Baseline C-reactive Protein Levels Research Articles

Effects of minimally invasive non-surgical therapy on C-reactive protein, lipoprotein-associated phospholipase A2, and clinical outcomes in periodontitis patients: A 1-year randomized, controlled clinical trial.

Growing evidence suggests the type of periodontal treatment could differentially influence the reduction of key cardiovascular risk mediators in periodontitis patients. This randomized, controlled clinical trial compared the impact of minimally invasive non-surgical therapy (MINST) with quadrant-wise subgingival instrumentation (Q-SI) on C-reactive protein (CRP) together with lipoprotein-associated phospholipase A2 (Lp-PLA2) levels, and clinical periodontal outcomes in patients with periodontitis. Moreover, it was evaluated if baseline CRP levels impacted the efficacy of non-surgical periodontal therapy protocols. Forty-two periodontitis patients were enrolled and randomly treated by means of MINST (n=21) or Q-SI (n=21). The outcomes assessed were serum CRP and Lp-PLA2, and periodontal parameters (probing depth [PD], clinical attachment level [CAL], full-mouth bleeding score [FMBS]), at baseline and at follow-ups at 1, 3, and 6 months and at 1 year after treatment. At 1 year, MINST significantly reduced, among others, mean PD (p=0.007), mean CAL (p=0.007), the number of pockets>4mm (p=0.011) and ≥6mm (p=0.005), and FMBS (p=0.048) compared to Q-SI. Generalized multivariate analysis evidenced that high baseline CRP (p=0.039) and FMBS (p=0.046) levels, together with MINST treatment (p=0.007) were significant predictors of PD reduction at 1-year follow-up. Moreover, the Jonckheere-Terpstra test showed that patients with high baseline CRP levels gained more benefits from MINST treatment at 1-year follow-up than they did from Q-SI. Patients receiving MINST showed a greater reduction in CRP levels than patients with Q-SI after 1 year of follow-up. Moreover, patients with high baseline levels of CRP and Lp-PLA2 gained more benefits from the MINST approach at 1-year follow-up.

C-Reactive Protein Does Not Predict Future Depression Onset in Adolescents: Preliminary Findings from a Longitudinal Study.

Introduction: Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of nonspecific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent versus adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents. Methods: Participants were 53 adolescents (age = 14.74 ± 1.92 years, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semistructured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after ∼1.5 years. Spearman's correlation between CRP levels and follow-up symptom severity were controlled for body mass index, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjusted p < 0.05 level. Results: After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity. Conclusion: CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.

Atorvastatin Treatment Significantly Increased the Concentration of Bone Marrow-Derived Mononuclear Cells and Transcutaneous Oxygen Pressure and Lowered the Pain Scale after Bone Marrow Cells Treatment in Patients with "No-Option" Critical Limb Ischaemia.

The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with "no-option" critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant.

Comparative analysis of the efficacy of seniprutug (BCD-180) and adalimumab in the treatment of active radiographic axial spondyloarthritis: results of a systematic review and matching-adjusted indirect comparison

Objective: to compare the clinical efficacy of seniprutug (BCD-180) and adalimumab (ADA) in the treatment of adults with active radiographic axial spondyloarthritis (r-axSpA).Materials and methods. Based on the results of a previously conducted systematic review, an unanchored matching-adjusted indirect comparison (MAIC) was performed, adjusting for confounding factors. The analysis was based on the results of randomized placebo-controlled clinical trials of seniprutug (BCD-180-2/ELEFTA, NCT05445076) and ADA (ATLAS, NCT00085644) that met the selection criteria. We chose ASAS40 and ASAS20 measurements at week 24 as efficacy outcomes. Initial BASDAI and BASFI indices, proportion of women in the study population, time from disease onset, and baseline C-reactive protein (CRP) levels were considered as confounders.Results and discussion. The MAIC showed a statistically significant advantage in the clinical efficacy of seniprutug (BCD-180) over ADA. When adjusted, the odds ratios (OR) with 95% confidence intervals (CI) for seniprutug (BCD-180)/ADA were 1.86 (1.15; 3.02) and 2.21 (1.34; 3.72) for ASAS40 and ASAS20, respectively, at week 24.Conclusion. The MAIC demonstrated statistically significant superiority of seniprutug (BCD-180) over ADA on the key efficacy endpoints ASAS40 and ASAS20 at week 24 in adults with active r-axSpA. The inclusion of the innovative domestic drug seniprutug into treatment paradigm of active r-axSpA will potentially reduce the socio-economic burden of this disease by providing an affordable, effective and safe therapy while optimizing healthcare costs

