bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Happiness Promote Career Success? Revisiting the Evidence
Authors: Walsh Lisa C. , Boehm Julia K. , Lyubomirsky Sonja
Published: January 2018

Empirical research demonstrates a relationship between happiness and career success. For example, happy people receive higher earnings, exhibit better performance, and obtain more favorable supervisor evaluations than their less happy peers. Researchers have posited that success leads to happiness, but Boehm and Lyubomirsky reviewed the relevant research in 2008 and argued that the alternative hypothesis—that happiness causes success—may be equally plausible. A decade later, we return to the literature to supplement studies we previously cited with new research and to determine whether the results of cross-sectional, longitudinal, and experimental investigations provide additional support for this hypothesis. We conclude that the evidence continues to persuasively suggest that happiness is correlated with and often precedes career success and that experimentally enhancing positive emotions leads to improved outcomes in the workplace.
A dislocation-based solution for stress introduced by arbitrary volume expansion in cylinders
Authors: Wen Jici , Wei Yujie
Published: January 2018

A cylindrical structure undergoing volume expansion and contraction is common in engineering practice. For example, the charging (discharging) process of axisymmetrical batteries will give rise to volume expansion (shrinkage). The nitriding process of axles for better fatigue performance also introduces volume expansion. Here, by taking the equivalence of volume expansion (or shrinkage) as continuous insertion (or distraction) of infinitesimal dislocations, we supply a framework to solve the stress field of a cylinder with arbitrary insertion (distraction) profile of materials along the radial direction. Under the assumptions that the volume expansion profile along the axis of a cylinder is uniform and the deformation is small so that the current configuration is regarded as the original, we supply analytical solutions of stress fields to several typical volume expansion or shrinkage profiles. Our analysis shows that different volume variation gives rise to either high tensile stress in the surface or hydrostatic tension in the core, and supplies distinct failure mechanisms in cylindrical batteries.
Improved Measurement of Vascular Access Pressure
Authors: Kleinekofort W.
Published: January 2018

Vascular access stenosis and thrombosis is one of the key problems for hemodialysis patients. Prospective monitoring of static venous dialysis pressures can be applied to detect outflow stenoses in a vascular access. However, the location of stenoses within the access may influence the diagnostic value of venous pressure measurements. Whereas a decrease in access flow occurs with all types of stenosis, strictures within the arterial anastomosis or between arterial and venous dialysis needle cannot be detected with venous pressure measurements alone.

A new approach is discussed, which bases on the improved measurement of static venous and arterial extracorporeal pressures. Extracorporeal pressure at zero blood flow depends on both the position of the heart relative to the extracorporeal blood circuit and the vertical offset between access site and fluid level in the bloodline. After hydrostatic correction of each pressure signal the normalized arterial and venous intra-access pressure ratio AP/MAP can be calculated. A venous stenosis leads to an increase in both arterial and venous pressure ratio. In case of access stenosis between arterial and venous needle the ratio of venous pressure to mean arterial pressure is normal, and only the arterial pressure ratio is elevated. In summary, a combination of arterial and venous pressure measurement is more sensitive and allows differentiation between mid-access and venous stenosis. Hydrostatic correction of the dialysis pressure signal is inevitable. To minimize the rate of access thrombosis, venous and arterial intra-access pressure should be considered when evaluating dialysis pressures as part of any access monitoring program.
Valved Central Venous Catheter Connected to Subcutaneous Port: A Multicenter Phase IV Study Based on a Cohort of 50 Oncology Patients
Authors: Biffi R. , Pittiruti M. , Gillet J.P. , Fobe D. , Hermanne J.P. , Pescio M. , Gourlia A. , Collet K. , Battelli C. , Cenciarelli S.
Published: January 2018

Purpose

Since technical aspects and clinical features of central venous valved catheters are far from being completely understood, a multinational group of investigators has decided to assess a new distally-valved catheter connected to a port, in the clinical setting of oncology patients undergoing chemotherapy, in an attempt to verify its safety and viability, while also investigating its practical features.

Methods

Our project was structured as a phase IV multicenter study. Hospitalized adults (ages 18–80 years) who had solid tumors and were candidate for intravenous chemotherapy met the criteria to enter the study. One single type of port was used (made of titanium, plastic and silicone) connected to a silicone, distally valved catheter (as manufactured by B. Braun Aesculap). A case report form was provided for each treated case; all relevant data regarding implantation and follow-up were entered into the form, mailed to a coordinating center (G. Chevillon, B. Braun Medical, France) and stored in a software database for statistical analysis.

Results

50 patients (from 6 participating centers) were included in this study. No major complications occurred at insertion. The most frequent clinical problem during follow-up was inability to draw blood samples (9% during the first chemotherapy cycle; 8% after the second cycle); blood obtained from the device was defined “unsuitable for hematology test” in 9% of the cases at first chemotherapy cycle and in 23% of the cases after the second cycle. No catheter obstruction occurred.

