An exploratory analysis of routine ferritin measurement upon admission and the prognostic implications of low-grade ferritinemia during inflammation.

BACKGROUND: Serum ferritin is usually measured in the presence of anemia or in suspected iron overload syndromes. Ferritin is also an acute-phase protein that is elevated during systemic inflammation. However, the prognostic value of routinely measuring ferritin upon admission to a medical facility is not clear. Therefore, we examined the association between ferritin concentrations measured at the time of hospital admission with 30-day and long-term mortality. METHODS: We obtained routine ferritin measurements taken within 24 hours of admission in 2,859 patients hospitalized in an internal medicine department. Multiple clinical and laboratory parameters were used to assess the association between ferritin and overall mortality during a median follow-up of 15 months (interquartile range [IQR] 8-22). RESULTS: Ferritin levels were associated with increased 30-day mortality rates (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.03-1.06) for each 100 ng/ml increase. Patients with intermediate (78-220 ng/ml) and high (>221 ng/ml) ferritin concentrations (2nd and 3rd tertiles) had higher 30-day mortality rates even after adjustment for age, sex, and existing co-morbidities (OR 2.05, 95% CI 1.70-2.5). Long-term overall mortality rates demonstrated a similar pattern across ferritin tertiles (hazard ratio [HR] 1.54, 95% CI 1.39-1.71). CONCLUSIONS: Routine admission ferritin concentrations are linearly and independently correlated with excess mortality risk in hospitalized patients, even those with apparently "normal" ferritin concentrations (<300 mg/ml). Thus, low-grade ferritinemia might not be an innocent finding in the context of the inflammatory response. Its potential biological and therapeutic implications warrant future research.

The CRP troponin test (CTT) stratifies mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI).

INTRODUCTION: The C-reactive protein (CRP)-troponin-test (CTT) comprises simultaneous serial measurements of CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. We sought to test its ability to stratify the short- and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI). METHODS: We examined 1,675 patients diagnosed with NSTEMI on discharge who had at least two successive measurements of combined CRP and cardiac troponin within 48 h of admission. A tree classifier model determined which measurements and cutoffs could be used to best predict mortality during a median follow-up of 3 years [IQR 1.8-4.3]. RESULTS: Patients with high CRP levels ( > 90th percentile, >54 mg/L) had a higher 30-day mortality rate regardless of their troponin test findings (16.7% vs. 2.9%, p < 0.01). However, among patients with "normal" CRP levels ( < 54 mg/L), those who had high troponin levels ( > 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate than patients with normal CRP and troponin concentrations (7% vs. 2%, p < 0.01). The CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and comorbidities (HR = 2.28 [95% CI 1.56-3.37], p < 0.01 for patients with high troponin and high CRP levels). CONCLUSIONS: Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially those with "normal" CRP levels. The CTT could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI and identify patients who could benefit from novel anti-inflammatory therapies.

Estimated C-reactive protein (CRP) velocity for rapidly distinguishing bacterial from other etiologies in children presenting to emergency department with remarkably elevated CRP levels.

The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults. This study aims to investigate the association between eCRPv and bacterial etiologies among pediatric patients with very elevated CRP levels. We conducted a retrospective analysis of patients under 18 years of age who had been admitted to our Pediatric Emergency Department from 2018 to 2020 with a fever and CRP levels ≥ 150 mg/L. Bacterial and non-bacterial etiologies were determined from hospital discharge diagnoses, which were monitored independently by three physicians from the research team. The records of 495 suitable patients (51.2% males, median age 3.2 years) were retrieved of whom 444 (89.7%) were eventually diagnosed with bacterial infections. The mean CRP levels were significantly higher for bacterial etiologies compared with other causes (209.2 ± 59.8 mg/L vs. 185.6 ± 35.8 mg/L, respectively, p < .001), while the mean eCRPv values did not differ significantly (p = .15). In a time course analysis, we found that specifically in patients presenting ≥ 72 h after symptom onset, only a eCRPv1 level > 1.08 mg/L/h was an independent predictor of bacterial infection (aOR = 5.5 [95% CI 1.7-17.8], p = .004).   Conclusion: Pediatric patients with very high CRP levels and fever mostly have bacterial infections. eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset, warranting further prospective investigations into CRP kinetics in pediatric patients. What is Known: • The use of a single C-reactive protein (CRP) value to differentiate between bacterial and non-bacterial causes is limited. • Estimated CRP velocity (eCRPv) has shown promise in enhancing such discrimination in adults, but data on CRP kinetics in pediatric patients is sparse. What is New: • eCRPv levels, unlike CRP values alone, can serve as the sole independent predictor of bacterial infection > 72 h from symptom onset in pediatric patients with remarkably elevated CRP levels.