Repurposing the Fibrosis-4 Score in Rheumatoid Arthritis: Data from the ESPOIR Cohort.

Background: We aimed to evaluate the value of the Fibrosis-4 (FIB-4) score as a prognostic factor in RA in the prospective ESPOIR cohort. Methods: We included patients from the ESPOIR cohort with a diagnosis of RA according to ACR/EULAR criteria. The formula for the FIB-4 score is as follows: [age (years) × aspartate transaminase level (U/L)]/[platelet count (109/L) × alanine aminotransferase level (U/L)1/2]. We used a linear mixed-effects model with a random effect of patient to account for repeated measures over time. Results: Overall, 647 of the 813 patients included met the ACR/EULAR criteria for RA, with no differential diagnosis during the first 10 years of follow-up. Of these patients, at baseline, 633 had a calculable FIB-4 score. Median FIB-4 score was 0.75 (interquartile range 0.53-0.99). On multivariate analysis, FIB-4 score was not independently associated with progression of Disease Activity Score in 28 joints over 10 years of follow-up, unlike baseline C-reactive protein level and SJC. Baseline FIB-4 score was not associated with the modified Sharp score at 5-year follow-up, unlike age and ACPAs. FIB-4 score was not associated with mortality (hazard ratio 1.1 [95% CI 0.46; 2.8], p = 0.77) or major adverse cardiovascular events (0.46 [0.13; 1.6], p = 0.22) over the 10-year follow-up. No significant change in FIB-4 score over time was related to treatments. Conclusions: The present prospective cohort study did not find a prognostic role of FIB-4 score in RA. Reassuringly, FIB-4 score was not increased with DMARD treatment after 10 years of follow-up.

Abstract WMP108: Association of Circulating Markers of Inflammation to Baseline and Progression of Carotid Artery Intima-Media Thickness

Introduction: There is strong evidence of an association between systemic inflammation and ischemic stroke. While the exact mechanism underpinning that association is unclear, there is evidence that systemic inflammation contributes to atherosclerosis progression. One measure of subclinical atherosclerosis, carotid artery intima-media thickness (CIMT), is independently associated with ischemic stroke. Because of mixed data on the association between systemic inflammation and CIMT progression, we sought to evaluate this relationship in a prospective cohort study. Hypothesis: Baseline elevation in circulating markers of inflammation are associated with CIMT progression in the Framingham Heart Study cohort. Methods: Among participants with two carotid ultrasounds (n=2350) about 10 years apart, 2,269 had data available on circulating markers of inflammation. Multivariable linear regression was used to assess the association between circulating markers of inflammation with internal carotid artery (ICA) CIMT. Analyses were adjusted for age, sex, hypertension, diabetes, APOE4, and body mass index (BMI), and baseline IMT. Results: Participants with higher baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), intracellular adhesion molecule, p-selectin, lipoprotein-associated phospholipase A2 (LPa) activity, homocysteine, isoprostanes (ISO), and CD40 ligand had significantly higher rates of ICA IMT progression adjusting for age, sex, hypertension, diabetes, APOE4, BMI, and baseline ICA IMT (Table). Participants with higher levels of CRP, IL-6, OPG, p-selectin, LPa activity, and ISO had greater follow-up ICA IMT adjusting for age, sex, hypertension, diabetes, APOE4, and BMI. Conclusion: Specific markers of inflammation are associated with increased later life carotid intima media thickening and carotid atherosclerosis progression, supporting a link between systemic inflammation and cerebrovascular disease.

