Median CRP Levels Research Articles

P0519 Upadacitinib in Acute Severe Ulcerative Colitis among previously anti-TNFa exposed patients

Abstract Background 25% of patients with ulcerative colitis (UC) experience acute severe UC (ASUC), with 40% risk of urgent colectomy1. Standard rescue therapy following intravenous steroids includes infliximab (IFX). Many admitted patients are previous non-responders to IFX. JAK inhibitors (JAKi) have a rapid onset of action and may have a role in ASUC. In earlier studies, results were based on heterogenous induction doses2 with patients previously exposed to anti-integrin α4β7, but not anti-TNFα agents3. The aim of our study was to report outcomes with an alternative JAKi, Upadacitinib, using a standard induction dose only among patients previously exposed to anti-TNF agents. Methods This retrospective study from February 2023 to October 2024, in a tertiary UK centre. Identified anti-TNF experienced patients admitted with ASUC fulfilling Truelove and Witts’ criteria. All patients treated with Upadacitinib were included. Outcomes were length of stay, colectomy rates and clinical response with biochemical markers (CRP and faecal calprotectin), simple Clinical Colitis Activity Index (SCCAI) score and endoscopic remission rates. Adverse events were also recorded. Results Ten patients received Upadacitinib 45 mg daily. The mean age of the patients was 39.7 years (±11.7) and 75% were male. Figure 1 shows previous exposure to biologics and immunomodulators. The mean follow-up period was 56 days, with no major side effects reported. The mean length of hospital stay was 6.5 days (±4.0) and the mean time from admission to Upadacitinib initiation was 6.5 days (± 2.8). Biochemical and clinical responses are shown in table 1. Biochemically, the median CRP levels at admission demonstrated statistically significant drop when compared to CRP levels at discharge (p = 0.008). The median drop in calprotectin levels was not statistically significant between admission and discharge (p = 0.225). Regarding clinical remission, the mean SCCAI score was 10.5 ± 2.55 prior to Upadacitinib, while it was 2.2± 2.0 on discharge (p= 0.005). The results are summarised in Table 1. Finally, endoscopic remission was observed in 3 patients who underwent surveillance colonoscopy at 3 months. There were no colectomies during 4-week follow-up.Upadacitinib offers promise as an alternative for treating ASUC in previously anti-TNFα exposed patients. None of our patients underwent colectomy with clinical and biochemical response. A randomised controlled study is warranted to confirm the findings. Conclusion Upadacitinib offers promise as an alternative for treating ASUC in previously anti-TNFα exposed patients. None of our patients underwent colectomy with clinical and biochemical response. A randomised controlled study is warranted to confirm the findings.

P0466 Impact of the COVID-19 Pandemic on Clinical Presentation and Management of Inflammatory Bowel Disease: A Multicentre Study in the West Midlands, UK

Abstract Background The COVID-19 pandemic disrupted healthcare systems globally, exacerbating disease severity and delaying management of chronic conditions like inflammatory bowel disease (IBD). This multicentre study investigates the pandemic’s impact on clinical presentation, treatment patterns, and outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) patients at two UK district hospitals. Methods A retrospective study was conducted between July 2017–June 2022 at two district hospitals, comparing pre- and post-COVID outcomes in UC and CD patients. Factors analyzed included disease extent, inflammatory markers, treatment patterns, diagnostic investigations, and patient outcomes, such as emergency surgery. Results Among 602 IBD patients (52.2% UC, 47.8% CD), the median age was 41 years (IQR 29), and 51.3% were male. Post-COVID, UC patients presented with more severe disease: UC E3 (Extensive Colitis) increased from 24.0% to 32.8% (p=0.01), while UC E1 (Proctitis) decreased from 18.4% to 7.4% (p=0.004). Median hospital stays rose from 4 to 6 days (p=0.03), with inflammatory markers showing significant increases—median CRP levels rose from 25 to 35 mg/L (p=0.016), and faecal calprotectin levels increased from 600 to 1800 µg/g (p<0.0001). Treatment patterns shifted, with reduced 5-ASA (77.6% to 59.3%, p=0.001) and immunosuppressant use (19.2% to 9.0%, p=0.004) but increased biologic therapy (27.2% to 31.7%, p=0.001). In CD, disease localization shifted significantly: terminal ileum involvement (CD L1) rose from 30.6% to 46.8% (p=0.001), while ileocolonic disease (CD L3) decreased from 45.9% to 31.1% (p=0.01). Imaging utilization nearly doubled, with CT/MRI use increasing from 36.7% to 71.6% (p<0.001). Post-COVID CD patients were younger, with median age decreasing from 42 to 39 years (p=0.05). Untreated cases in the younger cohort of age <43 years rose from 64% to 84% (p=0.004). Emergency surgery rates in both UC and CD and ITU admission rates remained unchanged pre- and post-COVID. Conclusion Post-COVID, UC patients presented with more extensive colitis, higher inflammatory markers, and longer hospital stays. CD patients showed shifts in disease localization, increased imaging use, and a younger, less-treated demographic. Delayed access to care likely fostered disease progression, compounded by pandemic-related psychological stress and immune dysregulation. Strengthening healthcare systems with robust referral pathways and timely IBD treatment is essential to mitigate impacts of any future systemic disruptions.

