaccination compared to others. Patients receiving steroid therapy had decreased post-vaccination antibody response compared to those without steroid treatment. No major post-vaccination infection was observed. Based on our results, myositis may be associated with an increased risk of COVID-19 infection. Independent risk factor for hospitalisation are longer disease duration and anti-Jo1 positivity. Anti-SARS-CoV2 vaccines seem safe and tolerable and strongly recommended for that population.

Home Management of COVID-19 Patients: A Successful Model in Non-severe COVID-19 Patients in the Developing World.

BackgroundAround 80-85% of coronavirus disease 2019 (COVID-19) cases were reported to have mild disease and home treatment of such patients was proved to be effective without significant morbidity or mortality. Therefore, the aim of this study was to assess the outcome of home management of non-severe COVID-19 infection in healthcare providers in the developing world.MethodsThis observational cohort study was conducted at the National Institute of Cardiovascular Diseases from June 2020 till January 2021. It included health care workers who tested positive for COVID-19 with non-severe infection and received home treatment. The COVID-19 management team monitored their symptoms and oxygen saturation over the phone. Need-based lab tests, X-rays, home proning, steroids, and oxygen were administered along with the standard intuitional management strategies. Study outcomes included duration of recovery, need for hospitalization, and expiry.ResultsA total of 128 patients were included, out of which 98 (76.6%) were male, and the mean age was 32.9 ± 5.9 years. Fever was the most common symptom, seen in 89.8% of patients. Most of the patients (85.9%) had no pre-existing comorbidities. Five patients received home oxygen therapy, seven received steroid therapy, and one received home pruning. The average time of recovery was 13.8 ± 8.1 days with no mortality; however, 14 (10.9%) patients were hospitalized due to worsening of symptoms.ConclusionHome treatment for COVID-19 patients with mild to moderate disease after appropriate risk assessment can be a safe and effective option to preserve hospital capacities for more needy and severely ill patients.

Idiopathic granulomatous mastitis and steroid use during the pandemic of COVID-19.

Steroid therapy is an immunosuppressive treatment and may have possible side effects in a pandemic period. However, the number of studies on the use corticosteroids for the treatment of idiopathic Granulomatous Mastitis (IGM) especially during the pandemic is almost negligible. The data of patients with the diagnosis of IGM between January-December 2020 in the General Surgery Clinic were retrospectively analyzed. The patients were explained in detail that steroid therapy is an immunosuppressive treatment and it may have possible side effects. Prednisolone 0.5-1mg/kg/day was given as steroid therapy. The treatment was planned for 4-6 months according to the severity of the symptoms and was completed by reducing it to a total dose of 10mg/month. Eleven patients were included in the study. Five patients had completed steroid treatment and continued their follow-up. In our study, a total of six patients were receiving steroid therapy. There is no consensus yet on the use of the steroid in the COVID-19 pandemic. Low doses Corticosteroids (<1mg/kg/day) don't have an effect on increase mortality in patients with severe COVID-19. We can think that low-dose corticosteroids used by many centers in IGM treatment do not have a negative effect on mortality.

Immunoglobulin G4-related Disease: A New Systemic Disease Emerging in Japan.

Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.

Characteristics and Outcomes of a Series of COVID-Associated Mucormycosis Patients in Two Different Settings in Egypt Through the Third Pandemic Wave.

PurposeTo report on the underlying risk factors, clinical characteristics, presentation, and survival of coronavirus disease 2019 (COVID-19) associated mucormycosis (CAM) cases referred for ophthalmological consultation in two different Egyptian settings during the third viral pandemic wave (April to August of 2021).MethodsA multicentric, retrospective analysis involving one public and two private hospitals in metropolitan Cairo, and two university hospitals in upper Egypt (Aswan and Assuit). Cases that fulfilled the diagnostic criteria of mucormycosis, with a prior or concurrent COVID-19 infection, were included.ResultsOf the 26 patients included in the final analysis, 15 (57.7%) were from Cairo and 11 (42.3%) were from upper Egypt. Twenty-five patients (96.2%) had poorly controlled diabetes mellitus and 20 (76.9%) had received corticosteroid treatment for COVID-19, of which 30.8% had mild or moderate disease. The median duration from COVID-19 till the onset of CAM was 20.5 days. No visual function could be detected in the affected eye of 16 patients (61.6%) on presentation. The mortality rate was 46.2% despite surgical debridement in half of the cases that died.ConclusionCAM continues to be a concrete threat throughout Egypt, especially in patients with poorly controlled diabetes mellitus and those who inadvertently receive steroid therapy. It remains to be seen if increased vaccination coverage and early detection due to increased awareness would result in declining rates and adverse sequelae of CAM. A national registry would allow for better monitoring of the disease trends.

