bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Tissue and Circulating Tumor DNA by Next-Generation Sequencing of Hepatocellular Carcinoma: Implications for Targeted Therapeutics
Authors: Ikeda Sadakatsu , Lim Jordan S. , Kurzrock Razelle
Published: February 2018

Hepatocellular carcinoma (HCC) has limited treatment options. Molecular analysis of its mutational landscape may enable the identification of novel therapies. However, biopsy is not routinely performed in HCC. The utility of analyzing cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is not established. We performed 32 ctDNA NGS analyses on 26 patients; 10 of these patients had tissue NGS (236 to 626 genes). ctDNA was evaluated using an assay that detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion alterations in 54 to 70 genes. The ctDNA demonstrated that 23 of 26 patients (88.5%) had ≥1 characterized alteration, and all these individuals had ≥1 potentially actionable alteration. The most frequently mutated gene was TP53 (16 of 26 patients, 61.5%). There were 47 unique characterized molecular alterations among 18 total gene alterations [variants of unknown significance (VUS) excluded)]. ctDNA and tissue NGS frequently showed different profiles, perhaps due to length of time between tissue and blood samples [median = 370 days (range, 29 to 876 days)]. Serial ctDNA evaluation in an illustrative patient treated with capecitabine demonstrated emergence of a new TP53 alteration after progression. In conclusion, ctDNA profiling is feasible in advanced HCC, and serial assessment using ctDNA NGS can reveal genomic changes with time. NGS of ctDNA provides a minimally invasive alternative for identifying potentially actionable gene alterations and potential molecular targeted therapies. Dynamic changes in molecular portfolio associated with therapeutic pressure in difficult-to-biopsy patients can be observed. Mol Cancer Ther; 17(5); 1114–22. ©2018 AACR.
Targeting PRPK Function Blocks Colon Cancer Metastasis
Authors: Zykova Tatyana , Zhu Feng , Wang Lei , Li Haitao , Lim Do Young , Yao Ke , Roh Eunmiri , Yoon Sang-Pil , Kim Hong-Gyum , Bae Ki Beom , Wen Weihong , Shin Seung Ho , Nadas Janos , Li Yan , Ma Weiya , Bode Ann M. , Dong Zigang
Published: February 2018

The biological functions of the p53-related protein kinase (PRPK) remain unclear. We have previously demonstrated that PRPK is phosphorylated by the T-LAK cell-originated protein kinase (TOPK) and that phosphorylated PRPK (p-PRPK) promotes colon cancer metastasis. Here, we analyzed colon adenocarcinomas from 87 patients and found that higher expression levels of p-PRPK were associated with later stages of metastatic dissemination (stage III and IV) as compared with earlier stages (stages I and II). Indeed, levels of p-PRPK were higher in metastatic versus malignant human colon adenocarcinomas. Knocking down PRPK expression attenuated colorectal liver and lung metastasis of colon cancer cells in vivo. An in vitro kinase assay indicated that active PRPK does not phosphorylate p53 directly. We found that PRPK phosphorylates survivin, a regulator of colon cancer metastasis. PRPK phosphorylates survivin at Thr34, which is important for survivin stability. Taken together, our data strongly suggest that the PRPK signaling pathway promotes colon cancer metastasis by modulating survivin stability, and that PRPK could be a new prognostic marker for the survival of colon cancer patients. In addition, we identified an FDA-approved bacteriostatic antibiotic, fusidic acid sodium salt (fusidic acid or FA) as an inhibitor of PRPK, and show that FA combined with 5-fluorouracil (5-FU) inhibited PRPK activity and colon cancer metastasis to the lung in mice. We contend that the combination of FA with 5-FU could be an alternative therapeutic strategy to traditional chemotherapy for colon cancer patients with poor prognosis. Mol Cancer Ther; 17(5); 1101–13. ©2018 AACR.
High Levels of TRIM14 Are Associated with Poor Prognosis in Hepatocellular Carcinoma
Authors: Dong Bingwei , Zhang Weibo
Published: February 2018

Background: Tripartite motif containing 14 (TRIM14) has been reported to play a critical role in tumor development. However, little is known about TRIM14 expression and its clinical significance in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the expression and prognostic value of TRIM14 in patients with HCC. Materials and Methods: The mRNA and protein levels of TRIM14 in HCC were evaluated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The association of TRIM14 expression with clinicopathological factors, overall survival (OS), and recurrence-free survival (RFS) was analyzed. Results: TRIM14 expression was significantly upregulated in HCC-related tissues. High TRIM14 expression correlated with C-reactive protein (p = 0.01), alanine aminotransferase (p = 0.02), tumor size (p = 0.005), lesion number (p = 0.023), vascular invasion (p = 0.041), tumor/node/metastasis (TNM) stage (p = 0.001), and Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.003). In addition, high TRIM14 expression was associated with poor OS and RFS (both p < 0.001). Cox regression analysis revealed that high TRIM14 expression was an independent prognostic factor for both OS (hazard ratio (HR) 1.657, 95% confidence interval (CI) 1.031-2.687; p = 0.018) and RFS (HR 2.297, 95% CI 1.184-2.312; p = 0.007). Conclusion: TRIM14 is a potential prognostic predictor for OS and RFS in patients with HCC.
Metachronous Spontaneous Remission of Melanoma Lung Metastasis and Mediastinal Lymph Node Metastases
Authors: Kappauf Herbert , Esser Gregor
Published: February 2018

