Predictors Of Disease Course Research Articles

Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response. We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay. ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone. Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Predictors of disease course in systemic juvenile idiopathic arthritis.

The aim of this study was to identify potential predictors of the disease course of systemic juvenile idiopathic arthritis (sJIA) at the time of diagnosis. This retrospective observational study was conducted in patients diagnosed with sJIA in our hospital between April 2009 and October 2023. The relationship between the disease course of sJIA patients and demographic, clinical, laboratory findings and complications was analysed. Of the 51 patients diagnosed with sJIA, 26 (51%) patients had monocyclic, 7 (13.7%) polycyclic, and 18 (35.2%) persistent disease course. The presence of arthritis, polyarticular involvement, and hip involvement at the time of diagnosis were associated with persistent disease course (P = .009, P = .003, P = .003). Serositis and higher white blood cell and neutrophil counts at the time of diagnosis were associated with a monocyclic disease course (P = .034, .002, .008). However, no significant correlation was found between macrophage activation syndrome and disease course (P = 1). sJIA patients with polyarthritis and hip involvement at disease onset may develop a persistent course. Although macrophage activation syndrome is an important complication of sJIA, its effect on the course of the disease was not found in this study.

Predictors of Complicated Disease Course in Adults and Children With Crohn’s Disease: A Nationwide Study from the epi-IIRN

Abstract Background Since data on predictors of complicated Crohn’s disease (CD) from unselected populations are scarce, we aimed to utilize a large nationwide cohort, the epi-IIRN, to explore predictors of disease course in children and adults with CD. Methods Data of patients with CD were retrieved from Israel’s 4 health maintenance organizations, whose records cover 98% of the population (2005-2020). Time-to-event modeled a complicated disease course, defined as CD-related surgery, steroid-dependency, or the need for >1 class of biologics. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results. Results A total of 16 659 patients (2999 [18%] pediatric-onset) with 121 695 person-years of follow-up were included; 3761 (23%) had a complicated course (750 [4.5%] switched to a second biologic class, 1547 [9.3%] steroid-dependency, 1463 [8.8%] CD-related surgery). Complicated disease was more common in pediatric- than adult-onset disease (26% vs 22%, odds ratio, 1.3; 95% confidence interval [CI], 1.2-1.4). In a Cox multivariate model, complicated disease was predicted by induction therapy with biologics (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6) and severity of laboratory tests at diagnosis (HR, 1.7; 95% CI, 1.2-2.2), while high socioeconomic status was protective (HR, 0.94; 95% CI, 0.91-0.96). In children, laboratory tests predicted disease course (HR, 1.8; 95% CI, 1.2-2.5), as well as malnutrition (median BMI Z score −0.41; 95% CI, −1.42 to 0.43 in complicated disease vs −0.24; 95% CI, −1.23 to 0.63] in favorable disease; P < .001). Conclusions In this nationwide cohort, CD course was complicated in one-fourth of patients, predicted by laboratory tests, type of induction therapy, socioeconomic status, in addition to malnutrition in children.

Evaluating Effective Therapeutic Options for Inhibitor Eradication in Patients with Acquired Hemophilia a: A 10-Year Single Center Experience

