Peak C-reactive Protein Research Articles

Characterizing CRP dynamics during acute infections.

C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4mg/L in viral infections without antibiotics to 140.9mg/L in Gram-negative bacteremia with antibiotics. CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients.

ORBI risk score and inflammatory response in patients with acute ST-elevation myocardial infarction

Abstract Background The ORBI risk score was developed to predict in-hospital cardiogenic shock (CS) in patients with ST-elevation myocardial infarction (STEMI) [1]. An inflammatory response is seen in STEMI and may precede CS. The association between ORBI score and systemic inflammatory response is of interest both for improving risk assessment of CS but also for identifying potential therapeutic targets. Methods Using data from one center in the Third DANish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction (DANAMI 3) trial, the inflammat ory status was detected by peak C-reactive protein level (CRP) and white blood cell count (WBC) analyzed from blood samples taken within 96 hours from percutaneous coronary intervention (PCI). Patients were stratified into two ORBI risk groups: ‘Low’ (0-7) and ‘intermediate-high’ (>=8). Patients with CS at the time of PCI were not included, nor were those with out-of-hospital cardiac arrest. Logistic- and Cox Proportional Hazards regression was used to assess the association between ORBI risk groups and 1/ an above-median inflammatory status, and 2/ one-year mortality when combining risk group with inflammatory status. Results Of 1603 patients included, at least one 0–96-hour CRP was available in 631 (39.4%), and WBC in 628 (39.2%) of patients. Mortality at 96 hours was 1.3%. Median CRP and median WBC in the ‘intermediate-high’ ORBI risk group were 61.5 mg/L (interquartile range (IQR) 16-158) and 12 x 10^9/L (IQR 8.8-15.8) vs. 14 (IQR 5-38.8) and 10 (IQR 8.3-12.8) in the ‘low-risk’ group (p<0.001). ‘Intermediate-high’ ORBI score was associated with increased odds of an above-median CRP (OR 3.34, 95% confidence interval (CI) 2.20-5.18, p<0.001), as well as increased odds of an above-median WBC (OR 2.24, 95%CI 1.50-3.38, p<0.001) in univariate analyses. In patients having CRP levels above the median compared to those below, the median age was higher (66 years vs. 60 years, p<0.001). The prevalence of chronic heart failure was greater (26% vs. 13%, p<0.001), as was the incidence of renal failure (6.1% vs. 1.2%, p=0.003). A higher number of patients were classified within Killip classes 3-4 (24% vs. 2.6%, p<0.001). For patients with WBC above the median versus those below, there was a higher prevalence of chronic heart failure (24% vs. 16%, p=0.009). Killip 3-4 was also more common (22% vs. 4.2%, p<0.001). Patients with CRP and WBC at or above the median and an ‘intermediate-high’ ORBI score faced a higher risk of one-year mortality (HR CRP: 5.23, 95%CI: 2.59-10.6, p<0.001 and HR WBC: 6.15, 95%CI 3.04-12.4, p<0.001, figure 1). Conclusions An ‘intermediate-high’ ORBI risk score in STEMI patients was associated with significantly higher odds of increased levels of systemic inflammation within 0-96 hours of admission. An intermediate-high score combined with an elevated inflammatory response was associated with a five to six-fold increased risk of one-year mortality.Fig. 1:KM-plot, 1 year (scale is 1-0.9)

Drug-induced acute tubulointerstitial nephritis: Serial C-reactive protein measurements might predict the course of acute kidney injury.

Elevated C-reactive protein (CRP) was proposed as a biomarker instead of renal biopsy in drug-induced acute tubulointerstitial nephritis (D-ATIN) in adults. However, there is no study in which patients were followed up with serial CRP without kidney biopsy. We evaluated the significance of CRP levels in predicting the clinical course of D-ATIN in children. Children with a clinical diagnosis of D-ATIN were evaluated for sex, age, symptoms, offending drug(s), latent period after exposure, blood pressure, urine output, urinalysis, eosinophiluria, urine albumin/total protein, serum creatinine, and CRP at presentation. In addition, serial CRP and creatinine levels were recorded daily until discharge and thereafter. Correlations of CRP with creatinine and of peak CRP with creatinine normalization time were evaluated. There were 13 patients (8 female, median age 15 years). None had oliguria or hypertension. Median CRP and creatinine at presentation were 36 mg/L and 1.6 mg/dL, respectively. Median times to peak CRP and creatinine were 6 and 7 days after drug exposure, respectively. The decrease in CRP preceded the fall in creatinine. Median CRP and creatinine normalization times after their peaks were 5 and 14 days, respectively. None required renal biopsy or corticosteroid treatment. CRP was correlated with creatinine throughout the study period. However, peak CRP was not correlated with creatinine normalization time. CRP was increased at presentation and decreasing CRP predicted favorable outcome. Renal biopsy and corticosteroid treatment could be postponed safely in these children.

The Role of Inflammation in Early Left Ventricular Thrombus Formation Following ST-Elevation Myocardial Infarction-A Matched Case-Control Study.

