Initiation Of Steroids Research Articles

S2626 Alcoholic Hepatitis and COVID-19: The Question of Steroids

INTRODUCTION: The SARS-CoV-2/Novel Coronavirus-19 (COVID-19) has created new challenges for managing acute alcoholic hepatitis (AH). The decision to initiate steroids in AH is now more difficult, as data suggests worsened outcomes in COVID-19 patients treated with steroids. How patients with AH respond to steroids while also COVID-19 infected is an open question. We present a case of severe AH in a COVID-19 infected patient who received steroids. CASE DESCRIPTION/METHODS: Fifty-seven-year-old man with chronic alcohol abuse and alcoholic cirrhosis with portal hypertension presented with dry cough, fatigue, and melena. He had been drinking 1 pint of vodka daily for 1 week. He had normal hemodynamics and oxygen saturation was 98% on room air. Rectal exam was unremarkable. Laboratory data showed normal BUN/Cr, Hgb/Hct 6.4 g/dL/21.6%, PLT 54 K/mL, total bilirubin/direct bilirubin 10.3 mg/dL/ 6.0 mg/dL, Alk Phos 162 IU/L, AST 260 IU/L, ALT 53, and INR 1.9. Viral hepatitis panel was unremarkable. COVID-19 PCR was positive. Chest x-ray revealed bibasilar opacities. Right upper quadrant ultrasound with doppler revealed liver with cirrhotic morphology and no portal vein thrombosis. MDF was 59.1. MELD score was 22. He was started on an octreotide infusion, IV pantoprazole, and IV ceftriaxone. On hospital day 3, he became encephalopathic and was started on lactulose and rifaximin. He developed hepatorenal syndrome and was treated with albumin. He then had worsening coagulopathy and a rising total bilirubin. MDF increased to 37 and prednisolone 40mg daily was started. Seven days into therapy, total bilirubin down trended and kidney function improved. Lille score was 0.980. Although the Lille score suggested he may be a steroid non-responder, his improved mental status, total bilirubin and kidney function led to the decision to treat for 28 days. DISCUSSION: The COVID-19 pandemic creates a new challenge in treating AH. The recommendation is that steroids should be avoided in viral infections. The decision to initiate steroids in patients with AH is influenced by the MDF. However, steroid initiation based on MDF becomes problematic as hepatic injury is a known consequence of COVID-19. Thus, an elevated score may not solely be related to alcohol-induced inflammation. In our case, risk of mortality appeared to be driven by AH and thus steroids were initiated. Despite being a non-responder per the Lille score, the patient improved. This case reveals that it may be safe to use steroids in patients with severe AH and COVID-19 positivity.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial.

BackgroundGranulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids.MethodsWe conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks.ResultsThe response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing.ConclusionsGMA shows effectiveness in inducing remission in UC patients not receiving steroid.

Managing rheumatoid arthritis during COVID-19.

The outbreak of coronavirus in the world has led to an uncertainty about treatment of patients with autoimmune disorders because of their weakened immune system coupled with immunosuppressive agents they take which predisposes them to a host of infections. Data on COVID-19 patients with underlying rheumatological diseases has been emerging mostly in the form of small case series and one global registry. From these data, it seems like our patients, although immunosuppressed, are not particularly susceptible to the coronavirus infection and if infected, do not have significantly worse outcomes than other patients. In fact, drugs like hydroxychloroquine, dexamethasone, and tocilizumab have been studied for treatment of COVID-19. However, this is only preliminary data, and since a few parts of the world are still grappling with the pandemic at its peak, we need to be equipped on how to protect and manage our immunosuppressed patients. Published evidence to guide treatment decisions are lacking and doubts regarding continuation and initiation of immunosuppressants remain. Rheumatoid arthritis (RA) is the most common immune-mediated disorder in COVID-19 patients, and in this review, we discuss how the commonly used drugs in RA alter the patients’ susceptibility to this infection. The review also summarizes the recommendations from the major bodies on how to manage this disease in these times.Key Points• Patients on immunosuppressive medications are not found to be at a greatly increased risk of acquiring COVID-19 infection.• Patients doing well on a stable dose of steroid and/or Disease-Modifying Antirheumatic Drugs (DMARDs) should be allowed to continue the same unless they get infected in which case, temporary stoppage of methotrexate and leflunomide may be considered.• Initiation of high-dose steroids, DMARDs, and biologics, if the clinical situation demands so, can be done.• Maintenance biologic therapy for stable patients should be individualized by the treating physician.

