Serum IgG4 Concentration is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis

Objectives: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and identify its clinical biomarker. Methods: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR and partial response groups: PR), and each parameter was compared statistically.Results: Male-female ratio was 5: 1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6mg/dL vs 255mg/dL, 206mg/dL, P=0.0059 and 0.0078). ROC analysis was performed between the non-responder (NC) and responder groups (CR+PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC was 0.793 and the values of sensitivity and specificity were 0.85 and 0.64, respectively, under the cut-off values of 67.6mg/dL. Conclusions: In the majority of iRPF patients, glucocorticoid therapy resulted in a favorable response. Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

Glucocorticoid therapy in assisted reproduction

As glucocorticoids are well-known as important regulators of stress and the immune system, their function and clinical use have elicited substantial interest in the field of reproduction. In particular, the effect of glucocorticoid therapy on endometrial receptivity during assisted reproduction, including in vitro fertilization (IVF) cycles, has led to a great deal of interest and controversy. However, previous studies have not been able to provide consistent and reliable evidence due to their small, non-controlled designs and use of different criteria. Considering the potential risk of exposure to glucocorticoids for mothers and fetuses in early pregnancy, the use of glucocorticoids in IVF cycles should be carefully evaluated, including the balance between risk and benefit. To date, there is no conclusive evidence that the use of glucocorticoids improves the pregnancy rate in IVF cycles with unselected subjects, and a further investigation should be considered with a proper study design.

340. Outcomes of COVID-19 in Hospitalized SOT Recipients: Experence in Colombia, South America

Background SOTs (SOT) recipients with COVID-19 are considered to be at high risk of severe clinical outcomes. Several descriptive studies have reported a high frequency of intensive care unit admission and death rates. There is a lack of evidence regarding the best approach for immunosuppressive therapy in SOT recipients with COVID-19. Methods We performed a single-centered, retrospective, observational study of all SOT recipients with SARS-CoV-2 confirmed infection RT-PCR from nasopharyngeal swab specimens who were admitted to the emergency department from March 25 to September 1, 2020. Glucocorticoid therapy was administered according to the criteria of the attending physician. We classified glucocorticoid dose as low dose therapy if the patient received dexamethasone 6 mg/day or methylprednisolone 40 mg/day, and a high dose if the patient received methylprednisolone 80–160 mg/day. Specimens collected within the first 48 hours were defined coinfection, while specimens collected after 48 hours were defined as hospital-acquired superinfection. Results Of a total of 43 SOT recipients with COVID-19, 17 (39%) required intensive care unit admission. 32 (74.4%) required glucocorticoid therapy: 13 received low dose and 19 high dose. 15 (34.8%) had secondary infections. A total of 12 (27.9%) presented hospital-acquired bacterial superinfections, mostly caused by P. aeruginosa, most of isolations were from respiratory tract cultures. The median time from hospital admission to superinfection diagnosis was 9 (7-13) days. Community-acquired co-infection at COVID-19 diagnosis was documented only in 3 (6.9%) patients, mostly caused by K. Pneumoniae, all isolations were from urine culture. Glucocorticoid therapy was indicated in 32 (80%) patients, 19 received high dose and 13 low doses. Overall hospital mortality was 17.5%. ICU mortality was 41%. Overall mortality in the high dose steroids group was 37 % vs . 0% in the low dose group. Conclusion Our results showed a higher frequency of superinfection in SOT recipients with COVID-19 compared to previous reports, and higher ICU mortality. Further studies are needed to establish the best approach for glucocorticoid therapy in SOT recipients with COVID-19. Disclosures All Authors: No reported disclosures

Pharyngeal Ulcer as the First Sign of Pemphigus

Pemphigus is a rare autoimmune mucocutaneous bullous disease that can be life-threatening. We report a case of pemphigus vulgaris with pharyngeal ulcer as the initial presentation that was treated with glucocorticoid therapy.

