Autoimmune Diagnosis Research Articles

IoMT-Based Automated Diagnosis of Autoimmune Diseases Using MultiStage Classification Scheme for Sustainable Smart Cities

The resolution of complex medical diagnoses using pattern recognition requires an artificial neural network-based expert system to automate autoimmune disease diagnosis in blood samples. This process is done using image-based computer-aided diagnosis (CAD) to reduce errors in the diagnosis process. This paper describes a Multistage Classification Scheme (MSCS), which uses antinuclear antibody (ANA) tests to identify and classify the existence of autoantibodies in the blood serum that bind to antigens found in the nuclei of mammalian cells. The MSCS classified HEp-2 cells into three stages by using Binary Tree (BT), Artificial Neural Network (ANN), and Support Vector Machine (SVM) as basic blocks. The Indirect Immunofluorescence (IIF) technique is used in the ANA test with Human Epithelial type-2 (HEp-2) cells as substrates. The efficiency of the proposed methodology is assessed using the dataset of ICPR 2016. The intermediate cells (IMC) and positive cells (PC) were separated in Stage 1 prior to preprocessing based on their total strength, and special preprocessing is applied to intermediate cells for improved output, and positive cells are subjected to mild preprocessing. The mean class accuracy (MCA) was 84.9% for intermediate cells and 95.8% for positive cells, although the carefully picked 24 features and SVM classifier were applied. ANN showed better performance by adjusting the weights using the SCGBP algorithm. So, the MCA is 88.4% and 97.1% for intermediate and positive cells, respectively. BT had an MCA of 95.3% for intermediate and 98.6% for positive. In Stage 2, the meta learners BT2, ANN2, and SVM2 were trained for an augmented feature set (24 + 3 results from base learners). Therefore, the performance of BT2, ANN2, and SV M2 was increased by 1.8%, 4.5%, and 4.1% as compared to Stage 1. In Stage 3, the final prediction was performed by majority voting among the results of the three meta learners to achieve 99.1% MCA. The proposed algorithm can be embedded into a CAD framework built for the ANA examination. The proposed model will improve operational efficiency, decrease medical expenses, expand accessibility to healthcare, and improve patient safety in the sector, enabling enterprises to lower unplanned downtime, develop new products or services, increase operational effectiveness, and enhance risk management.

Splenectomy outcomes in patients with autoimmune cytopenias and persistent antiphospholipid antibodies.

Splenectomy is a therapy for patients with treatment-refractory autoimmune cytopenias. Antiphospholipid antibodies (aPL) can be identified in 25%-85% of these patients. In this study, we sought to identify whether the presence of aPL was associated with worse outcomes in autoimmune cytopenia's patients who had undergone splenectomy. We conducted a retrospective cohort study of patients who underwent splenectomy from 2000 to 2018. We describe clinical characteristics and outcomes in patients with autoimmune cytopenia's diagnosis with positive determinations of aPL. Additionally, we performed a case-control sub-analysis 1:1 of the cases with autoimmune cytopenia's matched control patients with negative aPL determination. A splenectomy was performed in 707 patients, of which we included 34 for the analysis. The median age at the time of splenectomy was 37 years (range 19-61), 53% corresponded to immune thrombocytopenia (ITP) and 47% to autoimmune hemolytic anemia (AIHA). Compared with controls (n= 34), patients had more treatment lines in addition to steroids (p= .02). There were no differences in complete response rate, 65% in cases and 80% in controls (p= .17). However, there was numerically a higher incidence of early infections (21% of cases vs. 3% controls, p= .05). During the entire follow-up, 15% of aPL patients compared with 9% of control patients had a thrombotic event (p= .70). Splenectomy for treatment-refractory autoimmune cytopenia's patients with persistent aPL is an effective treatment despite some safety concerns related to early infections. These results suggest that the presence of aPL should not impact the decision to undergo splenectomy.