The Confusion between Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis as a Cause of Exfoliative Dermatitis: A Case Report

Background: Pustular psoriasis and Acute Generalized Exanthematous Pustulosis (AGEP) are grouped under pustular diseases, in which their clinical manifestations are similar. Those diseases can lead to exfoliative dermatitis. Purpose:To evaluate a specific histopathological examination in differentiating Pustular Psoriasis and AGEP. Case: A 55-year-old woman presented with sudden redness and diffused scaly skin with multiple pustules and also fever. She had taken Cefadroxil 2 days before the scales and pustules appeared. Leukocytosis and histopathological examination results from biopsy supported the diagnosis of AGEP. The patient was then hospitalized and received steroid therapy. Within the first week of tapering off, the scales disappeared but the pustules increased. After such clinical findings, the histopathological examination results were revisited and reassessed. Thus, we considered changing the diagnosis to Pustular Psoriasis, and the therapy was switched to Methotrexate. The patient had a better outcome, and the pustules slowly disappeared entirely. Discussion: It is often difficult to differentiate between the pustules in pustular psoriasis and AGEP unless by thorough history-taking and physical examinations. AGEP is characterized by a widespread of pustules with an acute febrile onset; while pustular psoriasis is an acute variant of psoriasis where pustules are spread over erythematous skin and accompanied by high fever and leukocytosis. Conclusion: Histopathological examination is the gold standard for the establishment of pustular psoriasis diagnosis. The histopathological characteristics of pustular psoriasis and AGEP are difficult to differentiate. Therefore, we need detailed history-taking and physical examination to establish the diagnosis.

Incidence and Attributing Factors of Impaired Blood Glucose in Non-Diabetic Patients on Steroid Therapy

Objective: To determine the incidence and attributing factors of impaired blood glucose in non-diabetic patients on steroid therapy. Methodology: This descriptive study was conducted at the Department of Medicine, Sheikh Zayed Hospital Lahore during 6 months from April 2019 to September 2019. Patients of both genders with age of 18-70 years and receiving steroid therapy (at least 1 pulse) were included. After taking ethical approval, 371 patients were counseled and explained the details of the study. A bolus of 1 gram Methylprednisolone was given and blood was drawn after 2 hours and blood glucose levels were measured. All the labs were acquired from same lab (Hospital lab) and glucometer to eliminate bias and confounding variables were controlled by exclusion. Data was collected via study proforma. Results: The average age of the patients was 43.75 ± 14.33 years with a range of 18 to 70 years. There were 42% males and 57%.1 females with a male to female ratio of 1:1.3. Average BMI of patients 27.34±3.72kg/m2. Impaired blood glucose was observed in 55% of patients after steroid pulse therapy. Frequency of impaired blood glucose after steroid pulse therapy was statistically insignificant according to age and BMI (p-&gt;0.05). Positive family history was significantly higher in a patient with impaired blood glucose after pulse therapy (p-0.001). Conclusion: Impaired blood glucose level was observed to be highly prevalent among non-diabetic patients receiving steroid pulse therapy. Female gender and positive family history of diabetes observed as attributing factors.

Tocilizumab as a Therapeutic Agent for Critically Ill Patients Infected with SARS-CoV-2.

Tocilizumab is an IL‐6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We evaluated patients treated with tocilizumab for a SARS‐CoV‐2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient’s date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID‐19).