There is limited data on the association between inflammation and the formation of early left ventricular thrombus (LVT) following ST-elevation myocardial infarction (STEMI). This study aimed to explore the predictive value of several inflammatory biomarkers for LVT formation following STEMI. Our cohort included 2534 consecutive patients admitted to the cardiac intensive care unit (CICU) with STEMI. The final analysis included 51 patients with LVT and 102 patients without LVT, matched for age, sex, anterior infarct and ejection fraction. Upon admission, patients with LVT had higher white blood cell counts (WBC) (12.8 ± 7 vs. 12.4 ± 4 ×103/µL, p = 0.01), higher absolute neutrophil counts (10.5 ± 4 vs. 8.6 ± 4 ×103/µL, p = 0.003), neutrophil-to-lymphocyte ratio (8.2 ± 6 vs. 4.8 ± 4, p = 0.04), and C-reactive protein (CRP) levels (35.9 ± 62 vs. 18.6 ± 40 mg/L, p = 0.04). Peak values for WBC and CRP were also higher in the LVT group (17.8 ± 8 vs. 14.6 ± 5 ×103/µL, p = 0.003 and 95.8 ± 82 vs. 64.2 ± 76 mg/L, p = 0.02, respectively). In univariate regression analysis, WBC upon admission (OR: 1.12, 95% CI: 1.02-1.21, p = 0.02), peak WBC (OR: 1.09, 95% CI: 1.02-1.17, p = 0.009), neutrophil count upon admission (OR: 1.15, 95% CI: 1.04-1.26, p = 0.004), and peak CRP (OR: 1.01, 95% CI: 1-1.01, p = 0.03) predicted LVT formation, which was also evident in multivariate regression models. WBC and neutrophil counts upon admission, as well as peak WBC and CRP, have additional predictive value for LVT formation following STEMI, beyond classical risk factors.

Clinical presentation and management of enterovirus and parechovirus infection in children: A single-centre study in regional Australia.

This study aims to analyse the clinical presentation caused by enterovirus (EV) and/or human parechovirus (HPeV) infection in children, as well as the management of such cases admitted to a regional hospital in Australia. Retrospective study reviewing medical records. Single hospital in regional Australia. All children under 18 years admitted over the 5-year period beginning from 1 January 2017 with confirmed EV and/or HPeV infection. Cases with clinically insignificant EV/HPeV isolation were excluded. Data collected included demographic data, signs and symptoms present, specimens of EV/HPeV isolation, co-occurring pathogens, peak C-reactive protein (CRP), antibiotic therapy, discharge diagnosis and follow-up after discharge. Overall, 27 patients fulfilled the inclusion criteria; 81.5% of the patients were ≤3 months of age with a median of 2 months (interquartile range 1-3); 74.1% were males. The most common clinical features were a fever ≥38°C and irritability/lethargy/high-pitched cry. 29.6% of the patients had co-occurring pathogens detected, and a CRP ≤10 mg/L was observed in 77.8% of cases. All but two children were treated with antibiotics while awaiting polymerase chain reaction results. The most common discharge diagnosis was meningitis. In all, 74.1% of the children attended follow-up appointments. EV and HPeV should be considered as a possible aetiology of fever and irritability/lethargy/high-pitched cry in children under 3 months.

Rhabdomyolysis-related acute kidney injury in patients with COVID-19.

Viral and bacterial infections may be complicated by rhabdomyolysis, which has a spectrum of clinical presentations ranging from asymptomatic laboratory abnormalities to life-threatening conditions such as renal failure. Direct viral injury as well as inflammatory responses may cause rhabdomyolysis in the course of coronavirus disease 2019 (COVID-19). When presented with acute kidney injury (AKI), rhabdomyolysis may be related to higher morbidity and mortality. To compare rhabdomyolysis-related AKI with other AKIs during COVID-19. A total of 115 patients with COVID-19 who had AKI were evaluated retrospectively. Fifteen patients had a definite diagnosis of rhabdomyolysis (i.e., creatine kinase levels increased to > 5 times the upper normal range with a concomitant increase in transaminases and lactate dehydrogenase). These patients were aged 61.0 ± 19.1 years and their baseline creatinine levels were 0.87 ± 0.13 mg/dL. Patients were treated according to national COVID-19 treatment guidelines. They were compared with patients with COVID-19 who had AKI due to other reasons. For patients with rhabdomyolysis, creatinine reached 2.47 ± 1.17 mg/dL during follow-up in hospital. Of these patients, 13.3% had AKI upon hospital admission, and 86.4% developed AKI during hospital follow-up. Their peak C-reactive protein reached as high as 253.2 ± 80.6 mg/L and was higher than in patients with AKI due to other reasons (P < 0.01). Peak ferritin and procalcitonin levels were also higher for patients with rhabdomyolysis (P = 0.02 and P = 0.002, respectively). The mortality of patients with rhabdomyolysis was calculated as 73.3%, which was higher than in other patients with AKI (18.1%) (P = 0.001). Rhabdomyolysis was present in 13.0% of the patients who had AKI during COVID-19 infection. Rhabdomyolysis-related AKI is more proinflammatory and has a more mortal clinical course.

