Diagnostic methods in sepsis: the need of speed

Objective: Sepsis is a common condition encountered in hospital environments. There is no effective treatment for sepsis, and it remains an important cause of death at intensive care units. This study aimed to discuss some methods that are available in clinics, and tests that have been recently developed for the diagnosis of sepsis. Methods: A systematic review was performed through the analysis of the following descriptors: sepsis, diagnostic methods, biological markers, and cytokines. Results: The deleterious effects of sepsis are caused by an imbalance between the invasiveness of the pathogen and the ability of the host to mount an effective immune response. Consequently, the host's immune surveillance fails to eliminate the pathogen, allowing it to spread. Moreover, there is a pro-inflammatory mediator release, inappropriate activation of the coagulation and complement cascades, leading to dysfunction of multiple organs and systems. The difficulty achieve total recovery of the patient is explainable. There is an increased incidence of sepsis worldwide due to factors such as aging population, larger number of surgeries, and number of microorganisms resistant to existing antibiotics. Conclusion: The search for new diagnostic markers associated with increased risk of sepsis development and molecules that can be correlated to certain steps of sepsis is becoming necessary. This would allow for earlier diagnosis, facilitate patient prognosis characterization, and prediction of possible evolution of each case. All other markers are regrettably constrained to research units.

Persistent Periodontal Disease Hampers Anti-Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis

Objective: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. Methods: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). Results: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). Conclusions: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction

Objective: Enhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event. Methods: Consecutive patients (n = 372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type alpha (TNF-alpha), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up. Results: The decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-alpha and CRP less intense during the first 5 days in LS than in HS patients (p < 0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r = 0.46; p < 0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p < 0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p < 0.05). Conclusion: Excessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Are antibiotics necessary after lower third molar removal?

Objective. Patients (n = 110) free of antibiotics, operated on by 3 surgeons ranging in clinical experiences, were evaluated for infection. Study Design. In the preoperative period and during the second and seventh postoperative days, the following parameters were analyzed: pain, infection, swelling, trismus, body temperature, C-reactive protein levels (CRP), and salivary neutrophil counts (SNC). During surgery, the following parameters were analyzed: systolic, diastolic, and mean arterial pressure; oximetry; heart rate; anesthesia quality; local anesthetic amount; bleeding; surgery difficulty; and surgery duration. Results. There were some differences in the surgery duration, local anesthetic amount, anesthesia quality, bleeding, pain experienced, trismus, CRP, and SNC, and no changes in hemodynamic parameters, rescue analgesic medication, wound healing, swelling, body temperature, confirmed case of dry socket, or any other type of local infection. Particularly, no systemic infections were found after lower third molar removal (LTMR). Conclusions. This study suggests that antibiotic prescriptions are unnecessary after LTMR when preoperative infections are absent. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114(suppl 5):S199-S208)

Is waist-to-height ratio a useful indicator of cardio-metabolic risk in 6-10-year-old children?

