Median C-reactive Protein Levels Research Articles

#406 High ferritin is not needed in hemodialysis patients: a retrospective study of total body iron and oral iron replacement therapy

Abstract Background and Aims In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. Although serum ferritin is useful as an indicator of iron stores, it does not necessarily reflect body iron levels in HD patients with unstable hematopoiesis since iron metabolism is a semi-closed system in vivo. In this study, we investigated total body iron (TBI), new index calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. Method We analyzed data on 105 courses of low-dose iron replacement therapy (50–120 mg of iron daily) administered to 83 patients with serum ferritin <60 ng/mL and Hb <12 g/dL undergoing maintenance hemodialysis at our institution. Low-dose oral iron replacement therapy was initiated between August 2016 and June 2023 and continued for at least seven months. All blood samples were collected at the start of hemodialysis at the beginning of the week. Blood examinations were performed twice a month, and patients were given darbepoetin alfa (DA), long-acting ESAs to maintain Hb at the target level of 10–12 g/dL, in accordance with the guidelines of the Japanese Society for Dialysis Therapy. Iron-related parameters were determined based on blood samples collected once a month, with TSAT calculated from serum iron (Fe) and total iron-binding capacity (TIBC), using the following equation. TSAT=Fe/TIBC × 100. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7, in two groups of patients, namely, iron-therapy responders and non-responders. Furthermore, we investigated factors associated with steady-state TBI. TBI was regarded as achieving a steady state during the course of therapy when the trend shifted from an increase and the difference from the value at one month was less than or equal to zero. TBI was calculated using the formula proposed by Cable et al (Transfusion. 2016, 56, 2005). Results Mean age was 68.1±12.6 years and median time on hemodialysis was 6.6 years. Of the 105 courses of therapy, 75 were delivered to men and 30 to women, and 66.7% of the patients had diabetic nephropathy. The patients had a mean Hb level of 10.4±0.7 g/dL, a mean serum ferritin level of 27.3±12.5 ng/mL, mean transferrin saturation (TSAT) of 18.1%±5.9%, and a median C-reactive protein level of 0.1 mg/dL at the start of each course. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900±447 vs. 1900±408 mg, Fig. 1). As for RBC iron, iron-therapy responders showed significant monthly increases up to month 3, whereas non-responders showed constant values. Regarding iron stores, iron-therapy responders showed significant monthly increases up to month 5, while non-responders showed a significant increase only at month 1. DA per body weight showed a significant decrease at month 3 and 4 in the effective group, but a slight increase in the non-responder group. Steady-state TBI did not correlate with Hb or serum ferritin, but was strongly correlated with body surface area (BSA) using the Du Bois formula [TBI=−791.914 + 1628.606 × BSA (m2); R2=0.88, p<0.001, Fig. 2]. Conclusion This study showed that hemodialysis patients can increase their body iron levels during oral iron replacement therapy and maintain them at the same level after sufficiency has been achieved, suggesting activation of a “mucosal block.” Furthermore, this result also suggests that determining iron sufficiency based on serum ferritin alone is difficult in HD patients with fluctuations in Hb. However, regression equations using steady-state TBI and BSA showed a high degree of fit. Therefore, BSA might potentially be used in estimations of TBI sufficiency, which may be useful for avoiding excessive iron dosage.

The Diagnostic Value of Soluble Triggering Receptor Expressed on Myeloid Cells for Patients with Acute Stone Pyelonephritis.

Soluble triggering receptor expressed on myeloid cells (sTREM-1) is a new biomarker that can be used for the diagnosis and monitoring of urinary system infections. This study aimed to evaluate the diagnostic performance of serum sTREM-1 in patients with a diagnosis of acute stone pyelonephritis (ASP). This prospective study included 46 patients with a diagnosis of ASP and a control group of 23 individuals without urinary system infection. Blood samples were taken from participants upon hospital admission, and basal serum sTREM-1 levels were analyzed using the ELISA method. Serum sTREM-1 concentrations were measured after treatment of ASP patients. Basal leukocyte counts, C-reactive protein (CRP) levels, procalcitonin (PCT), and sTREM-1 (98.6 vs. 68.4 pg/mL, p < 0.001) levels were higher in the ASP group compared to the control group. After treatment, the median leukocyte counts, PCT, and sTREM-1 levels decreased and were similar to those of the control group. The median CRP level also decreased after treatment, but it remained higher than that of the control group. In predicting patients with ASP, the baseline sTREM-1 exhibited a sensitivity of 74.6% and a specificity of 78.2%, while its diagnostic performance was lower than that of leukocyte counts, CRP, and PCT. Despite the findings that levels of sTREM-1 were higher upon hospital admission in patients with ASP and significantly decreased after treatment, the utility of sTREM-1 as a biomarker for predicting patients with ASP remains constrained when compared to established inflammatory markers.

