Changes In C-reactive Protein Research Articles

P376 Switching from intravenous to subcutaneous vedolizumab maintenance treatment; feasibility, safety and clinical outcome

Abstract Background Vedolizumab (VDZ) has until recently been available only as intravenous (i.v.) formulation, but the drug is now available also as subcutaneous (s.c.) formulation. In the present study, we aimed to assess the feasibility, safety and clinical outcome when switching a real world cohort of patients with inflammatory bowel disease (IBD) from i.v. to s.c. VDZ treatment. Methods All IBD-patients receiving i.v. VDZ at the department were identified using the medical records. Patients in the induction period or with planned change of medical treatment or surgery within, 3 months were not routinely switched. The dosage of s.c. VDZ was calculated based on current i.v. dose and interval. Patients were assessed at first and fourth injection and after, 3 months. The primary endpoint was percentage of patients still on s.c. treatment after, 3 months. Secondary endpoints were adverse events, clinical disease activity scores (Harvey Bradshaw index and Partial Mayo Score), C-reactive protein (CRP), fecal calprotectin (FC), VDZ treatment interval, plasma-VDZ, and patients’ preferred route of administration. Results In total, 108 patients were switched, 51 with ulcerative colitis (UC) and, 57 with Crohn’s disease (CD). After, 3 months, 95.3% (103/108) remained on s.c. treatment. Four patients had switched back to i.v. and one changed treatment to ustekinumab. Nineteen patients (17.6%) experienced injection site reactions (ISR), and twelve of these (63.2%) had repeated reactions. In three cases, patients were switched back to i.v. treatment due to ISR. No serious adverse events related to the switch were observed. The median interval between injections was, 12 (IQR:, 7–18) days. The median p-VDZ at three months was, 44.4 (IQR:, 28.9–64.7) mg/L. In the UC and CD patients, 92% (47/51) and, 72% (41/57) were in clinical remission at first injection, whereas the corresponding numbers after three months were, 88% (p=0.18) and, 83% (p=0.11), respectively. No significant change in CRP and FC was observed. Before switching, 25% of the patients reported that they would prefer i.v. treatment, 28% s.c. treatment and, 47% were indifferent. Three months after switching, the corresponding numbers were, 18%, 53% and, 29%, respectively (p<0.001). Conclusion Switching from i.v. to s.c. VDZ was feasible and safe. Approximately one out of six experienced an ISR but only, 3% were switched back to i.v. administration. At, 3 months follow-up there was no change in clinical remission rates, CRP and FC. Furthermore, patients’ attitude towards route of administration changed after switching. The present real world data demonstrate that s.c. maintenance VDZ treatment represents an attractive alternative to i.v. treatment.

Preliminary Effects of Mindfulness Training on Inflammatory Markers and Blood Pressure in Young Adult Survivors of Cancer: Secondary Analysis of a Pilot Randomized Controlled Trial.

This was a secondary analysis of a pilot randomized controlled trial (RCT) of mindfulness-based stress reduction (MBSR) among young adult (YA) survivors of cancer, which showed preliminary evidence for improving psychosocial outcomes. Secondary outcomes assessed were the feasibility of collecting biological data from YAs and preliminary effects of MBSR on markers of inflammation and cardiovascular function. Participants were randomized to 8-week MBSR or a waitlist control condition. Participants provided whole blood spot samples for analysis of C-reactive protein (CRP) and interleukin (IL)-6 as well as blood pressure data in-person at baseline and 16-week follow-up. Feasibility was assessed with rates of providing biological data. Linear mixed effects modeling was used to evaluate preliminary effects of MBSR on inflammatory markers and blood pressure over time. Of 126 total participants enrolled, 77% provided biological data at baseline (n = 48/67 MBSR, n = 49/59 control). At 16weeks, 97% of the 76 retained participants provided follow-up biological data (n = 34/35 MBSR, n = 40/41 control). Relative to the control group, MBSR was associated with decreased systolic blood pressure (p = 0.042, effect sizes (ES) = 0.45) and decreased diastolic blood pressure (p = 0.017, ES = 0.64). There were no changes in CRP or IL-6. This was the first study to explore the feasibility of collecting biological data from YA survivors of cancer and assess preliminary effects of MBSR on inflammatory and cardiovascular markers in an RCT. Minimally invasive biological data collection methods were feasible. Results provide preliminary evidence for the role of MBSR in improving cardiovascular outcomes in this population, and results should be replicated.

