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Τετάρτη 11 Οκτωβρίου 2017

Synthesis of Metal Nanoparticles in Metal-Phenolic Networks: Catalytic and Antimicrobial Applications of Coated Textiles

Abstract

The synthesis of metal nanoparticle (NP)-coated textiles (nanotextiles) is achieved by a dipping process in water without toxic chemicals or complicated synthetic procedures. By taking advantage of the unique nature of tannic acid, metal-phenolic network-coated textiles serve as reducing and stabilizing sites for the generation of metal nanoparticles of controllable size. The textiles can be decorated with various metal nanoparticles, including palladium, silver, or gold, and exhibit properties derived from the presence of the metal nanoparticles, for example, catalytic activity in water (>96% over five cycles using palladium nanoparticles) and antibacterial activity against Gram-negative bacteria (inhibition of Escherichia coli using silver nanoparticles) that outperforms a commercial bandage. The reported strategy offers opportunities for the development of hybrid nanomaterials that may have application in fields outside of catalysis and antimicrobials, such as sensing and smart clothing.

Thumbnail image of graphical abstract

Just dipping produces metal nanoparticle-coated textiles (nanotextiles) without involving toxic chemicals or complicated synthetic steps. This versatile method enables the incorporation of various metal nanoparticles of controllable size, including palladium, silver, or gold, on the textiles. These nanotextiles show >96% catalytic activity in water over five cycles and superior antibacterial activity when compared against a commercial antibacterial bandage.



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Ectopic pregnancy: exploration of its global research architecture using density-equalising mapping and socioeconomic benchmarks

Objective

About 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters.

Design

Retrospective, descriptive study.

Setting

On the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012.

Results

8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities.

Conclusions

This is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input.



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A county-level cross-sectional analysis of positive deviance to assess multiple population health outcomes in Indiana

Objective

To test a positive deviance method to identify counties that are performing better than statistical expectations on a set of population health indicators.

Design

Quantitative, cross-sectional county-level secondary analysis of risk variables and outcomes in Indiana. Data are analysed using multiple linear regression to identify counties performing better or worse than expected given traditional risk indicators, with a focus on 'positive deviants' or counties performing better than expected.

Participants

Counties in Indiana (n=92) constitute the unit of analysis.

Main outcome measures

Per cent adult obesity, per cent fair/poor health, low birth weight per cent, per cent with diabetes, years of potential life lost, colorectal cancer incidence rate and circulatory disease mortality rate.

Results

County performance that outperforms expectations is for the most part outcome specific. But there are a few counties that performed particularly well across most measures.

Conclusions

The positive deviance approach provides a means for state and local public health departments to identify places that show better health outcomes despite demographic, social, economic or behavioural disadvantage. These places may serve as case studies or models for subsequent investigations to uncover best practices in the face of adversity and generalise effective approaches to other areas.



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Comparison of the cerebroprotective effect of inhalation anaesthesia and total intravenous anaesthesia in patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis

Objective

Neurological dysfunction remains a devastating postoperative complication in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), and previous studies have shown that inhalation anaesthesia and total intravenous anaesthesia (TIVA) may produce different degrees of cerebral protection in these patients. Therefore, we conducted a systematic literature review and meta-analysis to compare the neuroprotective effects of inhalation anaesthesia and TIVA.

Design

Searching in PubMed, EMBASE, Science Direct/Elsevier, China National Knowledge Infrastructure and Cochrane Library up to August 2016, we selected related randomised controlled trials for this meta-analysis.

Results

A total of 1485 studies were identified. After eliminating duplicate articles and screening titles and abstracts, 445 studies were potentially eligible. After applying exclusion criteria (full texts reported as abstracts, review article, no control case, lack of outcome data and so on), 13 studies were selected for review. Our results demonstrated that the primary outcome related to S100B level in the inhalation anaesthesia group was significantly lower than in the TIVA group after CPB and 24 hours postoperatively (weighted mean difference (WMD); 95% CI (CI): –0.41(–0.81 to –0.01), –0.32 (–0.59 to –0.05), respectively). Among secondary outcome variables, mini-mental state examination scores of the inhalation anaesthesia group were significantly higher than those of the TIVA group 24 hours after operation (WMD (95% CI): 1.87 (0.82 to 2.92)), but no significant difference was found in arteriovenous oxygen content difference, cerebral oxygen extraction ratio and jugular bulb venous oxygen saturation, which were assessed at cooling and rewarming during CPB.

