Higher Serum C-reactive Protein Research Articles

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection – Derivation of a clinical risk score

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006–2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age> 65 years (2 points), male sex (2 points) and LDH> 770 U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60–0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41–0.66). A low-risk score of 0–1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

Serum Malondialdehyde-Modified Low-Density Lipoprotein as a Risk Marker for Peripheral Arterial Stiffness in Maintenance Hemodialysis Patients.

Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004-1.025), 1.044 (1.004-1.085) and 3.697 (1.149-11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

Clinical phenotypes of nontuberculous mycobacterial disease by cluster analysis based on pulmonary function

BackgroundNontuberculous mycobacterial pulmonary disease (NTM-PD) often exhibits pulmonary function impairment, such as obstructive or restrictive pattern, with variation among patients according to the damaged lesions in the lung. MethodsPatients with NTM-PD were consecutively enrolled between September 2019 and December 2020 at the Respiratory Infection Clinic of our hospital. Patients’ data were comprehensively collected through laboratory examinations, PFT, chest computed tomography, and questionnaires for the assessment of subjective symptoms and health-related quality of life (HRQOL). Hierarchical cluster analysis was performed using PFT parameters to compare the clinical findings among clusters. ResultsData of 104 patients were analyzed and classified into four clusters. The restrictive pattern with decreased forced expiratory volume in 1 s (FEV1) group showed high serum C-reactive protein and low albumin levels, severe radiological findings, and low HRQOL. In the restrictive pattern with preserved FEV1 group, HRQOL was as low as that in the restrictive pattern with decreased FEV1 group, and bacterial exacerbation was observed relatively frequently. HRQOL in the obstructive impairment group was maintained in comparison with that in the normal group. ConclusionNTM-PD phenotypes were identified using cluster analysis based on PFT. Two different severe phenotypes were also observed. In the early stages of NTM-PD, PFT may be useful in recognizing disease progression.

P422 Prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaire in Inflammatory Bowel Disease patients and its association with disease activity and quality of life

Abstract Background An association between active inflammatory bowel disease (IBD) and poor sleep quality has been proposed, however studies evaluating both subjective and objective assessment of disease activity and sleep quality are limited. Our study aimed to investigate the prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaires in IBD patients and its association with disease activity and quality of life. Methods A prospective observational study was conducted in Siriraj Hospital, Mahidol University, Bangkok, Thailand from March 2021 to December 2022. Eligible IBD patients were categorized into remission, mild, and moderate-to-severe groups, based on standard clinical disease activity scores. Demographic data, inflammatory markers, inflammatory bowel disease questionnaire (IBDQ), sleep questionnaire (Pittsburgh Sleep Quality Index, PSQI), and seven-day sleep data from wrist actigraphy (Actiwatch®, CamNtech, Cambridge, United Kingdom) were obtained. The prevalence of sleep disorder and group comparison were analyzed. Results Eighty-four participants (40 Crohn’s disease, 44 UC), consisting of 60 remission, 16 mild, and 8 moderate-to-severe disease activity, were enrolled. Baseline demographic data were comparable between each group. Lower hemoglobin and albumin levels, and higher serum C-reactive protein, and fecal calprotectin levels were found in the more clinically active groups (table1). Fifty patients (60%) had poor sleep defined by PSQI > 5 with a trend to be higher in the group with active symptoms (57% in remission, 63% in mild, and 75% in moderate-to-severe group, p=0.31). Using actigraphy, the group with moderate-to-severe symptoms tended to have longer sleep latency, more frequently awake after sleep, and poorer sleep efficiency than the other groups (Figure 1). Patients with more severe disease activity had poorer quality of life with a mean IBDQ of 190 in remission, 159 in mild, and 134 in moderate-to-severe group (p<0.001). Conclusion Poor sleep quality is common among IBD patients, even those with clinical remission. Those with more severe symptoms had poorer sleep quality and worse quality of life. Sleep assessment and treatment should be integrated into IBD standard clinical care.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

BackgroundVacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme1 (UBA1) gene and characterised by an overlap between autoinflammatory and haematologic disorders.Case presentationWe reported a case of a 67-year-Japanese man receiving peritoneal dialysis (PD) who had recurrent aseptic peritonitis caused by the VEXAS syndrome. He presented with unexplained fevers, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed high serum C-reactive protein concentration and increased cell count in PD effluent. He was treated with antibiotics for PD-related peritonitis, but this was unsuccessful. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images demonstrated intense FDG uptake in his left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and he was treated with oral prednisolone (PSL) 15 mg daily with good response. However, he was unable to taper the dose to less than 10 mg daily because his symptoms flared up. Since Tocilizumab was initiated, he could taper PSL dose to 2 mg daily. Sanger sequencing of his peripheral blood sample showed a mutation of the UBA1 gene (c.122 T > C; p.Met41Thr). We made a final diagnosis of VEXAS syndrome. He suffered from flare of VEXAS syndrome at PSL of 1 mg daily with his cloudy PD effluent. PSL dose of 11 mg daily relieved the symptom within a few days.ConclusionsIt is crucial to recognise aseptic peritonitis as one of the symptoms of VEXAS syndrome and pay attention to the systemic findings in the patients.

Dilute Povidone-Iodine Solution Soaking Is Ineffective in Improving Outcomes of Necrotizing Fasciitis Caused by Diabetic Foot.

Wound soaking is a physical debridement method that helps reduce bacterial colonization and consequently promotes wound healing. Although soaking in povidone-iodine solution was ineffective in reducing bacterial colonization in acute trauma wounds, there is still a lack of evidence supporting the efficacy of this method in treating severe soft tissue infection. This study aimed to explore the effects of wound soaking in 1% dilute povidone-iodine solution on necrotizing fasciitis caused by diabetic foot ulcers. We retrospectively reviewed and finally included 153 patients who were admitted because of diabetic foot ulcers after undergoing fasciotomy for necrotizing infection from January 2018 to December 2021. Results showed no statistical difference in the outcomes between patients in the soaking and nonsoaking groups. End-stage renal disease (P = 0.029) and high serum C-reactive protein level (P = 0.007) were the only independent factors for below-knee amputation in the univariate and multivariate logistic regression analyses. Therefore, soaking diabetic wounds with severe infection in 1% dilute povidone-iodine solution may not reduce the hospital length of stay, risk of below-knee amputation, and readmission rate.

Systemic inflammation adversely affects response to anamorelin in patients with pancreatic cancer.

Anamorelin, a selective ghrelin receptor agonist, has been approved for pancreatic cancer treatment in Japan. We aimed to investigate whether systemic inflammation, represented by the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP)-albumin ratio (CAR), could predict the effect of anamorelin in patients with advanced pancreatic cancer. This study included 31 patients who had received anamorelin for advanced pancreatic cancer between 2021 and 2023. Patients' NLR, PLR, LMR, and CAR were evaluated before anamorelin administration. The patients were classified as responders and non-responders based on whether they gained body weight after 3months of anamorelin administration. We investigated the association between systemic inflammation and anamorelin efficacy using a univariate analysis. Twelve (39%) patients were non-responders. A high serum CRP level (p = 0.007) and high CAR (p = 0.013) was associated with non-response to anamorelin. According to the receiver operating characteristics analysis, the CAR cutoff value was 0.06, and CAR ≥ 0.06 was a risk factor (odds ratio, 5.6 [95% confidence interval 1.2-27.1], p = 0.032) for non-response to anamorelin. CAR can be a predictor of non-response to anamorelin in patients with advanced pancreatic cancer, suggesting the importance of a comprehensive assessment of the inflammatory status.