Monocytosis in rational empirical antibacterial therapy in moderate forms of COVID-19

Microbiologically confirmed bacterial co-infection occurs in 1.2%–7% of hospitalized patients with COVID-19. The study of rational approaches to empirical antibacterial therapy (ABT) of SARS-CoV-2 virus-induced pneumonia continues. Glucocorticoid (GCS) therapy, the main method for pathogenetic treatment of moderate forms of CОVID-19, can lead to the development of neutrophilic leukocytosis. The criterion for the differential diagnosis of leukocytosis could be determining the quantity of peripheral blood monocytes. Assessing the significance of identifying the monocyte quantity can serve as an additional criterion for assigning empirical ABT in the treatment of pneumonia caused by the new coronavirus infection. The aim of the study was to identify the characteristics of glucocorticoid-induced leukocytosis in patients with moderate COVID-19. The study included 86 patients with a confirmed diagnosis of COVID-19 (ICD codes: U07.1, U07.2) of moderate severity. The patients were divided into 2 groups. The comparison group consisted of 40 patients who were prescribed ABT after the manifestation of leukocytosis on the background of glucocorticoid therapy. The control group included 46 people who were not prescribed ABT after the manifestation of leukocytosis on the background of glucocorticoid therapy and until the end of their stay in the hospital. We compared the parameters of the clinical blood tests (the absolute number of white blood cells, neutrophils and monocytes (×109/L)) on days 3, 6 and 9 from the start of GCS therapy. As a result, on the 3rd day, both groups had neutrophilic leukocytosis (>9.0×109/L) and absolute monocytosis (>0.8×109/L). There was a statistically signif icant decrease in the absolute number of white blood cells, neutrophils and monocytes by days 6 and 9, compared with day 3 from the start of glucocorticoid therapy. When comparing blood parameters between the groups, there was no statistically significant difference in the number of cells on the 3rd, 6th and 9th day of GCS therapy (p>0.05). Glucocorticoid-induced leukocytosis is associated with absolute monocytosis. The administration of ABT in response to the occurrence of leukocytosis in this study did not affect the change in the level of white blood cells. At the same time, a likely factor in reducing these indicators was a decrease in the daily dosage of corticosteroids.

Case Report: Afatinib-Induced Interstitial Pneumonia: Experiences and Lessons From Two Patients

Background: Afatinib has shown good efficacy in patients harboring uncommon EGFR mutations, but the incidence of afatinib-induced interstitial pneumonia should be alert as its rapid progression. Here, we report two cases of interstitial pneumonia during afatinib treatment.Case presentation: The first case was of a 58-year-old male with advanced lung adenocarcinoma (cT4bN3M1b) with exon 18 G719X and exon 20 S781I EGFR mutations and received afatinib therapy. After 68 days of therapy, he developed shortness of breath and fever. Drug-induced pneumonia was not diagnosed timely, the patient received empirical antibiotics and low-dose glucocorticoids. The pulmonary inflammation rapidly progressed and the patient died 15 days after symptom onset. The second case was of a 57-year-old man with stage IV (cT3N3M1b) lung adenocarcinoma with exon 21 L861Q EGFR mutation. He received afatinib as second-line therapy. Fever and shortness of breath occurred 22 days after afatinib therapy, he received empirical antibiotic therapy. Five days later, CT showed aggravated pulmonary inflammation, and afatinib-induced interstitial pneumonia was diagnosed. He received glucocorticoid therapy, and the pneumonia quickly improved.Conclusion: Although the incidence of EGFR-TKI-associated pneumonia is uncommon, high vigilance for drug-induced interstitial pneumonia is necessary during treatment. Early diagnosis and early glucocorticoid therapy could reverse lung injury.

Pregnancy in a woman with secondary osteoporosis. A case report

BACKGROUND: Glucocorticoid-induced osteoporosis is one of the most serious complications of prolonged (more than three months) systemic glucocorticoid therapy. Rapid bone loss occurs in the first months of treatment, which is a significant risk factor, especially during pregnancy and lactation. When taking systemic glucocorticoid therapy in a daily dose of 5 mg or more (in prednisone equivalent), the relative risk of vertebral fractures increases by 2.9 times. RESULTS: This article examines a clinical case of pregnancy and childbirth of 32-year-old woman diagnosed with secondary complicated osteoporosis during treatment with systemic glucocorticosteroids, who has a history of spine compression fractures during lactation after a previous pregnancy. Vitamin D deficiency was diagnosed and corrected during this pregnancy, which minimized the risk of fractures. A baby was delivered through the birth canal. Bisphosphonate therapy was started six months after birth. No new fractures were diagnosed within two years of observation. CONCLUSIONS: The approach to the management, diagnosis and delivery of pregnant patients with secondary osteoporosis treated long-term with glucocorticosteroids should be multidisciplinary. It is imperative to prescribe vitamin D and calcium preparations throughout pregnancy and lactation.