Biological Markers Of Inflammation Research Articles

Associations of Dietary Intake on Biological Markers of Inflammation in Children and Adolescents: A Systematic Review.

Background: In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood. Methods: Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE and Web of Science–Core Collection. A total of 53 articles were identified. Results: Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to a Western dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers. Conclusions: This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents.

Biopsychosocial determinants of cognitive impairment in a representative sample of English older population

AbstractBackgroundTo investigate various biopsychosocial determinants of cognitive health in later life, using the neuropsychological battery of tests administered in the Harmonised Cognitive Assessment Protocol Sub‐Study of the English Longitudinal Study of Ageing (ELSA‐HCAP).MethodELSA‐HCAP is a neuropsychological sub‐study of 1273 participants completed in 2018, as part of an international research collaboration designed to better measure and identify neurocognitive disorders in representative population‐based samples. ELSA‐HCAP was administered to participants across all range of cognitive abilities, but we oversampled those identified as having low cognitive scores in the most recent ELSA waves. The HCAP respondent interview covered a broad range of cognitive domains (memory, language, executive function, psychomotor speed, problem‐solving, and numeracy) known to be affected by the ageing process. We also linked ELSA‐HCAP with the previous measures collected across ELSA waves, including biomarkers, psychosomatic and social economic information of these individuals collected in ELSA main waves 4 years before in 2016. We used Structural Equation Modelling (SEM) to estimate direct and indirect associations between Apolipoprotein (APOE) e4 status, education, wealth, inflammatory markers, chronic conditions, quality of life, depression and overall cognitive performance based on multiple domains, as well as the potential mediating effects.ResultHigher levels of education and increased quality of life were protective of the overall cognition, independent of the level of wealth. Depression and chronic conditions were strong predictor of cognitive impairment. We also found significant effects of age and sex, with women showing a slight cognitive advantage compared to men. We did not found an effect of APOE4 allele on cognitive impairment in this study. We find a pathway between higher levels of education leading to higher wealth, which impacting the number of chronic conditions and indirectly impacting on the overall cognition. We also found an indirect effect of inflammatory markers via chronic conditions and depressive symptoms.ConclusionIn a subset sample of a nationally representative sample of English population, we found that specific psychosocial risk factors were associated with the overall cognition in later life. Biological inflammatory markers were indirectly associated with overall cognition via depressive symptoms and chronic conditions pathways.

Inflammatory markers for the early detection of post-operative infection: The same threshold for rectal and colic surgery?

Anastomotic fistula is the most fearsome complication following colorectal surgery. Numerous studies have demonstrated the interest of postoperative CRP assay as an early diagnostic marker. Must the critical threshold for biological inflammatory markers remain the same, whether resection be colic or rectal? This is a study based on a cohort constituted between 2011 and 2014, including 497 patients with planned colorectal resection. C-reactive protein and pro-calcitonin were measured daily from day before surgery to D4. All postoperative intra-abdominal complications were considered as an anastomotic fistula. Detection thresholds were calculated from the area under the ROC curve. An intra-abdominal septic complication occurred in 16.9% of the patients having undergone rectal resection vs. 9.9% of those having had colectomy (P=0.03). In the absence of complications there was no significant difference between the two groups in terms of postoperative inflammatory response as determined by either CRP or PCT assay. Following rectal resection, optimal area under the curve (AUC=0.87) corresponds to CRP on D4 for a threshold of 100mg/L:sensitivity 83.3%, NPV 95.3%. For colons with the same CRP at 100mg/L (AUC=0.71): sensitivity 63.6%, NPV 93.9%. Notwithstanding riskier surgery, the detection threshold for an anastomotic fistula following rectal surgery remains the same: CRP>100mg/L at D4.

Pharmacokinetics of lopinavir/ritonavir oral solution to treat COVID-19 in mechanically ventilated ICU patients.

BackgroundThe combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000–8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir.ObjectivesTo assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir.Patients and methodsMechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored.ResultsPlasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928–32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394–32 735).ConclusionsIn mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.

Social Integration, Daily Discrimination, and Biological Markers of Health in Mid- and Later Life: Does Self-Esteem Play an Intermediary Role?

