A Case of Clinically Amyopathic Dermatomyositis that was Refractory to Intensive Immunosuppressive Therapy including Tofacitinib, but Successfully Treated with Plasma Exchange Therapy

ABSTRACT Clinically amyopathic dermatomyositis (CADM) patients often develop rapidly progressive interstitial lung disease (RP-ILD). A high level of anti-melanoma differentiation-associated gene 5 antibodies (anti-MDA5 Ab) before treatment is associated with RP-ILD development, a poor treatment response, and poor survival. The prognosis of CADM patients remains poor due to ILD even with combined intensive immunosuppressive therapy. Recently, several additional therapies, including tofacitinib (TOF) and plasma exchange (PE) therapy, have been reported to be effective. We herein report a case of CADM-ILD with a high level of anti-MDA5 Ab that was refractory to combined intensive immunosuppressive therapy including TOF, but successfully treated with PE. The following are possible reasons why TOF was ineffective: 1) cytokines that were not suppressed by TOF played an important role in RP-ILD; 2) TOF was administered later than previously reported; and 3) TOF did not suppress pathological substances such as antibodies. On the other hand, PE removes cytokines and various pathological substances. Therefore, PE may be a more reasonable additional therapy for intractable CADM-ILD.

Overexpression of the GR Riborepressor LncRNA GAS5 Results in Poor Treatment Response and Early Relapse in Childhood B-ALL

Glucocorticoids (GCs) remain the cornerstone of childhood acute lymphoblastic leukemia (chALL) therapy, exerting their cytotoxic effects through binding and activating of the glucocorticoid receptor (GR). GAS5 lncRNA acts as a potent riborepressor of GR transcriptional activity, and thus targeting GAS5 in GC-treated chALL could provide further insights into GC resistance and support personalized treatment decisions. Herein, to study the clinical utility of GAS5 in chALL prognosis and chemotherapy response, GAS5 expression was quantified by RT-qPCR in bone marrow samples of chB-ALL patients at diagnosis (n = 164) and at end-of-induction (n = 109), treated with ALL-BFM protocol. Patients’ relapse and death were used as clinical end-points for survival analysis. Bootstrap analysis was performed for internal validation, and decision curve analysis assessed the clinical net benefit for chALL prognosis. Our findings demonstrated the elevated GAS5 levels in blasts of chALL patients compared to controls and the significantly higher risk for short-term relapse and poor treatment outcome of patients overexpressing GAS5, independently of their clinicopathological data. The unfavorable prognostic value of GAS5 overexpression was strongly validated in the high-risk/stem-cell transplantation subgroup. Finally, multivariate models incorporating GAS5 levels resulted in superior risk stratification and clinical benefit for chALL prognostication, supporting personalized prognosis and precision medicine decisions in chALL.

Associated factors with poor treatment response to initial glucocorticoid therapy in patients with adult-onset Still’s disease

Background High-dose glucocorticoids (GC) are first-line treatment for adult onset Still’s disease (AOSD), however some of the patients remain refractory to initial GC therapy, or rapidly relapse. The aim of this study was to identify prognostic factors for poor treatment response to initial GC therapy for AOSD. Methods Data on newly-diagnosed AOSD patients were extracted from our database (n=71, mean age 51.6 years). The primary outcome was a poor treatment outcome at 4 weeks, which was defined as failure to achieve remission or relapse after achieving remission within 4 weeks, followed by administration of two or more rounds of GC pulse therapy or of any other immunosuppressive drugs. Results The initial mean dose ± standard deviation of prednisolone was 0.82 ± 0.23 mg/kg/day, and 34 (47.3%) patients received GC pulse therapy at week 0. Twenty-nine of 71 patients exhibited a poor treatment outcome at 4 weeks (40.8%). The second round of GC pulse therapy or immunosuppressive drugs was added in 17 or 24 of the 29 patients, respectively. These patients had higher baseline white blood cell (WBC) counts, serum ferritin levels, systemic feature score based on clinical symptoms (modified systemic feature score, mSFS), more hemophagocytic syndrome (HPS) over the 4 weeks, and the higher severity score based on modified Pouchot score or severity index of the Japanese Ministry of Health, Labour and Welfare, than the remaining 42 patients. Multivariable logistic regression model identified baseline WBC count as a prognostic factor for poor outcome (odds ratio per 1,000/µl increment: 1.12, 95% CI 1.04-1.29), while thrombocytopenia, hyperferritinemia, and mSFS at baseline did not achieve statistical significance. Receiver-Operating Characteristic curve analysis showed that the optimal cut-off for WBC count was 13,050/µl. The Kaplan-Meier method showed the cumulative rate of poor treatment outcome to be 60.0% in patients with WBC ≥13,050/µl and 23.5% in those with WBC <13,050/µl. Conclusions A higher WBC count but not thrombocytopenia, hyperferritinemia, and mSFS at baseline was a significant prognostic factor for poor treatment outcome at week 4 in this retrospective cohort of AOSD patients. Our findings provide important information for determining the initial treatment strategy of newly-diagnosed AOSD.

