Editorial Board

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Contents

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Protective effect of Vaccinium arctostaphylos L. fruit extract on gentamicin-induced nephrotoxicity in rats

Abstract

Aminoglycosides are extensively used owing to advantages such as low cost and availability. Nephrotoxicity induced by antibiotics has been analyzed in different animal models. This study was aimed to investigate the effect of Vaccinium arctostaphylos L. fruit extract on gentamicin-induced nephrotoxicity in rats. In this experimental study, 25 rats were divided into five groups, including negative control (0.5 ml normal saline), positive control (80 mg/kg gentamicin and 0.5 ml normal saline), and three Vaccinium arctostaphylos L. fruit extract groups at 100, 200, and 400 mg/kg concentrations plus 80 mg/kg gentamicin. All administrations were done intraperitoneally for 7 days. Thirty days after the first injection, blood samples were taken from the heart. Serum creatinine (Cr), blood urea nitrogen (BUN), and sodium and potassium levels were measured. To prepare histological sections, the kidneys were kept in 10% formalin. Having prepared the histological sections, the volume of renal tubules (proximal and distal convoluted tubules and loop of Henle), renal vessels, interstitial tissue, and number and volume of renal glomeruli were measured. Vaccinium arctostaphylos L. fruit extract significantly increased serum urea (p = 0.023), creatinine (p = 0.009), volume of proximal convoluted tubules (p = 0.02), volume of distal convoluted tubules (p = 0.032), loop of Henle (p = 0.038), and glomeruli (p = 0.015). However, it significantly reduced the volume of vessels (p = 0.009) and interstitial tissue (p = 0.001). The 400 mg/kg concentration exerted the highest effect. Vaccinium arctostaphylos L. fruit extract has protective effects against gentamicin-induced renal impairments.

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Asymptomatic Pulmonary Artery Intimal Sarcoma with Chest Wall Metastasis as an Initial Manifestation: An Autopsy Case

Pulmonary artery intimal sarcoma (PAIS) is a rare mesenchymal malignancy arising in the pulmonary trunk or proximal pulmonary artery and shows intraluminal growth. Clinical manifestations in PAIS are predominantly related to the pulmonary artery embolism, so cases with initial symptoms related to an extrapulmonary metastasis are unusual. The present report describes an 82-year-old man without any cardiopulmonary symptoms who was detected with an abnormal shadow on chest radiography during a routine health checkup. Contrast medium-enhanced chest computed tomography revealed an enhancing mass in the right pulmonary artery, pulmonary nodules, and a chest wall tumor corresponding to the abnormal shadow observed using chest radiography. A core needle biopsy for the chest wall tumor determined a pathological diagnosis of unclassified sarcoma. The patient was diagnosed with PAIS on the basis of clinical, radiological, and pathological correlations. He was scheduled to receive supportive care, but died of respiratory failure 1 year from the first visit. An autopsy revealed the pleomorphic sarcoma occupying the entire lumen of the right pulmonary artery with the only site of extrapulmonary metastasis in the chest wall. We should be aware of rare cases of asymptomatic PAIS found through routine health checkups.

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Composite Scaffolds Based on Intestinal Extracellular Matrices and Oxidized Polyvinyl Alcohol: A Preliminary Study for a New Regenerative Approach in Short Bowel Syndrome

Pediatric Short Bowel Syndrome is a rare malabsorption disease occurring because of massive surgical resections of the small intestine. To date, the issues related to current strategies including intestinal transplantation prompted the attention towards tissue engineering (TE). This work aimed to develop and compare two composite scaffolds for intestinal TE consisting of a novel hydrogel, that is, oxidized polyvinyl alcohol (OxPVA), cross-linked with decellularized intestinal wall as a whole (wW/OxPVA) or homogenized (hW/OxPVA). A characterization of the supports was performed by histology and Scanning Electron Microscopy and their interaction with adipose mesenchymal stem cells occurred by MTT assay. Finally, the scaffolds were implanted in the omentum of Sprague Dawley rats for 4 weeks prior to being processed by histology and immunohistochemistry (CD3; F4/80; Ki-67; desmin; α-SMA; MNF116). In vitro studies proved the effectiveness of the decellularization, highlighting the features of the matrices; moreover, both supports promoted cell adhesion/proliferation even if the wW/OxPVA ones were more effective (). Analysis of explants showed a continuous and relatively organized tissue wall around the supports with a connective appearance, such as myofibroblastic features, smooth muscle, and epithelial cells. Both scaffolds, albeit with some difference, were promising; nevertheless, further analysis will be necessary.

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Reduced gray matter volume and respiratory dysfunction in Parkinson’s disease: a voxel-based morphometry study

The respiratory dysfunction of patients with Parkinson's disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morpho...

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Using Electroencephalography Measurements and High-quality Video Recording for Analyzing Visual Perception of Media Content

We present detection, acquisition, and analysis of eyeblink rates while watching media content.

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Calorie restriction induces reversible lymphopenia and lymphoid organ atrophy due to cell redistribution

Abstract

Calorie restriction (CR) without malnutrition increases life span and health span in multiple model organisms. In non-human and human primates, CR causes changes that protect against several age-related pathologies, reduces inflammation, and preserves or improves cell-mediated immunity. However, CR has also been shown to exhibit adverse effects on certain organs and systems, including the immune system, and to impact genetically different organisms of the same species differentially. Alternately, short periods of fasting followed by refeeding may result in the proliferation of bone marrow stem cells, suggesting a potential rejuvenation effect that could impact the hematopoietic compartment. However, the global consequences of CR followed by refeeding on the immune system have not been carefully investigated. Here, we show that individuals practicing long-term CR with adequate nutrition have markedly lower circulating levels of total leukocytes, neutrophils, lymphocytes, and monocytes. In 10-month-old mice, short-term CR lowered lymphocyte cellularity in multiple lymphoid tissues, but not in bone marrow, which appears to be a site of influx, or a "safe haven" for B, NK, and T cells during CR. Cellular loss and redistribution was reversed within the first week of refeeding. Based on BrdU incorporation and Ki67 expression assays, repopulating T cells exhibited high proliferation in the refeeding group following CR. Finally, we demonstrated that the thymus was not essential for T cell repopulation following refeeding. These findings are of potential relevance to strategies to rejuvenate the immune system in mammals and warrant further investigation.

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Metabolic Mapping: Quantitative Enzyme Cytochemistry and Histochemistry to Determine the Activity of Dehydrogenases in Cells and Tissues

Here, we present a protocol that can be used to microscopically visualize and quantify activity of dehydrogenases in cells and tissues and its kinetics, function and subcellular localization.