Background and ObjectivesThis cross-sectional study examines associations of social integration and daily discrimination with 4 biological markers of inflammation and cardiovascular health and tests whether self-esteem may mediate any of these effects.Research Design and MethodsData came from 746 participants of the National Survey of Midlife Development in the United States (MIDUS) Refresher (2011–2014) and MIDUS Refresher Biomarker Project (2012–2016). Structural equation modeling estimated direct and indirect associations of social integration and daily discrimination with glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL), C-reactive protein, and interleukin-6.ResultsSocial integration and daily discrimination were both significantly associated with self-esteem, which was in turn associated with HbA1c, HDL, and interleukin-6 levels. Social integration was indirectly associated with HbA1c, HDL, and interleukin-6 via self-esteem. Daily discrimination was directly associated with HbA1c, C-reactive protein, and interleukin-6 and was indirectly associated with HDL and interleukin-6 via self-esteem.Discussion and ImplicationsFindings identify social correlates of inflammation and cardiovascular risk and suggest that self-esteem may serve as a pathway for effects. Overall, results were somewhat mixed: Daily discrimination was directly associated with both self-esteem and 3 of the 4 biological markers of health; however, although social integration was strongly associated with self-esteem, it was only weakly and indirectly associated with biological health markers. Moreover, the indirect effects of daily discrimination on the biomarker outcomes—while significant—were notably smaller than its direct effects. Implications for theory, practice, and future research are discussed, including the need for further study of self-esteem and physical health across mid- and later life.

Assessment of saliva and gingival crevicular fluid soluble urokinase plasminogen activator receptor (suPAR), galectin‐1, and TNF‐α levels in periodontal health and disease

The aim of the study is to evaluate saliva and gingival crevicular fluid (GCF) levels of suPAR and galectin-1 in different periodontal health status and relationship between these molecules and TNF-α to understand the roles of these molecules in periodontal inflammation process. Soluble urokinase plasminogen activator receptor (suPAR) has been described as a biological marker of inflammation and immunological activation. Galectin-1, a member of the galectin family, is an anti-inflammatory cytokine. However, to date, levels of these two molecules in periodontal health and disease have not been well documented. A total of 60 individuals, 20 with chronic periodontitis (group P), 20 with gingivitis (group G), and 20 with healthy periodontium (group H) were recruited for this study. Full-mouth clinical periodontal measurements were recorded in periodontal charts. GCF and whole saliva samples were collected to determine the levels of suPAR, galectin-1, and TNF-α in study groups using enzymelinked immunosorbent assay (ELISA) method. The GCF total amount of suPAR, galectin-1, and TNF-α in GCF was similar in group P and G (P>.05). The GCF total amounts of these molecules in GCF were higher in the group G and P compared to the group H (P<.05), whereas the GCF concentrations of suPAR and galectin-1 were lower in the group G and P compared to the group H (P<.05).The saliva concentration of suPAR was significantly higher in group P compared to the group G and H (P<.05). It was also higher in the group G compared to the group H but there is no significant difference between the groups (P>.05). Salivary galectin-1 levels were similar in the study groups (P>.05). Increased levels of GCF suPAR, galectin-1, and saliva suPAR in periodontal disease suggest that these molecules may play a role in the periodontal inflammation. suPAR and galectin-1 may be considered as potential biomarkers in periodontal disease.

Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure

Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. ClinicalTrials.gov Identifier: NCT02106975.

Inflammation associated with coronary heart disease predicts onset of depression in a three-year prospective follow-up: A preliminary study

Depression frequently co-occurs with coronary heart disease (CHD), worsening clinical outcomes of both, and inflammation has been proposed as a biological link between these two disorders. The aim of the present study was to investigate the role of inflammation in the development of depression in CHD patients during a 3-year follow-up. We examined the inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), measured at baseline, as a potential predictor of later onset of depression.We recruited 89 CHD patients, who were assessed at baseline and then every 6 months, for three years. The sample included, at baseline, 25 depressed and 64 non-depressed CHD patients, as confirmed by Clinical Interview Schedule Revised (CIS-R). Depressive symptoms were assessed at baseline and all follow-up points by the Patient Health Questionnaire-9 (PHQ-9).In all CHD patients (n = 89), we found a significant positive correlation between hsCRP levels and the severity of depressive symptoms at baseline (PHQ-9, r = 0.23, p = 0.032). During follow-up, n = 21 patients (of the 64 non-depressed at baseline) developed depression, defined as being PHQ-9 positive (a score ≥ 10) in at least one follow-up assessment. Of these, n = 9 subjects were defined as developing clinically-significant depression, that is, having a positive PHQ-9 in at least 3 of the 6 follow-up assessments, implying a duration of symptoms of at least one year. We found that increased hsCRP values at baseline predicted future onset of depression. Specifically, baseline hsCRP values were higher in patients who later developed clinically-significant depression (mean ± SD; 6.76 ± 6.52 mg/L) compared with never-depressed (2.77 ± 3.13 mg/L; F(1,48) = 7.29, p = 0.010), even after controlling for baseline PHQ-9 scores.In conclusion, inflammation in CHD patients is associated with future development of clinically-significant depression. HsCRP, a reliable and ready-to-use biological marker of inflammation, may help to identify depression high-risk phenotypes even among CHD patients, who already have high baseline inflammation. Our study conveys important preliminary findings that will require further replication but that have the potential to affect the mental and physical health of a vulnerable group of individuals.