Conclusion

The distally valved catheter port tested in this study was reliable, safe and practical for long-term treatment of an oncology patients’ population undergoing chemotherapy. As most other reports and clinical trials dealing with other types of distally valved catheters pointed out, inability to draw viable blood samples (so called withdrawal occlusion) is a major concern in their clinical use. Mechanisms underlying this technical problem are still unclear.
Thrombotic Events of Arteriovenous Fistulae in Hemodialysis Patients Related to the C677T Thermolabile Variant of Methylenetetrahydrofolate Reductase
Authors: Trimarchi H. , Genoud V. , Schropp J. , CastañÓN M. , Freixas E. , Forrester M. , Pereyra H. , Kordich L.
Published: January 2018

Background

Hyperhomocysteinemia is a risk factor for thrombosis, a frequent complication of vascular access (VA) in hemodialysis (HD). The enzyme methylenetetrahydrofolate reductase (MTHFR) is necessary for the remethylation of homocysteine (Hcy) to methionine. It has been postulated that patients homozygous and, to a lesser extent, heterozygous for the C677T thermolabile variant of this enzyme present a reduced catalytic activity, with secondary increases in plasmatic Hcy levels (normal: 10 ± 5 μmol/L) and an elevated risk of vascular thromboses.

Methods

Sixty-two patients on chronic HD were divided into two groups: group A (n = 23, 37.1%) was normal for the enzyme (CC); group B (n = 39, 62.9%) was heterozygous (CT). Both groups were not different according to age, sex, time on HD, hematocrits (Hct), baseline levels of Hcy, folic acid and vitamin B12. After the 1st HD session patients were started on folic acid 10 mg/day and 500 μg/week of intravenous (i.v.) methylcobalamin.

Results

Two years later, thrombotic events were not different between the two groups. Group A = 5 (21.7%) vs. group B = 12 (30.7%), Hcy levels were significantly different between final and baseline measurements (group A 21.5 ± 5.2 vs. 16.6 ± 3.9 μmol/L, p = 0.02; group B 22.1 ± 8.9 vs. 16.1 ± 3.9 μmol/L, p = 0.008), folic acid (group A 22.1 vs. 346.9 ng/ml, range (r) = 166–527, p<0.001; group B 19.2 vs. 218.5 ng/ml, r = 138–298, p<0.001) and vitamin B12 (group A 1489 vs. 3192.3 pg/ml, r = 1494–4890, p = 0.01; group B 1086 vs. 1513.8 pg/ml, r = 1092–1934, p = 0.02).

Conclusions

HD patients heterozygous for the C677T variant of the enzyme MTHFR can present a similar risk of thrombotic events in arteriovenous fistulae (AVF) compared to patients normal for the enzyme at a 1-yr follow-up. These results could be explained by an adequate control of Hcy levels after folic acid and methylcobalamin replacement therapy.
Advantages of a nurse-led central venous vascular access service
Authors: Hamilton H.C.
Published: January 2018

Inserting central venous catheters for patients requiring parenteral nutrition (PN) is expensive and time consuming, particularly if operating theatre facilities are used. Expanding the role of a clinical nurse specialist, with previous experience in critical care, enabled this procedure to be performed percutaneously at the bedside, cutting costs, freeing medical staff time and improving patient care.
Accuracy of Implanted Port Placement with the use of the Electromagnetic CathTrack® catheter locator system
Authors: Popp M.B. , Dobrilovic N. , Matern W. , Korelitz J. , Morin R. , Foundas S. , Fegelman E. , Juergens C. , Schaefer S. , Brophy P.F.
Published: January 2018

Purpose

To test whether an electromagnetic guidance system such as CathTrack® would allow long-term central venous access devices to be reliably placed at a decreased cost and without radiation exposure to patients and staff. The following study was undertaken to verify accuracy of the CathTrack® system for catheter placement and to develop guidelines for its use.

Methods

Twenty-nine consecutive patients were prospectively enrolled in the study and taken to the operating room for implantation of a permanent central venous access port. By protocol, the CathTrack® system was used to guide initial catheter positioning using the center of the third intercostal space along the right sternal border as the desired external target. Fluoroscopy was then used to visualize tip position and relocate the catheter tip to the exact position desired by the surgeon.

Results

Catheter placement using the CathTrack® system was successfully accomplished in 27 out of 29 patients. In two instances CathTrack® was abandoned and fluoroscopy utilized because of difficulty in threading the initial guidewire into the superior vena cava.

