Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

[Controllable systemic destruction of old collagen fibers as a novel approach for rejuvenating biological aging in mammals.]

Aging of extracellular proteins colloidal systems is one of major synchronizing mechanism in mammal`s «biological clock¼. We hypothesized that induced controllable modification of connective tissue composition could reverse aging. In murine experimental models collagenase was used for selective destruction of old collagen. Oxygen consumption, urine hydroxyproline excretion, density and distribution of mature and old collagen and elastine fibers in dermal biopsies were determined. Collagenase injections significantly increased hydroxyproline excretion. We observed reduced density of mature and old collagen fibers and increased oxygen consumption in dermal biopsies after course of collagenase injections. Collagenase treatment intensified the destruction of mature and old collagen matrix and enhanced synthesis of new collagen and elastine fibers. Furthermore oxygen consumption increased. Our findings can be considered as indicator of collagenase systemic anti-aging (rejuvenation) activity.

24-Hour Profile of Blood Pressure, Heart Rate, Excretion of Electrolytes, and Locomotor Activity in Wistar-Kyoto and SHR Rats Under Conditions of Free-Run Rhythm.

We presented the results of our study of chronostructure of BP, HR, electrolyte excretion, and locomotor activity under conditions of "free-run rhythm" (light deprivation). In adult male Wistar-Kyoto (normotensive) and SHR (spontaneously hypertensive) rats, BP, biopotentials of the heart (ECG), and locomotor activity were recorded over 24 h by telemetric monitoring and the rate of excretion of electrolytes (Na+, K+, Ca2+, and Mg2+) during the nighttime and daytime hours was measured. It was found that under free-run rhythm, 24-h profiles of BP, HR, excretory function of the kidneys, and locomotor activity underwent more considerable changes in normotensive Wistar-Kyoto rats in comparison with hypertensive SHR rats. However, hypertensive rats demonstrated pronounced changes in rhythmic characteristics of HR, which can restrict adaptation reserves of the cardiovascular system.

Development of a clinical prediction model for the postthrombotic syndrome in a prospective cohort of patients with proximal deep vein thrombosis.

Essentials We developed a prediction model for postthrombotic syndrome (PTS) after deep vein thrombosis (DVT). High risk predictors were iliac vein DVT, BMI>35 and moderate-severe Villalta category. Patients with a score ≥4 had an odds ratio of 5.9 (95% CI 2.1-16.6) for PTS. SOX-PTS score may select DVT patients for close monitoring or aggressive strategies to treat DVT. SUMMARY: Background Postthrombotic syndrome (PTS) is a chronic complication that develops in 20-50% of patients after deep vein thrombosis (DVT). Although individual risk factors for PTS have been characterized, the ability to predict which DVT patients are likely to develop PTS remains limited. Objective To develop a clinical prediction score for PTS in patients with DVT. Methods The derivation cohort consisted of participants in the SOX Trial, a randomized double-blind placebo-controlled trial of elastic compression stockings versus placebo stockings worn for 2 years after DVT to prevent PTS in patients with a first proximal DVT, enrolled in 24 community and tertiary-care hospitals from 2004 to 2010. Multivariable logistic regression analysis of baseline characteristics was performed. The outcome was the occurrence of PTS, diagnosed starting from 6 months or later according to Ginsberg's criteria. Results Seven hundred and sixty-two patients were included in the analysis. The median follow-up was 728 days. The model includes three independent predictors, and has a range of possible scores from 0 to 5. High-risk predictors were: index DVT in the iliac vein; body mass index of ≥ 35 kg m-2 ; and moderate-severe Villalta severity category at DVT diagnosis. As compared with patients with a score of 0, those with a score of ≥ 4 had an odds ratio of 5.9 (95% confidence interval 2.1-16.6) for developing PTS. Conclusions To our knowledge, this is the first clinical prediction score for PTS. We identified three independent predictors that, when combined, predicted PTS risk after a first proximal DVT. The SOX-PTS score requires external validation before it can be considered for clinical use.

