Relapsing-remitting Course Research Articles

Burden, Causes, and Outcomes of Hospitalization in Patients With Giant Cell Arteritis: A US National Cohort Study.

Giant cell arteritis (GCA) has a relapsing-remitting course and is associated with a high burden of comorbidities, leading to repeated hospitalizations. This study was undertaken to investigate the burden, risk factors, causes, and outcomes of hospitalization and readmission in GCA patients in a US national cohort. Using the 2017 US National Readmission Database, we identified adults ≥50 years of age hospitalized with GCA between January and June 2017, with at least 6 months of follow-up. We estimated the burden of hospitalization including 6-month risk of readmission, total days spent in hospital, and costs, annually. We examined patient-, hospital-, and index hospitalization-related factors for 6-month readmission and total days of hospitalization using binomial logistic regression. Our study included 1,206 patients hospitalized with GCA (70% women, median age 77 years), with 13% of patients experiencing GCA-related ophthalmologic complications at index hospital admission. On follow-up, 3% died, and 34% of patients were readmitted within 6 months, primarily for infections (23%) and cardiovascular diseases (CVDs) (15%). Charlson comorbidity index (CCI) of ≥1, smoking, and obesity were associated with readmission. GCA patients spent a median of 5 days/year in hospital (interquartile range [IQR] 3-11), with those in the top quartile spending 19 days/year in hospital (IQR 14-26). GCA patients frequently experience unplanned health care utilization, with 1 in 3 patients experiencing readmission within 6 months, and 3% dying within the follow-up period. Infection and CVDs are common causes of readmission and may be related to glucocorticoid exposure. Population health management strategies are required in these vulnerable GCA patients.

Bilateral Facial Nerve Palsy as a Rare Presentation of Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE), a disease of the immune system, has a relapsing-remitting course. It is known to affect multiple organ systems of the body, including the nervous system. Cranial neuropathy, particularly facial neuropathy, is an unusual complication of SLE whose pathogenic mechanism is still not understood. Cardiac involvement, like myocarditis and papilledema, is another rare presentation of SLE. A 23-year-old male had bilateral lower motor neuron type of facial palsy which on a thorough investigation was found to be as a manifestation of SLE confirmed by antinuclear antibodies and double-stranded DNA antibody positive test. Electrocardiogram and echocardiography were suggestive of myocarditis. Fundus examination revealed Grade 2 papilledema. The patient was managed with symptomatic treatment along with corticosteroids, to which he responded gradually. Bilateral facial nerve lower motor neuron type palsy is a rare manifestation of SLE which should be diagnosed promptly and can be managed with corticosteroids. The clinician should also keep an eye on infrequent manifestations like myocarditis and papilledema.

Multiple Sclerosis: Inflammatory and Neuroglial Aspects.

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease's natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells.

Late-onset multiple sclerosis in Iran: A report on demographic and disease characteristics.

Today, it is estimated that around 5% of multiple sclerosis (MS) patients are in the late-onset category (age at disease onset ≥ 50). Diagnosis and treatment in this group could be challenging. Here, we report the latest update on the characteristics of Iranian patients with late-onset MS (LOMS). This cross-sectional study used the information provided by the nationwide MS registry of Iran (NMSRI). The registrars from 14 provinces entered data of patients with a confirmed diagnosis of MS by neurologists. Patients with disease onset at or later than 50 years of age were considered LOMS. Of 20,036 records, the late-onset category included 321 patients (1.6%). The age-standardized LOMS prevalence was around 75 per 100,000 people. 215 patients (67%) were female. Median Expanded Disability Status Scale (EDSS) was 3 (interquartile range: 1.5-5). The majority of the cases (56%) suffered from relapsing-remitting (RR) course while 20% were diagnosed with primary progressive (PP) MS. Significantly higher proportion of male sex, PPMS, and higher EDSS were seen in the late-onset group compared with early-onset and adult-onset cases (p-value < 0.05). Seventy-five (23%) patients did not receive any disease-modifying treatment. The more prominent degenerative pathology of LOMS may be the underlying mechanism of the observed differences in comparison to non-LOMS. There are substantial differences and knowledge gaps regarding LOMS which could be the subject of further research.