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Expanding the phenotype of TRAK1 mutations: hyperekplexia and refractory status epilepticus

Sir,

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Reply: Social communication in Tourette syndrome: a glimpse at the contribution of the insula and the prefrontal cortex

Sir,

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Social communication in Tourette syndrome: a glimpse at the contribution of the insula and the prefrontal cortex

Sir,

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Cancer recording in patients with and without type 2 diabetes in the Clinical Practice Research Datalink primary care data and linked hospital admission data: a cohort study

Objectives and setting

Conflicting results from studies using electronic health records to evaluate the associations between type 2 diabetes and cancer fuel concerns regarding potential biases. This study aimed to describe completeness of cancer recording in UK primary care data linked to hospital admissions records.

Design

Patients aged 40+ years with insulin or oral antidiabetic prescriptions in Clinical Practice Research Datalink (CPRD) primary care without type 1 diabetes were matched by age, sex and general practitioner practice to non-diabetics. Those eligible for linkage to Hospital Episode Statistics Admitted Patient Care (HES APC), and with follow-up during April 1997–December 2006 were included.

Primary and secondary outcome measures

Cancer recording and date of first record of cancer were compared. Characteristics of patients with cancer most likely to have the diagnosis recorded only in a single data source were assessed. Relative rates of cancer estimated from the two datasets were compared.

Participants

53 585 patients with type 2 diabetes matched to 47 435 patients without diabetes were included.

Results

Of all cancers (excluding non-melanoma skin cancer) recorded in CPRD, 83% were recorded in HES APC. 94% of cases in HES APC were recorded in CPRD. Concordance was lower when restricted to same-site cancer records, and was negatively associated with increasing age. Relative rates for cancer were similar in both datasets.

Conclusions

Good concordance in cancer recording was found between CPRD and HES APC among type 2 diabetics and matched controls. Linked data may reduce misclassification and increase case ascertainment when analysis focuses on site-specific cancers.

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Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis

Objective

Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis.

Study design

Systematic review and reanalysis of multiperson N-of-1 studies.

Data sources

Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English.

Study selection

N-of-1 studies of pharmacological interventions with at least two subjects.

Data synthesis

Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data.

Results

We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes.

Conclusions

Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed.

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Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2)

Introduction

The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2x2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD.

Methods and analysis

Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol–five dimensions–five levels of perceived problems (EQ5D-5L), St. George's COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale.

Ethics and dissemination

The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals.

Trial registration number

ISRCTN43245574; Pre-results.

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Equity and intrapartum care by skilled birth attendant globally: protocol for a systematic review

Introduction

Equity is a cross-cutting theme within the Sustainable Development Goals (SDGs) and central to the effort to improve maternal and child health globally. One key strategy to prevent maternal death set out in SDG 3 is assistance by a skilled birth attendant (SBA) at childbirth (indicator 3.1.2). However, the increased coverage of SBAs globally has not been reflected by the same degree of decrease in maternal mortality and has been reported to have higher levels of inequality than other maternal health interventions. There is a need to evaluate the extent of inequity in intrapartum care by SBAs and evaluate themes in determinants of inequity across regions and specific country characteristics.

Methods and analysis

The protocol for this review follows The Cochrane Handbook for Systematic Reviews and Preferred Reporting Items for Systematic Reviews and Meta-Analyses with equity extension 2012 guidelines. Studies of all languages and from all countries from 2004, the year when the WHO/ICM/FIGO joint statement on SBAs was published, and onwards will be included. PubMed/MEDLINE, CINAHL Complete, the Cochrane Library, POPLINE, the World Health Organization (WHO) Global Index Medicus, and grey literature will be searched. Our primary outcome is intrapartum care by SBA. Studies will be included if they evaluate equity and its determinants adapted from the Progress-Plus grouping of characteristics affecting health outcomes. Results will be stratified based on WHO, World Bank Group income and SDG regional groupings.

Ethics and dissemination

This review is a secondary analysis of published literature and does not require ethics review. Results will provide information regarding equity in intrapartum care by SBAs globally and will inform development of indicators for monitoring of inequity as well as global policy related to intrapartum care and maternal mortality. Results will be disseminated via peer-reviewed manuscript, international conferences and stakeholder websites.

PROSPERO registration number

CRD42017069021.

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Variation in minimum desired cardiovascular disease-free longevity benefit from statin and antihypertensive medications: a cross-sectional study of patient and primary care physician perspectives

Objective

Expressing therapy benefit from a lifetime perspective, instead of only a 10-year perspective, is both more intuitive and of growing importance in doctor–patient communication. In cardiovascular disease (CVD) prevention, lifetime estimates are increasingly accessible via online decision tools. However, it is unclear what gain in life expectancy is considered meaningful by those who would use the estimates in clinical practice. We therefore quantified lifetime and 10-year benefit thresholds at which physicians and patients perceive statin and antihypertensive therapy as meaningful, and compared the thresholds with clinically attainable benefit.

Design

Cross-sectional study.

Settings

(1) continuing medical education conference in December 2016 for primary care physicians;(2) information session in April 2017 for patients.

Participants

400 primary care physicians and 523 patients in the Netherlands.

Outcome

Months gain of CVD-free life expectancy at which lifelong statin therapy is perceived as meaningful, and months gain at which 10 years of statin and antihypertensive therapy is perceived as meaningful. Physicians were framed as users for lifelong and prescribers for 10-year therapy.

Results

Meaningful benefit was reported as median (IQR). Meaningful lifetime statin benefit was 24 months (IQR 23–36) in physicians (as users) and 42 months (IQR 12–42) in patients willing to consider therapy. Meaningful 10-year statin benefit was 12 months (IQR 10–12) for prescribing (physicians) and 14 months (IQR 10–14) for using (patients). Meaningful 10-year antihypertensive benefit was 12 months (IQR 8–12) for prescribing (physicians) and 14 months (IQR 10–14) for using (patients). Women desired greater benefit than men. Age, CVD status and co-medication had minimal effects on outcomes.

Conclusion

Both physicians and patients report a large variation in meaningful longevity benefit. Desired benefit differs between physicians and patients and exceeds what is clinically attainable. Clinicians should recognise these discrepancies when prescribing therapy and implement individualised medicine and shared decision-making. Decision tools could provide information on realistic therapy benefit.