Background Acquired hemophilia A (AHA) is a rare disorder characterized by emergence of neutralizing antibodies or inhibitors to factor VIII. The main treatment strategy for AHA involves control of bleeding with factor VIII bypassing agents and eradicating the autoantibodies using immunosuppressive therapy (IST) for restoration of normal hemostasis. Previous studies have demonstrated the effectiveness of both cyclophosphamide and rituximab in combination with steroids for treating AHA, however, clear guidelines for choosing between these agents for rapid inhibitor eradication are lacking. This retrospective study aimed to compare the effectiveness of cyclophosphamide and rituximab as first-line therapies for rapid antibody elimination and relapse prevention. Methods We queried our hospital electronic health record system using ICD 9/10 code to identify patients >18 years that had at least 2 inpatient or outpatient encounters for the diagnosis of AHA between 1 st July 2013 and 30 th June 2023. Variables collected included initial aPTT value, serial factor VIII activity & Bethesda inhibitor titer and immunosuppressive therapies used. Time to remission was defined when inhibitor titer was <1% along with improving factor VIII activity. At our institute, all patients received 1mg/kg of steroids initially, then either six cycles of 400mg/kg IV Cyclophosphamide every 28 days on day 1 along with 100mg of oral Prednisone days 1-5 or four cycles of IV Rituximab at a weekly dose of 375mg/m2 was used as 1 stline IST for patients with inhibitor titer >10%. Patients that did not achieve remission or those with persistently high inhibitor titers after 3 cycles of Cyclophosphamide were switched to 2 nd line therapy. In few patients oral Cyclophosphamide or Mycophenolate mofetil was used as maintenance therapy after 1 st or 2 nd line therapy. Bleeding control was achieved with use of rpFVIII or rFVII, FEIBA or emicizumab depending on product availability. Descriptive statistics (mean, SD) & openAI.ChatGPT-4 generated correlation coefficient was used for data analysis. Results A total of 11 male and 5 female patients were identified. The mean age at diagnosis was 69 years and the average length of follow up was 672 days. The mean aPTT value at diagnosis was 84.3 seconds. Inhibitor titer ranged from 1.5 to 329% with an average of 63.62%. Patients with low inhibitor titer of <10% received only steroids and all of them achieved remission without relapse. Rituximab as first-line therapy led to remission in 100% of cases, while only 28.5% of patients treated with cyclophosphamide achieved remission without needing second-line therapy. The time to remission was significantly shorter in patients treated with rituximab compared to cyclophosphamide (43.4vs148.7days). Additionally, none of the patients treated with rituximab experienced a relapse after 1 st remission, while 57% of patients treated with cyclophosphamide did and majority needed 2 nd line & maintenance therapy (Figure-1). Initial inhibitor titer had a moderate to strong positive correlation with the time to remission, the incidence of relapse, and the need for second line and maintenance therapy (Figure- 2). Conclusions Rituximab as first line IST appeared to be more effective than cyclophosphamide in achieving rapid remission and reducing incidence of relapse. Our analysis also revealed that initial inhibitor titer may serve as a useful predictor of disease course, potentially guiding therapeutic decision-making and eliminating need for cytotoxic medication or maintenance therapy. Future large prospective studies are needed to confirm these findings and further investigate other factors influencing therapeutic outcomes in patients with AHA.

Characteristics and predictors of disease course in children initially presenting with ADEM

ADEM is an inflammatory disease, with new onset polyfocal neurologic symptoms, encephalopathy and multifocal demyelination, typically in childhood. Initial diagnosis of ADEM is challenging and up to 20 % of children with MS or NMOSD are initially diagnosed with ADEM.We describe characteristics of patients with monophasic ADEM vs. recurrent demyelinating syndromes at onset and identify features consistent with monophasic course.This is a multicenter observational study of children with demyelinating disease, followed at 12 regional pediatric MS centers. Descriptive statistics were used to report patient characteristics, clinical/imaging features and outcomes. Logistic regression was used to predict features associated with monophasic course.As of July 2019, 837 children with final diagnosis of ADEM (n = 79), MS (n = 646) or NMOSD (n = 112) were identified. The mean follow-up was 5·7 +/- 3·2 years. ADEM patients were youngest with mean age at first event 5·2 +/- 3·8 years (p < 0.001) and male predominant (66 %) (p < 0·001). After 2 years of follow-up, 83 % of patients initially diagnosed with monophasic ADEM retained this diagnosis. In multivariable analysis, older age (OR 1·16 [95 % CI 1·02 – 1·33] for 1-year increase, p = 0·02), presenting with optic neuritis (OR 8.18 [95 % CI 1.88 – 35.64], p = 0·005) and presence of gadolinium enhancement (OR 4.08 [95 % CI 1.38 – 12.08], p = 0·011) were associated with reclassification of ADEM to MS, NMOSD or DDNOS within 2 years.Children with monophasic ADEM vs. those reclassified as other demyelinating disorders are younger at onset, and less likely to have optic neuritis or gadolinium-enhancing lesions at onset.