C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

BackgroundRight ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. MethodsThis cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. ResultsThe study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0–76.4]mg/L vs n=124, 45.4 [16.0–111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00–1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00–1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. ConclusionsAs an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

Eosinophilic bronchiectasis increases length and cost of hospitalization: a retrospective analysis in a hospital of southern China from 2012 to 2020

BackgroundThe concept of eosinophilic bronchiectasis has received clinical attention recently, but the association between blood eosinophil count (BEC) and hospital characteristics has rarely been reported yet. We aim to investigate the clinical impact of BEC on patients with acute bronchiectasis exacerbation.MethodsA total of 1332 adult patients diagnosed with acute exacerbation of bronchiectasis from January 2012 to December 2020 were included in this retrospective study. A propensity-matched analysis was performed by matching age, sex and comorbidities in patients with high eosinophil count (≥ 300 cell/µL) and low eosinophil count (< 300 cell/µL). Clinical characteristics, length of hospital stay (LOS), hospitalization cost and inflammatory markers were compared between the two groups.ResultsEosinophilic bronchiectasis occurred in approximately 11.7% of all patients. 156 propensity score–matched pairs were identified with and without high eosinophil count. Eosinophilic bronchiectasis presented with a longer LOS [9.0 (6.0–12.5) vs. 5.0 (4.0–6.0) days, p < 0.0001] and more hospitalization cost [15,011(9,753–27,404) vs. 9,109(6,402–12,287) RMB, p < 0.0001] compared to those in non-eosinophilic bronchiectasis. The median white blood cell (WBC), lymphocyte, platelet (PLT) and C-reactive protein (CRP) levels in eosinophilic bronchiectasis were significantly increased. Multivariate logistic regression analysis confirmed that the high levels of eosinophil count (OR = 13.95, p < 0.0001), worse FEV1% predicted (OR = 7.80, p = 0.0003) and PLT (OR = 1.01, p = 0.035) were independent prognostic factors for length of hospital (LOS) greater than 7 days.ConclusionEosinophilic bronchiectasis patients had longer length of hospital stay and more hospitalization cost compared to those in non-eosinophilic bronchiectasis group, which might be associated with the stronger inflammatory reaction.

Myocardial Perfusion Imaging and C-Reactive Protein in Myocardial Ischemia: A Retrospective Single-Center Study.

Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coronary heart disease. We investigated the relationship of CRP with findings from myocardial perfusion imaging (MPI). In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) who underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6 mg/L) within 1 month from MPI were included. The patients had no infection or recent acute coronary syndrome. The median CRP level was 4 mg/L (2, 10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (p = 0.006) and summed rest score (SRS) (p = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, p = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (p = 0.027 and p = 0.005, respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). a high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

(090) The Relationship Between C-Reactive Protein and Total Testosterone in Aging Men: Findings from the Baltimore Longitudinal Study of Aging