Evaluating risk factors, biomarkers and management of myocarditis following treatment with checkpoint inhibitors. A retrospective analysis

Abstract Immunotherapy is an exciting treatment of many malignancies. They upregulate the immune system to attack cancerous cells. Immune checkpoint inhibitor (ICIs) are among armamentarium of immunotherapy agents that target immune system negative regulation and are known to induce myocarditis [1]. This is a rare but increasingly recognised complication as immunotherapy regimens become more widely used as first line therapy for a range of tumour types. Due to its infrequent presentation, there remains uncertainty regarding its diagnosis and management [2]. We conducted a single centre retrospective analysis of patients undergoing immunotherapy at a cancer centre in United Kingdom. The cases were referred to the regional cardio-oncology service for suspected myocarditis. In this single center retrospective analysis, data of 60 patients with suspected myocarditis (based on symptoms, cardiac biomarkers or ECG) presenting over a 2 year period were evaluated. Of those 25 (42%) developed MRI-proven myocarditis with mean period to toxicity post treatment of 99.5 days. In the same time period 1027 patients experienced all-type immunotherapy related adverse events (irAEs) thus myocarditis accounted for 2.4% of all ICI-induced toxicity. 35% had significant pre-existing cardiac history including ischaemic heart disease, valvular disease and ventricular impairment. Patients with myocarditis had average peak troponin of 276 and average peak pro-BNP of 2,265. Less than 10% of patients with myocarditis had pre-existing autoimmune diagnosis (rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease). Average maximum grade toxicity was 3. The majority of patients were managed with steroids with 48% receiving intravenous methylprednisolone followed by oral prednisolone and 28% patients receiving only oral steroids. 44% of patients also required steroid sparing agents such as tacrolimus or mycophenalate mofetil. Steroid tapering was adjusted based on the patient's symptoms with 32% of patients needing dose escalation for a flare. No patients restarted immunotherapy once myocarditis had been identified and overall survival remained comparable to those without myocarditis. In conclusion, myocarditis is a late complication of ICIs with higher incidence among patients with significant cardiac history. Associated biomarkers are significantly elevated and correlate well with the presence of myocarditis. Steroids remain the mainstay of treatment for those who develop myocarditis secondary to immunotherapy but there is also an important role for other agents such as tacrolimus or mycophenalate mofetil. Funding Acknowledgement Type of funding sources: None.

Association of maternal autoimmune disease and early childhood infections with offspring autism spectrum disorder: A population-based cohort study.

The aim of this study was to examine potential synergistic effects between maternal autoimmune disease and early childhood infections and their association with autism spectrum disorder (ASD) in offspring. Both exposures have been associated with increased risk of ASD in previous studies, but potential synergistic effects remain underexplored. We conducted a population-based cohort study of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia from January 2002 to December 2008. Maternal autoimmune diagnoses and childhood infections before age 2 years were identified from linked maternal and child hospital admissions, and ASD diagnoses by age 9 years were identified from linked disability services data. Multivariable logistic regression assessed the association between each exposure and ASD and additive interaction between exposures, controlling for potential confounders. A total of 18,451 children exposed to maternal autoimmune disease were propensity score matched (1:2) to 36,902 unexposed children. Any maternal autoimmune disease (adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07-1.47) and any childhood infection before age 2 years (aOR 1.38, 95% CI 1.15-1.67) were each associated with ASD. However, there was no evidence of additive interaction between the two exposures (relative excess risk due to interaction [RERI] 0.128, 95% CI -0.418-0.675) resulting in increased odds of ASD in offspring. Future studies could examine potential interactions between other sources of maternal immune activation and childhood infection and impact on ASD and other neurodevelopmental disorders.

Applications of Peptide Microarrays in Autoantibody, Infection, and Cancer Detection.

The diversity of the antigen-specific humoral immune response reflects the interaction of the immune system with pathogens and autoantigens. Peptide microarray analysis opens up new perspectives for the use of antibodies as diagnostic biomarkers and provides unique access to a more differentiated view on humoral responses to disease. This review focuses on the latest applications of peptide microarrays for the serologic medical diagnosis of autoimmunity, infectious diseases(including COVID-19), and cancer.

Racial/Ethnic Differences in Psychiatric and Medical Diagnoses Among Autistic Adults.

