Non-active Disease Research Articles

Measured and predicted resting metabolic rate in patients with inflammatory bowel disease

ObjectiveThe present study aimed to compare measured and estimated resting metabolic rate (RMR) predicted by selected equations in patients with nonactive inflammatory bowel disease (IBD) on an outpatient university clinic regimen. Research Methods & ProceduresSeventy-two adult (≥20 years) IBD patients (45 with Crohn's disease-CD) had RMR measured (mRMR) by indirect calorimetry and also estimated by predictive equations (Cunningham, Henry, Anjos et al., and Marra et al.). Body composition was assessed by DXA. Absolute Bias (estimated - mRMR) and % Bias (Bias/mRMR) were calculated. Agreement was assessed as the limit of agreement (LoA) in the Bland & Altman approach. ResultsThere was no difference in age, body composition and mRMR between individuals with CD (5414.2 ± 1023.7 kJ/day) and ulcerative colitis (5443.9 ± 1008.9 kJ/day). Among the equations, only the Anjos et al.'s population-specific equation (-52.1 [642.0] kJ/day, P = 0.493; LoA: -1311; 1206 kJ/d) accurately estimated RMR. The equations of Marra et al. produced the highest % Bias (24.1 ± 14.8%). The Bland & Altman plots showed that the range of the LoA was relatively similar for all equations. In the simple regression analysis, the model with FFM resulted in a higher coefficient of determination (R2 = 0.51 for DC 0.74 for UC) compared to the model that included BM (R2 = 0.35 for DC and 0.65 for UC). ConclusionsAmong the equations analyzed, only Anjos et al.'s accurately estimated RMR in outpatients with nonactive IBD. However, caution is advised when applying it at the individual level, due to the wide observed LoA.

The circular RNA hsa_circ_0045800 serves as a favorable biomarker in pathogenesis of sjögren's syndrome

BackgroundCircular RNAs (circRNAs) play various roles in the development of many autoimmune diseases. However, their expression profiles and specific function in Sjögren's Syndrome remains largely unknown.ObjectivesWe aimed to investigate circRNAs potential diagnostic value in primary Sjögren's syndrome (pSS) and contribution to the pathogenesis of pSS.MethodsThis study included 102 subjects, 51 pSS patients and 51 healthy controls. The concentration of hsa_circ_0045800 was analyzed in peripheral blood mononuclear cells obtained from 51 pSS patients and 51 healthy controls by qRT-PCR. We established a receiver operating characteristic curve (ROC) to assess the biological diagnostic value of hsa_circ_0045800 for pSS. In addition, we analyzed the correlation between hsa_circ_0045800 and disease activity in Sjogren's syndrome. A differential analysis was also conducted on the concentration of hsa_circ_0045800 in patients in pSS patients before and after treatment. We studied the downstream mechanism of hsa_circ_0045800 through bioinformatics analysis and confirmed it using luciferase reporter gene assay.ResultsWe confirmed that the concentration of hsa_circ_0045800 was elevated 10.4-fold in peripheral blood mononuclear cells of pSS patients than in healthy controls (p = 0.00). In the pSS active disease group, the concentration of hsa_circ_0045800 is 2.5-fold higher compared to the pSS non-active disease group (p = 0.04). The concentration of hsa_circ_0045800 after treatment was decreased by 80% compared with that before treatment (p = 0.037), suggesting its utility as a potential marker for monitoring treatment efficacy. ROC curve analysis showed that the diagnostic value of hsa_circ_0045800 in pSS patients was significantly higher than that in healthy controls, with an area under the curve of 0.865, a sensitivity of 74%, and a specificity of 92%. The concentration of hsa_circ_0045800 is correlated with various clinical factors: the concentration of hsa_circ_0045800 is positively associated with age (r = 0.328, P = 0.019), oral dryness (r = 0.331, P = 0.017), while it is negatively correlated with HGB (r = -0.435, P = 0.001) and and hypothyroidism (r = -0.318, P = 0.023). Bioinformatics predictions and luciferase assays indicated that hsa_circ_0045800 acts as a molecular sponge for miR-1247-5p, with SMAD2 being a target gene of miR-1247-5p.ConclusionOur study results show that hsa_circ_0045800 potentially contributes to the development and progression of pSS via the miR-1247-5p/SMAD2 pathway. Peripheral blood mononuclear cells are directly involved in the pathogenesis of pSS, and the discovery of hsa_circ_0045800 in peripheral blood mononuclear cells highlights its potential as a novel biomarker for disease activity and diagnosis in patients with pSS.Key Points• The concentration of hsa_circ_0045800 was higher in peripheral blood mononuclear cells of pSS patients.• Hsa_circ_0045800 promoted pSS progression through miR-1247-5p–SMAD2 axis.• Hsa_circ_0045800 is a potential biomarker for pSS.