Early signaling of inflammation in patients following traumatic injury with accurately estimated time of injury by profiling C-reactive protein levels.

BACKGROUND: Despite its widespread use, the precise dynamics of CRP response in clinical practice remain poorly defined. We employed a novel quadratic model to explore the time-course analysis of CRP values in trauma patients with known precise time of injury. METHODS: Relevant data on all adult patients admitted to our hospital following traumatic incidents between January 1st 2010 to December 31, 2020 were retrospectively collected. Those with a documented time of injury and who underwent CRP evaluation within the first 24 h since injury were studied. RESULTS: Based on the findings from our annual health check-up center, we established a reference upper normal CRP value of 12.99 mg/L. Within the first 7 h after injury, the CRP levels of 8-9% of the 1545 study patients exceeded the reference threshold. The proportion of patients with CRP levels > 12.99 mg/L increased to 18.5% at 8-9 h later and rose sharply to 91.6% at 22-24 h later. Our quadratic model yielded the equation: CRP = 5.122-0.528xTime + 0.139xTime 2. It accounted for > 40% of the variance in CRP levels (R2 = 42.4%). CONCLUSIONS: Clear and prominent CRP elevations following atraumatic event are detected only 9-12 h following the insult. This novel finding has crucial implications for accurate CRP assessment of inflammatory responses to physical injuries.

Transitioning from having no metabolic abnormality nor obesity to metabolic impairment in a cohort of apparently healthy adults.

INTRODUCTION: The global prevalence of metabolic syndrome and its association with increased morbidity and mortality has been rigorously studied. However, the true prevalence of "metabolic health", i.e. individuals without any metabolic abnormalities is not clear. Here, we sought to determine the prevalence of "metabolically healthy" individuals and characterize the "transition phase" from metabolic health to development of dysfunction over a follow-up period of 5 years. METHODS: We included 20,507 individuals from the Tel Aviv Sourasky Medical Center Inflammation Survey (TAMCIS) which comprises apparently healthy individuals attending their annual health survey. A second follow-up visit was documented after 4.8 (± 0.6) years. We defined a group of metabolically healthy participants without metabolic abnormalities nor obesity and compared their characteristics and change in biomarkers over time to participants who developed metabolic impairment on their follow-up visit. The intersections of all metabolic syndrome components and elevated high sensitivity C-reactive protein (hs-CRP) were also analyzed. RESULTS: A quarter of the cohort (5379 individuals, (26.2%) did not fulfill any metabolic syndrome criteria during their baseline visit. A total of 985 individuals (12.7% of returning participants) developed metabolic criteria over time with hypertension being the most prevalent component to develop among these participants. Individuals that became metabolically impaired over time demonstrated increased overlap between metabolic syndrome criteria and elevated hs-CRP levels. The group that became metabolically impaired over time also presented higher delta values of WBC, RBC, liver biomarkers, and uric acid compared with participants who were consistently metabolically impaired. LDL-C (low-density lipoprotein cholesterol) delta levels were similar. CONCLUSIONS: Roughly one-quarter of apparently healthy adults are defined as "metabolically healthy" according to current definitions. The transition from health to metabolic dysfunction is accompanied with active inflammation and several non-metabolic syndrome biomarkers. Aggressive screening for these biomarkers, blood pressure and hs-CRP might help identify apparently healthy individuals at increased risk of developing metabolic syndrome over time.