P576 Fecal calprotectin could predict clinical and endoscopic response to ustekinumab therapy

Abstract Background Ustekinumab (UST) is one of the most used biologic drugs for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). However, not all patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response in this setting, with particular regard to mucosal healing. The aim of this multicenter study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. Methods We enrolled consecutive patients with CD or UC treated with UST for at least 48 weeks at four referral centers in the last 5 years. Therapeutic response was evaluated in terms of clinical remission (defined as a Partial Mayo Score &amp;lt;2 for patients with UC and as Harvey Bradshaw Index &amp;lt;5 for patients with CD, without concomitant corticosteroid therapy) and mucosal healing (defined as a Mayo Endoscopic Score &amp;lt;2 for UC and as the disappearance of ulcers for CD). We collected clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and at week 24. Results Among 196 patients enrolled (73 [37.2%] women), 167 were affected by CD, whereas 29 by UC. Globally, 128 (65.3%) patients achieved clinical remission and 83 (42.3%) endoscopic remission at 48 weeks of treatment. There were no group differences in age, sex, BMI, baseline clinical and endoscopic indexes, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [interquartile range] 391 [103, 1050] versus 825 [317, 1800] µg/mL,p=0.002). At week 24, lower calprotectin levels were observed in both the groups who achieved clinical (160 [50, 426] versus 439 [146, 1000] µg/mL,p&amp;lt;0.0001) and endoscopic remission (114 [43, 265] versus 392 [139, 912] µg/mL,p&amp;lt;0.0001) compared with non-responders. The effects of week-24 calprotectin levels on clinical remission (β= -0.003,p&amp;lt;0.0001) and endoscopic remission (β= -0.004,p&amp;lt;0.0001) remained significant in multivariable models adjusted for age, sex, and BMI. A cut-point of 268 µg/mL was identified as the optimal threshold of week-24 calprotectin for predicting clinical remission (sensitivity 65%, specificity 67%, ROC AUC 0.689), while a cut-point of 309 µg/mL was identified to predict endoscopic remission (sensitivity 79%, specificity 59%, ROC AUC 0.712). Conclusion Our data suggest that FC assessment after 24 weeks of treatment with UST could represent a promising early marker of response, even in terms of mucosal healing, in both CD and UC.

P965 Ulcerative proctitis treated with biologics: is it too hard to treat?