Conclusion

The CathTrack® electromagnetic locator system can be used to reliably position catheters for the establishment of long-term central venous access. Decreased cost and elimination of radiation exposure are distinct advantages of this system over fluoroscopy.
Hemodialysis Arteriovenous Fistulas: A Nineteenth Century View of a Twenty First Century Problem
Authors: Ross J.L.
Published: January 2018

This is a literature review which approaches the problem of successful use of arteriovenous fistulas for dialysis within the construct of Virchow's triad. By organizing the literature with regard to Virchow's concepts of blood flow, vascular injury, and thrombophilia an improved understanding arteriovenous fistula placement, maintenance and repair can be obtained. This process is designed to increase understanding and options for treatment by looking at this problem and using scientific knowledge gained in cardiology, oncology and vascular surgery medicine. Future approaches to fistulas will hopefully be a multifaceted and based in cellular pathophysiology as well as surgical and radiologic interventions and repairs.
Infection assessment of totally implanted long-term venous access devices
Authors: Brouns F. , Schuermans A. , Verhaegen J. , De Wever I. , Stas M.
Published: January 2018

Aim

Comparison of catheter tip versus port content culture techniques to assess infection in totally implanted vascular access devices (TIVAD).

Materials and methods

Comparison of pocket swab, catheter-tip and port content cultures after removing the silicon puncture septum in a prospectively collected consecutive series of 102 TIVAD removed for clinical suspicion of infection, between May 2000 and March 2003.

Results

102 totally implanted port-catheters in 98 patients, age ranging from 1 to 90 years (median 53 years), were removed 7 to 2616 days after insertion (median 210 days). Infection of the pocket surrounding the port was found in 21 cases, all proven by a positive culture of the pocket swab. Out of the remaining 81 cases without pocket infection, 32 had only a positive catheter tip culture, whereas 56 had a positive port content culture (p = 0.0002). Always the same microorganism was isolated in the 32 patients with positive catheter tip and port content cultures. The main organisms identified within TIVAD were Coagulase Negative Staphylococcus (CNS) (41 cases) and Candida sp (15 cases). Eight out of the 21 pocket infections were caused by Staphylococcus aureus.

Conclusion

In the presence of local signs of infection, taking cultures of the pocket surrounding the port is sufficient for diagnostic purposes. When infection is localized within the device only, port content cultures taken after removal of the silicon septum are more often positive than cultures of the catheter tip, and constitute therefore a more reliable tool for the assessment of TIVAD infection.
How to improve dialysis adequacy in patients with vascular access problems
Authors: Mandolfo S. , Borlandelli S. , Ravani P. , Imbasciati E.
Published: January 2018

Blood flow rate is a critical factor in the achievement of an adequate dialysis dose. The aim of this review is to evaluate the possibility of optimizing dialysis dose in terms of Kt/V in patients with reduced vascular access (VA) flow rate, considering effective blood flow (Qb eff), recirculation, access flow and hemodialyzer. In patients where the achievement of adequate blood flow rates are difficult to obtain and no surgical revision is necessary, to avoid under dialysis the increase in the treatment time should be the first choice solution. If such a solution is difficult for various reasons, a forced partial blood flow recirculation, especially in central venous catheters (CVCs) with reversed lines can be useful, on condition that the dialysis session is prolonged. The possibility of increasing the efficiency of dialysis through an increase in filter clearance has to be considered. Monitoring arterial pre-pump pressure (P asp) and optimizing ratio P asp/Qb eff during hemodialysis (HD) is one possible solution to improve blood flow rates, but it is necessary to educate and involve the staff. Recent developments in a new class of highly effective hemodialyzer due to dialysate distribution, has opened up interesting opportunities in terms of dialysis adequacy in patients with reduced VA flow rate
Carotid artery repair after erroneous insertion of a hemodialysis catheter: case report
Authors: Kaitzis D.G. , Balitas A.G. , Skandalos I.K. , Hatzibaloglou A.K.
Published: January 2018

The internal jugular vein is increasingly being used as a route for dual-lumen hemodialysis catheter placement. The use of jugular catheters as vascular access for hemodialysis can be associated with serious complications. The most frequent problems are the arterial puncture and haematoma. We present a rare complication of catheterization of the right common carotid artery during dual-lumen catheter placement into the right internal jugular vein. The complication was diagnosed the next day and the catheter was removed operatively. A review of the literature on complicated carotid artery catheterization is also presented.
Prediction of natalizumab anti-drug antibodies persistency
Authors: Deisenhammer Florian , Jank Marlies , Lauren Anna , Sjödin Anders , Ryner Malin , Fogdell-Hahn Anna , Sievers Claudia , Lindberg Raija , Jensen Poul Erik , Sellebjerg Finn , Christodoulou Louis , Birchler Mary , Pallardy Marc , Auer Michael , Liblau Roland ,   ABIRISK consortium
Published: January 2018

Background:

Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency.

Design/methods:

We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured.

Results:

Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67).