Abstract Introduction Elevated C-Reactive Protein (CRP) and testosterone deficiency are associated with advanced age and chronic inflammatory diseases, such as cancer, diabetes, and cardiovascular disease. Testosterone decreases inflammation through several mechanisms, and testosterone replacement therapy (TRT) has been shown to lower CRP levels in aging, hypogonadal men. While cross-sectional studies have shown an inverse relationship between CRP and total testosterone (TT) levels, mixed findings have been reported when individual components of metabolic syndrome are considered. We hypothesized that men with testosterone deficiency will have high levels of CRP. Objective We evaluated the relationship between CRP and TT levels in men from 2004-2018 using the Baltimore Longitudinal Study of Aging and specifically attempted to determine if low androgen status is associated with a high inflammatory profile independent of comorbidities. Methods Male participants with serum TT level measured during two separate visits &amp;gt;3 years apart were included in our cohort. CRP, High-Density Lipoprotein (HDL) and Triglyceride levels were collected via blood specimens. Comorbidity data were documented at each visit. Panel regression was used to analyze the relationship of a series of independent variables collected in pooled cross-sectional observations over time with a dependent variable for modeling. Results A total of 347 patients were included in this study (mean age = 69 ± 15, average follow up time = 6.7 ± 3.2 years). Participants had a median CRP level of 1.0 mg/dL and a median TT level of 446 ng/dL. On univariable analysis TT and HDL levels were associated with a decline in CRP, while BMI, congestive heart failure (CHF), Diabetes, and Triglycerides were associated with increased CRP. Age was not associated with CRP. On multivariable analysis, we found that increasing TT level was associated with a decline in CRP levels, independent of comorbidities (p = 0.018; Table 1). BMI was associated with a significant increase in CRP (p = 0.001, Table 1). Age, CHF, Diabetes, HDL, and Triglycerides were not significant predictors of CRP on multivariable analysis. Conclusions Lower levels of serum total testosterone are associated with an increased CRP in older men. Given the importance of CRP in pathogenesis of chronic disease, we highlight the potential benefits of restoring testosterone levels in older, hypogonadal men via TRT. Disclosure No.

Predictive value of C-reactive protein for postoperative liver-specific surgical site infections

BackgroundC-reactive protein is a useful biological tool to predict infectious complications, but its predictive value in detecting organ-specific surgical site infection after liver resection has never been studied. We aimed to evaluate the predictive value of c-reactive protein and determine the cut-off values to detect postoperative liver resection–surgical site infection. MethodsA multicentric analysis of consecutive patients with liver resection between 2018 and 2021 was performed. The predictive value of postoperative day 1, postoperative day 3, and postoperative day 5 C-reactive protein levels was evaluated using the area under the receiver operating characteristic curve. Cut-off values were determined using the Youden index in a 500-fold bootstrap resampling of 500 patients treated at 3 centers, who comprised the development cohort and were tested in an external independent validation cohort of 166 patients at a fourth center. ResultsAmong the 500 patients who underwent liver resection of the development cohort, liver resection–surgical site infection occurred in 66 patients (13.2%), and the median time to diagnosis was 6.0 days (interquartile range, 4.0–9.0) days. Median C-reactive protein levels were significantly higher on postoperative day 1, postoperative day 3, and postoperative day 5 in the liver resection–surgical site infection group compared with the non–surgical site infection group (50.5 vs 34.5 ng/mL, 148.0 vs 72.5 ng/mL, and 128.4 vs 35.2 ng/mL, respectively; P < .001). Postoperative day 3 and postoperative day 5 C-reactive protein–level area under the curve values were 0.76 (95% confidence interval, 0.64–0.88, P < .001) and 0.82 (95% confidence interval, 0.72–0.92, P < .001), respectively. Postoperative day 3 and postoperative day 5 optimal cut-off values of 100 mg/L and 87.0 mg/L could be used to rule out liver resection–surgical site infection, with a negative predictive value of 87.0% (interquartile range, 70.2–93.8) and 76.0% (interquartile range, 65.0–88.0), respectively, in the validation cohort. ConclusionPostoperative day 3 and postoperative day 5 C-reactive protein levels may be valuable predictive tools for liver resection–surgical site infection and aid in hospital discharge decision-making in the absence of other liver-related complications.

P553 The safety and efficacy of adalimumab 80mg weekly as maintenance therapy in pediatric Crohn’s Disease

Abstract Background Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD. Methods In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes. Results Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis. Conclusion Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.

Comparative Analysis of Microbial Species and Multidrug Resistance Patterns Associated with Lower Urinary Tract Infections in Preterm and Full-Term Births.