P0679 Therapeutic Drug Monitoring of the Infliximab (anti-TNF) Level with Bedside Kit in Inflammatory Bowel Disease

Abstract Background Approximately half (10-40%) of the Inflammatory Bowel Disease (IBD) patients using Infliximab (IFX) develop secondary loss of response due to drug levels falling below the therapeutic range. This study aims to identify drug levels, influencing factors and parameters that may be useful in predicting target drug levels. Methods The pre-infusion drug levels and associated laboratory parameters were evaluated in IBD patients on maintenance dose of IFX (5-15 mg/kg every 4-8 weeks) between Nov2021 - Oct2024. Drug levels were measured using a bedside kit capable of quantitatively detecting values between 0.4-20 µg/ml. Results In total, 931 single pre-infusion measurements from 415 different patients, and dual measurements at weeks 4 and 8 from 116 patients were separately evaluated. 82% of the patients in the single measurement group, and 84% in the double measurement group had Crohn’s disease(CD), rest having Ulcerative Colitis. The most used doses in the single measurement group were 5 mg/8 weeks and 10 mg/4 weeks (Table 1). In the single measurement group, median albumin was 4.4 (IQR: 0.5), and median CRP was 3.1 (IQR: 6.4). Drug levels were below 5 µg/ml in 33% of measurements. CRP showed a significant difference according to drug level groups (Table 2), while no such difference was observed for albumin. In the measurable IFX range (0.4-20 µg/ml), correlation analysis revealed a weak negative correlation between CRP and drug levels (r: -0.09, p: 0.03). Regression analysis showed that lower CRP, higher drug dose, and CD diagnosis were independently associated with achieving >5 µg/ml drug levels. In the dual measurement group: The median CRP levels of patients at weeks 4 and 8 were 2.1 (5.1) and 2.6 (6.2), respectively (p>0.05). Among patients with IFX levels >20 µg/ml at week 4, 79% maintained levels >5 µg/ml at week 8, while this rate dropped to 71% for those with levels >10 µg/ml. Only 67% of patients with levels >5 µg/ml at week 4 maintained a level of >5 µg/ml at week 8 (all p-values <0.001). Conclusion As drug levels increase, significant reductions in CRP levels are observed. Therefore, low CRP levels may predict the likelihood of achieving the therapeutic range. Dose adjustment should be considered in cases with high CRP levels. Achieving a high drug level (>20 µg/ml) at 4th week is an important indicator of achieving at least an acceptable drug level (>5 µg/ml) at the end of treatment. (8th week).

MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 gene variants in South African Indian and Caucasian psoriatic arthritis patients.

Methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine and folic acid metabolism. Tumour suppressor protein TP53 gene maintains cellular and genetic integrity. To date, no studies associated the MTHFR C677T rs1801133 and TP53 Pro72Arg rs1042522 with CRP levels and methotrexate (a folic acid antagonist) treatment outcomes in psoriatic arthritis (PsA) patients. The present study aimed to investigate whether the MTHFR rs1801133 and TP53 rs1042522 gene variants influences CRP levels and methotrexate treatment outcomes in South African Indian and Caucasian PsA patients. PsA patients (n=114) and healthy controls (n=100) were genotyped for the rs1801133 and rs1042522 using RFLP-PCR. (i) Results for rs1801133 genotyping: Caucasian patients had a higher frequency of the variant T-allele versus healthy Caucasian controls (40% versus 22%; OR=2.31, 95% CI=1.10-4.88, p=0.0379). Patients with the variant CT+TT genotypes had higher median CRP levels at baseline versus wildtype CC genotypes (11.70 (5.3-28.80) mg/mL versus 7.40 (5.00-15.05) mg/mL, p=0.0355). After 6 months of methotrexate treatment median CRP levels between genotypes reduced and remained similar. (ii) Results for rs1042522 genotyping: Indian patients had a higher frequency of the variant Arg-allele versus healthy Indian controls (42% versus 29%; OR=1.75, 95% CI=1.07-2.86, p=0.0275). In conclusion, patients with the MTHFR rs1801133 variant T-allele have elevated CRP levels, which can be ameliorated with methotrexate.

Idiopathic Retroperitoneal Fibrosis-Related Hydronephrosis: Evaluation of Comprehensive Management and Prediction of Inflammatory Markers for Stent-Free Outcomes.