One Incremental Stride for Doxycycline, One Substantial Advancement for Thyroid Eye Disease.

The aim of this study is to assess the effectiveness of a 12-week doxycycline treatment for thyroid eye disease (TED), an autoimmune condition associated with thyroid dysfunction. In this randomized controlled clinical trial, 82 patients were randomly assigned at a 1:1 ratio to receive doxycycline (50 mg) or to undergo no treatment. Various metrics, including margin reflex distance (MRD1 and MRD2), eyelid aperture, levator muscle function, lagophthalmos, proptosis, ocular motility, diplopia, and Graves' ophthalmopathy-specific quality-of-life (GO-QOL) scale scoring were assessed. Exclusion criteria were uncontrolled systemic diseases, tetracycline allergies, pregnancy, lactation, or age below 18. The mean age was 51.6 years (SD), 87.8% of participants were female, and all were Caucasians. By week 12, the doxycycline group exhibited a significant improvement rate based on MRD2 (from 4 to 15 participants with physiological findings), clinical activity score (from 7 to 35 participants with non-active disease), and GO-QOL (from 51.22% to 70.73% of participants with a good life quality). Doxycycline showcased anti-inflammatory and immunomodulatory effects in treating TED, suggesting its potential efficacy for TED and other orbit inflammatory conditions. However, these results warrant further validation through future research involving extended follow-up periods and larger cohorts.

N28 Stress and Inflammatory Bowel Disease – are there any differences during flare and remission?

Abstract Background Patients with Inflammatory Bowel Disease (IBD) often experience that stress has a negative effect on the disease. Studies have also shown a possible connection between stress and active IBD. This study aims to investigate the patients´ level of stress (both subjective and objective) in relapse and in remission. With this information we may determine if the levels of stress are higher in active disease compared to remission. Methods Inclusion criteria were having diagnosis with ulcerative colitis or Crohn`s disease, being over 18 years old, and having a flare in IBD. Measurements were made in cortisol in saliva and filling in the questionnaires Short Health Scale (SHS) and Perceived Stress Scale (PSS). All measurements were done at the beginning of the flare and then a second time when the patient was classified as being in remission. Flare and remission were determined by endoscopic examination and fecal calprotectin. Results A total of 20 patients completed the study. Median age was 45 years. A number of 17 (85%) had ulcerative colitis, and 12 (60%) were women. The levels of cortisol showed normal values both in active disease and in remission. Neither the results in PSS showed any differences between active and non-active disease. However, the results showed medium high values of stress in both measurements (table 1). SHS showed improvements in all four questions, but mostly in question 1 concerning symptoms. Conclusion No significant differences could be found in levels of stress when measuring cortisol and experienced stress in flare and in remission. However, the PSS showed that the participants had medium high levels of stress at both measurements. This could indicate a more constant stress in patients with IBD. A weakness in this study is the difficulty in measuring cortisol at the same time in each patient. Another weakness is the small population. There is still a need to examine the connection between stress and IBD. Concerning this study there is a wish to more closely investigate possible differences within each patient.

P519 Assessment of anal sphincter complex in pregnant patients with non-active perianal Crohns disease