Racial/ethnic disparities in access to diagnostic services are pervasive for autistic children. However, a few studies have examined racial/ethnic health disparities among autistic adults, who commonly experience higher rates of health conditions than non-autistic adults. We aimed at examining the intersection of autism and race/ethnicity in association with psychiatric and medical diagnoses. The study population included adult members of Kaiser Permanente Northern California enrolled from 2008 to 2012. We ascertained 1507 adults who had an autism diagnosis documented in their electronic medical records. We sampled a matched control group of adults without an autism diagnosis (N = 15,070) at a 10:1 ratio. Our sample was 46% White, 17% Hispanic, 16% Asian, 7% Black, and 14% other race/ethnicity. We compared health diagnoses (a) between autistic and non-autistic adults within strata of race/ethnicity and (b) across race/ethnicity within strata of autistic and non-autistic adults. Lastly, we examined the interaction between autism and race/ethnicity on both multiplicative and additive scales. Autistic adults were more likely to be diagnosed with most medical and psychiatric conditions compared with their non-autistic counterparts of the same race/ethnicity. Among autistic adults, Black, Hispanic, and Asian adults were less likely to be diagnosed with psychiatric conditions and Black and Hispanic autistic adults were more likely to be diagnosed with obesity than their White counterparts. In interaction models, we found that adults who were Black and autistic were disproportionately less likely to be diagnosed with psychiatric conditions and autoimmune disease and more likely to be diagnosed with hypertension than expected. Health vulnerabilities may be compounded at the intersection of autism and race/ethnicity. Future research should continue to apply an intersectional lens toward understanding and addressing these disparities. Our findings likely underestimate the health disparities that exist in uninsured autistic adults and those living in other parts of the United States.

Autoimmune multimorbidity and fatigue in women with idiopathic inflammatory myopathies: an international, patient-reported, e-survey

<h2>Abstract</h2><h3>Background</h3> Idiopathic inflammatory myopathies are a group of rare systemic autoimmune rheumatic diseases with substantial heterogeneity. We aimed to investigate gender differences in patient-reported outcomes and treatment regimens of people with idiopathic inflammatory myopathies. <h3>Methods</h3> This international, patient-reported, e-survey was conducted worldwide. We used data from the COVID-19 vaccination in autoimmune disease (COVAD) study, a large-scale, international, self-reported e-survey assessing the safety of COVID-19 vaccination in patients older than 18 years with autoimmune rheumatic diseases, including idiopathic inflammatory myopathies. The COVAD study was conducted in more than 80 health-care centres, including hospitals, clinics, and universities located in more than 50 countries worldwide and on social media platforms, such as Facebook and Twitter. The COVAD e-survey was open between April 1, 2021, and Dec 31, 2021. We extracted survey data regarding demographics; autoimmune rheumatic disease diagnosis; autoimmune multimorbidity (three or more autoimmune rheumatic disease diagnoses for each patient); current corticosteroid or immunosuppressant use; and patient-reported outcomes, including fatigue and pain Visual Analogue Scale (VAS), and PROMIS short form-physical function 10a (PF-10a). Gender was reported by participants with three options (men, women, or do not wish to disclose). Patient-reported outcomes and corticosteroid or immunosuppressant use were compared between men and women. Participants with inclusion body myositis were analysed separately due to the substantial difference in treatment and disease outcomes compared with other idiopathic inflammatory myopathy subtypes. Factors affecting each patient-reported outcome were determined using multivariable analysis. <h3>Findings</h3> The survey data were extracted on Aug 31, 2021, and 1202 complete responses from participants with idiopathic inflammatory myopathies were analysed. Five patients who did not wish to disclose gender were excluded. 845 (70·6%) of the remaining 1197 were women. Women were younger than men (median 58 years [IQR 48–68] <i>vs</i> 69 years [58–75]; p=0·00010). Autoimmune multimorbidity was more common in women than in men (94 [11·1%] of 845 <i>vs</i> 11 [3·1%] of 352; p<0·0001). Corticosteroid use was similar in men and women with idiopathic inflammatory myopathies (except for inclusion body myositis), whereas the distribution of immunosuppressants was different, with higher hydroxychloroquine use in women (131 [18·3%] of 717 <i>vs</i> 11 [6·9%] of 159 in men; p=0·0082). The median fatigue VAS was significantly higher in women than in men (5 [IQR 3–7] <i>vs</i> 4 [2–6]; p=0·0036), whereas the gender difference in pain VAS (median 3 [IQR 1–5] in women <i>vs</i> 2 [0–4] in men; p=0·064) and PROMIS PF-10a scores (38 [31–45] <i>vs</i> 39 [30–47]; p=0·29) was non-significant. There were no significant differences in patient-reported outcomes and treatment in participants with inclusion body myositis. The multivariable analysis of idiopathic inflammatory myopathies (except for inclusion body myositis) revealed that female sex, residence in high-income countries, a diagnosis of overlap myositis, and autoimmune multimorbidity were independent risk factors for higher fatigue VAS. <h3>Interpretation</h3> Women with Idiopathic inflammatory myopathies frequently have autoimmune multimorbidity and increased fatigue compared with men, calling for greater attention and further research on targeted treatment approaches. <h3>Funding</h3> None.

