Higher Baseline C-reactive Protein 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.

Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage.

The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies

BackgroundVadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies.MethodsOf 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20–24 divided by the mean hemoglobin (g/dL) at weeks 20–24. Multivariate analysis was performed to identify the variables affecting the resistance index.ResultsIndependent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20–24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD.ConclusionsIn this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat.Clinical trial registrationNCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial

BackgroundThe phase II CIGMA trial performed in 160 patients with severe community-acquired pneumonia (sCAP) found treatment with trimodulin (human polyvalent immunoglobulin [Ig]: ~ 23% IgM, ~ 21% IgA, ~ 56% IgG) was associated with a lower mortality in those patients with elevated baseline serum levels of C-reactive protein (CRP) and/or subnormal IgM.MethodsIn this post hoc analysis, the pharmacodynamic effects of trimodulin treatment (182.6 mg/kg/day for 5 days) were investigated on Ig replenishment, cellular markers of inflammation (absolute neutrophil [ANC] and lymphocyte [ALC] count, neutrophil-to-lymphocyte ratio [NLR]), and soluble markers of inflammation (procalcitonin [PCT] and CRP). The impact of these pharmacodynamic effects on mortality was also evaluated.ResultsCompared with healthy subjects, baseline serum levels of IgM, IgG, and ALC were significantly lower, and ANC, NLR, PCT and CRP significantly higher in sCAP patients (p < 0.0001). Low Ig concentrations increased with trimodulin. Normalization of ANC (analysis of variance [ANOVA] p = 0.016) and PCT (ANOVA p = 0.027) was more rapid with trimodulin compared with placebo. These and other effects were more evident in patients with low baseline IgM levels. Normalization of PCT and CRP levels was both steadier and faster with trimodulin treatment. In patients with low baseline ALC, trimodulin was associated with a lower 28-day all-cause mortality rate (14.5% vs 32.1% in placebo, p = 0.043) and more ventilator-free days ([VFD]; median VFD: 3.5 vs 11 in placebo, p = 0.043). These numerical differences were greater if baseline IgM was also low (low ALC, low IgM: 8.1% mortality vs 34.1% placebo, p = 0.006; 3 VFD vs 15 VFD, p = 0.009, respectively). Results were consistent in patients with high baseline CRP (low ALC, high CRP: 10.9% mortality vs 34.1% placebo, p = 0.011).ConclusionsThis post hoc pharmacodynamic analysis of a blinded phase II trial suggests that trimodulin compensates for, and more rapidly modifies, the dysregulated inflammatory response seen in sCAP patients. Trimodulin was associated with significantly lower mortality and more VFD in subgroups with high CRP and low ALC. This effect was particularly marked in patients who also had low baseline IgM values. These findings require confirmation in prospective trials.

Inflammatory Biomarkers and Outcomes in Multiple Myeloma Patients after CAR T-Cell Therapy