The postthrombotic syndrome: current evidence and future challenges.

Postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) that develops in 20-50% of patients. PTS manifests as a spectrum of symptoms and signs of chronic venous insufficiency that can impose significant morbidity and have a negative impact on quality of life. Chronic venous hypertension caused by a combination of residual venous obstruction and valvular reflux is believed to play a major role in the pathophysiology of PTS. The Villalta scale is the most widely applied clinical scale used to diagnose and define PTS. Proximal DVT and recurrent ipsilateral DVT are the two principal established risk factors for PTS, and efforts in recent years have been focused on identifying a combination of clinical and biomarker predictors that will define high-risk patients and possibly new therapeutic targets. The best way to prevent PTS is to prevent the occurrence of DVT, and to provide optimal anticoagulation for the acute phase of DVT once it occurs. Recent years have brought progress in our understanding of the role of endovascular techniques in the prevention and treatment of PTS and the subgroups of patients that may benefit from these modalities. Pharmacomechanical catheter-directed thrombolysis is the most promising interventional modality for prevention of PTS. This review summarizes the current state of evidence on PTS of the lower limbs, and highlights areas where uncertainty still exists that require further research.

Impact of adherence to local antibiotic prophylaxis guidelines on infection outcome after total hip or knee arthroplasty.

BACKGROUND: National guidelines exist regarding preoperative antibiotic treatment for the prevention of surgical site infection (SSI); however, there are no published studies showing rates of compliance with them. AIM: To establish compliance with national guidelines within our institution, and the impact of adherence, on SSI rate. METHODS: This was a retrospective observational study of 1019 patients undergoing hip or knee arthroplasty. Procedures were conducted at three metropolitan hospitals in Melbourne, Australia, throughout a 2.5-year period. Antibiotic prophylaxis recommendations were taken from the Australian Therapeutic Guidelines. FINDINGS: Of the procedures included, 61.3% adhered to prophylaxis guidelines, 38.7% did not. The total SSI rate was 2.7%; with an infection rate of 1.7% in those adherent to antibiotic guidelines, compared with a rate of 5.0% if non-adherent (P < 0.01). Overall, 98.4% of patients received a dedicated prophylactic antibiotic dose as per guidelines. Of the procedures, 1.7% lasted >4h with re-dosing being poorly adhered to (23.5% of procedures). In patients weighing >80kg (49.5% of surgeries), guideline-concordant dosing occurred in only 58.7% of cases. For patients >80kg without guideline-concordant dosing, the SSI rate was 6.6% and the odds ratio of SSI was 3.89 (confidence interval: 1.17-7.84; P = 0.01). CONCLUSION: Non-adherence to guidelines increased the risk of SSI in patients undergoing total knee and hip arthroplasty. Dosing adjustment recommendations of prophylaxis for patients weighing >80kg was poorly adhered to, and these patients were subsequently at higher risk of infection.

Para-aortic and pelvic extended-field radiotherapy for advanced-stage uterine cancer: dosimetric and toxicity comparison between the four-field box and intensity-modulated techniques.

BACKGROUND: In patients with advanced-stage endometrial carcinoma (eca), extended-field radiotherapy (efrt) is traditionally delivered by the 3-dimensional conformal (3d-crt) 4-field box technique. In recent years, the use of intensity-modulated radiotherapy (imrt) in gynecologic cancers has increased. We compared the delivery of efrt by the 3d-crt and contemporary imrt techniques. METHODS: After surgical staging and adjuvant chemotherapy in 38 eca patients, efrt was delivered by either imrt or 3d-crt. Doses to the organs at risk, side effects, and outcomes were compared between the techniques. RESULTS: Of the 38 eca patients, 33 were stage iiic, and 5 were stage ivb. In the imrt group, maximal doses to rectum, small intestine, and bladder were significantly higher, and mean dose to bladder was lower (p < 0.0001). Most acute gastrointestinal, genitourinary, and hematologic side effects were grade i or ii and were comparable between the groups. In long-term follow-up, only grade 1 cystitis at 3 months was statistically higher in the imrt patients. No grade iii or iv gastrointestinal or genitourinary toxicities were observed. No statistically significant differences in overall and disease-free survival or recurrence rates were observed between the techniques. CONCLUSIONS: In advanced eca patients, imrt is a safe and effective technique for delivering efrt to the pelvis and para-aortic region, and it is comparable to the 3d-crt 4-field box technique in both side effects and efficacy. For centres in which imrt is not readily available, 3d-crt is a valid alternative.