Severe immune-related hepatitis induced by immune checkpoint inhibitors: Clinical features and management proposal

Immune-related hepatitis (IRH) occurs in 1 to 18% of immune checkpoint inhibitor (ICI)-treated patients. Steroids are usually recommended for grade≥3 IRH, but their impact on IRH resolution and patient survival remains unclear. We retrospectively analyzed a prospective cohort of 339 patients treated at Saint-Louis Hospital (Paris, France) with ICIs for advanced melanoma. Cases of grade≥3 IRH were collected and analyzed. Two groups were compared for their biological features and time for IRH resolution and survival: patients who received steroids (steroids group: SG) and patients who did not (nonsteroids group: NSG). Grade≥3 IRH was observed in 21 patients. Thirteen were treated with steroids (SG), and 8 were not (NSG). The median time for toxicity resolution was 49 days in SG and 24 days in NSG (P=0.62). All but one patient showed a favorable outcome. Two-year survival was 56% in SG and 54% in NSG (P=0.83). Higher transaminase (P=0.002) and bilirubin (P=0.008) and lower prothrombin (P=0.035) levels were observed in SG than in NSG. For 8 (4 SG/4 NSG) patients, ICI was resumed without any hepatitis relapse. Favorable outcomes may be achieved spontaneously and with no steroids in patients with severe IRH. Steroid initiation should be discussed in cases of high bilirubin levels and decreased prothrombin levels. ICI could be resumed without hepatitis relapse. We propose a management algorithm for grade≥3 IRH that should be validated in larger and prospective cohorts.

Postsurgical Pyoderma Gangrenosum After Breast Surgery: A Plea for Early Suspicion, Diagnosis, and Treatment.

Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder. Although PG is a diagnosis of exclusion, prompt recognition is essential to attain the desired outcomes. From an aesthetic standpoint, this is especially critical with breast involvement and other body segments. We present a consecutive case series of four patients who developed PG following breast surgery and responded to early intervention. A chart review identified four patients who were identified as having developed PG after either aesthetic or reconstructive breast surgery. Their histories, associated risk factors, diagnosis, course of treatment, and results were documented. The PubMed database was then searched to find the literature for comparison. The average time from surgery to the onset of symptoms was 11days, and the average time from the onset of symptoms to the correct diagnosis of PG was 41days. The average length of steroid therapy was 25days. The average time from the initiation of steroids to complete wound closure was 51days. The average time from the onset of symptoms to complete wound closure bilaterally was 87days. All wounds healed with conservative management. Postsurgical PG is a rare but recognized cause of postoperative wound breakdown in patients who have undergone plastic surgery procedures to the breast. Early recognition and treatment can facilitate prompt reversal of the inflammatory process leading to complete wound healing and limitation of the morbidity that can be associated with the disease. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Utility of 18F-FDG PET/CT in Patients With Clinical Suspicion of Polymyalgia Rheumatica and Giant Cell Arteritis: A Prospective, Observational, and Cross-sectional Study.