Determination of etiology in patients admitted due to isolated leukopenia.

Patients with isolated leukopenia pose difficulties in diagnosis because there is no related guideline in the literature. In this study, our aim was to evaluate the clinical and laboratory associations of isolated, nonspecific (not related to neutropenia) leukopenia.In this retrospective data review study, patients who were admitted to Hacettepe University Hematology Outpatient Clinic between 2014 and 2019 due to leukopenia were evaluated. The patients with anemia (other than iron deficiency) or thrombocytopenia were excluded. Clinical and laboratory data and the final diagnoses (if present) of the remaining cases and especially of those without neutropenia (the most difficult group to diagnose) were evaluated.One hundred sixty-nine patients were included in the study. One hundred forty-four (85.2%) patients were female and 25 (14.8%) were male. One hundred ten of them had 1500/µL or higher neutrophil count. In these nonneutropenic cases, the etiological factors contributing to leukopenia were as follows: iron deficiency anemia (21.8%), other autoimmune/autoinflammatory diseases (17.3%), autoimmune thyroid disease (21.8%), autoimmune laboratory tests (2.7%), drugs (12.7%), infection (5.5%), hematopoietic disorder (2.7%), hypersplenism (2.7%), radiotherapy sequel (1.8%), and B12 deficiency (1.8%). No etiology was recognized in 44 patients. On the other hand, the etiological factors in patients with neutrophil count <1500/µL were as follows; iron deficiency anemia (10.2%), other autoimmune/autoinflammatory diseases (17%), autoimmune thyroid disease (5.1%), autoimmune laboratory tests (8.5%), drugs (8.5%), infection (6.8%), hematopoietic disorder (11.9%), hypersplenism (1.7%), radiotherapy sequel (1.7%), and B12 deficiency (1.7%). No etiology was recognized in 25 patients. Physicians ordered bone marrow examination more frequently in patients with neutropenia. If isolated antinuclear antibody positivity was also considered in favor of autoimmunity, 91/169 (53.8%) cases had an autoimmune diagnosis or laboratory finding.In the present study, the most frequent reasons of isolated leukopenia in nonneutropenic patients are found as iron deficiency anemia, other autoimmune/autoinflammatory diseases, and autoimmune thyroid disease. In neutropenic patients, the most frequent reasons of isolated leukopenia are found as iron deficiency anemia, autoimmune/autoinflammatory diseases, and hematopoietic disorders. Therefore, autoimmunity is detected as an important factor leading to isolated leukopenia.

Autoimmune Skin Disease Exacerbations Following COVID-19 Vaccination.