Post-COVID morphologically proved endocarditis: infective and nonbacterial forms

PurposeTo study clinical features of endocarditis and its possible mechanisms (infective and nonbacterial) in the long-term period after acute COVID-19.MethodsThree patients (two male and one female, age 64, 39 and 46 years) diagnosed with postcovid endocarditis were included in the study. One patient had severe bilateral coronavirus pneumonia; the other two had only fever and weakness. The diagnosis of COVID-19 was confirmed by seroconversion. The time of admission after COVID-19 was from 4 to 7 months. All patients had study for anti-heart antibodies (AHA), EchoCG, Holter ECG, and endomyocardial biopsy (EMB) with PCR for SARS-Cov2 and cardiotropic viruses. The indication for EMB was suspected myocarditis. Blood cultures and procalcitonin levels were tested in one patient due to a prolonged febrile fever.ResultsTwo variants of postcovid endocarditis have been diagnosed. The first variant was detected in two patients by EMB only. This patients had severe lymphocytic and giant cell myocarditis. In addition, EMB showed signs of lymphocytic endocarditis with infiltrates, marked thickening and fibrosis of the endocardium (Fig. 1). Some biopsy specimen were represented by fresh thrombotic masses, infiltrated with neutrophilic leukocytes. No intraventricular thrombus was detected on EchoCG and MRI. The second variant of postcovid endocarditis developed in a patient with bicuspid aortic valve and met the criteria of infectious endocarditis 2015: mobile vegetations on the valve with aortic regurgitation II, splenomegaly, irregular fever up to 39°C for six months, marked increase of CRP, procalcitonin and ferritin, hypochromic anemia, LV EF 25%. Blood culture was negative. After intravenous therapy with antibiotics and immunoglobulin, EMB confirmed the active lymphocytic myocarditis and only slight fibrosis of right ventricular endocardium. The bacteriological study of endocardium was negative. SARS-Cov-2 RNA was detected by PCR in myocardial biopsy specimens of two patients; the biopsy of one patient is in the study now. All patients had significantly elevated antibody titers to various cardiac antigens, but the level of antibodies to endothelial antigens remained completely normal. It is possible to suggest an active deposition of immune complexes in the endothelium. Two surviving patients receive steroid therapy (in case of IE with antibiotics).ConclusionsSARS-Cov-2 infection induces the prolonged non-bacterial thromboendocarditis or infective endocarditis. In both cases, autoimmune mechanisms play a significant role, as evidenced by the simultaneous lymphocytic/giant cell myocarditis and high titers of AHA. Long-term persistence of coronavirus in the myocardium can also be considered as an etiological factor of endocarditis. In favor of this hypothesis is the parietal thrombosis in the absence of bacterial infection. Corticosteroids and anticoagulants should be considered for the treatment of postcovid endocarditis.Funding AcknowledgementType of funding sources: None. Figure 1. The EMB in in postcovid endocarditis

Leukemic and Lymphomatous Optic Neuropathy: A Case Series.

Optic neuropathy in the context of leukemia and lymphoma raises concern for central nervous system involvement or relapse and warrants prompt evaluation and treatment. To date, a gold standard for the diagnosis and management of leukemic optic neuropathy has yet to be established. Case series and review of the literature. Two illustrative cases were selected to discuss their treatment course and outcome. We report 7 cases of patients with leukemia or lymphoma presenting with optic nerve infiltration. All patients received steroid therapy for presumed infiltrative optic neuropathy, and 4 patients underwent radiation therapy. Along with systemic chemotherapy, all patients received intrathecal chemotherapy except one. Three patients received chimeric antigen receptor T-cell therapy. Leukemic and lymphomatous optic neuropathy is difficult to diagnose and treat, and there is no gold standard for diagnosis or treatment in the current literature. We help clarify how this disease should be approached in a multidisciplinary fashion and on an individual basis to correctly diagnose and treat the vision loss, while considering the patient's long-term prognosis based on their systemic disease.