Background: Spontaneous remissions are rare but valid events in malignancies and in the past have led to the development of mainstay oncologic therapies. Case Report: We present a rare case of spontaneous regression of a solitary pulmonary melanoma metastasis with complete remission persisting for 28 months. Concurrent mediastinal nodal metastases progressed at the time of remission of the lung metastasis, but also demonstrated regression in follow-up fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. Metastatic nodes showed only minimal residual metabolic activity after 38 months of follow-up from the appearance of metastatic disease. Conclusion: This case report presents a rare spontaneous complete regression of a solitary pulmonary melanoma metastasis. Biological pathways involved in spontaneous regression in cancer are discussed.
Upper Gastrointestinal Surgery: Robotic Surgery versus Laparoscopic Procedures for Esophageal Malignancy
Authors: Biebl Matthias , Andreou Andreas , Chopra Sascha , Denecke Christian , Pratschke Johann
Published: February 2018

Background: The evolution of minimally invasive surgery (MIS) also extends to the field of esophageal surgery and has brought forth the development of several approaches of minimally invasive esophagectomy (MIE). Hybrid and total minimally invasive operative techniques have proven beneficial compared to open surgery and are currently evaluated against robotic-assisted minimally invasive esophagectomy (RAMIE). We aim to review the current literature regarding the position of MIE versus RAMIE. Methods: A systematic review of the relevant literature on minimally invasive esophageal surgery for cancer is presented. A PubMed search was carried out for the period of 1992-2018 with the following search terms: ‘esophageal cancer', ‘minimally invasive surgery', ‘resection', ‘transhiatal', ‘transthoracic', ‘MIE', ‘hybrid', ‘robotic resection', ‘RAMIE', ‘RATE'. Results: Hybrid and total minimally invasive operative techniques have proven beneficial, especially with regard to pulmonary complications, compared to open surgery. Oncologic outcomes appear equivalent between open and minimally invasive techniques. Currently, the position of RAMIE is being evaluated against other minimally invasive techniques. Conclusion: All minimally invasive techniques confer the expected reduction in perioperative morbidity compared to open surgery. However, MIS is still evolving with regard to specific technical challenges, especially anastomotic techniques.
Criadouro de Aedes aegypti em reservatório subterrâneo de água da chuva: um alerta
Authors: Bermudi Patricia Marques Moralejo , Kowalski Fernanda , Menzato Marcela Mori , Ferreira Millene da Cruz , Passos Willian Brendo Silva dos , Oku Vivian Janine Ambriola , Kumow Aline , Lucio Taís Vargas Freire Martins , Lima-Camara Tamara Nunes , Urbinatti Paulo Roberto , Chiaravalloti Neto Francisco
Published: February 2018

Descreve-se o encontro de criadouro subterrâneo de Aedes aegypti no bairro de Pinheiros, São Paulo, SP, ocorrido durante um programa de levantamento entomológico, realizado em 2016. Mesmo com intensa vigilância e controle vetorial, grande quantidade de mosquitos estava presente nessa área. Investigação minuciosa permitiu a detecção de Ae. aegypti em reservatório subterrâneo para armazenamento de água pluvial. Após a implantação de telas de proteção nos acessos, não foi mais detectada a presença do vetor. O uso frequente desse tipo de estrutura e o seu risco para a produção de mosquitos é discutido.
Genome‐Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β‐Blockers
Authors: Shahin Mohamed H. , Conrado Daniela J. , Gonzalez Daniel , Gong Yan , Lobmeyer Maximilian T. , Beitelshees Amber L. , Boerwinkle Eric , Gums John G. , Chapman Arlene , Turner Stephen T. , Cooper‐DeHoff Rhonda M. , Johnson Julie A.
Published: February 2018

Background

For many indications, the negative chronotropic effect of β‐blockers is important to their efficacy, yet the heart rate (
HR
) response to β‐blockers varies. Herein, we sought to use a genome‐wide association approach to identify novel single nucleotide polymorphisms (
SNP
s) associated with
HR
response to β‐blockers.

Methods and Results

We first performed 4 genome‐wide association analyses for
HR
response to atenolol (a β1‐adrenergic receptor blocker) as: (1) monotherapy or (2) add‐on therapy, in 426 whites and 273 blacks separately from the
PEAR
(Pharmacogenomic Evaluation of Antihypertensive Responses) study. A meta‐analysis was then performed between the genome‐wide association analysis performed in
PEAR
atenolol monotherapy and add‐on therapy, in each race separately, using the inverse variance method assuming fixed effects. From this analysis,
SNP
s associated with
HR
response to atenolol at a
P
<1E‐05 were tested for replication in whites (n=200) and blacks (n=168) treated with metoprolol (a β1‐adrenergic receptor blocker). From the genome‐wide association meta‐analyses,
SNP
rs17117817 near olfactory receptor family10 subfamily‐p‐member1 (

OR
10P1

), and
SNP
rs2364349 in sorting nexin‐9 (

SNX
9

) replicated in blacks. The combined studies meta‐analysis
P
values for the rs17117817 and rs2364349 reached genome‐wide significance (rs17117817G‐allele; Meta‐β=5.53 beats per minute, Meta‐
P
=2E‐09 and rs2364349 A‐allele; Meta‐β=3.5 beats per minute, Meta‐
P
=1E‐08). Additionally,
SNP
s in the

OR
10P1

and

SNX
9

gene regions were also associated with
HR
response in whites.