P104 Exploring the transcriptomic miRNA signatures of Egyptian Inflammatory Bowel Disease patients

Abstract Background Inflammatory Bowel Disease (IBD) is a chronic autoimmune gastrointestinal disease, sub-classified into Crohn’s disease (CD) and ulcerative colitis (UC). The two subclasses are characterized by a relapsing-remitting course with an increasingly high incidence and prevalence worldwide. Molecular mechanisms guarding the pathogenesis of these diseases remain, to the present day, ambiguous to researchers. MicroRNAs are 22 nucleotides long small noncoding RNAs that have been recently described as essential participants in immune cell development and the immune response to pathogens. During the past decade, genetic and epigenetic studies in IBD have been labeled as essential; since endoscopic assessment and biopsies provide limited data concerning early disease activity, factors for relapse, and response to treatment. To the best of our knowledge, IBD research has never addressed miRNA profiles in Egyptian CD and UC patients as compared to unaffected controls. Methods Therefore, this study aims to profile miRNAs in Egyptian patients suffering from UC and CD, using RNA-seq of total RNA extracted from colonoscopically obtained tissue pinch biopsies. Results The sequencing results showed that 30 miRNAs were uniquely expressed in tissue biopsies obtained from the CD patients, as compared to only 14 uniquely expressed in UC patients. Further web-based functional enrichment analysis showed that the miRNAs- in both disease groups- are mainly involved in six interlinked molecular pathways; including the JAK/STAT, WNT, PI3K/AKT, FOXO, MAPK, and NF-κB signaling pathways. One of the most interesting findings of the current study is the fact that the downregulation of the miR-204-5p in UC patients (log2 FC= 5.05)-as compared to CD patients- may be caused by the sponging effect of the MALAT1 long non-coding RNA (lncRNA); affecting related signaling pathways such as the Wnt/β-catenin signaling. This suggests an essential interplay between miRNAs and lncRNAs in shaping the molecular pathogenesis of UC vs. CD. Conclusion The results of the current study revealed explicit-previously undetermined- differences in the miRNA profiles of patients suffering from UC and CD. Such results are expected to impact the understanding of the difference in the molecular pathogenesis of IBD subtypes affecting patients’ response to treatment.

NEW ONSET OF INFLAMMATORY BOWEL DISEASE IN A PATIENT WITH EOSINOPHILIC ESOPHAGITIS: 10-YEAR CONSTELLATION OF AUTOIMMUNE GASTROINTESTINAL DISORDERS

Abstract INTRODUCTION Inflammatory bowel disease (IBD) is well known for concurrent immune-mediated disorders such as eosinophilic esophagitis, psoriasis, and rheumatoid arthritis.(1) For the past two decades, we are seeing an increased occurrence of eosinophilic esophagitis (EoE) in long standing IBD patients (2) (3) (4), but the question has arisen as to new onset IBD in chronic EoE patients. One study that involved 4814 patients demonstrated that the prevalence of eosinophilic esophagitis in IBD was 5 times higher compared to general population and EoE in IBD is 2 times higher than expected.(5) Multiple factors have been identified that may trigger the exact inflammatory response in IBD and EoE patients. Both diseases are associated with an exaggerated response to interleukins, especially IL-13 sharing cytokines and helper T cell mediated pathophysiology that is linked to disruption of the gastrointestinal tract barrier. (6) (7) CASE DESCRIPTION A 25-year-old healthy male presented back in 2012 with a history of three months of worsening dysphagia that resulted in 15-lb weight loss. Upper endoscopy showed esophagus with small caliber lumen, linear furrows, and thin concentric rings with microscopic evidence of eosinophilic esophagitis. Over the years he developed multiple episodes of persistent dysphagia, several endoscopies demonstrated pangastritis and duodenitis with a new pyloric and duodenal bulb stricture. Due to his remitting-relapsing course despite long-term medical treatment, patient underwent additional workup including an abdominal CT and upper endoscopy that showed worsening of the pyloric stricture that improved after balloon dilation. In 2020, the patient developed diarrhea, rectal bleeding, generalized abdominal pain and 21 lb weight loss despite medical treatment. Colonoscopy showed multiple erosions in the ileum and rectum not seen on previous studies. The biopsy indicated ulcerated mucosa with necrosis in the ileum and rectal area with mixed inflammatory infiltration with the presence of a non-caseating granuloma consistent with Chron’s disease. DISCUSSION It is unclear which disease manifest first or if it is a clustering and co-occurrence of diseases. The fact that both diseases share the same pathogenetic mechanism with overexpression of mucosal interleukin-13 (IL-13) causing loss of functionality of the gastrointestinal barrier could explain symptoms observed on both. Many studies demonstrated that IBD was diagnosed before EoE in almost 2/3 of the cases. The association of EoE-IBD is found significantly more in males and occurs at a younger age compared to IBD alone. Further studies will be needed in order to confirm the co-occurrence of diseases because of the increased risk of IBD-related complications and higher chance of requiring systemic corticosteroids and anti-TNF therapy in patients who have coexisting EoE-IBD.