Predictive value of markers of inflammation in the postthrombotic syndrome: a systematic review: inflammatory biomarkers and PTS.

BACKGROUND: The postthrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Inflammation may contribute to its pathophysiology. OBJECTIVES: We conducted a systematic review of studies that analyzed the association between biomarkers of inflammation and PTS in DVT patients. METHODS: The electronic databases PubMed, EMBASE, Medline, Scopus and Web of Science were searched for studies published until March 2015 that measured blood inflammation biomarker levels in adult DVT patients and reported their association with PTS development. Two reviewers independently performed full text assessment and data extraction. RESULTS: Ten studies were included. Nine reported on the association between C-reactive protein and PTS; Interleukin (IL)-6 was measured in six studies; IL-8 in four studies; Intracellular adhesion molecule (ICAM)-1 in three studies; IL-10 and vascular cell adhesion molecule-1 in two studies; and monocyte chemotactic protein-1, matrix metalloprotease-9, P-Selectin, tumor necrosis factor α and erythrocyte sedimentation rate were measured in one study. Studies differed in terms of populations included, exclusion criteria, methods used for biomarker measurement and statistical measures of association between biomarkers and PTS. We were able to metaanalyze results only for IL-6 and found no significant association. Descriptively, ICAM-1 was significantly associated with PTS in two out of three studies that measured it. Other biomarkers did not demonstrate a significant association with PTS. CONCLUSIONS: Our systematic review found conflicting results regarding the role of inflammatory biomarkers as predictors of PTS. ICAM -1 appears to be a promising marker for further investigation.

Stretched arc discharge in produced water.

The objective of the present study was to investigate the feasibility of stretching an arc discharge in produced water to increase the volume of produced water treated by plasma. Produced water is the wastewater generated by hydraulic fracturing of shale during the production phase in shale-oil or shale-gas exploration. The electric conductivity of produced water is in the range of 50-200 mS/cm, which provides both a challenge and opportunity for the application of plasmas. Stretching of an arc discharge in produced water was accomplished using a ground electrode and two high-voltage electrodes: one positioned close to the ground electrode and the other positioned farther away from the ground. The benefit of stretching the arc is that the contact between the arc and water is significantly increased, resulting in more efficient plasma treatment in both performance and energy cost.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Risk factors for colonization with extended-spectrum beta-lactamase-producing enterobacteriaceae on admission to rehabilitation centres.

Patients newly admitted to rehabilitation centres are at high risk of colonization with multidrug-resistant bacteria because many of them have experienced prolonged stays in other healthcare settings and have had high exposure to antibiotics. We conducted a prospective study to determine the prevalence of and risk factors for colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) in this population. Subjects were screened by rectal swab for ESBL-PE within 2 days of admission. Swabs were plated on chromagar ESBL plates and the presence of ESBL was verified by a central laboratory. A multilevel mixed effects model was used to identify risk factors for ESBL-PE colonization. Of 2873 patients screened, 748 (26.0%) were positive for ESBL-PE. The variables identified as independently associated with ESBL-PE colonization were: recent stay in an acute-care hospital for over 2 weeks (OR=1.34; 95% CI, 1.12, 1.6), history of colonization with ESBL-PE (OR=2.97; 95% CI, 1.99, 4.43), unconsciousness on admission (OR=2.59; 95% CI, 1.55, 4.34), surgery or invasive procedure in the past year (OR=1.49; 95% CI, 1.2, 1.86) and antibiotic treatment in the past month (OR=1.80; 95% CI, 1.45, 2.22). The predictive accuracy of the model was low (area under the ROC curve 0.656). These results indicate that ESBL-PE colonization is common upon admission to rehabilitation centres. Some risk factors for ESBL-PE colonization are similar to those described previously; however, newly identified factors may be specific to rehabilitation populations. The high prevalence and low ability to stratify by risk factors may guide infection control and empirical treatment strategies in rehabilitation settings.