Risk Factors for Persistent Staphylococcus aureus Bacteremia in Children.

Staphylococcus aureus is a leading cause of pediatric bacteremia. Persistent S. aureus bacteremia (SAB) is associated with increased morbidity and mortality in adults and children. Risk factors for S. aureus bacteremia have been well established, but there is a limited understanding of the factors that contribute to the development of persistent SAB in children. This is a single-center retrospective secondary analysis of a prospective observational study of pediatric patients hospitalized with S. aureus infection over a 3.5-year period at a large, quaternary, children's hospital. Two hundred fifty-nine children with confirmed S. aureus infection were enrolled in the study. Sixty-five of these were found to have bacteremia, with 28 (43%) developing persistent bacteremia. Patients with persistent SAB were culture-positive for a median of 3.5 days compared with 1 day for those without (P ≤ 0.001). Children with persistent SAB were more likely to have an identified osteoarticular source of infection (93%, n = 26 vs. 62%, n = 23; P = 0.008) and had a shorter median duration to culture positivity than those without persistent SAB (16 hours vs. 20 hours; P ≤ 0.001). In addition, children with persistent SAB had higher median values of presenting erythrocyte sedimentation rate, peak erythrocyte sedimentation rate, presenting C-reactive protein and peak C-reactive protein. Not surprisingly, hospital length of stay was longer in children with persistent SAB compared with those without. These findings suggest that a shorter time to culture positivity, osteoarticular infection, and higher presenting and peak values for select inflammatory markers are potential risk factors for persistent SAB in children.

Early Metabolomic and Immunologic Biomarkers as Prognostic Indicators for COVID-19.

This prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19-89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: -3.30 to -8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.

Technical feasibility and oncological outcomes of robotic esophagectomy compared with conventional thoracoscopic esophagectomy for clinical T3 or T4 locally advanced esophageal cancer: a propensity-matched analysis.

Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE.

A novel prediction model for myocardial fibrosis in patients suspected of myocarditis

Purpose: This study aimed at establishing a predictive method that consists of clinical, electrocardiographic (ECG), and laboratory parameters for myocardial fibrosis, especially as detected on cardiac magnetic resonance imaging (CMRI), in patients examined with suspicion of myocarditis.&#x0D; Materials and Methods: This study is a retrospective, single-centre study that includes patients admitted to our centre with suspected myocarditis between March 2020 and November 2023. Participants were categorised into two groups (myocardial fibrosis positive and myocardial fibrosis negative), and a detailed comparison of comorbidities, ECG changes, and laboratory parameters was performed. Multivariate analysis was conducted to identify independent predictors of myocardial fibrosis. A nomogram was constructed using the coefficients from the multivariate analysis to estimate the probability of myocardial fibrosis presence based on key predictors. &#x0D; Results: This study included 98 participants with a median age of 30 years, predominantly male (80.6%), with 14.3% having hypertension, 8.2% having diabetes mellitus, and 10.2% being smokers. The myocardial fibrosis-negative group exhibited higher levels of left ventricular ejection fraction and lymphocyte count. Conversely, the myocardial fibrosis-positive group showed higher levels of ECG changes at admission, peak C-reactive protein (CRP), CRP velocity, peak troponin, N-terminal pro-brain natriuretic peptide (NT-proBNP), monocytes, and platelets (PLT). In multivariate analysis, PLT, lymphocyte, monocyte, peak troponin, and ECG changes were identified as independent predictors of myocardial fibrosis. Receiving operating characteristic (ROC) curve analysis showed the model's diagnostic accuracy for predicting myocardial fibrosis (area under the ROC (AUC): 0.959, 95% confidence interval (CI), and p

Clinical Utility of Repeat Magnetic Resonance Imaging Studies Among Children With Acute Hematogenous Osteomyelitis.

There is limited guidance for whether repeat magnetic resonance imaging (MRI) studies are clinically impactful among children with acute hematogenous osteomyelitis (AHO) who fail to improve as expected. This study aimed to determine whether repeat MRIs changed management among children with AHO and identify clinical characteristics predictive of which patients benefit from repeat MRIs. Children admitted to a quaternary care pediatric hospital with AHO were identified during a 9-year period. Patients with chronic symptoms, non-hematogenous infections, or significant contributing comorbidities were excluded. Medical records were retrospectively reviewed for all MRIs performed 3 weeks before admission to 24 months after discharge. An MRI was considered clinically impactful if it identified a new infectious process (eg, abscess not seen on the initial MRI) or if it resulted in surgical intervention within 24 hours. Bivariable comparisons of categorical variables were performed, and multivariable logistic regression was used to assess the clinical factors of impactful repeat MRIs. Among the 239 included patients, 41 (17%) had more than 1 MRI performed during their clinical course, the majority of whom (53.7%) had a repeat MRI that impacted care. Patients who underwent repeat MRIs had longer hospitalizations (7 vs. 5 d, P <0.01), were more likely to have C-reactive protein (CRP) levels >20mg/dL (41% vs. 10%, P <0.01), and were more likely to have a delayed transition to oral antimicrobials (8.4 vs. 3.3d, P <0.01). Peak CRP >20mg/dL and prolonged bacteremia were found to be associated with increased odds of having an impactful repeat MRI, with adjusted odds ratios of 3.9 ( P =0.007) and 3.4 ( P =0.03), respectively. When used judiciously among ill children with complicated AHO, repeat MRI can be clinically impactful. Prospective studies are needed to better define which children with AHO benefit from repeat MRI. Level II evidence-this is a retrospective cohort study interested in determining the clinical utility of repeat magnetic resonance imaging studies for children with osteomyelitis.