ObjectiveTo define the proportions of agreement between fluorine‐18‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT), clinical diagnosis, and temporal artery biopsy (TAB) in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Furthermore, the association of 18F‐FDG PET/CT uptake patterns and clinical presentation of newly diagnosed PMR and GCA was investigated.MethodsEighty patients newly suspected of having PMR, GCA, or concomitant PMR and GCA were included and followed for 40 weeks. Every patient underwent an 18F‐FDG PET/CT scan before or within 3 days of initiation of steroids in case of GCA. FDG uptakes in 8 paired articular/periarticular sites and 14 arterial segments were evaluated based on a 4‐point visual grading scale.ResultsOf the 80 patients (female: 50 [62.5%]; mean age ± SD: 72.0 ± 7.9), 64 (80.0%) patients were diagnosed with pure PMR, 3 (3.7%) with pure GCA, and 10 (12.5%) with concomitant PMR and GCA. Additionally, three (3.7%) patients were diagnosed with seronegative rheumatoid arthritis during the follow‐up period. For the diagnosis of PMR, 18F‐FDG PET/CT had a proportion of agreement of 75.3 (64.2‐84.4), compared with clinical diagnosis. When comparing findings of 18F‐FDG PET/CT with TAB, 18F‐FDG PET/CT had a proportion of agreement of 93.0 (84.3‐97.7) in all included patients and 69.2 (38.6‐90.9) in the subgroup of patients with vasculitis. C‐reactive protein was significantly higher in patients with PMR activity on 18F‐FDG PET/CT compared with those without 18F‐FDG PET/CT activity (P value = 0.006).Conclusions18F‐FDG PET/CT is a powerful imaging technique in PMR and GCA that was in good agreement with clinical diagnosis and TAB.

Systemic Corticosteroid Use after Central Serous Chorioretinopathy Diagnosis

To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis. Retrospective claims-based analysis. A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and2015. We limited the study population to beneficiaries with incident CSC diagnosed by an eye care provider, excluding those with other major ophthalmologic comorbidities. We developed a non-CSC comparison cohort matched to CSC patients by age, sex, general health (Charlson Comorbidity Index), and geographic region. We compared systemic corticosteroid prescriptions before and after CSC diagnosis and by diagnosing provider (optometrist vs. ophthalmologist) and evaluated likelihood of steroids treatment among CSC versus matched control patients using logistic and Cox proportional hazard regression models. Systemic corticosteroid prescription frequency among CSC patients within 12 months pre-diagnosis and at 6, 12, and 24 months post-diagnosis, median time to steroid initiation and discontinuation, and odds of receiving steroids post-diagnosis among CSC and control patients. We identified 3418 CSC patients. Nearly 39% (n= 1326) were prescribed systemic steroids at some point during the analysis period, versus 23% of controls (4033 of 17 178 patients). Over 12% of CSC patients (n= 430) within 1 year pre-diagnosis, and nearly 12% (n=404) within 1 year post-diagnosis. Most patients who received steroids after diagnosis were steroid naive (n= 231). Among those receiving steroids, CSC patients demonstrated longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 years for non-CSC patients) and longer time to last steroid prescription (1.62 years vs. 0.35 years for non-CSC patients). Although CSC patients were significantly less likely to receive steroids within 6 months post-diagnosis compared with non-CSC patients (odds ratio, 0.72; 95% confidence interval, 0.59-0.89), they were significantly more likely to receive steroids by 2 years post-diagnosis. Prescribing patterns were similar for patients diagnosed by an ophthalmologist versus optometrist. Despite evidence showing that steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. Our results suggest a need for greater communication and collaboration among providers to ensure that clinical practice reflects evidence-based recommendations.

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study

To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500g) infants is associated with the development of necrotizing enterocolitis (NEC). Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n=2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition. The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n=269), compared with 3.9% in those who did receive early antibiotics (n=2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P<.05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P<.0001). In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.

AB0502 EVALUATION OF A NOVEL FAST TRACK PATHWAY FOR GIANT CELL ARTERITIS USING PET IN ADDITION TO TAUS AND TAB FOR EARLY DIAGNOSIS