Conclusion

This study demonstrates that anaesthesia with volatile agents appears to provide better cerebral protection than TIVA for patients undergoing cardiac surgery with CPB, suggesting that inhalation anaesthesia may be more suitable for patients undergoing cardiac surgery.



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Patient characteristics of the Accident and Emergency Department of Kenyatta National Hospital, Nairobi, Kenya: a cross-sectional, prospective analysis

Background

Resource-limited settings are increasingly experiencing a 'triple burden' of disease, composed of trauma, non-communicable diseases (NCDs) and known communicable disease patterns. However, the epidemiology of acute and emergency care is not well characterised and this limits efforts to further develop emergency care capacity.

Objective

To define the burden of disease by describing the patient population presenting to the Accident and Emergency Department (A&E) at Kenyatta National Hospital (KNH) in Kenya.

Methods

We completed a prospective descriptive assessment of patients in KNH's A&E obtained via systematic sampling over 3 months. Research assistants collected data directly from patients and their charts. Chief complaint and diagnosis codes were grouped for analysis. Patient demographic characteristics were described using the mean and SD for age and n and percentages for categorical variables. International Classification of Disease 10 codes were categorised by 2013 Global Burden of Disease Study methods.

Results

Data were collected prospectively on 402 patients with an average age of 36 years (SD 19), and of whom, 50% were female. Patients were most likely to arrive by taxi or bus (39%), walking (28%) or ambulance (17%). Thirty-five per cent of patients were diagnosed with NCDs, 24% with injuries and 16% with communicable diseases, maternal and neonatal conditions. Overall, head injury was the single most common final diagnosis and occurred in 32 (8%) patients. The most common patient-reported mechanism for head injury was road traffic accident (39%).

Conclusion

This study estimates the characteristics of the A&E population at a tertiary centre in Kenya and highlights the triple burden of disease. Our findings emphasise the need for further development of emergency care resources and training to better address patient needs in resource-limited settings, such as KNH.



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Is an opportunistic primary care-based intervention for non-responders to bowel screening feasible and acceptable? A mixed-methods feasibility study in Scotland

Objectives

We aimed to test whether a brief, opportunistic intervention in general practice was a feasible and acceptable way to engage with bowel screening non-responders.

Design

This was a feasibility study testing an intervention which comprised a brief conversation during routine consultation, provision of a patient leaflet and instructions to request a replacement faecal occult blood test kit. A mixed-methods approach to evaluation was adopted. Data were collected from proformas completed after each intervention, from the Bowel Screening Centre database and from questionnaires. Semi-structured interviews were carried out. We used descriptive statistics, content and framework analysis to determine intervention feasibility and acceptability.

Participants

Bowel screening non-responders (as defined by the Scottish Bowel Screening Centre) and primary care professionals working in five general practices in Lothian, Scotland.

Primary and secondary outcome measures

Several predefined feasibility parameters were assessed, including numbers of patients engaging in conversation, requesting a replacement kit and returning it, and willingness of primary care professionals to deliver the intervention.

Results

The intervention was offered to 258 patients in five general practices: 220 (87.0%) engaged with the intervention, 60 (23.3%) requested a new kit, 22 (8.5%) kits were completed and returned. Interviews and questionnaires suggest that the intervention was feasible, acceptable and consistent with an existing health prevention agenda. Reported challenges referred to work-related pressures, time constraints and practice priorities.

Conclusions

This intervention was acceptable and resulted in a modest increase in non-responders participating in bowel screening, although outlined challenges may affect sustained implementation. The strategy is also aligned with the increasing role of primary care in promoting bowel screening.