The rise of multidrug-resistant organisms has significantly complicated the clinical management of urinary tract infections (UTIs), particularly in the context of pregnancy. This study aimed to identify and analyze the significant differences in microbial species and multidrug resistance patterns associated with UTIs in preterm versus full-term births, determine the bacterial species significantly associated with preterm birth, and describe the antibiotic resistance patterns affecting pregnant women with UTIs. This case-control study was conducted in western Romania and focused on pregnant women with UTIs admitted from 2019 to 2023. Data were retrospectively collected from 308 patients with positive cultures. Statistical analyses, including the Chi-square test, Fisher's exact test, and logistic regression models, were employed to compare the proportions of microbial species and resistance patterns between preterm (n = 126) and full-term (n = 182) birth groups and identify factors independently associated with preterm birth. The study found no significant differences in demographic or lifestyle factors between the groups. However, significant differences were observed in several infection and inflammation markers. The median white blood cell count was higher in the preterm group (12.3 vs. 9.1, p = 0.032), and the median C-reactive protein level was significantly higher in the preterm group (18 vs. 7, p < 0.001). The preterm group exhibited a higher incidence of multidrug-resistant organisms, notably ESBL-producing organisms (19.8% vs. 4.4%, p < 0.001) and carbapenem-resistant Enterobacteriaceae (4.8% with p = 0.003). Notably, the resistance to amoxicillin was significantly higher in the preterm group (20.6% vs. 6.6%, p < 0.001). Significant bacterial associations with preterm births included Group B Streptococcus (OR 2.5, p = 0.001) and Enterobacter spp. (OR 1.8, p = 0.022). The study confirmed significant differences in microbial species and multidrug resistance patterns between UTIs associated with preterm and full-term births. The higher prevalence of certain bacteria and increased resistance to commonly used antibiotics in the preterm group underscore the need for tailored antimicrobial therapies and robust microbial identification in managing UTIs during pregnancy.

COVID-19 and tuberculosis coinfection: A case-control study from a tertiary care center in South India.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB), are presently the major infectious diseases imposing a consequential public health threat and their coinfection has a significant impact on the outcome. To evaluate the clinical features and outcomes of COVID-19-TB coinfected cases compared to solely COVID-19-infected cases. A retrospective observational study was conducted between August 1, 2020, to February 28, 2022, at a tertiary care hospital. In this case-control study, an equal number of gender-age-matched COVID-19 and TB coinfected patients and COVID-19 cases without TB were included using simple random sampling. The data was analyzed using SPSS v 26. Categorical variables were compared using the Chi-square test, and an independent t-test or Mann-Whitney U test was applied for the quantitative variables in the univariate analysis. A P-value of less than 0.05 was considered significant. A total of 27 patients were included in each group. Upper lobe involvement (44%) and pleural effusion (22%) were significantly more common in TB-COVID-19 cases when compared to the control group (7% and 4%, respectively; P < 0.05). Moreover, median levels of C-reactive protein and ferritin were significantly higher in TB-COVID-19 coinfection. Chest radiology and a higher level of certain biomarkers like C-reactive protein and ferritin can help to suspect TB in COVID-19 patients and vice-versa.

Baseline 18f-Fluorodeoxyglucose PET/CT Radiomics Predicts Outcome in Newly Diagnosed Intravascular Large B-Cell Lymphoma