Background: :Giant Cell Arteritis (GCA) is a common primary systemic vasculitis (1). Its predilection for the temporal artery can result in permanent visual loss if left untreated. Over 25% of patients have involvement of large vessels, such as the aorta, resulting in an increased risk of aneurysm formation and dissection. (3)Diagnosis of GCA is largely clinical and temporal artery biopsy (TAB) has long been the gold standard for diagnosis. In recent years temporal artery ultrasound (TAUS) has emerged as an effective, non-invasive tool to aid diagnosis. Positron-emission tomography (PET) can also be utilised to detect the presence of large vessel involvement but is currently not used in many centres for diagnostic purposes and requires further standardisation and validation (2). The challenge arises from these investigations losing sensitivity in the days following steroid treatment, meaning that rapid access is key to confirm diagnosis.Objectives:To evaluate the impact of the introduction of a fast track pathway (FTP) on prompt diagnostics and treatment.To improve our understanding of the use of PET at diagnosis and compare this to the gold standard TAB, and to TAUS, in our institution.Methods:Cohort 1: 32 patients, all presenting before FTP implementation, identified from outpatient clinics and referrals to the Rheumatology team. Time taken from steroid initiation to TAUS/TAB was extracted from clinical records. Outcomes for this group included number of years on steroid (steroid burden).Cohort 2: 21 patients all referred after implementation of a new GCA FTP. This group contains all patients referred as query GCA, not just those with positive diagnoses. Time from steroid initiation to TAUS/TAB was recorded. The FTP included the addition of PET imaging within 72 hours.Results:Cohort 1: 20 (63%) patients had TAB and 3 (9%) had TAUS. The average time from starting steroid to investigation was 5.2 days and 2 days respectively. The average steroid burden in patients with no confirmatory test was 11 years. If patients had just a single diagnostic test this value dropped to 3 years.Cohort 2: 11 (52%) had TAB, 10 (48%) had TAUS and 11 (52%) had PET. In positive GCA diagnoses, time from steroid start to investigations was 7.2 days, 1 day and 3.2 days respectively. In patients with a negative diagnosis the time frames were 13 days, 1 day and 1.7 days respectively. Sensitivity for TAB was 45.5% and TAUS 40%. Specificity for TAB and TAUS was 100%. These results are comparable to similar studies (4). PET sensitivity was 63.6% and specificity 100%.Table 1.Sensitivity, specificity, predictive valuesTABTAUSPET CTSensitivity (%)45.540.063.6Specificity (%)100100100PPV (%)100100100NPV (%)33.357.155.6Conclusion:Prompt diagnostics, best facilitated through a FTP, can reduce steroid burden in GCA even if only one confirmatory test is available. Patients with a low clinical suspicion of GCA and negative TAUS or a high clinical suspicion and positive TAUS stand little to gain from TAB. These findings summarise the first 6 months of our GCA FTP. Continued evaluation of PET in our FTP is needed to understand its role in diagnosis, particularly in patients at risk of vascular complications.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients with Active Ulcerative Colitis During the COVID-19 Outbreak (EXPECT Study): A Multicenter Prospective Clinical Trial

Background: During the COVID-19 pandemic, safe treatment of inflammatory bowel disease is required. Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC) with few adverse events. Therefore, elucidating the effectiveness of GMA without steroids is important in the current situation. The aim of this study was to investigate the effectiveness of GMA in active UC patients who are not receiving steroids. Methods: A single-arm, open-label, and multicenter prospective clinical trial was conducted at ten facilities in Japan.UC patients who had insufficient responses to 5-aminosalicylic acid without steroids received GMA twice a week for five consecutive weeks. The primary and secondary endpoints were the induction of a response and endoscopic mucosal healing in the patients who achieved a response. Findings: A total of 67 patients were enrolled. The response rate of all patients who received GMA ten times was 58·2%. Of the 39 patients who achieved a response, 74·4% achieved endoscopically confirmed mucosal healing. Both the median Mayo score and ulcerative colitis endoscopic index of severity score were significantly decreased in the patients who achieved a response. The response rate of the patients who were suffering from their first episode was significantly higher than that of those with relapse-remitting UC (80·0% [16/20] vs. 48·9% [23/47], p=0·029). Undergoing the first episode of UC (odds ratio [OR]: 4·952, 95% confidence interval [CI]: 1·292-18·981, p>0.001) was defined as an independent predictor of a response. Interpretation: This study strongly suggest that GMA shows promising effectiveness in inducing remission in active UC patients who are not receiving steroid treatment. We expect that GMA can be made available during the COVID-19 pandemic. Trial Registration: UMIN registration No. 000013702 Funding Statement: Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease to HN). Declaration of Interests: MM reports personal fees from Janssen Pharmaceutical K.K., and commercial research funding from AbbVie GK. and Nippon Kayaku Co., Ltd. SN reports receiving personal fees from EA Pharma Co., Ltd., AbbVie GK., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. KH reports receiving research funding from EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. HN reports receiving personal fees from AbbVie GK., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Pfizer Lnc., Cell gene Corporation., EA Pharma Co., Ltd., Zeria Pharmaceutical CO., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Daiichi Sankyo Company, Limited., JIMRO Co., Ltd., as well as grants for commissioned/joint research from Hoya Group Pentax Medical, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. All other authors declare no competing interests. Ethics Approval Statement: The protocol of the clinical trial was approved by the IRB at each institution. Informed consent to participate in the study was obtained from each participant before inclusion.