Background: Childhood obesity is a public health problem worldwide. Visceral obesity, particularly associated with cardio-metabolic risk, has been assessed by body mass index (BMI) and waist circumference, but both methods use sex-and age-specific percentile tables and are influenced by sexual maturity. Waist-to-height ratio (WHtR) is easier to obtain, does not involve tables and can be used to diagnose visceral obesity, even in normal-weight individuals. This study aims to compare the WHtR to the 2007 World Health Organization (WHO) reference for BMI in screening for the presence of cardio-metabolic and inflammatory risk factors in 6–10-year-old children. Methods: A cross-sectional study was undertaken with 175 subjects selected from the Reference Center for the Treatment of Children and Adolescents in Campos, Rio de Janeiro, Brazil. The subjects were classified according to the 2007 WHO standard as normal-weight (BMI z score > −1 and < 1) or overweight/obese (BMI z score ≥ 1). Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glycemia, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), Homeostatic Model Assessment – Insulin Resistance (HOMA-IR), leukocyte count and ultrasensitive C-reactive protein (CRP) were also analyzed. Results: There were significant correlations between WHtR and BMI z score (r = 0.88, p < 0.0001), SBP (r = 0.51, p < 0.0001), DBP (r = 0.49, p < 0.0001), LDL (r = 0.25, p < 0.0008, HDL (r = −0.28, p < 0.0002), TG (r = 0.26, p < 0.0006), HOMA-IR (r = 0.83, p < 0.0001) and CRP (r = 0.51, p < 0.0001). WHtR and BMI areas under the curve were similar for all the cardio-metabolic parameters. A WHtR cut-off value of > 0.47 was sensitive for screening insulin resistance and any one of the cardio-metabolic parameters. Conclusions: The WHtR was as sensitive as the 2007 WHO BMI in screening for metabolic risk factors in 6-10-year-old children. The public health message “keep your waist to less than half your height” can be effective in reducing cardio-metabolic risk because most of these risk factors are already present at a cut point of WHtR ≥ 0.5. However, as this is the first study to correlate the WHtR with inflammatory markers, we recommend further exploration of the use of WHtR in this age group and other population-based samples.

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Abstract Introduction Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy. Methods Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls. Results At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values. Conclusions Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation

INTRODUCTION: Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. OBJECTIVES: To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. METHODS: Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. RESULTS: The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). CONCLUSIONS: C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of Creactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

Migrant labor and wear-out in manual sugarcane harvesting in São Paulo, Brazil

The scope of this paper is to describe the work of manual sugarcane harvesters, assessing the nutritional behavior and body composition between the beginning and the end of the harvest. A descriptive longitudinal study was made of harvesters in Piracicaba, São Paulo, Brazil, who answered a socio-demographic questionnaire and authorized measurement of Body Mass Index, Body Fat Percentage and Arm Muscle Circumference at three stages. Creatine kinase on the skeletal isoform, C-reactive protein and plasma urea were measured at the end of the harvest. Thirty male migrant harvesters with ages ranging from 18 to 44 from the Northeast (Ceará) were assessed over a nine-month period. The workers suffered significant body fat and weight loss in the first half of the harvest. Eighteen workers had abnormal levels of creatine kinase and four - out of 24 who had donated blood - had altered urea levels. Sugarcane harvesting work causes weight and body fat loss and gains in the lean body mass index, which suffers wear-out when working on consecutive harvests. It can also cause changes in biochemical markers of chronic systemic inflammation. Further studies will make it possible to comprehend the relationships between stress, wear-out, labor longevity and health in sugarcane harvesting.

Intrinsic organization of the suprachiasmatic nucleus in the capuchin monkey

The suprachiasmatic nucleus (SCN), which is the main circadian biological clock in mammals, is composed of multiple cells that function individually as independent oscillators to express the self-sustained mRNA and protein rhythms of the so-called clock genes. Knowledge regarding the presence and localization of the proteins and neuroactive substances of the SCN are essential for understanding this nucleus and for its successful manipulation. Although there have been advances in the investigation of the intrinsic organization of the SCN in rodents, little information is available in diurnal species, especially in primates. This study, which explores the pattern of expression and localization of PER2 protein in the SCN of capuchin monkey, evaluates aspects of the circadian system that are common to both primates and rodents. Here, we showed that PER2 protein immunoreactivity is higher during the light phase. Additionally, the complex organization of cells that express vasopressin, vasoactive intestinal polypeptide, neuron-specific nuclear protein, calbindin and calretinin in the SCN, as demonstrated by their immunoreactivity, reveals an intricate network that may be related to the similarities and differences reported between rodents and primates in the literature.

Biomarkers and Bacterial Pneumonia Risk in Patients with Treated HIV Infection: A Case-Control Study

Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIVinfected patients do not currently exist. Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 mg/mL in cases vs. 1.93 mg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.