Profiling risk factors for separation of infection complications in patients with gastrointestinal and nodal diffuse large B-cell lymphoma

ObjectiveTo identify risk factors for infection complications in patients with gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) and nodal DLBCL (N-DLBCL) during treatment, respectively.MethodsTotal 51 GI-DLBCL patients and 80 N-DLBCL patients were included after retrieving clinical data from a single medical center in the past ten years. Logistic regression analysis was utilized to analyze patients’ data, including baseline demographics, treatments and laboratory values, to determine independent risk factors of infection in these patients.ResultsTotal 28 of 51 patients (54.9%) in the GI-DLBCL group and 52 of 80 patients (65%) in the N-DLBCL group were observed infection events during treatment. A multivariate logistic regression model revealed that Ann-arbor stage IV (P = 0.034; odds ratio [OR]: 10.635; 95% confidence interval [CI]: 1.152-142.712), extra-nodal lesions ≥ 2 (P = 0.041; OR: 23.116; 95%CI: 1.144-466.949) and high serum lactate dehydrogenase (LDH) at the time of diagnosis (LDH > 252U/L; P = 0.033; OR: 6.058; 95%CI: 1.159–31.659) were independent risk factors for the development of infection in patients with GI-DLBCL after systemic treatment. In the N-DLBCL group, high serum C-reactive protein (CRP) (P = 0.027; OR: 1.104; 95%CI: 1.011–1.204) and a low platelet count (P = 0.041; OR: 0.991; 95%CI: 0.982-1.000) at routine blood tests just before infection occurred were identified as significant risk factors related to infection events during treatment.ConclusionsDiscordant independent risk factors induced infection may be present during the treatment in patients with GI-DLBCL and N-DLBCL. Close monitoring these risk factors is likely an effective strategy to prevent microbial infections in these patients.

Predictive effects of S100β and CRP levels on hemorrhagic transformation in patients with AIS after intravenous thrombolysis: A concise review based on our center experience.

Hemorrhagic transformation (HT) is one of the most dangerous complications after intravenous thrombolysis in patients with acute ischemic stroke (AIS). Therefore, we want to explore the predictive effects of peripheral blood S100β and C-Reactive Protein (CRP) levels on hemorrhagic transformation after intravenous thrombolysis in AIS patients. Ninety-two AIS patients who had been treated in Huai'an Second People's Hospital from January 2018 to December 2021 were retrospectively selected. Patients were divided into hemorrhagic transformation (HT) groups (24 cases) and no HT groups (68 cases) based on whether there was hemorrhagic transformation within 24 h after intravenous thrombolysis. General clinical data from the HT group and no HT group were compared. A multivariate logistic regression model was used to analyze the potential risk factors of HT after intravenous thrombolysis in patients with AIS. A receiver operating curve (ROC) was used to analyze the predictive value of risk factors for HT. High serum S100β, CRP levels, and National Institutes of Health Stroke Scale (NIHSS) scores were found to be risk factors for HT after intravenous thrombolysis in patients with AIS (all P < .05). The ROC curve analysis showed that critical value of S100β, CRP level, and NIHSS score for predicting intravenous thrombolytic HT in AIS patients were 0.335, 8.700, and 14.50, respectively, and their sensitivities were 0.750, 0.971, and 0.333 (P < .05), respectively. High serum S100β and CRP levels are risk factors for HT after intravenous thrombolysis in AIS patients and have predictive influence of the occurrence of HT in AIS patients.

Strong impact of sarcopenic state defined by skeletal muscle mass index on postoperative complication of Crohn's disease patients