Связь полиморфизма гена KIF1B (rs10492972) с клиническим фенотипом и ответом на лечение при рассеянном склерозе на примере популяции Томской области

The relationship was studied between the rs10492972 polymorphism of the KIF1B gene and the risk of multiple sclerosis (MS), clinical phenotype of disease and response to disease modifying drugs (DMD) treatment in the patient’s population of Tomsk region. The study group included 152 patients; the control group consisted of 689 healthy volunteers. The results showed the impact of the risk allele C of KIF1B (rs10492972) gene polymorphism on the progressive forms of MS development (especially on primary progressive MS), and the relationship of the T allele with an early onset and relapsing-remitting course. The risk allele C also showed an association with the lack of response to second-line DMD therapy. The results of our study confirmed the association of the KIF1B (rs10492972) gene’s allele C with an unfavorable course of MS.

Combination therapy in inflammatory bowel disease: Current evidence and perspectives.

Inflammatory Bowel Diseases (IBD) are chronic nonspecific intestinal inflammatory diseases with a relapsing-remitting course, including Ulcerative Colitis (UC) and Crohn's Disease (CD). Combination therapy has been proposed as a strategy to enhance treatment efficacy in IBD. The aim of this study is to summarize current evidence and perspectives on combination therapies in IBD. Electronic databases such as PubMed, Ovid Embase, Medline, and Cochrane CENTRAL were searched to identify relevant studies. Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy in inducing and maintaining remission in IBD. Data on the combination of other biological agents such as adalimumab, vedolizumab, ustekinumab, and immunosuppressors is lacking or showed conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis (ASUC). Dual Targeted Therapy, which is the combination of two biological agents and/or small molecules, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Some safety concerns such as adverse events (serious and opportunistic infections) and malignancies (lymphoma and nonmelanoma skin cancer) were raised in combination therapies. Combination therapies seem to be effective in some IBD patients such as refractory IBD patients or patients with extraintestinal manifestations, but it might be associated with an increased risk of adverse events and malignancies.

Spasticity treatment patterns among people with multiple sclerosis: a Swedish cohort study

BackgroundSpasticity is common among people with multiple sclerosis (MS), but there are few studies of spasticity treatment patterns. We aim to describe associations with spasticity treatment measured primarily by oral...

Cognate microglia-T cell interactions shape the functional regulatory T cell pool in experimental autoimmune encephalomyelitis pathology.

Microglia, the parenchymal brain macrophages of the central nervous system, have emerged as critical players in brain development and homeostasis. The immune functions of these cells, however, remain less well defined. We investigated contributions of microglia in a relapsing-remitting multiple sclerosis paradigm, experimental autoimmune encephalitis in C57BL/6 x SJL F1 mice. Fate mapping-assisted translatome profiling during the relapsing-remitting disease course revealed the potential of microglia to interact with T cells through antigen presentation, costimulation and coinhibition. Abundant microglia-T cell aggregates, as observed by histology and flow cytometry, supported the idea of functional interactions of microglia and T cells during remission, with a bias towards regulatory T cells. Finally, microglia-restricted interferon-γ receptor and major histocompatibility complex mutagenesis significantly affected the functionality of the regulatory T cell compartment in the diseased central nervous system and remission. Collectively, our data establish critical non-redundant cognate and cytokine-mediated interactions of microglia with CD4+ T cells during autoimmune neuroinflammation.