Etanercept with extracorporeal photopheresis (ECP) for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation.

7543 Background: Acute graft versus host disease (aGVHD) is a well-described complication of allogeneic stem cell transplantation (allo-SCT). Complete response to steroids is achieved in 40-50% of cases, with steroid refractory GVHD requiring second line therapy. Currently, there is no accepted standard of care in this setting. In our study, we assessed the safety and efficacy of etanercept with ECP for steroid refractory aGVHD in a single center tertiary care hospital. Methods: Thirty adult patients who underwent peripheral blood allo-SCT and developed steroid-refractory aGVHD between January 2010 - July 2019 were retrospectively analyzed. Patients were planned to receive etanercept 25 mg subcutaneously twice weekly for at least 4 weeks. Safety was assessed by estimating infection related mortality. For efficacy, we analyzed the change in grade of aGVHD using the Wilcoxon signed-rank test. Results: Median age at the time of allo-SCT was 57.6 years and the most common indication for transplant was Myelodysplastic syndrome. Median time from allo-SCT to steroid initiation was 39.5 days (range 14-183 days). Median time from steroid initiation to etanercept was 6 days, with 7.5 median number of etanercept doses received. A total of 25 patients (83.3%) received ECP. As depicted in the table, there was a significant improvement in severity of aGVHD after etanercept therapy compared to that before its initiation. Overall response rate was 83.3%, while overall mortality was 86.7%. Median overall survival for responders was 306 days (range 59-2005 days) and for non-responders was 181 days (range 89-261 days). Death attributed to infection alone occurred in 28% (n=7), infection along with GVHD in 28% (n=7) and infection with relapsed disease in 1 patient. Active infection within 6 months of transplant occurred in 93.3% patients. Conclusions: The use of Etanercept with ECP resulted in improvement of steroid refractory aGVHD following allo-SCT, with responses noted in the majority of patients. High rates of infection related mortality were also noted and remain a cause of concern. [Table: see text]

Cumulative steroid doses and response rates to immune checkpoint inhibitors in metastatic cancer.