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Assessing whether early attention of very preterm infants can be improved by an omega-3 long-chain polyunsaturated fatty acid intervention: a follow-up of a randomised controlled trial

Introduction

Docosahexaenoic acid (DHA) accumulates in the frontal lobes (responsible for higher-order cognitive skills) of the fetal brain during the last trimester of pregnancy. Infants born preterm miss some of this in utero provision of DHA, and have an increased risk of suboptimal neurodevelopment. It is thought that supplementing infants born preterm with DHA may improve developmental outcomes. The aim of this follow-up is to determine whether DHA supplementation in infants born preterm can improve areas of the brain associated with frontal lobe function, namely attention and distractibility.

Methods and analysis

We will assess a subset of children from the N-3 (omega-3) Fatty Acids for Improvement in Respiratory Outcomes (N3RO) multicentre double-blind randomised controlled trial of DHA supplementation. Infants born <29 weeks' completed gestation were randomised to receive an enteral emulsion containing 60 mg/kg/day of DHA or a control emulsion from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age.

Children will undergo multiple measures of attention at 18 months' corrected age. The primary outcome is the average time to be distracted when attention is focused on a toy. Secondary outcomes are other aspects of attention, and (where possible) an assessment of cognition, language and motor development with the Bayley Scales of Infant and Toddler Development, Third Edition.

A minimum of 72 children will be assessed to ensure 85% power to detect an effect on the primary outcome. Families, and research personnel are blinded to group assignment. All analyses will be conducted according to the intention-to-treat principal.

Ethics and dissemination

All procedures were approved by the relevant institutional ethics committees prior to commencement of the study. Results will be disseminated in peer-reviewed journal publications and academic presentations.

Trial registration number

ACTRN12612000503820; Pre-results.

https://ift.tt/2LrqffP

Relevance of MTHFR polymorphisms with response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer: a meta-analysis

Objective

To evaluate the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer.

Design

Meta-analysis.

Methods

We searched PubMed, Embase and Web of Science databases from inception up to October 2017 for relevant studies. The statistical analysis was performed using STATA V.12.0 software. The pooled ORs and 95% CIs were used to assess the strength of the association under the allele, dominant and recessive models. We also conducted subgroup analysis stratified by cancer type, ethnicity and study design. Additionally, the sensitivity analysis was performed by sequential omission of individual studies, and the publication bias was detected using both Begg's test and Egger's test.

Results

A total of 2020 patients from 12 studies were included in this meta-analysis. The results showed that there was no significant association between MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and the clinical response to fluoropyrimidine-based chemotherapy under all of the three genetic models (T vs C: OR 0.93, 95% CI 0.76 to 1.15; C vs A: OR 0.88, 95% CI 0.56 to 1.40. CT+TT vs CC: OR 0.94, 95% CI 0.72 to 1.23; AC+CC vs AA: OR 0.80, 95% CI 0.47 to 1.35. TT vs CC+CT: OR 1.02, 95% CI 0.74 to 1.39; CC vs AA+AC: OR 1.15, 95% CI 0.50 to 2.67). When stratified by cancer type, ethnicity or study design, the association was still not significant in all subgroups.

Conclusions

This meta-analysis suggested that MTHFR polymorphisms could not be considered as reliable factors for predicting the response to fluoropyrimidine-based chemotherapy in oesophagogastric cancer.

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Danish method study on cervical screening in women offered HPV vaccination as girls (Trial23): a study protocol

Introduction

The first birth cohorts of women offered human papillomavirus (HPV) vaccination as girls are now entering cervical screening. However, there is no international consensus on how to screen HPV vaccinated women. These women are better protected against cervical cancer and could therefore be offered less intensive screening. Primary HPV testing is more sensitive than cytology, allowing for a longer screening interval. The aim of Trial23 is to investigate if primary HPV testing with cytology triage of HPV positive samples is a reasonable screening scheme for women offered HPV vaccination as girls.

Methods

Trial23 is a method study embedded in the existing cervical screening programme in four out of five Danish regions. Without affecting the screening programme, women born in 1994 are randomised to present screening with liquid-based cytology every third year (present programme arm) or present screening plus an HPV test (HPV arm). The study started 1 February 2017 and will run over three screening rounds corresponding to 7–8 years.

Analyses

The primary endpoint is cervical intraepithelial neoplasia grade 3 or above. The trial is undertaken as a non-inferiority study including intention-to-treat and per-protocol analyses. The potential effect of primary HPV screening with a 6-year interval will be calculated from the observed data.

Ethics and dissemination

The study protocol has been submitted to the ethical committee and deemed a method study. All women are screened according to routine guidelines. The study will contribute new evidence on the future screening of HPV vaccinated birth cohorts of women. All results will be published in open-access journal.

Trial registration

NCT03049553; Pre-results.

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Risky business: a longitudinal study examining cigarette smoking initiation among susceptible and non-susceptible e-cigarette users in Canada

Objectives

Given that many adolescent e-cigarette users are never-smokers, the possibility that e-cigarettes may act as a gateway to future cigarette smoking has been discussed in various studies. Longitudinal data are needed to explore the pathway between e-cigarette and cigarette use, particularly among different risk groups including susceptible and non-susceptible never-smokers. The objective of this study was to examine whether baseline use of e-cigarettes among a sample of never-smoking youth predicted cigarette smoking initiation over a 2-year period.

Design

Longitudinal cohort study.

Setting

89 high schools across Ontario and Alberta, Canada.

Participants

A sample of grade 9–11 never-smoking students at baseline (n=9501) who participated in the COMPASS study over 2 years.

Primary and secondary outcome measures

Participants completed in-class questionnaires that assessed smoking susceptibility and smoking initiation.

Results

Among the baseline sample of non-susceptible never-smokers, 45.2% of current e-cigarette users reported trying a cigarette after 2 years compared with 13.5% of non-current e-cigarette users. Among the baseline sample of susceptible never-smokers, 62.4% of current e-cigarette users reported trying a cigarette after 2 years compared with 36.1% of non-current e-cigarette users. Overall, current e-cigarette users were more likely to try a cigarette 2 years later. This association was stronger among the sample of non-susceptible never-smokers (AOR=5.28, 95% CI 2.81 to 9.94; p<0.0001) compared with susceptible never-smokers (AOR=2.78, 95% CI 1.84 to 4.20; p<0.0001).

Conclusions

Findings from this large, longitudinal study support public health concerns that e-cigarette use may contribute to the development of a new population of cigarette smokers. They also support the notion that e-cigarettes are expanding the tobacco market by attracting low-risk youth who would otherwise be unlikely to initiate using cigarettes. Careful consideration will be needed in developing an appropriate regulatory framework that prevents e-cigarette use among youth.

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Factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation: a retrospective case study in Southeast China

Objective

The aim of this study was to evaluate factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of congenital choledochal malformation (CCM).