Comparative analysis of CRP as a biomarker of the inflammatory response intensity among common viral infections affecting the lungs: COVID-19 versus influenza A, influenza B and respiratory syncytial virus.

Severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) is associated with significant morbidity and mortality. C-reactive protein (CRP) is a useful inflammatory biomarker for patients admitted with an infection. This study aimed to compare CRP level as an indicator of inflammation severity between SARS-CoV-2 and common respiratory viral infections. A cross-sectional study of all adult patients hospitalized in the internal medicine department, geriatric department, or internal intensive care unit between 02/2012 and 06/2021 with laboratory-confirmed respiratory viral infection was performed. SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV) were studied. Patients with laboratory-confirmed concurrent viral or bacterial infections were excluded. Patients with malignancy were also excluded. Age, gender, comorbidities, and CRP level upon admission were compared between groups. Univariate and multivariable analyses were applied. Among 1124 patients, 18.2% had SARS­CoV­2, 48.3% influenza A, 18.9% RSV, and 14.6% influenza B. SARS­CoV­2 patients were significantly younger (median 69.4 vs. ≥ 76 years) and had lower Charlson score (median 3 vs. ≥ 4 in other groups) compared to patients with other viral pathogens. After adjustment for patients' age, gender and comorbidities, SARS­CoV­2 patients had a higher probability (OR = 1.84-2.02, p < 0.01) of having CRP values in the upper quartile (> 117 mg/L) compared to all other viral pathogens while between all others there was no significant difference. To conclude, a higher CRP level upon admission is approximately twice more common among SARS-CoV-2 patients compared to other widespread respiratory viruses which may demonstrate the higher intensity of inflammation caused by SARS-CoV-2.

Cholinergic Dysfunction in Patients with Psoriatic Arthritis and Immunocompetent Controls: A Cross-Sectional Study.

BACKGROUND: The parasympathetic system and its main neurotransmitter, acetylcholine, contributes to homeostasis of inflammation. Cholinergic dysregulation is thought to contribute to the pathogenesis of inflammatory rheumatic diseases. Cholinesterase activity in patients with psoriatic arthritis (PsA) has not been investigated. OBJECTIVES: To compare the cholinesterase activity in patients with PsA and immunocompetent controls and to explore the correlation between cholinergic status (CS) and PsA disease activity. METHODS: Serum acetylcholinesterase (AChE) and total cholinesterase activity were measured in patients with PsA (n=88) and matched controls (n=84). Cholinergic activity before and 3-6 months after the initiation of a biologic treatment was evaluated in seven patients with PsA. RESULTS: The levels of AChE and CS were similar in both PsA patients and controls. PsA patients treated with biologics had significantly lower levels of AChE and CS compared to patients treated with non-biologics: 447.4 vs. 526 substrate hydrolyzed/min/ml, P = 0.005, and 1360.9 vs. 1536, P = 0.029, respectively. We found an association between C-reactive protein levels, AChE activity (r = 0.291, P = 0.008), and cholinergic status (r = 0.247, P = 0.026) in patients with PsA but not in controls. No correlation between AChE activity, cholinergic status, and the indices of PsA disease activity was found. After initiating or switching biologic treatment in 7 patients, AChE levels remained stable. CONCLUSIONS: We demonstrated similar cholinesterase activity in patients with psoriatic arthritis and controls, highlighting a potential effect of biologic treatment on cholinergic activity in patients with PsA.

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

Left atrium volume and ventricular volume ratio algorithm as indication of pulmonary hypertension etiology.