This study investigated the efficacy of comprehensive management and predictable inflammatory markers for idiopathic retroperitoneal fibrosis (iRPF)-related hydronephrosis outcomes. Patients with iRPF-related hydronephrosis underwent surgical (ureteral stent and/or nephrostomy tube placement) and medical (corticosteroid-based multiple immunosuppressants) management were classified according to stent-indwelling outcomes. Univariate analysis of clinical profiles was conducted to screen possible predictors of hydronephrosis remission. In a series of 38 patients, 52.6% achieved hydronephrosis remission and stent/tube removal (stent-free group). The median indwelling time in the stent-free group (12 months) was significantly lower than that in the treatment-failure group (37 months, p<0.05). Mean retroperitoneal mass diameters was significantly reduced (anteroposterior by 11.66 mm (95% CI 2.31-21.01), transverse by 15.41 mm (95% CI 3.37-27.46), suprainferior by 30.53 mm (95% CI 4.87-56.19); p<0.05) during the treatment course, in line with mean renal pelvis width (by 36.2%) and renal function parameters (serum creatinine by 16.9%, blood urea nitrogen by 12.9%). Renal function improved (36.9%) or remained stable (44.7%) in most patients, the mean estimated glomerular filtration rate increasing by 8.7% (from 55.4 mL/min/1.73 m2 to 60.2 mL/min/1.73 m2). At the initial diagnosis, median serum immunoglobulin IgG and CRP levels were significantly higher in the stent-free group than in the treatment-failure group (IgG 17.55 g/L vs. 13.50 g/L, CRP 19.60 mg/L vs. 3.15 mg/L; p<0.05). Decline in serum IgG (-5.80 g/L vs. -2.30 g/L), CRP (-18.93 mg/L vs. -1.72 mg/L) and erythrocyte sedimentation rate (-22.00 mm/h vs. -1.50 mm/h) levels in the stent-free group surpassed those in the treatment-failure group (p<0.05). Comprehensive management benefits iRPF patients with hydronephrosis by preserving renal function. The 24-month scale might guide stent/tube removal. Elevated inflammatory markers (IgG and CRP) at the initial iRPF diagnosis and IgG, CRP, and erythrocyte sedimentationrate (ESR) variations associated with hydronephrosis outcomes.

Procalcitonin serum level in patients with pemphigus vulgaris: can it be used as an inflammatory biomarker?

Procalcitonin (PCT) is a peptide precursor of calcitonin, considered as an infection marker in many settings. Recently, a few studies reported its rise in some inflammatory processes such as still's disease, anaphylactic shock and Kawasaki disease. To investigate the serum level of PCT in patients with pemphigus vulgaris (PV) and examine the relationship between serum level of PCT and the severity of disease. A cross-sectional study was conducted on 50 patients with PV, visited at a tertiary care hospital from August 2021 to May 2023. After recording the demographic and clinical characteristics of patients, PCT level as well as CRP and ESR levels were measured and analyzed. The median ESR, CRP and procalcitonin serum level for the patients was 6.40mm/hr, 11.00mg/dL and 0.025 ng/ml, respectively. Considering the mean serum PCT level of normal population which is reported as < 0.1 ng/ml, its level among our patients was in a normal range. A significant and positive correlation was observed between procalcitonin and ESR, as well as CRP. In opposite to PCT, CRP and ESR levels showed a significant and positive correlation with disease severity (P values: 0.002 and < 0.001, respectively). Our findings suggest that PCT might not be useful as a biomarker of inflammatory milieu or prognostic factor in patients with PV without any infection.

Can Opportunistic Use of Computed Tomography Help Reveal the Association Between Hepatic Steatosis and Disease Severity in Hospitalized COVID-19 Patients?

To measure hepatic steatosis (HS) in hospitalized COVID-19 patients using unenhanced chest computed tomography (CT) imaging and to evaluate the relationship between disease severity and prognosis in adult patients.This retrospective study included 152 consecutive hospitalized COVID-19 patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test. The COVID-19 Reporting and Data System (CO-RADS) and the chest CT score were evaluated. HS measurements were performed based on CT images using a single region of interest placed on the right liver lobe (segments V-VII). HS was defined as a liver attenuation value <40 Hounsfield units. Data were collected and compared with the patients' prognostic parameters.Of the 152 inpatients, 137 patients (90.1%) had a CT score ≥3 and 109 patients (71.7%) had a CO-RADS score ≥4, 43 (28.2%) had HS. All patients with HS (100%) and 94/109 (86.2%) patients without HS had a CT score ≥3. There was a statistically significant difference between the two groups in terms of chest CT score (p=0.006). There was no statistically significant difference between the two groups in terms of CO-RADS score (p=0.291). The median CRP levels were significantly increased in patients with HS compared to patients without HS (p=0.023). There was no significant difference in ICU hospitalization and mortality due to the presence of HS (p>0.05).The current study revealed significantly higher chest CT scores in COVID-19 patients with HS measured on CT compared to those without HS. Opportunistic use of CT images for the detection of HS can be considered as an adjunctive tool in the risk analysis of COVID-19 patients hospitalized due to COVID-19 pneumonia.The severity of COVID-19 disease is increased in hospitalized patients with hepatosteatosis compared to patients with a normal liver. Density measurements for the evaluation of HS using opportunistic CT applications can be considered as an adjunctive tool in the prognostic evaluation of hospitalized patients with COVID-19 pneumonia. · Parlak AE, Erdem Toslak İ, Turkoglu Selcuk N. Can Opportunistic Use of Computed Tomography Help Reveal the Association Between Hepatic Steatosis and Disease Severity in Hospitalized COVID-19 Patients?. Fortschr Röntgenstr 2024; DOI 10.1055/a-2369-8377.