Conclusion:

High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.
Research in carceral contexts: confronting access barriers and engaging former prisoners
Authors: Watson Tara Marie , van der Meulen Emily
Published: January 2018

Prison systems, with the ability to reject or approve applications for conducting research with incarcerated populations, function as shapers of carceral knowledge and thus can potentially close opportunities for new qualitative studies as well as affect the quality and richness of the data obtained. This article describes a collaborative research process wherein access to current prisoners was not granted, and only former prisoners who were not on parole were eligible to participate in the study. We provide a unique reflective analysis of how access barriers altered the scope of our research and may have impacted our findings were it not for a change in our recruitment plan. We also incorporate insights from multiple literatures that speak to the value, challenges, and ethical concerns associated with doing research with former prisoners. Our contribution to the qualitative carceral literature sparks new questions worthy of further in-depth exploration, in particular how to more meaningfully involve former prisoners in the research process.
Dementia in Eastern Mediterranean countries: A systematic review
Authors: Yaghmour Sara Mahmoud , Bartlett Ruth , Brannelly Tula
Published: January 2018

Globally, there is an increase in the older population, whose lives are affected by local cultural norms. In Eastern Mediterranean countries, dementia is conventionally hidden from view with few dedicated services or recognition for diagnosis. The aim of this systematic review is to explore the limited literature on dementia and cognitive impairment among older people in Eastern Mediterranean countries to present an evaluation of current practices and to consolidate knowledge for future planning. Thirty-three studies were identified for inclusion in the review, and four themes were apparent. Firstly, prevalence, comorbidity and gender: In Eastern Mediterranean countries, many studies identify that the prevalence of dementia is high. As is the case elsewhere, many older adults in Eastern Mediterranean countries have at least one coexisting long-term condition, and some experience low life-satisfaction. Secondly, culture: In Eastern Mediterranean countries, the older adult is highly respected, and placement outside of the family home is considered an abandonment of family duty. The term dementia carries stigma, and it is widely believed that dementia is caused by ‘fate’. Thirdly, recognition and tools: There is a lack of verified assessment instruments to assess for dementia. Despite concerns about the cultural appropriateness of the Mini-Mental State Exam, particularly for people who have low literacy levels, and low literacy being the norm in Eastern Mediterranean countries, the Mini-Mental State Examination is the main assessment instrument. Translation and transition of non-Arabic assessment instruments and tools with psychometric properties presents a challenge for clinicians. Finally, workforce issues: health care workers lack knowledge about dementia, as dementia care is a relatively recent addition to the nursing and medical syllabi. While there were some inconsistencies in the papers published, many of the articles call for increasing educational programmes and health and social care policies to promote improved and practical gerontological nursing and medicine. Health care professionals need education about sociocultural, religious, and language needs to deliver improved culturally sensitive care.
Totally Percutaneous Fenestration via the “Cheese-Wire” Technique to Facilitate Endovascular Aneurysm Repair in Chronic Aortic Dissection
Authors: Stern Jordan R. , Cafasso Danielle E. , Schneider Darren B. , Meltzer Andrew J.
Published: January 2018

Here, we describe a totally percutaneous technique for longitudinal fenestration of a chronic dissection flap in the setting of endovascular aneurysm repair (EVAR), where the septum would otherwise preclude proper endograft sealing. This technique is demonstrated in a 65-year-old man with a history of open surgical repair of a Stanford type A aortic dissection, with a type B component that was managed nonoperatively. The patient developed aneurysmal degeneration of the infrarenal aorta during follow-up, and his anatomy was well suited for EVAR with the exception of a chronic dissection flap dividing the proximal seal zone. Using bilateral percutaneous access, a wire was passed through an existing fenestration in the septum from true to false lumen and snared from the contralateral side. Downward traction on this through-wire was then used as a “cheese-wire” to divide the septum longitudinally and clear it from the proximal fixation site. Removal of the septum provided an adequate proximal seal zone for the endograft, and standard infrarenal EVAR was then performed with a good technical result. Longitudinal fenestration using this technique is a useful adjunctive maneuver to facilitate EVAR in the setting of chronic aortic dissection and is safely achievable via a totally percutaneous approach.
Random vibration of vehicle with hysteretic nonlinear suspension under road roughness excitation
Authors: Hua CR , Zhao Y , Lu ZW , Ouyang H
Published: January 2018

The analysis of random vibration of a vehicle with hysteretic nonlinear suspension under road roughness excitation is a fundamental part of evaluation of a vehicle’s dynamic features and design of its active suspension system. The effective analysis method of random vibration of a vehicle with hysteretic suspension springs is presented based on the pseudoexcitation method and the equivalent linearisation technique. A stable and efficient iteration scheme is constructed to obtain the equivalent linearised system of the original nonlinear vehicle system. The power spectral density of the vehicle responses (vertical body acceleration, suspension working space and dynamic tyre load) at different speeds and with different nonlinear levels of hysteretic suspension springs are analysed, respectively, by the proposed method. It is concluded that hysteretic nonlinear suspensions influence the vehicle dynamic characteristic significantly; the frequency-weighted root mean square values at the front and rear suspensions and the vehicle’s centre of gravity are reduced greatly with increasing the nonlinear levels of hysteretic suspension springs, resulting in better ride comfort of the vehicle.
The application of proportional–integral–derivative–type fuzzy controller for synchronized XY motion gantry stage system
Authors: Mao Wei-Lung , Hung Chung-Wen , Suprapto
Published: January 2018