Transvenous Embolization for Cerebrospinal Fluid-Venous Fistula. A Case Series from a Single Community-Academic Center

Transvenous embolization is a new treatment for spinal cerebrospinal fluid (CSF)-venous fistula, with only 1 reported large case series from the center that invented this technique. We report the clinical and radiographic data of 5 consecutive patients who were diagnosed with CSF-venous fistula at a single community-academic medical center and were treated with transvenous embolization. All patients provided consent for this report. Institutional review board approval was not required because of the retrospective nature of this study describing standards of care. Five patients, 3 men and 2 women, with a median age of 57 years, were diagnosed between March and December 2021with spontaneous intracranial hypotension (SIH) as a result of CSF-venous fistula. Two patients were originally referred for middle meningeal artery embolization for chronic subdural hematoma. All fistulae were in the thoracic spine at a single level in 3 patients, 2 levels in 1 patient, and multiple levels in 1 patient. Transvenous embolization was technically successful in all cases, with no significant complications. Four patients (80%) had complete or near-complete resolution of clinical symptoms and returned to baseline function and employment status. One patient (20%) has had a remitting relapsing course. Posttreatment brain magnetic resonance imaging showed resolution of spontaneous intracranial hypotension findings in 4 patients (80%) and minimal changes in 1 patient (20%), who had significant clinical improvement. Transvenous embolization for the treatment of CSF-venous fistula is feasible and seems effective in the short-term. The results reported by the previous case series can be reproduced in other centers with available expertise and adherence to published diagnostic and treatment protocols.

Neutrophil‐to‐Lymphocyte and Platelet‐to-Lymphocyte Ratio in Children with Multiple Sclerosis

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory condition that affects the central nervous system. MS in children often manifests with a relapsing-remitting disease course. Recently, blood neutrophil-to-lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have proposed as a potentially useful markers of clinical outcome in autoimmune/inflamatory diseases. The aim of this study was to clarify the association of NLR and PLR in children with MS. Materials and Methods: Ten patients with MS and 11 healthy controls were enrolled in the study. NLR and PLR were calculated using complete blood count data. Results: The serum NLR and PLR level in relaps period with MS patients were significantly higher than those of remission period with MS patients and controls (P &lt; 0.001). Conclusions: To our knowledge, this is the first study which investigated the role of NLR and PLR as inflammatory biomarkers in patients with MS. Our results demonstrate that NLR and PLR levels are higher in patients with relaps period compared with controls and remission period. NLR and PLR, a simple and easily obtainable parameters, can be used to identify relaps period in MS.

PRESENTATION OF ACUTE CEREBROVASCULAR ACCIDENT IN A YOUNG ADULT WITH THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

PRESENTATION OF ACUTE CEREBROVASCULAR ACCIDENT IN A YOUNG ADULT WITH THROMBOTIC THROMBOCYTOPENIA PURPURA (TTP)

Machine learning techniques for prediction of multiple sclerosis progression

Patients afflicted by multiple sclerosis experience a relapsing-remitting course in about 85% of the cases. Furthermore, after a 10/15-year period their situation tends to worse, resulting in what is considered the second phase of multiple sclerosis. While treatments are now available to reduce the symptoms and slow down the progression of the disease, the administration of drugs must be adapted to the course of the disease, and predicting relapsing periods and the worsening of the symptoms can greatly improve the outcome of the treatment. For this reason, indicators such as the patient-reported outcome measures (PROMs) have been largely used to support early diagnosis and prediction of future relapsing periods in patients affected by multiple sclerosis. However, such indicators are insufficient, as the prediction they provide is often not accurate enough. In this paper, machine learning techniques have been applied to data obtained from clinical trial, in order to improve the prediction capabilities and provide doctors with an additional instrument to evaluate the clinical situation of patients. After the application of correlation indicators and the use of principal component analysis for the reduction of the dimensionality of the feature space, classification algorithms have been applied and compared, in order to identify the best suiting one for our purposes. After the application of re-balance algorithms, the accuracy of the machine learning-based prediction system reaches 79%, demonstrating the capability of the framework to correctly predict future progression of disability.