Role of mechanical thrombectomy among large vessel stroke patients during the coronavirus disease (COVID-19) pandemic

PurposeThe aim of our study is to provide insights derived from experience at multiple centers regarding the outcomes of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in COVID-19 patients and compare them with those in non-COVID-19 patients during the coronavirus disease (COVID-19) pandemic.ResultsCOVID‐19 positive patients were younger than COVID‐19 negative patients (62.1 ± 2.69 versus 69.5 ± 2.2, P < 0.001). There was a significant difference between COVID-19 and non-COVID-19 groups in the median D-dimer levels (6 vs. 4.5; P < 0.001), median ESR levels (63 vs. 38; P < 0.001) and median CRP levels (110 vs. 48.5; P < 0.001), respectively. Median time from stroke symptoms onset to hospital admission was significantly higher among COVID-19 positive patients (366 vs. 155 min; P < 0.001). COVID‐19 positive patients with LVO presented with a higher median NIH Stroke Scale score at presentation (16 versus 8, P < 0.001) and lower median Alberta Stroke Program Early CT Score (ASPECTS) on admission (6 versus 8, P < 0.001). Patients with COVID-19 had significantly higher percentages of poor functional outcomes as scored using the mRS grades 3–5 in comparison to non-COVID-19 patients (69.2% vs. 13.6%; P = 0.002), but there was no significant difference between both groups in complications such as early cerebral re-occlusion, intracerebral hemorrhage, or in-hospital mortality (P > 0.05).ConclusionMechanical thrombectomy has effectively managed patients with LVO stroke. LVO stroke in COVID-19 patients occur at a young age, and have multi-territory vascular involvement. Poor functional outcomes post thrombectomy in COVID-19 patients, irrespective of timely, successful angiographic recanalization.

Mutations in the TP53, VEGFA, and CTH Genes as Key Molecular Markers for the Diagnosis of Glioblastoma.

Background Brain cancer, particularly glioblastoma (GBM), is a global health problem. Despite therapy advances, GBM patients have a poor prognosis. The progression and etiology of GBM may be linked to gene polymorphisms in the VEGFA, TP53, and CTHgenes, among others. However, the genetic variations and their interaction in GBM are not fully understood. This study examines the effects of mutations in the VEGFA, TP53, and CTH genes on GBM. Methodology Tissue and blood samples were obtained for hematological, biochemical, and genetic analysis from 18 patients diagnosed with GBM as well as 28 healthy individuals. Standard methods were adopted to perform hematological and biochemical analyses, whereas mutational landscape and expression profiles were obtained from publicly accessible databases. Tissue samples were processed for genomic DNA extraction, and genotype determination was carried out through conventional polymerase chain reaction (PCR) and Sanger sequencing. Results The study involved 18 patients with grade IV GBM beforetreatment and 28 healthy individuals. The patients consisted of11 men (61%) and seven females (39%), while healthy individuals included 14 (50%) males and 14 (50%) females. Sixty-seven percentof patients were under 50, 17% between 51 and 60, and 17% over 61, compared to healthy individualswho were 61% under 50, 7%between 51 and 60, and 32% over 60. GBM patients showed higher neutrophil and monocyte counts (median 81% (63.9, 83.5) and 4.2% (3.8-7.3)), respectively, and lower lymphocyte counts (median 13.4% (8.8, 28.40)) compared to controls. The median values of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed no significant differences between the control and GBM groups. GBM patients had significantly higher median CRP levels of 2.55 (1.6, 98) than controls. Analysis of databases revealed a high prevalence of mutations in TP53, with splice region variants, missense variants, and intron variants being the most common. VEGFA and CTH also displayed mutations, primarily missense and intron variants. Gene expression analysis showed significantly higher levels of TP53 and VEGFA in GBM patients compared to controls. CTH expression also exhibited a slight increase in GBM patients. Sanger sequencing identified three mutations in the TP53 gene, including a novel mutation (11915C>A) not previously reported in external databases. Additionally, novel mutations were found in the VEGFA (841G>GA, 919T>TG) and CTH (28398A>AC, 28399A>AT) genes. Conclusions This study highlights the immune dysregulation, inflammation, and genetic variations in GBM.The findings emphasize the potential importance of the TP53, VEGFA, and CTH genes as targets for therapies and diagnostic biomarkers of GBM. Further study is necessary to comprehend these genetic variations' functional implications and their use in personalized GBM treatment.

Glucocorticoid treatment and clinical outcomes in patients with polymyalgia rheumatica: A cohort study using routinely collected health data

ObjectiveWe aimed to describe the following in patients with polymyalgia rheumatica (PMR): (1) real-world glucocorticoid (GC) therapy, (2) improvement in inflammatory parameters associated with disease activity (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), and (3) incidence of GC-related adverse events (AEs). MethodsA cohort study was conducted using a Japanese electronic medical records database. We included newly diagnosed PMR patients aged≥50years with baseline CRP levels≥10mg/L and/or ESR>30mm/h and an initial GC dose of≥5mg/day. The outcomes were GC dose, inflammatory parameters, and GC-related AEs. ResultsA total of 373 PMR patients (mean age, 77.3 years) were analyzed. The median initial GC dose was 15.0mg/day, which gradually decreased to 3.5mg/day by week 52. The median cumulative GC dose at week 52 was 2455.0mg. The median CRP level on day 0 was 64.3mg/L, which decreased during weeks 4–52 (1.4–3.2mg/L). At week 52, 39.0% of patients had a CRP level>3.0mg/L. The cumulative incidence of GC-related AEs at week 52 was 49.0% for osteoporosis, 30.2% for diabetes, 14.9% for hypertension, 12.2% for peptic ulcer, 11.3% for dyslipidemia, 2.9% for glaucoma, and 4.3% for serious infection. The incidence of osteoporosis and diabetes increased with the GC dose. ConclusionThe incidence of GC-related AEs was associated with the GC dose in PMR patients. Further research is required to identify treatment strategies that can effectively control PMR disease activity while minimizing GC use.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients’ care.