BACKGROUND: Pressure overload of the right heart (pulmonary hypertension [PH]) can be an acute or a chronic process with various pathophysiologic changes affecting the dimensions of the heart chambers. The automatic four-chamber volumetric analysis tool is now available to measure the volume of the cardiac chambers in patients undergoing a computed tomography pulmonary angiogram (CTPA). PURPOSE: To characterize the volumetric changes that occurred in response to increased systolic pulmonary arterial pressures (sPAP) in acute events, such as acute pulmonary embolism (APE), compared with other etiologies. MATERIAL AND METHODS: Consecutive patients who underwent CTPA and echocardiography within 24 h between 2011 and 2015 were included. Differences in cardiac chamber volumes were investigated in correlation to the patients' sPAP. RESULTS: The final cohort of 961 patients included 221 (23%) patients diagnosed with APE. The right (RV) to left (LV) ventricular volume ratio (VVR) was higher, while the left atrial (LA) volume index was smaller (P < 0.001) in the patients with APE. A decision tree for the prediction of APE showed that an RV to left VVR >2.8 was characteristic of APE, whereas an LA volume index >37.5 mL/m² was more compatible with PH due to other etiologies (P < 0.001). CONCLUSION: The combination of VVR and LA volume index may help in differentiating between APE and chronic PH. CTPA-based volumetric information may be used to help clarify the underlying etiology of the dyspnea.

Early signaling of bacteremia in patients who present to the department of emergency medicine with relatively low C-reactive protein (CRP) concentrations.

OBJECTIVES: Examiningthe usefulness of C-reactive protein velocity (CRPv) as an early biomarker for the presence of bacteraemia in patients presenting to the Department of Emergency Medicine with acute infection/inflammation and suspected bacteraemia. METHODS: A retrospective study examining a cohort of patients who presented to the E.R and in whom blood cultures were taken. CRPv was calculated as the difference in mg/hour/litter between two consecutive CRP tests performed within 12 h. RESULTS: 256 patients were included in the cohort. Using CRPv in patients who at first presented with a relatively low (17.9 ≤ mg/L 1stquartile) CRP concentration, we found an AUC of 0.808 ± 0.038 (p < 0.001) for the presence of positive versus negative blood cultures (what is AUC?). This was better than the AUC that was obtained when the WBC for the same purpose. CONCLUSIONS: CRPv may be a useful biomarker in the identification of patients with suspected bacteremiaand a low CRP-a challenging situation for clinicians who may underestimate the severity of illness in this patient group.

Reduced C-reactive protein level at hospital admission in patients treated with Tocilizumab - An attention may be required.

Background: C-reactive protein (CRP) is a marker of inflammation and infection. The main proinflammatory cytokine that leads to CRP gene expression is IL-6. The study aimed to compare CRP level between patients who were treated with Tocilizumab (TCZ), an il-6 receptor blocker, and other advanced anti-inflammatory treatments (AAIT), as well as with other admitted and non-admitted populations. Methods: A cross-sectional study of all patients (≥18 years) hospitalized at tertiary medical center between December 2009 and February 2020 and treated before hospitalization with (AAIT). Only the first hospitalization of each patient was included. Women admitted to obstetrics department were excluded. Demographic data, first blood tests results, and comorbidities were collected. Results: The study included 563 patients treated with AAIT (2.5% received TCZ). Patients treated with TCZ were older (median 75 vs. 50 years, p < 0.001), had higher Charlson score (median 5 vs. 1, p < 0.001) and more infectious diseases at admission (50% vs. 23.4%, p = 0.05). Patients treated with TCZ had lower CRP levels (median 0.5 vs. 25 mg/l, p < 0.001) and more common normal values (64.3% vs. 20.8%, p < 0.001) compared to patients treated with other AAIT.CRP level in patients treated TCZ (median 0.5 mg/l) was lower than that of 58,548 patients admitted to the hospital between 2010 and 2020 (median 12.55 mg/l, p < 0.001) and not statistically different from 140 non-admitted randomly selected individuals without acute disease (1.33 mg/l, p = 0.294). Conclusion: Tocilizumab is associated with lower levels of CRP in patients admitted to acute care hospital. This finding must be considered by treating physician to avoid misinterpretation of CRP results.