Assessment of Clinical Efficacy of Dexamethasone in Patients with Moderate COVID-19

The host immune response, primarily manifested by hypercytokinemia, obviously plays a key role in the development of severe novel coronavirus disease, COVID-19. Currently, numerous therapies aimed at suppressing the hyperinflammatory response and the "cytokine storm" are being investigated. One of these methods is the use of corticosteroids, particularly dexamethasone.The aim was to assess the clinical efficacy of dexamethasone in patients with moderate bilateral multifocal pneumonia caused by SARS CoV-2 virus.Material and methods. Sixty-nine patients aged from 31 to 88 years hospitalized in Almazov National Research Center and the Semashko City Hospital No 38 with SARS CoV-2 coronavirus infection complicated by moderate (semiquantitative visual pulmonary lesion grading system CT 2-3 corresponding to 25-50% and 50-75% parenchymal involvement, respectively) community-acquired bilateral multifocal pneumonia were retrospectively studied. Group 1 included 39 patients with moderate coronavirus infection who received therapy according to the current version of the temporary guidelines (TG) of the Ministry of Health of the Russian Federation, including dexamethasone. The drug was administered parenterally twice daily in a dosage of 12 mg in the morning and 8 mg in the evening for the first three days, then the dose was gradually reduced over 5-7 days. No Interleukin-6 inhibitors were administered to patients in this group. Group 2 was composed of 30 patients who received therapy according to the current version of TG, including a parenteral interleukin-6 inhibitor (tocilizumab, olokizumab, or sarilumab) following the standard regimen. Patients in this group were not administered with dexamethasone.Results. CT scans corresponding to severity grade 3 and 4 (50-75% and >75% involvement, respectively) lung lesions on Day 7 were found in 35.89% of group 1 patients, while similar CT scans were found in 50% of patients who received interleukin-6 inhibitors (P=0.33). On Day 14 no significant differences in this parameter were revealed as well. Duration of fever in the dexamethasone group was 3.69 (0.62;6.76) days, while in the control group it was 3.95 (0.61;7.29) days (P=0.98). There was a tendency to decreased blood Creactive protein (CRP) values in the dexamethasone group on days 5 and 7. The frequency of transfer of patients to the ICU and hospital stay duration did not differ significantly between the groups.Conclusion. Dexamethasone has comparable clinical efficacy with IL-6 antagonists in the comprehensive treatment of patients with moderate COVID-19 disease, which is confirmed by the chest CT evolution, duration of fever, and changes in serum CRP.

Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein.

Recent evidence suggests that pancreatic inflammation plays a pivotal role in the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy but few data are available for distal pancreatectomy (DP). The aim of this study was to evaluate the impact of early biochemical markers on the occurrence of CR-POPF after DP. Clinical and laboratory data for 432 consecutive DP patients were reviewed. Serum amylase was evaluated on postoperative day (POD) 1, and drain fluid amylase (DFA) and C-reactive protein (CRP) were evaluated on POD 2 and 3. Receiver operator characteristic (ROC) curves were performed for all biochemical markers and an area under the curve (AUC) was computed. Multivariable regression analyses to identify the factors associated with CR-POPF and severe postoperative morbidity (Clavien-Dindo grade ≥ 3) were performed. At 90 days after surgery, CR-POPF occurred in 155 (36%) patients, severe complications in 66 (15%) patients. ROC curve analyses showed that DFA on POD2 had the largest AUC (0.753, p < 0.001), followed by serum amylase on POD 1 (0.651, p < 0.001), serum CRP on POD3 (0.644, p < 0.001), and CRP change between POD 2 and POD 3 (0.644, p < 0.001). Multivariable analysis identified male gender (OR 2.29, 95% CI 1.36-3.86; p = 0.002), DFA ≥ 1500 U/Lon POD2 (OR 4.63, 95% CI 2.72-7.89; p < 0.001), serum amylase ≥ 100 U/L on POD 1 (OR 1.72, 95% CI 1.01-2.93; p = 0.046), and CRP increase by at least 25mg/L on POD 3 compared to the previous day (OR 1.89, 95% CI 1.11-3.21; p = 0.019) as independent predictors of CR-POPF, yielding a valid regression model (AUC 0.765, 95% CI 0.714-0.816, p < 0.001). Postoperative serum amylase and CRP trajectory represent useful early biochemical markers for CR-POPF in addition to DFA. Our findings suggest that these laboratory tests should be incorporated into clinical practice to aid postoperative patient and drain management.