FLT3 Ligand Kinetic Profile Predicts Response to Treatment and Event-Free Survival (EFS) in Adults with High-Risk MDS/CMML Receiving CPX-351: A GFM Study

Background: Our group recently reported, in a prospective multicentre phase 2 study of 31 patients with higher-risk (HR)-MDS or CMML receiving CPX-351 as first-line induction treatment 87% of overall responses (including 64.5% of CR/ CR according to ELN2017 criteria), and 93.5% of the patients could be bridged to transplant (GFM-CPX MDS trial, Peterlin et al. Lancet Haematol 2023). We had also previously reported, in AML, that the soluble forms of FLT3 ligand (FL) and IL6 could be prognostic factors of refractoriness to chemotherapy and overall survival (OS) (Peterlin et al. Cancer Medicine, 2021). A secondary objective of the GFM-CPX MDS trial was to assess the prognostic value of these two cytokines in HR-MDS/CMML receiving CPX-351. Methods: All patients included in the GFM-CPX MDS trial (clinicaltrials.gov#NCT04273802), induction chemotherapy with CPX-351 (44 mg Daunorubicin/100 mg Aracytine/m 2 on days 1, 3, and 5) also consented for the present biological FLAM-MDS sub-study. Using a new cytokine multiplex assay from Milliplex (MILLIPLEX®), FL levels (expressed in pg/mL) were evaluated on Day (D) 1, D8, D15 and D22 of the first cycle of induction; IL-6 (expressed in pg/mL) and CRP (known to be correlated with IL6, expressed in mg/L, normal value 0-5) levels were evaluated on D1 and D22 only. Patients who failed to achieve response (CR or CRi or MLFS, ELN2017 criteria) after the first induction cycle could receive a second one. The impact on CR/CRi rate after one cycle of CPX-351, OS and EFS of FL, IL-6 and CRP dosages and their kinetic profile during this first cycle were studied. Results: Dosages could be performed in 28 of the 31 patients included ( Table 1). Overall response (CR+CRi+MLFS) after cycle 1 was achieved in 24 (87%, MLFS n=7, CR+CRi n=17) patients; 3/4 non-responders received a second induction (1 achieved CR). Allograft was performed in 26/28 (93%). With a median follow-up of 18 months for surviving patients, 1y and 18-month OS were 79% and 75%, respectively. 1y and 18-month EFS were both 76%, respectively. Achieving CR/CRi versus MLFS/non-response was associated with better 1-y EFS (71% (52-96) vs 27% (10-72), p=0.009) but not 1-y OS (82% (66-100) vs 73% (51-100), p=0.8). Median (range) FL levels were 4.5 [0- 33.5] on D1, 74.1 [4.1-296.6] at D8, 326.6 [47.4-678] at D15 and 381.3 [4.4-800.1] at D22. As in AML (Peterlin et al, 2021), patients could be categorized according to three FLc kinetic profiles: i) sustained increase from D 1 to 22 (FLI group n=17, 61% of the cohort), ii) increase from D 1 to 15, then decrease on D 22 (FLD group, n=9, 32% of the cohort) and iii) persistent low levels (&amp;lt;100 pg/mL from D 1 to 22, FLL group, n=2, 7% of the cohort). Median (range) IL6 levels were 11 (0-587.8) on D1 and 179.8 (0-531) on D22. Increase of IL6 levels between D1 and D22 was observed in 19 patients (68%) and decrease in 7, while 2 patients had no IL6 detectable at either times. Finally, median (range) CRP levels were 2.3 (0-108) on D1 and 40.5 (7.2-323) on D22. Increase of CRP level was observed in most patients between D1 and D22 (n=25, 96%). There was no correlation between IL6 and CRP levels on D1 (p=0.64) or D22 (p=0.48). CR/CR rates, 1-y OS and EFS were not correlated with FL levels (&amp;lt; vs &amp;gt; median) at the 4 time points considered. However, a FLD kinetic profile was significantly associated with higher CR/CRi rates (100% vs FLI 47% vs FLL 50%, p=0.002) and 1-y EFS (78% (55-100) vs FLI 47% (28-78) vs FLL: 0%, p=0.003), Figure 1). 1-y OS was similar between the 3 FL kinetic profile groups (FLD: 89% (71-100) vs FLI 76% (59-100) vs FLL 50% (13-100), p=0.7)). In multivariate analysis, taking into account age, gender, R-IPSS and the FL kinetic profile during cycle 1 of CPX-351, a FLD kinetic profile was the only factor associated with higher CR/CRi rate (OR: 24.2, 95%CI: 2.4-3278, p=0.004) and better EFS (OR: 21.91; 95%CI: 2.47-194.77, p=0.006). Levels and kinetic profiles of IL6 and CRP had no impact on CR/CRi rates, OS and EFS. Conclusion: As in AML, FL kinetic profile predicts response and survival in HR-MDS/CMML. A FLD kinetic profile was the only factor independently associated with higher CR/CRi rates and better EFS. These results have to be confirmed on larger cohorts. Other treatment approaches may be of interest in patient with a non FLD profile.