Abstract Background Pregnant IBD patients are more likely to undergo Cesarean delivery (CS).. Active perianal Crohn’s disease (PCD) is the only Crohns - related indication for CS. The rationale for CS in this group is that active PCD damages the sphincters and therefore a vaginal delivery may exacerbate the damage to the point of fecal incontinence. Pregnant PCD patients with non-active PCD are commonly not offered CS. We suspect that lack of active PCD does not necessarily attest for the physiological function of the anal complex sphincter and that vaginal delivery may exacerbate their condition to the point of incontinence. Therefore, we conducted a prospective trial to examine, prior to delivery, the anatomy and physiology of the sphincter complex in our cohort and weather pregnant patients with non-active PCD suffer from sphincter damageMethods All consecutive pregnant patients with Non-active PCD were enlisted. Patients underwent physical examination, anal manometry and Trans Rectal Ultra Sound (TRUS) before conception or during pregnancy before delivery. Active PCD was defined as: Perianal abscess, fistulas with active drainage, severe fissures and stricture. Non active PCD was defined as history of prior PCD, history of surgery for perianal fistula or old scars from previous abscess drainage. Results There were 13 patients who were enlisted to our study. Table 1 describes the TRUS, Manometry and pregnancy details. There were 9 patients (69%) with evidence of sphincter damage in our cohort including external and/or internal sphincter of at least 30 degrees of the muscle radius. Of them, 6 had posterior damage and 4 had anterior damage. In Manometry all patients had either normal or satisfying results. Three patients were strongly recommended to choose CS due to the sphincter damage. Conclusion patients with non-active PCD and future intent to deliver should be assessed routinely regarding their sphincter complex status. This should include TRUS, manometry and clinical evaluation. We discuss with each patient the advantages and disadvantages of vaginal delivery versus CS, weighing the risk of repeated CS (mainly placenta previa and accreta) against the risk of incontinence. Maternal age, Obstetrical history and estimated fetal weight at delivery are the main factors to consider. Although it is still unclear if detected muscle injury affect clinical incontinence, it is our practice to recommend CS for patients with significant muscle damage. We emphasize our recommendation specifically in patients with anterior damage because potentially delivery damage would be to the same area

The use of BRAF-inhibitors as monotherapy and in combination with cytosine arabinoside and 2-chloro-2’deoxyadenosine in pediatric patients with different forms of Langerhans cell histiocytosis

Background. Langerhans cell histiocytosis (LCH) is a rare disease that occurs due to abnormal proliferation and expansion of myeloid precursors. The occurrence of mutations in genes that encode key kinases of MAPK-signaling pathway leads to its pathological activation and has been shown the cause of disease. Mutations in BRAF and MAP2K1 genes are the most frequent among LCH patients. The effectiveness of BRAF-inhibitors in LCH patients has been shown in numerous studies.The purpose of the study – analyze the experience of BRAF-inhibitor vemurafenib administration as monotherapy and in combination with cytosine arabinoside (ARA-C) and 2-chloro-2'-deoxyadenosine (2-CdA) in pediatric patients with different forms of LCH.Materials and methods. Fifteen patients with various forms of LCH were enrolled in the study. BRAF mutations were detected in 14 patients, mutation in the MAP2K1 gene was detected in one case. Patients with “risk organ” (RO) involvement were included in the first group (n = 9). These patients received combined therapy with vemurafenib and ARA-C/2-CdA. Patients without RO involvement, included in group 2 (n = 6), received vemurafenib as monotherapy. The assessment of the response to the therapy in group 1 was carried out in accordance with the DAS scale, in group 2 in accordance with the RECIST v1.1. The toxicity assessment in both groups was carried out in accordance with the CTCAE v5.0.Results. All patients in group 1 achieved non-active disease status with a median of 35 (28–61) days. In group 2 partial response to vemurafenib was achieved in 5 cases. Relapse after targeted therapy termination was diagnosed in two patients. Photodermatitis was the most common side effect of targeted therapy.Conclusions. The use of vemurafenib was effective in both groups. There were no cases of grade III–IV toxicity according to CTCAE v5.0 associated with vemurafenib administration in this study. The combination of vemurafenib and ARA-C/2-CdA showed high efficacy and good tolerability in group 1. Two cases of disease relapse after targeted therapy cessation in group 2 show that the monotherapy approach does not always allow to achieve long-term remission in LCH patients.

The mean platelet volume (MPV) in patients with systemic lupus erythematosus (SLE) and its correlation with disease activity: a cross-sectional/case–control study

Introduction: Systemic lupus erythematosus (SLE) is a systemic disease, with unknown etiology. The authors aimed in this study to determine the connection between mean platelet volume (MPV) and disease activity of SLE. Although it has been studied in other rheumatological conditions like rheumatoid arthritis, its role in adult patients with SLE needs to be defined, especially in Syria. Materials and methods: The authors have included in a cross-sectional study, 80 patients with SLE and 80 controls. The SLE group was divided into two groups based on their disease activity index: the active disease group and the non-active disease group. In all groups, MPV and erythrocyte sedimentation rate (ESR) were analyzed. Clinical findings and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were evaluated in all patients. Results: MPV was significantly lower in SLE patients compared to the control group (8.49±1.2 fl and 10.0±0.5 fl, respectively) (P=0.001). A decrease in MPV below the cut-off value (7.2 fl) increased the risk of active disease by an odds ratio of 9.79 (95% CI: 3.4–27.9) (P<0.001). Conclusion: MPV may be a disease activity indicator in patients with SLE. MPV is reduced in patients with active SLE and presents an inverse correlation with SLEDAI.

Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.

Much of the current literature on treatment patterns and disability progression in multiple sclerosis (MS) does not distinguish between the relapsing-remitting and progressive subtypes (including primary [PPMS] and secondary progressive MS [SPMS]), or between active/nonactive disease. Current treatment options for progressive MS are limited, with only one approved product for PPMS and none specifically for nonactive SPMS. Here we report treatment patterns, disability progression, and unmet needs among patients with active and nonactive PPMS and SPMS. The annual, cross-sectional survey from the Adelphi Disease Specific Program was used to collect physician-reported data on US adult patients with PPMS and SPMS, including active and nonactive disease. Treatment patterns (including the proportion of patients who were untreated with a disease-modifying therapy [DMT]), disability progression, and unmet need are described from 2016 to 2021. Data were collected for 2067 patients with progressive MS (PPMS, 1583; SPMS, 484). A substantial proportion of patients were untreated across all groups, and this was highest for nonactive PPMS (~ 43%). The proportion of untreated patients generally declined over time but remained high in 2018-2021 (~ 10-38%). Among treated patients, the proportion receiving infusions increased over time to ~ 34-46%, largely driven by ocrelizumab use after approval. Disability progression was reported for most patients (> 50%), including many who were receiving a DMT. Across all disease subtypes, when physicians were asked about the greatest unmet need with current DMTs, they most frequently cited effectiveness (~ 63-87%), and specifically slowing disease progression (~ 32-59%). This analysis of physician-reported data reveals that patients with progressive MS, particularly those with nonactive disease, frequently remain untreated or continue to decline despite treatment with available DMTs. Thus there is an enduring need for safe and effective treatments for this underserved population.

Assessment of patient-reported symptoms and distress in IgG4-related disease (IgG4-RD): Development, clinical validation, and content validation of the IgG4-RD Symptom Severity Index

ObjectiveIgG4-related disease (IgG4-RD), a multi-organ autoimmune disease, causes diverse manifestations that can lead to symptoms and distress. We developed and validated the Symptom Severity Index (SSI) to assess symptom burden. MethodsA pilot SSI was tested in n = 5; several gaps were identified. Twenty semi-structured qualitative interviews were performed to expand the item set and identify missing symptoms. Subsequent changes resulted in the current SSI; it was administered with quality of life (QOL) measures to n = 136. We assessed symptom burden and the construct validity of the SSI. A distress score for each symptom is calculated by multiplying symptom frequency (“Never” [0 points] to “Every Day” [3 points]) by associated distress (“None” [0 points] to “Very Much” [4 points]). Each distress score is summed to calculate a total SSI score. ResultsThe SSI assesses the frequency and distress of 24 symptoms. Among n = 136 with ≥ 1 SSI, 90% experienced ≥ 1 symptom and 88% had distress. The median SSI score was 6.5 (IQR 3.0, 18.0). Fear of more severe disease was observed in 49%. The SSI inversely correlated with the SF-36 (r= - 0.51, p<0.001), the feeling thermometer (r= - 0.28, p<0.001), and the EQ-5D (r= - 0.28, p<0.001). The median SSI score was higher during active vs non-active disease among n = 52 who completed >1 SSI (15 [6, 26] vs. 3 [2, 14], p = 0.008). ConclusionsSymptoms and distress are common in IgG4-RD and associated with worse health-related QOL. The SSI has face, content, and construct validity; it corresponds with QOL measures.

Effects of baseline age and disease duration on the efficacy and safety of siponimod in patients with active SPMS: Post hoc analyses from the EXPAND study.