Gantry systems in which two linear motors are used to drive a single axis provide flexible and efficient solutions for a wide range of material handling applications. It is an important issue to find a way to drive the parallel stage to achieve a synchronous motion effectively and precisely. In this research, the proportional–integral–derivative–type fuzzy controller structure is presented for precision trajectory tracking control in synchronized XY motion gantry stage system. Three proportional–integral–derivative–type fuzzy controllers are designed for each axis, and the complete membership functions and rule table are developed to fulfill the better tracking capability. The controller parameters, which include the scaling factor of fuzzy rules and proportional–integral structures, are searched using the cross-mixing global artificial bee colony algorithm. The algorithm can optimize these parameters based on the integral of the time-weighted absolute error criterion. MATLAB system identification tool is used to find the equivalent coupled transfer functions of the gantry system. The proposed cross-mixing global artificial bee colony algorithm is utilized to offer the better convergence speed and avoid the local optimal solution in the searching process. The simulation results and experimental results on star and circle reference contours are presented to show that the proposed cross-mixing global artificial bee colony–based fuzzy controller indeed accomplish the better tracking performances in motion control application.
How to Express Tumor Markers in Bronchoalveolar Lavage
Authors: Caro Gómez de Terreros F.J. , Álvarez-Sala R. , Prados M.C. , Callol L. , Gómez de Terreros Sínchez F.J. , Villamor J.
Published: January 2018

Introduction

Bronchoalveolar lavage (BAL) is a fundamental technique in the diagnosis of different respiratory diseases including lung cancer. Tumor marker values can be determined in the BAL fluid, but controversy still exists about how to express the results.

Objective

The aim of this study was to determine the best method of expressing tumor markers in BAL, either referring to total proteins or volume of fluid recovered.

Patients and Methods

A prospective, randomized, non-blind study was carried out. Seventy-six patients (72 men and 4 women) diagnosed with lung cancer and 17 subjects without respiratory disease were included. BAL was performed in all patients and the fluid retrieved was divided into two fractions: a bronchiolar fraction (F0) and an alveolar fraction (F1). Five tumor markers: cytokeratin fragment 19 (CYFRA 21–1), squamous cell carcinoma antigen (SCC), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and neuron-specific enolase (NSE) as well as total protein were measured in both fractions. The concentrations were expressed in relation to the volume of BAL fluid recovered (ng or mU/mL) and in milligrams of total protein of lavage fluid (ng or mU/mg TP). The SPSS 11.01 software was used for statistical analysis. Mann-Whitney U test and ROC curves were developed when significant differences were found.

Results

We found significant differences in the CYFRA 21-1 values in the two BAL fractions and in both ways of expressing its concentration; in SCC in F1 expressed in ng/mg TP; in TPA in F0 expressed in mU/mg TP; in TPS in both fractions expressed in mU/mg TP, and in NSE in both fractions in ng/mg TP. The markers that best differentiated tumors from controls (ROC curves) were CYFRA 21-1 in F0 and NSE in both fractions in ng/mg TP.

Conclusions

Our study demonstrates that the concentrations of tumor markers in BAL expressed in relation to total protein were more effective than if expressed in mL of BAL fluid collected.
MUC3 and MCA Serum Levels and Steroid Receptor Content in Breast Cancer
Authors: Quaranta M. , Coviello M. , Daniele A. , Abbate I. , Durrant L.G. , Paradiso A. , Schittulli F.
Published: January 2018

Mucins are an important class of complex glycoproteins expressed by many epithelial cells and their malignant counterparts. The aim of this study was to determine the serum levels of MUC3 and mucin-like carcinoma-associated antigen (MCA) in patients with primary breast cancer and to analyze the possible relationships between these two mucins and the steroid receptor status. The preoperative basal serum levels of MUC3 (ELISA assay with monoclonal antibody 1143/B7) and MCA (EIA assay with anti-MCA mouse monoclonal antibody b-12) were determined in 44 patients with breast cancer while estrogen receptor (ER) and progesterone receptor (PgR) levels were measured by the dextran-coated charcoal method in the cytosol of neoplastic tissue. MUC3 was expressed in 43/44 serum samples while high MCA serum levels were found in 16/44 only; the mean values of both markers did not correlate with menopausal status, tumor size, nodal involvement or ER. The only significant difference observed was a lower median value of MCA in patients with small tumors (T1–T2). No statistically significant correlation between MUC3 and MCA, MUC3 and ER or MCA and ER was observed; a statistically significant direct correlation between MUC3 and PgR+ status and a statistically significant inverse correlation between MCA and PgR+ were observed. Our results suggest that further investigations are necessary to establish whether progesterone can modulate MUC3 and MCA expression in breast cancer.
Lack of Association of Cyp1B1*3 Polymorphism and Ovarian Cancer in a Caucasian Population
Authors: Cecchin E. , Russo A. , Campagnutta E. , Martella L. , Toffoli G.
Published: January 2018