Design

A 3-year retrospective study was undertaken between January 2013 and December 2015 in four centres in China.

Setting

This involved a retrospective chart review of paediatric patients with CCM in four large hospitals in Southeast China.

Participants

Sixty-five paediatric patients with CCM were included in this study. We derived all available information on patient demographics, clinical characteristics, preoperative complications and surgical methods from the charts of all these patients.

Interventions

Univariate and multivariate logistic regression analyses were used to evaluate factors significantly affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM.

Results

Twenty-three of the 65 case surgeries were performed using laparoscopic technique, and 42 surgeries were performed by conventional open surgery. The median operating time was 215 min (range 120–430 min). The morphological subtype of CCM and the presence of cholecystitis or cholangitis were the only factors found to affect the operating time (p<0.05). Logistic regression analysis confirmed cholangitis as an independent risk factor.

Conclusions

The morphological subtype of CMM and the presence of cholecystitis or cholangitis are factors affecting the operating time for complete cyst excision and Roux-en-Y hepaticojejunostomy in paediatric cases of CCM, whereas cholangitis is an independent risk factor.

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Prevalence of tobacco use and perceptions of student health professionals about cessation training: results from Global Health Professions Students Survey

Introduction

Health professionals play an important role in providing advice to their patients about tobacco prevention and cessation. Health professionals who use tobacco may be deterred from providing cessation advice and counselling to their patients. We aimed to provide prevalence estimates of tobacco use among student health professionals and describe their attitudes towards tobacco cessation training.

Methods

Country-wise aggregate data from the Global Health Professions Student Survey on 'current cigarette smoking' (smoking cigarettes on 1 or more days during the past 30 days), and 'current use of tobacco products other than cigarettes' (chewing tobacco, snuff, bidis, cigars or pipes, 1 or more days during the past 30 days) were analysed. For each WHO region, we estimated mean prevalence rates of tobacco use weighted by the population of the sampling frame and aggregate proportions for 'health professionals' role' and 'cessation training' indicators using 'metaprop' command on Stata V.11.

Results

A total of 107 527 student health professionals participated in 236 surveys done in four health profession disciplines spanning 70 countries with response rates ranging from 40% to 100%. Overall, prevalence of smoking was highest in European countries (20% medical and 40% dental students) and the Americas (13% pharmacy to 23% dental students). Other tobacco use was higher in eastern Mediterranean (10%–23%) and European countries (7%–13%). In most WHO regions, ≥70% of the students agreed that health professionals are role models, and have a role in advising about smoking cessation to their patients and the public. Only ≤33% of all student health professionals in most WHO regions (except 80% dental students in the Eastern Mediterranean region) had received formal training on smoking cessation approaches and ≥80% of all students agreed that they should receive formal cessation training.

Conclusions

Tobacco control should take place together with medical educators to discourage tobacco use among student health professionals and implement an integrated smoking cessation training into health professions' curricula.

https://ift.tt/2KVVNcs

Primary gastric melanoma: a rare presentation

Description

A man in his early 50s presented to the emergency department with complaints of abdominal pain and dark tarry stools. He reported 3/10 burning left upper quadrant abdominal pain that started 2 days before. The pain radiated to the epigastric region and the patient was unsure what exacerbates or relieves the pain. Starting around the same time, the patient had 8 to 10 black tarry stools daily, which were loose in consistency, which were coming out of his ostomy bag. Review of systems was positive for weakness, fatigue, nausea, abdominal pain and change in stools. The patient has a history of T4 caecal adenocarcinoma with metastasis to bladder diagnosed in 2014, for which he underwent right hemicolectomy, low anterior resection, radical cystectomy and colostomy with urostomy that was reversed 2 years later. He also underwent chemotherapy/radiation therapy with (FIFLORI) leucovorin calcium (folinic acid), fluorouracil and irinotecan hydrochloride. Vitals showed a temperature of 97.5°F, pulse...

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Coronary artery fistula and mid-cavitary obstructive hypertrophic cardiomyopathy: a rare association

We report a case of a 60-year-old man with a history of angina on exertion (New York Heart Association Class II) who was found to have mid-cavitary obstructive hypertrophic cardiomyopathy on two-dimensional echocardiography and whose coronary angiogram showed right coronary artery–left ventricular fistula, with no significant coronary atherosclerosis suggestive of ischaemic heart disease. The patient was started on beta-blocker therapy, and on follow-up his angina improved. The patient had a benign course and did not have any progressive heart failure or acute coronary syndrome on follow-up. This case report highlights a rare association of mid-cavitary obstructive hypertrophic cardiomyopathy with coronary artery fistula.

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Personalised 3D-printed model of a chest-wall chondrosarcoma to enhance patient understanding of complex cardiothoracic surgery

Description

Novel technologies, such as additive manufacturing (also termed three-dimensional (3D) printing), play an important role in surgical planning. Their role in enhancing a patient's understanding of their medical condition and increasing their satisfaction with their treatment is also gaining increased attention in medicine and surgery. As an illustration, we describe the case of a 65-year-old Caucasian man who presented with left-sided anterior chest-wall pain which was associated with a visible palpable lump. He had a body mass index of 27 kg/m², and CT of the thorax demonstrated a 62 mm x 60 mm x 48 mm tumour involving multiple structures, including the left fourth to sixth ribs, costal cartilages and the pericardium overlaying the right ventricle (figure 1). Transthoracic echocardiography showed normal ventricular function without any indication of tumour infiltration into the myocardium.

Figure 1

Axial (right) and sagittal (left) CT slices of the thorax demonstrating a large chondrosarcoma...

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Neisseria meningitidis sepsis in a patient with acute epiglottitis and respiratory failure

A 78-year-old female patient presented to our emergency department with a 5-day history of throat pain, hoarseness and a progressive and dolorous submandibular swelling. Due to non-conclusive clinical examination and the stable but visibly affected patient, we performed a neck CT scan with intravenous contrast, which showed the thumbprint sign typical for acute epiglottitis. Within minutes, the patient's condition deteriorated and the patient was close to respiratory exhaustion. As intubation was severely complicated by massive swelling of the supraglottic soft tissue, the patient went into hypoxaemia and eventually cardiac arrest. After initiating reanimation protocol, eventually the airway was secured and Return of spontaneous circulation (ROSC) achieved after around 5 min. The initially sampled blood cultures revealed Neisseria meningitidis bactera emia and the patient was successfully treated accordingly. In patients with swelling of the upper airway, rapid clinical deterioration is possible. Diagnostics should not delay therapy, including administration of empiric antibiotics, steroids and intubation.