Ameliorative effects of epigallocatechin-3-gallate nanoparticles on 2,4-dinitrochlorobenzene induced atopic dermatitis: A potential mechanism of inflammation-related necroptosis.

Atopic dermatitis (AD) is a common autoimmune and chronic inflammatory cutaneous disease with a relapsing-remitting course. Necroptosis is a regulated necrotic cell death mediated by receptor-interacting protein 1 (RIP1), receptor-interacting protein 3 (RIP3), and mixed lineage kinase domain-like pseudokinase (MLKL), which is activated by tumor necrosis factor-α (TNF-α). However, the mechanism and the role of necroptosis have not been delineated in AD progression. (-)-Epigallocatechin-3-gallate (EGCG), the main biological activity of tea catechin, is well known for its beneficial effects in the treatment of skin diseases. Here, PEG-PLGA-EGCG nanoparticles (EGCG-NPs) were formulated to investigate the bioavailability of EGCG to rescue cellular injury following the inhibition of necroptosis after AD. 2,4-dinitrochlorobenzene (DNCB) was used to establish AD mouse models. As expected, topically applied EGCG-NPs elicited a significant amelioration of AD symptoms in skin lesions, including reductions in the ear and skin thickness, dermatitis score, and scratching behavior, which was accompanied by redox homeostasis restored early in the experiment. In addition, EGCG-NPs significantly decreased the expression of inflammatory cytokines like TNF-α, interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-17A (IL-17A) in a time-dependent manner than those of in AD group. As a result, the overexpression of RIP1, RIP3, and MLKL in the entire epidermis layers was dramatically blocked by EGCG-NPs, as well as the expression ofphosphorylated p38 (p-p38), extracellular signal-regulated kinase 1 (ERK1), and extracellular signal-regulated kinase 2 (ERK2). These findings promote that EGCG-NPs formulation represents a promising drug-delivery strategy for the treatment of AD by maintaining the balance of Th1/Th2 inflammation response and targeting necroptosis.

Divergent complement system activation in two clinically distinct murine models of multiple sclerosis.

Multiple sclerosis (MS) is a neurological disease featuring neuroinflammation and neurodegeneration in young adults. So far, most research has focused on the peripheral immune system, which appears to be the driver of acute relapses. Concurrently, the mechanisms underlying neurodegeneration in the progressive forms of the disease remain unclear. The complement system, a molecular component of the innate immunity, has been recently implicated in several neurological disorders, including MS. However, it is still unknown if the complement proteins detected in the central nervous system (CNS) are actively involved in perpetuating chronic inflammation and neurodegeneration. To address this knowledge gap, we compared two clinically distinct mouse models of MS: 1) proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis (rEAE) resembling a relapsing-remitting disease course, and 2) Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) resembling a progressive disease. Real-time PCR was performed in the spinal cord of rEAE mice, TMEV-IDD mice and age-matched sham controls to quantify gene expression for a broad range of complement components. In both experimental models, we found significantly increased expression of complement factors, such as C1q, C3, CfB, and C3aR. We showed that the complement system, specifically the classical complement pathway, was associated with TMEV-IDD pathogenesis, as the expression of C1q, C3 and C3aR1 were all significantly correlated to a worse disease outcome (all P≤0.0168). In line with this finding, C1q and C3 deposition was observed in the spinal cord of TMEV-IDD mice. Furthermore, C1q deposition was detected in spinal cord regions characterized by inflammation, demyelination, and axonal damage. Conversely, activation of the classical complement cascade seemed to result in protection from rEAE (C1q: P=0.0307). Interestingly, the alternative pathway related to a worse disease outcome in rEAE (CFb: P=0.0006). Overall, these results indicate potential divergent roles for the complement system in MS. The chronic-progressive disease form is more reliant on the activation of the classic complement pathway, while protecting from acute relapses. Conversely, relapsing MS appears more likely affected by the alternative pathway. Understanding the functions of the complement system in MS is critical and can lead to better, more targeted therapies in the future.