e15133 Background: Steroids are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether steroids have an effect on immune checkpoint inhibitor (CPI) efficacy compared patients receiving steroids vs. no steroids. This comparison may be confounded by different rates of irAEs and a known association of irAEs with higher response rates to CPIs. There is a paucity of CPI efficacy data in relation to the total dose of concomitant steroids. Methods: We retrospectively collected data from patients treated with CPIs alone, who received steroids during their CPI treatment at a single institution. IrAEs were defined using the CTCAEv5 criteria. Response rate (RR) and progression were defined per RECIST v1.1. Kaplan Meier and Cox proportional hazard regression methods were used to estimate the survival probability and hazard ratios (HR). Results: We identified 260 patients with stage IV cancer who received steroids concurrently with CPI treatment. A total of 111 patients (42.7%) received ≥1000mg prednisone equivalence during the course of their CPI treatment, and the remaining 149 patients (57.3%) received &lt; 1000mg PED. There was no difference in progression free survival (PFS) between the two cohorts [HR of 0.923 for &lt; 1000 mg PED group; p = 0.6016] or in overall survival (OS) [0.854 for &lt; 1000 mg PED group, p = 0.3308]. Median PFS for the &lt; 1000mg group was 5.9 months (mo), vs 6.3 mo in the ≥1000mg group. Median OS for the &lt; 1000mg group was 15.76 mo, vs 11.53 mo in the ≥1000mg group. The RR was numerically higher in the prednisone &lt; 1000mg cohort at 29.53% vs 20.72% in the ≥1000mg cohort, however not statistically significant (p = 0.1082). Basic characteristics including sex, race, tumor type, and smoking status, were similar between the two groups. There was a statistically significant difference in BMI distribution and steroid indication (irAE indication higher in &gt;1000 mg PED cohort than non-irAE) between the two groups. Conclusions: PFS, OS, and RR were not different between patients who received &gt;1000mg vs. &lt; 1000mg PED during CPI therapy. These data suggest that even high doses and protracted courses of corticosteroids may not hinder CPI efficacy. However, differences in our primary endpoint PFS may be confounded by difference in BMI and rates of irAEs between each cohort, which are both known to be associated with improved CPI efficacy. Further analyses to account for these differences along with how timing of steroid initiation affects CPI-efficacy will be completed by time of presentation.

A case of toxic epidermal necrolysis with refractory acute respiratory distress syndrome

Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous reaction with several complications. Although acute respiratory distress syndrome (ARDS) is rare, it can cause rapid and potentially fatal pulmonary dysfunction. Here, we present a case of TEN with ARDS attributed to acetaminophen. Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous reaction with several complications. Although acute respiratory distress syndrome (ARDS) is rare, it can cause rapid and potentially fatal pulmonary dysfunction. Here, we present a case of TEN with ARDS attributed to acetaminophen. A 49-year-old woman with cerebral palsy was admitted to our hospital with a high fever and erythema of the face and trunk that developed 1 day earlier. She took acetaminophen twice at 4 and 1 day before admission. The erosion covered approximately 30% of the body surface area, and hemorrhagic erosions were observed on the lips (Figure 1A). TEN was diagnosed, with a severity-of-illness score (SCORTEN) of 3. Chest computed tomography (CT) revealed a bilateral infiltrative shadow in the lower lung fields (Figure 1B). Aspiration pneumonia was diagnosed. All medications were discontinued, and methylprednisolone pulse therapy (steroid pulse; 1000 mg/d for 3 days) was administered with antibiotics. On Day 2, she developed acute-onset dyspnea (SpO2: 70%-80%). Chest CT revealed spreading of the bilateral diffuse infiltrative shadow (Figure 1C). ARDS induced by TEN was diagnosed, and mechanical ventilation was initiated. Intravenous immunoglobulin therapy (IVIg; 400 mg/kg/d for 5 days) was administered after steroid pulse therapy, leading to rapid improvements in the skin and mucosal involvement. The prednisolone dosage was tapered to 30 mg/d, and re-epithelialization was completed on Day 19. Nevertheless, the ARDS responded poorly, and steroid pulse therapy was repeated on Days 19-21. Thereafter, the chest shadow and dyspnea gradually improved, and prednisolone was slowly tapered to 5 mg/d on Day 100. However, she developed an ARDS relapse a few days later and received steroid pulse therapy. The chest CT findings improved, although she could not be weaned from mechanical ventilation upon discharge at Day 150. A drug-induced lymphocyte stimulation test was positive for acetaminophen (stimulation index: 803%), and a patch test was negative. Reports describe an approximate respiratory complication rate of 40% during the acute phase of SJS/TEN.1 Prost et al reported that approximately 25% of SJS/TEN patients required mechanical ventilation (MV); of these cases, 57% had a fatal outcome.2 Lebargy et al reported that dyspnea, hypoxia, increased bronchial secretions, and normal chest X-rays within the first 3 days of illness indicated early bronchial involvement.3 To date, however, few case reports have described the features of SJS/TEN with ARDS. Three of 138 patients with SJS/TEN who were treated at our hospitals from 2000 to 2019 developed ARDS, of whom two (including the present case) survived. The third and fatal case did not begin treatment until more than 1 week postonset. Evidence regarding the effective treatment of pulmonary complications with SJS/TEN is lacking. Although antibiotics and steroids are commonly used,1 the effectiveness of systemic steroid therapy for ARDS remains controversial; some studies reported effectiveness,4, 5 while others reported no survival benefit.6, 7 Moreover, steroid-induced infections tend to worsen prognosis. We conclude that steroid initiation promptly after onset, followed by IVIg, may have contributed to our patient's survival. Additional case studies are needed to support future treatment development. The authors declare no conflict of interest.