All-cause and Infection-attributable Mortality Amongst Adults With Bloodstream Infection-a Population-based Study.

Bloodstream infections (BSIs) are common, life-threatening infections. However, it remains unclear whether deaths following BSIs are primarily from uncontrolled infection or underlying comorbidities. We aimed to determine the overall mortality, infection-attributable mortality, and causes of death for four leading BSI pathogens. This retrospective cohort study was conducted within the Secure Anonymized Information Linkage Databank, containing anonymized population-scale electronic health record data for Wales, UK. We included adults with Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, and Staphylococcus aureus BSI between 2010 and 2022 using linked data from Public Health Wales and the Office for National Statistics. Thirty-day all-cause and sepsis-specific mortality, as a proxy for infection-attributable mortality, were compared using Cox proportional hazards and competing risk regression, respectively. We identified 35 691 adults with BSI (59.6% E coli). Adjusted analyses revealed that all organisms had a higher 30-day mortality versus E coli with Pseudomonas aeruginosa the highest (hazard ratio, 1.96 [1.76-2.17], P < .001). Cancer was the leading cause of death following BSIs for all organisms, particularly deaths occurring between 30 and 90 days (35.9%). A total of 25.5% of deaths within 30 days involved sepsis. Methicillin-resistant Staphylococcus aureus was associated with the highest sepsis mortality versus E coli (hazard ratio, 2.56 [2.10-3.12], P < .001). Peak C-reactive protein was positively associated with increased sepsis mortality (P < .001). This population-level study challenges the assumption that most deaths following BSIs are directly attributable to uncontrolled infection, particularly subacutely more than 30 days from BSI. Our findings underscore the need for reevaluating clinical trial design and developing better preventive strategies for BSIs.

Construction of a risk prediction model for bronchiolitis obliterans in children with refractory Mycoplasma pneumoniae pneumonia

To explore the establishment of a risk prediction model for concurrent bronchiolitis obliterans (BO) in children with refractory Mycoplasma pneumoniae pneumonia (RMPP). A retrospective study included 116 RMPP children treated in the Department of Pediatrics of Xiangya Changde Hospital from June 2021 to December 2023. Eighty-one cases were allocated to the training set and thirty-five cases to the validation set based on a 7:3 ratio. Among them, 26 cases in the training set developed BO, while 55 did not. The multivariate logistic regression was used to select variable factors for constructing the BO risk prediction model. Nomograms were drawn, and the receiver operating characteristic (ROC) curve was used to assess the discriminative ability of the model, while calibration curves and Hosmer-Lemeshow tests evaluated the model's calibration. Multivariate logistic regression analysis indicated that several factors were significantly associated with concurrent BO in RMPP children, including length of hospital stay, duration of fever, atelectasis, neutrophil percentage (NEUT%), peak lactate dehydrogenase (LDH), ferritin, peak C reactive protein (CRP), oxygenation index (PaO2/FiO2), ≥2/3 lung lobe consolidation, pleural effusion, bronchial mucous plugs, bronchial mucosal necrosis, and arterial oxygen partial pressure (PaO2) (P<0.05). ROC curve analysis for the training set indicated an area under the curve of 0.904 with 88% sensitivity and 83% specificity; the validation set showed an area under the curve of 0.823 with 76% sensitivity and 93% specificity. The Hosmer-Lemeshow test's Chi-square values for the training and validation sets were 2.17 and 1.92, respectively, with P values of 0.221 and 0.196, respectively. The risk prediction model for BO in RMPP children based on logistic regression has good performance. Variables such as length of hospital stay, duration of fever, atelectasis, peak LDH, peak CRP, NEUT%, ferritin, ≥2/3 lung lobe consolidation, pleural effusion, bronchial mucous plugs, bronchial mucosal necrosis, PaO2/FiO2, andPaO2 can be used as predictors.