Conclusions

This study highlights

OR
10P1

and

SNX
9

as novel genes associated with changes in
HR
in response to β‐blockers.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00246519.
Hypoxia Inducible Factor 1α Plays a Key Role in Remote Ischemic Preconditioning Against Stroke by Modulating Inflammatory Responses in Rats
Authors: Yang Jian , Liu Cuiying , Du Xiangnan , Liu Menglei , Ji Xunming , Du Huishan , Zhao Heng
Published: February 2018

Background

Limb remote ischemic preconditioning (
RIPC
) protects against brain injury induced by stroke, but the underlying protective mechanisms remain unknown. As hypoxia inducible factor 1α (
HIF
‐1α) is neuroprotective in stroke and mediates neuroinflammation, we tested the hypothesis that
HIF
‐1α is a key factor of
RIPC
against stroke by mediating inflammation.

Methods and Results

Stroke was induced by transient middle cerebral artery occlusion in rats, and
RIPC
was conducted in both hind limbs. The
HIF
‐1α
mRNA
was examined by quantitative reverse transcription polymerase chain reaction after
RIPC
. In addition, inflammatory cytokines in the peripheral blood and brain were measured using the AimPlex multiplex immunoassays. Data showed that
RIPC
reduced the infarct size, improved neurological functions, and increased
HIF
‐1α
mRNA
levels, interleukin (
IL
)‐4, and
IL
‐10 protein levels in the peripheral blood. Intraperitoneal injection of the
HIF
activator, dimethyloxaloylglycine, reduced the infarct size and inhibited interferon‐γ protein levels, while promoting
IL
‐4 and
IL
‐10 protein levels, while decreasing interferon‐γ protein levels in both the peripheral blood and ischemic brain. In addition, injection of dimethyloxaloylglycine had a synergistic effect with
RIPC
on reducing infarction and improving neurological functions, as well as decreasing interferon‐γ in the peripheral blood and ischemic brain. In contrast, injection of the
HIF
inhibitor, acriflavine hydrochloride, abolished the protective effects of
RIPC
on infarction, and reduced
IL
‐4 and
IL
‐10 protein levels in both the peripheral blood and ischemic brain.

Conclusions

We conclude that
HIF
‐1α plays a key role in
RIPC
, likely mediated by a systemic modulation of the inflammatory response.
High‐Sensitivity Troponin T and C‐Reactive Protein Have Different Prognostic Values in Hemo‐ and Peritoneal Dialysis Populations: A Cohort Study
Authors: Chen Titi , Hassan Hicham C. , Qian Pierre , Vu Monica , Makris Angela
Published: February 2018

Background

Dialysis patients have an exceedingly high mortality rate. Biomarkers may be useful tools in risk stratification of this population. We evaluated the prognostic value of high‐sensitivity cardiac troponin T (hs‐
cTnT
) and CRP (C‐reactive protein) in predicting adverse outcomes in stable hemodialysis and peritoneal dialysis (
PD
) patients. Variability in hs‐
cTnT
was also examined.

Methods and Results

A retrospective cohort study included 574 dialysis patients (hemodialysis 347,
PD
227). Outcomes examined included mortality and major adverse cardiovascular events, with median follow‐up of 3.5 years. hs‐
cTnT
was an independent predictor of both outcomes in hemodialysis and
PD
patients. Increased risk only became significant when hs‐
cTnT
reached quintile 3 (>49 ng/L). Area under the receiver operating curve analysis showed that the addition of hs‐
cTnT
to clinical parameters significantly improved its prognostic performance for mortality in
PD
patients (
P
=0.002). CRP was an independent predictor of both outcomes in
PD
patients only. Only CRP in the highest quintile (>16.8 mg/L) was associated with increased risk. hs‐
cTnT
remained relatively stable for the whole follow‐up period for hemodialysis patients, whereas for
PD
patients, hs‐
cTnT
increased by 23.63% in year 2 and 29.13% in year 3 compared with baseline (
P
<0.001).

Conclusions

hs‐
cTnT
and CRP are useful tools in predicting mortality and major adverse cardiovascular events in hemodialysis and
PD
patients. Given that hs‐
cTnT
levels increase over time in
PD
patients, interval monitoring may be valuable for risk assessment. In contrast, hs‐
cTnT
in hemodialysis patients has little interval change and progress monitoring is not indicated.
Physical Activity Measured by Implanted Devices Predicts Atrial Arrhythmias and Patient Outcome: Results of IMPLANTED (Italian Multicentre Observational Registry on Patients With Implantable Devices Remotely Monitored)
Authors: Palmisano Pietro , Guerra Federico , Ammendola Ernesto , Ziacchi Matteo , Luigi Pisanò Ennio Carmine , Dell'Era Gabriele , Aspromonte Vittorio , Zaccaria Maria , Di Ubaldo Francesco , Capucci Alessandro , Nigro Gerardo , Occhetta Eraldo , Maglia Giampiero , Ricci Renato Pietro , Boriani Giuseppe , Accogli Michele , Botto Gian Luca , Bertaglia Emanuele , Zoni Berisso Massimo , Nissardi Vincenzo , Santini Luca , Soldati Ezio , Stabile Giuseppe , Landolina Maurizio , Padeletti Luigi
Published: February 2018

Background

To determine whether daily physical activity (PA), as measured by implanted devices (through accelerometer sensor), was related to the risk of developing atrial arrhythmias during long‐term follow‐up in a population of heart failure (HF) patients with an implantable cardioverter defibrillator (ICD).