Acinetobacter spp. bloodstream infection in hematological patients: a 10-year single-center study

PurposeThis study investigated the clinical and antimicrobial characteristics of Acinetobacter spp. bloodstream infection (BSI) in hematological patients. Risk factors for 30-day mortality and carbapenem-resistant Acinetobacter spp. (CRA) BSI acquisition were also identified.MethodsWe reviewed forty hematological patients with Acinetobacter spp. BSI in a large Chinese blood disease hospital between 2013 and 2022. The remaining CRA isolates were subjected to whole-genome sequencing.ResultsThe 30-day mortality rate was high at 35%. Hematological patients with Acinetobacter spp. BSI often presented with severe conditions and co-infections at multiple sites. All strains were colistin-susceptible and 40.0% were CR. Multivariate analysis identified several risk factors associated with CRA BSI acquisition, including previous exposure to carbapenems within 30 days and CRA colonization. Very severe aplastic anaemia, tetracycline-resistant Acinetobacter spp. BSI, and unresolved neutropenia after infection were closely associated with 30-day mortality. Non-survivors often presented with higher median PCT and CRP levels and severe complications, such as intracranial infection, cardiac dysfunction, respiratory failure, and severe sepsis or septic shock. Our study also identified inappropriate empirical antibiotic therapy as an independent predictor of 30-day mortality (OR: 11.234, 95% CI: 1.261–20.086, P = 0.030). This study was the first to report A. oleivorans as a human pathogen, and to identify its unique oxacillinase, OXA-325.ConclusionAn environment-originated non-pathogenic species can become pathogenic when the body’s immunity is compromised. Our results also highlighted the importance of improving neutropenia after infection, treating severe organ dysfunction, and administering appropriate empirical antibiotic therapy to reduce mortality in this patient population.

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data.

Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. A total of 226 stage II/III colon cancer patients with a median age of 59years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

Reliability of C-reactive protein as an inflammatory marker in patients with immune-mediated inflammatory diseases and liver dysfunction.

CRP is an acute-phase reactant widely used clinically as a marker of inflammation. CRP is a protein synthesized by hepatocytes. Previous studies have shown lower CRP levels in response to infections in patients with chronic liver disease. We hypothesized that CRP levels would also be lower during active immune-mediated inflammatory diseases (IMIDs) in patients with liver dysfunction. This retrospective cohort study used Slicer Dicer in Epic, our electronic medical record system, to search for patients with IMIDs both with and without concomitant liver disease. Patients with liver disease were excluded if there was no clear documentation of liver disease staging. Patients were also excluded if a CRP level was not available during disease flare or active disease. Arbitrarily, we considered normal CRP as ≤0.7 mg/dl, mild elevation of CRP as ≥0.8 and <3mg/dl, and elevated CRP as ≥3mg/dl. We identified 68 patients with both liver disease and IMIDs (RA, PsA and PMR) and 296 patients with autoimmune disease and without liver disease. Presence of liver disease had the lowest odds ratio (odds ratio = 0.25, P < 0.0001) of having an elevated CRP during flare. Each specific IMID, except SLE and IBD, had higher median CRP levels during active disease episodes in patients without liver disease than in those with liver disease. Overall, IMID patients with liver disease had lower serum CRP levels during active disease than their counterparts without liver dysfunction. This observation has implications for clinical use of CRP level as a reliable marker of disease activity in patients with IMIDs and liver dysfunction.

P404 Persistence of subcutaneous infliximab after switching from intravenous in a French national cohort of IBD patients in remission

Abstract Background Subcutaneous infliximab (IFX-SC) was launched in France for the treatment of patients with inflammatory bowel disease (IBD) in 2021. Real-life and pharmacokinetic (PK) data after switching from intravenous infliximab (IFX-IV) to IFX-SC are needed. The PEREM study is a French multicenter prospective cohort aiming to describe the persistence of IFX-SC after switch from IFX-IV. Methods IBD patients in steroid-free clinical remission [Harvey Bradshaw Index (HBI) ≤ 4 for Crohn’s disease (CD) and partial Mayo score (PMS) ≤ 2 with each subscore ≤ 1 for UC] for at least 6 months on IFX-IV therapy were proposed to switch to IFX-SC as part of routine care. Patients were included in 40 centers between Oct 2021 and May 2022. Clinical scores (HBI, PMS), biological samples (CRP and fecal calprotectin - FC), PK and anti IFX antibodies (ATI) were evaluated 3, 6, 12 and 24 months after switch. In case of IFX-SC discontinuation, time and reason for withdrawal were documented. Safety and adverse events of interest were recorded. The primary endpoint was IFX-SC persistence at 12 months. As not all patients met this primary endpoint at the time of writing this abstract, we present here the results at 6 months (M6). Results Among the 444 patients included [44% female, median age: 37 years (Min, Max: 18-88), 72% Crohn’s], 71% were receiving IFX-IV at a dose of 5 mg/kg every 8 weeks and 84% were treated on monotherapy. Among the 417 patients analyzed, five withdrew their consent before the M6 visit and 324 were assessed at M6; 25/324 (7.7%) discontinued IFX-SC before M6 (seven for relapse, twelve for intolerance, two for pregnancy, four for unknown reasons) including one (0.3%) switch back to IFX-IV. Rate of survival without IFX-SC discontinuation at M6 was 92.6% (95% CI 89.3-95.1). Among the patients evaluated at M6, median clinical scores did not vary between inclusion and M6: HBI from 0 (IQR: 0-1) to 0 (IQR: 0-1), PMS from 0 (IQR: 0-0) to 0 (IQR: 0-0), respectively. The median CF and CRP levels were respectively 52 μg/g (IQR: 19-142) at inclusion and 37 μg/g (IQR: 14-129) at M6, and 1 mg/L (IQR: 1-4) at inclusion and 1 mg/L (IQR 0-4) at 6 months. At baseline, median infliximab levels were 6.6 μg/mL (min, max: 0-29) and 20 μg/mL (min, max: 0.3- 79.2) at M6. No major safety signals were recorded. Conclusion In a national real-life multicenter cohort, rate of persistence of IFX-SC after 6 months was 92.6% in IBD patients switched in remission, without significant clinical or biological changes. Treatment switch was associated with an increase in IFX levels. These data are confirming the good efficacy and safety of IFX-SC after switch.