COVID-19 and myocardial injury: Targeting elevated biomarkers for potential novel therapies

BackgroundThe prevalence of COVID-19 as the primary diagnosis among hospitalized patients with myocardial injury has increased during the pandemic and targeting elevated oxidant stress and inflammatory biomarkers may offer a potential role for novel therapies to improve outcomes. MethodsAt a single VA Medical Center from January 1 through December 31, 2021, troponin assays from patients being evaluated in the Emergency Room for consideration of admission were analyzed and peak levels from each patient were considered abnormal if exceeding the Upper Reference Limit (URL). Among admitted patients with an elevated troponin level, ICD-10 diagnoses were categorized, biomarker elevations were recorded, and independent predictors of death in patients with COVID-19 were determined at a median of 6-months following admission. ResultsOf 998 patients, 399 (40 %) had a negative troponin and were not included in the analysis. Additional patients with an elevated troponin were also excluded, either because they were not admitted (n = 68) or had a final diagnosis of Type 1 MI (n = 117). Of the remaining 414 patients with an elevated peak troponin, COVID-19 was the primary diagnosis in 43 patients (10 %) and was the 4th most common diagnosis of patients admitted with myocardial injury behind congestive heart failure, sepsis, and COPD or pneumonia. At a median of 6-months following admission, 18 (42 %) of the COVID-19 patients had died and independent predictors of death (Odd Ratio: Confidence Intervals) were age (1.18: 1.06‒1.37), Troponin level (Log 10 transformed) (16.54: 2.30‒266.65) and C-Reactive Protein (CRP) (1.30: 1.10‒1.65). ConclusionsNewly diagnosed COVID-19 during the pandemic was a common cause of elevated troponin in hospitalized patients without a Type 1 MI. Age, peak troponin level and peak CRP level were independent predictors of poor outcomes and suggest a need to target these cardiac biomarkers, potentially with novel antioxidant or anti-inflammatory therapies.

Risk Factors and Outcomes for Hematotoxicity Following Tisagenlecleucel for Pediatric B-Acute Lymphoblastic Leukemia

Background: Hematotoxicity following chimeric antigen receptor (CAR) T-cell therapy is increasingly recognized as a distinct adverse event. The CAR-HEMATOTOX score has been developed as a prognostic tool for subsequent development of prolonged cytopenias in adults with lymphoma. However, risk factors in children and young adults (CAYA) with B-acute lymphoblastic leukemia (B-ALL) receiving CAR T cell therapy are less well-defined. We sought to describe incidence, outcomes, and risk factors for prolonged severe neutropenia in CAYA treated with tisagenlecleucel. Methods: This was a multi-institutional retrospective study involving CAYA ≤26 years of age with B-ALL treated with tisagenlecleucel who underwent leukapheresis and manufacturing between August 2017 and March 2020, with data collected through the Pediatric Real World CAR Consortium (PRWCC). Of 185 patients infused, 41 patients were excluded from analysis due to missing data (n=10), refractory disease/death from leukemia (n=27) or non-relapse mortality (n=4) prior to day 35 post-CAR T. Severe prolonged neutropenia was defined as absolute neutrophil count (ANC) &amp;lt;500 cells/mm 3 for ≥30 days. For those with severe neutropenia pre-CAR T, day 0 of severe neutropenia was considered the day of CAR T-cell infusion. Statistical analyses included comparisons using Mann-Whitney and Fisher's exact tests, receiver operating characteristic (ROC) curves to determine cut points with optimal sensitivity and specificity, univariate logistic regression, Kaplan-Meier curves for recovery from neutropenia, overall survival (OS) and relapse free survival (RFS). Results: Of 144 patients, 23 (15.9%) met the definition of severe prolonged neutropenia and 121 (84%) did not. For lymphodepleting chemotherapy, 139 (96.5%) received standard fludarabine (30mg/m 2/dose x 4) and cyclophosphamide (500mg/m 2 x 2). Pre- and post-infusion characteristics are shown in Table 1. Pre-infusion, higher pre-infusion C-reactive protein (CRP), ferritin, bone marrow disease burden, and lower ANC and platelet counts were associated with severe prolonged neutropenia. Post-infusion, any grade cytokine release syndrome (CRS), severe CRS, CRS with hemophagocytic lymphohistiocytosis (HLH)-like manifestations, any grade neurotoxicity, peak CRP and ferritin, use of tocilizumab and steroids, and presence of infections within 30 days were associated with severe prolonged neutropenia. With univariate logistic regression, pre-infusion inflammatory markers, cytopenias, and bone marrow disease burden associated with severe prolonged neutropenia and of these, disease burden &amp;gt;15% had the highest odds ratio (Figure 1). Post-infusion infections and inflammatory toxicities, particularly CRS with HLH-like toxicities, as well as peak CRP, and peak ferritin, were associated with severe prolonged neutropenia. Peak ferritin &amp;gt;3800 ng/ml had the highest odds ratio. In patients with severe prolonged neutropenia, OS was inferior (p&amp;lt;0.0001) and RFS trended towards being inferior (p=0.052), compared to those without. Groups with or without severe prolonged neutropenia were also subdivided into &amp;gt;15% or ≤15% pre-infusion bone marrow disease burden subgroups. OS was similar between patients without severe prolonged neutropenia that had &amp;gt;15% or ≤15% pre-infusion disease burden, but patients with severe prolonged neutropenia and &amp;gt;15% disease burden had inferior OS, suggesting prolonged severe neutropenia may have independent prognostic value. Conversely, RFS was inferior in patients in the subgroups with &amp;gt;15% disease burden compared to those with ≤15%, regardless of occurrence of severe prolonged neutropenia. Discussion/Conclusions: We describe incidence, risk factors and outcomes for the development of severe prolonged neutropenia in CAYA with B-ALL following tisagenlecleucel. While there are similarities in risk factors with the CAR-HEMATOTOX score that has been validated in adults, in CAYA with B-ALL high disease burden pre-infusion and severe inflammation post-infusion were identified as the strongest risk factors for prolonged neutropenia. Identification of risk factors unique to the CAYA B-ALL population allows for tailored risk mitigation in higher risk patients and may help improve outcomes in CAYA at increased risk of prolonged severe neutropenia following tisagenlecleucel.