Subconjunctival Bevacizumab Injection for Corneal Neovascularization in Interstitial Keratitis

We describe the use of subconjunctival Bevacizuamb as an adjunct in the treatment of viral interstitial keratitis in a 17-year-old boy. He presented with a 3 months history of gradually progressive diminution of vision. The presenting visual acuity was 20/120 in the right eye and counting fingers close to face in the left eye. Examination revealed bilateral disc shaped stromal edema with leash of blood vessels entering the superior quadrant of the cornea. Subconjunctival injection of 0.1 mL (2.5 mg) of commercially available Bevacizumab (100 mg/4 mL; Avastin) was given under topical anesthesia along with initiation of topical steroids in the form of Betamethasone 0.1%. After 2 weeks of injection there was a remarkable reduction in corneal edema as documented by AS-OCT with improvement in visual acuity. We report here our experience with subconjunctival injection of bevacizumab for corneal vascularization in a patient with interstitial viral keratitis.

Provider views on perioperative steroid use for patients with newly diagnosed pediatric brain tumors.

Cerebral edema from brain tumors can cause neurological impairment. Steroids treat edema but with possible adverse effects. We surveyed providers regarding steroid use in newly diagnosed patients with brain tumors to determine if practices are standard or markedly variable. An anonymous voluntary online survey was sent to members of neuro-oncology consortiums. Four clinical scenarios were provided and questions regarding initiation of steroids, type, dose, formulation, and duration were asked. Demographic information was collected. 369 providers received the survey, 76 responded (20.6% response rate). The proportion of providers who would start steroids significantly differed among scenarios (scenario 1 vs 2, p < 0.001; 2 vs 3, p < 0.001; 1 vs 3, p < 0.001). 75 (98.7%) providers would start steroids for vasogenic edema (scenario 1) and 55 (72.4%) for obstructive hydrocephalus (scenario 2). 16 (21.1%) would start steroids for vasogenic edema but not obstructive hydrocephalus. The odds of choosing to start steroids in patients with obstructive hydrocephalus were 7.59 times more (95% CI: 2.29, 25.13) if providers felt symptoms would improve within 24h. All would use dexamethasone. A significant difference was seen between the proportion of providers who would give a loading dose if vasogenic edema with neurological deficits were noted versus vasogenic edema alone (57.9% vs 43.4%; p = 0.002). These results suggest that providers recommend dexamethasone for patients with vasogenic edema and obstructive hydrocephalus. Variability remains with dosing schedule. Further studies are needed to identify the most appropriate use of steroids for newly diagnosed CNS tumor patients with the goal to create steroid management guidelines.

Extended Letermovir Administration, Beyond Day 100, Is Effective for CMV Prophylaxis in Patients with Graft Versus Host Disease