Methods and Results

The study population was divided into 2 equally sized groups (PA cutoff point: 3.5 h/d) according to their mean daily PA recorded by the device during the 30‐ to 60‐day period post‐ICD implantation. Propensity score matching was used to compare 2 equally sized cohorts with similar characteristics between lower and higher activity patients. The primary end point was time free from the first atrial high‐rate episode (AHRE) of duration ≥6 minutes. Secondary end points were: first AHRE ≥6 hours, first AHRE ≥48 hours, and a combined end point of death or HF hospitalization. Data from 770 patients (65±15 years; 66% men; left ventricular ejection fraction 35±12%) remotely monitored for a median of 25 months were analyzed. A PA ≥3.5 h/d was associated with a 38% relative reduction in the risk of AHRE ≥6 minutes (72‐month cumulative survival: 75.0% versus 68.1%; log rank
P
=0.025), and with a reduction in the risk of AHRE ≥6 hours, AHRE ≥48 hours, and the combined end point of death or HF hospitalization (all
P
<0.05).

Conclusions

In HF patients with ICD, a low level of daily PA was associated with a higher risk of atrial arrhythmias, regardless of the patients' baseline characteristics. In addition, a lower daily PA predicted death or HF hospitalization.
Conditioning a Professional Exchange Field for Social Innovation
Authors: Huq Jo-Louise
Published: February 2018

Social innovation is about solving important problems in new ways. In professional exchange fields, however, structuring and constraining forces make introducing new solutions exceedingly difficult, and known pathways that introduce new solutions are unlikely to be successful. In this article, I examine how social innovation can be encouraged in a professional exchange field. I identify three kinds of disrupting action (entwining problems, reconfiguring arrangements, and actively waiting) that can be used to encourage social innovation. These actions interrupt and expand essential elements of professionals’ work and they condition parts of the field to be supportive of and susceptible to social innovation. This research contributes to literature in three ways. First, it examines social innovation in a setting that has not been explored, uncovering an amalgamation of pathways that encourage social innovation. Second, it describes three types of disrupting action that set pathways in motion. Third, it conceptually links disrupting action to social innovation.
A comparative evaluation of the effectiveness of virtual reality, 3D visualization and 2D visual interactive simulation: an exploratory meta-analysis
Authors: Akpan Ikpe Justice , Shanker Murali
Published: February 2018

Research on the application of 3D visualization and virtual reality (VR) in discrete-event simulation (DES) has received increased attention in the past two decades. The increasing popularity of the 3D display in DES is mainly due to superior display capabilities and the associated benefits that it offers. However, the 2D display also continues to enjoy active use to date, thus provoking some fierce debates questioning the need for the 3D and VR if the 2D interface suffices. Several studies comparing the effectiveness of the different visualization methods also produce different conclusions. This paper undertakes a meta-analysis of the different positions and synthesizes the findings from 162 studies on the impacts of the 2D display versus 3D/VR on user performance on various DES tasks. The results highlight four key findings. First, the perception that the 2D display is more effective for model development is misleading as 3D/VR offers overall better performance and quality of models. Second, 3D/VR enables more effective performance than 2D display for model verification and validation. Third, 3D/VR decreases the time taken for verification, validation, experimentation, and analysis of results, but can increase model development time. Finally, the latent variables such as the application domains and nature of the problems tackled have no direct or indirect influence on the efficacy of the 3D display/VR versus 2D on DES task performance.
‘Nice apartments, no jobs’: How former villagers experienced displacement and resettlement in the western suburbs of Shanghai
Authors: Jiang Yanpeng , Waley Paul , Gonzalez Sara
Published: February 2018

In this paper, we document the displacement and resettlement of over 11,000 villagers who were removed from their homes and relocated in modern apartment blocks to make way for the construction of a new business district in the western suburbs of Shanghai. We examine the expectations and concerns of displaced residents before and after their relocation. Our findings showed that while the former villagers recognised the improvement in their physical surroundings, they were deeply concerned about their loss of rental income resulting from the demolition of their former homes, in which they housed unregistered migrants. They felt unfairly treated by government throughout the relocation process and saw themselves as being decanted into a new village-in-the-city. These results paint a much more unequivocal picture of resident dissatisfaction than is found in some other recent research.
The Impact of Applying Quality Management Practices on Patient Centeredness in Jordanian Public Hospitals: Results of Predictive Modeling
Authors: Hijazi Heba H. , Harvey Heather L. , Alyahya Mohammad S. , Alshraideh Hussam A. , Al abdi Rabah M. , Parahoo Sanjai K.
Published: February 2018