Older age and longer disease duration (DD) may impact the effectiveness of disease-modifying therapies in patients with multiple sclerosis (MS). Siponimod is a sphingosine 1-phosphate receptor modulator approved for the treatment of active secondary progressive MS (SPMS) in many countries. The pivotal phase 3 EXPAND study examined siponimod versus placebo in a broad SPMS population with both active and non-active disease. In this population, siponimod demonstrated significant efficacy, including a reduction in the risk of 3-month confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP). Benefits of siponimod were also observed across age and DD subgroups in the overall EXPAND population. Herein we sought to assess the clinical impact of siponimod across age and disease duration subgroups, specifically in participants with active SPMS. This study is a post hoc analysis of a subgroup of EXPAND participants with active SPMS (≥1 relapse in the 2 years before the study and/or ≥1 T1 gadolinium-enhancing magnetic resonance imaging lesion at baseline) receiving oral siponimod (2mg/day) or placebo during EXPAND. Data were analyzed for participant subgroups stratified by age at baseline (primary cut-off: <45 year ≥45 years; and secondary cut-off: <50 years or ≥50 years) and by DD at baseline (<16 years or ≥16 years). Efficacy endpoints were 3mCDP and 6mCDP. Safety assessments included adverse events (AEs), serious AEs, and AEs leading to treatment discontinuation. Data from 779 participants with active SPMS were analyzed. All age and DD subgroups had 31-38% (3mCDP) and 27-43% (6mCDP) risk reductions with siponimod versus placebo. Compared with placebo, siponimod significantly reduced the risk of 3mCDP in participants aged ≥45 years (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.48-0.97), <50 years (HR: 0.69; 95% CI: 0.49-0.98), ≥50 years (HR: 0.62; 95% CI: 0.40-0.96), and in participants with <16 years DD (HR: 0.68; 95% CI: 0.47-0.98). The risk of 6mCDP was significantly reduced with siponimod versus placebo for participants aged <45 years (HR: 0.60; 95% CI: 0.38-0.96), ≥45 years (HR: 0.67; 95% CI: 0.45-0.99), <50 years (HR: 0.62; 95% CI: 0.43-0.90), and in participants with <16 years DD (HR: 0.57; 95% CI: 0.38-0.87). Increasing age or longer MS duration did not appear to increase the risk of AEs, with an observed safety profile that remained consistent with the overall active SPMS and overall SPMS populations in EXPAND. In participants with active SPMS, treatment with siponimod demonstrated a statistically significant reduction in the risk of 3mCDP and 6mCDP compared with placebo. Although not every outcome reached statistical significance in the subgroup analyses (possibly a consequence of small sample sizes), benefits of siponimod were seen across a spectrum of ages and DD. Siponimod was generally well tolerated by participants with active SPMS, regardless of baseline age and DD, and AE profiles were broadly similar to those observed in the overall EXPAND population.

Pilot study to estimate the safety and effectiveness of hydroxyurea and methotrexate recurrent langerhans cell histiocytosis (LCH-HU-pilot).

This study was a non-blinded, multicenter, single-arm study. Recurrent (relapsed) LCH is defined as the appearance of new lesions or the enlargement of preexisting lesions due to LCH. In this study, all patients received hydroxyurea, and if the treatment response was unsatisfactory, methotrexate was added. The duration of treatment was 48 weeks. The primary endpoint was the rate of non-active disease achievement, which was 24 weeks after initiating hydroxyurea administration. No active disease is defined as the resolution of all the signs and symptoms related to LCH.

Relapses of multisystem/multifocal bone Langerhans cell histiocytosis in paediatric patients: Data analysis from the JLSG-96/02 study.

We assessed relapse patterns in paediatric patients with relapsed Langerhans cell histiocytosis (LCH) who were initially treated with the JLSG-96/02 protocol. We analysed 187 relapse events in 101 relapsed LCH patients [31 with multifocal bone (MFB) and 70 with multisystem (MS) at LCH diagnosis] among a total 317 patients enrolled in JLSG-96/-02 studies. Relapse of LCH was defined as an exacerbation of the non-active disease (NAD) condition. Of the 317 patients, 101 (31.9%) had the first relapse at 1.5 years after initiation of therapy. The first relapse and subsequent relapses did not differ between patients with MFB and MS disease. Of the 187 relapse events, relapse occurred as a single-system disease (n=159; 85%), in which isolated bone relapse (n=104; 55%) was the most common. Relapse at MS disease with the risk of organ involvement is extremely rare. After relapse(s), most patients underwent chemotherapy (122/187; 65%) and 87% of them achieved NAD status again. The incidence of permanent consequences was significantly higher in patients with relapses than in those without relapses. In the JLSG cohort, bone relapse most occurred in both MFB and MS patients. Most relapses could be effectively controlled by repeated administration of the initial chemotherapy.

