Early serum TARC reduction predicts prognosis in advanced-stage Hodgkin lymphoma patients treated with a PET-adapted strategy.

Among patients with advanced-stage classical Hodgkin lymphoma (cHL) receiving ABVD chemotherapy, PET performed after the first two treatment cycles (PET-2) has prognostic value. However, 15% of patients with a negative PET-2 will experience treatment failure. Here we prospectively evaluated serum thymus and activation-regulated chemokine (TARC) levels, to improve risk assessment in patients treated according to HD0607 PET-driven trial (#NCT00795613). In 266 patients with available serum samples, who have agreed to participate in a sub-study for assessment of the role of TARC monitoring, serum TARC levels were measured at baseline and at time of PET-2 by commercially available ELISA test kits. The primary end-point was to evaluate the association between TARC after 2 ABVD cycles and PFS. Median TARC-2 values were significantly higher in PET-2-positive patients compared to PET-2-negative patients (P = .001), and in patients with treatment failure compared to those in continuous CR (P = .01). The 4-year PFS significantly differed between patients with TARC-2 >800 pg/mL vs ≤800 pg/mL (64% vs 86%, P = .0001). Moreover, among PET-2-negative patients, elevated TARC-2 identified those with a worse prognosis (74% vs 89%; P = .01). In multivariable analysis, TARC-2 >800 pg/mL was a significant independent predictor of PFS in the whole study population (HR 2.39, P = .004) and among the PET-2-negative patients (HR 2.49, P = .02). In conclusion, our results indicate that TARC-2 serum levels above 800 pg/mL suggest the need for a stringent follow-up in PET-2-negative patients, and the evaluation of new drugs in PET-2-positive, who will likely fail to respond to intensification with escalated BEACOPP.

Baseline and Postoperative C-reactive Protein Levels Predict Long-Term Survival After Lung Metastasectomy.

BACKGROUND: Blood level of C-reactive protein (CRP) at diagnosis is a well-know prognostic bio-marker in different primary tumors, but its role has not been investigated in resectable lung metastases. The aim of our study is to assess the predictive value of baseline (CRP0) and 3rd postoperative day (CRP3) levels on long-term survival of patients undergoing lung metastasectomy. METHODS: A total of 846 consecutive patients underwent the first pulmonary resection for lung metastases between January 2003 and December 2015, including 611 (72%) single surgical procedures, 235 (28%) multiple metastasectomies, 501 (59%) epithelial primary tumors, 276 (33%) sarcomas, 66 (8%) melanomas, 286 (33.8%) with 0 risk factors (CRP0 ≤ 2 and CRP3 ≤ 84 mg/L) and 560 (66.2%) with ≥ 1 risk factor (CRP0 > 2 and/or CRP3 > 84 mg/L). RESULTS: Cumulative 5-year survival was 57% in patients with low CRP (0 risk factors) versus 43% in high CRP (≥ 1 risk factor, p < 0.0002), 62% versus 50% respectively for epithelial tumors (p < 0.0140), and 51% versus 34% for sarcomas (p < 0.0111). Multivariable Cox analysis confirmed a mortality hazard ratio of 2.5 at 1-year and 1.5 at 5-years in patients with high CRP. CONCLUSIONS: Baseline and postoperative CRP levels predict survival of patients with resectable lung metastases. These data provide a rationale for prospective clinical trials testing the efficacy of anti-inflammatory or immune-modulating agents as "adjuvant" therapy after lung metastasectomy, in patients with elevated pre- and/or postoperative CRP levels.

Application of Controlled Shear Stresses on the Erythrocyte Membrane as a New Approach to Promote Molecule Encapsulation.

Human red blood cells (RBCs) have a remarkable capacity to undergo reversible membrane swelling. Resealed erythrocytes have been proposed as carriers and bioreactors to be used in the treatment of various diseases. This work is aimed at developing a setup allowing the encapsulation of test molecules into erythrocytes by inducing reversible pore formation on the RBC membrane through the application of controlled mechanical shear stresses. The designed setup consists of two reservoirs connected by a glass capillary. Each reservoir is connected to a compressor; during the tests, the reservoirs were in turn pressurized to promote erythrocyte flow through the capillary. The setup was filled with a suspension of erythrocytes, phosphate buffer, and FITC-dextran. Dextran was chosen as the diffusive molecule to check membrane pore dimensions. Samples of the suspension were withdrawn at scheduled times while the setup was operating. Flow cytometry and stereo-optical microscopy analyses were used to evaluate the erythrocyte dextran uptake. The setup was shown to be safe, well controlled, and adjustable. The outcomes of the experimental tests showed significant dextran uptake by RBCs up to 8%. Microscopy observations highlighted the formation of echinocytes in the analyzed samples. Erythrocytes from different donors showed different reactions to mechanical stresses. The experimental outcomes proved the possibility to encapsulate test molecules into erythrocytes by applying controlled mechanical shear stresses on the RBC membrane, encouraging further studies.