C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response

BackgroundC-reactive protein (CRP) has been proposed as a biomarker for pulmonary exacerbation (PEx) diagnosis and treatment response. CRP >75mg/L has been associated with increased risk of PEx treatment failure. We have analyzed CRP measures as biomarkers for clinical response during the STOP2 PEx study (NCT02781610). MethodsCRP measures were collected at antimicrobial treatment start (V1), seven to 10 days later (V2), and two weeks after treatment end (V3). V1 log10CRP concentrations and log10CRP change from V1 to V3 correlations with clinical responses (changes in lung function and symptom score) were assessed by least squares regression. Odds of intravenous (IV) antimicrobial retreatment within 30 days and future PEx hazard associated with V1 and V3 CRP concentrations and V1 CRP >75 mg/L were studied by adjusted logistic regression and proportional hazards modeling, respectively. ResultsIn all, 951 of 982 STOP2 subjects (92.7%) had CRP measures at V1. V1 log10CRP varied significantly by V1 lung function subgroup, symptom score quartile, and sex, but not by age subgroup. V1 log10CRP correlated moderately with log10CRP change at V3 (r2=0.255) but less so with lung function (r2=0.016) or symptom (r2=0.031) changes at V3. Higher V1 CRP was associated with greater response. CRP changes from V1 to V3 only weakly correlated with lung function (r2=0.061) and symptom (r2=0.066) changes. However, V3 log10CRP was associated with increased odds of retreatment (P = .0081) and future PEx hazard (P = .0114). DiscussionDespite consistent trends, log10CRP change was highly variable with only limited utility as a biomarker of PEx treatment response.

Dementia Family Caregivers’ Ambivalent Feelings and Cardiovascular Risk: Longitudinal Correlates

Cross-sectional data show that caregivers’ ambivalent feelings are associated with psychological distress. The association of ambivalent feelings with caregivers’ cardiovascular risk has not been studied. For this purpose we analyzed preliminary data from the Spanish Longitudinal Caregiving Spanish Longitudinal Study (CUIDA-LONG). One-year follow-up data were available for 96 dementia family caregivers. The following variables were assessed: sociodemographics, body mass index (BMI), disruptive behaviors, ambivalence, depressive symptomatology and cardiovascular risk with the inflammatory biomarker C-reactive protein (CRP). A hierarchical regression model was tested. Sociodemographic variables and change over time in stressors, ambivalence and depression were entered as predictors of change in CRP. 27% of the variance in CRP was explained through the model. More time since being a caregiver, higher BMI and greater increase in ambivalence contributed significantly to an increase in CRP. Ambivalent feelings contribute significantly to the cardiovascular risk of those who care for a relative with dementia.

High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch-Herxheimer Reaction in Patients with Active Syphilis.

BackgroundThe Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.MethodsThis prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.ResultsTwenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986–19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033–26,150 ng/mL] vs 3489 ng/mL [IQR 924–160,640] ng/mL, p = 0.0059, 95% CI 4002–17,098 ng/mL, area under the curve 0.799, 95% CI 0.632–0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).ConclusionA high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.

Determination of Association of Hyperchloremia with Rise in Inflammatory Markers, Serum Creatinine and Anaemia in COVID-19 Patients in Intensive Care Unit – A Prospective Follow-up Study

Hyperchloremia leads to adverse effects like increase in pro-inflammatory mediators, anaemia and renal dysfunction. Aim of this study is to determine the association of hyperchloremia with rise in C-reactive protein (CRP), serum ferritin, lactate dehydrogenase (LDH), serum creatinine and anaemia in COVID-19 patients in intensive care unit (ICU). It was a single-centre study, 62 COVID-19 patients participated. Change in CRP, serum ferritin, LDH, serum creatinine, haemoglobin between day one and day three of ICU admission were noted. Outcome in terms of in-hospital mortality was noted. Hyperchloremia (&gt;106mmol/L) or rise in chloride by &gt; 5mmol/L was seen in 13/62 (20.96%) patients. It was not associated with a rise in CRP, ferritin, LDH, creatinine, drop in hemoglobin within 72 hours or in-hospital mortality. 44/62 (71%) patients survived and were discharged from hospital. Multivariate logistic regression showed that if age and gender are also considered, there is a 25 times higher chance of having had a significant ferritin rise (&gt; 95 ng/mL) in 72 hours of ICU admission among those who died. (p=0.01). Hyperchloremia (&gt;106mmol/L) or a rise in chloride by &gt; 5mmol/L in 72 hours of ICU admission was not associated with a significant increase in CRP, LDH, ferritin, serum creatinine within 72 hours of ICU admission or mortality in moderate-severe COVID-19 patients. If age and gender are taken into consideration, there is a 25 times higher chance of having had a significant ferritin rise (&gt; 95 ng/mL) in 72 hours of ICU admission among those who died.