Local Community Policy and The Value of Local Wisdom of The Kemang Plant

Kemang plant is a plant that has the value of local wisdom in certain areas, especially in Bogor and Sukabumi. This study aims to determine the values of environmental policy and the value of local wisdom which is the basis for mysticism in specific communities toward the Kemang plant. The method used is qualitative with a descriptive analysis research design. The research sample consisted of 46 people who were taken by random sampling technique. The variables studied are indicators of plant availability, utilization of plants, aspects of local knowledge, local social processes, and circulating local wisdom values. The local community uses the plant as food and board, based on field results that the Kemang plant is experiencing extinction. 95% of the community believes that Buyut nonactive disease if passes the Kemang plant, its Buyut is nonactive will experience active disease. 89% of people with Buyut disease have the condition.

Effects of Laser Therapy on Periodontal Status in Adult Patients Undergoing Orthodontic Treatment.

Orthodontic treatment with fixed devices should only be indicated in case of a stable, non-active periodontal disease status. Throughout orthodontic treatment, a careful assessment of the periodontal status is advised. Due to its anti-inflammatory and antimicrobial effects, laser therapy is frequently used as an adjunct to classic periodontal therapy. The aim of this study was to evaluate the advantages and limitations of the use of laser therapy on periodontal status during orthodontic treatment. Throughout the 9 months during which this placebo-controlled, single-blind clinical trial was conducted, 32 patients were included in the study, divided into two groups: microscope "+" (patients who observed the bacteria within the dental plaque-sample examination on the screen of a dark-field microscope in real time) and microscope "-" (patients who did not see the oral pathogens using a dark-field microscope). For all patients, using the split-mouth study design, laser therapy was applied to one hemiarch (HL), whereas the other hemiarch received treatment without active light (HC). After one month, by analyzing the main indicators of periodontal health status, we found that the plaque index (PI) and bleeding on probing (BOP) values were significantly decreased after receiving treatment (for PI: HL-p = 0.0005, HC-p = 0.0297; for BOP: HL-p = 0.0121, HC-p = 0.0236), whereas the probing-depth (PD) values remained almost the same as before treatment (HL-p = 1.5143; HC-p = 1.4762). Conclusions: The use of the dark-field microscope proved to be beneficial in sensitizing patients to the presence of bacteria in the oral cavity and motivated them to strictly follow the rules of oral hygiene. Laser treatment can be a valuable aid in periodontal therapy, but only in adjunction with mechanical therapy.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio and disease activity in rheumatoid arthritis: A systematic review and meta-analysis.

Inflammatory indexes derived from routine haematological parameters, particularly the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have been shown to discriminate between patients with and without rheumatoid arthritis (RA). However, their capacity to discriminate between RA patients with and without active disease has not been systematically appraised. We searched PubMed, Web of Science, Scopus and Google Scholar, from inception to June 2022, for studies comparing NLR and/or PLR values between RA patients with and without active disease. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. In 18 studies (2122 RA patients with active disease, mean age 50 years, 20% males; 1071 RA patients with nonactive disease, mean age 50 years, 25% males), active disease was associated with significantly higher NLR (standard mean difference, SMD=0.37, 95% CI 0.19 to 0.55, p < .001; low certainty of evidence) and PLR values (SMD=0.48, 95% CI 0.32 to 0.64, p < .001; low certainty of evidence). In sensitivity analysis, the SMD values were not substantially influenced by sequentially removing individual studies. There was no publication bias. In meta-regression, the effect size was not associated with other study and patient characteristics, including sex, Disease Activity Score-28, C-reactive protein and erythrocyte sedimentation rate. NLR and PLR can significantly discriminate between RA patients with and without active disease. Further studies are required to determine their diagnostic performance, singly or in combination with other parameters, in routine practice.