Crowned dens syndrome: a case report followed by an update on differential diagnosis and treatment

Introduction Crowned dens syndrome (CDS) is a rare clinical presentation of chondrocalcinosis or calcium pyrophosphate crystal deposition (CPPD) disease, characterized by fever, neck pain and stiffness, associated with increased biological markers of inflammation. Diagnosis is made mainly via imaging, and the best modality remains the magnetic resonance imaging (MRI) of the neck showing calcification and calcium pyrophosphate crystals deposition around the odontoid process (1). The aim of this report is to increase awareness of this rare and ill-known clinical tableau and to review its complications and the latest modalities of its diagnosis and treatment. Clinical case: An 83-year-old female patient presented to the emergency department (ED) of the Middle East Institute of Health (MEIH) with severe acute onset neck stiffness and pain of 10/10 intensity, radiating to the submandibular area and reaching the occipital part of the head, associated with nausea and 2 episodes of chills one day prior to presentation. Patient denied any recent history of trauma or surgery of the head and neck. Physical exam at that time was only remarkable for marked limitation of neck motion, and positive Kernig and Brudzinski signs. No skin changes, facial sinuses tenderness, cervical lymphadenopathies or neck swellings were noted. Vital signs at ED were within normal range except for a low grade fever. Laboratory work-up upon presentation showed hyperleukocytosis (WBC = 14000/mm3) with left shift and a C-reactive protein (CRP) of 189 mg/L (0-5 mg/L). Chest X-Ray only showed degenerative osteoarthritis of the thoracic spinal vertebrae. CT-scan of the brain without IV contrast done urgently showed no acute changes. As Clinical and biological features were suggestive of acute meningitis, cultures were taken including blood, urine and CSF fluid from lumbar puncture. The patient was admitted to the hospital for IV antibiotic treatment with a large spectrum carbapenem and close observation. On next 2 days, the patient continued to develop low grade fever with a fluctuating pattern, and levofloxacin and amikacin shots were added for maximal bacterial coverage. Urine and blood culture yielded positive for Escherichia Coli only resistant to penicillin. CSF fluid analysis and culture was unremarkable. So, the patient continued to receive IV antibiotics for urinary tract infection and bacteremia. And although the cultures were sensitive to the antibiotics given, the patient continued to suffer from fever, headache, neck stiffness with minimal improvement and response to IV acetaminophen. Laboratory markers continued to increase and CRP reached 325. The patient then underwent a series of imaging and laboratory tests to determine the cause of fever, including CT-scan of the chest, abdomen and pelvis with IV contrast, widal, wright, Rose Bengal, stool analysis, stool culture, clostridium difficile toxins, transthoracic and transesophageal cardiac ultrasound that were all negative. Finally, neck MRI was done to rule out spondylodiscitis or a cervical abscess and showed evidence of osteoarthritis on multiple cervical spinal levels, calcification of the odontoid process of C2, and thickening of the synovium and posterior ligaments (Fig C – D). Those results were compatible with a CT-scan of the neck then done and was in favor of a corona of calcification around the odontoid process suggesting a crowned dens syndrome (Fig A – B). The patient was put on colchicine therapy, and started to improve slowly, then corticosteroids were added and yielded a faster improvement. The C-reactive protein finally started to drop until reaching 23 mg/L upon the discharge. The patient was finally discharged on NSAIDs and colchicine. And after 1 month, the patient was seen in an outpatient setting where she reported dramatic improvement of her symptoms.