Targeting the patient’s needs and preferences has become an important contributor for improving care delivery, enhancing patient satisfaction, and achieving better clinical outcomes. This study aimed to examine the impact of applying quality management practices on patient centeredness within the context of health care accreditation and to explore the differences in the views of various health care workers regarding the attributes affecting patient-centered care. Our study followed a cross-sectional survey design wherein 4 Jordanian public hospitals were investigated several months after accreditation was obtained. Total 829 clinical/nonclinical hospital staff members consented for study participation. This sample was divided into 3 main occupational categories to represent the administrators, nurses, as well as doctors and other health professionals. Using a structural equation modeling, our results indicated that the predictors of patient-centered care for both administrators and those providing clinical care were participation in the accreditation process, leadership commitment to quality improvement, and measurement of quality improvement outcomes. In particular, perceiving the importance of the hospital’s engagement in the accreditation process was shown to be relevant to the administrators (gamma = 0.96), nurses (gamma = 0.80), as well as to doctors and other health professionals (gamma = 0.71). However, the administrator staff (gamma = 0.31) was less likely to perceive the influence of measuring the quality improvement outcomes on the delivery of patient-centered care than nurses (gamma = 0.59) as well as doctors and other health care providers (gamma = 0.55). From the nurses’ perspectives only, patient centeredness was found to be driven by building an institutional framework that supports quality assurance in hospital settings (gamma = 0.36). In conclusion, accreditation is a leading factor for delivering patient-centered care and should be on a hospital’s agenda as a strategy for continuous quality improvement.
Associations Between Secret-Keeping and Quality of Life in Older Adults
Authors: Maas Joyce , Wismeijer Andreas A. J. , Van Assen Marcel A. L. M.
Published: February 2018

This study examined the effects of secrecy on quality of life in a sample consisting of older adults (>50 years; N = 301). Three key components of secrecy were examined with the Tilburg Secrecy Scale-25 (TSS25; possession of a secret, self-concealment, and cognitive preoccupation). The TSS25 distinguishes between the tendency to conceal personal information (self-concealment) and the tendency to worry or ruminate about the secret (cognitive preoccupation), thereby enabling investigation of the effects of secrecy on quality of life in detail. Confirming previous findings in younger samples, we found a positive effect of possession of a secret on quality of life, after controlling for both TSS25’s self-concealment and cognitive preoccupation. This suggests that keeping secrets may have a positive association with quality of life in older adults as well, as long as they do not have the tendency to self-conceal and are not cognitively preoccupied with their secret.
Politics, Bureaucracy, and Employee Retention: Toward an Integrated Framework of Turnover Intent
Authors: Ali Susannah Bruns
Published: February 2018

In today’s politically contentious times where the role of the federal government and career federal workers is continually challenged, it is critical that we understand how the political world affects career choices among federal employees. This study proposes a theoretical framework that integrates the political environment into concepts of turnover intent among public sector employees based on research examining open systems and the administrative presidency. The framework is then explored through interviews with federal employees, former appointees, and lobbyists to understand the impacts of the broad political environment on individuals.
The Deviated Nose and the Nasal Airway
Authors: Maran A G D
Published: February 2018

The pathology of the deviated nose is discussed in relation to its bony and cartilaginous components. The importance of the interlocking stresses within the septal cartilage is pointed out especially with respect to continuing deformation after trauma.

The methods of rhinometry are analysed and normal airflow through the nose is described. The effects on the nasal airway of a caudal dislocation of the septum, an angulation at the valve area, a high septal deflection and an excessively wide choana are discussed.

In the treatment of a deviated bony segment the difficulties of medial and lateral osteotomies are described. The indications for a septoplasty are thought to be a dislocated caudal end, a tip deviation and an external lateral angulation. The submucous resection of the septum should be reserved for resolved haematoma and cartilage absorption. The importance of the patient's priorities in deciding what operation to do are pointed out.

Finally the experimental work on the effect of cartilage and mucoperichondrium resection on nasal growth is reviewed. It is suggested that a child with a severe septal deflection and airway obstruction should be offered a septoplasty taking care not to damage the mucoperichondrium.
Integrating building modelling with future energy systems
Authors: Jenkins David
Published: February 2018

The low-carbon building design process for a building engineer is often confined to construction, building services and occupancy. However, as we see coincident changes in climate, technologies, fuels and operation, it becomes important to extend this understanding to include wider energy systems, while clarifying the importance of the built environment within that system. With energy systems, such as the National Grid, involving multiple actors from different disciplines, a key challenge is to provide guidance and future projections that are translated into different discipline-specific vernaculars, but with a genesis of common assumptions. More generally, integration across the disciplines must be reflected by modelling approaches, policy-making frameworks and outputs. This article will demonstrate the initial stages of the energy demand research of the Centre of Energy Systems Integration project, where novel modelling techniques are being used to explore the effect of future buildings on national energy systems.

Practical application: The tools and techniques described within this article are designed with future industry practice in mind. The driver is the increased importance of external factors outside the traditional building envelope in determining the energy and carbon performance of a building (or buildings). Building engineers, and others within building design teams, require a new portfolio of tools and resources to better account for the impact of buildings on wider energy systems and vice versa. The role of such practitioners is therefore likely to evolve.
Comparison of Pediatric Intracapsular Tonsillectomy and Extracapsular Tonsillectomy: A Cost and Utility Decision Analysis
Authors: Baik Grace , Brietzke Scott E.
Published: February 2018

Objectives

To use decision analysis modeling to compare utility and cost outcomes of intracapsular tonsillectomy (ICT) and extracapsular tonsillectomy (ECT). To use sensitivity analysis to determine the most important factors influencing outcomes favoring one surgical method versus another.

Study Design

Decision analysis model.

Setting

Hypothetical cohort.

Subjects and Methods

A decision analysis model was created with computer software comparing the results of ICT and ECT. The model featured complications with completion tonsillectomy, such as postsurgical bleed, dehydration, and tonsillar regrowth. Outcomes were quantified with a utility scale ranging from 0.95 (1 surgical procedure without complications) to 0.55 (ICT, regrowth requiring completion ECT, post‐ECT bleeding). Costs measured out‐of‐pocket costs for an insured patient and factored in different recovery times for ECT versus ICT.