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Association between childhood allergic diseases, educational attainment and occupational status in later life: systematic review protocol

Introduction

Childhood allergic diseases may prevent affected children from achieving their academic potential. Potential mechanisms include absence from school due to illness and medical appointments. Experience of symptoms in classes or leisure time, and stigma associated with visible signs and symptoms, including skin disease, requirements for medication during school time or the need for specific diets, may also contribute to reduced educational attainment. Studies have investigated the association between specific allergic diseases and educational attainment. The aim of this study is to systematically review the literature on allergic diseases, educational attainment and occupational status, and if possible, calculate meta-analytic summary estimates for the associations.

Methods

Systematic electronic searches in Medline, EMBASE, Cochrane, Cumulative Index to Nursing & Allied Health Literature (CINAHL), PsycINFO and education Resources Information Center (ERIC); hand search in reference lists of included papers and conference reports; search for unpublished studies in clinical trial registers and the New York Academy of Medicine Grey Literature Report; data extraction; and study quality assessment (Newcastle-Ottawa Scale) will be performed.

Analysis

Data will be summarised descriptively, and meta-analysis including meta-regression to explore sources of heterogeneities will be performed if possible.

Ethics and dissemination

Dissemination in a peer-reviewed, open-access, international scientific journal is planned.

PROSPERO registration number

CRD42017058036.



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Investigating Canadian parents' HPV vaccine knowledge, attitudes and behaviour: a study protocol for a longitudinal national online survey

Introduction

Human papillomavirus (HPV), a sexually transmitted infection, can cause anogenital warts and a number of cancers. To prevent morbidity and mortality, three vaccines have been licensed and are recommended by Canada's National Advisory Committee on Immunisation (for girls since 2007 and boys since 2012). Nevertheless, HPV vaccine coverage in Canada remains suboptimal in many regions. This study will be the first to concurrently examine the correlates of HPV vaccine decision-making in parents of school-aged girls and boys and evaluate changes in parental knowledge, attitudes and behaviours over time.

Methods and analysis

Using a national, online survey utilising theoretically driven constructs and validated measures, this study will identify HPV vaccine coverage rates and correlates of vaccine decision-making in Canada at two time points (August–September 2016 and June–July 2017). 4606 participants will be recruited to participate in an online survey through a market research and polling firm using email invitations. Data cleaning methods will identify inattentive or unmotivated participants.

Ethics and dissemination

The study received research ethics board approval from the Research Review Office, Integrated Health and Social Services University Network for West-Central Montreal (CODIM-FLP-16–219). The study will adopt a multimodal approach to disseminate the study's findings to researchers, clinicians, cancer and immunisation organisations and the public in Canada and internationally.



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Assessment of potential predictors of calretinin and mesothelin to improve the diagnostic performance to detect malignant mesothelioma: results from a population-based cohort study

Objectives

Mesothelin and calretinin are blood-based markers for malignant mesothelioma. The objective of this study was to analyse the markers in plasma samples from cancer-free men and to identify factors influencing their concentrations to minimise false-positive test results when using these markers for the early detection of malignant mesothelioma.

Setting

The present analyses used data and archived blood samples of the population-based Heinz Nixdorf Recall Study among elderly people collected from 2011 to 2014.

Participants

A total of 569 men (median age 70 years) without a malignant disease at the time of blood sampling were selected for these analyses.

Primary and secondary outcome

Mesothelin and calretinin concentration in plasma samples.

Results

We observed 24 mesothelin concentrations ≥1.5 nM (specificity 95.8%, 95% CI 93.8% to 97.2%) and 34 calretinin concentrations ≥1.0 ng/mL (specificity 94.0%, 95% CI 91.7% to 95.7%). Only five men had both markers above these cut-offs. Renal dysfunction and hypertension were major predictors of elevated mesothelin in addition to age. Regarding calretinin, the effect of renal dysfunction was slightly weaker and hypertension was not associated with increased concentrations. However, a diagnosis of cancer after blood collection and bronchial asthma were associated with positive calretinin results.

Conclusions

The combined determination of mesothelin and calretinin results in only few false-positive marker tests. Both markers are mainly influenced by renal dysfunction. The determination of cystatin C concentrations may be informative when interpreting the test results.