Biological quality control for extracorporeal photochemotherapy: Assessing mononuclear cell apoptosis levels in ECP bags of chronic GvHD patients.

Extracorporeal photochemotherapy (ECP) is a treatment approved by the FDA for cutaneous T-cell lymphoma, and it is currently used off-label for graft-versus-host disease (GvHD) and other conditions. In agreement with good practices for the therapeutic use of human cells, quality control has to be performed to validate the ECP procedure with the off-line technique. Since no gold-standard biological test is available, we assessed the apoptosis generated in the ECP bag using a flow cytometric analysis. Thirty-one ECP procedures performed on 13 patients with chronic GvHD were studied by monitoring the induction of mononuclear cell (MNC) apoptosis using annexin V/propidium iodide double staining; residual lymphocyte proliferation to standard mitogens was also measured in 17 of the procedures. The kinetics of apoptosis was analyzed at different times in MNCs untreated or treated with 8-methoxy-psoralen plus ultraviolet A; the variation (ΔAPOPTOSIS ) after 24 h revealed the efficacy of the treatment. In 88.6% of the 31 ECP procedures, ΔAPOPTOSIS was >15% (the "alerting" threshold for ΔAPOPTOSIS was set at 15% on the basis of our data); in the remainder (19.4%), the increment in apoptosis was lower. In four procedures, the proliferation assay was useful for assessing the effect of ECP on the apheretic bag. In conclusion, both flow cytometric assays enabled a biologically significant result to be obtained. In our opinion, the apoptosis test-being faster and easier than the proliferation test-could be a reliable way to validate ECP procedures.

Identification of the novel HLA-C allele, HLA-C*04:520.

HLA-C*04:520, a novel HLA-C allele, differs from HLA-C*04:01:01 by one mismatch in exon 5.

Testing of human papillomavirus in lung cancer and non-tumor lung tissue.

BACKGROUND: Risk factors for lung cancer, such as cigarette smoking, environmental pollution, asbestos, and genetic determinants, are well-known, whereas involvement of the human papillomavirus (HPV) is still unclear. METHODS: We examined a series of 100 lung cancer patients from Italy and the UK for the presence of HPV DNA in both lung tumor specimens and adjacent non-tumoral specimens from the same patients. Thirty-five of the most clinically relevant HPV types were assayed using PCR amplification of the highly conserved L1 region of the viral genome followed by hybridization with specific probes. RESULTS: No HPV was detected in tumor specimens nor in normal lung tissue of any patient. CONCLUSIONS: These data indicate that, in this Western series, HPV is not associated with the risk of lung cancer. Our findings will help refine estimates of lung cancer risk in patients affected by a common viral infection involved in other types of human cancer.

Comparing BamHI-W and CE-marked assays to detect circulating Epstein-Barr Virus (EBV) DNA of nasopharyngeal cancer patients in a non-endemic area.

OBJECTIVES: Plasma Epstein-Barr Virus (EBV)-DNA is a well-established prognostic biomarker in nasopharyngeal carcinoma (NPC). Different methods for assessment include single-copy gene targeted, European Conformity (CE)-marked assays, which are mostly employed in non-endemic settings, vs multiple-copy gene targeted, in-house BamHI-W based assays, which currently represent the most widely used method for EBV-DNA quantification. To date, evidence concerning the commutability of these different assays is still limited. MATERIALS AND METHODS: From August 2016 to March 2018, 124 plasma and 124 whole blood (WB) samples from 93 NPC patients were collected at different time-points for each patient. EBV-DNA viral load was quantified in pre- (n = 12) and post-treatment (n = 9), follow-up (n = 53), and recurrent/metastatic (R/M) (n = 50) phase. For each sample, one in-house BamHI-W vs three different CE-marked plasma assays were compared; the performance of plasma vs WB matrix was also assessed. Quantitative agreement of EBV-DNA values was evaluated by linear correlation and Bland-Altman analysis. RESULTS: A statistically significant (p = 0.0001) agreement between all CE-marked and the BamHI-W assays was found using plasma matrix, regardless of clinical phase. The results obtained in copies/ml were comparable to those expressed in IU/ml. When using WB matrix, the number of positive detections increased in the post-treatment phase. CONCLUSIONS: Our retrospective comparison supported an agreement between Plasma BamHI-W and CE-marked assays in measuring EBV-DNA for non-endemic NPC patients. There were no significant interferences from different measurement units (IU/ml vs copies/ml). Further evaluations are needed to better clarify the role of WB.