Results

Based on baseline parameters, ECT had higher cumulative utility than ICT. Utility model results were highly dependent on the value of having a single uncomplicated surgery, as well as on the tonsillar regrowth rate. Utility was equal at a regrowth rate of 1.64%; rates above this value favored ECT. The base cost model showed that ICT ($4177.92) was less expensive than ECT ($4546.91), although ICT with regrowth had the highest outcome cost ($8393.91). ECT and ICT costs were equal at a tonsil regrowth rate of 17.8% and at a recovery period of 7.4 days.

Conclusion

Utility decision modeling based on best estimates for baseline parameters suggests that ECT may be slightly superior to ICT, but cost analysis suggests the opposite. However, the comparative results are highly dependent on subtle changes in the tonsil regrowth rate and the potential difference in recovery time.
Cancer patients’ experiences of living with venous thromboembolism: A systematic review and qualitative thematic synthesis
Authors: Benelhaj Naima B , Hutchinson Ann , Maraveyas Anthony M , Seymour Julie D , Ilyas Muhammad Waqas , Johnson Miriam J
Published: February 2018

Background:

Cancer-associated thrombosis is common. Recommended treatment is daily injected low-molecular-weight heparin for 6 months. Most studies focus on prophylaxis and treatment; few have explored the patients’ experience.

Aims:

To identify and synthesise the available literature concerning patients’ experience of cancer-associated thrombosis.

Design:

Systematic literature review and qualitative thematic synthesis.

Data source:

MEDLINE, Embase, CINAHL, PsycINFO (until 10/2016; limited to English) were searched. Eligible papers were qualitative studies of adult patients’ experience of cancer-associated thrombosis. Two researchers screened titles/abstracts/papers against inclusion criteria with recourse to a third for disagreements. Critical Appraisal Skills Programme qualitative checklist tool was used for quality appraisal.

Results:

A total of 1397 articles were identified. Five qualitative studies (total n = 92; age range 32–84 years) met the inclusion criteria. Participants had various cancer types. Most had advanced disease and were receiving palliative care. Four major themes emerged from the data: knowledge deficit (patients and clinicians), effects of cancer-associated thrombosis (physical and psychological), effects of anticoagulation and coping strategies.

Conclusion:

The cancer journey is difficult in itself, but thrombosis was an additional, frightening and unexpected burden. Although the association between cancer and thromboembolism is well-known, cancer patients are not routinely educated about the risk or warning symptoms/signs of thromboembolism which may otherwise be misattributed to the cancer by patient and clinician alike. This systematic review highlights the impact of cancer-associated thrombosis on the lives of cancer patients, and calls for education for patients and clinicians to be part of routine care and further work to address this patient priority.
20-HETE synthesis inhibition promotes cerebral protection after intracerebral hemorrhage without inhibiting angiogenesis
Authors: Han Xiaoning , Zhao Xiaochun , Lan Xi , Li Qian , Gao Yufeng , Liu Xi , Wan Jieru , Yang Zengjin , Chen Xuemei , Zang Weidong , Guo Austin M , Falck John R , Koehler Raymond C , Wang Jian
Published: February 2018

20-HETE, an arachidonic acid metabolite synthesized by cytochrome P450 4A, plays an important role in acute brain damage from ischemic stroke or subarachnoid hemorrhage. We tested the hypothesis that 20-HETE inhibition has a protective effect after intracerebral hemorrhage (ICH) and then investigated its effect on angiogenesis. We exposed hippocampal slice cultures to hemoglobin and induced ICH in mouse brains by intrastriatal collagenase injection to investigate the protective effect of 20-HETE synthesis inhibitor N-hydroxy-N′-(4- n-butyl-2-methylphenyl)-formamidine (HET0016). Hemoglobin-induced neuronal death was assessed by propidium iodide after 18 h in vitro. Lesion volume, neurologic deficits, cell death, reactive oxygen species (ROS), neuroinflammation, and angiogenesis were evaluated at different time points after ICH. In cultured mouse hippocampal slices, HET0016 attenuated hemoglobin-induced neuronal death and decreased levels of proinflammatory cytokines and ROS. In vivo, HET0016 reduced brain lesion volume and neurologic deficits, and decreased neuronal death, ROS production, gelatinolytic activity, and the inflammatory response at three days after ICH. However, HET0016 did not inhibit angiogenesis, as levels of CD31, VEGF, and VEGFR2 were unchanged on day 28. We conclude that 20-HETE is involved in ICH-induced brain damage. Inhibition of 20-HETE synthesis may provide a viable means to mitigate ICH injury without inhibition of angiogenesis.
Comprehensive Geriatric Assessment in Elderly Cancer Patients: An Experience in an Outpatient Population
Authors: Arnoldi Ermenegildo , Dieli Maria , Mangia Marina , Minetti Bruno , Labianca Roberto
Published: February 2018

Aims and background

Cancer is an age-related disease, and the increase in life expectancy will lead to a progressive increase of cancer cases in the elderly (≥70 years of age). We have created a group called GONG (Gruppo Oncologico Geriatrico) to apply cancer geriatric assessment in elderly cancer patients, in order to select which of them are eligible for oncological treatment or supportive care only.