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Right-sided hydrothorax: a peritoneal dialysis dilemma

We present a 23-year-old female patient with a chief complaint of progressively worsening dyspnoea of 2 days duration. Her medical history was significant for end stage renal disease secondary to membranoproliferative glomerulonephritis. A peritoneal dialysis (PD) catheter was placed 8 weeks prior to admission. She did not miss any of the PD sessions prior to this admission. Vital signs were significant for hypoxemia. Physical examination was remarkable for right-sided basilar crackles with no other signs of fluid overload. A chest X-ray demonstrated the presence of a large right-sided pleural effusion. Right-sided thoracentesis was performed, with subsequent pleural fluid analysis concerning for a pleuroperitoneal leak. CT peritoneography performed confirming the diagnosis as contrast material leaked through the inferior vena cava (IVC) diaphragmatic foramen into the right pleural space. Surgical intervention was deferred in light of the close proximity of the defect to the IVC. The patient was transitioned to haemodialysis for temporary cessation of PD.

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Successful pregnancies and reduced treatment requirement while breast feeding in a patient with congenital hypoparathyroidism due to homozygous c.68C>A null parathyroid hormone gene mutation

A female patient with consanguineous parents presented at the age of 4 with isolated hypoparathyroidism due to a parathyroid hormone (PTH) gene mutation. She was managed with alfacalcidol and calcium supplements, and developed normally. Her consanguineous parents described symptoms suggestive of hypocalcaemia but had normal serum calcium and low normal PTH levels. A molecular diagnosis obtained in her adulthood revealed the presence of homozygous point mutation (c.68C>A) in exon 2 introducing a premature stop codon resulting in a non-functional precursor protein. This mutation has been reported only once before. Our patient remained on stable doses of alfacalcidol during pregnancy, but stopped all supplementation while breast feeding. This case confirms that alternative mechanisms (likely breast-derived parathyroid hormone-related protein) contribute to calcium homeostasis during breast feeding. Heterozygotes for the c.68C>A mutation may have latent hypoparathyroidism and maintain calcium homeostasis except during prolonged hypocalcaemia. This would suggest incomplete dominance, or a dose effect of the wild-type PTH allele.

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Chronic pancreatitis with Bochdalek hernia causing right-sided pleural effusion in a previously asymptomatic adult

A 41-year-old man with a medical history of chronic back pain, seizure disorder, alcohol and tobacco abuse presented with acute shortness of breath. Chest X-ray showed a large right-sided pleural effusion. Pleural fluid analysis was significant for an elevated amylase level, suggestive of pleural effusion secondary to pancreatitis. Magnetic resonance cholangiopancreatography (MRCP) revealed a persistent right-sided pleural effusion in connection with a right pararenal space fluid collection via a Bochdalek hernia. An endoscopic ultrasound found hyperechoic strands and foci, and pancreatic parenchyma consistent with chronic pancreatitis, as well as a pseudocyst in the pancreatic head. A chest tube was ultimately placed to continuously drain the pleural effusion. The patient was discharged and was referred to gastroenterology for outpatient follow-up. This case illustrates a rare presentation of chronic pancreatitis with a Bochdalek hernia as a right-sided pleural effusion in a patient who was previously asymptomatic.

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Thromboatheromatous coarctation of the aorta diagnosed with intraoperative TOE during emergent open aneurysm clipping

A woman in her 50s presenting for emergent intracranial surgery was discovered to have a large incongruity in blood pressure between her right arm and her other extremities. Intraoperative rescue transoesophageal echocardiography (TOE) revealed a large thromboatheromatous burden in her descending aorta resulting in a functional coarctation. Usually diagnosed via CT imaging, we present what we believe to be the first published case diagnosed intraoperatively using TOE. After the diagnosis was made, blood pressure goals were adjusted to provide sufficient perfusion distally and her surgery was completed otherwise uneventfully.

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Synchronous oesophageal and gastric sarcomatoid carcinoma: first reported case in Australia

A 75-year-old retired teacher presents with dysphagia and weight loss for a duration of 6 months. Her gastroscopy showed two synchronous submucosal masses. A 7 cm polypoid mass was seen at the distal oesophagus, arising from a thick stalk and a 4 cm mass seen at the cardia. The biopsies showed high-grade sarcomatoid cancer. Staging CT scan and Positron Emission Tomography scan did not show any distant metastasis except a lesion in the rectum that was subsequently found to be tubulovillous adenoma on transanal excision. The patient was managed with Ivor Lewis oesophagectomy. The biopsies of resection specimen showed spindle cell/sarcomatoid carcinoma with a component of poorly differentiated neuroendocrine carcinoma in oesophageal tumour and a small component of conventional invasive squamous cell carcinoma in tumour at cardia. The patient recovered well after surgery. Since then, she has completed adjuvant chemoradiotherapy. No recurrence has been noted in 10 months follow-up.

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Sedation for gastrointestinal endoscopy in Australia: what is the same and what is different?

Purpose of review The purpose of this article is to review the practice of sedation for adults having gastrointestinal endoscopy in Australia and to compare it with practice in other countries. Recent findings The practice of sedation for endoscopy in Australia is dominated by anaesthesiologists, who have a preference for deep propofol-based sedation. The recent literature includes a number of guidelines for sedation developed by multidisciplinary groups, anaesthesiologists and gastroenterologists in Australia and other countries. The appropriate health practitioner to provide deep sedation and general anaesthesia, to use propofol for sedation and to manage higher risk patients remains controversial. The estimated risks associated with endoscopy vary by provider, sedation technique and study design (prospective or retrospective, single- or multicentre). New airway management techniques are being investigated that may be useful in patients at high risk of hypoventilation and hypoxia. Summary Endoscopy sedation is safe but more high-quality, multicentre observer-blinded randomized controlled trials are required. Correspondence to Kate Leslie, AO, FAHMS, Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Parkville, VIC 3050, Australia. Tel: +61 3 93427540; e-mail: kate.leslie@mh.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Measuring quality of recovery in perioperative clinical trials