PB2279: REDUCED ABSOLUTE COUNT OF MONOCYTES IN PATIENTS CARRYING HEMATOLOGICAL NEOPLASMS AND SARS-COV2 BREAKTHROUGH INFECTION

Background: Clinical course of COVID-19 depends on several patient-specific risk factors, including immune function, that is largely compromised in cancer patients. Aims: To identify predictors of outcome in COVID-19 breakthrough infection in patients carrying hematological neoplasms. Methods: We prospectively evaluated clinical outcome of 120 consecutive adult patients (including 34 cases of COVID-19 breakthrough after two full doses of BNT162b2 vaccine) with underlying hematological malignancies and a SARS-CoV-2 infection. Results: The median value of anti-SARS-CoV-2 antibodies (IgG) titer was 4.7 (range 1.1–38.7 BAU), as measured at one month from the documented viral clearance in 66/86 unvaccinated patients, showing that 42/66 (64%) patients were seroconverted. Among the fully vaccinated patients, the anti-SARS-CoV-2 antibodies (IgG) titer was 5.2 (range 0–13.1 BAU) in 24/34 tested patients, showing that none of them achieved a protective titer (>40 BAU) at one month after two doses of BNT162b2 vaccine. Among fully vaccinated patients the achievement of viral clearance by day 14 was more frequent than in unvaccinated patients. Increased 30-day mortality was associated with presence of active/progressing disease and absolute monocyte count lower than 400 cells/uL. In unvaccinated patients of our series, the median OS was 10.4 months (95% CI. 9.6–11.3), which was affected in univariate analysis, by presence of: active disease (p = 0.003), pre-infection absolute count of monocytes less or equal to 400 cells/mmc (p = 0.04), hospitalization due to COVID-19 (p < 0.0001), lack of viral clearance at 14 days (p = 0.005) and lack of seroconversion (p = 0.04). The difference in survival was consistent throughout all subgroups tested, independent of whether the patients were aged below or above 70 years, of female or male sex, or suffered from myeloid, lymphoid or plasma cell neoplasm. Following PSM there was no statistical difference in 30-day mortality, rate of hospitalization for intensive cure and viral clearance at 14 days between fully vaccinated and unvaccinated patients, where adjusted odds ratios (AOR) and 95% confidence intervals (CI) have been reported. Increased 30-day mortality was associated with the presence of active/progressing disease and absolute monocyte count lower than 400 cells/uL (presence of non-active disease versus active/progressing disease: AOR −0.64, 95% CI: −1.09–0.2; absolute monocyte count (AMC) less than 400 cells/uL versus AMC ≥ 400 cells/uL, AOR 0.68, 95% CI: 0.14–1.21). Results of multivariable analysis of OS showed that the pre-infection absolute count of monocytes less or equal to 400 cells/mmc (p = 0.008), active or progressive disease of the underlying hematological malignancy (p = 0.009), COVID-19 severity identified by hospitalization requirement (p = 0.004) and lack of viral clearance at 14 days (p = 0.03) were independent predictors of 1-year OS in unvaccinated patients affected by hematological neoplasms tested positive for SARS-CoV-2 infection. Summary/Conclusion: Taken together, our results indicate that absolute monocyte count determined one month before any documented SARS-CoV-2 infection could identify patients affected by hematological neoplasms with increased risk of inferior overall survival.

Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine

To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Patients With Inflammatory Bowel Disease Show IgG Immune Responses Towards Specific Intestinal Bacterial Genera.

IntroductionInflammatory bowel disease (IBD) is characterized by a disturbed gut microbiota composition. Patients with IBD have both elevated mucosal and serum levels of IgG-antibodies directed against bacterial antigens, including flagellins. In this study, we aimed to determine to which intestinal bacteria the humoral immune response is directed to in patients with IBD.MethodsFecal and serum samples were collected from patients with IBD (n=55) and age- and sex-matched healthy controls (n=55). Fecal samples were incubated with autologous serum and IgG-coated fractions were isolated by magnetic-activated cell sorting (MACS) and its efficiency was assessed by flow cytometry. The bacterial composition of both untreated and IgG-coated fecal samples was determined by 16S rRNA-gene Illumina sequencing.ResultsIgG-coated fecal samples were characterized by significantly lower microbial diversity compared to the fecal microbiome. Both in patients with IBD and controls, serum IgG responses were primarily directed to Streptococcus, Lactobacillus, Lactococcus, Enterococcus, Veillonella and Enterobacteriaceae, as well as against specific Lachnospiraceae bacteria, including Coprococcus and Dorea (all P<0.001), and to Ruminococcus gnavus-like bacteria (P<0.05). In contrast, serological IgG responses against typical commensal, anaerobic and colonic microbial species were rather low, e.g. to the Lachnospiraceae members Roseburia and Blautia, to Faecalibacterium, as well as to Bacteroides. Patients with IBD showed more IgG-coating of Streptococcus, Lactobacillus, and Lactococcus bacteria compared to healthy controls (all P<0.05). No differences in IgG-coated bacterial fractions were observed between Crohn’s disease and ulcerative colitis, between active or non-active disease, nor between different disease locations.ConclusionThe IgG immune response is specifically targeted at distinct intestinal bacterial genera that are typically associated with the small intestinal microbiota, whereas responses against more colonic-type commensals are lower, which was particularly the case for patients with IBD. These findings may be indicative of a strong immunological exposure to potentially pathogenic intestinal bacteria in concordance with relative immune tolerance against commensal bacteria.