BackgroundVaccination against COVID-19 reduces the risk of severe COVID-19 disease and death. However, few studies have examined the safety of the COVID-19 vaccine in patients with autoimmune skin disease.ObjectivesWe sought to determine the incidence of disease exacerbation in this population following COVID-19 vaccination as well as the associated factors.MethodsWe performed a chart review of all patients seen in the autoimmune skin disease clinic of the principal investigator during the study period. All patients included for analysis were systematically and prospectively asked about COVID-19 vaccination status, manufacturers, vaccine dates, autoimmune symptoms after the vaccine, and timing of symptom onset using a standardized template as part of their visit. Demographics and autoimmune disease diagnosis were also collected. Analysis used Chi-square and Fisher’s exact tests.Results402 subjects were included for analysis. 85.6% of patients were fully vaccinated, with 12.9% unvaccinated and 1.5% partially vaccinated. 14.8% of fully vaccinated patients reported worsening autoimmune signs and symptoms after the vaccine. Fully vaccinated dermatomyositis patients were more likely to report worsening autoimmune signs and symptoms after the vaccine (22.7%) than fully vaccinated lupus erythematosus patients (8.6%) (p=0.009). Patients fully vaccinated with the Moderna vaccine trended towards an increased likelihood of reporting worsening autoimmune signs and symptoms after the vaccine (19.1%) than those with the Pfizer-BioNTech vaccine (12.0%) (p=0.076). Of the patients who had autoimmune symptoms after vaccination, 20% had symptoms after the 1st dose, 82% after the 2nd dose, and 4% after the 3rd dose with median onset (95% confidence interval) of 7 (2,14), 14 (14,21), and 18 (7,28) days later, respectively.ConclusionsMore fully vaccinated dermatomyositis patients had exacerbation of autoimmune signs and symptoms after the vaccine than fully vaccinated lupus erythematosus patients. However, given the risks of COVID-19, clinicians should still promote vaccination in most patients with autoimmune skin disease.

Neuronal intermediate filament paraneoplastic autoimmunity complicating avelumab therapy of Merkel cell carcinoma

A 67-years-old woman developed subacute oculomotor nerve palsy and cerebellar gait instability while receiving avelumab as immunotherapy for Merkel cell carcinoma. Brain MRI revealed oculomotor nerve T2/FLAIR hyperintensity and contrast enhancement, CSF cell number and protein concentration were slightly increased. Antibodies against intracellular and surface antigens were excluded through commercial assays, but home-made immunohistochemistry on rat brain sections showed a “neurofilament-like” pattern. Antibodies against neuronal intermediate filament (NIF-IgG) were thus tested and resulted positive in both serum and CSF, confirming the diagnosis of NIF-IgG autoimmunity. Avelumab was discontinued and treatment with steroids and intravenous immunoglobulins led to partial improvement.

Health Outcomes of 215 Mothers of Children With Autoimmune Congenital Heart Block: Analysis of the French Neonatal Lupus Syndrome Registry.

Transplacental passage of maternal anti-SSA and anti-SSB antibodies, potentially associated with maternal autoimmune diseases, can cause neonatal lupus syndrome. Given the paucity of data in this setting, we report short- and long-term outcomes of mothers of offspring with congenital heart block (CHB). This retrospective study included anti-SSA/SSB antibody-positive mothers of fetuses with high-degree CHB and focused on their health status before pregnancy, at CHB diagnosis, and thereafter. We analyzed 215 women with at least 1 pregnancy with CHB. Prior to this diagnosis, only 52 (24%) mothers had been diagnosed with an autoimmune disease, mainly systemic lupus erythematosus (SLE; n = 26, 12%) and Sjögren syndrome (SS; n = 16, 7%). Six more were diagnosed with an autoimmune disease during the index pregnancy. Of the 157 mothers (73%) with no such diagnosis at childbirth, 77 (49%) developed one after a median follow-up of 11 years (range: 21 days to 54 years). By the end of follow-up, 135 women (63%) had an autoimmune disease diagnosis, mainly SLE (n = 54, 25%) and SS (n = 72, 33%). Three patients with SLE had renal involvement, and only 6 (3%) had required an immunosuppressive drug at any point. The symptoms best predicting autoimmune disease development were arthralgia and myalgia (P < 0.001), dry syndrome (P = 0.01), and parotid swelling (P = 0.05). One-quarter of the patients had an autoimmune disease diagnosis at the time of the fetal CHB diagnosis. Nearly half of those without an initial diagnosis progressed during follow-up, most without severe manifestations. Severe diseases such as lupus nephritis were rarely seen, and immunosuppressive drugs were rarely required.

Patients with severe COVID-19 do not have elevated autoantibodies against common diagnostic autoantigens.