Purpose of review Perioperative studies increasingly report patient-centered outcomes, but few provide a valid, global measure of a patient's health status after surgery and anesthesia. This review considers three quality of recovery (QoR) scales. Recent findings The 9-item (QoR Score), 15-item (QoR-15), and 40-item (QoR-40) QoR scales have been extensively validated in perioperative settings, and have also been used as outcome measures in numerous surgery and anesthesia studies. A range of clinical trials are presented to illustrate the value of the QoR scales in perioperative medicine research. Summary The QoR Score, QoR-15, and QoR-40 are valid and recommended endpoints for perioperative clinical trials, and there is guidance as to what constitutes a minimal clinically important difference. These recovery scales are sensitive to a change in health status and, as numerical data, optimize statistical power when used in the design of a clinical trial. They are closely correlated with conventional measures of outcome such as analgesic consumption, pain scores, nausea and vomiting, and hospital stay. Although conventional measures may be considered patient-centered, each are incomplete by themselves. QoR scores provide a meaningful overall evaluation of a patient's recovery after surgery and anesthesia. Correspondence to Paul S. Myles, Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Road, Melbourne 3004, VIC, Australia. Tel: +61 39076 2000; fax: +61 39076 2813; e-mail: p.myles@alfred.org.au Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The outcome to axitinib or everolimus after sunitinib in metastatic renal cell carcinoma

We aimed to investigate the different outcomes in patients with metastatic renal cell carcinoma treated with second-line axitinib or everolimus after sunitinib. Patients treated in 16 oncological centres in Italy were included, and those receiving axitinib or everolimus from January 2013 onwards were analysed for outcomes. Descriptive statistical tests were used to highlight differences between groups. The Kaplan–Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Data on 634 patients with metastatic renal cell carcinoma treated with first-line sunitinib have been obtained. A total of 182 patients received a second-line therapy with everolimus (79 patients, 43%) or axitinib (103 patients, 57%), respectively. The median PFS was 4.6 [95% confidence (CI): 2.6–6.5] months for patients treated with everolimus and 5.5 (95% CI: 4.3–6.7) months for patients treated with axitinib (P=0.7). The median OS was 13.9 (95% CI: 10.4–17.4) months for patients treated with everolimus and 12.0 (95% CI: 7.9–16.2) months for patients treated with axitinib (P=0.3). No differences were found based on length of first-line treatment. Major limitations are the retrospective nature of the study and the lack of a prospective evaluation of the progression. This study reports no significantly differences between everolimus and axitinib in terms of both PFS and OS. Furthermore, the length of first-line treatment cannot be used as such a predictive factor and cannot suggest the use of a molecule compared with another. Correspondence to Roberto Iacovelli, MD, PhD, Medical Oncology Unit, Integrated University Hospital of Verona (AOUI), Piazzale L.A. Scuro 10, 37134 Verona, Italy Tel: +39 045 812 115; fax: +39 045 802 7410; e-mail: roberto.iacovelli@aovr.veneto.it Received December 19, 2017 Accepted March 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Dabrafenib and trametinib treatment-associated fevers in metastatic melanoma causing extreme elevation in procalcitonin in the absence of infection

Febrile illnesses are common in the management of metastatic solid organ malignancies. Traditionally they occur in the setting of immunosuppression and neutropenia owing to cytotoxic therapy necessitating consideration of systemic infections. Systemic markers of inflammation, such as C-reactive protein and procalcitonin (PCT), may be used to assist in determining the aetiology of a fever in such patients. Newer anticancer therapies may cause significant noninfectious fevers and may result in a rise in inflammatory markers, despite the absence of an infection. We present a case of a critically unwell febrile patient being treated with dabrafenib and trametinib for advanced melanoma. The patient had an extreme elevation in PCT in the absence of infection. We discuss the presentation of fevers related to dabrafenib and trametinib therapy in the management of advanced melanoma, and the utility of PCT in the management of fevers in advanced solid organ malignancies. Correspondence to Samantha E. Bowyer, MBBS (Hons), DMedSci, FRACP, St John of God Subiaco Hospital, Suite C202, 12 Salvado Road, Subiaco, Western Australia 6008, Australia Tel: +61 893 826 111; fax: +61 864 659 250; e-mail: tim@drtimclay.com.au Received March 5, 2018 Accepted May 10, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Co-delivery of paclitaxel and gemcitabine by methoxy poly(ethylene glycol)–poly(lactide-coglycolide)-polypeptide nanoparticles for effective breast cancer therapy

Traditional chemotherapeutic drugs have shown limited clinical curative effects in antitumor therapy. The application of multidrug combination and adjuvant-drug carriers is a feasible strategy to overcome the limitations while minimizing the dosage of single drug and acquiring the synergistic effects in tumor therapy. However, the systemic toxicity, drug resistance, and tumor recurrence are still unavoidable. Here we develop core–shell nanoparticles (NPs) to encapsulate paclitaxel (PTX) and gemcitabine (GEM) for breast cancer therapy. We find that the NPs could encapsulate PTX and GEM, with an encapsulation efficiency of 96.3 and 95.13%, respectively. Moreover, the drug loading of these NPs is 2.71% (PTX) and 2.64% (GEM). Notably, the co-delivery of GEM and PTX performs enhanced anticancer effect compared with the PTX alone or GEM alone therapy at the same concentration, which indicates a synergistic effect. Moreover, encapsulation of PTX and GEM by methoxy poly(ethylene glycol)–poly(lactide-coglycolide) also shows enhanced anticancer effects (81.5% tumor inhibition) and reduced systemic toxicity in vivo compared with free drugs (65% tumor inhibition). Together with those results, co-delivery of PTX and GEM by methoxy poly(ethylene glycol)–poly(lactide-coglycolide) might have important potencies in clinical applications for breast cancer therapy. Correspondence to Mingzhi Zhang, PhD, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe Road, No. 1, Erqi Square, Zhengzhou 450000, People's Republic of China Tel/fax: +86 371 6697 0906; e-mail: mingzhi_zhang1@163.com or Correspondence to Yonggang Shi, MSc, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Jianshe Road, No. 1, Erqi Square, Zhengzhou 450000, People's Republic of China Tel/fax: +86 371 6697 0906; e-mail: shiyong737@126.com Received October 20, 2017 Accepted March 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands

There is little evidence on the costs associated with the route of administration of oncology drugs. We investigated time and resource use for hospitals and patients and compared healthcare and societal costs for intravenous (IV) and subcutaneous (SC) administration of trastuzumab and rituximab. Data for the preparation and administration of both drugs were collected at the hospital pharmacy and at the oncology day care unit. Patients completed a questionnaire for obtaining information on societal costs (productivity losses, informal care and traveling expenses). A total of 126 patients were recruited in six hospitals; 82 received trastuzumab (37 IV and 45 SC) and 44 received rituximab (23 IV and 21 SC). The costs per administration (including societal cost but excluding drug costs) were €167 and €264 for IV and €76 and €146 for SC trastuzumab and rituximab, respectively. The costs for SC administration were lower in all categories. The largest cost component was related to time spent at the day care unit (overhead costs). This resulted in savings of €47 for SC trastuzumab and €69 for SC rituximab. The costs related to time of healthcare professionals was €9 lower for both drugs. The costs for consumables resulted in another €12 savings. Societal costs were €22 lower for SC trastuzumab and €28 lower for SC rituximab. Although administration costs are relatively a small part of the total costs, important savings can be generated by switching to an SC route of administration especially because a large number of patients receive oncology drugs and patients receive more than one administration. Correspondence to Margreet G. Franken, PhD, Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands Tel: +31 10 408 1372; e-mail: franken@imta.eur.nl Received January 10, 2018 Accepted April 24, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical management of a pituitary gland metastasis from clear cell renal cell carcinoma