Calorie Restriction With Exercise Intervention Improves Inflammatory Response in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

Background/Purpose: In this systematic review and meta-analysis, we assessed the effects of exercise (EX) combined with calorie restriction (CR) intervention on inflammatory biomarkers, and correlations between biomarkers and participants’ characteristics were calculated in overweight and obese adults.Methods: An article search was conducted through PubMed, Web of Science, EMBASE, the Cochrane database, Scopus, and Google Scholar to identify articles published up to April 2021. Studies that examined the effect of EX + CR intervention on inflammatory biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and compared them with a CR trial in overweight and obese adults were included. We calculated the pooled effect by meta-analysis, identified the correlations (between inflammatory biomarkers and participants’ characteristics) through meta-regression, and explored the beneficial variable through subgroup analysis. The Cochrane risk of bias tool and Methodological Index for Non-randomized Studies were used to assess the risk of bias for the included trials.Results: A total of 23 trials, including 1196 overweight and obese adults, were included in the meta-analysis. The pooled effect showed that EX + CR intervention significantly decreased CRP levels (P = 0.02), but had no effect on IL-6 (P = 0.62) and TNF-α (P = 0.11). Meta-regression analysis showed that the effect of EX + CR on CRP, IL-6, and TNF-α changes was correlated with lifestyle behavior of adults (Coef. = −0.380, P = 0.018; Coef. = −0.359, P = 0.031; Coef. = −0.424, P = 0.041, respectively), but not with age and BMI. The subgroup analysis results revealed that participants with sedentary lifestyle behavior did not respond to EX + CR intervention, as we found no changes in CRP, IL-6, and TNF-α concentrations (P = 0.84, P = 0.16, P = 0.92, respectively). However, EX + CR intervention significantly decreased CRP (P = 0.0003; SMD = −0.39; 95%CI: −0.60 to −0.18), IL-6 (P = 0.04; SMD = −0.21; 95%CI: −0.40 to −0.01) and TNF-α (P = 0.006; SMD = −0.40, 95%CI: −0.68 to −0.12) in adults without a sedentary lifestyle or with a normal lifestyle. Furthermore, the values between sedentary and normal lifestyle subgroups were statistically significant for CRP, IL-6, and TNF-α.Conclusion: Our findings showed that combination EX + CR intervention effectively decreased CRP, IL-6, and TNF-α in overweight and obese adults with active lifestyles, but not with sedentary lifestyle behavior. We suggest that ‘lifestyle behavior’ is a considerable factor when designing new intervention programs for overweight or obese adults to improve their inflammatory response.

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

C-Reactive Protein as a Predictor of Complicated Acute Pancreatitis: Reality or a Myth?

IntroductionC-reactive protein (CRP) has been reported as a predictor of the severity of acute pancreatitis (AP). However, there is conflicting evidence in the literature. The proposed cut-off values and intervals for best prediction include an absolute value of 150 at 48 hours; an absolute value of 190 at 48 hours; and the interval change in CRP of 90 at 48 hours. The current study assesses the value of CRP at different intervals and cut-offs in predicting complicated acute pancreatitis (CAP) and compares its performance against other available predictors like neutrophil to lymphocyte ratio (NLR); Glasgow scoring system and modified CT severity index (MCTSI). MethodsAnalysis of prospectively maintained data for index episodes of acute pancreatitis managed in 225 patients over a period of five years (2014-2018) was done. CAP was defined by using revised Atlanta classification and included all the AP patients with local and or systemic complications. It was used as a gold standard. Diagnostic and predictive performance of different biochemical markers and multifactorial scoring systems were determined by analyzing receiving operating curves (ROCs), the area under the curve (AUC), sensitivity, specificity, and predictive values (positive and negative). ResultsOut of 225 patients, 122 were female while 103 patients were male. CAP developed in 47 patients (20.9%) while 178 (79.1%) patients had mild AP. Overall, in-hospital mortality rate was 1.8% (n=4). ROC analysis demonstrated that CRP at admission had low discriminatory value (AUC= 0.54, p-value=0.74). CRP at 48 hours had AUC of 0.70 (p-value=0.007). At a cut-off of 150, the positive predictive value (PPV) of 150 was 30 %. The PPV of CRP at 48 hours at a cut-off of 190 was 28%. Interval change in CRP at 48 hours greater than 90 had a PPV of 26 %. Further comparison of CRP with other scoring systems like Glasgow scoring system (AUC= 0.65), NL ratio (AUC=0.54), and MCTSI was performed. Among the single predictors, although, NL ratio showed good sensitivity at a cut-off value of 4.7 (87.23%), however, its discriminatory power was negligible (AUC=0.542, p-value=0.513). The overall best performance was achieved by the MCTSI scoring system at a cut-off of 3 (AUC=0.90, sensitivity=83.33 %, specificity=100%, diagnostic accuracy=94.49%). ConclusionCRP measured at admission or at 48 hours has a very limited role in the prediction of CAP. Along with other scoring systems, its negative predictive value should be used to predict cases with mild AP which can help in clinical decision making for early discharge or management of such patients on ambulatory care basis. MCTSI scoring system can be used in cases with high suspicion of CAP.