[Introduction] Treatment outcomes of intravascular large B-cell lymphoma (IVLBCL), a rare subtype of extra-nodal diffuse large B-cell lymphoma (DLBCL), have dramatically improved in recent years. However, prognostic factors for IVLBCL are largely unknown. Several studies have explored the potential of the baseline 18F-fluorodeoxyglucose (FDG) PET/CT radiomics features to identify patients with poor prognosis. For example, metabolic tumor volume (MTV) reflects the FDG-avid tumor burden, and the maximum distance between the largest lesion and any other lesion quantifies the dissemination of the tumor, and both factors are inversely related to overall survival (OS) and progression-survival (PFS) in DLBCL. In this study, we explored prognostic impact of FDG PET/CT radiomics features in newly diagnosed IVLBCL. [Methods] We retrospectively evaluated patients with histopathologically proven newly diagnosed IVLBCL according to the 2008 World Health Organization criteria between January 2010 through February 2022 from hospitals participating in the North Japan Hematology Study Group (NJHSG). Quantitative analysis of all FDG PET/CT was performed using Metavol (Hokkaido University, Sapporo, Japan), with exclusion of physiological accumulation. MTV was defined as the volume of lymphoma lesions visualized on PET/CT scans with standardized uptake value (SUV) peaks greater than or equal to hepatic SUV peak. To quantify the dissemination of the tumor, we calculated the number of the body areas (head-neck, chest, abdomen, upper-extremities, lower-extremities) having BM lesions with a higher SUV peak than liver SUV peak. Patients with BM lesions spread across 4-5 areas were defined as cases having widely disseminated lesions (WDL). Progression-free survival (PFS) was defined as the time from the start of treatment to the first of progression, relapse, or death from any cause. Patients undergoing upfront autologous stem-cell transplantation (auto-SCT) were censored at the time of transplantation. [Results] We identified fifty-two IVLBCL patients (age 30-89 years, median 65 years; 57.7% male) who performed FDG PET/CT at diagnosis. Twenty-eight patients (54.9%) had poor performance status (ECOG PS ≥2), and 49 patients (94.2%) showed stage III-IV. Forty-nine patients (94.2%) had 2 or more extranodal involvement. Elevated serum LDH level was observed in 49 cases (94.2%) (median, 623.5 IU/L; range, 147-4907 IU/L). The median serum levels of soluble IL-2 receptor (sIL-2R), ferritin, and C-reactive protein (CRP) were 4496.5 IU/mL (range, 321-19900 IU/mL), 655.15 ng/mL (range, 50-6657 ng/mL), and 6.905 mg/dL (range, 0.11-25.86 mg/dL), respectively. The median MTV was 415.527 cm 3 (range, 0-3000 cm 3). ROC analysis revealed that the cutoff value of the MTV &amp;gt; 388 cm 3 could predict progression events within 2 years. Area under curve was 0.71 (95% CI: 0.564-0.857). Twenty-nine patients (55.8%) were classified as having MTV &amp;gt; 388 cm 3 (high MTV). Twenty-three patients (44.2%) had WDL. Fifty-one (98.1%) patients received chemotherapy, all of which was rituximab-containing regimen. Three patients (5.8%) received upfront auto-SCT. Median follow-up duration was 48.8 months (range, 5.8-140.5 months) in survivors. Age, LDH level, number of extranodal lesions, clinical stage, and PS did not affect OS and PFS. Although the high MTV and WDL did not significantly affect OS ( P = 0.095, P = 0.173, respectively; Log-rank), these findings did correlate significantly with poor PFS ( P = 0.011, P = 0.042, respectively; Log-rank). Thus, we defined a high MTV or a WDL as poor PET findings. Thirty-two patients had poor PET findings. Importantly, patients with poor PET findings showed significantly poor OS and PFS compared to patients without (2-year OS: 71.2% vs. 93.3%, P = 0.015, 2-year PFS: 45.5% vs. 93.8%, P = 0.001; Log-rank, Fig. 1, 2). [Conclusion] This is the largest study to assess prognostic impact of FDG PET/CT radiomics features on newly diagnosed IVLBCL. Poor PET findings were significantly correlated with worse OS and PFS.

Phase 2 Study of Anakinra to Prevent CRS and Neurotoxicity after Treatment with Lisocabtagene Maraleucel: Planned Interim Analysis