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19) presents occasionally with an aberrant autoinflammatory response, including the presence of elevated circulating autoantibodies in some individuals. Whether the development of autoantibodies against self-antigens affects COVID-19 outcomes remains unclear. To better understand the prognostic role of autoantibodies in COVID-19, we quantified autoantibodies against 23 markers that are used for diagnosis of autoimmune disease. To this end, we used serum samples from patients with severe [intensive care unit (ICU)] and moderate (ward) COVID-19, across two to six consecutive time points, and compared autoantibody levels to uninfected healthy and ICU controls. Acute and post-acute serum (from 1 to 26 ICU days) was collected from 18 ICU COVID-19-positive patients at three to six time points; 18 ICU COVID-19-negative patients (sampled on ICU day 1 and 3); 21 ward COVID-19-positive patients (sampled on hospital day 1 and 3); and from 59 healthy uninfected controls deriving from two cohorts. Levels of IgG autoantibodies against 23 autoantigens, commonly used for autoimmune disease diagnosis, were measured in serum samples using MSD® U-PLEX electrochemiluminescence technology (MSD division Meso Scale Discovery®), and results were compared between groups. There were no significant elevations of autoantibodies for any of the markers tested in patients with severe COVID-19. Sample collections at longer time points should be considered in future studies, for assessing the possible development of autoantibody responses following infection with SARS-CoV-2.

Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies. We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status. Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36]; and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter. Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.

Mapping anorexia nervosa genes to clinical phenotypes.

Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes. Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations. Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex. Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.

The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results

Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3-<16 years) who completed their 2-year study visit. Participants were treated at the investigator's discretion. Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n= 11, 39%), myelin oligodendrocyte glycoprotein-associated demyelination (n= 8, 29%), multiple sclerosis (MS) (n= 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n= 3, 11%), and acute disseminated encephalomyelitis (n= 2, 7%). Two participants (7%; 95% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI,-0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60-90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n= 2 participants, 3 eyes), MS (n= 2 participants, 2 eyes), and isolated ON (n= 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48-0.88 [20/50+1-20/150-1]). Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).

P/Q-Type Calcium Channel Antibodies and Late Life First Break Psychosis: A Case Report

<h3>Introduction</h3> Paraneoplastic Syndrome, described in the 1940s, a phenomenon of cancer presenting with multiple different manifestations, not directly related to tumor itself, has had an overdue recognition with these conditions still being studied and researched, especially when it comes to Paraneoplastic Syndromes presenting with Neuropsychiatric Disorders (Lorraine C. Pelosof, 2010). In the psychiatric and neurological literature, there is slow yet gradual recognition of new onset psychosis in patients with no prior history of such, which are attributable to autoantibodies of different types. In some psychiatric literature, this presentation is termed as autoimmune psychosis (Thomas A Pollak, 2020). Currently known autoantigens include NMDAR, Gamma-Aminobutyric Acid Receptor- B (GABABR), Gamma-Aminobutyric Acid Receptor- A (GABAAR), components of voltage gated potassium channel (VGKC) complex, dopamine D2 receptor (D2R)(Nese Sinmaz, 2015). Autoimmune N-methyl-D-aspartate (NMDA) receptor encephalitis has been of particular interest to psychiatrists with it being the most studied paraneoplastic syndrome, as 77% of affected patients first present to psychiatry with a broad range of symptoms (Jennifer L.Kruse, 2015). Very few and limited data have been found on the association between voltage gated calcium channel (P/Q type) and psychosis. In this poster, we describe a case of an individual presenting with late onset first episode of psychosis, with positive P/Q channel antibodies. <h3>Methods</h3> Previous studies and reviews over the past 10 years were reviewed using PubMed, Medline and Google Scholar. Search terms were "psychosis", "autoimmune psychosis", "autoantibodies and psychosis" "geriatric psychosis" "P/Q-type Calcium channel" "Paraneoplastic syndrome" "very late onset psychosis". We reviewed available literature with regards to first episode of psychosis in old age and possible association with P/Q-type voltage gated calcium channel. <h3>Results</h3> DiscussionVery late onset psychosis is delineated as onset of psychosis after the age of 60 years (Howard, 2000). Prevalence of late life psychosis is 23%, however 60% of new onset psychosis in older individuals are of secondary etiology (Cohen, 2015). Psychosis in the elderly individuals could be primarily due to Very Late Onset Schizophrenia Like Psychosis (VLOSLP) vs secondary causes (Delirium, Dementia, Drugs/illicit substances/toxin, Medical conditions). In the discussed case, the patient presented with first episode of psychosis at the age of 70. The extensive workup was positive for P/Q-type Calcium channel binding antibody. Per literature review, the positive predictive value for an autoimmune neurological diagnosis (Lambert-Eaton syndrome or diverse encephalomyeloneuropathic phenotypes) among patients with positive values for P/Q -type calcium channel antibodies < 0.10 nM is 19%. The positive predictive value for a cancer diagnosis (diverse types) among patients positive for P/Q-type calcium channel antibody is 21%; approximately 18% are historical neoplasms, and 3% are detected prospectively (Zalewski NL, 2016). A spectrum of psychiatric autoimmunity beyond NMDA-R IgG is still under-recognized (Jennifer L.Kruse, 2015). In a retrospective case control study conducted by Dr. Jennifer L.Kruse in Mayo clinic, out of the 213 adult psychiatric inpatient 3 patients were found to have positive P/Q-type Calcium channel, who manifested with delusional parasitosis, mood disorder with psychotic features, and Major Depressive Disorder with Psychotic features (Jennifer L.Kruse, 2015). Another international case study found genetic association between voltage gated Calcium channel and Schizophrenia (Wen Li1, 2018). While these studies indicate the potential association between voltage gated Calcium channel and psychosis, limited case studies and research could be found on the association, extent and elaboration of the aforementioned. <h3>Conclusions</h3> While there is progressively enriched literature on psychosis due to Paraneoplastic syndrome, specifically Anti NMDA receptor encephalitis, there is not much mention of correlation between P/Q-type calcium channel binding antibodies and psychosis. Cases with rare presentations as above warrant elaborate workup. Along with the abovementioned etiologies, given the increased incidence of psychosis due to autoimmune antibodies, addition of full autoimmune antibody panel should be considered. Shared clinical experience, research and prospective clinical studies will direct developing guidelines for evaluation, management and prognostic indicators of Paraneoplastic Syndromes with Neuropsychiatric symptoms, particularly due to autoimmunity against voltage gated calcium channel (P/Q-type). <h3>This research was funded by</h3> There are no financial conflicts of interest to disclose