Profile and Outcome of Children with Opsoclonus Myoclonus Ataxia: A Tertiary Care Hospital Experience from India

AbstractOpsoclonus myoclonus ataxia syndrome (OMAS) is a rare but treatable, often paraneoplastic neuroimmunologic condition. This is a retrospective chart review of 8 patients diagnosed in the past 11 years at a tertiary care hospital. The mean age of children with OMAS was 21.2 ± 8 months. There was a female preponderance (62.5%). Median symptom duration was 24.5 days (interquartile range [IQR] 12.7; 97.5). All patients had ataxia and irritability; 6 had opsoclonus.An underlying neurogenic tumor was identified in 87.5% (⅞) of the patients by computed tomography (CT)/magnetic resonance imaging. Neuroblastoma was detected in ⅘ with normal 24-hour urinary vanillylmandelic acid and 2 had negative metaiodobenzylguanidine scan.All patients received adrenocorticotropic hormone/steroids for a median of 9.5 months (IQR 5.3; 13.5) with clonazepam. Five received intravenous immunoglobulin (IVIG), including repeated cycles in ⅘. Two received rituximab. One child with relapsing-remitting course received pulse dexamethasone and cyclophosphamide, resulting in improvement. Clonazepam restored ambulation in one with delayed diagnosis and failure of response to steroids. Six patients underwent tumor resection and four needed chemotherapies.Median follow-up was 15 months (IQR 10.7; 23.2). Mean OMAS-severity scale reduced from 10 to 1.4 in the IVIG group and 10.6 to 5.3 in those who did not receive IVIG. Cognitive delay and behavioral issues were seen in 100% treated with steroids only; 50 and 25%, respectively, treated with multimodal immunotherapy. Five had relapses, one with tumor recurrence.Thorax and abdomen CT scan was found to be a sensitive tool for tumor detection. Better motor and cognitive behavioral outcome were noted in patients who received adjunctive IVIG.Future studies on optimum investigation and treatment protocol in various resource settings are needed.

Constrained multiple instance learning for ulcerative colitis prediction using histological images

Background and Objective: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) affecting the colon and the rectum characterized by a remitting-relapsing course. To detect mucosal inflammation associated with UC, histology is considered the most stringent criteria. In turn, histologic remission (HR) correlates with improved clinical outcomes and has been recently recognized as a desirable treatment target. The leading biomarker for assessing histologic remission is the presence or absence of neutrophils. Therefore, the finding of this cell in specific colon structures indicates that the patient has UC activity. However, no previous studies based on deep learning have been developed to identify UC based on neutrophils detection using whole-slide images (WSI).Methods: The methodological core of this work is a novel multiple instance learning (MIL) framework with location constraints able to determine the presence of UC activity using WSI. In particular, we put forward an effective way to introduce constraints about positive instances to effectively explore additional weakly supervised information that is easy to obtain and enjoy a significant boost to the learning process. In addition, we propose a new weighted embedding to enlarge the relevance of the positive instances.Results: Extensive experiments on a multi-center dataset of colon and rectum WSIs, PICASSO-MIL, demonstrate that using the location information we can improve considerably the results at WSI-level. In comparison with prior MIL settings, our method allows for 10% improvements in bag-level accuracy.Conclusion: Our model, which introduces a new form of constraints, surpass the results achieved from current state-of-the-art methods that focus on the MIL paradigm. Our method can be applied to other histological concerns where the morphological features determining a positive WSI are tiny and similar to others in the image.