Interrelationship between reproductive hormones and acute phase proteins during estrous cycle and pregnancy in Spanish purebred broodmares

In some species, female steroid hormones modify the profile of acute phase proteins (APPs) during the estrous cycle and pregnancy, according to the ovulation, embryonic implantation and placental development; however, nowadays there's no experimental evidence for equine species. Objectives of this study were: to compare the serum amyloid A (SAA), haptoglobin (Hp) and C-reactive protein (CRP) concentrations between cyclic and pregnant mares, and to analyze the influence of estradiol-17β (E2) during estrous cycle or estrone sulfate (E1) during pregnancy, and progesterone (P4) on these proteins to assess their potential role to identify the cyclicity or pregnancy in Spanish mares. Blood samples were taken from 20 Purebred Spanish mares on the day of ovulation (day 0), on days +5 and +16 post-ovulation, and then, monthly during the whole pregnancy. SAA, Hp and CRP did not change between day 0, +5 and +16 post-ovulation days. P4 concentrations were significantly higher on day +16 than on days +5 and 0; and E2 concentrations were significantly higher on day 0 than day +5. On the other hand, pregnancy was characterized by a progressive increase in the Hp, variable modifications of E1 and P4 concentrations, without changes in SAA and CRP. The absence of significant differences in the APPs between days 0, +5 and +16, suggested that these proteins cannot be used as biomarkers of diagnosis of heat or pregnancy in Spanish mares, at least early, since the Hp later increases during the gestation. Nevertheless, it is possible to use them for comparative purposes with other equine breeds, as supervisor instrument of health status in breeding females as diagnostic tools to monitor pregnancy's development and/or subclinical reproductive inflammations, that could lead to the early embryonic death.

Maternal C3 complement and C-reactive protein and pregnancy and fetal outcomes: A secondary analysis of the PEARS RCT-An mHealth-supported, lifestyle intervention among pregnant women with overweight and obesity.

Objectives:Elevated circulating levels of complement component 3 (C3) and C-reactive protein (CRP) have been linked with adverse pregnancy outcomes. Lifestyle interventions may hold potential to ameliorate these effects. We investigated the effect of an antenatal healthy lifestyle intervention on maternal C3 and CRP concentrations and assessed their relationship with maternal and fetal metabolic markers and outcomes.Study design:Secondary analysis of data from the Pregnancy Exercise And Nutrition Research Study (PEARS) randomized controlled trial.Methods:Women (n = 406) with C3 and CRP concentrations determined in early pregnancy (14–16 weeks) and/or late pregnancy (28-weeks) with corresponding fasting glucose, insulin, c-peptide, and lipid profiles were included in the analysis. Pregnancy outcomes included: diagnoses of gestational diabetes (GDM), pre-eclampsia (PET) or pregnancy induced hypertension (PIH), pre-term birth (delivery < 37 weeks), low birth weight (<2500 g), small-for-gestational age (SGA) defined using < 5th or 10th centile for birthweight and cord blood measures of glucose and lipid metabolism. T-tests investigated changes in C3 and CRP over time. Chi-square, Pearson’s’ correlations and multiple regression investigated relationships with outcomes.Results:The PEARS intervention did not influence maternal C3 or CRP concentrations in pregnancy. There was no relationship between CRP concentrations and any maternal or infant outcome. Women who developed GDM had higher C3 concentrations in early (p = 0.01) and late pregnancy (p = 0.02). Women who developed PIH/PET had lower C3 concentrations in early (p = 0.02), but not late (p = 0.10) pregnancy. Maternal C3 concentrations in early pregnancy were a small but significant predictor of maternal insulin concentrations in early (β = 0.40, 95% CI 0.27, 0.53; p < 0.001) and late (β = 0.30, 95% CI 0.17, 0.43p < 0.001) pregnancy, early total cholesterol (TC), and both early and late triglycerides, LDL and HDL Cholesterol concentrations (all p < 0.001). Women who delivered SGA babies (<10th centile) had lower C3 concentrations than women who did not in both early (p < 0.001) and late pregnancy (p = 0.01). No relationship between maternal C3 or CRP and fetal glucose concentrations or lipid profiles was observed.Conclusion:Maternal C3 may play a role in multiple adverse pregnancy outcomes including cardiometabolic ill-health. Further research on this, and strategies to reduce C3 in a pregnant population, are warranted.