Metabolically Healthy Obesity Is a Misnomer: Components of the Metabolic Syndrome Linearly Increase with BMI as a Function of Age and Gender.

OBJECTIVES: We aimed to examine the relationships between body mass index (BMI) and metabolic syndrome (MS) components as a function of age and gender across weight categories. METHODS: This cross-sectional study included 19,328 subjects who participated in a health-screening program. We analyzed 14,093 apparently healthy subjects with a BMI ≥ 18.5 kg/m2 (ranging from 18.5 to 46 kg/m2). RESULTS: At a BMI of 18.5 kg/m2, 16% of subjects had one or more MS components (MS ≥ 1). The number of MS components increased linearly with BMI. The most prevalent components for MS1-4 were hypertension (in men) and increased waist circumference (in women). Among 6391 non-obese subjects with MS = 0, there was a linear increase in blood pressure, glucose, and triglycerides, as well as a decline in high-density lipoprotein cholesterol, as BMI increased. In 2087 subjects with a BMI ≥ 30 kg/m2, a true normometabolic state (MS = 0) was observed in only 7.5%, declining to less than 1% at a BMI ≥ 36 kg/m2 (ATP criteria). Women were metabolically protected relative to men between the ages of 30 and 50 years. CONCLUSIONS: (A) MS components increase linearly with BMI from the lowest normal BMI and continue to increase with age and BMI; (B) metabolically healthy obesity is rare in subjects with a high BMI and declines with age; (C) hypertension is the most common component in men; and (D) in women, MS components are seen at older ages than in men for the same BMI. Metabolic health declines with age and BMI in nearly all subjects with obesity.

The effect of body mass index reduction on intraocular pressure in a large prospective cohort of apparently healthy individuals in Israel.

PURPOSE: To investigate the effect of change in body mass index (BMI) on intraocular pressure (IOP) in a large cohort of apparently healthy volunteers who underwent an annual comprehensive screening examinations. METHODS: This study included individuals who were enrolled in the Tel Aviv Medical Center Inflammation Survey (TAMCIS) and had IOP and BMI measurements at their baseline and follow up visits. Relationships between BMI and IOP and the effect of change in BMI on IOP were investigated. RESULTS: A total of 7,782 individuals had at least one IOP measurement at their baseline visit, and 2,985 individuals had ≥2 visits recorded. The mean (SD) IOP (right eye) was 14.6 (2.5) mm Hg and mean (SD) BMI was 26.4 (4.1) kg/m2. IOP positively correlated with BMI levels (r = 0.16, p<0.0001). For individuals with morbid obesity (BMI≥35 kg/m2) and ≥2 visits, a change in BMI between the baseline and first follow-up visits correlated positively with a change in the IOP (r = 0.23, p = 0.029). Subgroup analysis of subjects who had a reduction of at least 2 BMI units showed a stronger positive correlation between change in BMI and change in IOP (r = 0.29, p<0.0001). For this subgroup, a reduction of 2.86 kg/m2 of BMI was associated with a reduction of 1 mm Hg in IOP. CONCLUSIONS: BMI loss correlated with reduction in IOP, and this correlation was more pronounced among morbidly obese individuals.

Association of inflammatory markers with hearing loss in young adults.

OBJECTIVES: To assess the correlation between inflammatory markers (IM) and hearing loss (HL) in a large cohort of apparently healthy individuals. DESIGN: A cross sectional study. SETTING: Tel-Aviv Medical Center (a tertiary referral center) Inflammatory Survey Participants Individuals who attended the Tel-Aviv Medical Center Inflammatory Survey (TAMCIS) for a routine annual health check. RESULTS: Out of 2,500 individuals included in the final study cohort, 1,170 (47.3%) had some hearing impairment. Those with a hearing loss in 1 or both ears had significantly higher levels of neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and red blood cell counts. There was a difference between low- and high- frequencies losses associated with the inflammatory status. CONCLUSIONS: IM levels were associated with the presence of a HL, supporting a link between inflammatory changes and hearing loss.