Septic elbow arthritis in children: Epidemiology and outcome

IntroductionSeptic elbow arthritis is a rare disease, especially in children. The aim of this study was to report the functional outcome of our pediatric population with both demographic and microbiological features. MethodsWe retrospectively reviewed all our cases of pediatric septic elbow arthritis between 2007 and 2017. Demographic, microbiological, biological, and radiological features were analyzed. Functional outcome was evaluated according to the Morrey Elbow Performance Score (MEPS). ResultsIn total, 14 cases were reviewed. The mean age was 9 years. Microbiological findings revealed Staphylococcus aureus in 10 cases. The mean white blood cells count in synovial fluid was 101,306 cells per mm 3. The skin was the most frequently reported entry portal. The mean MEPS score was 86.13 points (excellent in eight cases, good in three cases, fair in two cases, and poor in two cases). Stiffness was observed in three cases. No growth disturbance was reported. DiscussionSeptic elbow arthritis in children is rare. Biological inflammatory markers are sensitive but not specific. White blood cell count in the synovial fluid is specific. S. aureus is the most frequently cultured agent. Treatment is based on surgical debridement, antibiotics, and elbow immobilization. Concomitant osteomyelitis is frequent and should be diagnosed and treated simultaneously. Functional outcomes are usually satisfactory in contrast to osteomyelitis. ConclusionPediatric septic elbow arthritis is rare. It may be primary or secondary to trauma and surgery of the elbow. Demographic, biological, and microbial features are similar to those reported for osteomyelitis; however, functional outcomes are better with a negligible rate of growth disturbance.

P1736The association of biological markers of inflammation with the severity of cardiofibrosis in patients with ST-segment elevation myocardial infarction

P1736The association of biological markers of inflammation with the severity of cardiofibrosis in patients with ST-segment elevation myocardial infarction

The Role of Combining Biochemical Markers in Assessing the Endoscopic Activity in Ulcerative Colitis

Ulcerative colitis (UC) isa chronic, idiopathic and recurrent inflammatory bowel disease (IBD), characterized by periods of activity and remissionwhose monitoring requires invasive explorations associated with discomfort for the patient and important costs. Mucosal healing became one of the most important therapeutic targets in UC. The aim of our study was to identify a score, made up of noninvasive, available, used in current clinical practice biochemical markers, which should correlate with endoscopic activity in UC. We conducted a prospective study on 114 patients with UC. All patients were assessed both for biological inflammatory markers: erythrocyte sedimentation rate (ESR),C- reactive protein (CRP), fibrinogen, platelets, albumin, fecal calprotectin (FC) and by colonoscopy to estimate the endoscopic activity using Mayo score. By linear regression, we tried to identify a biochemical score correlated with endoscopic activity. Out of the serological markers,ESR (p=0.014), CRP(p= 0.021) and fibrinogen (p=0.035) correlated with the endoscopic activity of the disease. The best sensitivity to determine the endoscopic activity was given by FC (96.05%) with a predictable negative value of 91.1% (p=0.001). The score determined by linear regression: 1 (ESR]15mm/1h) x 0.305 + 1(fibrinogen]340.5mg/dL) x 0.309+1 (CRP] 5 mg/L) + 1 (calprotectin]200 μg/g) had an increased positive predictive value compared to each and one biomarker, nevertheless, with a sensitivity and specificity inferior to that of FC. Up to now, it is the first attempt to achieve a score made up exclusively of biological markers. The obtained score, although with an increased accuracy, has proven to have a lower predictability in comparison with FC used individually and cannot entirely replace colonoscopy.

Role of cytokines and inflammation in heart function during health and disease.

By virtue of their actions on NF-κB, an inflammatory nuclear transcription factor, various cytokines have been documented to play important regulatory roles in determining cardiac function under both physiological and pathophysiological conditions. Several cytokines including TNF-α, TGF-β, and different interleukins such as IL-1 IL-4, IL-6, IL-8, and IL-18 are involved in the development of various inflammatory cardiac pathologies, namely ischemic heart disease, myocardial infarction, heart failure, and cardiomyopathies. In ischemia-related pathologies, most of the cytokines are released into the circulation and serve as biological markers of inflammation. Furthermore, there is an evidence of their direct role in the pathogenesis of ischemic injury, suggesting cytokines as potential targets for the development of some anti-ischemic therapies. On the other hand, certain cytokines such as IL-2, IL-4, IL-6, IL-8, and IL-10 are involved in the post-ischemic tissue repair and thus are considered to exert beneficial effects on cardiac function. Conflicting reports regarding the role of some cytokines in inducing cardiac dysfunction in heart failure and different types of cardiomyopathies seem to be due to differences in the nature, duration, and degree of heart disease as well as the concentrations of some cytokines in the circulation. In spite of extensive research work in this field of investigation, no satisfactory anti-cytokine therapy for improving cardiac function in any type of heart disease is available in the literature.