Shear-Induced Encapsulation into Red Blood Cells: A New Microfluidic Approach to Drug Delivery.

Encapsulating molecules into red blood cells (RBCs) is a challenging topic for drug delivery in clinical practice, allowing to prolong the residence time in the body and to avoid toxic residuals. Fluidic shear stress is able to temporary open the membrane pores of RBCs, thus allowing for the diffusion of a drug in solution with the cells. In this paper, both a computational and an experimental approach were used to investigate the mechanism of shear-induced encapsulation in a microchannel. By means of a computational fluid dynamic model of a cell suspension, it was possible to calculate an encapsulation index that accounts for the effective shear acting on the cells, their distribution in the cross section of the microchannel and their velocity. The computational model was then validated with micro-PIV measurements on a RBCs suspension. Finally, experimental tests with a microfluidic channel showed that, by choosing the proper concentration and fluid flow rate, it is possible to successfully encapsulate a test molecule (FITC-Dextran, 40 kDa) into human RBCs. Cytofluorimetric analysis and confocal microscopy were used to assess the RBCs physiological shape preservation and confirm the presence of fluorescent molecules inside the cells.

Trends in prevalence in human papillomavirus types and their association with cervical dysplasia: an analysis on 15 138 women over 20 years.

To investigate trends in prevalence of various human papillomavirus types in order to assess the unmet clinical needs for women affected by human papillomavirus-related disease. Data of consecutive 15 138 patients undergoing human papillomavirus DNA testing from 1998 to 2018 were retrospectively identified. Human papillomavirus types were classified at high-risk according to the classification of the International Agency for Research on Cancer. The International Agency for Research on Cancer included seven human papillomavirus types covered by nine-valent vaccine and five not yet covered by any available vaccines. Overall, 4159 (65.3%), 1500 (23.5%) and 714 (11.2%) women had human papillomavirus types covered by nine-valent vaccination, not covered by nine-valent vaccination and co-infections of human papillomavirus types of both groups. At least one high-risk human papillomavirus type(s) was detected in 1241 patients with genital dysplasia: 832 (67.1%), 291 (23.4%) and 118 (9.5%) women had human papillomavirus types covered by nine-valent vaccination, not covered by nine-valent vaccination and co-infections of human papillomavirus types of both groups. Over the twenty-year study period, the number of human papillomavirus types not covered by nine-valent vaccine increased dramatically (from 4 to 16%; P < 0.001, P for trend). Similarly, looking at patients with genital dysplasia, high-risk human papillomavirus types not covered by nine-valent vaccine increased from 3 to 13% (P < 0.001, P for trend). Our data highlight that human papillomavirus types covered by nine-valent vaccine represent are the main types associated with genital dysplasia. However, over the study period, we observed an increasing prevalence of confections and high-risk human papillomavirus types not covered by the nine-valent vaccine, thus suggesting the need of developing more complete vaccines against human papillomavirus.

Serological proteome analysis of Staphylococcus aureus isolated from sub-clinical mastitis.

Staphylococcus aureus is the most common aetiologic agent of contagious bovine mastitis. Studies of the molecular epidemiology of S. aureus strongly suggest that some genetic subsets of strains are particularly well adapted for causing infections in cattle. This communication reports the setup of experimental protocols to identify the immunogenic proteins expressed by one of the most common field isolated strain of S. aureus responsible for sub-clinical mastitis cases. The serological proteome analysis (SERPA) approach applied consists of three main steps: two-dimensional electrophoresis-based separation of the proteins contained in field isolated S. aureus extracts enriched for surface proteins, detection of immunogenic spots using anti-serum collected from sub-clinical mastitis cases and identification of antigens by mass spectrometric-based methodologies. The study allowed to identify three immunogenic proteins: DNAase translocase FtsK, ribosomal proteins S1 and a Tell-like protein.

Nomogram-based prediction of cervical dysplasia persistence/recurrence.