BackgroundMalnutrition impacts the clinical course of Crohn's disease; however, there is little evidence of its influence on perioperative adverse events. We assessed whether nutritional indicators are associated with postoperative complications in surgical treatment of Crohn's disease. Methods137 patients with Crohn's disease who underwent surgical treatment between January 2011 and December 2020 were included. Skeletal muscle index was calculated by a single CT slice. We analyzed the risk factors for adverse events. Results37 % of patients had postoperative complications. Adverse events occurred more frequently in patients with high serum C-reactive protein, low serum albumin, prognostic nutritional index <38.3, skeletal muscle index <38.9 cm2/m2, abdominoperineal resection, long surgical duration, and mass hemorrhage. Among patients with skeletal muscle index <38.9 cm2/m2, patients who experienced adverse events had higher visceral fat index compared with those who did not (0.85 vs. 0.45, P = 0.04). Multivariate analysis revealed that skeletal muscle index <38.9 cm2/m2 and low serum albumin were the independent risk factors for postoperative complications (Odds ratio, 2.85; 95 % confidence interval, 1.13–7.16; P = 0.03, 2.62; 1.09–6.26; P = 0.03, respectively). Separated by sex, low serum albumin (<3.5 and <2.8 g/dL, male and female, respectively) and skeletal muscle index (<38.9 and <36.6 cm2/m2, male and female, respectively) were statistically related to postoperative complications. ConclusionsSkeletal muscle index is the most useful nutritional predictor of postoperative complications in Crohn's disease patients among other nutritional indices. We believe that these patients are at high risk of postoperative complications and need appropriate nutritional support in the perioperative period.

Clinical predictors and outcomes of non-expandable lung following percutaneous catheter drainage in lung cancer patients with malignant pleural effusion.

Non-expandable lung (NEL) often occurs during pleural fluid drainage in patients with malignant pleural effusion (MPE). However, data regarding the predictors and prognostic impact of NEL on primary lung cancer patients with MPE receiving pleural fluid drainage, compared to malignant pleural mesothelioma (MPM), are limited. This study was aimed to investigate the clinical characteristics of lung cancer patients with MPE developing NEL following ultrasonography (USG)-guided percutaneous catheter drainage (PCD) and compare the clinical outcomes between those with and without NEL. Clinical, laboratory, pleural fluid, and radiologic data and survival outcomes of lung cancer patients with MPE undergoing USG-guided PCD were retrospectively reviewed and compared between those with and without NEL. Among 121 primary lung cancer patients with MPE undergoing PCD, NEL occurred in 25 (21%). Higher pleural fluid lactate dehydrogenase (LDH) levels and presence of endobronchial lesions were associated with development of NEL. The median time to catheter removal was significantly extended in those with NEL compared to those without (P = .014). NEL was significantly associated with poor survival outcome in lung cancer patients with MPE undergoing PCD, along with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS), the presence of distant metastasis, higher serum C-reactive protein (CRP) levels, and not receiving chemotherapy. NEL developed in one-fifth of lung cancer patients undergoing PCD for MPE and was associated with high pleural fluid LDH levels and the presence of endobronchial lesions. NEL may negatively affect overall survival in lung cancer patients with MPE receiving PCD.

#5963 THE ASSOCIATION OF FRAILTY, DENTAL STATUS, İNFLAMMATION AND MALNUTRITION İN HEMODIALYSIS PATIENTS

Abstract Background and Aims Persistent low-grade inflammation and malnutrition in chronic kidney disease (CKD) are associated with so many CKD complications. Frailty, the state of increased vulnerability often associated with aging, had a higher incidence in CKD patients regardless of age. In this study, we aimed to investigate the frequency of frailty among hemodialysis patients and volunteers with normal kidney function to define its relationship with inflammatory markers, biochemical parameters and dental status. Method A cohort of 86 CKD patients with hemodialysis (HD) and 74 volunteers with normal kidney function (similar in terms of age and gender distribution) were included in this study. Both groups were evaluated by the Clinical Frailty Scale in three groups as non-brittle, pre-frail and frail. Demographic characteristics, biochemical parameters and dental status were recorded. Results 21 of 86 patients (24.4%) were frail in CKD patients with HD, and 4 of 76 patients (5.4%) in the control group were frail (p&amp;lt;0.001). The frail individuals in the HD group were older (p&amp;lt;0.001), had more systemic diseases (p&amp;lt;0.001), had higher serum C-Reactive Protein (CRP) levels (p&amp;lt;0.001), lower serum albumin levels (P = .001), lower serum creatinine levels (p&amp;lt;0.003). When the number of teeth is evaluated; the number of patients with more than 20 teeth was significantly lower in the frail group than in the non-frail group (p&amp;lt;0.001). Conclusion In our study, the frequency of fraility in hemodialysis patients was found to be significantly higher than in the control group. The lower albumin and serum creatinine levels, the higher CRP levels and the lower number of teeth suggest the relationship between frailty with dental status, malnutrition and inflammation in hemodialysis patients. It can be concluded that improvements in oral health and/or inflammation status can contribute to the improvement of frailty in this patient group.