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Posterior fossa progressive multifocal leukoencephalopathy: first presentation of an unknown autoimmune disease

We present a case of a 57-year-old man who presented with progressive cerebellar dysarthria and cerebellar ataxia. Additional investigations confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML) in the posterior fossa. This is a demyelinating disease of the central nervous system, caused by an opportunistic infection with John Cunningham virus. PML has previously been considered a lethal condition, but because of careful monitoring of patients with HIV and of patients using immunosuppressive drugs it is discovered in earlier stages and prognosis can be improved. Our patient had no known immune-compromising state, but further work-up revealed that the PML was most likely the first presentation of a previous untreated autoimmune disorder: sarcoidosis.



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Subclinical meningoventriculitis as a cause of obstructive hydrocephalus

Communicating hydrocephalus may complicate infantile bacterial meningitis, typically presenting with systemic features of infection. We report a rare case of 'subclinical meningoventriculitis' causing obstructive hydrocephalus and its challenging management. A healthy 10-week-old immunocompetent male patient presented with failure to thrive and vomiting, secondary to presumed gastro-oesophageal reflux. The child was neurologically alert, afebrile with normal inflammatory markers. Progressive macrocephaly prompted an MRI confirming triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic third ventriculostomy was performed however abandoned intraoperatively due to the unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week course of intravenous ceftriaxone was commenced for Escherichia coli meningoventriculitis. However, the child was readmitted 18 days postoperatively with acute hydrocephalus requiring a ventricular washout and staged ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference measurements are paramount in the assessment of a paediatric patient. In an immunocompetent child, a subclinical fibropurulent meningoventriculitis can result in several management challenges.



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A unique case of nephrogenic systemic fibrosis from gadolinium exposure in a patient with normal eGFR

A 57-year-old woman presented with swelling and thickening of the skin of the lower extremities. Three months prior to presentation, patient had MRI with gadolinium as part of an evaluation for suspected pancreatic malignancy. Creatinine levels at the time of gadolinium exposure were 0.9–1.2 mg/dL, with a corresponding estimated glomerular filtration rate of 64 mL/min/1.73m2 by modification of diet in renal disease equation. Twenty-four-hour urine creatinine clearance was performed as an outpatient following development of symptoms. This revealed a creatinine clearance of 23 mL/min, suggestive of advanced chronic kidney disease despite an estimated glomerular filtration rate of 64 mL/min/1.73m2. Skin biopsy was positive for sclerosing dermopathy. These findings, in addition to the temporal association with gadolinium exposure, led to the diagnosis of nephrogenic systemic fibrosis.



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Allergic bronchopulmonary mycosis presenting as a new lung mass

Description

A 69-year-old man with invasive pancreatic ductal adenocarcinoma underwent pancreaticoduodenectomy and adjuvant chemotherapy. Three years later, a right upper lobe (RUL) lung mass was noted on surveillance imaging, suspicious for disease recurrence. He was treated for bronchitis and remained asymptomatic 4 months later with an unremarkable physical exam. Chest imaging (figure 1A,B) showed an RUL central mass with an infiltrative pattern of growth and right paratracheal adenopathy that is negative for malignancy on endobronchial ultrasound-guided needle aspiration. Bronchoalveolar lavage and brushing grew branching septate hyphae identified as Bipolaris species. The presence of cylindrical bronchiectasis with bronchial wall thickening, mucus plugging, peripheral eosinophilia (810 cells/µL), elevated total serum immunoglobulin E (422.6 IU/mL) and negative aspergillus antibodies suggested allergic bronchopulmonary mycosis (ABPM) caused by Bipolaris species. After 3 months of therapy with prednisone and posaconazole, the mass-like consolidation was completely resolved (figure 1C,D).

Figure 1

Chest CT...



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Unusual case of prosthetic joint infection caused by Francisella Tularensis

Tularaemia is a zoonotic infection caused by Francisella tularensis.Ulceroglandular, glandular, oculoglandular, pharyngeal, typhoidal and pneumonic types are the different types of the disease. Infection of prosthetic joints occurs at an exceedingly uncommon rate. We report a case of prosthetic joint infection involving the hip with F. tularensis, which to the best of our knowledge after a thorough literature review is the second of its kind.