In very few years, several treatments have significantly improved the prognosis of patients with metastatic renal cell carcinoma (RCC). Despite this, the clinical outcomes of specific subgroups of patients including those with central nervous metastases still remain poor. In this population, a very infrequent and poorly described site of metastases is the pituitary gland. Because of the important endocrinal function and the anatomic site of this specific organ, clinical management of this complication requires several additional precautions compared with other central nervous metastases. Here, we describe a case of a single pituitary metastasis from clear cell RCC in a patient who showed a surprising progression-free survival and overall survival to sunitinib first-line treatment. Because of the uncommon clinical course of the disease of our patient and the atypical site of metastases, we want also to underline the importance of further investigation of molecular pathways associated with a favorable prognosis in patients with metastatic clear cell RCC. *Vincenzo Di Nunno and Veronica Mollica contributed equally to the writing of this article. Correspondence to Francesco Massari, MD, Division of Oncology, Sant'Orsola-Malpighi Hospital, Via Albertini n.15, 40138 Bologna, Italy Tel: +39 051 214 2223; fax: +39 051 636 2764; e-mail: fmassari79@gmail.com Received March 4, 2018 Accepted April 17, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma

Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen synthase kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD-8, and 9-ING-41) suppressed the growth of neuroblastoma cells, whereas 9-ING-41, a clinically relevant small-molecule GSK-3β inhibitor with broad-spectrum preclinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and an increase in neuroblastoma cell apoptosis. Mouse xenograft studies showed that the combination of clinically relevant doses of CPT-11 and 9-ING-41 led to greater antitumor effect than was observed with either agent alone. These data support the inclusion of patients with advanced neuroblastoma in clinical studies of 9-ING-41, especially in combination with CPT-11. Correspondence to Andrew P. Mazar, PhD, Monopar Therapeutics, Inc. 5 Revere Drive, Suite 200, Northbrook, IL 60062, USA Tel: +1 847 388 0349 x403; e-mail: mazar@monopartx.com Received March 23, 2018 Accepted May 1, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Survival outcomes in patients with non-small-cell lung cancer treated with erlotinib

Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment of advanced stage (IIIB or IV) NSCLC (August 2008). In the pivotal trial supporting initial subsidy, erlotinib increased overall survival (OS) by 2 months compared with placebo (adjusted hazard ratio, 0.70; 95% confidence interval: 0.58–0.85). We examined the effectiveness of erlotinib in a 'real-world' setting by measuring survival outcomes in NSCLC patients treated in two tertiary metropolitan public hospitals in Queensland. We extracted data from the electronic oncology prescribing system (CHARM) for NSCLC patients prescribed erlotinib (1 September 2009 to 1 February 2015). Survival estimates and analyses were generated using Kaplan–Meier curves. 134 patients received at least one dose of erlotinib during the study period. At the date of data extraction 113 patients had died. The median patient age was 64 years and 55% were men. The median duration of treatment was 2.0 months. The median OS was 5.8 months. The median progression-free survival (time from start of erlotinib to disease progression or death from any cause) was 3.6 months. The use of erlotinib in the two Queensland sites was consistent with the pivotal trial used to support subsidy. The median OS was somewhat less than the trial (5.8 vs. 6.7 months), which could be because of the hospital cohort including frailer patients who were unsuitable for parenteral chemotherapy, and the mixed epidermal growth factor receptor mutation status of the hospital cohort. Correspondence to Samantha A. Hollingworth, BSc, MPH, PhD, School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba QLD 4102, Australia Tel: +61 733 461 981; fax: +61 733 461 999; e-mail: s.hollingworth@uq.edu.au Received October 24, 2017 Accepted April 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2sgnrt9

Promising effects of eribulin for cystic lung metastases of epithelioid sarcoma: a case report

Epithelioid sarcoma (ES) is a rare and aggressive type of soft tissue sarcoma with resistance to systemic chemotherapy. Therefore, new treatment options are required for patients with advanced ES. Eribulin is a novel potential treatment option for patients with inoperative sarcoma. We herein report a case of a 27-year-old Japanese man with cystic lung metastases from an ES in the left forearm, resulting in long-term stable disease. A solid, metastatic sarcomatous nodule appeared in the right lung, as shown by computed tomography, within the first 2 months after surgery. After the lung metastasis was detected, he underwent a total of 37 cycles of chemotherapy in six regimens. However, multiple cystic lung metastases had progressed in segments S6 and S9/10; hence, eribulin treatment was initiated. After two courses of eribulin, the excess fluid density material in the cystic metastases was completely absorbed, and an additional four courses of treatment resulted in shrinkage of the cystic metastases. These effects lasted for 13 months without severe adverse effects. Cystic lung metastases are an extremely rare consequence of soft tissue sarcoma, and eribulin is one of the most promising options for the treatment of advanced ES. Correspondence to Tadashi Iwai, MD, Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-Machi, Abeno-Ku, Osaka 545-8585, Japan Tel: +81 666 453 851; fax: +81 666 466 260; e-mail: qq329xpd@opal.ocn.ne.jp Received March 27, 2018 Accepted May 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Use of pertuzumab and trastuzumab during pregnancy

Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of breast cancer. Until now, there have been no reports on the use of pertuzumab during pregnancy and on its potential effects on the fetus. Herein, we present a breast cancer patient who received trastuzumab and pertuzumab treatment during the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed with invasive ductal carcinoma of the breast was found to be negative for estrogen receptor and progesterone receptor and positive for human epidermal growth factor receptor in the immunohistochemical examination. At the time of diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab, pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six courses of therapy, she had near-complete response, and, after administration of the same course of treatment for two additional cycles, treatment with pertuzumab plus trastuzumab was continued. While she was being followed-up with remission, a 20-week pregnancy was detected. A fetal ultrasound examination showed oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus was monitored. After 7 weeks of follow-up, fetal growth retardation and anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no urinary system pathology, but macroscopic and microscopic hyperplasia of the right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab during pregnancy may be associated with an unresolved oligohydramnios and/or anhydramnios risk. Extreme caution should be used when these monoclonal antibodies are administered during pregnancy. Correspondence to Nilgun Yildirim, MD, Department of Medical Oncology, Dr Ersin Arslan Training and Research Hospital, Gaziantep 27000, Turkey Tel: +90 342 221 0700/+90 505 254 3251; fax: +90 342 221 0142; e-mail: drnilgunsari@yahoo.com Received February 21, 2018 Accepted May 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Turning cancer's metabolic plasticity into fragility- an evolving paradigm