Introduction: CAR T-cell therapy is an effective tool for the treatment of multiple myeloma but produces a systemic inflammatory response which can manifest as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and other neurologic toxicities, and hyperferritinemia. Understanding the factors associated with these complications can help clinicians better evaluate their patients' candidacy for CAR T-cell therapy. In this study, we assessed whether baseline values of inflammatory biomarkers were associated with outcomes after CAR T-cell therapy. Methods: We retrospectively reviewed multiple myeloma patients who underwent CAR T-cell therapy with commercial products or on clinical trials at The Mount Sinai Hospital between 2017 and 2023. We gathered data on lab parameters that we felt were indicative of patients' baseline inflammatory status including C-reactive protein (CRP), ferritin, D-dimer, fibrinogen, absolute lymphocyte count (ALC), and absolute neutrophil count (ANC). Baseline data were collected prior to lymphodepletion. Outcomes of interest were occurrence and maximum grade of CRS and ICANS, occurrence of delayed neurotoxicity, attainment of peak ferritin ≥5000 within 30 days of infusion, progression-free survival (PFS), and overall survival (OS). Univariate logistic regression was used to assess the association between baseline labs and CRS, ICANS, delayed neurotoxicity, and peak ferritin ≥5000. Ordinal logistic regression was used to assess the baseline labs' association with maximum grade of CRS and ICANS, while proportional cox regression was used to assess their association with OS and PFS. The percentage of bone marrow plasma cells pre-CAR T, which we used as a surrogate for tumor burden, was included as a covariate on multivariable analyses. Results: A total of 101 patients treated with CAR T cells were included - 45 with ciltacabtagene autoleucel, 37 with idecabtagene vicleucel, and 19 with other products on clinical trials. Median age was 63 (range 37-82), median baseline marrow plasma cells percentage was 5% (range 0%-95%), and median follow-up was 11.9 months. Patients had a median (IQR) CRP of 4.0 mg/L (1.8, 11.8), ferritin of 174 ng/mL (68, 364), D-dimer of 0.6 mcg/L (0.4, 1.2), fibrinogen of 397.0 mg/dL (334.0, 477.5), ALC of 0.8 x10 3/µL (0.5, 1.1), and ANC of 2.7 x10 3/µL (1.9, 3.6). CRS occurred in 88.2% of patients (3.9% grade ≥3), ICANS in 15.7% (all grade &amp;lt;3), and delayed neurotoxicity in 5.9% (all grade &amp;lt;3). Increased baseline fibrinogen and ferritin were significantly associated with inferior OS even after adjusting for covariates (p-values 0.031 and 0.010, respectively). Every 143 mg/dL increase in fibrinogen increased the hazard of death by 83.7%, while every 500 ng/mL increase in ferritin increased the hazard of death by 27.5%. Patients with higher baseline CRP had a trend towards inferior OS (30.2% increased hazard of death per 20 mg/L CRP increase, p = 0.055). Baseline CRP, D-dimer, fibrinogen, ferritin, ALC, and ANC were not associated with PFS. Higher baseline ALC was associated with both increased odds of ICANS (110.2% increased odds of ICANS for every 0.5 x10 3/µL increase in ALC, p = 0.019 on multivariable analysis) and increased grade of ICANS (p = 0.023 on multivariable analysis). None of the assessed biomarkers were associated with peak ferritin ≥5000 (aside from baseline ferritin), occurrence of CRS, maximum grade of CRS, or delayed neurotoxicity. Conclusion: Although CAR T-cell therapy is a highly effective treatment option for patients with multiple myeloma, outcomes of infused patients can be highly variable. Serologic biomarkers like fibrinogen and ferritin are routinely assessed in patients undergoing CAR T-cell therapy and could offer value as predictors of outcomes. We found that higher fibrinogen and ferritin values at baseline were associated with inferior OS after CAR T-cell therapy, even after controlling for tumor burden. Higher baseline ALC was also associated with higher risk of ICANS and higher grade of ICANS, an important toxicity to consider for patients receiving CAR T. Baseline fibrinogen, ferritin, and ALC may be incorporated into assessments of the risk of CAR T-cell therapy for multiple myeloma patients.

Risk factors for infective endocarditis in patients receiving hemodialysis: A propensity score matched cohort study.

In patients receiving hemodialysis, infective endocarditis (IE) may present in a similar way to other causes of bacteremia, which may delay early diagnosis and can lead to worse outcomes. In this study, we aimed to identify the risk factors for IE in hemodialysis patients with bacteremia. This study was conducted on all patients diagnosed with IE and receiving hemodialysis between 2005 and 2018 in Salford Royal Hospital. Patients with IE were propensity score matched with similar hemodialysis patients with episodes of bacteremia between 2011 and 2015 (non-IE bacteremic (NIEB)). Logistic regression analysis was used to predict the risk factors associated with infective endocarditis. There were 35 cases of IE, and these were propensity matched with 70 NIEB cases. The median age of the patients was 65 years with a predominance of males (60%). The IE group had higher peak C-reactive protein compared to the NIEB group (median, 253 mg/L vs. 152, p = 0.001). Patients with IE had a longer duration of prior dialysis catheter use than NIEB patients (150 vs. 28.5 days: p = 0.004). IE patients had a much higher 30-day mortality rate (37.1% vs. 17.1%, p = 0.023). Logistic regression analysis showed previous valvular heart disease (OR: 29.7; p < 0.001), and a higher baseline C-reactive protein (OR: 1.01; p = 0.001) as significant predictors for infective endocarditis. Bacteremia in patients receiving hemodialysis through a catheter access should be actively investigated with a high index of suspicion for infective endocarditis, particularly in those with known valvular heart disease and a higher baseline C-reactive protein.

Association between baseline C‑reactive protein level and survival outcomes for cancer patients treated with immunotherapy: A meta‑analysis.