Intralesional Bleomycin for the Treatment of Resistant Palmoplantar and Periungual Warts

Introduction. Periungual, palmar, and plantar warts are difficult to treat with poor treatment response. Intralesional (IL) bleomycin has shown promising results for their treatment in a few reports. However, we need further evidence before opting it for treating difficult sites and resistant warts. Hence, we conducted this study to assess the efficacy and safety of IL bleomycin for the treatment of resistant palmoplantar and periungual warts. Methods. In this retrospective study, we included all patients who were given IL bleomycin for warts over a year. Maximum three sittings of bleomycin (1 mg/ml) were given monthly, and they were followed up for 3 months after the procedure. The response was categorized as complete, near-complete, significant, moderate, mild, and no clearance for 100%, 75–99%, 50–74%, 25–49%, 1–25%, and 0% clearance, respectively. Results. Out of 29 patients, follow-up details were available only in 19 patients (53 warts). The mean duration was 2.5 ± 1.47 years. The number of past interventions ranged from 2–4. Wart clearance after the first intervention was complete in 36.84%, near-complete in 26.31%, significant in 26.31%, and moderate in 10.53%. Wart clearance after the last intervention was complete in 89.47% and near-complete in 10.52% of patients. However, during 3 months of follow-up after the last injection, 15.78% had a recurrence. None of them had severe local and systemic side effects. Conclusions. IL bleomycin could be a better treatment option for the treatment of resistant and difficult warts. However, we observed a higher recurrence rate even in a shorter follow-up. Hence, we need further studies with larger samples.

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

Intraluminal pulmonary vein stenosis is a disease with significant morbidity and mortality, though recent progress has been made using multimodal therapy with antiproliferative agents. The aim of this study was to evaluate the association between aspiration and poor treatment response in patients with intraluminal pulmonary vein stenosis. A retrospective, single-center cohort analysis was performed of patients treated with a combination of imatinib mesylate and multimodal anatomic relief between March 2009 and November 2019. Analysis focused on 2-ventricle patients due to small numbers and clinical heterogeneity of single ventricle patients. Among the 84 patients included, 15 had single ventricle physiology and 69 had 2-ventricle physiology. Among the 2-ventricle group, multivariable analysis revealed that patients with clinical aspiration had nearly five times higher odds of poor treatment response than patients without aspiration (OR 4.85, 95% CI [1.37, 17.2], p = 0.014). Furthermore, male patients had higher odds of poor treatment response than their female counterparts (OR 3.67, 95% CI [1.04, 12.9], p = 0.043). Aspiration is a novel, potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology.

Ablation in Pancreatic Cancer: Past, Present and Future

The insidious onset and aggressive nature of pancreatic cancer contributes to the poor treatment response and high mortality of this devastating disease. While surgery, chemotherapy and radiation have contributed to improvements in overall survival, roughly 90% of those afflicted by this disease will die within 5 years of diagnosis. The developed ablative locoregional treatment modalities have demonstrated promise in terms of overall survival and quality of life. In this review, we discuss some of the recent studies demonstrating the safety and efficacy of ablative treatments in patients with locally advanced pancreatic cancer.