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Cryptococcus neoformans osteomyelitis and intramuscular abscess in a liver transplant patient

Cryptococcus neoformans is an important pathogen that can cause severe illness and mortality in immunocompromised patients. We highlight here the case of a 53-year-old man presenting to hospital 4 years postliver transplant with fever, acute renal failure and a medial thigh lesion. Initially treated as bacterial sepsis, the patient failed to improve on broad-spectrum antibiotics. Further investigations revealed disseminated cryptococcemia complicated by patellar osteomyelitis and an intramuscular abscess. Unfortunately, although the patient initially showed signs of clinical improvement after starting standard antifungal agents, he deteriorated and died secondary to acute renal failure. Osteomyelitis is a rare manifestation of cryptococcal infection for which there is often a significant delay to diagnosis and treatment. This is the fourth reported case of cryptococcal osteomyelitis in a liver transplant patient and underlines the importance of considering fungal infections in the differential diagnosis of osseous lesions in solid organ transplant and other immunocompromised patients.



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Syncope from radiation-induced baroreceptor failure

Orthostatic hypotension has a vast differential that has been previously described throughout the literature. However, baroreceptor failure as a sequela of head and neck radiation is not often recognised as an important cause of dramatic haemodynamic variability. As a result, individuals suffering from baroreceptor failure likely have been undertreated. Herein, we report a case of a patient with a history of radiation to the neck for squamous cell carcinoma of the tongue and resultant baroreceptor failure resulting in syncope.



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Live 'Baby dance among the red blood cells

Description

A 35-year-old woman presented to outpatients with a 1-week history of high-grade fever and generalised malaise. General and systemic examination was unremarkable. On evaluation, her complete haemogram was within normal limits; however peripheral smear revealed the presence of thread-like larval forms of filaria, belonging to the species Wuchereria bancrofti. A wet mount preparation of the centrifuged whole blood sample was done, which demonstrated 'dancing' microfilaria, recorded in real time (see online ).

Dancing adult worms can be visualised within the dilated lymphatic channels on high-resolution ultrasound by their characteristic wriggling type movements, known as the 'filarial dance sign'.1 A wet mount of blood from a patient with microfilaraemia can demonstrate 'dance sign' of the baby worms under a microscope, identical to the parental wriggling movements. Microfilariae are larval forms, released into the blood from adult female worms inhabiting the regional lymphatic vessels. Circulating microfilariae are...



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Erdheim-Chester disease: atypical presentation of a rare disease

We report the clinical case of an adult patient referred to our hospital because of trismus due to a tumour in the right infratemporal and pterygomaxillary fossa. He referred hyporexia, weight loss and right trigeminal neuralgia. On physical examination, he had trismus and diplopia. On neuroimaging, the tumour invaded the central nervous system affecting the right temporal lobe and orbit, and the sellar region. Tumour biopsy revealed foamy histiocytes and isolated giant multinuclear cells immunoreactive to CD68 and negative to CD1a and S100. A diagnosis of Erdheim-Chester disease was made. Non-evidence of large bone involvement was found in neither plain radiographs nor Technetium 99 m bone scintigraphy. BRAFV600E mutation analysis was negative. Because of raised intracranial pressure, a debulking surgery of the intracranial histiocytic process was performed. The patient improved his symptoms and remains clinically stable after 12 months of treatment with pegylated interferon-α–2a 180 µg/weekly.



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Improved knowledge of and difficulties in palliative care among physicians during 2008 and 2015 in Japan: Association with a nationwide palliative care education program

BACKGROUND

Palliative care education for health care professionals is a key element in improving access to quality palliative care. The Palliative Care Emphasis Program on Symptom Management and Assessment for Continuous Medical Education (PEACE) was designed to provide educational opportunities for all physicians in Japan. As of 2015, 57,764 physicians had completed it. The objective of this study was to estimate the effects of the program.