CYP1B1 is the enzyme with the highest efficiency of conversion of estradiol to 4-hydroxyestradiol in humans. This metabolite has a well-known carcinogenic effect interacting with genomic DNA and has been hypothesized to be partly responsible for the role played by estrogens in ovarian cancer development. A polymorphism has been described for this enzyme causing a Leu to Val substitution in position 432 (CYP1B1*3). The Val432 allele has a higher efficiency of conversion of estradiol to 4-hydroxyestradiol and has been reported to increase the risk of ovarian cancer. A previous study reported a higher, significant prevalence of CYP1B1*3 polymorphism in ovarian cancer patients of mixed ethnicity. The aim of this study was to investigate the role of CYP1B1*3 polymorphism as a risk factor for ovarian cancer in a Caucasian population. The polymorphism frequency was determined in 223 cases of ovarian cancer and compared with that of 280 healthy female blood donors. Genetic analysis was performed on genomic DNA from PBMC and RFLP methods were used for mutation detection. No significant difference between cases and controls was found. These results do not support a favoring role of CYP1B1*3 in ovarian cancer development in our population.
Therapeutic Strategies to Improve the Efficacy of Oxaliplatin in Gastrointestinal Tumors
Authors: Sarmiento R. , Saponiero A. , Gasparini G.
Published: January 2018

The pharmacological characteristics of oxaliplatin make it one of the better chemotherapeutics to be combined with novel molecular-targeted anticancer treatments for the therapy of gastrointestinal tumors. The purposes of this review article are to report the preliminary data of combined therapy of oxaliplatin with inhibitors of angiogenesis or epidermal growth factor receptor and to suggest novel oxaliplatin-based therapeutic strategies. It is hypothesized that well designed, personalized, molecular-based treatments may improve the efficacy of oxaliplatin for the treatment of colorectal, gastric and pancreatic cancer. It is mandatory to rationalize such an approach by adequate determination of predictive surrogate biomarkers of response related to the targets in each single tumor against which therapy is aimed, using standardized assays and quality control.
Association of Human Papillomavirus with Prostate Cancer: Analysis of a Consecutive Series of Prostate Biopsies
Authors: Carozzi F. , Lombardi F.C. , Zendron P. , Confortini M. , Sani C. , Bisanzi S. , Pontenani G. , Ciatto S.
Published: January 2018

The study purpose was to investigate the association of human papillomavirus (HPV) infection with prostate cancer. The presence and type of HPV DNA were investigated by polymerase chain reaction in the preservation fluid of 60 consecutive prostate core biopsies (29 benign, 31 malignant). The material was inadequate (no DNA found at β-globin testing) in four benign and five cancer biopsies. HPV DNA was found in 17 of 26 (65.3%) cancer and 12 of 25 (48.0%) benign biopsies (χ2 = 0.94, p = 0.33). High-risk HPV type positivity was observed in 14 of 26 (53.8%) cancer and in five of 25 (20.0%) benign biopsies (χ2 = 4.38, p = 0.03). Twenty-three of 29 cases were positive at L1 region testing with MY09/11 primers; testing with primers directed to the E6/E7 region revealed six further HPV-positive cases (four cancer, two benign). The presence of HPV in prostate tissue suggests a possible reservoir for sexual transmission of types with oncogenic potential. Our findings also suggest a possible role of high-risk HPV infection in the etiology of prostate cancer and encourage further research into this issue.
Serum Cathepsin H as a Potential Prognostic Marker in Patients with Colorectal Cancer
Authors: Schweiger A. , Christensen I.J. , Nielsen H.J. , Sørensen S. , Brünner N. , Kos J.
Published: January 2018

Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly increased in patient sera, the median level was 8.4 ng/mL versus 2.1 ng/mL in 90 healthy blood donors (p<0.0001). A weak association of cathepsin H levels was found with patient age (p=0.02) but not with Dukes’ stage, sex, or the level of carcinoembryonic antigen (CEA). In survival analysis a significant difference was found between the group of patients with low cathepsin H (first tertile) who had a poor prognosis and the remaining patients (p=0.03). The risk of patients was further stratified when cathepsin H levels were combined with CEA. Patients with high CEA and low cathepsin H had the highest risk of death with a hazard ratio of 2.72 (95% CI 1.73–4.28), p<.0001. Our results show that the prognostic information of cathepsin H differs from that of the related cathepsins B and L and suggest different roles during the progression of malignant disease.
The Favorable Prognostic Significance of Surgery-Induced Hyperprolactinemia in Node-Positive Breast Cancer Patients: Ten-Year Disease-Free Survival Results
Authors: Bignami A. , Lissoni P. , Brivio F. , Galbiati F. , Pescia S. , Messina G. , Frontini L. , Meregalli S. , Gardani G.S.
Published: January 2018