Abstract Background Patients with ulcerative proctitis are widely considered a challenging population because the reported reduced response rate to conventional medical treatment. On the other hand, data on the role of biological therapies in this specific cohort are currently scarce Methods We retrospectively evaluated all patients with proctitis (defined as the mucosal inflammation of only the rectum with ulcerative colitis confirmed by histology) treated with biologics (infliximab, adalimumab, vedolizumab -VDZ-, ustekinumab -UST) and tofacitinib (TOFA) at four referral centers in the last 5 years. All patients were treated with concomitant topical mesalamine. We included in this study only patients who underwent colonoscopy at baseline and after 52 weeks of treatment, in order to evaluate therapeutic response in terms of mucosal healing (defined as a Mayo Endoscopic Score -MES- &amp;lt;2), besides that clinical remission (defined as a Partial Mayo Score -PMS- &amp;lt;2 without oral or topical corticosteroid therapy). We collect clinical and demographic data, as well as fecal calprotectin (FC) and C-Reactive Protein (CRP) levels at baseline and after the induction of therapy Results Among 64 patients enrolled (age 50.8±16.5 years, 29 [45.3%] women), 33 (51.6%) were treated with anti-TNF), 15 with VDZ, 13 with UST, and 3 with TOFA. Globally, 51 (79.7%) patients achieved clinical remission and 37 (57.8%) patients achieved endoscopic remission at 52 weeks. There were no group differences in age, sex, BMI, disease duration, PMS, MES, drug, or baseline CRP levels between patients achieving or not either clinical or endoscopic remission. Baseline calprotectin levels were lower in patients who achieved endoscopic remission (median [IQ range] 297 [158, 475] versus 442 [230, 1545] µg/mL, p=0.036), but not in those who achieved clinical remission. After the induction phase, lower calprotectin levels were observed in patients achieving clinical (46 [15, 166] versus 553 [72, 1649] µg/mL, p=0.001) and endoscopic remission (38 [15, 112] versus 328 [52, 2171] µg/mL, p=0.0002), compared with non-responders. The effects of post-induction calprotectin levels on clinical remission (β= -0.001, p=0.020) and endoscopic remission (β= -0.007, p=0.006) remained significant in multivariable models adjusted for age, sex, BMI, disease duration, and biological treatment. A cut point of 200 µg/mL post-induction was identified to predict endoscopic remission (sensitivity 92%, specificity 64%, ROC AUC 0.781) Conclusion High rates of clinical and endoscopic remission with biological therapies could be achieved in patients with ulcerative proctitis. Fecal calprotectin levels after the induction of biological therapies seem to predict the therapeutic response in patients with ulcerative proctitis

P1022 One-year safety and effectiveness of ustekinumab in patients with Crohn’s disease: The K-STAR study

Abstract Background We aimed to investigate the safety and effectiveness of ustekinumab (UST) for Korean patients with Crohn’s disease (CD). Methods Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn’s Disease patients treated with STelARa) study from April 2018 to April 2022. After single intravenous infusion of UST ~6 mg/kg, UST 90 mg subcutaneous injection was followed at week 8 and then maintenance treatment with subcutaneous UST 90 mg every 8 or 12 weeks were given, following up to week 52 to 66. Both adverse events and clinical effectiveness of UST therapy were analyzed (ClinicalTrials.gov Identifier: NCT03942120). Results Of the 464 patients enrolled from 44 medical centers across South Korea, 457 and 428 patients (Crohn’s disease activity index 150 or over) were included in the safety analysis and effectiveness analysis set, respectively (Table 1). At week 16–20 after starting UST, rates of clinical response, clinical remission and corticosteroid-free remission were 75.0% (321/428), 64.0% (274/428), and 61.9% (265/428), respectively (Figure 1A). At week 52–66, rates of clinical response, clinical remission and corticosteroid-free remission were 62.4% (267/428), 52.6% (225/428), and 50.0% (214/428), respectively (Figure 1B). Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171/428) and 41.6% (178/428) of patients at week 16–20 and week 52–66, respectively. Bio-naïve patients exhibited significantly higher rates of combined effectiveness than bio-experienced patients (50.3% vs. 30.7% at week 16–20, p&amp;lt;0.001; 47.7% vs. 36.0% at week 52–66, p=0.014) (Figure 1A;1B). No additional benefits were observed with the concomitant use of immunomodulators. Using a multivariable analysis using backward selection, colonic involvement (vs. ileal involvement, odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12–0.89; p=0.028), ileocolonic involvement (vs. ileal involvement, OR, 0.45; 95% CI, 0.23–0.89; p=0.021), baseline C-reactive protein levels (OR, 0.90; 95% CI, 0.84–0.97; p=0.009), and the exposure to two or more biologics (vs. bio-naïve, OR, 0.38; 95% CI, 0.20–0.73; p=0.003) were inversely associated with achieving clinical remission at week 52–66. Any adverse events and serious adverse events were observed in 28.2% (129/457) and in 12.7% (58/457), respectively with no new safety signal associated with UST treatment. Conclusion UST was well-tolerated, effective, and safe as induction and maintenance therapy for patients with CD in Korea. The results from this study enhance our understanding of the role of UST in managing CD patients with diverse characteristics and may help inform clinical decisions.