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https://ift.tt/2ILVtAw

SOCIO-ECOLOGICAL CORRELATES OF EXERCISE AT CARDIAC REHABILITATION COMPLETION

Objectives To describe: (1) the amount of physical activity (PA) in cardiac rehabilitation (CR) graduates by sex, and (2) the correlates of their PA. Design Secondary analysis of baseline data from a randomized trial was undertaken. Graduates were recruited from 3 CR programs. Participants completed a questionnaire which assessed constructs from the Socio-ecological model (i.e., individual-level, social and physical-environmental levels). PA was measured objectively using an ActiGraph GT3X accelerometer. Multi-level modeling was performed. Results 255 patients consented, of which 200 (78.4%) completed the survey and provided valid accelerometer data. Participants self-reported engaging in a mean of 184.51±129.10 (standard deviation) minutes of moderate-to-vigorous-intensity PA (MVPA) per week (with men engaging in more than women, p<.05 accelerometer data revealed participants engaged in minutes of mvpa with meeting recommendations. the mixed models socio-ecological correlate significantly related to greater self-reported was self-regulation accelerometer-derived neighborhood aesthetics conclusions approximately one-quarter cr program completers are achieving recommendations although two-thirds perceive they are. programs should exploit accelerometry and promote skills namely self-monitoring goal-setting positive reinforcement time management relapse prevention. patients be encouraged exercise pleasing locations. funding: this work supported by a grant-in-aid from heart stroke foundation canada ontario award number: prof. grace her toronto general western hospital peter munk cardiac centre university health network. stephanie prince is funded fellowship canadian institute research an endowed strategic ottawa foundation. funders played no role design study collection analysis or interpretation writing manuscript. conflict interest: authors declare that have interest. statement human rights: has been approved appropriate institutional national ethics committee performed accordance ethical standards as laid down declaration helsinki its later amendments comparable standards. on welfare animals: article does not contain any studies animals authors. informed consent: consent obtained all individual corresponding author: sherry l. phd. school kinesiology science bethune york keele street m3j ip3 canada. email: sgrace copyright wolters kluwer inc. rights reserved.>

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Pronator Syndrome: An Uncommon Median Nerve Entrapment Syndrome

Not Applicable for Visual Vignette Correspondence: Ying Liang LOW, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Email: ying_liang_low@nuhs.edu.sg Author Disclosures: There are no competing interests; no funding, grants or equipment provided for the project from any source; and no financial benefits to the authors. This article has not been presented in any form previously. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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(OA48) Prospective In-Silico Quality Assurance Study of Contouring Target Volumes in Thoracic Tumors Within a Cooperative Group Setting

Target delineation variability is a significant technical impediment in multi-institutional, including cooperative group, trials which employ intensity modulated radiotherapy (IMRT), as there is real potential for clinically meaningful variance in radiotherapy plans submitted to future studies. However, little is known how best to optimize protocols to account for multimodality imaging (e.g. PET, 4DCT) in the treatment planning process. The goal of this study is to determine the variability of target delineation among observers from different institutions as part of SWOG Radiotherapy Committee's multi-institutional in-silico quality assurance study of target delineation in patients with superior sulcus tumors.

https://ift.tt/2salBKU

Accelerated vascular aging and persistent cognitive impairment in older female breast cancer survivors

Abstract

Advances in breast cancer treatment have markedly increased survivorship over the past three decades, with over 3.1 million survivors expected to live into their 70s and 80s. Without symptom relief interventions, nearly 35% of these survivors will have life-altering and distressing cognitive symptoms. This pilot study explored associations between serum markers of vascular aging, laterality in cerebral oxygenation, and severity of cognitive impairment in women, 12–18 months after chemotherapy for stage 2/3 invasive ductal breast cancer. Fifteen women (52–84 years) underwent a brief cognitive assessment (Montreal Cognitive Assessment [MOCA]) and blood draws to assess markers of vascular aging (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], and insulin growth factor-1 [IGF-1]). All underwent a computer-based test protocol that is known to increase blood flow within the frontal lobes. Percent cerebral oxyhemoglobin saturation (rcSO₂) was recorded during and after testing. Laterality in rcSO₂ was defined by ≥ 3% difference between left and right rcSO₂ (|rcSO₂ mean_{RIGHT –} mean_LEFT|). Eight participants had MOCA scores between 21 and 25 points, suggestive of mild cognitive impairment. Neither CRP (r = −.24) nor IL-6 (r = .34) nor TNF-α (r = .002) were associated with MOCA scores. Higher IL-6 was associated with greater laterality (r = .41). MOCA scores were significantly lower in subjects with laterality in rcSO₂ than in those without laterality (F_(1,14) = 13.5, p = 003). Lower IGF-1 was significantly associated with greater laterality (r = − .66, p = .007) and lower cognitive function (r = .58). These findings suggest that persistent cognitive impairment is associated with phenotypical changes consistent with accelerated vascular aging.

https://ift.tt/2ILUz6X

Hepatocellular nodules in vascular liver diseases

Abstract

Hepatocellular nodules have been recognized in vascular liver diseases for a long time and mostly described and studied in the imaging literature. Some confusions in their identification and overlap in their definitions exist, especially in this specific clinical context. Pathology descriptions report the development of nodular regenerative hyperplasia, large regenerative nodule, and focal nodular hyperplasia, as adaptive responses of the liver parenchyma to the modified blood flow. True neoplastic hepatocellular nodules such as hepatocellular adenoma and hepatocellular carcinoma can also appear, mainly in Budd-Chiari syndrome, and have to be correctly diagnosed. This is more difficult for the radiologist in these diseased livers, leading more frequently to perform liver biopsies. We describe the histology of each type of well-differentiated hepatocellular nodules and provide some clues for their differential diagnosis. A review of the literature gives an historical perspective of the problem and enlightens the frequency and the subtypes of hepatocellular nodules found in the most common vascular liver diseases.

https://ift.tt/2ktVuum

The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma

Abstract

Background

Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown.

Methods

We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot.

Results

We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes.

Conclusions

Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

https://ift.tt/2xegEWz