The Clinical and Laboratory Efficacy of HA 330 Treatment Combined with Continuous Renal Replacement Therapy in Septic Shock Patients: A Case Series

Introduction: Blood purification therapy is a method used to enable cytokine removal and to improve disturbed immune homeostasis in patients with sepsis or septic shock. This study aimed to evaluate the impact of HA 330 treatment on biochemical and hemodynamic parameters and cytokine levels in adult patients with septic shock. Methods: Critically ill patients with septic shock who received continuous veno-venous hemodiafiltration and HA 330 treatment were included in this prospective observational study. Biochemical and hemodynamic parameters were followed throughout HA 330 treatment. Serum interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, high-mobility group box1 (HMGB-1) protein, IL-10 levels were analyzed by ELISA method, before and after each HA 330 session. Results: A total of 18 critically ill patients were included in this study. The median APACHE 2 score was 22.2 ± 7.49 and median SOFA score 9.6 ± 5.44 on intensive care unit admission. SOFA scores were significantly decreased on the 3rd day of HA 330 treatment, compared to 2nd day scores (p = 0.017). Median leukocyte value was significantly decreased (p = 0.027 and p = 0.024), while hemodynamic parameters remained unchanged throughout the HA 330 treatment. Median CRP and procalcitonin levels were significantly reduced at day 3 of HA 330 treatment compared to the baseline (p = 0.015 and p = 0.033, respectively). Serum IL-1 β, IL-6, IL-8, TNF-a, HMGB-1, and IL-10 levels decreased insignificantly by 11.5%, 26.4%, 11.4%, 37.9%, 0.02%, and 35.5%, respectively, at the end of the hemoperfusion treatment compared to the pre-treatment. Conclusion: The administration of HA 330-based hemoperfusion in septic shock patients revealed improvements in SOFA scores, leukocyte count, and CRP and procalcitonin levels. However, there was no statistically significant change in concentrations of inflammatory cytokines and hemodynamic parameters during HA 330 treatment.

Thrombotic Manifestations in Patients with Vexas Syndrome

Introduction: VEXAS syndrome, caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1) gene, is a late-onset and progressive autoinflammatory disease. Main hematologic manifestations include macrocytic anemia, thrombocytopenia, and dyspoiesis. Concomitant diagnoses of myelodysplastic syndrome (MDS) and plasma cell dyscrasia (PCD) are common. Venous thromboembolism (VTE) and arterial thrombosis (AT) have been reported. We describe the incidence and characteristics of thrombosis in a large cohort of 86 patients with VEXAS syndrome, along with detailed coagulation profiles in a subgroup of patients. We also explore potential predictors of thrombosis, and effect on overall survival (OS). Methods: Two cohorts of patients with confirmed VEXAS were included. Thirty patients were evaluated at the National Institutes of Health (NIH) Clinical Center and 56 patient records reviewed from referring institutions. Logistic regression models were used to determine predictors of thrombosis. Cox proportional hazards models and Kaplan Meier curves were used for survival analysis. Results: The total population consisted of 86 patients. Eighty-five patients (99%) were male with a median age of 64 years (range, 40-84 years) at disease onset. Hematologic manifestations included macrocytic anemia in 63 (73%), MDS in 25 (29%) and PCD in 17 (20%) patients. Thrombosis occurred in 45 patients (52%); 41 (48%) had VTE and 11 (12%) had AT, with a median time to event from disease onset of 18 and 34 months, respectively; five patients (5%) had both VTE and AT. Among VTE, there were 26 (30%) deep venous thrombosis (DVT), 12 (14%) pulmonary embolism (PE), and 7 (8%) superficial thrombophlebitis. Twenty-two (54%) of VTE cases were unprovoked. Recurrent VTE was seen in 15 (17%) of patients, among which 9 (53%) occurred while receiving anticoagulation. Arterial events included myocardial infarction in 7 (8%) patients, stroke in 2 (2%) patients, and peripheral arterial occlusion in 2 (2%) patients. Recurrent AT was seen in 2 (2%) patients. Patients from the NIH cohort underwent extensive coagulation testing. Fourteen patients (46%) had a positive lupus anticoagulant (LA), which was persistently positive 12 weeks apart in 8 of 9 patients re-tested. Of these 8 patients, 6 had a VTE, 1 had a stroke and 1 did not have thrombotic manifestations. Thirteen patients (43%) with thrombotic events were negative for LA. Median levels of fibrinogen, D-dimer, Factor (F) VII, FIX, and especially von Willebrand factor (VWF) and FVIII, were high in 15 tested VEXAS patients, but there was no significant difference between those with and without thrombosis (Table 1). Of 10 patients with high VWF and 17 with high FVIII activity, 6 (60%) and 9 (53%) had a thrombotic event, respectively; these correlated with high levels of CRP and ESR. No patients were found to have abnormal antithrombin III activity, Factor V Leiden, or prothrombin gene mutations. No difference in age, UBA1 gene mutation, median levels of CRP and ESR, presence of MDS or PCD was found between patients with or without thrombosis; MDS, PCD and UBA1 gene mutation were also not predictive of thrombosis. Among inflammatory disease manifestations, cardiac involvement (myocarditis, pericarditis, or pericardial effusion) correlated with the presence of any thrombosis (p = 0.03). When considering VTE alone, cardiac manifestations strongly predicted PE and DVT (p = 0.004 and p = 0.005 respectively), while the presence of chondritis correlated with PE (p = 0.02). Presence of thrombosis did not impact OS (Figure 1). Conclusions: Patients with VEXAS syndrome are at high risk of thrombosis, mainly venous, which can be recurrent despite anticoagulation therapy. The underlying etiology remains unclear, but many VEXAS patients have positive LA, high VWF and FVIII levels, suggesting inflammation, endothelial activation and/or an immune process as pathophysiologic. Cardiac manifestations, including myocarditis, pericarditis, and pericardial effusion, significantly correlated with thrombosis in general, while chondritis correlated with presence of PE. Presence of thrombosis did not impact OS. Given the high incidence of thrombosis, VEXAS patients should be carefully risk assessed for VTE and considered for prophylactic anticoagulation, and indefinite treatment if thrombosis has occurred. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Point-of-care C-reactive protein test results in acute infections in children in primary care: an observational study

