ECG Changes Through Immunosuppressive Therapy Indicate Cardiac Abnormality in Anti-MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a dermatomyositis (DM)-specific antibody, is strongly associated with interstitial lung disease (ILD). Patients with idiopathic inflammatory myopathy (IIM) who are anti-MDA5 antibody positive [anti-MDA5 (+)] often experience chest symptoms during the active disease phase. These symptoms are primarily explained by respiratory failure; nevertheless, cardiac involvement can also be symptomatic. Thus, the aim of this study was to investigate cardiac involvement in anti-MDA5 (+) DM. A total of 63 patients with IIM who underwent electrocardiography (ECG) and ultrasound cardiography (UCG) during the active disease phase from 2016 to 2021 [anti-MDA5 (+) group, n = 21; anti-MDA5-negative (-) group, n = 42] were enrolled in the study, and their clinical charts were retrospectively reviewed. The ECG and UCG findings were compared between the anti-MDA5 (+) and anti-MDA5 (-) groups. All anti-MDA5 (+) patients had DM with ILD. The anti-MDA5 (+) group showed more frequent skin ulcerations and lower levels of leukocytes, muscle enzymes, and electrolytes (Na, K, Cl, and Ca) than the anti-MDA5 (-) group. According to the ECG findings obtained during the active disease phase, the T wave amplitudes were significantly lower for the anti-MDA5 (+) group than for the anti-MDA5 (-) group (I, II, and V4–6 lead; p < 0.01; aVF and V3, p < 0.05). However, the lower amplitudes were restored during the remission phase. Except for the E wave, A wave and Sep e’, the UCG results showed no significant differences between the groups. Four patients with anti-MDA5 (+) DM had many leads with lower T wave and cardiac abnormalities (heart failure, diastolic dysfunction, myocarditis) on and after admission. Though anti-MDA5 (+) patients clinically improved after immunosuppressive therapy, some of their ECG findings did not fully recover in remission phase. In conclusion, anti-MDA5 (+) DM appears to show cardiac involvement (electrical activity and function) during the active phase. Further studies are necessary to clarify the actual cardiac condition and mechanism of these findings in patients with anti-MDA5 (+) DM.

Treatment Patterns and Economic Burden Among Elderly Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents: A SEER-Medicare Analysis

Introduction: Previously, we assessed the economic burden of newly diagnosed acute myeloid leukemia (AML) among Medicare patients and found that the economic burden of relapse is high, at approximately 1.2 and 1.6 times the monthly per-patient costs associated with early and late post-remission therapy, respectively (Tabah A, et al. Blood 2020:136(suppl 1):45). A notably high proportion of patients (55%) received ≥ 1 cycle of a hypomethylating agent (HMA). Therefore, the objective of this study was to assess the economic burden of AML among a subgroup of elderly patients who received only HMA monotherapy during induction and then achieved disease remission. Healthcare resource utilization (HCRU) and costs associated with various phases (ie, induction, post-remission therapy, and post-relapse) were assessed. Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, which comprised Medicare claims (parts A, B, and D from 2007 through 2016) and the US National Cancer Institute's SEER database (cancer diagnoses from 2007 to 2015). Included patients had an AML diagnosis in the SEER registry, were ≥ 65 years of age at the AML diagnosis date, had initiated HMA (and no other active treatment) in the outpatient (OP) setting during the first induction cycle post-AML diagnosis, and had an International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code for AML remission following the initiation of induction therapy. Patients were excluded if they had another blood malignancy (including a history of myelodysplastic syndromes), had received hematopoietic stem cell transplantation, or were enrolled in a clinical trial. The induction therapy period was defined as the first initiation of HMA post diagnosis (index date) to the end of the cycle during which a patient had a code for AML remission. The 6-month period prior to the index date was defined as the baseline period. The post-remission phase ended at the earliest of relapse or end of follow-up (ie, death, end of eligibility, or end of available data [December 31, 2016]). The post-relapse phase was from the date of first AML relapse ICD-9/10 code after remission to the end of follow-up. Patient characteristics during the baseline period were summarized descriptively. HCRU and costs (adjusted to 2019 US dollars) associated with induction and post-remission therapy were assessed during days that were part of a treatment cycle. The average per-patient monthly HCRU and costs were reported for the induction, post-remission, and post-relapse phases. Results: A total of 71 patients with newly diagnosed AML (azacitidine: n = 31; decitabine: n = 40) received HMA induction therapy and achieved remission. The median age at AML diagnosis was 78.8 years, 50.7% of patients were male, and 85.9% were White. The mean ± standard deviation (median) time from index date to the end of follow-up was 16.0 ± 12.3 (14.0) months. A total of 63.4% of patients (n = 45) received post-remission therapy. Among all patients, 43.7% relapsed and 85.9% died by the end of follow-up. OP visits were the most common type of visit across all phases with 95.6% of patients having ≥ 1 OP visit during post-remission therapy and 83.9% during the post-relapse phase. Inpatient (IP) visits were highest in the post-relapse phase with 77.4% of patients having ≥ 1 IP visit. The monthly mean per-patient healthcare costs were highest for the post-relapse phase, followed by post-remission therapy, and induction (Table). Costs associated with the OP setting were the greatest contributor to the induction costs (48.9%) while costs associated with the IP setting were the drivers of the costs in the post-remission therapy (56.2%) and post-relapse (72.8%) phases. Conclusions: The economic burden of AML treated with HMA induction therapy was highest in the post-relapse phase, at approximately 1.7 and 1.6 times the monthly per-patient costs during the induction and post-remission therapy phases, respectively. In addition, IP costs made up nearly two-thirds of total monthly per-patient costs in the post-relapse phase, up from approximately 44% and 56% of the induction and post-remission therapy phases, respectively. Treatment options that extend the post-remission phase would reduce the high economic burden associated with AML relapse. Figure 1 Figure 1. Disclosures Brunner: Celgene, Forty Seven Inc, Jazz: Other: Advisory Board; Novartis, Celgene, Takeda, AstraZeneca: Research Funding. Huggar: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Copher: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Zhou: Sanofi: Research Funding; Analysis Group: Current Employment, Other: Employee of Analysis Group which received consulting fees for this project . Zichlin: Analysis Group, Inc.: Consultancy, Current Employment; GlaxoSmithKline: Research Funding. Anderson: Analysis Group, which received consultancy fees from GSK: Consultancy, Current Employment. Downes: nalysis Group (employment), Bristol Myers Squibb (consultancy): Consultancy, Current Employment. McBride: BMS: Current Employment.

Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis

<b><i>Introduction:</i></b> Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. <b><i>Methods:</i></b> Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. <b><i>Results:</i></b> The microarray results indicated significantly higher expression levels of cancer-related genes <i>PIM2</i> and <i>SPI1</i> in the active group than in the remission and control groups (<i>p</i> &#x3c; 0.05). Real-time PCR confirmed that <i>PIM2</i> and <i>SPI1</i> expression levels were significantly higher, whereas <i>TP53</i> and <i>APC</i> expression levels were significantly lower, in the active-phase group than in the remission and control groups (<i>p</i> &#x3c; 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. <b><i>Conclusions:</i></b> Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.

Can the AHCL System Be Used in T1D Patients with Borderline TDDI? A Case Report

(1) Background: Intensive insulin therapy using continuous subcutaneous insulin infusion (CSII) with continuous real-time glucose monitoring (rt CGM) is the best option for patients with T1D. The recent introduction of a technology called Advanced Hybrid Closed Loop (AHCL) represents a new era in the treatment of type 1 diabetes, the next step towards better care, as well as improving the effectiveness and safety of therapy. The aim is to present the case of a T1D patient with a borderline total daily dose of insulin being treated with the Medtronic AHCL system in automatic mode. (2) Materials and Methods: A 9-year-old boy, from October 2020, with type 1 diabetes in remission was connected to the Minimed™ 780G (AHCL) system in accordance with the manufacturer’s recommendations (daily insulin dose > 8 units, age > 7). Records of the patient’s history were collected from visits to The Department of Children’s Diabetology, as well as from the Medtronic CareLink™ software and the DPV SWEET program from October 2020 to April 2021. (3) Results: The patient’s total daily insulin requirement decreased in the first 6 weeks after the AHCL was connected, which may reflect the remission phase (tight glycemic control with a healthy lifestyle). The lowest daily insulin requirement of 5.7 units was also recorded. In a three-month follow-up of the patient treated with AHCL, it was found that for almost 38% of the days the insulin dose was less than 8 IU. (4) Conclusions: The AHCL system allows safe and effective insulin therapy in automatic mode, as well as in patients with a lower daily insulin requirement. The AHCL system should be considered a good therapeutic option for patients from the onset of T1D, as well in the remission phase.

