Lower CRP Research Articles

High eosinophil counts aid in diagnosing Kawasaki disease in febrile children

Abstract Background Several recent studies have validated the newfound significance of elevated eosinophils in Kawasaki disease (KD). However, this finding was not incorporated into the suggested laboratory criteria outlined by the Kawasaki Disease Committee of the American Heart Association for assessing children with incomplete KD. Purpose We aimed to determine the potential benefits of including eosinophil levels in the laboratory evaluation of KD. Methods A retrospective cohort study involved 77,934 febrile children (FC, not KD) and 1,970 subjects diagnosed with KD. Participants were recruited from four hospitals, comprising two medical centers and two regional hospitals. The AHA recommends specific laboratory tests—white blood cell count, hemoglobin, platelet count, ALT levels, albumin, and urinalysis—for evaluating incomplete KD in children with a higher CRP than 30mg/dL. The first four items are standard blood assays. Additionally, we introduced high eosinophil counts as a new diagnostic criterion for identifying children with KD. Results All these five laboratory findings (anemia for age defined as below the 5th percentile), platelet count >450,000/mm3, white blood cell>15,000/mm3, ALT>40 U/L, and eosinophil count >190/mm3) are significantly different between KD children and FC. The proportion of having these features is higher in KD children than in FC (19.3% vs. 8.0% in anemia for age, 20.5% vs. 10.3% in thrombocytosis, 37.0% vs. 18.1% in leukocytosis, 45.7% vs. 5.8% in elevated ALT, and 62.6% vs. 29.3% in high eosinophils). Elevated eosinophil counts are most commonly associated with KD among these five parameters. Furthermore, when incorporating the parameter of elevated eosinophil counts, the proportion of KD children with at least two abnormalities rose from 35.4% to 60.7%. In a subgroup analysis of children with KD presenting at least two abnormalities, the proportion rose from 38.7% to 63.5% in the high CRP group (≧ 3.0 mg/L) and 21.6% to 49.0% in the low CRP group (< 3.0 mg/L), respectively. Conclusions Higher eosinophil counts are vital markers in KD children. This aids in the identification of additional potential KD cases, especially in those exhibiting low CRP levels.

Vulvar necrotizing wounds: Unveiling mortality-associated parameters and assessing the efficacy of VAC therapy

IntroductionVulvar Necrotizing Fasciitis (VNF) is a critical, severe soft tissue infection characterized by aggressive progression and significant morbidity and mortality. Rapid diagnosis and immediate, comprehensive treatment, including antibiotic therapy, meticulous surgical debridement, and multidisciplinary care, are crucial for improving outcomes. This study aimed to investigate mortality-related factors in VNF and evaluate treatment modalities, focusing on Vacuum-Assisted Closure (VAC) therapy versus traditional debridement. MethodsThis retrospective study analyzed data from 22 VNF patients. Criteria included adults diagnosed with vulvar necrotizing infections, excluding those transferred or not completing treatment at the center. The study examined mortality-related factors and the efficacy of VAC therapy compared to debridement, considering treatment costs and outcomes. ResultsAnalysis divided patients into survivors (13) and non-survivors (9). Higher heart rate, elevated WBC and CRP levels, and higher Clavien-Dindo scores were associated with increased mortality. VAC therapy, compared to traditional debridement, resulted in significantly lower CRP levels and reduced treatment costs. However, other parameters such as the length of hospital stay and debridement frequency showed no significant differences. ConclusionThe study highlights that older age, systemic inflammation, and severe postoperative complications are key factors associated with higher mortality in VNF. VAC therapy emerges as a promising modality, effectively reducing systemic inflammation and healthcare costs. Nonetheless, the retrospective nature and the small sample size of the study limit the generalizability of the findings. Future research, particularly larger, multicentric studies, is essential to further explore and validate the effectiveness of VAC therapy in VNF management.

Genetic susceptibility and clinical features of CYP2D6 associated with systemic lupus erythematosus in a Chinese population.