DNA methylation and inflammation marker profiles associated with a history of depression

Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified six significant (Šidák corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Šidák corrected P = 1.27 × 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.

La fièvre méditerranéenne familiale

Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation. Usually attacks last 1 to 3days and spontaneously stop. A daily oral colchicine intake of 1 to 2mg/day is able to prevent attack's occurrence, frequency, intensity and duration among most patients. Colchicine is also able to prevent the development of inflammatory amyloidosis, the most severe complication of FMF. This state of the art article will focus on the diagnosis of FMF, the treatment and an update on the pathophysiology including the recent described dominant form of MEFV-associated new auto-inflammatory diseases.

Effects of ambient particulate matter on aerobic exercise performance

Background/ObjectiveWintertime thermal inversions in narrow mountain valleys create a ceiling effect, increasing concentration of small particulate matter (PM2.5). Despite potential health risks, many people continue to exercise outdoors in thermal inversions. This study measured the effects of ambient PM2.5 exposure associated with a typical thermal inversion on exercise performance, pulmonary function, and biological markers of inflammation. MethodsHealthy, active adults (5 males, 11 females) performed two cycle ergometer time trials outdoors in a counterbalanced design: 1) low ambient PM2.5 concentrations (<12 μg/m3), and 2) an air quality index (AQI) ranking of “yellow.” Variables of interest were exercise performance, exhaled nitric oxide (eNO), c-reactive protein (CRP), forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1). ResultsDespite a significant difference in mean PM2.5 concentration of 9.3 ± 3.0 μg/m3 between trials (p < .001), there was no significant difference (p = .424) in the distance covered during low PM2.5 conditions (9.9 ± 1.7 km) compared to high PM2.5 conditions (10.1 ± 1.5 km). There were no clinically significant differences across time or between trials for eNO, CRP, FVC, or FEV1. Additionally, there were no dose-response relationships (p > .05) for PM2.5 concentration and the measured variables. ConclusionAn acute bout of vigorous exercise during an AQI of “yellow” did not diminish exercise performance in healthy adults, nor did it have a negative effect on pulmonary function or biological health markers. These variables might not be sensitive to small changes from acute, mild PM2.5 exposure.

Sex Differences in Inflammatory Response and Acid-Base Balance in Prepubertal Children with Severe Sepsis.

The severity and prognosis of various acute inflammatory conditions, such as sepsis, differ between males and females. The mechanisms underlying these sex differences probably involve both hormonal and genetic factors. In order to evaluate a possible genetic influence, we reviewed clinical signs and biological inflammatory markers of prepubertal children with severe sepsis admitted to the pediatric intensive care unit (PICU). A total of 142 prepubertal children, 66 girls and 76 boys, suffering from severe sepsis and admitted to the PICU were included. The survival rate demonstrated a tendency to be higher in females (P = 0.14). Maximum white blood cell count (23,800 cells/μL [15,110-34,600] in girls vs. 19,025 cells/μL [12,358-26,098] in boys, P = 0.02), neutrophil count (16,944 cells/μL [10,620-27,540] vs. 13,756 cells/μL [8410-20,110], P = 0.03), and C-reactive protein level (26.2 mg/dL [15.7-33.6] vs. 18.8 mg/dL [11.1-30.0], P = 0.04) were all significantly higher in girls. Girls also exhibited significantly longer fever duration (2 days [1-6] vs. 1 day [1-3] for the boys, P <0.01), lower pH on admission (7.32 [7.25-7.39] vs. 7.37 [7.31-7.43] P = 0.03), and lower base excess (-6 mEq/L [-10.7 to -0.8] vs. -2.3 mEq/L [-6.6 to -2.6], P <0.01), as well as lower bicarbonate levels (19.1 mEq/l [15.9-24.0] vs. 21.15 mEq/l [18.3-26.68], P = 0.04), when compared with the boys. Our study revealed higher neutrophilic inflammation, as well as lower pH on admission, in girls with severe sepsis; associated with longer fever duration, which could contribute to better pathogen clearance. However, further studies are needed to demonstrate the link between acidosis and modulation of the immune response.