It has been shown that each manipulation of the mammary region, including breast surgery, may stimulate prolactin secretion. However, it has also been observed that in more than 50% of breast cancer patients surgical removal of the tumor is not followed by enhanced prolactin secretion. This might be indicative of an altered psychoneuroendocrine control of the mammary gland, which could lead to the onset of more biologically aggressive breast cancer. In fact, surgery-induced hyperprolactinemia has been proven to be associated with a better prognosis in terms of survival in node-negative breast cancer patients. The present study was performed to investigate the impact of postoperative hyperprolactinemia on the disease-free survival (DFS) of breast cancer patients with axillary node involvement. The study included 100 consecutive node-positive breast cancer patients who were followed for at least 10 years. Surgery-induced hyperprolactinemia occurred in 45/100 (45%) patients without any significant correlation with the main prognostic variables including number of involved nodes and ER status. The two groups of patients received the same adjuvant therapies. After a median follow-up of 151 months, the recurrence rate in patients with surgery-induced hyperprolactinemia was significantly lower than in patients with no postoperative hyperprolactinemia (23/45 vs 43/55, p<0.01). Moreover, DFS was significantly longer in hyperprolactinemic patients than in patients who had no enhanced secretion of prolactin postoperatively. In agreement with the results described previously in node-negative breast cancer, our study demonstrates the favorable prognostic significance of surgery-induced hyperprolactinemia in terms of DFS duration also in breast cancer patients with axillary node involvement, independent of the other well-known prognostic variables, thereby confirming that the psychoneuroendocrine status of cancer patients may influence the prognosis of their disease.
Analysis of T-Cell Clonality Pattern in Tumor Samples of Breast Cancer Patients
Authors: Cikota B.M. , Branković-Magić M.V. , Jović V.S. , Radulović S.S. , Magić Z.M.
Published: January 2018

Purpose and methods

A large body of experimental evidence has confirmed that different tumors, including breast carcinomas, can stimulate specific T-cell-mediated immune responses. In this study we have analyzed patterns of T-cell clonality in tumor samples of 54 breast cancer patients classified as lymph node negative, N0 (n=16), or lymph node positive, N+ (n=38). The clonality of T-cells was analyzed by the PCR-PAGE method.

Results

Monoclonal/oligoclonal (M/O) T-cell populations were found in 15 breast cancer patients, nine N+ and six N0. In all analyzed groups (N+ + N0, N+, N0) the incidence of relapse was not significantly different between patients with M/O and patients with polyclonal T-cells. Comparison of disease-free interval (DFI) between patients divided according to the presence of TCR? monoclonality/oligoclonality showed a marginally significant difference only in the group of N+ patients within the first 24 months of follow-up. Patients with a M/O T-cell population had a shorter DFI than patients with a polyclonal T-cell population. This difference was not observed when the complete follow-up period was considered in the same group of patients. Furthermore, there was no significant difference in overall survival (OS) between patients with M/O and patients with polyclonal T-cells.

Conclusion

Our results imply that tumor infiltrating T-cells are usually polyclonal. The pattern of T-cell clonality does not correlate with the incidence of relapse and the duration of DFI and OS in the analyzed groups of breast cancer patients, excluding N+ patients with M/O T-cells who had a shorter DFI in the first 24 months of follow-up. This observation suggests that polyclonal T-cell populations may provide a broader spectrum of T-cell-mediated antitumor response.
Detection of Circulating CEA-IgM Complexes in Early Stage Colorectal Cancer
Authors: Castaldi F. , Marino M. , Beneduce L. , Belluco C. , De Marchi F. , Mammano E. , Nitti D. , Lise M. , Fassina G.
Published: January 2018

We have recently shown that alpha fetoprotein (AFP) and squamous cell carcinoma antigen (SCCA), biomarkers associated with hepatocellular carcinoma, may be detected in patient sera as circulating immune complexes with IgM, and that assessment of serum levels of AFP-IgM and SCCA-IgM may be used for the detection of liver cancer. In this study we measured the levels of carcinoembryonic antigen (CEA) as free form (FCEA) and complexed to IgMs (CEA-IgM) in sera of patients affected by colorectal carcinoma (CRC) at different stages as well as in healthy subjects. FCEA levels were above the 5 ng/mL cutoff in 43% of CRC patients (31/72) and CEA-IgM levels were above the 200 AU/mL cutoff in 38% of CRC patients (27/72). Serum levels of CEA-IgM immune complexes (IC) and FCEA did not overlap and 64% of patients (46/72) were positive for at least one marker without compromising the detection specificity (94%). Early detection of CRC was significantly improved by CEA-IgM IC assay. CRC patients at an early stage (stage 1) had elevated CEA-IgM levels in 29% of cases (7/24), while FCEA levels were elevated in only 8% of cases (2/24). These results indicate that CEA-IgM is a complementary serological marker to FCEA which is much more sensitive for early stage CRC, and that the combination of these biomarkers may be useful in the early detection of colorectal cancer.
Usefulness of CDK5RAP3, CCNB2, and RAGE Genes for the Diagnosis of Lung Adenocarcinoma
Authors: Stav D. , Bar I. , Sandbank J.
Published: January 2018