P1145: OUTCOMES AND TREATMENT PATTERNS AFTER FIRST RELAPSE IN PATIENTS WITH WALDENSTRÖM MACROGLOBULINEMIA

Background: Waldenström macroglobulinemia (WM) is a rare, B cell lymphoma, with a relapsing-remitting course. Despite expansion of therapeutic options, WM remains incurable. Data on outcomes of patients (pts) after first relapse or primary refractory disease are sparse. Frequently used salvage therapies include chemoimmunotherapy (CIT), proteasome inhibitor (PI) based regimens and Bruton tyrosine kinase inhibitors (BTKi). Aims: Analyze the outcomes of pts with WM after initial relapse and/or refractory (RR) disease and the impact of the type of therapy used in the second line setting. Methods: ecords of pts with WM seen at Mayo Clinic between 2000 and 2021 were reviewed. Pts with RRWM requiring second line therapy were included in the primary analysis. Response rates were assessed per the modified IWWM-6 criteria. All time to event analyses, barring progression free survival 2 (PFS2), were calculated from the start of the second line treatment, using the Kaplan Meier method. Pts were grouped based on sequence of therapy and response to frontline treatment for additional subgroup analysis. Results: Records of 220 pts with WM were reviewed; 92 had RRWM and were treated with a second line therapy. For the entire cohort, frontline regimens included dexamethasone, rituximab, cyclophosphamide (DRC) (n=93, 42%), bendamustine rituximab (BR) (n=71, 32%), bortezomib, dexamethasone, rituximab (BDR) (n=33, 15%), BTKi (n=20, 9%), and other (n=3, 1%). Median follow-up of RRWM cohort from second line therapy was 5.1 years (95% CI: 4.5-6.3). Pts with RRWM received the following therapies at first relapse: BR (n=24, 26%), BTKi (n=24, 26%), PI (n=17, 19%), DRC (n=6, 7%), autologous transplant (n=4, 4%), and other (n=17, 18%). Following second-line treatment, the overall response rate and major response rate (MRR) were 72% and 67% (CR=5%, VGPR=15%, and PR=47%), respectively. The median PFS was 2.7 years (CI: 1.7-4). 2-year overall survival (OS) rate was 87%. The median PFS2 from frontline therapy was 7.03 years (CI: 5.5-9.8). Baseline characteristics were similar for subgroups in all the following subgroup analyses. With first-line therapy, 54% of pts (n=50) achieved MRR vs. 46% (n=42) who did not. The former group had similar progression-free survival (PFS) rates as well as overall survival (OS) rates and response rates (MRR and ORR) to the second-line treatment compared to their counterparts who did not achieve MRR with the frontline regimen (Table). Thiry one pts received BTKi as either first or second line and 61 pts received no BTKi in either line. As expected, the BTKi group was enriched for pts with MYD88L265P mutation (n=29, 94%) vs 49% (n=30) in the no BTKi group, p<0.001. The outcomes between the 2 groups were comparable (Table). The group that received frontline BTKi followed by CIT/PI based Rx as second line (n=7) was compared to that receiving frontline CIT/PI based Rx followed by BTKi (n=21). The outcomes were similar (Table). Image:Summary/Conclusion: Currently available second line therapies are effective in RRWM. Achieving MRR with frontline regimen does not significantly affect overall outcomes with the second-line therapy. Although follow up is short, using a BTKi as the first- or second-line therapy appears to show comparable outcomes after second line treatment as compared to not treating with a BTKi in the upfront setting or in second-line setting. Similarly, using frontline BTKi followed by CIT as second line shares similar outcomes to treating with CIT initially followed by a BTKi. These findings require confirmation in prospective studies.

Usefulness and prognostic value of diagnostic tests in patients with possible chronic inflammatory demyelinating polyradiculoneuropathy.

Recent guidelines define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and possible CIDP. The aims of our study were to evaluate the value of diagnostic tests to support the diagnosis of CIDP in patients with possible CIDP and to identify prognostic factors of therapeutic success. We conducted an observational retrospective two-center study between 2014 and 2019. We selected patients with a clinical presentation suggesting CIDP, but whose electrodiagnostic (EDX) test results did not meet the EFNS/PNS 2021 criteria. We analyzed epidemiologic and clinical features, axonal loss on EDX, cerebrospinal fluid (CSF), somatosensory evoked potentials (SSEPs), plexus magnetic resonance imaging (MRI), nerve biopsy, and therapeutic response. We selected 75 patients, among whom 30 (40%) responded to treatment. The positivity rates of CSF analysis, MRI and SSEPs were not influenced by the clinical presentation or by the delay between symptom onset and medical assessment. A high protein level in CSF, female gender, and a relapsing-remitting course predicted the therapeutic response. It is important to properly diagnose suspected CIDP not meeting EFNS/PNS 2021 EDX criteria by using supportive criteria. Specific epidemiological factors and a raised CSF protein level predict a response to treatment. Further prospective studies are needed to improve diagnosis and the prognostic value of diagnostic tests in CIDP.