The widespread introduction of screening methods allow to identify cervical dysplasia before having invasive cancer. The risk of developing cervical dysplasia persistence/ recurrence following conization represent a major health issue. Although several studies tried to identify predictors for cervical dysplasia persistence/recurrence, no previous study has been conducted to develop a risk calculator. The current study aimed to identify predictors of cervical dysplasia persistence/recurrence among women undergoing primary conization. We aimed to build nomograms estimating the risk of developing cervical dysplasia recurrence. Data of consecutive women with diagnosis of high-risk human papillomavirus (HPV) undergoing conization were retrospectively evaluated (1503 patients). The risk of developing cervical dysplasia persistence/recurrence was assessed with Kaplan-Meier and Cox's hazard models. Additionally, two nomograms were built to estimate likelihood of cervical dysplasia recurrence: the first based on baseline and operative parameters and the second focusing on type-specific HPV detected. The performance of the above nomograms was assessed using concordance index. A total of 1503 patients were analyzed. After a mean (SD) follow-up of 48.6 ( ± 17.5) months, 84 (5.6%) patients required secondary conization. By multivariate analysis, HIV infection [hazard ratio (HR): 7.78; 95% confidence interval (CI): 2.77-21.81; P < 0.001], positive margins (HR: 26.2; 95% CI: 14.1-48.71; P < 0.001) and persistence of HPV (HR: 6.82; 95% CI: 4.15-11.21; P < 0.001) correlated with cervical intraepithelial neoplasia 2+ persistence/recurrence. The importance of those variables was corroborated by our first nomogram. The second nomogram suggested the impact of type-specific HPV infection in predicting cervical dysplasia persistence/ recurrence. HPV16, HPV18, HPV33, HPV35 and HPV45 were the HPV types most commonly associated with cervical dysplasia persistence/recurrence. The concordance index was greater than 0.70 for both nomograms, thus suggesting the reproducibility of our models. We developed the first two nomograms predicting this risk. The findings of this study require external validation. Once validated our data might be useful to plan a tailored postoperative surveillance of women receiving primary conization.

Monitoring Vitamin B12 in Women Treated with Metformin for Primary Prevention of Breast Cancer and Age-Related Chronic Diseases.

Metformin (MET) is currently being used in several trials for cancer prevention or treatment in non-diabetics. However, long-term MET use in diabetics is associated with lower serum levels of total vitamin B12. In a pilot randomized controlled trial of the Mediterranean diet (MedDiet) and MET, whose participants were characterized by different components of metabolic syndrome, we tested the effect of MET on serum levels of B12, holo transcobalamin II (holo-TC-II), and methylmalonic acid (MMA). The study was conducted on 165 women receiving MET or placebo for three years. Results of the study indicate a significant overall reduction in both serum total B12 and holo-TC-II levels according with MET-treatment. In particular, in the MET group 26 of 81 patients and 10 of the 84 placebo-treated subjects had B12 below the normal threshold (<221 pmol/L) at the end of the study. Considering jointly all B12, Holo-TC-II, and MMA, 13 of the 165 subjects (10 MET and 3 placebo-treated) had at least two deficits in the biochemical parameters at the end of the study, without reporting clinical signs. Although our results do not affect whether women remain in the trial, B12 monitoring for MET-treated individuals should be implemented.

Predicting Factors for High-Grade Cervical Dysplasia in Women With Low-Grade Cervical Cytology and Nonvisible Squamocolumnar Junction.

OBJECTIVE: To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. METHODS: Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. RESULTS: Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ ( P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). CONCLUSIONS: High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy.

Artificial intelligence estimates the impact of human papillomavirus types in influencing the risk of cervical dysplasia recurrence: progress toward a more personalized approach.

The objective of this study was to determine whether the pretreatment human papillomavirus (HPV) genotype might predict the risk of cervical dysplasia persistence/recurrence. Retrospective analysis of prospectively collected data of consecutive 5104 women who underwent the HPV-DNA test were matched with retrospective data of women undergoing either follow-up or medical/surgical treatment(s) for genital HPV-related infection(s). Artificial neuronal network (ANN) analysis was used in order to weight the importance of different HPV genotypes in predicting cervical dysplasia persistence/recurrence. ANN simulates a biological neuronal system from both the structural and functional points of view: like neurons, ANN acquires knowledge through a learning-phase process and allows weighting the importance of covariates, thus establishing how much a variable influences a multifactor phenomenon. Overall, 5104 women were tested for HPV. Among them, 1273 (25%) patients underwent treatment for HPV-related disorders. LASER conization and cervical vaporization were performed in 807 (59%) and 386 (30%) patients, respectively, and secondary cervical conization in 45 (5.5%). ANN technology showed that the most important genotypes predicting cervical dysplasia persistence/recurrence were HPV-16 (normalized importance: 100%), HPV-59 (normalized importance: 51.2%), HPV-52 (normalized importance: 47.7%), HPV-18 (normalized importance: 32.8%) and HPV-45 (normalized importance: 30.2%). The pretreatment diagnosis of all of those genotypes, except HPV-45, correlated with an increased risk of cervical dysplasia persistence/recurrence; the pretreatment diagnosis was also arrived at using standard univariate and multivariable models (P<0.01). Pretreatment positivity for HPV-16, HPV-18, HPV-52 and HPV-59 might correlate with an increased risk of cervical dysplasia persistence/recurrence after treatment. These data might be helpful during patients' counseling and to implement new vaccination programs.