Risk factors for bronchopleural fistula after lobectomy for lung cancer.

Bronchopleural fistula (BPF) after lobectomy for lung cancer is a rare but serious complication. This study aimed to stratify the risk factors of BPF. Patients who underwent lobectomy without bronchoplasty and preoperative treatment for lung cancer between 2005 and 2020 were retrospectively reviewed. We examined the association between the incidence of BPF and background factors, including comorbidities, preoperative blood test results, respiratory function, surgical procedure, and extent of lymphadenectomy. Among the 3,180 patients who underwent lobectomy, 14 (0.44%) developed BPF. The median interval from surgery to BPF onset was 21 days (range, 10-287). Two of the 14 patients died of BPF (mortality rate, 14%). All 14 patients who developed BPF were men and had undergone right lower lobectomy. Other factors significantly associated with the development of BPF were older age, heavy smoking, obstructive ventilatory failure, interstitial pneumonia, history of malignancy, history of gastric cancer surgery, low serum albumin levels, and histology. Multivariable analysis in the subgroup of men who underwent right lower lobectomy revealed that high level of serum C-reactive protein and a history of gastric cancer surgery were significantly associated with BPF, whereas bronchial stump coverage was inversely associated with BPF. Men who underwent right lower lobectomy were at increased risk of BPF. The risk was higher when the patient had high serum C-reactive protein or a history of gastric cancer surgery. Bronchial stump coverage might be effective in patients at high risk of BPF.

INCREASED SERUM SCLEROSTIN LEVEL IS A RISK FACTOR FOR PERIPHERAL ARTERY OCCLUSIVE DISEASE IN PATIENTS WITH HYPERTENSION

Objective: Sclerostin is associated with endothelial inflammation and vascular calcification and therefore contributes to atherosclerosis disease. Hypertension is one of risk factors of peripheral arterial occlusive disease (PAOD), is associated with increased mortality in patients with hypertension. The aim of this study was to determine the relationship between serum sclerostin level and PAOD in patients with hypertension. Design and method: Fasting blood samples and baseline characteristics were obtained from 92 hypertensive patients. ABI values were measured using an automated oscillometric device. Patients with ABIs of &lt;0.9 were categorized into the low ABI group. The serum sclerostin and dickkopf-1 (DKK1) concentrations were determined using commercially available enzyme-linked immunosorbent assays. Results: In total, 14 patients with hypertension (15.2%) were in the low ABI group. When compared to those in the normal ABI group, the low ABI group had high rates of diabetes mellitus (P = 0.044) as well as the high serum C-reactive protein levels (P = 0.001) and sclerostin levels (P &lt; 0.001), but the serum DKK1 level did not find this association (P = 0.639). The multivariable logistic regression analysis revealed that serum levels of sclerostin (odds ratio [OR]: 1.052, 95% confidence interval [CI]: 1.018–1.088, P = 0.002) was independently associated with PAD in patients with hypertension. Conclusions: Serum levels of sclerostin, but not DKK1, were associated with PAOD in patients with hypertension.