P843 Effectiveness and tolerability of methotrexate combined with biologics in patients with Crohn’s disease: A multicenter observational study

Abstract Background Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn’s disease (CD). Methods We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission. Results MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p &amp;lt; 0.001), and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037). Conclusion MTX combination therapy with biologics was effective and tolerable in patients with CD.

P1015 Subcutaneous infliximab effectively manages clinical outcomes of Inflammatory Bowel Disease independently of various confounding factors

Abstract Background Since its approval, many inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but the association of various confounding factors with clinical outcomes is still elusive. Methods The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 database analysis, three studies from France and the United Kingdom1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) &amp;lt;5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) &amp;lt;3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. After adjustment with inverse probability of treatment weights (IPTW), the association of various parameters on clinical outcomes was assessed with marginal structural models (MSMs), by comparing the estimated marginal means (EMMs) of remission rates at 6M between patients in each subgroup. Results The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching to SC IFX with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. The overall clinical remission and persistence rates at 6M after switching were 84.7% and 94.5%, respectively. Pre-switch IV IFX regimens, immunomodulator (IMM) use, age, baseline fecal calprotectin (FC) level, or baseline C-reactive protein (CRP) level were not associated with persistence. Persistence rate was &amp;gt;90% regardless of body mass index (BMI), although it was higher for patients &amp;lt;25 kg/m2 BMI (98.1%). Assessment with MSMs indicated that the clinical remission rate of CD, but not UC, was expected to be significantly lower only if patients were treated with escalated IV IFX before switching rather than standard 5 mg/kg Q8W regimen (p=0.01; Table 1). No association with high BMI, IMM use, age, ≥150 μg/g FC, and ≥5 mg/L CRP was found in both CD and UC (Table 1). Perianal disease was not associated with CD remission either. Conclusion The ASSEMBLE-1 results confirm that switching from IV to SC IFX is well accepted and effectively manages the clinical outcomes of the disease regardless of various confounding factors in IBD patients. However, further studies are warranted to explore the association of pre-switch IV IFX regimens with clinical outcomes. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.

C-Reactive Protein As A Response Indicator In Drug-Naïve Patients With Major Depressive Disorder: A Hospital-Based Study

Abstract Objective: C-reactive protein (CRP) is an indicator of the inflammatory process in the body, and is associated with the pathogenesis of depression through its purported effect on neurotransmitter function in the brain. Current research aims to study the relationship between the levels of CRP and the rate of remission of major depressive disorder with first-line antidepressant therapy. Methods: This hospital-based prospective study included thirty patients by purposive sampling technique. Patients with first-episode MDD with no history of antidepressant exposure and other medical comorbidity were recruited for pharmacotherapy with escitalopram, a first-line antidepressant. Patients taking antidepressants, anti-inflammatory medicines, having co-morbid conditions or other psychiatric conditions were excluded. The baseline CRP levels were measured and depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HRSD) at weeks 0, 6 and 12. The patients with low (≤5 mg/l) and high (&gt;5 mg/l) CRP levels were compared for remission rates at week 12 using Kaplan–Meier survival analysis. Results: Amongst the 30 cases, 11(36.7%) were males and 19(63.3%) were female patients. The mean age was 35.95±7.85 years. Both groups were matched concerning age, gender, BMI and baseline HRSD score (p&gt;0.05). As per Kaplan–Meier survival analysis, a significantly higher proportion of patients had remission of MDD at the 12th week having CRP levels ≤5 mg/l than the patients with CRP levels &gt;5 mg/dl (p=0.002). Conclusion: This research concluded that after an adequate trial with a standard antidepressant, higher levels of CRP could lead to poorer remission rates in MDD subjects and could represent a sub-group of patients with treatment resistance.

Use of inflammatory markers as predictor for mechanical ventilation in COVID-19 patients with stages IIIb-V chronic kidney disease?