Effect of Tobacco Smoking Cessation on C-Reactive Protein Levels in A Cohort of Low-Dose Computed Tomography Screening Participants.

Smokers have higher levels of C-Reactive Protein (CRP) compared to never smokers. The role of smoking cessation on CRP is still under debate. Using data from two screening studies conducted in Italy in 2000-2010 on 3050 heavy smokers (including 777 ex-smokers), we estimated multivariate odds ratios (OR) for high CRP (i.e. ≥2 mg/L) according to smoking status. Moreover, in a longitudinal analysis based on 975 current smokers, with a second measurement of CRP after an average study period of 3.4 years, we estimated the changes in CRP according to smoking cessation. Prevalence of high CRP at baseline was 35.8% among ex-smokers and 41.1% among current smokers (significant OR for ex- vs. current smokers: 0.79). After four years since smoking cessation, CRP levels significantly decreased with increasing years of cessation (significant OR for ex-smokers since more than 8 years: 0.55). In the longitudinal analysis, no significant reduction in CRP was found for time since smoking cessation (ORs: 1.21, 1.04, and 0.91 for ex-smokers since 1 year, 2-3 years, and ≥4 years, respectively). In the largest prospective study available so far, we found that smoking cessation has a favourable effect on CRP, but this benefit is not evident in the short-term.

Inflammatory status and lung function predict mortality in lung cancer screening participants.

Low-dose computed tomography (LDCT) screening trials have based their risk selection algorithm on age and tobacco exposure, but never on pulmonary risk-related biomarkers. In the present study, the baseline inflammatory status, measured by C-reactive protein (CRP) level, and lung function, measured by forced expiratory volume in 1 s (FEV1), were tested as independent predictors of all-cause mortality in LDCT-screening participants. Between 2000 and 2010, 4413 volunteers were enrolled in two LDCT-screening trials, with evaluable baseline CRP and FEV1 values: 2037 were included in the discovery set and 2376 were included in the validation set. The effect of low FEV1 or high CRP alone or combined was evaluated by Kaplan-Meier mortality curves and hazard ratio (HR) with 95% confidence interval (CI) by fitting Cox proportional hazards models. The overall mortality risk was significantly higher in participants with FEV1 of up to 90% (HR: 2.13, CI: 1.43-3.17) or CRP more than 2 mg/l (HR: 3.38, CI: 1.60-3.54) and was still significant in the fully adjusted model. The cumulative 10-year probability of death was 0.03 for participants with FEV1 of more than 90% and CRP up to 2 mg/l, 0.05 with only FEV1 of up to 90% or CRP above 2 mg/l, and 0.12 with FEV1 of up to 90% and CRP above 2 mg/l. This predictive performance was confirmed in the two external validation cohorts with 10-year mortality rates of 0.06, 0.12, and 0.14, and 0.03, 0.07, and 0.14, respectively. Baseline inflammatory status and lung function reduction are independent predictors of all-cause long-term mortality in LDCT-screening participants. CRP and FEV1 could be used to select higher-risk individuals for future LDCT screening and preventive programs.

Potential impact of introducing a nonavalent HPV vaccination.