Predictors of disease course and long-term outcomes of idiopathic intracranial hypertension in children and adolescents.

This study provides insights into predictive factors for an unfavorable disease course, persistent headaches, and poor visual outcomes in patients with childhood IIH. Patients with persistent headaches may have a variant of a chronic pain syndrome warranting a different therapeutic approach. • Childhood-onset Idiopathic Intracranial hypertension (IIH) is a heterogenous disease. The knowledge on disease trajectory and long-term outcomes and its predictors is limited. • A higher opening pressure and factors suggestive of the metabolic syndrome predict an unfavorable disease coursewhereasfemale sex and disease recurrence are significantly associated with poor visual outcomes • A third of the patients diagnosed with IIH experience ongoing headachesdespite achieving favorable visual outcomes.This subset, characterized by lower disease-severity indicators at onset may represent a distinct subgroup warranting a different therapeutic approach.

Disease Endotypes Predict the Severity of Mucous Membrane Pemphigoid

Mucous membrane pemphigoid is an autoimmune disease with variable clinical presentation and multiple autoantigens. To determine whether disease endotypes could be identified on the basis of the pattern of serum reactivity, the clinical and diagnostic information of 70 patients with mucous membrane pemphigoid was collected, and reactivity to dermal or epidermal antigens, using indirect immunofluorescence, and specific reactivity to bullous pemphigoid (BP) autoantigens BP180 and BP230, collagen VII, and laminin 332 were evaluated. Most patients had lesions at multiple mucosae, with the most prevalent being oropharyngeal (mouth, gingiva, pharynx; 98.6%), followed by ocular (38.6%), nasal (32.9%), genital or anal (31.4%), laryngeal (20%), and esophageal (2.9%) sites and skin (45.7%). Autoantigen profiling identified BP180 (71%) as the most common autoantigen, followed by laminin 332 (21.7%), collagen VII (13%), and BP230 IgG (11.6%). Reactivity to dermal antigens predicted a more severe disease characterized by a higher number of total sites involved, especially high-risk sites, and a decreased response to rituximab. In most cases, identification of dermal indirect immunofluorescence reactivity is an accurate predictor of disease course; however, confirmation of laminin 332 reactivity is important, with dermal indirect immunofluorescence positivity because of an increased risk of solid tumors. In addition, the ocular mucosae should be monitored in patients with IgA on direct immunofluorescence.

Mucosal Atrophy Predicts Poorer Outcomes in Pediatric Ulcerative Colitis-A National Inception Cohort Study.

Outcomes in pediatric ulcerative colitis (UC) are heterogeneous and predictors of disease course eagerly sought. Mucosal atrophy (MA) is characterized by histological abnormalities of colonic intestinal glands. To determine the prevalence of MA in a national inception cohort of pediatric UC and its impact on outcomes. Irish children < 16 years old with UC are diagnosed at a single referral center. At diagnosis, patients underwent phenotyping by Paris classification and activity assessment by Pediatric Ulcerative Colitis Activity Index. Biopsies from all colonic segments were evaluated for MA. Patients were followed prospectively. The primary outcome was corticosteroid-free remission at 1 year. Secondary outcomes included relapse, treatment escalation, and colectomy by 2 years. Of 251 pediatric patients with UC (mean age 11.8 years, 55% male), 38 (15%) had MA on diagnostic biopsy. Baseline characteristics were similar between groups with/without MA and there was no difference in steroid-free remission or rates of moderate-severe UC at 1 year. Patients with MA had higher use of steroids (29% vs 15%, P = 0.04) and immunomodulators (40% vs 21%, P = 0.04) at 6 months, higher biologic use at 1 year (34% vs 16%, P = 0.03), earlier first relapse (mean ± SD 29.4 ± 26.1 vs 46.7 ± 43.4 weeks after diagnosis, P = 0.02), and higher colectomy rates by 2 years (21% vs 8%, P = 0.01). Children with MA at diagnosis had higher colectomy rates despite earlier treatment escalation and similar baseline severity scores. We identify MA as a promising new prognostic marker in children with newly diagnosed UC.