Studies have shown elevated C-reactive protein (CRP) to predict mechanical ventilation (MV) in patients with coronavirus disease 2019 (COVID-19). Its utility is unknown in patients with chronic kidney disease (CKD), who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance. To assess whether an association exists between elevated inflammatory markers and MV rate in patients with stages IIIb-V CKD and COVID-19. We conducted a retrospective cohort study on patients with COVID-19 and stages IIIb-V CKD. The primary outcome was the rate of invasive MV, the rate of noninvasive MV, and the rate of no MV. Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables. Cutoffs for variables were CRP: 100 mg/L, ferritin: 530 ng/mL, D-dimer: 0.5 mg/L, and lactate dehydrogenase (LDH): 590 U/L. 290 were screened, and 118 met the inclusion criteria. CRP, D-dimer, and ferritin were significantly different among the three groups. On univariate analysis for invasive MV (IMV), CRP had an odds ratio (OR)-5.44; ferritin, OR-2.8; LDH, OR-7.7; D-dimer, OR-3.9, (P < 0.05). The admission CRP level had an area under curve-receiver operator characteristic (AUROC): 0.747 for the IMV group (sensitivity-80.8%, specificity-50%) and 0.663 for the non-IMV (NIMV) group (area under the curve, sensitivity-69.2%, specificity-53%). Our results demonstrate a positive correlation between CRP, ferritin, and D-dimer levels and MV and NIMV rates in CKD patients. The AUROC demonstrates a good sensitivity for CRP levels in detecting the need for MV in patients with stages IIIb-V CKD. This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation and reduced clearance due to CKD alone.

Baseline C-reactive protein predicts efficacy of the first-line immune checkpoint inhibitors plus chemotherapy in advanced lung squamous cell carcinoma: a retrospective, multicenter study

AimsTo investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC).Materials and methodsIn this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups.ResultsOf the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12–2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13–4.44; p = 0.033).ConclusionIn patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Characteristics of Inflammatory Markers in Diabetic Foot Patients and Their Relationship With Prognosis of Diabetic Foot Ulcers

To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers. The clinical data of diabetic foot patients (n=495) admitted to West China Hospital, Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers. White blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale. Neutrophil percentage (NE%) was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients. NE%, CRP, PCT, and IL-6 levels were positively correlated with the severity of diabetic foot, with the respective odds ratio (OR) at 95% confidence interval (CI) being 1.038 (1.019-1.056), 1.019 (1.012-1.026), 8.225 (2.015-33.576), and 1.017 (1.008-1.025). Using Wagner grade-0 patients as the reference, patients with higher WBC were more likely to progress to Wagner grade 2, 3, and 4, with the respective OR (95% CI) values being 1.260 (1.096-1.447), 1.188 (1.041-1.356), and 1.301 (1.137-1.490); patients with higher ESR were more likely to progress to Wagner grade 3 and 4, with the respective OR (95% CI) values being 1.030 (1.006-1.054) and 1.045 (1.019-1.071). Baseline ESR (P=0.008), CRP (P=0.039), and IL-6 (P=0.033) levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission. The levels of WBC, NE%, ESR, PCT, and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment. The higher the levels of NE% and IL-6, the worse the prognosis of diabetic foot ulcers became, with the respective OR (95% CI) values being 1.030 (1.010-1.051) and 1.008 (1.002-1.013). The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers. Elevated baseline NE% and IL-6 levels suggest a poor prognosis. Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

CTIM-38. NEUROTOXICITY AND MANAGEMENT OF PRIMARY AND SECONDARY CNS LYMPHOMA AFTER ADOPTIVE IMMUNOTHERAPY WITH CD19-DIRECTED CAR T-CELLS