Dynamics of C-reactive protein level after orthopedic surgeries

BackgroundOnly two studies present the results of the dynamics of C-reactive protein (CRP) after a large number of orthopedic surgeries. The aim of the study was to investigate the dynamics of CRP levels and determine the influence of various factors on the CRP level after various orthopedic surgeries using big data tools. MethodsA total of 16042 operated patients were included in the study. ResultsThe tendency of peak values to increase by 2–3 days after surgery with subsequent decrease was the same in all subgroups without surgical site infections (SSI). In patients with SSI, the higher preoperative CRP level changed to a peak on day 3 after surgery with a subsequent drop and increase after day 6 in case of probably unsuccessful sanitation. The peak value of CRP significantly correlates with the duration of surgery (r = 0.1072, p < 0,0001). Older patients tend to exhibit higher CRP value (r = 0.2219, p < 0.001). The peak values of CRP in women were significantly greater than those in men. ConclusionIn cases without SSI, the peak of CRP values occurs on the second or third day after surgery, a secondary increase in CRP levels may indicate a risk of complications. The peak CRP value correlates with the duration of surgery. In clinical practice, relationship between gender, age and the level of CRP should not be one of the indicators influencing the assessment of the risk of a threat to the patient's health, since the results of various studies are contradictory.

D-dimers as a prognostic plasma biomarker in patients with a first episode of acute pericarditis

Abstract Introduction/Background At present the impact of plasma biomarkers in predicting outcome of patients with isolated acute pericarditis (AP) has been poorly investigated. Purpose This study aimed to investigate the prognostic role of fibrin d-dimers (DD), an easily obtainable biomarker, in patients with AP. Methods This is a prospective clinical study enrolling 265 consecutive patients hospitalized between September 2010 and May 2019 with a first episode of AP. At baseline demographics, clinical features, laboratory, imaging findings and treatment were recorded. All patients were followed-up for a minimum period of 18 months. DD measurement at presentation was at the discretion of the examining physician since their measurement is not performed as per protocol in patients with suspected AP. End-points included cardiac tamponade, new-onset atrial fibrillation, pericardial drainage, recurrent/constrictive pericarditis and death. Results DD were measured in 165 out of 265 patients (62.3%, median levels 1456 ng/ml) at presentation. Among them 121 patients (73.3%) presented with elevated age-adjusted DD levels. Patients with elevated DD compared to those without depicted a higher rate of pleural (69.4%, vs 38.6%, p&amp;lt;0.001) and pericardial effusions (89.3% vs 72.7%, p=0.009). Concerning baseline laboratory values, patients with elevated DD presented with lower hematocrit and higher platelet counts, admission and peak C-reactive protein levels, as well as serum Glutamic pyruvic transaminase (SGPT) (Figure 1). In terms of outcome patients with elevated DD depicted a trend towards a greater prevalence of pericardial tamponade vs those without (14.9% vs 4.5% respectively, p=0.07). No significant difference was observed in the remainder of the endpoints during a median follow-up of 51 months. Notably, 43.8% of patients with elevated DD underwent computed tomography pulmonary angiography (CTPA), with all of the examinations being negative for pulmonary embolism. Conclusion Elevated DD plasma values in AP patients is a marker of high inflammatory burden. A trend of this plasma biomarker elevation and in-hospital cardiac tamponade was also observed. DD elevation in AP patients should be interpreted with caution and should not prompt unnecessary investigations (such as CTPA).

Phosphorus Disruption Is Associated with the Incidence and Severity of Neurotoxicity Symptoms in CD19-Targeted CAR-T Cell Therapy: A Pooled Clinical Trial Analysis