BACKGROUND CD19 chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for patients (pts) with relapsed/refractory B-cell malignancies, but they remain limited by significant toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). While a more favorable toxicity profile had been reported with lisocabtagene maraleucel (liso-cel), based on our real-world experience CRS and ICANS are still observed in 70% and 30% of pts, respectively (Portuguese et al., ASH abstract #172978). Data from our group (Gazeau, TCT, 2023) and others (Strati, Blood, 2023; Park, Nat Med, 2023) suggested the recombinant interleukin-1 receptor antagonist anakinra may successfully prevent and treat CRS and ICANS. Thus, we conducted a phase 2 investigator-initiated clinical trial of anakinra to prevent CRS and ICANS after liso-cel (NCT04359784). We report here our planned interim analysis (n = 15). METHODS Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma receiving liso-cel per the FDA label were eligible for this study. Anakinra was administered at 200 mg/day SC from day 0 through day +13 after liso-cel infusion, with the first dose administered approximately 2-4 hours prior to liso-cel infusion. CRS and ICANS severity were assessed per 2019 ASTCT criteria. The primary endpoint was the absence of any grade CRS assessed using the Bayesian optimal phase 2 design.The primary endpoint was not met if ≥6 of the first 15 pts developed any grade CRS. RESULTS Nineteen pts were screened for the study and 15 pts were enrolled. All 15 pts received liso-cel and all doses of SC anakinra. All pts were evaluable for toxicity assessment; 12 pts were evaluable for disease response assessment at day +28 (n = 3, no measurable disease prior to lymphodepletion [LD]). Pt and disease characteristics are shown in Table 1. Eleven pts (73%) had diffuse large B-cell lymphoma, 3 (20%) had active CNS involvement, and 5 (33%) had bulky disease (≥5 cm). Median pre-LD serum ferritin and C-reactive protein (CRP) were 153 ng/mL (IQR, 129-231) and 6.8 (IQR, 1.5-17.2), respectively. All 15 pts received anakinra as planned without dose adjustment or interruption. There were no injection-site reactions or AEs attributed to anakinra. Two pts developed infections during anakinra treatment and were both due to mild Clostridium difficile colitis requiring oral antibiotics. Eight pts (53%) developed any grade CRS, including 1 (7%) case of grade 3 CRS. Four pts (27%) developed any grade ICANS, including 3 (20%) with grade 3 (Figure 1). Median CRS onset and duration were 2 and 2.5 days, respectively, and median ICANS onset and duration were 6 and 9 days, respectively. Three pts (20%) required tocilizumab (range, 0-1 doses), 4 (50%) required dexamethasone (median total dose, 5 mg; range, 0-200 mg), and 1 (12%) required high-dose methylprednisolone. The best overall response rate (ORR) by Lugano criteria was 67% (complete response, n = 5 [42%]). Study pts were retrospectively compared to pts who received liso-cel per standard of care off trial without prophylactic anakinra at our center (n = 42). Despite higher median pre-LD CRP and IL-6 levels, the incidence of CRS was lower in anakinra-treated compared to anakinra-untreated pts (53% vs. 69%, respectively) with comparable median duration of CRS (2.5 vs. 3 days, respectively). The incidence and duration of ICANS were similar (27% vs. 28%; median 9 vs. 8 days, respectively), as was the incidence and duration of hospitalization (67% vs. 74%, median 9.5 vs. 10 days, respectively). Based on Locally Estimated Scatterplot Smoothing (LOESS) estimates, time from liso-cel infusion to CRP normalization was faster in patients receiving anakinra (9 days) compared to those receiving liso-cel alone (14 days). CONCLUSION Low-dose SC anakinra prophylaxis during liso-cel treatment was very well tolerated with preserved anti-tumor efficacy. While our primary endpoint was not reached at our planned interim analysis, we observed lower CRS rates and faster resolution of CRS in comparison to a real-world cohort of pts receiving liso-cel without prophylactic anakinra. To further enhance the preventative effects of anakinra, we plan to change the administration route from SC to intravenous, and to allow anakinra dose uptitration for the last 10 participants in the study.

Prognostic Significance of C-Reactive Protein in Lenvatinib-Treated Unresectable Hepatocellular Carcinoma: A Multi-Institutional Study.

Serum C-reactive protein (CRP) is an established biomarker for acute inflammation and has been identified as a prognostic indicator for hepatocellular carcinoma (HCC). However, the significance of the serum CRP level, specifically in HCC patients treated with lenvatinib, remains unclear. We retrospectively analyzed 125 HCC patients who received lenvatinib treatment at six centers. Clinical characteristics were assessed to identify clinical associations between serum CRP and HCC prognosis. The median overall serum CRP level was 0.29 mg/dL. The cohort was divided into two groups: the low-CRP group with a serum CRP < 0.5 mg/dL and the high-CRP group with a serum CRP ≥ 0.5 mg/dL. The low-CRP group exhibited significantly longer overall survival (OS) than the high-CRP group (22.9 vs. 7.8 months, p < 0.001). No significant difference was observed for progression-free survival (PFS) between the high- and low-CRP groups (9.8 vs. 8.4 months, p = 0.411), while time-to-treatment failure (TTF) was significantly longer in the low-CRP group (8.5 vs. 4.4 months, p = 0.007). The discontinuation rate due to poor performance status was significantly higher in the high-CRP group (p < 0.001). A baseline serum CRP level exceeding 0.5 mg/dL was identified as an unfavorable prognostic factor in HCC patients receiving lenvatinib treatment.

Impact of C-Reactive Protein on Long-Term Cardiac Events in Stable Coronary Artery Disease Patients with Chronic Kidney Disease.