Surge in Procalcitonin Levels Post ATG During Stem Cell Transplantation for Aplastic Anemia: A Diagnostic Dilemma with Sepsis?

Allogenic Stem Cell Transplantation (AlloSCT) has paved way for curative therapy in numerous hematologic diseases such as Aplastic Anemia. Anti-Thymocyte Globulin (ATG), a polyclonal T-cell antibody is an integral part of the numerous conditioning regimens. Its purpose is the T-cell depletion of the recipient, which is of utmost importance for the prevention of graft rejection and successful engraftment. Febrile responses after ATG administration pose a diagnostic dilemma in these patients who are frequently neutropenic [1]. During the conditioning phase before AlloSCT, patients undergo substantial immunosuppression and immune-alteration under the effect of pharmacotherapy and total body irradiation. Conditioning with ATG can be associated with febrile episodes, circulatory instability and/or respiratory insufficiency. The severity of this reaction especially in a neutropenic patient can closely resemble sepsis. Since blood cultures can take a few days in reporting, biochemical markers of inflammation, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) levels have a diagnostic value. In contrast to CRP, Procalcitonin is a sensitive and specific marker for systemic bacterial infection and fungal sepsis [2,3]. We observed a surge in procalcitonin levels after ATG administration in a patient suffering from severe aplastic anemia undergoing conditioning for allogenic bone marrow transplantation from a matched sibling donor. The patient weighing 72 kilograms, received rabbit ATG as GVHD prophylaxis at the rate 1.5mg/kg (5 vials of 25mg each) on Day - 3 of conditioning and developed high grade fever with chills, reaching a peak temperature of 103.6 degrees Fahrenheit. Microbiological cultures and procalcitonin levels were sent to rule out sepsis as part of the protocol. First line intravenous antibiotics were started and antipyretics were administered. Fever settled on its own once the ATG therapy was completed. On day -2 and -1, the same dose of ATG was given and the patient did not develop any febrile episodes. The median PCT elevation on day 1 after ATG infusion was 87.68mcg/L, nearly 70 times the baseline level. Patient was clinically stable with no features of sepsis. There was a steady decline in PCT levels over the next 4 days, 58.54, 24.79, 4.38 and 1.13 (mcg/L) respectively. No derangements in liver function tests or renal function tests were observed. Subsequently, the microbiological cultures were sterile ruling out sepsis. Several previous reports suggested limited diagnostic value of PCT and CRP in the presence of anti-T-lymphocyte antibodies. Dornbusch et al. compared 15 consecutive febrile episodes after T cell antibody infusion without clinical signs of infection with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gramnegative sepsis. They concluded that during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release. The median PCT elevation on day1 after T-cell antibody infusion was nearly 40 times the baseline [4]. In our patient, the levels reached 70 times the baseline value probably related to higher ATG dose according to the weight of the patient. Brodska et al., prospectively evaluated the validity of CRP and PCT to diagnose infection in patients receiving ATG prior to hematopoietic stem cell transplantation. They assessed renal and liver functions and their relationship to PCT and CRP changes. They found no interrelationship between PCT levels and BL markers of renal or liver functions (P &gt; 0.05 for all comparisons) [5]. Similarly in our patient, no derangements in LFT or RFTs were seen. To conclude, febrile episodes during treatment with ATG are associated with markedly elevated levels of PCT directly proportional to the dose of ATG given. This causes a diagnostic dilemma with sepsis and early use of antimicrobials, which may be kept in reserve during actual crisis in the post-transplant period. In such a scenario, detailed clinical assessment of patient’s condition and careful interpretation of biochemical and microbiological investigations is of utmost importance for judicious use of antimicrobials in this era of emerging antibiotic resistance.

Analysis of CRP, Antithrombin, Fibrinogen, and Hematological Changes in 433 Patients with PTE.