Structural lung disease following allergic bronchopulmonary aspergillosis complicating pediatric cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) complicating cystic fibrosis (CF) is frequently associated with significant structural lung damage as assessed by computed tomography (CT) scanning. Using a validated CF scoring system (structural lung disease [SLD]score) we examined the degree of structural lung disease in a group of 25 children with CF who had received steroid therapy for ABPA (CF-ABPA) and compared our findings to a matched group of CF patients without ABPA (CF-CON) using both cross-section and longitudinal analysis. Further, we examined the structure-function correlation between CT findings and lung function. Mean SLD score (expressed as a percentage of maximal score) was significantly higher (worse) in the CF-ABPA group than the CF-CON group (29.3% CF-ABPA vs. 18.7% CF-CON p < .05). CF-ABPA patients showed significantly greater rate of development of structural lung disease over time than CF-CON patients (6.8% per year vs 1.4% p < .01). We found no correlation between lung function and the degree of structural lung disease. ABPA in children with CF is associated with significantly more structural lung disease than that found in children with CF without ABPA. Despite interventive steroid therapy lung disease progresses more rapidly in those patients with ABPA and CF than control patients with CF.

Gallbladder wall thickening in patients with IgG4-related diseases, with special emphasis on IgG4-related cholecystitis

Objectives Gallbladder (GB) wall thickening sometimes occurs in patients with autoimmune pancreatitis (AIP), a condition for which the name, IgG4-related cholecystitis, was proposed. We examined the radiological findings of the GB in patients with IgG4-related diseases and clinical features of patients with GB wall thickening and presented a hypothesis of its pathogenesis. Materials and methods GB wall thickening was defined by thickness ≥ 4 mm. GB wall thickness was examined in 258 patients with IgG4-related disease. Clinical and imaging findings of 200 patients with AIP with and without GB wall thickening were then compared. Results GB wall thickening was detected in 58 patients (29%) with AIP and two patients with isolated IgG4-related sclerosing cholangitis. In the 60 GBs examined, wall thickening was diffuse, with the walls possessing a smooth inner surface. No GB wall thickening was detected among the 56 patients with IgG4-related disease without AIP or IgG4-related sclerosing cholangitis. Bile duct stenosis was detected in 56 patients (97%) with AIP with GB wall thickening. Intraductal ultrasonography indicated cystic duct wall thickening connected to bile duct wall thickening in 11 of 14 (79%) patients with AIP or IgG4-related sclerosing cholangitis with GB wall thickening. Forty-eight patients in whom IgG4-related cholecystitis was diagnosed experienced resolution of the GB wall thickening after receiving steroid therapy. Conclusions Most cases of GB wall thickening in IgG4-related diseases are closely associated with IgG4-related sclerosing cholangitis and may be a manifestation of IgG4-related disease throughout the biliary tract, including the bile duct, cystic duct, and GB.

Autoimmune Hemolytic Anemia as a Complication of Congenital Anemias. A Case Series and Review of the Literature.

Congenital anemias may be complicated by immune-mediated hemolytic crisis. Alloantibodies are usually seen in chronically transfused patients, and autoantibodies have also been described, although they are rarely associated with overt autoimmune hemolytic anemia (AIHA), a serious and potentially life-threatening complication. Given the lack of data on the AIHA diagnosis and management in congenital anemias, we retrospectively evaluated all clinically relevant AIHA cases occurring at a referral center for AIHA, hemoglobinopathies, and chronic hemolytic anemias, focusing on clinical management and outcome. In our cohort, AIHA had a prevalence of 1% (14/1410 patients). The majority were warm AIHA. Possible triggers were recent transfusion, infection, pregnancy, and surgery. All the patients received steroid therapy as the first line, and about 25% required further treatment, including rituximab, azathioprine, intravenous immunoglobulins, and cyclophosphamide. Transfusion support was required in 57% of the patients with non-transfusion-dependent anemia, and recombinant human erythropoietin was safely administered in one third of the patients. AIHA in congenital anemias may be challenging both from a diagnostic and a therapeutic point of view. A proper evaluation of hemolytic markers, bone marrow compensation, and assessment of the direct antiglobulin test is mandatory.

Post-COVID-19 rhino-orbito-cerebral mucormycosis: a new addition to challenges in pandemic control.