Patients and methods

We applied this model to evaluate 153 patients from March 2004 to August 2005. Our model included three categories of patients: frail (at least one of the following items: Activities of Daily Living scale <80, ≥3 comorbidities unrelated to the tumor according to the Charlson Index, performance status ≤60/≥3 according respectively to Karnofsky and the ECOG scale, ≥1 geriatric syndrome); borderline (patients with multiple comorbidities not affecting performance status or ability in daily activities); non-frail.

Results

Applying the aforementioned criteria, we found 30 borderline, 14 frail and 109 non-frail patients. Statistical analysis showed a significant difference in mortality between frail and non-frail patients (P <0.05), whereas there was no difference between borderline and non-frail patients.

Conclusions

Our model was thus able to identify patients at higher risk of death. These results confirm the importance of cancer geriatric assessment also for the clinical evaluation of oncological patients. Additional randomized studies with a larger number of patients, also in an adjuvant setting, should be performed to confirm the effectiveness of this approach.
Male Breast Cancer in a Young Patient Treated with Nipple-Sparing Mastectomy: Case Report and Review of the Literature
Authors: Luini Alberto , Gatti Giovanna , Brenelli Fabricio , Silva Luzemira Santos , Ivaldi Giovanni , Vento Anna Rita , Gentilini Oreste
Published: February 2018

Male breast carcinoma is an uncommon phenomenon, accounting for less than 1% of all malignancies of the breast. The approximate annual incidence in Europe is 1 in 100,000 cases. The highest incidence occurs 5-10 years later in men than in women, with a peak at 60 to 67 years of age. We here describe a case of male breast carcinoma in a young patient (44 years of age), which is quite unusual in the pattern of breast carcinoma presentation.
Late Brain Metastases from Breast Cancer: Clinical Remarks on 11 Patients and Review of the Literature
Authors: Piccirilli Manolo , Sassun Tanya Enny , Brogna Christian , Giangaspero Felice , Salvati Maurizio
Published: February 2018

Aims and Background

Late brain metastases from breast cancer are a rare event. Only a few cases have been reported in the English literature. The authors describe the clinical and pathological remarks, together with treatment modalities, removal extent and overall survival, of 11 patients in whom brain metastases were detected more than 10 years from the primary tumor.

Patients and Methods

Between January 1997 and April 2001, we hospitalized 11 patients, all females, with a histologically proven diagnosis of brain metastasis from breast invasive ductal carcinoma. We defined ‘late metastasis’ as those metastases that appeared at least 10 years after the breast cancer diagnosis. The median age at the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a median latency time from breast cancer diagnosis of 16 years (range, 11-30).

Results

Ten patients underwent surgery followed by adjuvant radiotherapy (whole brain radiotherapy). Two of them received, after whole brain radiotherapy, stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy, performed by neuronavigator, followed by palliative corticosteroid therapy. Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4 years).

Conclusions

Although late brain metastases are a rare event, specific neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should be correlated to the presence of a cerebral metastasis, in a patient with a previous history of breast cancer. The longer latency time from breast cancer to brain metastasis could be explained by the “clonal dominance” theory and by different genetic alterations of the metastatic cell, which could influence the clinical history of the disease.
Utility of the Clinical Practice of Admnistering Thrombophilic Screening and Antithrombotic Prophylaxis with Low-Molecular-Weight Heparin to Healthy Donors Treated with G-Csf for Mobilization of Peripheral Blood Stem Cells
Authors: Martino Massimo , Luise Francesca , Oriana Vincenzo , Console Giuseppe , Moscato Tiziana , Mammì Corrado , Messina Giuseppe , Massara Elisabetta , Irrera Giuseppe , Piromalli Angela , Lombardo Vincenzo Trapani , Laganà Carmelo , Lacopino Pasquale
Published: February 2018

The aim of the study was to verify the utility of the clinical practice of administering thrombophilic screening and antithrombotic prophylaxis with low-molecular-weight heparin to healthy donors receiving granulocyte colony-stimulating factor to mobilize peripheral blood stem cells. Thrombophilia screening comprised of testing for factor V Leiden G1691A, prothrombin G20210A, the thermolabile variant (C677T) of the methylene tetrahydrofolate reductase gene, protein C, protein S, factor VIII and homocysteine plasmatic levels, antithrombin III activity, and acquired activated protein C resistance.

We investigated prospectively 72 white Italian healthy donors, 39 men and 33 women, with a median age of 42 years (range, 18-65). Five donors (6.9%) were heterozygous carriers of Factor V Leiden G1691A; two healthy donors had the heterozygous prothrombin G20210A gene mutation; C677T mutation in the methylene tetrahydrofolate reductase gene was present in 34 (47.2%) donors in heterozygous and in 7 donors (9.7%) in homozygous.

Acquired activated protein C resistance was revealed in 8 donors of the study (11.1%). The protein C plasmatic level was decreased in 3 donors (4.2%); the protein S level was decreased in 7 donors (9.7%). An elevated factor VIII dosage was shown in 10 donors (13.9%) and hyperhomocysteinemia in 9 donors (12.5%). Concentration of antithrombin III was in the normal range for all study group donors. The factor V Leiden mutation was combined with the heterozygous prothrombin G20210A in 2 cases and with protein S deficiency in one case; 2 healthy donors presented an associated deficiency of protein C and protein S. Although none of these healthy subjects had a previous history of thrombosis, low-molecular-weight heparin was administered to all donors during granulocyte colony-stimulating factor administration to prevent thrombotic events. No donor experienced short or long-term thrombotic diseases after a median follow-up of 29.2 months.