We used oligonucleotide microarrays with probe sets to 22,283 genes to analyze the gene expression profile of lung adenocarcinoma. Cancerous and noncancerous tissue samples were obtained from 23 patients with stage I or II lung cancer; 18 tissue pairs and 5 cancerous tissues. A list of 2065 genes that differentiate between cancerous and noncancerous tissues was generated using Winsorized paired t-tests. We analyzed CDK5RAP3 and CCNB2, which are involved in cell cycle progression, and RAGE. The first 2 of these 3 genes proved to be overexpressed in tumor tissue, whereas the RAGE gene was suppressed in tumor tissue. When CDK5RAP3 and CCNB2 were examined in individual patients we found that in cases where one of these genes was only slightly overexpressed the other was highly overexpressed. The combined expression of the 2 cell cycle genes was found to be statistically significant for differentiating between cancerous and noncancerous tissues. Inclusion of the data for the RAGE gene made the differentiation more powerful. The gene expression ratio gave a clear result: when CDK5RAP3 was expressed more than RAGE, the tissue was carcinomatous, and vice versa. We therefore conclude that these 3 genes may be used as a very reliable biomarker of lung adenocarcinoma.
Elevation of Serum CA 125 and D-Dimer Levels associated with Rupture of Ovarian Endometrioma
Authors: Uharček P. , Mlynček M. , Ravinger J.
Published: January 2018

Background

Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis.

Case report

A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient.

Conclusion

Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.
High Expression of Nuclear Factor of Activated T Cells in Chinese Primary Non-Small Cell Lung Cancer Tissues
Authors: Zhang K. , Li N. , Chen Z. , Shao K. , Zhou F. , Zhang C. , Mu X. , Wan J. , Li B. , Feng X. , Shi S. , Xiong M. , Cao K. , Wang X. , Huang C. , He J.
Published: January 2018

Purpose

Nuclear factor of activated T cells (NFAT) has been reported to be involved in the development of various types of cancer including adenocarcinoma of the breast. This research was the first to investigate NFAT protein expression in primary non-small cell lung cancer (NSCLC) tissues from Chinese patients.

Methods

NFAT protein expression was determined in 130 surgically resected primary NSCLC and matched normal tissues by immunohistochemical analysis. The association between NFAT expression and clinical categorical variables was further analyzed with the SPSS software.

Results

We found that NFAT expression was much higher in 85 tumor tissues (65.4%) and lower in 45 tumor tissues (34.6%) compared with the matched normal tissues. Further statistical analysis by the chi-square test showed that high expression of NFAT proteins was significantly associated with tumor differentiation (p=0.045), invasion (p=0.031), histology (p<0.0001), tumor size (p=0.038) and cigarette smoking history (p=0.024). However, there was no correlation between the expression of NFAT proteins and pTNM classification, and no difference in 5-year survival rate between patients with high or low expression of NFAT proteins. Multivariate logistic regression analysis for the correlation between NFAT protein expression levels and various characteristics showed a significant association with histology (p=0.008, OR=0.273).

Conclusion

Our results revealed that high NFAT expression was present in Chinese NSCLCs and that NFAT expression might be involved in the process of human lung cancer development.
Standardization of PSA Measures: A Reappraisal and an Experience with WHO Calibration of Beckman Coulter Access Hybritech Total and Free PSA
Authors: Vignati G. , Giovanelli L.
Published: January 2018

Prostate-specific antigen (PSA) is the serum biomarker most widely used in prostate diseases. Since there is significant variation in PSA results among non-equimolar assays, the 90:10 ratio of complexed PSA to free PSA (the Stanford standard) was proposed as standardization; this became the basis for the PSA mass standards WHO 96/670 for tPSA and 96/668 for fPSA. Nevertheless, recent publications underlined the lack of interchangeability between different commercial assays, all claimed to be equimolar and calibrated to the WHO standard. Importantly, the WHO calibration yields about 16–20% lower PSA results. Manufacturers that have chosen to calibrate existing assays to the mass value of WHO 96/760 have introduced a significant negative bias compared to the Hybritech assay calibration; this bias is transferred to clinical evaluation if the cutoff of 4 ng/mL, clinically validated for the Hybritech assay, is maintained with the WHO calibration. Beckman Coulter recently provided the option of calibrating the Access Hybritech PSA and free PSA assays to the WHO standard introducing a different clinical cutoff. Using two different reagent lots, we tested about 200 routine patients for tPSA and fPSA with both calibrations; we also calculated the f/tPSA ratio with both calibrated methods. Moreover, we verified the analytical sensitivity and inter- and intra-assay variability. In accordance with the claim of the manufacturer, the results obtained with the WHO calibration showed a negative bias of about 25% and, as expected, no significant difference was found for % f/tPSA. The same bias was found when retesting samples of the External Quality Assessment Scheme of the Institute of Clinical Physiology of the National Research Council in Pisa. Based on this experience we decided for the moment to keep the Hybritech calibration, in order to avoid cutoff changes during patient follow-up. Moreover, we have started to provide information to clinicians aimed at the alignment of our results with the WHO standardization.