Pre-Existing Autoimmune Disease and Mortality in Patients Treated with Anti-PD-1 and Anti-PD-L1 Therapy.

Although indications for immune checkpoint inhibitors (ICIs) have dramatically increased in the past decade, ICIs have been associated with autoinflammatory immune-related adverse events, which can resemble autoimmune diseases (ADs). Little is known about the impact of baseline AD on mortality in cancer patients treated with ICIs. Here, we identified 17 497 patients with preexisting autoimmune diagnoses prior to treatment with antiprogrammed cell death receptor-1 or antiprogrammed cell death ligand-1 therapy and 17 497 matched controls through the TriNetX Diamond network of more than 200 million patients across the United States and Europe. Using a Cox proportional hazards model, we found that patients with history of AD were not at higher risk of mortality than non-AD patients (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1 to 1.07; P = .05). Additionally, history of Hashimoto disease (HR = 0.75, 95% CI = 0.62 to 0.90; P = .002) and vitiligo (HR = 0.52, 95% CI = 0.34 to 0.81; P = .003) were statistically significantly associated with decreased mortality. This suggests that underlying AD need not be a contraindication to inclusion in clinical trials and administration of ICI for treatment of cancer.

DEVELOPMENT AND VALIDATION OF A MACHINE LEARNING TOOL FOR EARLY DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE IN THE PRIMARY CARE SETTING: A POPULATION BASED STUDY