This study aims to explore possible susceptibility genes and clinical features for systemic lupus erythematosus (SLE) patients in a Chinese population. Expanding on the results of a prior single-center observational study involving 60 systemic lupus erythematosus patients, a subsequent single-center prospective observational study was conducted on SLE patients undergoing treatment at Nanfang Hospital Affiliated to Southern Medical University from 2021 to 2023. The identification process for drug-related target genes entailed an extensive search across PharmGKB (https://www.pharmgkb.org/), the Clinical Pharmacogenetics Implementation Consortium (CPIC),and PubMed literature databases, to pinpoint common drugs and target single nucleotide polymorphisms(SNPs)for SLE. Blood samples were individually collected and genotyped using MassARRAY® high-throughput nucleic acid mass spectrometry. Genotype frequency differences were assessed through Chi-square tests against both the larger East Asian population as well as kidney transplant recipients. Data collection relied on electronic medical records, encompassing demographic details(age, gender),medication regimens(hormones, NSAIDs, hydroxychloroquine, DMARDs, biologic agents, stomach medications, calcitriol, etc.),laboratory indicators(RF, Anti-CCP antibody, ESR, CRP, anti-ANA antibodies, dsDNA antibodies, anti-SM antibodies, S m. RNP antibodies, A LT, ALB, CR, UA, WBC, PLT, HGB, Ca, K, Glu, CHOL, TG, LDL-C, HDL-C) and lupus activity scores(SLEDAI-2K). Possible disease susceptibility genes were categorized, and SPSS26 software facilitated statistical analyses. The research encompassed a total of 137 SLE patients along with 50 SNPs. After conducting statistical analyses, it emerged that there existed significant disparities in CYP2D6 gene (rs1065852) distribution when compared against allele mutation rates within both East Asian populations (p < .05) and kidney transplant patients(p < .05). Wild-type gene (GG) constituted 14% of cases while mutant gene (GA + AA) constituted 86%. Allele mutation rate (A63.6%) was significantly higher among SLE patients (RR = 0.802; p = .0355). Furthermore, the variant rs1065852 genotype (GA + AA) demonstrated significant associations with lower CRP levels, higher HGB levels, and higher HDL-C levels (p < 0 0.05). The metabolic enzyme CYP2D6 may be used as susceptibility gene for predicting systemic lupus erythematosus and are correlated with CRP and other indicators.

Effect of Combination of Point-of-Care C-Reactive Protein Testing and General Practitioner Education and Long-Term Effect of Education on Reducing Antibiotic Prescribing for Children Presenting with Acute Infections in General Practice in Latvia: A Randomized Controlled Intervention Study.

Antibiotics are often overprescribed in children in general practice. We investigated whether the availability of C-reactive protein point-of-care testing (CRP POCT) in daily practice and general practitioner (GP) education reduces antibiotic prescribing for children with acute infections and whether GP education has a long-term effect on antibiotic prescribing. This was a randomized controlled intervention study with randomization at the GP practice level. Eligible patients were children aged 1 month to 17 years presenting to general practice with an acute infection. In the first study period, one GP group received combined interventions (CRP POCT was provided for daily use in combination with a live educational session), while the second GP group continued usual care. During the second study period, the GP groups were switched. During this period, the long-term education effect was evaluated in the GP group, which had previously received both interventions: the CRP POCT was no longer available in their practices in accordance with the study protocol, but education could have a lasting effect. Antibiotic prescribing at index consultation. GP with combined intervention enrolled 1784 patients, GP with usual care enrolled 886 patients, and GP with long-term education effect enrolled 647 patients. Most of the patients had upper (76.8%) and lower (18.8%) respiratory infections. In total, 29.3% of the study patients received antibiotic prescriptions. Adjusted binary logistic regression analysis showed no differences for the primary outcome between GPs with usual care and GPs with combined intervention (aOR 0.89 (0.74-1.07), p = 0.20), but significantly lower antibiotic prescribing was observed for GPs with long-term education in comparison with GPs with usual care (aOR 0.75 (0.59-0.96), p = 0.02); however, after multilevel analyses, any differences in the antibiotic prescription between intervention groups became non-significant. GPs widely used CRP POCT when it was available in practice (for 69.1% of patients in the combined intervention group), but rarely measured CRP in the laboratory in the usual care group (8.8% (n = 78)) or long-term education group (14.8% (n = 98)). The majority of the tested patients had low CRP levels (below 20 mg/L); despite this, up to 35.4% of them received antibiotic prescriptions. Our results show that the availability of CRP POCT and educational training for GPs together did not reduce antibiotic prescribing, and one-time education did not have a long-term effect on antibiotic prescribing.

Predictors of Permanent Vision Loss in Giant Cell Arteritis

ABSTRACT To report on the occurrence and characteristics of eye manifestations and determine the predictors of permanent vision loss (PVL) in patients with giant cell arteritis. Case-control study. Retrospective cohort study of 258 patients diagnosed with giant cell arteritis (GCA) over a 20- year period at a single institution. Eighty nine of 258 patients (34.5%) with GCA had vision symptoms and 56 (21.7%) developed PVL. Acute loss of vision with no preceding ocular symptoms occurred in 28.5%; for those with symptoms, median time to vision loss was 4.5 days. Bilateral clinical eye involvement was present in 38%, mostly anterior ischemic optic neuropathy (AION), rarely vascular occlusions. Vision loss was severe with acuity of count fingers or less or mean deficit −20 decibels or less in at least one eye in 80% of patients with PVL. Following initiation of GC treatment, 23% of patients continued to have further vision loss and only 5% showed improvement. We found predictors of PVL by multivariate analysis to be increased age (OR 1.05, p0.040), jaw claudication (OR 2.29, p = .040), diplopia (OR 2.74, p = .039), increased platelets (OR 2.98, p = .020) and lower CRP (OR 0.63, p = .004). We found there is a 27.3% decrease in the odds of having PVL when CRP value is doubled, keeping all other variables fixed. Permanent vision loss was 3.07 times more likely in the absence of polymyalgia rheumatica and 4.25 times more likely in patients without headaches. Ocular involvement in GCA is common, usually severe with little chance of recovery. Detailed analysis of visual acuity and visual field loss in our PVL cohort adds valuable data to the literature which lacks this information. Older patients with jaw claudication, diplopia, and increased platelets are at higher risk for permanent vision loss, especially when PMR and headache are absent and acute phase reactants lower.