AB0724 CANDIDATE PREDICTIVE BIOMARKERS OF POOR TREATMENT RESPONSE IN OLIGOARTICULAR ONSET JUVENILE ARTHRITIS TO EARLY STEROID INJECTIONS

Background:Intra-articular corticosteroid injections are the first-line antirheumatic drugs of oligoarticular onset juvenile arthritis. Despite significant advances in treatment (anti-TNF, block IL6) this choice of pediatric chronic joint disease still remains relevant. Pediatric rheumatologists and to this day there are no consensus on the best modality for treatment.Objectives:The aim of this study was to search of biomarkers ineffective of early intra-articular steroid injections of oligoarticular onset juvenile arthritis.Methods:Clinical, imaging, laboratory data (blood and synovial fluid), and effect of early isolated intra-articular injections (is-IAI) of triamcinolone acetonide 92 children (89% girls) aged median (IQR) 4,2 (1,6 – 7,6) years with oligoarticular onset juvenile arthritis without extra-articular manifestations (oligo-JA) were collected retrospectively and analyzed. All children were met ILAR criteria. Triamcinolone acetonide (TA) was administered intra-articular at a dose of 20-40 mg with an injection interval of 3-6-12 months which was depended on the activity of the disease. All children were divided into two groups: active / inactive arthritis based on the effectiveness of local corticosteroid treatment. The average follow-up was 48 [38; 62] months.Results:32 children (35%; all girls) were achieved remission oligo-JA after is-IAI of TA with mean of 2 [1,75; 2] injection per joint (inactive arthritis > 24 months). The mean interval between two consecutive is-IAI was 7 [5,25; 10] months. Other children did not achieve inactive oligo-JA after is-IAI of TA with mean of 3 [2; 4] injection per joint. The mean interval between first two consecutive injection was 5,5 [4,25; 7] months and other injections - 2 [2; 3] months. All children who did not achieve remission oligo-JA for is-IAI were treated by DMARDs. Statistical analyses were performed to determine the relationships between clinical, instrumental, laboratory signs and efficacy is-IAI of TA. Measures included the number of swollen or tender joints [active joint counts]; biological inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum and synovial fluid level of interleukin 6 (IL6) and tumor necrosis factor alfa (TNF-α)]; autoimmunity [titer of antinuclear factor (ANF)] and physicians’ assessment of JIA disease activity [clinical Juvenile Arthritis Disease Activity Score including maximal 10 joints (cJADAS10)]. Efficacy is-IAI of TA was no associated significantly with number of active joint of onset oligo-JA, cJADAS10, serum level of CRP mg/ml, ESR mm/h, IL6 pg/ml and TNF-α pg/ml, titer of ANF. The mean inflamed synovial fluid of IL6 levels 2208 [710; 4564] / 3234 [1265; 16902] pg/ml and TNF-α levels 3,3 [2,5; 3,8] / 1,1 [0,6; 3,7] pg/ml at onset of inactive and active oligo-JA were not significantly differ. The analysis revealed a correlation between a short phase of beneficial effect after is-IAI of TA and risk of activity disease (with an inactive phase of arthritis less than 3 months, the risk activity was OR = 2.09, p <0.001; with an inactive phase less than 2 months - OR = 8.9, p <0.001).Conclusion:TA is an effective and safe treatment in children with oligo-JA. Research was revealed that about a third of children with oligo-JA achieved inactive arthritis of average after two intra-articular injections of TA (all girls). There are no biomarkers for prediction of poor treatment response in oligo-JA to early steroid injections. But a short phase of beneficial effect after is-IAI of TA may be sign of risk activity disease. In addition boys with oligoarticular onset juvenile arthritis may be considered like potentially ineffective for local steroid therapy.References:[1]Kozhevnikov A.N., Pozdeeva N.A., Konev M.A., Maricheva O.N., Afonichev K.A., Novik G.A. X-ray diagnosis of juvenile chronic oligoarthritis. Bulletin of Siberian Medicine. 2017; 16 (3): 224–234 DOI:10.20538/1682-0363-2017-3-224–234.Disclosure of Interests:None declared

New Predictive Biomarkers for Ovarian Cancer

Ovarian cancer is the eighth-most common cause of death among women worldwide. In the absence of distinctive symptoms in the early stages, the majority of women are diagnosed in advanced stages of the disease. Surgical debulking and systemic adjuvant chemotherapy remain the mainstays of treatment, with the development of chemoresistance in up to 75% of patients with subsequent poor treatment response and reduced survival. Therefore, there is a critical need to revisit existing, and identify potential biomarkers that could lead to the development of novel and more effective predictors for ovarian cancer diagnosis and prognosis. The capacity of these biomarkers to predict the existence, stages, and associated therapeutic efficacy of ovarian cancer would enable improvements in the early diagnosis and survival of ovarian cancer patients. This review not only highlights current evidence-based ovarian-cancer-specific prognostic and diagnostic biomarkers but also provides an update on various technologies and methods currently used to identify novel biomarkers of ovarian cancer.