Differentiating between bacterial and viral infections by estimated CRP velocity.

PURPOSE: Differentiating between acute viral and bacterial infection is challenging due to the similarity in symptom presentation. Blood tests can assist in the diagnosis, but they reflect the immediate status and fail to consider the dynamics of an inflammatory response with time since symptom onset. We applied estimated C-reactive protein (CRP) velocity (eCRPv), as derived from the admission CRP level divided by time from symptom onset, in order to better distinguish between viral and bacterial infections. METHODS: This cross-sectional study included patients admitted to the emergency department with a confirmed viral (n = 83) or bacterial (n = 181) infection. eCRPv was defined as the ratio between the absolute CRP level upon admission to time from symptom onset (in hours). Absolute CRP and eCRPv values were compared between the 3 groups. RESULTS: Bacterial patients presented with higher CRP levels (133 mg/L) upon admission compared to viral patients (23.31 mg/L) (P < 0.001). Their median value of eCRPv velocity was 4 times higher compared to the viral patients (1.1 mg/L/h compared 0.25 mg/L/h, P < 0.001). Moreover, in intermediate values of CRP (100-150 mg/L) upon admission, in which the differential diagnosis is controversial, high eCRPv is indicative of bacterial infection, eCRPv >4 mg/L/h represents only bacterial patients. CONCLUSIONS: During an acute febrile illness, the eCRPv value can be used for rapid differentiation between bacterial and viral infection, especially in patients with high CRP values. This capability can potentially expedite the provision of appropriate therapeutic management. Further research and validation may open new applications of the kinetics of inflammation for rapid diagnosis of an infectious vs. a viral source of fever.

Evaluation of hemodynamically significant pericardial effusion by analysis of cardiac chambers volume by computed tomography.

OBJECTIVE: Pericardial effusion may present clinically as pleuritic chest pain, dyspnea, or hemodynamic compromise and is a frequent finding in computerized tomographic pulmonary angiography (CTPA) exams. We hypothesized that CTPA-based analysis of the cardiac chamber volumes can be used to predict the hemodynamic significance of pericardial effusion (HsPE) as compared with echocardiography. METHODS: Retrospective analysis of consecutive patients who underwent CTPA and echocardiography between January 2009 and November 2017 that ruled-out acute pulmonary embolism was included. Differences in cardiac chamber volumes were investigated in correlation to echocardiographic evidence of HsPE. RESULTS: The final cohort included 208 patients, of whom 22 (11%) were diagnosed with HsPE. The HsPE patients had much smaller right cardiac chamber volumes (Median 78.8 ml (IQR 72.4-89.1)) than patients without HsPE (Median 115.1 ml (IQR 87.4-150). A decision tree for the prediction of HsPE showed multiple cutoff values. Right atrium (RA) volume had the best accuracy (area under the curve 0.851, 95% confidence interval 0.776-0.925, p < .001) for predicting the presence of HsPE. An RA volume ≤86 ml yielded a sensitivity of 95.5%, a specificity of 64%, and a NPV of 99.2% for the presence of HsPE. CONCLUSION: CTPA-based volumetric information with focus on the RA volume may help predict the presence of HsPE. ADVANCES IN KNOWLEDGE: Pericardial effusion is a frequent finding in CTPA exams. Our study shows that CTPA-based volumetric information can predict the presence of HsPE with RA volume as the best indicator.

Sepsis Related Mortality Associated with an Inflammatory Burst in Patients Admitting to the Department of Internal Medicine with Apparently Normal C-Reactive Protein Concentration.