Network analysis of depressive symptoms and C-reactive protein levels in major depressive disorder

BackgroundC-reactive protein (CRP) levels have been implicated in the severity and symptomatology of major depressive disorder (MDD). The aim of this study was to explore the structure of depressive symptoms in patients with MDD according to different groups of CRP levels using network analysis. MethodsThe study included 864 individuals (mean age = 54.05, 67.48 % male) diagnosed with MDD from the 2015–2020 National Health and Nutrition Examination Survey (NHANES). Analyses examined how depressive symptoms and CRP level were related to each other, and how the network structure of depressive symptoms differed across groups with different CRP levels. ResultsA direct positive correlation was observed between CRP levels and specific depressive symptoms (e.g., appetite change, energy loss, and feelings of worthlessness). Moreover, there was a stronger correlation between depressive symptoms in the medium CRP and high CRP groups compared to the low CRP group. Furthermore, it was observed that there were notable structural differences between the high-CRP and moderate-CRP groups. LimitationsThe study is based on cross-sectional data, which precludes the drawing of causal conclusions. Furthermore, it does not take into account confounding factors such as body mass index (BMI) and lifestyle. ConclusionsThe findings underscore the pivotal role of CRP as a marker of the severity of depressive symptoms. Routine CRP level testing and anti-inflammatory therapies may be beneficial for depressed patients with elevated CRP levels in clinical practice.

The association of inflammatory markers with frailty and in-hospital mortality in older COVID-19 patients

IntroductionDuring the COVID19 pandemic, older patients hospitalized for COVID-19 exhibited an increased mortality risk compared to younger patients. While ageing is associated with compromised immune responses and frailty, their contributions and interplay remain understudied. This study investigated the association between inflammatory markers and mortality and potential modification by frailty among older patients hospitalized for COVID-19. MethodsData were from three multicenter Dutch cohorts (COVID-OLD, CliniCo, Covid-Predict). Patients were 70 years or older, hospitalized for COVID-19and categorized into three frailty groups: fit (Clinical frailty score (CFS) 1–3), pre-frail (CFS 4–5), and frail (CFS 6–9). Immunological markers (lymphocyte count, neutrophil count, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammation index (SII)) were measured at baseline. Associations with in hospital mortality were examined using logistic regression. ResultsA total of 1697 patients were included from COVID-OLD, 656 from Covid-Predict, and 574 from CliniCo. The median age was 79, 77, and 78 years for each cohort. Hospital mortality rates were 33 %, 27 % and 39 % in the three cohorts, respectively. A lower CRP was associated with a higher frailty score in all three cohorts (all p < 0.01). Lymphocyte count, neutrophil count, NLR, PLR, or SII, were similar across frailty groups. Higher CRP levels were associated with increased in-hospital mortality risk across all frailty groups, across all cohorts (OR (95 % CI), 2.88 (2.20–3.78), 3.15 (1.95–5.16), and 3.28 (1.87–5.92)), and frailty did not modify the association between inflammatory markers and in-hospital mortality (all p-interaction>0.05). ConclusionWhile frailty is a significant factor in determining overall outcomes in older patients, our study suggests that the elevated risk of mortality in older patients with frailty compared to fit patients is likely not explained by difference in inflammatory responses.

B Cells Isolated from Individuals Who Do Not Respond to the HBV Vaccine Are Characterized by Higher DNA Methylation-Estimated Aging Compared to Responders.

Healthcare workers (HCWs) are a high-risk group for hepatitis B virus (HBV) infection. Notably, about 5-10% of the general population does not respond to the HBV vaccination. In this study, we aimed to investigate DNA methylation (DNAm) in order to estimate the biological age of B cells from HCW of both sexes, either responder (R) or non-responder (NR), to HBV vaccination. We used genome-wide DNA methylation data to calculate a set of biomarkers in B cells collected from 41 Rs and 30 NRs between 22 and 62 years old. Unresponsiveness to HBV vaccination was associated with accelerated epigenetic aging (DNAmAge, AltumAge, DunedinPoAm) and was accompanied by epigenetic drift. Female non-responders had higher estimates of telomere length and lower CRP inflammation risk score when compared to responders. Overall, epigenetic differences between responders and non-responders were more evident in females than males. In this study we demonstrated that several methylation DNAm-based clocks and biomarkers are associated with an increased risk of non-response to HBV vaccination, particularly in females. Based on these results, we propose that accelerated epigenetic age could contribute to vaccine unresponsiveness. These insights may help improve the evaluation of the effectiveness of vaccination strategies, especially among HCWs and vulnerable patients.