Pericardial Fluid Analysis in Diagnosis and Prognosis of Patients Who Underwent Pericardiocentesis

In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results. Patients were grouped into those with and without underlying malignancy. A Cox proportional hazards model was used to analyze the association of variables with mortality. The study included 179 patients; 50% had an underlying malignancy. There were no significant differences in pericardial fluid protein and lactate dehydrogenase between the 2 groups. Diagnostic yield from pericardial fluid analysis was greater in the malignant group (32% vs 11%, p = 0.002); 72% of newly diagnosed malignancies had positive fluid cytology. The 1-year survival was 86% and 33% in nonmalignant and malignant groups, respectively (p <0.001). Of 17 patients who died within the nonmalignant group, idiopathic effusions were the largest group (n = 6). In malignancy, lower pericardial fluid protein and higher serum C-reactive protein were associated with increased risk of mortality. In conclusion, pericardial fluid biochemistry has limited value in determining the etiology of pericardial effusions; fluid cytology is the most important diagnostic test. Mortality in malignant pericardial effusions may be associated with lower pericardial fluid protein levels and a higher serum C-reactive protein. Nonmalignant pericardial effusions do not have a benign prognosis and close follow-up is required. In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results. Patients were grouped into those with and without underlying malignancy. A Cox proportional hazards model was used to analyze the association of variables with mortality. The study included 179 patients; 50% had an underlying malignancy. There were no significant differences in pericardial fluid protein and lactate dehydrogenase between the 2 groups. Diagnostic yield from pericardial fluid analysis was greater in the malignant group (32% vs 11%, p = 0.002); 72% of newly diagnosed malignancies had positive fluid cytology. The 1-year survival was 86% and 33% in nonmalignant and malignant groups, respectively (p <0.001). Of 17 patients who died within the nonmalignant group, idiopathic effusions were the largest group (n = 6). In malignancy, lower pericardial fluid protein and higher serum C-reactive protein were associated with increased risk of mortality. In conclusion, pericardial fluid biochemistry has limited value in determining the etiology of pericardial effusions; fluid cytology is the most important diagnostic test. Mortality in malignant pericardial effusions may be associated with lower pericardial fluid protein levels and a higher serum C-reactive protein. Nonmalignant pericardial effusions do not have a benign prognosis and close follow-up is required.

Fueling the flames of colon cancer - does CRP play a direct pro-inflammatory role?

Systemic inflammation, diagnostically ascribed by measuring serum levels of the acute phase reactant C-reactive protein (CRP), has consistently been correlated with poor outcomes across cancer types. CRP exists in two structurally and functionally distinct isoforms, circulating pentameric CRP (pCRP) and the highly pro-inflammatory monomeric isoform (mCRP). The aim of this pilot study was to map the pattern of mCRP distribution in a previously immunologically well-defined colon cancer (CC) cohort and explore possible functional roles of mCRP within the tumor microenvironment (TME). Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 43 stage II and III CC patients, including 20 patients with serum CRP 0-1 mg/L and 23 patients with serum CRP >30 mg/L were immunohistochemically (IHC) stained with a conformation-specific mCRP antibody and selected immune and stromal markers. A digital analysis algorithm was developed for evaluating mCRP distribution within the primary tumors and adjacent normal colon mucosa. mCRP was abundantly present within tumors from patients with high serum CRP (>30 mg/L) diagnostically interpreted as being systemically inflamed, whereas patients with CRP 0-1 mg/L exhibited only modest mCRP positivity (median mCRP per area 5.07‰ (95%CI:1.32-6.85) vs. 0.02‰ (95%CI:0.01-0.04), p<0.001). Similarly, tissue-expressed mCRP correlated strongly with circulating pCRP (Spearman correlation 0.81, p<0.001). Importantly, mCRP was detected exclusively within tumors, whereas adjacent normal colon mucosa showed no mCRP expression. Double IHC staining revealed colocalization of mCRP with endothelial cells and neutrophils. Intriguingly, some tumor cells also colocalized with mCRP, suggesting a direct interaction or mCRP expression by the tumor itself. Our data show that the pro-inflammatory mCRP isoform is expressed in the TME of CC, primarily in patients with high systemic pCRP values. This strengthens the hypothesis that CRP might not only be an inflammatory marker but also an active mediator within tumors.