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP ≥10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP ≥10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings.

C-reactive protein in solid tumors: Clinically meaningful change and prognosis.

e15036 Background: C-Reactive Protein (CRP) has been associated with overall survival (OS) in both solid and hematologic malignancies. CRP is used alone or in conjunction with other variables e.g., albumin to create prognostic scores, yet use in clinical practice is limited. One barrier is the lack of guidelines quantifying clinically relevant changes. The aim of this study was to determine important changes in CRP and any association with OS. Methods: This was a retrospective cohort study of electronic medical record data. Subjects were included if they had a solid tumor, ≥2 CRP measurements post diagnosis, ≥7 days apart, age ≥18. They were divided into Baseline High CRP (HCRP≥10 mg/L), and Baseline Normal CRP (NCRP &lt; 10 mg/L) groups and analyzed separately. Median (range) and counts (%) were reported. Variables compared with parametric or nonparametric tests. CRP change (∆ = (2nd CRP-1st CRP)/1st CRP) cut-off points were determined by Receiver Operator Curves or dividing groups into tertiles for sensitivity and specificity. We report the Kaplan-Meier survival plots and Cox Proportional Hazard Survival Models. Results: 4931 solid tumors were identified with CRP values; 1473 ≥2 CRP at least one week apart. N = 943 HCRP; N = 530 NCRP. HCRP were more likely to have gastrointestinal cancers, high white blood cell count, liver disease, metastatic disease, undergone surgery. NCRP were more likely breast or skin cancer, female, higher BMI, longer OS. 50% ↓ or 2-fold ↑ in CRP from baseline were statistically relevant cut-off points. In HCRP, estimated OS for ≥50% and &lt; 50% ↓ in CRP was, mean (SE), 87(2) and 81(4) months respectively; a six-month difference. In NCRP, estimated OS for ≥2 and &lt; 2-fold ↑ was 90(3) and 105(3) respectively; a fifteen-month difference. In the COX models, ≥ 50% CRP ↓ in HCRP was associated with 40% lower mortality risk; ≥ 2x CRP ↑ in NCRP was associated with 2-fold ↑ mortality risk. Conclusions: CRP level changes with cut-off points of either a 50% reduction or a 2-fold ↑ from baseline correlated with better and worse OS respectively, during follow up of solid tumors. This was both statistically and clinically important. CRP has the characteristics of an ideal tumor biomarker. This could aid in disease prognostication and impact treatment decision making in routine clinical practice. [Table: see text]

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357.

BI 730357 is investigated as an oral treatment of plaque psoriasis. We analyzed the impact of three dosage regimens on the Psoriasis Area and Severity Index (PASI) response with modeling based on phase I and II data from 109 healthy subjects and 274 patients with moderate-to-severe plaque psoriasis. The pharmacokinetics (PK) was characterized by a two-compartment model with dual absorption paths and a first-order elimination. Higher baseline C-reactive protein was associated with lower clearance and patients generally had lower clearance compared with healthy subjects. A bounded integer PK/pharmacodynamic model characterized the effect on the observed PASI. The maximum drug effect was largest for patients with no prior biologic use, smaller for patients with prior use of non-interleukin-17 inhibitors, and smallest for patients with prior interleukin-17 inhibitor use. The models allowed robust simulation of large patient populations, predicting a plateau in PASI outcomes for BI 730357 exposure above 2000 nmol/L.

Antibiotic Therapy for Pulmonary Exacerbations in Cystic Fibrosis-A Single-Centre Prospective Observational Study.