Background Hypophosphatemia due to increased cell metabolic activity as seen in refeeding syndrome and sepsis, has a similar neurologic presentation to immune effector cell-associated neurotoxicity syndrome (ICANS), an associated risk of CAR-T cell therapy. CAR-T patients who develop ICANS are observed to have a higher incidence and more severe degrees of hypophosphatemia (Tang et al, 2022). We further explored the association of hypophosphatemia and other electrolyte disturbances with ICANS incidence across pooled CAR-T clinical trial patients to assess how serum electrolytes correlated with risk of ICANS. Methods We analyzed 593 patients with relapsed/refractory B-cell acute lymphoblastic leukemia or non Hodgkin's lymphoma, with ICANS (n=325), and without ICANS (n=268) treated with CD19-targeted CAR-T cell therapy across pooled clinical trial data from the Medidata Enterprise Data Store. Patients were grouped by ICANS status. A Fisher exact test was performed for categorical variables. A Mann-Whitney was performed for numerical variables. Variables of interest were baseline patients characteristics (age, gender, indication) and ICANS status. Common lab values investigated were nadir values and time to nadir for phosphate (Phos), magnesium (Mg), calcium (Ca), and potassium (K), peak value for C-reactive protein (CRP), and creatinine (Cr) at the time of infusion. To assign a hypo- phosphatemia, -kalemia, -magnesemia and -calcemia status to each patient, we used thresholds of &amp;lt;2 mg/dL, 3.5 mmol/L, 1.5 mg/dL and 2.0 mmol/L respectively. We performed a univariable logistic regression with ICANS status as the outcome variable and the following: Baseline value at infusion for Mg, K, Phos, Ca, CrNadir values between day 0 and 14 for Mg, K, Phos, Ca, CrSlope (between baseline and nadir) for Mg, K, Phos, Ca, CrPeak CRP, Cr and Urate between day 0 and 14 The odds ratios were calculated. Kaplan Meier curves were plotted. The log rank test was performed for time to event of ICANS, grouped by hypo- phosphatemia, -kalemia, -magnesemia and -calcemia status. We performed an analysis on the effect of the preemptive use of electrolyte replacement. We defined preemptive use as any electrolyte replacement given to patients either before the occurrence of ICANS or if patients did not get ICANS. For those with hypophosphatemia, we examined the preemptive use of electrolyte replacements for any electrolyte excluding Phos and any electrolyte with Phos. For those 2 groups we compared the rates of ICANS. Results CRS, and hypo- phosphatemia, -kalemia, -magnesemia and -calcemia status were statistically significantly different between ICANS and no ICANS groups. When looking at the nadir values, these 4 electrolyte disturbances were also statistically significant, with lower values associated with ICANS. For the time to nadir, only K was significant and higher for the ICANS group. Peak CRP was also higher for patients with ICANS, but did not meet the 0.05 threshold to be statistically significant. For the univariate logistic regression, variables positively associated with ICANS and significant were peak values for creatinine and CRP, OR of 3.8 (1.6-9.2) and 2.1 (0.9 - 5.0) respectively. Variables negatively associated with ICANS and significant were nadir values for Phos (OR 0.3 (0.1 - 0.8)), K (OR 0.2 (0.1-0.7)), Ca (OR 0.2 (0.1-0.6)), Mg (OR 0.17(0.1-0.5)) and urate (0.3(0.1-1)), and slope for Mg (OR 0.0 (0.0-0.2)). When plotting the Kaplan Meier curves, ICANS seems to develop sooner for patients with either hypo- phosphatemia, -kalemia, -magnesemia or -calcemia and the log rank test showed to be statistically significant (Figure 1). Among the patients with hypophosphatemia, the use of Phos as part of electrolyte replacement reduces the ICANS rate: 52% (0.39-0.65) versus 71% (0.58-0.84) for the electrolyte replacement without Phos. Conclusion Our data demonstrate that ICANS incidence is associated with disruptions in serum phosphorus levels, and that supplementation of phosphorus is able to mitigate the incidence of ICANS as well. Monitoring phosphorus may serve as a useful biomarker for ICANS, while goal directed phosphorus supplementation may serve as an inexpensive and readily available means to treat or prevent ICANS. Prospective studies with goal-directed phosphorus repletion are necessary to further study the therapeutic impact of electrolyte supplementation on ICANS incidence and severity.

Cladribine and Cyclophosphamide Lymphodepletion Prior to Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma

Introduction : Chemotherapy-based lymphodepletion (LD) with fludarabine and cyclophosphamide (Flu/Cy) is a standard preparatory step for chimeric antigen T-cell (CAR T) therapy and its importance for optimal CAR T expansion and efficacy is well-established. An international Flu shortage required our center and others to utilize alternative agents for LD or risk interruption in patient therapy. When unable to utilize Flu as part of the LD regimen for patients with relapsed/refractory large B-cell lymphoma (RR LBCL) that required CD19-directed CAR T as a standard of care therapy, our center adopted a standard operating procedure to substitute Flu with Cladribine (Clad), an alternate purine analogue with similar chemical structure, as part of Clad/Cy LD prior to axicabtagene ciloleucel (axi-cel). Here we report outcomes in these patients. Methods : We performed a retrospective, single-center analysis of consecutive RR LBCL patients who received Clad/Cy LD prior to axi-cel at Moffitt Cancer Center between 8/2022 and 1/2023, and compared outcomes to a historical cohort, consisting of 144 Flu/Cy axi-cel LBCL patients treated between 11/2017 and 2/2021. The Clad/Cy LD regimen, given as standard care, maintained Cy at 500 mg/m 2 and substituted Flu 30 mg/m 2 with Clad 5 mg/m 2/day with both agents given on Days -5, -4, and -3. For efficacy we compared best overall response (BOR) at 90 days and progression-free survival (PFS) comparing the two LD regimens. For safety we compared the rates of cytokine release syndrome (CRS) and neurotoxicity as graded by ASTCT criteria. We also performed correlative analyses exploring absolute lymphocyte count (ALC) kinetics, axi-cel expansion by quantitative PCR, and changes in the cytokine milieu as assessed by the enzyme-linked immunosorbent Ella™ system (Bio-Techne, Oxford, UK) at serial time points following infusion. Results : 23 patients received Clad/Cy LD followed by axi-cel for R/R DLBCL. Baseline characteristics of the study cohort based on LD are shown in the Table. Compared to the historical cohort, Clad/Cy patients received axi-cel after fewer lines of treatment (median 2 [range, 1-3] vs 2 [range, 1-7]; Rank-Sum test p&amp;lt;0.01) and had a greater proportion of relapsed (not refractory) disease (52% vs 22%, p&amp;lt;0.01). The 90-day BOR did not differ between the Clad/Cy and Flu/Cy groups (79% vs 84%; P=0.54) with a similar distribution of complete (22% vs 24%) and partial responders (57% vs 60%). With a median follow-up of 4.6 (95% CI, 3.2-6.2) months for Clad/Cy and 24.2 (95% CI, 21.5-25.8) months for Flu/Cy cohorts, PFS was similar (Figure 1B, Log-Rank p=0.84). Rates of CRS grade ≥ 2 were higher in the Clad/Cy cohort (70% vs 44%; p=0.02), but no CRS grade ≥ 3 was observed in the Clad/Cy compared to 13 (9%) of Flu/Cy patients, including three grade 5 events. Neurotoxicity ≥ grade 2 (44% vs 43%; p=0.77) and peak C-reactive protein levels (15 vs Flu/Cy 12; p=0.3) did not differ for the Clad/Cy and Flu/Cy cohorts. Both regimens had comparable peak axi-cel copy numbers (Clad/Cy 7.9 × 10 6 vs Flu/Cy 5.1 × 10 6 copies/µg). Clad/Cy resulted in a predictable decrease in the ALC from Day -5 to Day 0, but a less profound degree of lymphopenia on Day 0 (0.04 vs 0.02; p&amp;lt;0.01) with ALC 0 achieved later (Day +2 [IQR, +1 to +4] vs Day +1 [IQR, -1 to +2] for Flu/Cy). The median magnitude of change of cytokine levels (Delta = Day -5 - Day 0 concentration) differed between Clad/Cy and Flu/Cy for all tested analytes except IL-6 (3.4 vs 4.6 pg/mL for Flu/Cy; p=0.29). Clad/Cy resulted in greater increases in IL-2 (0.5 vs 0.2 for Flu/Cy; p=0.01) and GM-CSF (2.0 vs 0.9 for Flu/Cy; p=0.03), whereas Flu/Cy had higher IL-15 (31.4 vs 16.8 for Clad/Cy; p&amp;lt;0.01). Interestingly, IFN-γ tended to increase in Clad/Cy and to decrease in Flu/Cy (1.2 vs 0.0; p=0.01). Conclusions : Clad/Cy LD is feasible for axi-cel conditioning in the treatment of RR LBCL. Although it resulted in less profound LD on the day of CAR T infusion, a later ALC nadir, and a different cytokine milieu compared to Flu/Cy, it was associated with similar peak axi-cel expansion and, at short term follow-up, there appears to be similar initial efficacy and toxicity. Future analyses focusing on response durability and long-term toxicities such as infections and post-CAR T cytopenias are warranted.

CT findings of 144 in-hospital patients with influenza pneumonia: A retrospective analysis

Patients with influenza infection during their period of admission may have worse computed tomography (CT) manifestation according to the clinical status. This study aimed to evaluate the CT findings of in-hospital patients due to clinically significant influenza pneumonia with correlation of clinical presentations. In this retrospective, single center case series, 144 patients were included. All in-hospital patients were confirmed influenza infection and underwent CT scan. These patients were divided into three groups according to the clinical status of the most significant management: (1) without endotracheal tube and mechanical ventilator (ETTMV) or extracorporeal membrane oxygenation (ECMO); (2) with ETTMV; (3) with ETTMV and ECMO. Pulmonary opacities were scored according to extent. Spearman rank correlation analysis was used to evaluate the correlation between clinical parameters and CT scores. The predominant CT manifestation of influenza infection was mixed ground-glass opacity (GGO) and consolidation with both lung involvement. The CT scores were all reach significant difference among all three groups (8.73±6.29 vs 12.49±6.69 vs 18.94±4.57, p<0.05). The chest CT score was correlated with age, mortality, and intensive care unit (ICU) days (all p values were less than 0.05). In addition, the CT score was correlated with peak lactate dehydrogenase (LDH) level and peak C-reactive protein (CRP) level (all p values were less than 0.05). Concomitant bacterial infection had higher CT score than primary influenza pneumonia (13.02±7.27 vs 8.95±5.99, p<0.05). Thin-section chest CT scores correlated with clinical and laboratory parameters in in-hospital patients with influenza pneumonia.