Biomarkers of Inflammation in Peripheral Blood during Treatment with Inhaled Corticosteroids in Patients with Asthma

BACKGROUND: The main attribute of asthma is inflammation, which leads to airway remodelling, bronchial hyper-reactivity and reversible or partly reversible airway obstruction. According to GINA, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, in particular, mast cells, eosinophils (Eo), and T lymphocytes. Many cells and mediators take part in creating the asthmatic inflammatory reaction, but eosinophils play a central role.AIM: The aim of this study was to show the values of biological inflammatory markers (IL-5, Eo, and ECP) during treatment with ICS by non-invasive methods.MATERIAL AND METHODS: This study includes 30 patients of the Pulmonology and Allergology Clinic, Skopje, with confirmed asthma, treated with ICS. In all of the patients, we followed Eo count, ECP and IL-5 in peripheral blood at the beginning of the study, after 2 and six months treatment. Following the parameters during treatment with ICS we registered changes in all of the tested parameters.RESULTS: Our results show high level of the tested biomarkers at the beginning of the study, IL-5 in all patients (100%), Eosinophils in 80%, and ECP in 90% of the asthmatics. Following the parameters during treatment with ICS we registered changes in all of the tested parameters.CONCLUSIONS: Our conclusion is that the ICS objectively suppress the inflammatory reaction in asthma and the biologic markers (IL-5, Eo and ECP), which we have followed, can measure the accomplished effect. They could be used in everyday practice, not only as diagnostic parameters but also as valid therapeutic guides in the treatment of asthma.

Usefulness of plasma neutrophil gelatinase-associated lipocalin concentration for predicting the severity and mortality of patients with community-acquired pneumonia

BackgroundThe usefulness of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration for predicting the outcome of community-acquired pneumonia (CAP) is unclear. We evaluated the prognostic value of plasma NGAL concentration for predicting disease severity in comparison with other widely used biological markers of inflammation in patients with CAP. MethodsNGAL, procalcitonin, and C-reactive protein concentrations were measured in 362 patients with CAP, who were followed for up to 30days. The Pneumonia Severity Index (PSI) and CURB-65 score were obtained for all patients. ResultsThe median plasma NGAL concentration increased with CAP severity classified according to the PSI. Plasma NGAL concentration was higher in nonsurvivors than in survivors. The AUC for predicting mortality was highest for NGAL concentration (0.871), followed by that for PSI (0.865) and procalcitonin concentration (0.744). Multivariable logistic regression analysis showed that plasma NGAL concentration was an independent predictor of hospital mortality in CAP patients. Plasma NGAL concentration correlated positively with C-reactive protein and procalcitonin concentrations, CURB-65 score, and PSI. ConclusionsPlasma NGAL concentration is a valuable biological marker in the assessment of the severity and prediction of the prognosis of patients with CAP in the emergency department.

A novel approach to evaluating the benefit of post-urinary tract infection renal ultrasonography, using decision curve analysis.

The benefit of post-urinary tract infection (UTI) sonography to detect clinically significant renal abnormalities remains a subject open to debate. Decision curve analysis (DCA) is a novel method for evaluating the clinical usefulness of diagnostic tests. Our objective was to determine, using DCA, the benefit of post-UTI sonography and of post-UTI sonography with biological markers of inflammation to predict the risk of recurrence of febrile UTI in children aged 2 to 24months without known uropathy. We retrospectively analyzed all children aged 2 to 24months, without known uropathy, who presented with a first episode of febrile UTI between 2009 and 2012 and followed them for 30months. We then used DCA to estimate the benefit of post-UTI sonography or post-UTI sonography + biological markers of inflammation for detecting the risk of recurrence. A total of 318 children [144 boys (45.3 %) and 174 girls (54.7%)], with a mean age of 6.9 ± 5.6months, were identified. Of these, 210 children presented with a significant inflammation [66.2%; 95% confidence interval (CI) 61.0-71.4], and 30 (9.4%; 95% CI 6.2-12.6) presented with abnormal post-UTI sonographic findings. Eighteen (5.7%; 95% CI 3.1-8.2) children presented with recurrent UTI at 30months. There were significantly more recurrences in those children who presented with abnormal sonographic findings than in those who did not (relative risk 7.68; 95% CI 3.03-19.46). However, taking into account the effect of false-positives and false negatives, the DCA revealed that for threshold probabilities of >30%, at which patients/doctors are concerned about unnecessary interventions (whether tests or treatments), neither post-UTI sonography nor post-UTI sonography + biological markers of inflammation have sufficient value to improve care.