Chronic inflammation is associated with atherosclerosis development. Chronic kidney disease (CKD) is an independent risk factor for cardiovascular events and is associated with chronic inflammation. We aimed to investigate the influence of C-reactive protein (CRP), an important marker of inflammation, on the clinical outcomes of patients with CKD and stable coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Among patients with stable CAD and CKD who underwent PCI, 516 patients whose CRP levels were available before the PCI procedure were identified. The patients were divided into two groups according to the CRP levels: those with CRP ≥ 2.0 mg/L (high-CRP group) and those with CRP ＜2.0 mg/L (low-CRP group). The primary endpoint of this study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and unplanned revascularization. Overall, the mean age of the patients was 72.5±9.7 years, and 20.7% were female. The median CRP level was 1.43 mg/L (0.6-4.9 mg/L). The median follow-up period was 3.6 years. The occurrence of MACE was significantly higher in the high-CRP group than in the low-CRP group (log-rank p＜0.001). Notably, the incidence rate of cardiac death was significantly higher in the high-CRP group (log-rank p＜0.001). According to the multivariable analysis, CRP level ≥ 2.0 mg/L was found to be a significant predictor of MACE (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.04-2.28, p=0.003), as well as estimated glomerular filtration rate (HR: 0.98, 95% CI: 0.97-0.99, p＜0.01). High-CRP levels adversely affect long-term cardiac events in patients with stable CAD and CKD.

Racial and ethnic differences in clinical outcomes among patients with multiple myeloma treated with CAR T-cell therapy

AbstractIdecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain US Food and Drug Administration approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 patients with RRMM (28% patients of racial and ethnic minority groups) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic White patients with RRMM. Compared with Hispanic and non-Hispanic White patients, non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P = .02) and baseline ferritin (362.0 vs 307.0 vs 680.5, respectively; P = .08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P = .04). Although best overall response rate was lower among Hispanic patients (59%) than among non-Hispanic Black (86%) and White patients (86%; P = .01), there were no racial and ethnic differences in progression-free or overall survival. We provide, to our knowledge, the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all patients with RRMM. These findings should be confirmed in larger samples of diverse patients with RRMM, with longer follow-up time.

Evaluation of new generation systemic immune-inflammation markers to predict urine culture growth in urinary tract infection in children.

Systemic inflammation has been implicated in the development and progression of urinary tract infection (UTI). Accordingly, the aim of this study is to determine whether the white blood cell (WBC), C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are useful markers to predict of urine culture growth in children with UTI. The second aim of this study is to evaluate the prevalence of UTI pathogens, antibiotic resistance patterns, and empirical treatment options in children diagnosed with UTI based on laboratory and clinical findings. The study population comprised 413 cases (positive urine culture) and 318 cases (negative urine culture) of pediatric patients with UTI. There was no statistically significant difference observed in the median levels of hemoglobin, hematocrit, and platelet between the negative and positive culture groups. The median levels of monocytes, WBC, NLR, SII, and CRP of the patients with a positive urine culture were shown to be statistically significantly higher than the patients with a negative urine culture. The AUC value was 0.747 (0.710-0.784) for CRP with a cutoff value of 3.2, the sensitivity value was 56.4%, and the specificity value was 98.4% in terms of UTI. The AUC value was 0.733 (0.697-0.769) for SII with a cutoff value of 600, the sensitivity value was 58.4%, and the specificity value was 83.0%. The AUC value was 0.732 (0.697-0.769) for NLR with a cutoff value of 2, the sensitivity value was 57.4%, and the specificity value was 81.1%. WBC, CRP, NLR, PLR, and SII could potentially serve as useful independent diagnostic or complementary markers for disease in children diagnosed with UTI who exhibit a positive urine culture. Escherichia coli was found to be the most common causative agent, and the commonly prescribed antibiotic was cephalosporin. However, it was observed that all identified agents of pediatric UTIs in our center exhibited high resistance to cefuroxime, trimethoprim-sulfamethoxazole, cefixime, ampicillin, and ceftriaxone.

A Single-Center Evaluation of Pediatric Measles Cases in Istanbul, Türkiye, in 2019.

Although measles can be prevented and eliminated by vaccination, it is a highly contagious viral disease that can lead to serious complications, disability, and death. The aim of this retrospective study was to evaluate the characteristics of measles cases in a single center. All children with clinically suspected measles who attended the Pediatric Clinic at Esenler Maternity and Child Health Hospital in Istanbul, Türkiye, between January 1 and June 30, 2019 were included in the analysis. None of the children with measles were fully vaccinated. The incidence and duration of conjunctivitis were significantly higher in the unvaccinated group than in the partially vaccinated group (P = 0.027 and P = 0.019, respectively). Unvaccinated patients had a significantly lower median leukocyte count (P = 0.019) and significantly higher median C-reactive protein level (P = 0.021). The vitamin A level and leukocyte count were moderately positively correlated (r = 0.698; P = 0.008). Children should be fully vaccinated in order to prevent measles.