ObjectiveTo investigate the characteristics of coagulation indicators, such as C-reactive protein (CRP), antithrombin (AT), and fibrinogen (FB) in patients with pulmonary thromboembolism (PTE) and their relationship with PTE.MethodsThe clinical characteristics, CRP, AT, FB, plasma D-dimer (D-D) and platelet (PLT) counts, and blood coagulation indicators of 433 patients with PTE diagnosed by computed tomographic pulmonary angiography (CTPA) were comprehensively analyzed, and the relevant clinical significance was discussed.ResultsThe total incidence of PTE was 1.60% (433/270,983 cases), and the age group with the highest incidence was over 60 years old. D-D increased in 412 (95.2%) patients. PLT was normal in 331 (76.4%) cases, but decreased in 53 (12.3%) cases and increased in 49 (11.3%) cases. CRP increased in 76.0% (288/379 cases) and was normal in 24.0% (91/379 cases). AT decreased in 109 (25.2%) cases and FB increased in 102 (23.6%) cases. There were no significant changes in other coagulation indexes. CRP was positively correlated with PLT and FB (r = 0.1026, t = 2.0118, P < 0.05, and r = 0.5360, t = 12.2963, P < 0.01, respectively). CRP was negatively correlated with AT (r = –0.2005, t = 4.0100, P < 0.01).ConclusionThe incidence of PTE was higher in hospitalized patients. Most patients with PTE have increased CRP and FB and decreased AT, and these levels may be related to the occurrence of PTE.

Duration of intravenous antibiotic treatment for acute exacerbations of cystic fibrosis: A systematic review

BackgroundAcute exacerbations of Cystic Fibrosis (AECF) are associated with significant morbidity. Recommendations are to treat for 2-3 weeks despite limited data. Spirometry is a measure of clinical response yet appears to plateau at 7-10 days. While durations <9 days have been associated with poorer outcomes, a duration of 10 days may be as effective as 14 days, potentially conferring advantages in terms of cost and adverse events. A 2019 Cochrane review by Abbott et al. did not identify any randomised controlled trials (RCT) comparing durations of treatment. Utilising data from non-randomised studies (NRS), we report a systematic review of intravenous antibiotic treatment, exploring changes in FEV1 (Forced Expiratory Volume in 1 second), CRP (C-reactive protein) and peripheral WBC (white blood cell) count in studies with different treatment durations. Study design and methodsSystematic review of published literature following a search of MEDLINE, Embase, CINAHL and the Cochrane Clinical Trials register. Guidelines from the Preferred Reporting items for Systematic reviews and Meta-Analysis (PRISMA) and reporting Meta-analysis of Observational studies (MOOSE) statement were followed. ResultsNo randomised controlled trials were identified that specifically examined duration of treatment during AECF. This study included all relevant RCTs and also NRS, grouping according to study characteristics, such as length of treatment, location, year, and also characteristics of the patient population. 52 studies, comprising 79 subgroups, and 1,597 patients, were identified. Mean change (95%CI) in ppFEV1 was 10.13 (9.21-11.05). There was no significant difference in change in ppFEV1 for studies treating for 10-12 days; 8.85 (7.47-10.23), vs 13-15 days; 10.68 (9.53-11.82). Similar changes in CRP and WBC were seen irrespective of treatment duration. ConclusionThis systematic review provides evidence that shorter durations of treatment may be associated with similar changes in FEV1, CRP and WBC compared with longer durations.

Bioelectrical Phase Angle, Muscle Damage Markers and Inflammatory Response After a Competitive Match in Professional Soccer Players

Abstract Introduction. The purposes of this study were 1) to evaluate changes from baseline levels in bioelectrical phase angle (PhA) and markers of muscle damage and inflammation in professional players 36 h after a soccer match, and 2) to analyze the relationships between PhA and markers of muscle damage and inflammation in order to investigate if PhA might be a useful parameter to monitor recovery. Material and methods. Eighteen male professional soccer players participated in this study. Plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities, plasma C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations, and PhA were measured before and 36 h after a competitive match. Results. Changes in LDH and CK 36 h after the match were greater than their reference change values (RCV). Changes in CRP and IL-6 were, however, lower than their corresponding RCV. 36 h after the match, significant correlations were observed between PhA and LDH (r = 0.714, p = 0.001), PhA and CK (r = 0.787, p = 0.000), and PhA and CRP (r = 0.554, p = 0.017). Conclusions. Although IL-6 and CRP have been traditionally analyzed together to monitor inflammation after intense exercise, since 36 h after the match they have already returned or started to return to baseline levels, the use of them alone is not a good option to monitor inflammation throughout recovery. PhA might be used as a predictor of muscle damage and inflammation, but further studies covering the whole recovery period are warranted.

Osteocalcin Is Independently Associated with C-Reactive Protein during Lifestyle-Induced Weight Loss in Metabolic Syndrome.