<h3>Introduction</h3> Patients who are seropositive for cytomegalovirus (CMV) prior to allogeneic stem cell transplant (ASCT), have a ∼30% incidence of CMV reactivation (Teira, Blood 2016). Letermovir is commonly used for CMV prophylaxis in this cohort. In the phase III trial for letermovir, prophylaxis was only continued through week 14 (∼day 100). The incidence of CMV reactivation increased significantly after week 18 post ASCT. It was hypothesized that late reactivation in some patients was due to graft versus host disease (GVHD) and glucocorticoid use (Marty, NEJM 2017). To our knowledge, no data has been published regarding the efficacy of extended letermovir prophylaxis in patients with GVHD, who are receiving high dose glucocorticoids. <h3>Methods</h3> We retrospectively identified all patients that received an ASCT between January 2018 and August 2019 at Columbia University Medical Center and were given letermovir for CMV prophylaxis. We further limited our analysis to the subset of patients that were diagnosed with acute or chronic GVHD and continued letermovir after the diagnosis of GVHD regardless of the day 100 milestone. <h3>Results</h3> We identified 12 patients that continued letermovir after the diagnosis of GVHD (Table 1). The median duration of letermovir after the diagnosis of GVHD was 5 months. 10/12 patients received letermovir beyond 100 days post-transplant. The remaining 2 patients have had less than 100 days follow up post-transplant to date. Only 3 patients (25%) who continued letermovir after GVHD diagnosis showed evidence of CMV reactivation, which was not clinically significant, while on the drug. Notably, all 3 patients had received post-transplant cyclophosphamide. 2 patients had received grafts from haploidentical donors and 1 patient from an 8/10 mismatched unrelated donor. All 3 had low level viremia (< 1000 IU/ml), and the viremia resolved without alternate antivirals in all patients. The median CD4 count after the initiation of steroids was 62 cells/uL. The median CD4+ T cell count was lower in the CMV reactivation group compared to the no reactivation group (25 vs 103 cells/uL). 2/3 patients had CMV reactivation after stopping letermovir. There were no major differences in the timing of GVHD onset and the dose of steroids used in the reactivation vs no reactivation group. In summary we show that extended letermovir prophylaxis is effective in CMV-seropositive patients that develop GVHD and require systemic immunosuppression. Despite low level viremia in 3/12 patients, there was no need to switch any patients to alternate antivirals. Patients that developed low level CMV reactivation had lower CD4 counts compared to patients who did not reactivate. Post transplant cyclophosphamide is a potential risk factor for CMV reactivation in GVHD patients on extended letermovir. These findings should be confirmed in a prospective study.

Impact of Early Steroid Initiation During Immune Checkpoint Inhibition

Impact of Early Steroid Initiation During Immune Checkpoint Inhibition

Impact of early introduction of steroid on immune-checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer treated

Impact of early introduction of steroid on immune-checkpoint inhibitors (ICI) in patients with advanced non-small cell lung cancer treated

Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy

BackgroundIntegrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4+ T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned. MethodsStudy within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4+ T-cells per μL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRISFRENCH) or by a clinical IRIS diagnosis of the physician (IRISCLINICAL). The primary outcomes were the association between INI and the occurrence of IRISFRENCH and IRISFRENCH+CLINICAL in multivariable logistic regression. Findings672 patients with a median CD4+ T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRISFRENCH as well as IRISFRENCH+CLINICAL (OR 2·43, 95%CI:1·45–4·07, and OR 2·17, 95%CI:1·45–3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRISFRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRISFRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRISFRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p=0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed. InterpretationIn HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters. FundingThe ATHENA database is maintained by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment.

Corticosteroid-Induced Regression of Glioblastoma: A Radiographic Conundrum

Corticosteroid-induced regression of lesion contrast enhancement on imaging studies is most commonly appreciated with primary central nervous system lymphoma; however, although exceedingly rare, a limited number of primary and metastatic intracranial lesions have been reported to exhibit similar radiographic changes subsequent to corticosteroid therapy. To date, there have been six cases of glioblastoma reported to exhibit such changes. Lesion transformation on repeat imaging after the initiation of steroids represents a diagnostic dilemma for clinicians when attempting to differentiate between a diagnosis of glioblastoma and lymphoma. Stereotactic biopsy may be inadvertently postponed due to high clinical suspicion for steroid-induced cytotoxicity traditionally seen with lymphomatous cells. To highlight this radiographic conundrum, we present a rare case of corticosteroid-induced regression of glioblastoma and discuss the relevant literature. To our knowledge, this is the first case report to describe the molecular profile of a glioblastoma that underwent corticosteroid-induced regression.