Abstract BACKGROUND Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for systemic B-cell lymphomas; however, efficacy data for patients with CNS involvement are limited. Also, there are concerns about increased neurotoxicities (denoted by the term 'ICANS') when the target antigen is present within the CNS. METHODS We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a five-year period. RESULTS Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; one patient with two CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe ICANS (grade 3-4) after 7/45 transfusions (15.6%). No fatalities were directly attributed to ICANS. A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Similar response rates were seen in both patients with parenchymal and leptomeningeal involvement. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (HR per mg/d: 1.16, p = 0.031). If bridging therapy was warranted, the use of ibrutinib translated into favourable CNS-progression free survival (5 versus 1 month, HR 0.28, CI 0.1-0.7; p = 0.010). CONCLUSION CAR T-cells exhibit promising anti-tumor effects and a favourable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted to boost the success of such therapy.

Abstract 17714: Randomized Clinical Trial Comparing Bare Metal Stents Plus Oral Colchicine versus Drug-Eluting Stents for the Prevention of Hard Clinical Outcomes. Two Years Follow-Up Results

Introduction: Percutaneous coronary intervention (PCI) for ischemic heart disease is common and stent selection. Bare metal stents (BMS) or drug-eluting stents (DES) impact outcomes. Colchicine has been shown to reduce cardiac events. The long-term efficacy of BMS plus colchicine (BMS+C) vs DES in terms of major adverse cardiovascular events (MACE) is unknown. We presented preliminary results at AHA 2022, we are reporting extended follow-up. Hypothesis: PCI with BMS+C have similar MACE compared to DES-treated patients (pts). Methods: Multicenter, randomized clinical trial (RCT) enrolled PCI pts from February 2020 to April 2022, randomly assigned to BMS+C or DES and followed at 1, 6, 12 months, and then annually until 5 years. BMS+C received 0.5 mg oral colchicine BID for 3 months. Primary endpoint (EP) compared cost and incidence of MACE, a composite of death, myocardial infarction, stroke, or ischemic-driven target vessel revascularization. Due to the cost difference between devices a non-inferiority 15% threshold level was estimated. Secondary EP included individual components of primary EP and overall costs. Drug tolerance was analyzed. Baseline and 1-month C-Reactive Protein (CRP) levels were assessed and a delta difference was compared. An IRB and local authorities approved the protocol (NCT04382443). Results: We included 205 pts in each arm. Baseline characteristics were similar, Acute Coronary Syndromes was 78% vs 74.6% (p=0.24). Syntax Score was 22.2+/-11.4 vs 21.1+/- 9.4, respectively (p=0.49). Follow-up was 25 +/- 5 months. Primary and secondary EP are presented in the table. 5% of BMS+C pts withdraw from the drug due to side effects. Delta CRP between groups showed 5.4 +/- 6.4 vs 1.6 +/- 1.7, BMS vs DES, p&lt;0.001. Conclusions: In this RCT of pts with ACS and low Syntax score, a strategy with BMS+C was non-inferior to DES in terms of long-term clinical outcomes. Colchicine diminished inflammation markers. Cumulative costs were lower in the BMS+C group. cost.

CRP Monitoring in Early Hospitalization: Implications for Predicting Outcomes in Patients with COVID-19.

Elevated C-reactive protein (CRP) levels have been associated with poorer COVID-19 outcomes. While baseline CRP levels are higher in women, obese individuals, and older adults, the relationship between CRP, sex, body mass index (BMI), age, and COVID-19 outcomes remains unknown. To investigate, we performed a retrospective analysis on 824 adult patients with COVID-19 admitted during the first pandemic wave, of whom 183 (22.2%) died. The maximum CRP value over the first five hospitalization days better predicted hospitalization outcome than the CRP level at admission, as a maximum CRP > 10 mg/dL independently quadrupled the risk of death (p < 0.001). Males (p < 0.001) and patients with a higher BMI (p = 0.001) had higher maximum CRP values, yet CRP levels did not impact their hospitalization outcome. While CRP levels did not statistically mediate any relation between sex, age, or BMI with clinical outcomes, age impacted the association between BMI and the risk of death. For patients 60 or over, a BMI < 25 kg/m2 increased the risk of death (p = 0.017), whereas the reverse was true for patients <60 (p = 0.030). Further impact of age on the association between BMI, CRP, and the risk of death could not be assessed due to a lack of statistical power but should be further investigated.