DOP58 predictors of complicated disease course in CD in an administrative database: a nationwide study from the epi-IIRN

Abstract Background Several studies have proposed models to predict disease outcomes in Crohn’s disease (CD), but with limited accuracy, often due to small sample size. We aimed to use a large nationwide cohort to explore predictors of disease course in CD. Methods Data of patients diagnosed with CD in the epi-IIRN cohort 2005-2020 were retrieved from the four Israeli Health-Maintenance-Organizations covering 98% of the population. The following potential predictors were explored: demographic data, laboratory results, induction medications, change in medications during the induction period, extra-intestinal manifestations, perianal disease, and diagnostic delay. The primary outcome was complicated disease course defined as CD-related surgery, steroid-dependency, or need for more than one biologic class. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results into five groups of disease severity (minimal, mild, moderate, severe, and extreme). A Cox proportional hazard model with Bonferroni correction to adjust for multiple comparisons was sought to assess the relationship between predictors and time to complicated outcome. A nomogram was created by conversion of the hazard ratios from the model to points on a scale between 0 to 100. Results A total of 19,263 patients with 140,354 person-years of follow-up were included, of whom 6,874 (36%) had complicated disease course. In a Cox multivariable regression model, complicated disease course was predicted by diagnostic delay (HR 1.2 [95%CI 1.09-1.33]), induction therapy with biologics (HR 2.8 [2.21-3.64]), severity of laboratory tests prior to diagnosis (HR 1.6 [1.28-1.99]) and perianal disease (HR 1.5 [95%CI 1.4-1.6]; Figure 1). Specifically in the laboratory tests, there was a gradual increase in rates of patients who had complicated disease course amongst the disease severity clusters (p&amp;lt;0.001; Figure 2). These variables formed a model to predict time to complicated disease, with fair accuracy during the first year from diagnosis (AUC 0.69 [95%CI 0.65-0.73]; Figure 3). Conclusion In this nationwide cohort, complicated disease course was apparent in a third of patients and predicted by diagnostic delay, serum laboratory tests, perianal disease and type of induction therapy. Our results also highlight the ability of clustering analyses to define clinically meaningful categories in administrative database of CD.

P852 predictors of complicated disease course in UC in an administrative database: a nationwide study from the epi-IIRN

Abstract Background There is uncertainty about the ability to predict disease course in UC, often since prediction studies are small and include selected population. We aimed to use a large nationwide cohort to explore predictors of disease course in UC. Methods Data of patients diagnosed with UC in the epi-IIRN cohort 2005-2020 were retrieved from the four Israeli Health-Maintenance-Organizations covering 98% of the population. The following potential predictors were explored: demographic data, laboratory results, induction medications, and extra-intestinal manifestations. The primary outcome was complicated disease course defined as colectomy, steroid-dependency, or need for more than one biologic class. Hierarchical clustering categorized disease severity at diagnosis based on available laboratory results into four groups of disease severity (mild, moderate, severe, and extreme). Results A total of 15,111 UC patients with 114,208 person-years of follow-up were included, of whom 2,213 (14%) had complicated disease course. The latter was predicted in a Cox multivariable regression model by induction therapy with biologics (HR 3.84 [2.4-6.12]) and severity of laboratory tests prior to diagnosis (HR 1.41 [1.03-1.92]). The use of topical treatment (5-ASA or steroids enema/suppository) as monotherapy was protective with a decreased risk of complicated disease course (compared with untreated, HR 0.5 [0.38-0.63). Younger age of diagnosis (HR of pediatric-onset compared to adult-onset 1.79 [1.48-2.15]) and recent year of diagnosis (HR 1.03 [1-1.04]) were also associated with complicated outcome. Jews had 23% reduced risk of complicated disease course compared with Arabs (HR 0.77 [0.60-0.97]) (Figure 1). Specifically in the laboratory tests, there was a gradual increase in complicated disease amongst the disease severity clusters (p&amp;lt;0.001; Figure 2). Conclusion In this nationwide cohort, complicated disease course was apparent in 14% of patients and predicted by serum laboratory tests and induction therapy with biologics. Jewish ethnicity and topic therapy (reflecting proctitis) were associated with better outcomes.