Association of Changes in C-Reactive Protein Level Trajectories Through Early Adulthood With Cognitive Function at Midlife: The CARDIA Study.

Late-life inflammation has been linked to dementia risk and preclinical cognitive decline, but less is known about early adult inflammation and whether this could influence cognition in midlife. We aimed to identify inflammation levels through early adulthood and determine association of these trajectories with midlife cognition. We used data from the Coronary Artery Risk Development in Young Adults study to identify inflammation trajectories (C-reactive protein [CRP] level <10 mg/L) over 18 years through early adulthood (age range 24-58) in latent class analysis and to assess associations with cognition 5 years after the last CRP measurement (age range 47-63). Six cognitive domains were evaluated from tests of verbal memory, processing speed, executive function, verbal and category fluency, and global cognition; poor cognitive performance was defined as a decline of ≥1 SD less than the mean on each domain. The primary outcome was poor cognitive performance. Logistic regression was used to adjust for demographics, smoking, alcohol use, physical activity, and APOE 4 status. Among 2,364 participants, the mean (SD) age was 50.2 (3.5) years; 55% were female, and 57% were White. Three CRP trajectories emerged over 18 years: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Compared with lower stable CRP, both consistently higher (adjusted odds ratio [aOR] 1.67, 95% CI 1.23-2.26) and moderately/increasing (aOR 2.04, 95% CI 1.40-2.96) CRP had higher odds of poor processing speed; consistently higher CRP additionally had higher odds of poor executive function (aOR 1.36, 95% CI 1.00-1.88). For memory (moderately/increasing aOR 1.36, 95% CI 1.00-1.88; consistently higher aOR 1.18, 95% CI 0.90-1.54), letter fluency (moderately/increasing aOR 1.00, 95% CI 0.69-1.43; consistently higher aOR 1.05, 95% CI 0.80-1.39), category fluency (moderately/increasing aOR 1.16, 95% CI 0.82-1.63; consistently higher aOR 1.11, 95% CI 0.85-1.45), or global cognition (moderately/increasing aOR 1.16, 95% CI 0.82-1.63; consistently higher aOR 1.11, 95% CI 0.85-1.45), no association was observed. Consistently higher or moderate/increasing inflammation starting in early adulthood may lead to worse midlife executive function and processing speed. Study limitations include selection bias due to loss to follow-up and reliance on CRP as the only inflammatory marker. Inflammation is important for cognitive aging and may begin much earlier than previously known.

High C-Reactive Protein Serum Levels as a Risk Factor for Preeclampsia

Introduction: Preeclampsia is a hypertensive syndrome in pregnancy characterized by increased blood pressure, proteinuria, and complications such as liver dysfunction and visual impairment. This condition is associated with an inflammatory reaction and failure of trophoblast invasion of maternal arteries, which involves an increase in proinflammatory cytokines that indirectly induce CRP production. However, data showing the value of CRP levels as an indicator of the incidence of preeclampsia in Indonesia is minimal. This study aims to evaluate CRP levels as a predictor of preeclampsia.Methods: This case-control study involved pregnant women with preeclampsia and normal pregnant women who went to the Obstetric Emergency Installation at Prof. Hospital. Dr. I.G.N.G Ngoerah Denpasar. All data were obtained from patient medical records and then analyzed using the SPSS v.22.Results: This study involved 56 pregnant women consisting of 28 normotensive pregnant women (control) and 28 pregnant women with preeclampsia (cases) at Prof. Dr. I.G.N.G. Ngoerah General Hospital Denpasar from January to December 2023. The median age was 27.5 years (control) and 26.0 years (cases), with an age range of 18–40 years. The median BMI WAS 21.65 kg/m2 (controls) and 21.80 kg/m2 (cases). Most patients in both groups were nulliparous (50.0%, controls; 42.9%, cases). Based on ROC analysis, the CRP cut-off value of 7.76 mg/dL has a sensitivity of 76.7%, specificity of 78.6%, and an area under the curve (AUC) of 0.737, where pregnant women with high CRP (≥7.76 mg/dL) had a 12.048-fold higher risk (95%CI 3.496–41.515; p &lt; 0.001) of experiencing preeclampsia compared to pregnant women with low CRP levels.Conclusion: High serum CRP levels are a risk factor for preeclampsia. These findings indicate that measuring CRP levels can be a potential tool for identifying the risk of preeclampsia in the pregnant population.