Significance of the Diagnosis of Executive Functions in Patients with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a progressive chronic disease of the Central Nervous System (CNS). Cognitive decline occurs rather rarely in relapsing–remitting multiple sclerosis (RRMS) compared to other types. The present study aimed to assess executive functions (EF) in relation to clinical and demographic variables in patients with RRMS. The study involved 22 individuals with RRMS (aged 23 to 49 years) and 22 matching controls. All the individuals with RRMS were in the remission phase. The assessments were carried out using MoCA, BDI-II, Halstead Category Test, Porteus Maze Test, verbal fluency tasks and Stroop Colour-Word Interference Test. The findings show that the two groups differed significantly in all the tests. All patients with RRMS in the remission phase presented at least one cognitive deficit, observed in general cognitive functioning, abstract reasoning or other executive functions, i.e., fluency, interference suppression, planning, or ability to modify activity in response to feedback. The deficits in most cases (except for those measured with the MoCA, Category Tests and phonemic fluency), are not related to intensity of depression and duration of the disease. Findings suggest that the diagnostic process in the case of patients with RRMS may include psychological assessment focusing on potentially existing cognitive, mainly executive, deficits and their severity.

Dramatic increase in lever-pressing activity in rats after training on the progressive ratio schedule of cocaine self-administration

Transition from the highest rate of lever-pressing activity during the unloading (extinction) phase of a cocaine self-administration session to an extremely low activity rate during the remission phase is in many cases gradual. This makes it difficult to assess the duration of the unloading phase after a fixed ratio 1 (FR1) or breakpoint after a progressive-ratio (PR) self-administration session. In addition, 3–5 days of training under the PR schedule results in a dramatic and persistent increase in the rate of presses during PR sessions and in the unloading phase following FR1 self-administration sessions. The goals of this study were to find the definition of the last press demarcating the border between the unloading and remission phases of the session and to determine if this border was also affected by PR training. Rats were trained to self-administer cocaine under the FR1 schedule and then under the PR schedule of drug delivery. Distributions of inter-press intervals (IPIs) during the unloading phase in sessions before and after PR training were compared. It was found that the distribution of cocaine-induced IPIs during the unloading phase was lognormal, bimodal, and independent of previously injected cocaine unit doses. The first mode represented intervals within the short bouts of stereotypic presses and the second mode represented intervals between bouts. The two modes were approximately 0.7 s and 21 s during unloading prior to and 0.6 s and 1.5 s after PR self-administration training. The total number of presses per unloading phase increased eightfold. When the FR1 schedule was restored, the intervals between bouts remained very short for at least 7–10 days and only then started a gradual increase towards baseline levels. The last unloading press was defined as the press followed by the IPI longer than the defined criterion. PR training resulted in a substantial and long-lasting increase in lever-pressing activity during unloading. The duration of the unloading phase did not depend on the rate of lever-pressing activity.

Physical, Emotional, Medical, and Socioeconomic Status of Patients With NMOSD: A Cross-Sectional Survey of 123 Cases From a Single Center in North China

Objective: This study aimed to assess the physical, emotional, medical, and socioeconomic conditions of patients with neuromyelitis optica spectrum disorder (NMOSD) in North China.Methods: A cross-sectional survey of patients with NMOSD was performed, based on an established questionnaire from the Multiple Sclerosis Patient Survival Report 2018. Logistic regression analysis was conducted to define the significant determinants of certain physical or emotional characteristics of patients. A total of 123 patients were included.Results: A total of 63.4% of participants were initially diagnosed with conditions other than NMOSD, with a median delay of 6 months for accurate diagnosis. An aggregate of 72.2% of patients had one or more relapses, corresponding to an annual relapse rate of 0.8. Paresthesia was the most frequent physical symptom among patients both at disease onset (53.7%) and throughout the duration of the disease (86.2%). Onset in elderly (&gt;50 years) patients was associated with an annual Expanded Disability Status Scale increase ≥1, compared with onset in younger (&lt;30 years) patients (P = 0.001, OR = 7.83). A total of 76.4% of patients had received attack-prevention treatments in the remission phase, and 31.7 and 10.6% of patients had ever been administered rituximab and traditional Chinese medicine, respectively. Additionally, 63.4 and 43.1% of patients reported participating in few or no social activities and being out of work because of the disease. To be noted, 76.4% of patients reported suffering from negative emotions, with the most frequent being worry (60.2%), with 20.3% of patients experiencing suicidal thoughts. The inability to work and participating in few or no social activities due to NMOSD were two determinants of experiencing negative emotions (Pwork = 0.03, ORwork = 3.34; Psocialactivities = 0.02, ORsocialactivities = 3.19).Conclusion: This study reported patient perspectives on NMOSD in North China, whereby demonstrating that the inability to work and participating in few or no social activities due to NMOSD rather than the physical impairment caused by the disease, was directly associated with patients experiencing negative emotions. This insight offers potential ways to manage patients' negative emotions by enhancing family and social support and facilitating active employment.