Bone-derived osteocalcin has been suggested to be a metabolic regulator. To scrutinize the relation between osteocalcin and peripheral insulin sensitivity, we analyzed changes in serum osteocalcin relative to changes in insulin sensitivity, low-grade inflammation, and bone mineral density following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). Participants with MetS were randomized to a weight loss program or to a control group. Before and after the 6-month intervention period, clinical and laboratory parameters and serum osteocalcin levels were determined. Changes in body composition were analyzed by dual-energy X-ray absorptiometry (DXA). In participants of the intervention group, weight loss resulted in improved insulin sensitivity and amelioration of inflammation. Increased serum levels of osteocalcin correlated inversely with BMI (r = −0.63; p < 0.001), total fat mass (r = −0.58, p < 0.001), total lean mass (r = −0.45, p < 0.001), C-reactive protein (CRP) (r = −0.37; p < 0.01), insulin (r = −0.4; p < 0.001), leptin (r = −0.53; p < 0.001), triglycerides (r = −0.42; p < 0.001), and alanine aminotransferase (ALAT) (r = −0.52; p < 0.001). Regression analysis revealed that osteocalcin was independently associated with changes in CRP but not with changes in insulin concentration, fat mass, or bone mineral density, suggesting that weight loss-induced higher serum osteocalcin is primarily associated with reduced inflammation.

Transient deterioration of albumin-bilirubin scores in early post-dose period of molecular targeted therapies in advanced hepatocellular carcinoma with 50% or higher liver occupation: A STROBE-compliant retrospective observational study.

Real-world clinical cases of molecularly targeted agent (MTA) administration to patients with advanced hepatocellular carcinoma (HCC) with ≥50% liver occupation have been reported, but treatment outcomes have rarely been described. We have encountered several cases in which albumin–bilirubin (ALBI) scores deteriorated markedly and C-reactive protein (CRP) levels elevated in the early post-dose period. The present study therefore investigated early clinical changes in ALBI score and CRP levels after initiating MTA in advanced HCC patients with ≥50% liver occupation, focusing on antitumor response at 6 weeks.This retrospective study included 46 HCC patients with liver occupation ≥50% and 191 patients with <50%, Child-Pugh score ≤7, and Eastern Cooperative Oncology Group Performance Status scores of 0 or 1, who were treated with sorafenib or lenvatinib as first-line systemic therapy at our hospital between June 2011 and January 2020. We analyzed their medical records up to March 2020 and investigated the outcomes and changes in CRP and ALBI scores classified according to antitumor response at 6 weeks.Overall survival was significantly longer in patients with partial response (PR) + stable disease (SD) (13.7 months) than in patients with progressive disease (PD) (1.7 months, P < .001) in the ≥50% group. Patients with antitumor response of PR + SD at 6 weeks in the ≥50% group showed more marked deterioration of ALBI score at 2 weeks than those in the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. Focusing on patients with PD at 6 weeks, ALBI score deteriorated over time in both groups. Regarding CRP, on 6-week PR + SD patients, a significant increase in CRP levels at 1 and 2 weeks was evident in the >50% group compared to the <50% group. These significant differences between groups had again disappeared at 4 and 6 weeks. In PD patients, no difference between groups in CRP elevation occurred at 1 and 2 weeks.In MTA treatment for patients with ≥50% liver occupation, to obtain an antitumor response of PR + SD, adequate management might be important considering transient deteriorated ALBI scores and elevated CRP levels.

Longitudinal associations between C-reactive protein and cognitive performance in normative cognitive ageing and dementia.

systemic inflammation appears to play an important role in the pathogenesis and expression of Alzheimer's disease and other dementias. Previous research has found that elevated levels of serum C-reactive protein (CRP) is associated with poorer cognitive functioning and increased risk for dementia. However, most studies are limited by single CRP measurements, which fail to capture long-term inflammatory exposures or dynamic changes in inflammation and cognition which may occur across repeated measurements. using data from 3,563 older adults aged 65-101 from the Health and Retirement Study, we examined bivariate changes in CRP and cognition measured repeatedly over a 10-year follow-up. Bivariate multilevel models estimated the effect of time-varying CRP on cognition among cognitively healthy older adults and in a subset of 427 participants who reported incident dementia onset during the follow-up period. in cognitively healthy participants, CRP was associated with lower level of cognitive functioning, but not rate of change over time. This effect was significant in participants under 80years of age (b = -0.09, standard error (SE) = 0.05, P = 0.04), but not in older participants. In participants with incident dementia, those with higher CRP experienced smaller rates of cognitive decline, leading up to dementia diagnosis. elevated levels of CRP predict poorer cognition and increased dementia risk in cognitively healthy adults under the age of 80. Conversely, increased CRP may confer protective effects on cognition in the prodromal stage of dementia.