Abstract BACKGROUND Although 3,000,000 Americans are afflicted with Inflammatory Bowel Disease (IBD) encompassing Crohn’s Disease (CD) and Ulcerative Colitis (UC)1, timely diagnosis is a challenge due to non-specific and overlapping symptoms.2 More than 20% of patients may be initially misdiagnosed3 causing delayed diagnosis and treatment, potentially leading to increased risk of complications2 and irreversible mucosal damage.4 Artificial intelligence (AI) models can alert physicians to patients who would otherwise be misdiagnosed, potentially improving patient outcomes and reducing costs. We aimed to develop PredictAI, a proprietary AI Gradient Boosted Decision Tree based machine learning algorithm and test its accuracy in identifying undiagnosed CD and UC in the primary care setting. METHODS This was a retrospective study of 2,471,267 patients’ electronic medical records (EMR) from Maccabi Healthcare Services in Israel. Sufficient data was available between the years 2010-2020, of which 2 consecutive years (2015-2016) were pre-assigned to the test set. Inclusion criteria were: (i) CD or UC ICD code as defined by Maccabi’s Registry,5 (ii) no other autoimmune disease diagnosis, (iii) at least 4 years of data antedating first suspicion by primary care physician (PCP) of IBD were available. First suspicion was defined as any diagnostic test, procedure, or referral to a specialist, indicating suspicion of IBD. Here we included adult data only. RESULTS Of 2,471,267 patients, 1,214 had a first-time diagnosis of IBD and available antedating data in the years 2015-2016. Of these, PredictAI identified 126, 120, 104, 93 patients 1, 2, 3 and 4 years prior to initial PCP suspicion, respectively. For CD, it predicted 83/229 (36%) of patients 1 year prior to PCP initial suspicion of disease, 70/211 (33%) patients 2 years prior, 60/179 (33%) patients 3 years prior and 56/148 (38%) patients 4 years prior. Discriminatory accuracy area under the curve (AUC) was 76%, 75%, 75% and 78%, 1, 2, 3 and 4 years before initial PCP suspicion, respectively (Figure 1). Corresponding early-identification ratio and discriminatory accuracy for UC was 42/238 (17%, AUC=71%), 50/225 (22%, AUC=70%), 44/187 (23%, AUC=72%) 37/161 (23%, AUC=74%), for 1,2,3 and 4 years before initial PCP suspicion of UC, respectively (Figure 2). Specificity for CD and UC each was above 90%. CONCLUSIONS PredictAI accurately identified CD and UC diagnosis in 17-38% of patients presenting to primary care up to 4 years prior to PCP’s initial suspicion, potentially reducing time to diagnosis.

A practical case: features of the autoimmune insulin syndrome diagnosis

Autoimmune Insulin syndrome (AIS), also named Hirata disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). AIS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (medication or a viral infection) acts on an underlying predisposing genetic background. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglucemia. The article presents a case of Hirata disease diagnosing of a patient of the therapy department of the Multidisciplinary Medical Center of the Bank of Russia.Purpose: Determining of the features of the diagnosis of Autoimmune Insulin syndrome (Hirata disease)Materials and methods: the article presents a clinical case of the diagnosis of Autoimmune insulin syndrome (Hirata disease), focuses on the diagnostic significance of laboratory tests. The article is intended for general practitioners, endocrinologists, gastroenterologists.

Joint segmentation and classification task via adversarial network: Application to HEp-2 cell images

The recognition of epithelial type 2 (HEp-2) cells has become an important tool for detecting autoimmune diseases diagnosis by using indirect immunofluorescence (IIF) images. For many medical image tasks, the accurate segmentation is considered as the primary step for the classification task, which inspires researchers to solve problems by jointly implementing multiple tasks. For this reason, we devise a hybrid network architecture, which combines the segmentation and classification networks for the final classification of HEp-2 cells, where a multi-task generative adversarial networks (GANs) is employed to produce accurate segmentation masks for improving the latter classification performance. Specifically, the devised generation and discrimination subnetworks establish the GANs architecture for the accurate segmentation masks of HEp-2 cells. Also, the original images are utilized as the conditional input, which are concatenated by the generated masks and the ground-truth to train the discriminator for two tasks: the first task determines whether the generated mask is a ground-truth or not and the other one distinguishes the category of the processed HEp-2 cell image. Furthermore, the ResNet-34 and MobileNetv3 are used as segmentation and classification base network, respectively. We modify the MobileNetv3 structure by adding the channel of the middle outputs, which is called augmented channel MobileNetv3 (ACM-Net). Both the discriminator and classifier share the weights of ACM-Net. The extensive experiments on the public ICPR 2016 task1 dataset show that the proposed hybrid-task based GANs structure can obtain promising segmentation and classification performance via jointly training mode, which achieves a Dice of 97.04% and for segmentation and a prediction accuracy of 98.82% for classification, respectively.