Prevalence of vitamin D deficiency and the effect of vitamin D3 supplementation on response to anti-tuberculosis therapy in patients with extrapulmonary tuberculosis

BackgroundWe aimed to assess serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations in extrapulmonary tuberculosis (EPTB) patients and to evaluate the effect of vitamin D3 supplementation on their treatment course.MethodsSerum 25(OH)D3concentrations were measured in 47 newly diagnosed EPTB patients and 42 controls. Vitamin D-deficient EPTB patients were randomly assigned to receive 50,000 IU of vitamin D3 (cholecalciferol) orally once a week for 6 weeks (total 300,000 IU), followed by maintenance doses of 1000 IU a day besides anti-TB drugs or the first line anti-TB treatment only. Follow up serum 25(OH)D3 concentrations were measured after 3 months of starting vitamin D3 supplementation. Both groups were evaluated for clinical, laboratory, and radiological outcomes after treatment.ResultsSerum 25(OH)D3 concentrations were significantly lower among TB cases (17.1 ± 5.5 nmol/L) compared to healthy controls (51.8 ± 27.3 nmol/L), and vitamin D deficiency was observed in all EPTB patients (n = 47). Patients in VD3 supplementation group had significantly higher weight gain and serum albumin level at 2 months and end of treatment, higher hemoglobin concentration at the end of treatment, significantly lower CRP and ESR at 2 months and at the end of treatment. In cases with TB pleurisy, a significant higher rate of full resolution of pleural fluid after 6 months of anti-TB treatment and shorter treatment duration were noted compared to the other group.ConclusionsVitamin D deficiency is prevalent in EPTB patients, in whom, vitamin D supplementation is a useful adjunctive therapy to anti-TB drugs and improves treatment course.

Comparison of the therapeutic effects of three minimally invasive approaches for laparoscopic cholecystectomy combined with common bile duct exploration—— a 5-year retrospective analysis

ObjectiveThe aim of this retrospective study was to explore the indications for three minimally invasive approaches—T-tube external drainage, double J-tube internal drainage, and primary closure—in laparoscopic cholecystectomy combined with common bile duct exploration.MethodsThree hundred eighty-nine patients with common bile duct stones who were treated at the Second People's Hospital of Hefei between February 2018 and January 2023 were retrospectively included. Patients were divided into three groups based on the surgical approach used: the T-tube drainage group, the double J-tube internal drainage group, and the primary closure group. General data, including sex, age, and BMI, were compared among the three groups preoperatively. Surgical time, length of hospital stay, pain scores, and other aspects were compared among the three groups. Differences in liver function, inflammatory factors, and postoperative complications were also compared among the three groups.ResultsThere were no significant differences among the three groups in terms of sex, age, BMI, or other general data preoperatively (P > 0.05). There were significant differences between the primary closure group and the T-tube drainage group in terms of surgical time and pain scores (P < 0.05). The primary closure group and double J-tube drainage group differed from the T-tube drainage group in terms of length of hospital stay, hospitalization expenses, and time to passage of gas (P <0.05). Among the three groups, there were no statistically significant differences in inflammatory factors or liver function, TBIL, AST, ALP, ALT, GGT, CRP, or IL-6, before surgery or on the third day after surgery (P > 0.05). However, on the third day after surgery, liver function in all three groups was significantly lower than that before surgery (P<0.05). In all three groups, the levels of CRP and IL-6 were significantly lower than their preoperative levels. The primary closure group had significantly lower CRP and IL-6 levels than did the T-tube drainage group (P < 0.05). The primary closure group differed from the T-tube drainage group in terms of the incidences of bile leakage and electrolyte imbalance (P < 0.05). The double J-tube drainage group differed from the T-tube drainage group in terms of the tube dislodgement rate (P < 0.05).ConclusionAlthough primary closure of the bile ducts has clear advantages in terms of length of hospital stay and hospitalization expenses, it is associated with a higher incidence of postoperative complications, particularly bile leakage. T-tube drainage and double J-tube internal drainage also have their own advantages. The specific surgical approach should be selected based on the preoperative assessment, indications, and other factors to reduce the occurrence of postoperative complications.

Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.