Association between thrombophilia and the post-thrombotic syndrome: a systematic review and meta-analysis.

BACKGROUND: The postthrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT), occurring in 20-40% of patients. Identifying risk factors for PTS may be useful to provide patients with prognostic information and target prevention strategies. OBJECTIVE: To conduct a systematic review to assess whether, among patients with DVT, inherited and acquired thrombophilias are associated with a risk of PTS. METHODS: We searched the electronic databases PubMed, EMBASE, Scopus, and Web of Science for studies published from 1990 to 2013 that assessed any thrombophilia in adult DVT patients and its association with the development of PTS. We calculated odds ratios and 95% confidence intervals for PTS according to the presence of thrombophilia. Meta-analysis was performed using the random-effects model. RESULTS: Sixteen studies were included: 13 assessed factor V Leiden (FVL), 10 assessed prothrombin mutation, five assessed protein S and C deficiencies, three assessed antithrombin deficiency, four assessed elevated FVIII levels, and six assessed antiphospholipid antibodies. None of the meta-analyses identified any thrombophilia to be predictive of PTS. Both FVL and prothrombin mutation appeared protective among studies including patients with both first and recurrent DVT and studies in which more than 50% of patients had an unprovoked DVT. CONCLUSIONS: Our meta-analysis did not demonstrate a significant association between any of the thrombophilias assessed and the risk of PTS in DVT patients. Other biomarkers in the pathophysiological pathway may be more predictive of PTS.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Boundary effects on effective conductivity of random heterogeneous media with spherical inclusions.

It is common to determine the effective conductivity of heterogeneous media by assuming stationarity of the random local properties. This assumption is not obeyed in a boundary layer of a body of finite size. The effect of different types of boundaries is examined for a two-phase medium with spherical inclusions of given conductivity distributed randomly in a matrix of a different conductivity. Exact solutions are derived for the apparent conductivity and the boundary layer thickness. The interaction between the spheres and the boundaries is fully incorporated in the solutions using a spherical harmonics expansion and the method of images. As applications, the corrections for the effective conductivity are given for two cases of finite bodies: the Maxwell sphere and a cylinder of flow parallel to the axis.

Carriage of methicillin-resistant Staphylococcus aureus on admission to European rehabilitation centres--a prospective study.

This study aimed to determine the prevalence of and risk factors for methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients newly admitted to rehabilitation centres. It is a prospective study examining MRSA carriage on admission to seven rehabilitation wards in four countries. Risk factors for MRSA carriage were analysed using univariate and multivariate analyses. A total of 1204 patients were studied. Among them, 105 (8.7%) had a positive admission MRSA screening result. The MRSA carriers were more likely to be male, to have had a recent stay in another long-term-care facility or >2 weeks acute-care hospital stay, history of colonization with MRSA, reduced level of consciousness, peripheral vascular disease and pressure sores. In multivariable logistic regression male gender (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.4-3.6, p 0.001), history of MRSA positivity (OR 6.8, 95% CI 3.8-12.3, p <0.001), peripheral vascular disease (OR 2.5, 95% CI 1.2-5, p 0.013), recent stay in another long-term-care facility (OR 2.1, 95% CI 1.3-3.5, p 0.004), or long (>2 weeks) acute-care hospital stay (OR 1.9, 95% CI 1.2-3, p 0.004), remained significant risk factors for MRSA carriage. MRSA carriage is common on admission to rehabilitation centres but less so, than previously described in long-term-care facilities. Male gender, history of MRSA positivity, previous hospitalization and peripheral vascular disease may predict MRSA carriage, and may serve as indicators for using pre-emptive infection control measures.