People with cystic fibrosis experience bronchopulmonary exacerbations, leading to lung damage, lung function decline, increased mortality, and a poor health-related quality of life. To date, there are still open questions regarding the rationale for antibiotic use and the optimal duration of antibiotic therapy. This prospective single-center study (DRKS00012924) analyzes exacerbation treatment over 28 days in 96 pediatric and adult people with cystic fibrosis who started oral and/or intravenous antibiotic therapy in an inpatient or outpatient setting after clinician diagnosis of bronchopulmonary exacerbation. Biomarkers of exacerbation were examined in terms of their ability to predict response to treatment and the need for antibiotic therapy. The mean duration of antibiotic therapy was 14 days. Inpatient treatment was associated with a poorer health status, but no significant difference was found in the modified Fuchs exacerbation score between inpatients and outpatients. A significant increase of in-hospital FEV1, home spirometry FEV1, and body-mass index and a significant decrease of the modified Fuchs symptom score, C-reactive protein, and 8 out of the 12 domain scores of the revised cystic fibrosis questionnaire were demonstrated after 28 days. However, a trend towards a FEV1 decline in the inpatient group on day 28 could be demonstrated, while FEV1 was maintained in the outpatient group. Correlation analyses of changes between baseline and day 28 show a strong positive correlation between home spirometry and in-hospital FEV1, strong negative correlations between FEV1 and the modified Fuchs exacerbation score and between FEV1 and C-reactive protein, and a moderately negative correlation between FEV1 and the three domains of the revised cystic fibrosis questionnaire. Responders and non-responders to antibiotic therapy were defined in terms of FEV1 improvement after therapy. A higher baseline C-reactive protein, a greater decrease in C-reactive protein, a higher baseline modified Fuchs exacerbation score, and a greater decrease in the score after 28 days could be found in the responder group, while other baseline and follow-up parameters like FEV1 showed no significant differences. Our data show that the modified Fuchs exacerbation score is applicable in a clinical setting and can detect acute exacerbations regardless of health status. Home spirometry is a useful tool for outpatient exacerbation management. A change in C-reactive protein and a modified Fuchs score change are suitable follow-up markers of exacerbation due to their strong correlation with FEV1. Further studies are needed to assess which patients would benefit from a longer duration of antibiotic therapy. C-reactive protein at exacerbation onset and C-reactive protein decline during and after therapy better predict antibiotic therapy success than FEV1 at therapy onset, while the modified Fuchs score indicates exacerbation regardless of the need for antibiotic therapy, suggesting that antibiotic therapy is only part of exacerbation management.

New-onset giant cell arteritis with lower ESR and CRP level carries a similar ischemic risk to other forms of the disease but has an excellent late prognosis: a case-control study.

Biopsy-proven giant cell arteritis (GCA) occasionally presents without acute-phase reaction. In this setting, GCA may be initially overlooked and glucocorticoid treatment unduly delayed, potentially increasing ischemic risk. From an inception cohort of patients with newly diagnosed, biopsy-verified GCA, we retrieved all cases without elevation of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level before starting glucocorticoid treatment. We compared the baseline features and outcomes of these patients and two additional patients recruited after GCA diagnosis with those of 42 randomly selected patients with high baseline ESR and CRP. Of 396 patients, 14 (3.5%) had lower baseline values of both ESR and CRP. Lower baseline ESR and CRP were associated with fewer American College of Rheumatology criteria met (p < 0.001, 95% CI -1.1; -0.9), and less jaw claudication (p = 0.06, 95% CI 0.8; 44.9), but similar rates of permanent blindness (p = 1.0). Patients with lower ESR and CRP also showed obvious differences regarding mean blood cell counts and mean hemoglobin level, but also less anti-cardiolipin antibody positivity (p = 0.04, 95% CI 0.8; ∞) and hepatic cholestasis (p = 0.03, 95% CI 1.0; 422). Patients with lower ESR and CRP had fewer GCA relapses (p = 0.03, 95% CI -1.1; -0.1), fewer glucocorticoid-induced complications (p = 0.01, 95% CI -2.0; -0.1), and successfully stopped glucocorticoids sooner than the other patients (18.3months vs 34months in average, p = 0.02, 95% CI -27;-0.9). Biopsy-proven GCA presenting with lower ESR and CRP is not an exceptional occurrence. It is clinically less typical but carries similar ischemic risk to other forms of the disease. Conversely, the late GCA prognosis of these patients is excellent.

Real-World Effectiveness and Risk Factors for Discontinuation of Ustekinumab in Ulcerative Colitis