BackgroundAcute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients’ characteristics, care setting, preliminary diagnosis, and management.MethodsA prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium.ResultsIn this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR < 5–29). Children below 5 years of age and those presenting to a paediatrician had a higher median CRP. Median CRP in patients with serious infections was 21 mg/L (IQR 6 to 63.5). Pneumonia had a median CRP of 48 mg/L (IQR 13–113). In the episodes with antibiotics prescription, median CRP level was 29 mg/L (IQR 10–58) compared to 7 mg/L (IQR < 5–19) when they were not prescribed.ConclusionA low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule.Trial registrationClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).

Cutibacterium acnes endocarditis: a multicenter case series

Abstract Background Infective endocarditis (IE) due to Cutibacterium acnes (C. acnes) (formerly known as Propionibacterium acnes) is challenging to diagnose. It is suggested that patients often present without fever nor inflammatory parameters. Meanwhile, cardiac abscesses and valve dysfunction are often reported, with a high percentage of patients requiring cardiac surgery [1–7]. No study has yet confirmed the atypical presentation of IE caused by C. acnes. Purpose To study clinical characteristics and outcomes of patients with C. acnes IE. Methods A multinational retrospective case series was conducted. Patients who were diagnosed with definite IE according to the modified Duke criteria between 2010 and 2020 were included. There were six participating hospitals. Cases were identified by positive blood cultures or positive valve/prosthesis cultures. Clinical data was retrieved from medical records. Results We identified 61 cases of C. acnes IE. Patients were predominantly male (n=58, 95%) and had previous cardiac surgery (n=56, 91.8%), which in most cases consisted of aortic valve replacement or Bentall procedures (n=34, 60.7% and n=13, 23.2% respectively). The median time between index surgery and presentation was 31 months (IQR 15.9–69.3). At presentation, fever was absent in 59% of patients (n=36). Most patients experienced symptoms for one to two weeks prior to hospital presentation (41%). At presentation, the median CRP level was 35.5 mg/L (IQR 10.0–70.8). Moreover, in 23% of patients (n=14), the median CRP level was not elevated (&amp;lt;10.0 mg/L). The median leucocyte count at presentation was 9.8x109/L (IQR 8.0–12.3), and thus not exceeding the upper limit of the normal range (10.0x109/L). Approximately half of the blood cultures became positive. In addition, the median time to positivity of blood cultures was seven days (IQR 6–9) and 82.4% of patients had a time to positivity of more than five days. (Redo) surgery was performed in 40 patients (65.5%). Peroperatively, valve dehiscence was observed in 19 patients (47.5%) and vegetations and abscesses were present in 16 patients (40%). The 30-day and one-year mortality rates were 4.9% and 11.5% respectively. Eight patients experienced relapse IE during follow-up of which seven initially received conservative treatment. Conclusion IE due to C. acnes predominantly concerns males with prosthetic heart valves. The diagnostic process in C. acnes IE is difficult due to its atypical presentation, with frequent absence of fever and inflammatory parameters. Meanwhile, blood cultures remain negative in approximately half of the patients. Moreover, the time to positivity of blood cultures is one week, which further delays the diagnostic process. Redo surgery is required in a high percentage of patients. Funding Acknowledgement Type of funding sources: None.