When MRI would be useful in patients without evidence of sacroiliitis on radiographs?

We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count.

E19 Gamma-glutamyl transpeptidase level is correlated with disease activity in oligoarticular and polyarticular Juvenile idiopathic arthritis

Abstract Introduction Gamma-glutamyl transpeptidase (GGT) level was found to be correlated with disease activity indexes in rheumatoid arthritis [1]. This association was not yet investigated in children with oligoarticular and polyarticular Juvenile idiopathic arthritis (JIA). Objectives The present study aims to investigate the correlation between GGT level and disease-related parameters in oligoarticular and polyarticular JIA. Methods We performed a retrospective study including patients with oligoarticular and polyarticular JIA responding to the 2001 International League of Associations for Rheumatology (ILAR) classification. Sociodemographic, disease-related parameters (age of onset, disease duration, patient global assessment (PGA), Pain Visual Analogue Scale (VAS), C-Reactive protein (CRP) level, Erythrocyte Sedimentation Rate (ESR), disease activity assessed using the Juvenile Arthritis Disease Activity Score (JADAS) based on ESR), and GGT level were collected. Continuous variables were expressed with median and Interquartile range (IQR). Spearman correlation was used to assess the association between GGT levels and disease-related data. Results Eleven patients were included with a median age of 12 (IQR: 10–15) years and 8 females. Median disease duration was 4 (IQR: 4–7) years and median age of onset was 8 (IQR: 5–10) years. Five patients had oligoarticular JIA, 3 had a polyarticular with positive Rheumatoid Factor (RF) form, 2 had a polyarticular with negative RF form and one had an undifferentiated JIA. Median JADAS was 3.6 (IQR: 0–9). Median ESR, CRP, and GGT levels were 14 (10–19) mm/H, 1.8 (2–6.4) mg/l, and 14 (12–16) IU/l, respectively. A strong positive correlation was found between GGT level and JADAS (r = 0.749, P = 0.008). Level of CRP and ESR were not correlated with GGT level. Besides, patient global assessment and pain VAS were positively correlated with GGT level (r = 0.670, P = 0.049; r = 0.814, P = 0.014, respectively). No correlation was found between GGT level and disease duration and number of tender or swollen joints. Conclusion The GGT level was significantly higher in patients with more active disease, higher pain, and global assessment. This suggests that GGT level can be used as a marker of disease activity as in JIA. References 1 Vergneault H, Vandebeuque E, Codullo V, Allanore Y, Avouac J. Disease Activity Score-28 using γGT permits a dual evaluation of joint activity and cardiovascular risk. J Rheumatol 2020.

Prevalence of Disease-Related Malnutrition and Micronutrients Deficit in Patients with Inflammatory Bowel Disease: A Multicentric Cross-Sectional Study by the GSMII (Inflammatory Bowel Disease Study Group).

Inflammatory bowel disease (IBD) patients might experience disease-related malnutrition (DRM), but prevalence and risk factors are not well defined. The primary aim of the study was to define the prevalence of DRM and micronutrient deficiency in IBD patients; the secondary aim was to assess variables related to DRM. A multicenter, cross-sectional study was performed including consecutive adult IBD patients during a period of 2 weeks. Nutritional status was assessed with the body mass index (BMI) and the Malnutrition Universal Screening Tool. DRM was defined according to European Society for Clinical Nutrition and Metabolism guidelines. Among the 295 enrolled patients, the prevalence of DRM was 23%, with no statistical difference between Crohn's disease and ulcerative colitis. Compared with well-nourished patients, patients with DRM showed higher rate of hospitalization in the previous month, were more often receiving systemic steroids, and had lower hemoglobin, albumin, and prealbumin levels and higher median C-reactive protein levels. At univariate logistic regression, current hospitalization, hospitalization in the previous month, low serum albumin, low BMI, high C-reactive protein, high Crohn's Disease Activity Index, and female sex were variables related to DRM. At the multivariate logistic regression, low BMI, current hospitalization and hospitalization in the previous month were significantly associated with DRM. In 23% of IBD patients, a deficiency of at least 1 micronutrient was observed, with no difference between ulcerative colitis and Crohn's disease. DRM and microelements malnutrition are frequent conditions in the IBD population. DRM seems to be associated with disease activity and hospitalization.