Radiologic zebra line sign in a patient with Langerhans cell histiocytosis on bisphosphonate therapy.

A 3-year-old boy was diagnosed with multi-system Langerhans cell histiocytosis (LCH) with bone, skin, lung, lymph node, and bone marrow involvement at 8 months of age. He achieved non-active disease (NAD) after chemotherapy with prednisolone, vincristine, and cytarabine. However, the patient presented with bone lesion relapse. Despite re-initiation of vinblastine and prednisolone, his bone lesion progressed, prompting treatment with three cycles of cladribine. While it provided some improvement, he presented with bone lesion relapse soon after cladribine therapy. Due to the recurrence of the bone lesion, we administered bisphosphonate therapy using monthly zoledronic acid for 6 months in addition to conventional chemotherapy, which resolved his bone lesion. The patient achieved NAD for 1 year. While he did not present with bone pain, radiographs obtained during bisphosphonate therapy revealed a “dense metaphyseal band sign,” also known as “zebra line sign,” at the tibia and fibula (Figure 1A−D). Nevertheless, 2 years after initiation of bisphosphonate therapy, his growth remained steady (Figure 1E). LCH is characterized as both neoplastic and inflammatory disease. Osteoclasts are crucial in the pathogenesis of LCH, especially in lytic bone lesions. Previous reports revealed that bisphosphonate therapy, including pamidronate and zoledronate, was effective in patients with LCH. Bisphosphonates reduce the activity of osteoclasts by inhibiting their recruitment, thereby resulting in the uncoupling of bone remodeling. The zebra line sign refers to the line of cartilage calcification persisting from the metaphysis into the diaphysis [1, 2]. This radiologic finding reflects the administration of bisphosphonate [3]. Although the zebra line sign seems to be a normal reaction to bisphosphonate therapy, hematology-oncology specialists are not familiar with this finding. In addition, the long-term side effects (e.g., short stature and fracture) remain unknown. This study highlights the importance of long-term follow-up to evaluate the safety profile of bisphosphonates in patients with LCH. The authors declare no conflict of interest.

Splenic size as a marker for active inflammation in Crohn's disease

PurposeThe spleen, one of the major organs of the reticuloendothelial system, frequently enlarges in a variety of inflammatory states. We propose measurement of splenic volume as an additional marker for inflammatory bowel disease activity. MethodsThis is a retrospective study of patients with Crohn's disease who had computed tomography (CT) exams. Demographic data of the patients was recorded. To determine activity of the disease we analyzed clinical records, lab results and findings on CT scan. Splenic size and volume was calculated on each exam. ResultsThe study cohort includes 90 patients with Crohn's disease who underwent 188 [R1.4] CT exams over 6 years. Splenic volume was found to be significantly larger in patients with CD compared to published values for a healthy population. However, the mean splenic volume was 324 cm ± 130.3 did not show significant difference between the group of active 339.2 ± 118.4, and non-active disease 304.2 ± 144.2 (p 0.21 for splenic volume). Interestingly, when splenic volume/BMI index (SV/BMI) was calculated, it was found to be significantly larger in patients with active diseases, 15.26 ± 4.86 compared to non-active phase, 11.69 ± 5.19 (p 0.004). ConclusionSplenic size is enlarged in patients with Crohn's disease compared to standard published literature of normal individuals. While there is no statistically significant difference in our study between splenic volume in Crohn's disease patients with active versus nonactive disease, indexed splenic volume, as an additional marker, may add value to the assessment of patient with CD and monitoring of the disease activity.