P762 Population Pharmacokinetic Model of Intravenous Infliximab in Korean Patients with Crohn’s Disease

Abstract Background Infliximab (IFX), a monoclonal antibody approved for treating Crohn’s disease (CD), is known to show differing drug clearances in patients according to several clinical factors. However, information on the population pharmacokinetics (PKs) of intravenous (IV) IFX is lacking for Korean patients with CD. Therefore, in this study, we aimed to establish a PK model of IV IFX for this population. Methods We retrospectively analyzed data of CD patients treated with IV IFX at Asan Medical Center, a tertiary university hospital, from April 2019 to March 2022. Serum trough IFX concentration, clinical laboratory values, Crohn’s disease activity index, and demographic data were collected. NONMEM® version 7.5 was used for nonlinear mixed effects modeling. Results Of the one hundred patients included for analysis in this study, 72 were male (72.0%) (Table 1). No patient had detectable antibodies to IFX. [SJ1] A total of 823 serum IFX concentration data were collected and analyzed for fitting according to the minimization of objective function value and weighted residuals. As a result, a one-compartment population PK model with first-order elimination best described the serum trough IFX concentration measurements. Population PK estimates were 0.012 L/h for clearance (CL) (95% confidence interval: 0.012–0.013) and 6.301 L for the volume of distribution (V) (95% confidence interval: 5.932–6.671) (Table 2). Covariate analysis showed that CL and V increased as body weight increased. CL was higher in patients with low serum albumin, high serum C-reactive protein, and older age, with differing coefficients for each covariate (Figure 1). The final covariate model predicted the observed concentration-time profiles of IFX reasonably well (Figure 2). Conclusion We established a population PK model of IV IFX for CD patients in Korea. The final covariate model showed that the CL of IFX was affected by serum albumin and C-reactive protein levels, in addition to body weight and age.

Biomarkers of Inflammation and Progression During Immunotherapy in Patients With Metastatic Renal Cell Carcinoma.

Biomarkers that would identify patients unlikely to respond to immunotherapy with immune checkpoint inhibitors (ICIs) remain an unmet medical need. In the present study, we have retrospectively evaluated the association between biomarkers of immune activation and outcome in metastatic renal cell carcinoma (mRCC) patients treated with ICIs. The laboratory and clinical data of 79 consecutive patients with histologically confirmed mRCC treated with ICI-based immunotherapy have been analyzed. Patients who progressed or died at 4 months had higher prognostic score, higher serum C-reactive protein (CRP) and neopterin, and urinary neopterin, and lower serum albumin and hemoglobin concentration. Biomarkers of activation of immune response, in particular serum neopterin/creatinine ratio, are associated with outcome in mRCC patients treated with ICI immunotherapy.

Predictive role of selected biomarkers in differentiating gram-positive from gram-negative sepsis in surgical patients: a retrospective study.

Patients after major surgery are at high risk of developing sepsis, which is accompanied by elevated serum levels of C-reactive protein (CRP) and procalcitonin (PCT). This study aimed to examine the differences in serum biomarker levels concerning the causative agent of sepsis in surgical patients. A retrospective study was carried out in the surgical intensive care unit (ICU) and included 81 septic patients admitted from January 2019 to May 2022, who had positive blood cultures (BC). Serum levels of PCT, CRP, white blood cells (WBC) and platelet counts were recorded on the day of the positive BC and over the following 3 days. Patients with gram(-) sepsis had significantly higher PCT levels, and lower platelet count compared to patients with gram(+) sepsis. High PCT and low platelets levels in all measurements were a significant predictor of gram(-) isolate with the highest predictive value on the third day after BC sampling, with AUROC 0.821 (95% CI: 0.692-0.950), P = 0.001, and AUROC 0.676 (95% CI: 0.541-0.811), P = 0.02, respectively. In multivariate logistic regression, platelets the day after BC sampling and PCT on the third day made a significant contribution in distinguishing gam(+) from gram(-) BC. Age and high serum CRP levels were significant predictors of poor outcomes. PCT and platelets may be useful biomarkers for predicting the causative agent of sepsis in surgical patients.