Background: Patients who are admitted to the Department of Internal Medicine with apparently normal C-reactive protein (CRP) concentration impose a special challenge due the assumption that they might not harbor a severe and potentially lethal medical condition. Methods: A retrospective cohort of all patients who were admitted to the Department of Internal Medicine with a CRP concentration of ≤31.9 mg/L and had a second CRP test obtained within the next 24 h. Seven day mortality data were analyzed. Results: Overall, 3504 patients were analyzed with a mean first and second CRP of 8.8 (8.5) and 14.6 (21.6) mg/L, respectively. The seven day mortality increased from 1.8% in the first quartile of the first CRP to 7.5% in the fourth quartile of the first CRP (p < 0.0001) and from 0.6% in the first quartile of the second CRP to 9.5% in the fourth quartile of the second CRP test (p < 0.0001), suggesting a clear relation between the admission CRP and in hospital seven day mortality. Conclusions: An association exists between the quartiles of CRP and 7-day mortality as well as sepsis related cause of death. Furthermore, the CRP values 24 h after hospital admission improved the discrimination.

Age-Dependent Biomarkers for Prediction of In-Hospital Mortality in COVID-19 Patients.

Background: Several biomarkers and models have been proposed to predict in-hospital mortality among COVID-19 patients. However, these studies have not examined the association in sub-populations. The present study aimed to identify the association between the two most common inflammatory biomarkers in the emergency department and in-hospital mortality in subgroups of patients. Methods: A historical cohort study of adult patients who were admitted to acute-care hospital between March and December 2020 and had a diagnosis of COVID-19 infection. Data on age, sex, Charlson comorbidity index, white blood cell (WBC) count, C-reactive protein (CRP), and in-hospital mortality were collected. Discrimination ability of each biomarker was observed and the CHAID method was used to identify the association in subgroups of patients. Results: Overall, 762 patients (median age 70.9 years, 59.7% males) were included in the study. Of them, 25.1% died during hospitalization. In-hospital mortality was associated with higher CRP (median 138 mg/L vs. 85 mg/L, p < 0.001), higher WBC count (median 8.5 vs. 6.6 K/µL, p < 0.001), and higher neutrophil-to-lymphocyte ratio (NLR) (median 9.2 vs. 5.4, p < 0.001). The area under the ROC curve was similar among all biomarkers (WBC 0.643, NLR 0.677, CRP 0.646, p > 0.1 for all comparisons). The CHAID method revealed that WBC count was associated with in-hospital mortality in patients aged 43.1−66.0 years (<11 K/µL: 10.1% vs. 11+ K/µL: 27.9%), NLR in patients aged 66.1−80 years (≤8: 15.7%, >8: 43.3%), and CRP in patients aged 80.1+ years (≤47 mg/L: 18.8%, 47.1−149 mg/L: 43.1%, and 149.1+: 71.7% mortality). Conclusions: WBC, NLR, and CRP present similar discrimination abilities. However, each biomarker should be considered as a predictor for in-hospital mortality in different age groups.

Early Detection of Inflammation-Prone STEMI Patients Using the CRP Troponin Test (CTT).

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p < 0.01. Furthermore, patients with both high CRP and high troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p < 0.01. These patients also had the highest all-cause mortality rates after a median follow-up of 4.5 years compared to the rest of the cohort; 42.9% vs. 12.7%, p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents.

A machine learning model for predicting deterioration of COVID-19 inpatients.

The COVID-19 pandemic has been spreading worldwide since December 2019, presenting an urgent threat to global health. Due to the limited understanding of disease progression and of the risk factors for the disease, it is a clinical challenge to predict which hospitalized patients will deteriorate. Moreover, several studies suggested that taking early measures for treating patients at risk of deterioration could prevent or lessen condition worsening and the need for mechanical ventilation. We developed a predictive model for early identification of patients at risk for clinical deterioration by retrospective analysis of electronic health records of COVID-19 inpatients at the two largest medical centers in Israel. Our model employs machine learning methods and uses routine clinical features such as vital signs, lab measurements, demographics, and background disease. Deterioration was defined as a high NEWS2 score adjusted to COVID-19. In the prediction of deterioration within the next 7-30 h, the model achieved an area under the ROC curve of 0.84 and an area under the precision-recall curve of 0.74. In external validation on data from a different hospital, it achieved values of 0.76 and 0.7, respectively.