P158 Intestinal Ultrasound at IBD diagnosis predicts surgery – a Copenhagen IBD cohort study

Abstract Background The disease course of inflammatory bowel disease (IBD) is heterogeneous and unpredictable. Currently, we are unable to predict which patients will need IBD-related bowel resection in the first year after diagnosis. Intestinal Ultrasound (IUS) has been proven as a non-invasive modality for assessing disease activity in IBD. However, the evidence for IUS as a predictor of disease course is still limited. Here we present novel data on the predictive value of IUS performed at the time of IBD diagnosis. Methods Patients with new-onset IBD are currently being included in the ongoing multicentre prospective inception cohort study, the IBD Prognosis Study (May 2021 – April 2023). IUS is performed at the time of diagnosis and the patients are followed prospectively. Patients with proctitis are not assessed with IUS. The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is calculated for the most inflamed segment with a high score indicating severe disease activity. IBUS-SAS (0-100) incorporates the bowel wall thickness (BWT), bowel wall stratification, colour Doppler signal, and inflammatory fat. Surgery was defined as an IBD-related bowel resection. Patients treated with corticosteroids for &amp;gt; 72 hours or with any IBD-treatment &amp;gt; two weeks prior to IUS were excluded from analysis. In this abstract, we report our preliminary results after including patients for 16 months. Results IBUS-SAS at diagnosis was available in 133 patients (out of 242 included). 68 patients were diagnosed with Crohn’s disease (CD) (ilieal: 22, colonic: 23, ileocolonic: 23) and 65 patients were diagnosed with ulcerative colitis (UC) or unclassified IBD (left-sided colitis: 20, extensive colitis: 45). Median follow-up was 226 days. During follow-up 10 patients underwent surgery (7.5%). These included 4 patients with UC (extensive colitis: 3, left-sided colitis: 1) and 6 patients with CD (ileal: 2, colonic: 2, ileocolonic: 2). Mean IBUS-SAS at diagnosis was 92.6 among patients who underwent surgery during follow-up vs. 48.8 for patients who did not undergo surgery (p&amp;lt;0.0001). Distribution of scores is shown in Figure 1. Mean BWT at diagnosis was 8.3 mm among patients who underwent surgery during follow-up vs. 5.0 mm for patients who did not undergo surgery (p&amp;lt;0.0001). In total, 12 patients had an IBUS-SAS &amp;gt; 90 at diagnosis and among these 7 (58.3%) were operated during follow-up. Figure 2 shows a Kaplan-Meier Curve of surgical free survival stratified by IBUS-SAS at diagnosis. Conclusion IUS activity at diagnosis of IBD seems to have the capability to predict short term risk of IBD-related surgery. Our results suggest IUS might be used at diagnosis to identify patients at high risk of IBD-related surgery.

Characteristics of patients with juvenile dermatomyositis from 2001-2021 at a tertiary care center.

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in the pediatric population and can represent a medical emergency. However, many features of JDM remain poorly understood, disease presentation is highly variable, and predictors of disease course have yet to be identified. This retrospective chart review included 47 JDM patients seen at a tertiary care center over a 20-year period. Characteristics such as demographics, clinical signs and symptoms, antibody positivity, dermatopathology features, and treatments were recorded. All patients had evidence of cutaneous involvement, whereas 88.4% experienced muscle weakness. Constitutional symptoms and dysphagia were commonly present. The most frequent cutaneous findings were Gottron papules, heliotrope rash, and nailfold changes. Anti-TIF1? was the most prevalent myositis-specific autoantibody. Management involved systemic corticosteroids in nearly all cases. Strikingly, the dermatology department was only involved in the care of four in every ten (19/47) patients. Prompt recognition of the strikingly reproducible skin findings present in JDM can improve disease outcomes in this population. This study highlights the need for increased education of such pathognomonic findings as well as more multidisciplinary care. In particular, a dermatologist should be involved in the care of patients presenting with muscle weakness and skin changes.