Predictive Effect of System Inflammation Response Index for Progression of Chronic Kidney Disease in Non-Dialyzing Patient.

Scant research has been conducted on the interplay between the systemic inflammation response index (SIRI) and chronic kidney disease (CKD). The present study endeavors to meticulously scrutinize the association between SIRI and renal function. Additionally, we aim to assess its efficacy in predicting the progression of CKD in non-dialysis patients. Adult patients with CKD who were not undergoing dialysis were enrolled, and follow-up data were obtained. Data from distinct groups were extracted and meticulously compared. A comprehensive analytical approach was adopted, including logistic regression analysis, Kaplan-Meier analysis, Cox proportional hazards regression analysis, and subgroup analysis. Our study included 1420 patients, with a mean age of 61 ± 17 years, and 63% were male. 244 (17.2%) patients experienced the progression of CKD. As the level of ln(SIRI) increased, patients tended to be older, with a higher proportion of males, and increased prevalence rates of hypertension, stroke, heart failure, and progression of CKD. Additionally, the levels of baseline creatinine and C-reactive protein were elevated, while the levels of estimated glomerular filtration rate and hemoglobin decreased. Upon adjusting for demographic and biochemical variables, logistic regression analysis indicated that ln(SIRI) was independently associated with advanced CKD in pre-dialysis patients (OR=1.59, 95% CI: 1.29-1.95, P<0.001). Moreover, Cox proportional-hazard analysis revealed that ln(SIRI) independently predicted CKD progression (HR: 1.3, 95% CI: 1.07-1.59, P=0.009). Conducting a subgroup analysis, we observed significant interactions between ln(SIRI) levels and gender (p<0.001), age (p=0.046), and hypertension (p=0.028) in relation to the progression of CKD. Our study's findings demonstrate a significant association between SIRI and fundamental renal function, and independently establish a correlation between SIRI and the progression of CKD in pre-dialysis patients. These observations suggest that SIRI holds promise as a potential predictor for CKD progression.

Suggested Flowchart Through Integrated C-Reactive Protein and White Blood Cell Count Analysis for Screening for Early Complications After Gastric Bypass: a Single-Center Retrospective Study.

Early leakage detection following bariatric procedures is crucial, but a standardized evaluation method is lacking. The aim was to validate the potential benefits of postoperative day 1 (POD1) C-reactive protein (CRP) levels and white blood cell (WBC) counts in distinguishing at-risk patients following Roux-en-Y gastric bypass (RYGB) while considering the impact of obesity-related chronic inflammation. Retrospective analysis of 261 consecutive patients aged 18-65 years with a body mass index (BMI) of 32.5-50 kg/m2 who underwent primary RYGB between 2017 and 2022. Sequential changes in CRP levels and WBC counts measured 48 h preoperatively and on POD1 morning were collected and compared between patients with/without complications and in patients without complications stratified by preoperative CRP levels. Female patients and those with a higher BMI tended to have higher baseline CRP levels, which were positively related to postoperative CRP. Patients experiencing complications had higher WBC counts and a higher prevalence of WBC counts >14,000/μl (77.8% vs. 25.4%; p<0.001) than those without complications. Baseline CRP ≥ 0.3 mg/dl, a longer operative time, and blood loss >10 ml were significantly more common with WBC counts above 14,000/μl; a reasonable range of change in WBC count (∆WBC) derived from its positive correlation to postoperative WBC count (r=0.6695) may serve as a useful complementary indicator. An individualized CRP threshold setting and integrated interpretation of the WBC count can be more appropriate than using static criteria for differentiating at-risk patients after RYGB. Further studies are needed to validate these findings and determine their generalizability.