ObjectiveTo document and analyse demographic data, clinical presentation, possible interventions for early clinical detection and management of post-COVID-19 rhino-orbito-cerebral mucormycosis (ROCM).Method32 patients having history of SARS-CoV-2 infection with features of ROCM were observed in terms of their history, presenting features, clinical, microbiological examination, type of surgical intervention, surgical sites of involvement which were subsequently analyzed.ResultsThe mean (± S.D.) age of patients was 57 ± 13 years. All patients were diabetic. Mean (± S.D.) time of onset of ROCM symptoms, since onset of COVID-19 symptoms was 18 (± 4) days. 12.5% patients were fully vaccinated. 78.1% patients received steroid therapy; 28.1% received high flow nasal oxygen. 87.5% patients had blurring of vision, 65.62% headache, 59.37% cheek and eyelid swelling, 50% proptosis, 46.87% ophthalmoplegia, 40.62% ptosis, 40.62% loss of sensation over cheek, 25% orbital pain. Examination of specimen with KOH mount revealed Mucor spp. in all patients. 87.5% patients underwent endoscopic sinus surgery with debridement with/without orbital clearance; 56.25% maxillectomy; 25% orbital exenteration. 87.5% patients had paranasal sinus involvement, 43.75% orbit sparing orbital apex, 68.75% orbit with orbital apex. 81.25% patients had involvement of pterygopalatine fossa±infratemporal fossa. 50% patients had disease in Vidian canal and pterygoid wedge. 25% of patients had involvement of palate and 56.25% cheek and eyelid soft tissues.ConclusionA judicious COVID treatment protocol, high index of suspicion, close monitoring of high-risk patients and early institution of treatment can prevent case severity and reduce mortality.

Identification of patients with COVID-19 who are optimal for methylprednisolone pulse therapy.

BackgroundCorticosteroids have been reported to reduce the mortality rates in patients with coronavirus disease 2019 (COVID-19). Additionally, the role of high-dose methylprednisolone pulse therapy in reducing mortality in critically ill patients has also been documented. The purpose of this study is to identify patients with COVID-19 who are suitable for methylprednisolone pulse therapy.MethodsThis was a retrospective study that included patients with COVID-19 receiving methylprednisolone pulse therapy (≥250 mg/day for 3 days) with subsequent tapering doses at our hospital between June 2020 and January 2021. We examined the differences in background clinical factors between the surviving group and the deceased group.ResultsOut of 156 patients who received steroid therapy, 17 received methylprednisolone pulse therapy. Ten patients recovered (surviving group) and seven patients died (deceased group). The median age of the surviving and deceased groups was 64.5 years (range, 57-85) and 79 years (73-90), respectively, with a significant difference (p=0.004). Five of the deceased patients (71%) had developed serious complications associated with the cause of death, including pneumothorax, pneumomediastinum, COVID-19-associated pulmonary aspergillosis, cytomegalovirus infection, and bacteremia. On the other hand, out of the 10 survivors, only one elderly person had cytomegalovirus infection and the rest recovered without complications.ConclusionAdministration of methylprednisolone pulse therapy with subsequent tapering may be an effective treatment in patients with COVID-19 up to the age of early 70s; however, severe complications may be seen in elderly patients.

Clinical valuables related to resolution of complete or advanced atrioventricular block after steroid therapy in patients with cardiac sarcoidosis.

BackgroundPrediction of atrioventricular block (AVB) resolution after steroid therapy in patients with cardiac sarcoidosis (CS) is difficult.MethodsWe identified 24 patients with CS and complete or advanced AVB receiving steroid therapy. AVB resolution was assessed by reviewing surface electrocardiogram and the percentage of ventricular pacing required on subsequent device interrogation reports.ResultsAVB resolution was noted in eight (33%) patients 1 year after receiving steroid therapy. Univariate Cox regression analysis demonstrated that left ventricular ejection fraction (LVEF) (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01‐1.14, P = .016), interval from recognized AVB to start of steroid therapy (HR 0.98, 95% CI 0.95‐0.99, P < .001), and lysozyme (HR 1.51, 95% CI 1.12‐2.19, P = .013) were significantly associated with resolution of AVB. Combination of area under the curve (AUC) of each variable that was significantly related to resolution of AVB (AUC, 0.969; 95% CI 0.921‐1.000, P < .001) was tended to be higher compared with each variable alone.ConclusionsA shorter interval from recognition of AVB to start of steroid therapy, higher LVEF, and higher lysozyme levels were significantly associated with resolution of AVB after steroid therapy in patients with CS. The combination of each variable could be able to distinguish patients with resolution of AVB from those without.