1078. Vaccine-induced antibody level predicts the clinical course of breakthrough infection of COVID-19 caused by delta and omicron variants: a prospective observational cohort study

Abstract Background This study aimed to determine the effect of vaccine on clinical course of delta and omicron variant infection. Furthermore, we tried to evaluate the utility of antibody level against spike protein as a predictor of disease course of COVID-19 in vaccinated patients. Methods Between December 11, 2021 and February 10, 2022, we performed a prospective observational cohort study in an institution of South Korea. Among adult patients admitted due to COVID-19, individuals with confirmed delta and omicron variant infection were included. Multivariable logistic regression analysis was performed to determine the association between antibody level and clinical course of breakthrough infection in vaccinated patients. The relationship between antibody level and cycle threshold (Ct) values was confirmed using a generalized linear model. We used the antibody titers collected within 7 days of symptom onset or diagnosis and the Ct values tested on days 5-7 days after initial diagnosis. Figure 1.Study flow diagram. A, Study flow of enrollment. B, Severe acute respiratory syndrome coronavirus 2 diagnosis, antibody to spike protein test, variant type assay*Patients were diagnosed at a median of 2 days (interquartile range [IQR] 1–3) after symptom onset.¶Antibody tests were performed at a median of 4 days (IQR 2–6) after symptom onset or diagnosis, whichever was earlier.† Variant-type assays were conducted at a median of 4 days (IQR 3–5) after diagnosis. Results Of 161 patients with delta and omicron variant infection, 106 vaccinated patients (39 delta and 67 omicron) had available serum samples. The geometric mean titers of antibodies in patients who experienced the fever (≥37.5°C), hypoxia (≤94% of SpO2), pneumonia, C-reactive protein (CRP) elevation ( &amp;gt;8 mg/L) or lymphopenia (&amp;lt; 1,100 cells/μL) during hospitalization were 1201.5 U/mL, 98.8 U/mL, 774.1 U/mL, 1335.1 U/mL, and 1032.2 U/mL, respectively, which were lower compared with those who did not (p&amp;lt; 0.05 for all). Increase in antibody level of vaccinated patients with delta and omicron infection was associated with decrease in occurrence of fever (aOR, 0.23; 95% CI, 0.12-0.51), hypoxia (aOR, 0.23; 95% CI, 0.08-0.7), CRP elevation (aOR, 0.52; 95% CI, 0.29-0.0.94), and lymphopenia (aOR, 0.57; 95% CI, 0.33-0.98) during hospitalization, regardless of virus type or booster vaccination status. Data from 33 patients who had Ct values suitable for analysis showed a positive correlation between antibody levels and Ct values (p=0.02). Table 1.Association of antibody titres and variables with clinical courses during hospitalisation in vaccinated patients with breakthrough infections caused by delta and omicron variantsMultivariable logistic regression analysis was performed to determine the effect of antibody levels on the clinical course of breakthrough infections. Fever, hypoxia, pneumonia, CRP elevation, or lymphopenia were selected as variables representing the clinical course. Confounding factors were included in each multivariable model, as described below. Antibody titres were log10 transformed for analyses. Abbreviations: OR, odds ratio; CI, confidence interval; BT, body temperature; SpO2, percutaneous oxygen saturation; CRP, C-reactive protein; CCI, Charlson comorbidity index.a Multivariable analysis adjusted for age and sex.b Multivariable analysis adjusted for age, sex, immunocompromised status, and variant type.c Multivariable analysis adjusted for age, sex, immunocompromised status, CCI, and variant type‡d Multivariable analysis adjusted for sex‡ and variant type.f Multivariable analysis adjusted for sex, CCI, and variant type.†Presence of pneumonia was determined using chest radiography.‡ In addition to antibody titre, the omicron variant was associated with a decrease in the occurrence of pneumonia (OR, 0.150; 95% CI, 0.050-0.448); females were associated with a decrease in the occurrence of CRP elevation (OR, 0.431; 95% CI, 0.194-0.955).Figure 2.Comparison of antibody levels between vaccinated patients with or without specific signs during hospitalisation This analysis included 106 patients with delta and omicron variant infections whose serum samples were collected within 7 days of symptom onset or diagnosis. Antibody levels are described as box plots of medians with interquartile ranges. BT, body temperature; SpO2, percutaneous oxygen saturation; w/o, without; CRP, C-reactive protein Figure 3.Association of antibody titres and Ct valuesData from 33 patients, with Ct values measured 5–7 days after diagnosis, showed a positive correlation between antibody levels and Ct values (slope: 0.0004, p=0.022)Abbreviations: Ct, cycle threshold; PCR, polymerase chain reaction Conclusion Antibody levels are predictive of the clinical course of COVID-19 in vaccinated patients with delta and omicron variant infections. Our data highlight the need for concentrated efforts to monitor patients with SARS-CoV-2 infection who are at risk of low antibody levels. Disclosures All Authors: No reported disclosures.

MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer.

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn’s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs.

Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital.

Leigh syndrome (LS) is a heterogeneous neurodegenerative disease and the most frequent pediatric manifestation of mitochondrial disease. In the largest patient collection to date, this study aimed to provide new insights into the clinical and genetic spectrum of LS, defect-specific associations, and predictors of disease course and survival. Clinical, metabolic, neuroimaging, onset, and survival data were collected from the medical records of 209 patients referred to the Beijing Children's Hospital with symmetrical basal ganglia and/or brainstem neuroimaging changes indicative of LS by 30 centers from the Chinese network of mitochondrial disease (mitoC-NET) between January 2013 and July 2021 for exploratory analysis. Pathogenic variants were identified in 52 genes, most frequently MT-ATP6, SURF1, and PDHA1. Maternally inherited variants accounted for 42% (heteroplasmy level ≥90% in 64%). Phenotypes spanned 92 Human Phenotype Ontology terms. Elevated serum lactate (144/195), global developmental delay (142/209), and developmental regression (103/209) were most frequent. Discriminating neuroimaging and/or clinical features were identified for MT-ATP6 (m.9176T>C), MT-ND5, PDHA1, SUCLG1, and SURF1. Poorest survival was associated with MT-ND5, MT-ATP6 (m.8993T>C and m.9176T>C), SURF1, and ALDH5A1 (≤50% 3year's survival), in contrast to milder defects with specific treatment (ECHS1 and SLC19A3, 100% 3 year's survival). Our data define phenotype, onset, and survival of LS in a defect-specific manner, identifying features discriminating between genetic defects and predictive of disease outcome. These findings are essential to early diagnosis, in optimizing family counseling, and to the design and monitoring of future clinical trials, the next frontier of LS research. ANN NEUROL 2022;91:466-482.

Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics: A Population-based Study From The epidemiology group of the Israeli IBD Research Nucleus (epiIIRN).

Both perianal and pediatric-onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult-onset perianal CD and their disease course. We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD-9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease. A total of 12,905 patients were included (2186 [17%] pediatric-onset, 10,719 [83%] adults), with a median follow-up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6-4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1-3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid-dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age. PCD is more common in pediatric-onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.

DOP10 Intestinal Ultrasound at IBD diagnosis predicts major disease events – A Copenhagen IBD cohort study