To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

Effects of early enteral nutrition on persistent inflammation, immunosuppression, and catabolism syndrome in critically ill patients: A claims database study using a propensity score analysis

Background & AimsEarly enteral nutrition (EEN) potentially improves immune-related outcomes via the maintenance of intestinal immunity; however, the effects of EEN on clinical outcomes, including infectious complications, are controversial. Therefore, we herein investigated whether EEN affected persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which represents the immunocompromised state after critical illness. MethodsThis retrospective cohort study utilized the administrative claims database of inpatients and laboratory findings. Patients admitted to and treated in the intensive care unit (ICU) for more than 3 consecutive days were included. The primary outcome, a composite of PICS or mortality on day 14 after admission, was compared between the EEN group, which received enteral nutrition (EN) on the first 3 days (day 0, 1, or 2), and the late enteral nutrition (LEN) group, which did not receive EN on the first 3 days, but then received EN on days 3 through 7, using a propensity score-matched analysis. Secondary outcomes included the composite outcome on day 28, in-hospital mortality, the Barthel index, and laboratory data. Patients who met at least two of the following conditions were diagnosed with PICS: CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/μL. ResultsA total of 7,530 matched pairs were generated after propensity score matching. The primary outcome was significantly lower in the EEN group (risk difference -3.0%, 95% confidence interval (CI) -4.5 to -1.4%), whereas mortality did not significantly differ. The 28-day composite outcome was similar in the 2 groups (risk difference -1.5%, 95% CI -2.8% to -0.2%, no significant difference in mortality). There was no significant difference in in-hospital mortality between the EEN and LEN groups; however, the Barthel index at discharge was higher in the EEN group (the medians, 50 vs 45, P=0.001). Laboratory data showed lower Albumin and CRP on day 14 in the EEN group, but no other significant differences. ConclusionsIn patients admitted to the ICU, EEN was associated with a lower incidence of PICS on days 14 and 28, but was not associated with mortality. This positive association was not observed in sepsis, cardiac diseases, or gastrointestinal diseases.

Comparative analysis of lysophospholipid metabolism profiles and clinical characteristics in patients with high vs. low C-reactive protein levels in acute exacerbations of chronic obstructive pulmonary disease

BackgroundThe precise role of lysophospholipids (LysoPLs) in the pathogenesis of acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) remains unclear. In this study, we sought to elucidate the differences in serum LysoPL metabolite profiles and their correlation with clinical features between patients with low versus high CRP levels. MethodsA total of 58 patients with AECOPD were enrolled in the study. Patients were classified into two groups: low CRP group (CRP < 20 mg/L, n = 34) and high CRP group (CRP ≥ 20 mg/L, n = 24). Clinical data were collected, and the LysoPL metabolite profiles were analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) and identified by matching with the LipidBlast library. ResultsNineteen differential LysoPLs were initially identified through Student's t-test (p < 0.05 and VIP > 1). Subsequently, four LysoPLs, LPC(16:0), LPE(18:2), LPC(22:0), and LPC(24:0), were identified by FDR adjustment (adjusted p < 0.05). These four lysoPLs had a significant negative correlation with CRP. Integrative analysis revealed that LPC (16:0) and LPC (22:0) correlated with less hypercapnic respiratory failure and ICU admission. ConclusionAECOPD patients with high CRP levels demonstrated a distinctive LysoPL metabolism profile, with LPC (16:0), LPE(18:2), LPC(22:0), and LPC(24:0) being the most significantly altered lipid molecules. These alterations were associated with poorer clinical outcomes.

1472-P: Low CRP Alleles in HNF1A Are Associated with Increased Risk of Cardiovascular Disease—A Meta-analysis

1472-P: Low CRP Alleles in HNF1A Are Associated with Increased Risk of Cardiovascular Disease—A Meta-analysis

Predictors of severe hematotoxicity after CAR T-cell therapy.