Introduction: Ustekinumab (UST) has been approved for the treatment of moderate-to-severe ulcerative colitis (UC). Real-world data showing the effectiveness and safety of UST are necessary to confirm the results of clinical trials for applicability in daily clinical practice. Although some studies have reported real-world evidence of UST, only few studies have confirmed its effectiveness in the real world. The aim of this study was to assess the short- and long-term effectiveness, durability, safety, and risk factors for discontinuation of UST in UC in clinical practice. Methods: This was a retrospective, single-center, observational study. From March 2020 to January 2023, all consecutive patients with active UC who were treated with UST at Nagoya University Hospital were included. The primary outcome was the clinical remission rate at weeks 2–8 and weeks 24–48. The secondary outcomes included clinical response, persistence of UST therapy, endoscopic changes during follow-up, risk factors for UST discontinuation, and occurrence of any adverse events. The clinical effectiveness was evaluated using the Lichtiger score. Results: A total of 31 patients were included in this study. The clinical remission rates were 9.7%, 29.0%, 54.8%, and 64.5% at weeks 2, 8, 24, and 48, respectively. Twelve (38.7%) patients discontinued UST during the follow-up period. The probability of continuing UST was 93.5%, 80.6%, 77%, and 70% at weeks 2, 8, 24, and 48, respectively. The major reason for discontinuation of UST was primary failure (75.0%). A high baseline C-reactive protein (CRP) level was a significant risk factor for the discontinuation of UST. No adverse events were observed in this study. Conclusion: UST is effective for patients with UC. High CRP levels were identified as a risk factor for UST discontinuation. The findings of this study would help clinicians to select appropriate treatment options for patients with UC by identifying the risk factors for treatment discontinuation.

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

Background: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. Methods: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7–9, n-3 and n-6 FAs (patterns ω7–9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. Results: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). Conclusions: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies

Background and aimsThis study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. Methods and resultsIndividual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99–1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01–2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14–1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. ConclusionEvidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. Clinical trial registrationURL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Twenty-Year Survival of Patients Operated on for Non-Small-Cell Lung Cancer: The Impact of Tumor Stage and Patient-Related Parameters.

Simple SummarySurgery is the mainstay treatment of non-small-cell lung cancer, but its impact on survival beyond 15 years has never been reported so far. We studied retrospectively clinical characteristics and short and long-term survival of a single-institution patient population whose baseline data were prospectively collected. All patients underwent major lung resection between June 2001 and December 2002. Vital status was obtained by checking INSEE database and verifying if reported as “non-death” by the hospital administrative database and direct phone interviews with patients of families. A total of 345 patients were analyzed; 15-year and 20-year overall survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were increasing age at surgery, lower BMI, weight loss, higher baseline C-reactive protein, pathological stage, and, among patients with adenocarcinoma, higher grade. Increasing age, cumulative smoking, lower BMI, and pathological stage were independent predictors of long-term survival at Cox multivariate analysis. We conclude that very-long-term survivals can be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determines longer outcomes suggesting that both initial tumor aggressiveness and host characteristics act beyond the period usually taken into account in oncology.Surgery is the mainstay treatment of non-small-cell lung cancer (NSCLC), but its impact on very-long-term survival (beyond 15 years) has never been evaluated. Methods: All patients operated on for major lung resection (Jun. 2001–Dec. 2002) for NSCL in the Thoracic Surgery Department at Paris-Hôtel-Dieu-University-Hospital were included. Patients‘ characteristics were prospectively collected. Vital status was obtained by checking INSEE database and verifying if reported as “non-death” by the hospital administrative database and direct phone interviews with patients of families. Results: 345 patients were included. The 15- and 20-year survival rates were 12.2% and 5.7%, respectively. At univariate analysis, predictors of worse survivals were: increasing age at surgery (p = 0.0042), lower BMI (p = 0.009), weight loss (p = 0.0034), higher CRP (p = 0.049), pathological stage (p = 0.00000042), and, among patients with adenocarcinoma, higher grade (p = 0.028). Increasing age (p = 0.004), cumulative smoking (p = 0.045), lower BMI (0.046) and pathological stage (p = 0.0026), were independent predictors of long-term survival at Cox multivariate analysis. In another model, increasing age (p = 0.013), lower BMI (p = 0.02), chronic bronchitis (p = 0.03), lower FEV1% (p = 0.00019), higher GOLD class of COPD (p = 0.0079), and pathological stage (p = 0.000024), were identified as independent risk factors. Conclusions: Very-long-term survivals could be achieved after surgery of NSCLC, and factors classically predicting 5- and 10-years survival also determined longer outcomes suggesting that both initial tumor aggressiveness and host’s characteristics act beyond the period usually taken into account in oncology.

The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

BackgroundThe relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy.MethodsAll associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias.ResultsThirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521).ConclusionsHigh baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.