A multicenter validation of computerized tomography models as predictors of non- optimal primary cytoreduction of advanced epithelial ovarian cancer.

AIMS: To compare the validity of four predictive models of preoperative computerized tomography (CT) scans in predicting suboptimal primary cytoreduction in patients treated for advanced ovarian cancer. PATIENTS AND METHODS: Preoperative CT scans of patients with stage III/IV epithelial ovarian cancer who underwent primary cytoreductive surgery at one of four medical centers were reviewed by radiologists blinded to surgical outcome. The validity of each set of CT criteria previously published by Nelson, Bristow, Dowdy, and Qayyum as predictors of suboptimal cytoreduction was assessed. RESULTS: Data of 123 patients were evaluated. Optimal cytoreduction (largest diameter of residual tumor < or =1cm) was obtained in 90 (73.2%) patients. All CT models were able to significantly predict surgical outcome (p<0.02). The respective sensitivity, specificity, and accuracy of the CT models to predict sub-optimal cytoreduction was 64%, 64% and 64% for Nelson's criteria, 70%, 64% and 66% for Bristow's criteria, 79%, 60%, and 65% for Dowdy's criteria, and 67% 57% and 60% for Qayyum's criteria. CONCLUSIONS: Apart from Dowdy's criteria, the accuracy rates of CT predictors of suboptimal cytoreduction in the original cohorts could not be confirmed in this cross validation. This study underscores the difficulty in devising universally applicable selection criteria or models that reliably predict surgical outcome across institutions and surgeons.

[Temperature dependence of conformational properties of natural lipid oligomer chains: computer simulation].

The conformational properties of several oligomeric chain molecules at T = 278 and T = 403 K have been studied using Monte Carlo computer simulations. Hydrocarbon oligomers with methylene-interrupted cis double bonds in the main chain were considered. These oligomers are typical constituents of natural lipid molecules. The characteristics of the shape of C-H and C-C bond orientation distribution functions with respect to the principal axis of inertia of the chains and their temperature dependences were studied. It was found that the temperature sensitivity of not only the common geometric characteristics of the polyunsaturated chain is significantly reduced compared with the saturated one, but also that of local characteristics, i. e., the shape of each bond orientation distribution function of the polyunsaturated chain. The relationship between the properties of lipid polyunsaturated hydrocarbon chains and their functions in natural membrane systems, in particular their possible role in the stabilization or optimization of lipid-protein interactions, was discussed.

[Effect of cholesterol on the bond ordering in hydrated unsaturated lipid bilayers].

Molecular dynamics computer simulations of hydrated bilayers of unsaturated phosphatidylcholines in which double bonds are in the states: 18:0/18:1(n-9)cis (PC), 18:0/18:2(n-6)cis (PC), 18:0/18:3(n-3)cis (PC), 18:0/20:4(n-6)cis (PC), and 18:0/22:6(n-3)cis in the presence of cholesterol (40 mol%) and its absence have been performed. The simulation have been performed at 303 K and 1 atm, under the conditions corresponding to the experimentally observed liquid-crystalline state of the bilayer from phosphatidylcholine. The C-C and C-H bond order parameter profiles with respect to the bilayer normal and the C-C bond orientation distribution functions have been calculated. The widths of the functions and positions of their maxima have been determined. The dependence of these characteristics on the type of the bond, the degree of unsaturation of the chain, the presence of cholesterol in the bilayer, and the bond order parameters have been analyzed.