7024 Background: The EHA/EBMT immune effector cell-associated hematotoxicity (ICAHT) grading system characterizes hematotoxicity after CAR T-cell therapy based on depth and duration of neutropenia (Rejeski et al, Blood, 2023). We evaluated pre- and post-infusion factors associated with grade 3-4 ICAHT and developed a predictive model in 602 patients with hematologic malignancies undergoing CAR T-cell therapy at Fred Hutch Cancer Center. Methods: Grading of early hematotoxicity (day-0-30 after CAR T-cell cell infusion) was automated using the heatwaveR package. Associations with 50 patient, disease-related, and laboratory factors, and grade 3-4 ICAHT were modeled using univariate and multivariable logistic regression. Results: The most common disease types were aggressive non-Hodgkin lymphoma (NHL; n = 293; 49%), indolent NHL (n = 150; 25%), and acute lymphoblastic leukemia (ALL; n = 94; 16%). The most common CAR T-cell products were the investigational CD19 CAR T-cell product JCAR014 (n = 197; 33%), axicabtagene ciloleucel (n = 129; 21%), and lisocabtagene maraleucel (n = 73; 12%). Incidences of early ICAHT grades 1, 2, 3, and 4 were 319 (53%), 96 (16%), 60 (10%), and 35 (6%) patients, respectively. Baseline patient factors associated with grade 3-4 ICAHT included ALL (reference: aggressive NHL, OR = 4.18, 95% CI, 2.41-7.26, p &lt; 0.001) , Hispanic or Latino ethnicity (OR = 2.17, 95% CI, 1.07-4.20, p = 0.025), and lower age (OR = 1.03, 95% CI, 1.02-1.05, p &lt; 0.001). Pre-lymphodepletion (LD) laboratory factors associated with grade 3-4 ICAHT in univariate analyses included lower ANC (OR = 6.67 per log10 cells/μL, 95% CI, 4.0-11.1, p &lt; 0.001), LDH (OR = 8.70per log10U/L, 95% CI, 4.03-19.4, p &lt; 0.001), CRP (OR = 3.18 per log10mg/L, 95% CI, 2.06-5.07, p &lt; 0.001), and ferritin (OR = 6.07 per log10mg/L, 95% CI, 3.65-10.6, p &lt; 0.001). Peak CRP (OR = 15.6, 95% CI, 7.27-36.4, p &lt; 0.001), peak ferritin (OR = 7.41, 95% CI, 5.02-11.3, p &lt; 0.001), peak CRS grade (OR = 2.01, 95% CI, 1.59-2.56, p &lt; 0.001), and peak ICANS grade (OR = 1.51, 95% CI, 1.29-1.77, p &lt; 0.001) after CAR T-cell infusion were also strongly associated with grade 3-4 ICAHT. A multivariable model using restricted cubic splines and including disease type, pre-LD ANC, pre-LD LDH, peak CRP, peak ferritin, and CRS grade demonstrated high discrimination to predict grade 3-4 ICAHT (C-index = 0.89). Internal validation using bootstrapping showed near-perfect calibration without overfitting. Sensitivity and specificity based on the Youden criteria was 74% and 90%, respectively. The sensitivity and specificity of the CAR-HEMATOTOX score in predicting grade 3-4 ICAHT was 93% and 30%, respectively. Conclusions: We identified pre- and post-infusion predictors of grade 3-4 ICAHT and internally validated a multivariable logistic regression model including disease-type, pre-LD ANC, pre-LD LDH, peak CRP, peak ferritin, and CRS grade. We plan to further evaluate our model in an external cohort.

Combined Charlson comorbidity/C-Reactive Protein Index Is a Novel Predictor in Renal Cell Carcinoma: Analysis of the International Marker Consortium for Renal Cancer (INMARC) Registry

ObjectiveTo evaluate predictive ability of a novel combined index, Charlson comorbidity index and C-reactive protein (CCI-CRP), for outcomes in renal cell carcinoma (RCC), and compare predictive outcomes with of CCI-CRP to its separate components and to the UCLA integrated staging system (UISS). Patients and MethodsWe retrospectively analyzed INMARC registry of RCC patients. Receiver Operator Characteristics (ROC) analysis was fitted to identify threshold defining low-CRP (LCRP) and high-CRP (HCRP). Patients were stratified according to CCI [low-CCI ≤ 3 (LCCI); intermediate-CCI 4-6 (ICCI); high-CCI > 6 (HCCI)] and CRP level. Kaplan-Meier analysis (KMA) was conducted for overall (OS) and cancer-specific survival (CSS). Based on survival analysis distribution we proposed a new stratification: CCI-CRP. Model performance was assessed with ROC/area under the curve (AUC) analysis and compared to CCI and CRP alone, and UISS. ResultsWe analyzed 2,890 patients (median follow-up 30 months). ROC identified maximum product sensitivity and specificity for CRP at 3.5 mg/L. KMA revealed 5-year OS of 95.6% for LCRP/LCCI, 83% LCRP/ICCI, 73.3% LCRP/HCCI, 62.6% HCRP/LCCI, 51.6% HCRP/ICCI and 40.5% HCRP/HCCI (P < .001). From this distribution, new CCI-CRP is proposed: low CCI-CRP (LCRP/LCCI and LCRP/ICCI), intermediate CCI-CRP (LCRP/HCCI and HCRP/LCCI), and high CCI-CRP (HCRP/ICCI and HCRP/HCCI). AUC for CCI-CRP showed improved performance for predicting OS/CSS vs. CCI alone (0.73 vs. 0.63/0.77 vs. 0.60), CRP alone (0.73 vs. 0.71/0.77 vs. 0.74) and UISS (0.73 vs 0.67/0.77 vs 0.73). ConclusionsCCI-CRP, exhibits increased prognostic performance for survival outcomes in RCC compared to CCI and CRP alone, and UISS. Further investigation is requisite.