Abstract Background The disease course of inflammatory bowel disease (IBD) is heterogeneous and highly unpredictable. Intestinal Ultrasound (IUS) is a non-invasive modality capable of assessing disease activity in IBD. IUS is reliable, patient-friendly, and allows frequent monitoring of disease activity. However, the evidence for IUS as a predictor of disease course is still limited. Here we present novel data on the predictive value of IUS performed at the time of IBD diagnosis. Methods Patients with new-onset IBD are currently being included in the ongoing multicentre prospective inception cohort study, the IBD Prognosis Study. During the first five years following diagnosis, patients undergo regular clinical, biochemical, endoscopic, and imaging assessments. IBD treatment and disease events are prospectively recorded. IUS is performed at diagnosis, after three months, and hereafter annually. Patients with proctitis do not undergo assessment with IUS. The newly developed IUS score, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), is calculated for the most inflamed segment, with a high score indicating severe disease activity. The score incorporates bowel wall thickness (BWT), bowel wall stratification, colour Doppler signal, and inflammatory fat. In this abstract, we report our preliminary results after including patients for six months. Results IBUS-SAS at diagnosis was available in 60 patients. 32 patients were diagnosed with Crohn’s disease (ilieal: 7, colonic: 19, ileocolonic: 6) and 28 patients were diagnosed with ulcerative colitis (UC) or unclassified IBD (proctitis: 1, left-sided colitis: 8, extensive colitis: 19). The mean IBUS-SAS at diagnosis was 51.1, with a mean BWT of 5.2 mm. Major clinical outcomes were initiation of biologic therapy, n=12 (20.0%), IBD-related bowel resection, n=5 (8.3%), IBD-related hospitalisation, n=19 (31.7%). The mean IBUS-SAS at diagnosis was 66.2 among patients with the combined endpoint of any of these disease outcomes during follow-up vs. 34.7 for no major outcomes (p&amp;lt;0.001), see Figure 1. Additionally, we found that all patients with an IBUS-SAS above 80 at diagnosis had been hospitalised and started on systemic steroids. So far, 20 patients had an IUS follow-up scan after three months showing a mean IBUS-SAS reduction by 17.0 points (p=0.008). Conclusion We present data on the predictive value of early IUS in new-onset IBD. IUS activity at diagnosis of IBD seems to have the capability to predict short term disease outcome. At diagnosis, high IBUS-SAS is associated with major disease events such as starting biological therapy, IBD-related bowel resection, and IBD-related hospitalisation. Furthermore, response to treatment is reflected by a decrease in IBUS-SAS after three months.

Современные подходы к диагностике и лечению минимальной печеночной энцефалопатии у пациентов с циррозом печени

Hepatic encephalopathy (HE) is one of the most common and dangerous complications of cirrhosis. HE is considered a predictor of death within the first year after onset in more than 60% of patients. Recently, studies have focused on minimal HE (MHE) which is characterized by medical, social, and clinical relevance. MHE patients are a risk group for cirrhosis complications and hospital admission. This demonstrates the need for early therapeutic and preventive measures for MHE. This paper provides information on current diagnostic and treatment tools for MHE in cirrhosis and illustrates the efficacy of various therapies on the outcomes and quality of life in these patients. The authors conclude that one should rely on studies establishing the efficacy of rifaximin-α to regress MHE, improve the quality of life and reduce the risks of complications and decompensation in cirrhosis compared to other medications. Meanwhile, further studies are needed to reveal favorable and unfavorable predictors of disease course and to optimize therapeutic and preventive measures in these patients. KEYWORDS: cirrhosis, hepatic encephalopathy, minimal hepatic encephalopathy, psychometric tests, lactulose, L-ornithine-L-aspartate, rifaximin-α FOR CITATION: Bakulin I.G., Ivanova K.N. Up-to-date diagnostic and treatment approaches to minimal hepatic encephalopathy in cirrhosis. Russian Medical Inquiry. 2022;6(5):272–277 (in Russ.). DOI: 10.32364/2587-6821-2022-6-5-272-277

Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

Background. Diffuse large B-cell lymphoma (DLBCL) amounts for 30-40 % of all adult non-Hodgkin's lymphomas. After R-CHOP immunochemotherapy 40 % of patients develop early relapsed or therapy-refractory disease. The conventional prognostic parameters in DLBCL are not always effective. Therefore, exploring further predictors of disease course remains an issue. Aim. To assess the prognostic value of pAKT1 and рSy&lt; expression in DLBCL. Materials &amp; Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cutoff of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher's exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test). Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index &gt; 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk&lt; expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49-10.9; p &lt; 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54-7.30; p = 0.002). Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk&lt; markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.