Real-world effectiveness and safety of golimumab in rheumatoid arthritis treatment: A two-center study in Taiwan.

The real-world outcomes of golimumab (GLM) use have been rarely studied in Asian patients with rheumatoid arthritis (RA). This study assessed the real-world effectiveness and safety of GLM in a Taiwanese cohort. One hundred and eight GLM-treated RA patients were enrolled. Predictors of a good European League Against Rheumatism (EULAR) response at 24 months and drug retention were identified through multivariate analyses. After 24 months of GLM treatment, the mean Disease Activity Score using 28 joint counts with the erythrocyte sedimentation rate (DAS28-ESR) decreased from 6.7 to 3.1 (p < 0.001). Up to 58.9% of patients achieved a good EULAR response at 24 months. Multivariate logistic regression analysis revealed that after adjustment for other variables, a higher baseline C-reactive protein was an independent negative predictor of good EULAR responses (odds ratio, 0.82; 95% confidence interval [CI], 0.67-0.99; p = 0.043). During the mean follow-up period of 38.3 months, 15 (13.9%) patients discontinued GLM due to treatment failure. In multivariate analysis, high baseline ESR level, high DAS28-ESR, and the experience of biologic therapy were independent risk factors for GLM discontinuation (adjusted hazard ratio [HR], 1.03; 95% CI, 1.01-1.05; p = 0.003; adjusted HR, 2.93; 95% CI, 1.42-6.08; p = 0.004; and adjusted HR, 5.00; 95% CI, 1.75-14.26; p = 0.003, respectively). In receiver operator characteristic curve analysis, the optimal cutoff values of baseline ESR and DAS28-ESR for predicting drug survival were 52 mm/h (sensitivity: 60.0% and specificity: 77.4%) and 7.7 (sensitivity: 46.7% and specificity: 94.3%), respectively. During the follow-up period, 22 patients (20.4%) developed adverse events. The safety profile of GLM in this study was comparable with that in previous clinical trials. GLM was effective and safe for the real-life management of Taiwanese RA patients and showed a high retention rate in biologic-naive patients compared with biologic-experienced patients.

Immune-endocrine biomarkers associated with mental health: A 9-year longitudinal investigation from the Hertfordshire Ageing Study

BackgroundThe study of neural-endocrine-immune system interactions has led to substantial advances in our understanding of neuropsychiatric disorders. Growing evidence reveals the pivotal roles of inflammatory cytokines signalling the brain to produce neurochemical, neuroendocrine, and neuroimmune changes which affect mood and behaviour. Ageing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the longitudinal associations between baseline values and conditional changes (independent of baseline) in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults. MethodsData from 347 subjects (200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline (1994/5, mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health (Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores (top sex-specific third) and low mental health scores (bottom sex-specific third) were examined using logistic regression. ResultsLower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: dehydroepiandrosterone sulphate ratio (men only) and higher baseline C-reactive protein (CRP) (women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust (p < 0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated. ConclusionThis study provides further evidence of the role of the HPA axis and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men were linked to poorer mental health. Further research is warranted to confirm these findings. This could lead to the search for potential biomarkers to stratify medications as well as developing novel intervention targets to improve mental health at older age.

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma

BackgroundRecent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients.MethodsThe optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% CI 0.47–0.92). Patient cohort was dichotomized into normal (n = 66; < 3.14 mg/dl) and high baseline (n = 21; ≥ 3.14 mg/dl) CRP groups.ResultsNo significant differences in age, sex, comorbidities influencing the systemic inflammatory state, Karnofsky performance status (KPS), tumor size, extent of resection, or MIB-1 index were identified between the two groups defined by the baseline CRP levels. Univariable analysis demonstrated that a high CRP level (≥ 3.14 mg/dl) is significantly associated with a shortened progression-free survival (PFS) (hazard ratio (HR): 6.05, 95% CI 1.15–31.95, p = 0.03). Multivariable Cox regression analysis considering age, extent of resection, KPS, tumor size, and baseline CRP confirmed that an elevated CRP level (≥ 3.14 mg/dl) is an independent predictor of shortened PFS (HR: 7.20, 95% CI 1.08–48.14, p = 0.04).ConclusionsThe baseline CRP level thus serves as an independent predictor of PFS. Further investigations of the role of inflammation and tumor inflammatory microenvironment in the prediction of prognosis in sporadic VS are needed.Graphical abstract