Our data do not support this clinical practice because there is no evidence that the combination of granulocyte colony-stimulating factor to previous hypercoagulable conditions results in thrombotic events.
Sphincter Preservation in Four Consecutive Phase II Studies of Preoperative Chemoradiation: Analysis of 247 T3 Rectal Cancer Patients
Authors: Gambacorta Maria Antonietta , Valentini Vincenzo , Coco Claudio , Manno Alberto , Doglietto Giovanni B , Ratto Carlo , Cosimelli Maurizio , Miccichè Francesco , Maurizi Francesca , Tagliaferri Luca , Mantini Giovanna , Balducci Mario , La Torre Giuseppe , Barbaro Brunella , Picciocchi Aurelio
Published: February 2018

Aims and Background

To evaluate the impact of preoperative chemoradiation on sphincter preservation in patients with low- medium locally advanced resectable rectal cancer treated by four chemoradiation schedules.

Materials and Methods

Between 1990 and 2002, 247 patients were treated according to four schedules of chemoradiotherapy: FUMIR (5-fluorouracil, mitomycin, external beam radiotherapy 37.8 Gy), PLAFUR (cisplatinum, 5-fluorouracil, external beam radiotherapy 50.4 Gy), TOMRT (raltitrexed, external beam radiotherapy 50.4 Gy), and TOMOXRT (raltitrexed, oxaliplatin, external beam radiotherapy 50.4 Gy). Four to five weeks after chemoradiation, patients were restaged and surgery was performed 2-3 weeks later.

Results

Overall, the sphincter-saving surgery was performed in 82.5% of patients. In patients candidate to an abdominoperineal resection before chemoradiaton (distance tumor-anorectal ring, <30 mm) a sphincter-saving surgery was possible in 58% of cases: 44% (FUMIR), 52% (PLAFUR), 63% (TOMRT), 76% (TOMOXRT) (P <0.017). The involved surgeons kept the same surgical criteria in performing sphincter-saving surgery. After chemoradiation, patients with tumor location still between 0 and 30 mm received sphincter-saving surgery according to the protocols: 33% (FUMIR), 42% (PLAFUR), 50% (TOMRT), 64% (TOMOXRT) (P = 0.066)

Conclusions

Even though the surgeons’ skill in performing sphincter-saving surgery could be improved with time, the high rate of this procedure in the latest schedules suggests an impact of the new drugs in promoting tumor downsizing and therefore sphincter-saving surgery.
In Vivo Evaluation of Melanoma Thickness by Multispectral Imaging and An Artificial Neural Network. A Retrospective Study on 250 Cases of Cutaneous Melanoma
Authors: Marchesini Renato , Bono Aldo , Tomatis Stefano , Bartoli Cesare , Colombo Ambrogio , Lualdi Manuela , Carrara Mauro
Published: February 2018

Aims and Background

Noninvasive diagnostic methods such as dermoscopy, sonography, palpation or combined approaches have been developed in an attempt to preoperatively estimate melanoma thickness. However, the clinical presentation is often complex and the evaluation subjective. Multispectral image analysis of melanomas allows selection of features related to the content and distribution of absorbers, mainly melanin and hemoglobin, present within the lesion. Hence, it is reasonable to assume that the same features might be useful to predict melanoma thickness.

Methods

A multispectral image system was used to analyze in vivo 1939 pigmented skin lesions. The lesion selection was based on clinical and/or dermoscopic features that supported a suspicion for melanoma. All the lesions were then subjected to surgery for the histopathological diagnosis, and 250 were melanomas. From the multispectral images of the melanomas, we selected 12 features, seven of which were used to train and test an artificial neural network on 155 and 95 melanomas, respectively.

Results

Sensitivity (i.e., melanoma ≥0.75 mm thick correctly classified) and specificity (i.e., melanoma <0.75 mm thick correctly classified) evaluated from the receiving operating characteristic curves ranged from 76 to 90% and from 91 to 74%, respectively.

Conclusions

Our approach provides results similar to those obtained with other methods and has the advantage that it is not related to the expertise of the clinician. In addition, the physical interpretation of the selected features suggests a possible role of spectrophotometry as an objective method to study the natural history of the early phases of the disease.
P53 Gene Mutations in Surgical Margins and Primary Tumor Tissues of Patients with Squamous Cell Carcinoma of the Head and Neck
Authors: Tunca Berrin , Erisen Levent , Coskun Hakan , Cecener Gulsah , Ozuysal Sema , Egeli Unal
Published: February 2018

Aims and Background

The frequency of p53 mutations in primary tumors, the effect of the mutations on some clinical and pathological features of head and neck squamous cell carcinoma, and the impact of p53 mutations in the surgical margins on local recurrence were determined.

Material and Methods

We investigated the presence of p53 mutations in primary tumor samples and in the surgical margins of 34 patients with head and neck cancer using single strand conformational polymorphism and sequencing analysis.

Results

The p53 mutations (codons 175addAT, 175delGC, 206G→A, and 248delC) were found in the primary tumor samples of 15 of 34 patients (44.12%) and in the surgical margins of 5 of the 15 tumors (33.33%) with p53 mutations.

Conclusions

We found no statistically significant association between the presence of p53 mutations in the primary tumor, the clinical and pathological features, or outcome of head and neck squamous cell carcinoma in this study. Furthermore, the presence of p53 mutations in the surgical margins may not increase the risk of local-regional recurrence, but probably increases the risk of developing distant metastases or second primary tumors.