#2291 ANCA negative vasculitis—the unmet need within small vessel vasculitis

Abstract Background and Aims ANCA negative small vessel vasculitis with renal involvement has been described in a number of cohorts. Though comprehensive studies comparing these individuals to ANCA positive patients are lacking and they are routinely excluded from clinical trials. Whilst the numbers are smaller than those with ANCA positivity, they still make up a large proportion of small vessel vasculitidies (Fig. 1). The absence of detectable circulating ANCA is thought to indicate a distinct spectrum of the disease. There remains unanswered questions regarding the pathophysiology, diagnosis and management of patients with seronegative AAGN. We present data from Croatian referral center. Method Study included 106 AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact test and continuous with Kruskal-Wallis test. Statistical difference was then analysed post hoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results 106 AAV patients with renal involvement were included: 66 (61.1%) MPA, 20 (18.5%) GPA, 20 (18.5%) RLV. 14 (13%) were PR3-ANCA positive, 57 (52.8%) MPO ANCA positive, 5 (4.6%) PR3-ANCA+MPO-ANCA and 32 (29.6%) ANCA negative patients. ANCA negative patients were comparatively younger (p = 0.02) and presented with more renal limited vasculitis (RLV; p &amp;lt; 0.001), lower BVAS (p = 0.003) and lower CRP (p = 0.001). ANCA negative patients usually presented with nephrotic syndrome compared to positive ones which presented with rapid progressive nephritic syndrome or acute nephritic syndrome (p = 0.027). 24-hour proteinuria levels were higher in ANCA negative group (p = 0.003). Though statistical difference was not reached, there was tendency for ANCA negatives to receive less plasmapheresis (p = 0.074). Histologically there were no differences between ANCA positive and ANCA-negative patients. On sub analysis ANCA negatives versus individual seropositive groups, there was tendency that ANCA negatives and MPO-ANCA patients had lower percentage of glomerular crescents (p = 0.092) but more acute tubular damage (p = 0.087). There were no differences in clinical outcomes between the groups. Conclusion ANCA negative vasculitis form a large proportion of small vessel vasculitidies and present with different clinical laboratory and histological (renal) characteristics than ANCA positive ones. More often than not disease seems to be renal limited and patients tend to be younger. Due to the rarity of the disease, there remains unanswered questions regarding the pathophysiology, diagnosis and management of these patients. This study highlights noteworthy distinctions between the two groups. Whether these differences warrant adjustments in treatment algorithms or a reconsideration of the classification of small vessel vasculitis remains to be determined. Further investigation into the pathogenetic mechanisms of seronegative AAVs is essential.

#2361 The influence of glucose biocompatible solutions to the clinical outcomes of patients treated with continuous ambulatory peritoneal dialysis

Abstract Background and Aims The use of biocompatible glucose solutions is associated with longer preservation of residual renal function and less frequent occurrence of complications in patients on peritoneal dialysis. The aim of this study was to examine the influence of conventional and biocompatible glucose solutions to laboratory parameters and clinical outcomes of PD patients during a four-year period at Zvezdara University Medical Center. Method This retrospective study included 25 incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) during the follow up period from 2018 to 2022. During 2018/2019 these patients used conventional solutions (Dianeal PD4) containing lactate as a buffer, while due to the change in solution production technology in 2020/2021, all patients were transferred to a biocompatible solution (Physioneal 40) with lactate and bicarbonate as a buffer. Clinical outcomes were compared in relation to the administered solution: pain during infusion (measured by a Visual Analogue Scale—VAS), correction of anaemia and bicarbonate, average annual 24h diuresis and 24h ultrafiltration, occurrence of CAPD peritonitis. The statistical significance of the differences between the two periods was checked using the SPSS. Results The average age of 25 patients was 61 ± 14 years, of which 59.1% were male and 40.9% female. The average BMI was 28.5 ± 5.30 kg/m2, and the most common comorbidities were HTA and DM. No statistically significant difference was found for the values of Le, albumin, Hb, PTH, bicarbonate, and K (p ˃ 0.05). During the use of biocompatible solutions, patients had statistically significantly lower Na values (138.84 ± 2.63 vs 137.17 ± 2.41 mmol/l, p = 0.0116, 95% CI 137.15– 138.84) and lower CRP values (15.3 ± 3.3 mg/l vs 7.7 ± 3.2, p = 0.0003, 95% CI 18.60-4.50). Although the dialysis exposure was longer, the rate of peritonitis was lower during the use of biocompatible solutions, but without a statistically significant difference (0.40 episodes per patient-year, vs 0.31 episodes per patient-year, p ˃ 0.05). No statistical significance was found in 24h diuresis value (900 ml vs 750 ml, p = 0.167.95% CI 686.90–1203.31) but the value is expected to be lower due to dialysis duration. Conclusion Our study showed that patients treated with the CAPD method while using a biocompatible solution have statistically significantly higher values of 24h ultrafiltration, lower Na and CRP values and less occurrence of pain during infusion, which significantly affects the quality of life. Although this may indicate better preservation of the peritoneal membrane, a prospective and randomized study is needed to clarify these potential differences.