OBJECTIVE: To test the theoretical utility of incorporating nonavalent vaccination against HPV into a clinical setting. METHODS: The present retrospective study included data from consecutive patients who underwent HPV-DNA testing between January 1, 1998, and December 31, 2015. Changes in the prevalence of different HPV types were assessed during three periods (T1, 1998-2003; T2, 2004-2009; and T3, 2010-2015) using XY analysis. RESULTS: The study included a total of 13 665 patients. Overall, 1361, 5130, and 7174 patients were included in the T1, T2, and T3 periods, respectively. The quadrivalent vaccine would have potentially protected against HPV in 71.5% (973/1361), 46.5% (2385/5130), and 26.5% (1901/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The nonavalent vaccine could have protected against HPV in 92.5% (1259/1361), 72.3% (3709/5130), and 58.1% (4168/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The proportion of patients with genital dysplasia grade 2+ who did not have infections with HPV genotypes covered by the quadrivalent or nonavalent vaccines increased across the three periods (P<0.001 for trend). For all study periods, the protection provided by the nonavalent vaccine would have been superior to the quadrivalent vaccine (χ2 test P<0.001). CONCLUSION: The introduction of a nonavalent vaccine could improve protection against HPV infections and HPV-related genital dysplasia.

Characterization of cell wall associated proteins of a Staphylococcus aureus isolated from bovine mastitis case by a proteomic approach.

Staphylococcus aureus causes different pathologies in humans and animals. In particular, it is involved in intramammary infections in cows, causing economic losses and milk-safety problems. Although it is well-known that surface components (proteins and capsular polysaccharides) and exotoxins are virulence factors involved in the pathogenesis of bovine mastitis, less is known about the precise biochemical identity of such molecules. Therefore, mapping of surface proteins using specific disease- and environment-isolates provides a benchmark for strain comparison of pathogens with different pathogenic characteristics and antibiotic resistance mechanism and can aid in defining specific vaccine and therapeutic targets. In this study, we used a proteomic approach on protein extracts of lysostaphin-treated S. aureus in isotonic conditions, to produce a reproducible and well resolved 2-D electrophoresis (2-DE) reference map of surface associated proteins of isolated S. aureus from a case of bovine mastitis. The most abundant protein components were identified by Matrix assisted laser desorption ionisation-time of flight (MALDI-TOF) mass spectrometry.

C-reactive protein level predicts mortality in COPD: a systematic review and meta-analysis.

The prognostic role of baseline C-reactive protein (CRP) in chronic obstructive pulmonary disease (COPD) is controversial. In order to clarify this issue, we performed a systematic review and meta-analysis to assess the predictive effect of baseline CRP level in COPD patients. 15 eligible articles focusing on late mortality in COPD were included in our study. We performed a random-effects meta-analysis, and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals on mortality for the comparison between the study-specific highest category of CRP level versus the lowest category. In overall analysis, elevated baseline CRP levels were significantly associated with higher mortality (HR 1.53, 95% CI 1.32-1.77, I2=68.7%, p<0.001). Similar results were observed across subgroups. However, higher mortality risk was reported in studies using a cut-off value of 3 mg·L-1 (HR 1.61, 95% CI 1.12-2.30) and in those enrolling an Asiatic population (HR 3.51, 95% CI 1.69-7.31). Our analysis indicates that baseline high CRP level is significantly associated with higher late mortality in patients with COPD. Further prospective controlled studies are needed to confirm these data.

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer.

BACKGROUND: Higher blood levels of C-reactive protein (CRP) have been associated with shorter survival in patients with cardiovascular, chronic obstructive pulmonary disease and cancer. We investigated the impact of baseline and postoperative CRP levels on survival of patients with operable lung cancer (LC). PATIENTS AND METHODS: CRP values at baseline (CRP0) and 3 days after surgery (CRP3) were measured in a consecutive series of 1750 LC patients who underwent complete resection between 2003 and 2015. Patients were classified as having 0 (N = 593), 1 (N = 658) or 2 (N = 553) risk factors: CRP0 and/or CRP3 values above the respective median value. The effect of higher CRP was evaluated by Kaplan-Meier mortality curves and adjusted hazard ratio (HR) with 95% confidence interval (CI), by fitting Cox proportional hazards models. RESULTS: Cumulative proportions of 5-year survival were 67% for 0 risk factors, 58% for 1 risk factor and 41% for 2 risk factors (P < 0.0001). The overall 5-year mortality risk was significantly higher in patients with 1 risk factor (adjusted hazard ratio [aHR] 1.43 [95% CI 1.14-1.79]), or 2 risk factors (aHR 2.49 [95% CI 1.99-3.11]). A significant impact on survival was observed in each tumour-node-metastasis stage group, and in the subset of non-smokers. Postoperative 30-day mortality was significantly higher in patients with 2 risk factors only (aHR 2.2% versus 0.6%, p < 0.0475). CONCLUSIONS: Baseline and postoperative CRP levels predict immediate and long-term mortality in all stages of operable lung cancer. Patients with higher CRP levels could be candidate to randomised adjuvant trials with anti-inflammatory agents.