P062 Effects of exposure to steroids on the PredictSURE whole blood prognostic assay in Inflammatory Bowel Disease

Abstract Background Accurately predicting disease course at diagnosis is critical to facilitate personalized therapy in inflammatory bowel disease (IBD). PredictSURE IBDTM is a whole blood qPCR assay that was developed to predict prognosis in newly diagnosed, treatment-naïve IBD patients – classifying them into IBDhi (high-risk) or IBDlo (low-risk). The current recommendation is that PredictSURE IBDTM should not be used in those who have commenced steroids. In this study, we aimed to determine the impact of steroid therapy on the performance of PredictSURE IBDTM. Methods Whole blood was serially taken from patients admitted with severe IBD requiring intravenous (IV) steroids (pre-steroid, day 3, day 5; n=10, cohort 1) and from patients receiving oral steroids as outpatients (pre-steroid, week 1, week 6; n=10, cohort 2). An independent cohort of 43 IBD patients, all within 3 months of diagnosis and on corticosteroid treatment (41 systemic and 2 topical, cohort 3) was recruited. RNA was extracted and analyzed with PredictSURE IBDTM (PredictImmune, UK). Patients were prospectively followed and treated according to routine clinical management by physicians blinded to the test results, and clinically stratified according to one of the original definitions used to construct and validate the test (need for step up to immunosuppressive or biological therapy or surgery). Results In cohorts 1 and 2, both oral and intravenous steroids affected the PredictSURE IBDTM result: misclassification as IBDlo occurred in 5/8 IBDhi patients receiving oral, and 5/7 IBDhi patients receiving IV, steroids. In 60% this change was detectable early (within 1 week of oral steroids and 3 days of IV steroids). Steroids did not affect the classification of IBDlo patients. Consistently, the prognostic accuracy was limited in patients already receiving steroids (cohort 3). After a median follow-up of 31.8 [IQR 18.7 - 42.1] months, 35 (81%) patients required step-up therapy. PredictSure IBDTM correctly classified only 23 (54%) patients with accuracy of 0.53 (sensitivity: 0.51, specificity: 0.63, positive likelihood ratio: 1.38, negative likelihood ratio: 0.77). Seventeen (80%) of the misclassifications were clinically high-risk patients who were predicted as IBDlo. Time to treatment escalation was similar between patients classified as IBDhi or IBDlo after starting steroid therapy (p= 0.47) (Figure 1). Conclusion The prognostic accuracy of PredictSURE IBDTM is limited if performed after steroid therapy has begun, most likely because of the misclassification of high-risk patients as low risk. Therefore, the test should only be performed in patients with active disease who are not receiving steroid therapy, as currently recommended.

Effect of Corticosteroids on Mortality in Hospitalized COVID-19 Patients Not Receiving Invasive Mechanical Ventilation.

The most beneficial effect of corticosteroid therapy in COVID‐19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID‐19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single‐center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID‐19) patients who did not receive IMV (OSCI 3–5). Included were 1,311 COVID‐19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3–9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In‐hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81–1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56–1.17, P = 0.26). COVID‐19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35–0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID‐19 with OSCI 3–5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.

Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis

Background & AimsIn patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes.MethodsWe performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes.ResultsAt baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity.ConclusionsAt baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders.Lay summaryPatients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.

Are People Who Received Steroid Therapy Prone to Osteonecrosis of Femoral Head? A Systematic Review

Are People Who Received Steroid Therapy Prone to Osteonecrosis of Femoral Head? A Systematic Review