METHODS

This study was an analysis of 2 nationwide observational studies from 2008 and 2015. We conducted 2 questionnaire surveys for representative samples of physicians. The measurements used were the Palliative Care Knowledge Test (range, 0-100) and the Palliative Care Difficulties Scale (range, 1-4). Comparisons were made with the unpaired Student t test and with a multivariate linear regression model using 2 cohorts and a propensity score–matched sample.

RESULTS

This study analyzed a total of 48,487 physicians in 2008 and a total of 2720 physicians in 2015. Between 2008 and 2015, physicians' knowledge and difficulties significantly improved on the Palliative Care Knowledge Test with total scores of 68 and 78, respectively (P < .001; effect size, 0.40) and on the Palliative Care Difficulties Scale with total scores of 2.65 and 2.49, respectively (P < .001; effect size, 0.29). Propensity-score matching resulted in 619 untrained physicians matched to 619 trained physicians, and physicians who trained with the PEACE program had a higher knowledge score (74 vs 86; P < .001; effect size, 0.64) and a lower difficulties score (2.6 vs 2.3; P < .001; effect size, 0.42).

CONCLUSIONS

Physicians' knowledge of and difficulties with palliative care improved on a national level. The PEACE program may have contributed to these improvements. Cancer 2017. © 2017 American Cancer Society.



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The TERT hypermethylated oncologic region predicts recurrence and survival in pancreatic cancer

Future Oncology, Ahead of Print.


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What role does stereotactic ablative radiotherapy have in advanced castrate-resistant prostate cancer?

Future Oncology, Ahead of Print.


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NIH Funds Pediatric Data Resource Center [News in Brief]

New portal to help identify genetic pathways underlying childhood cancer and birth defects.



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Paxillin binding to the cytoplasmic domain of CD103 promotes cell adhesion and effector functions for CD8+ resident memory T cells in tumors

CD8+/CD103+ tissue resident memory T cells (TRM cells) accumulate in several human solid tumors where they have been associated with a favorable prognosis. However, the role of CD103 - the α subunit of the integrin αEβ7 (also known as CD103) - in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE/CD103 chain. Binding to immobilized recombinant (r)E-cadherin-Fc of CD103 integrin expressed on tumor-specific CTL clones promotes phosphorylation of Pxn and Pyk2 and binding of Pxn to the αE/CD103 subunit tail. Inhibition of Pxn phosphorylation by the Src inhibitor saracatinib or its knockdown via shRNA dramatically altered adhesion and spreading of freshly isolated CD8+/CD103+ lung-tumor-infiltrating lymphocytes (TIL) and CD103+ tumor-specific CTL clones. Inhibition of Pxn phosphorylation with saracatinib in these CTL clones also severely compromised their functional activities toward autologous tumor cells. Using Jurkat T cells as a model to study CD103 integrin activation, we demonstrated a key role of serine residue S1163 of the αE chain intracellular domain in polarization of CD103 and recruitment of lysosomes and Pxn at the contact zone of T lymphocytes with rE-cadherin-Fc-coated beads. Overall, our results show how Pxn binding to the CD103 cytoplasmic tail triggers αEβ7 integrin outside-in signaling that promotes CD8+ T-cell migratory behavior and effector functions. These results also explain the more favorable prognosis associated with retention of TRM cells in the tumor microenvironment.

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DDB2 is a Novel Regulator of Wnt-Signaling in Colon Cancer

Deregulation of the Wnt/β-catenin signaling pathway drives the development of colorectal cancer (CRC) but understanding of this pathway remains incomplete. Here we report that the damage-specific DNA-binding protein DDB2 is critical for β-catenin-mediated activation of RNF43, which restricts Wnt signaling by removing Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and β-catenin at an upstream site in the RNF43 gene, enabling functional interaction with distant TCF4/β-catenin binding sites in the intron of RNF43. This novel activity of DDB2 was required for RNF43 function as a negative feedback regulator of Wnt signaling. Mice genetically deficient in DDB2 exhibited increased susceptibility to colon tumor development in a manner associated with higher abundance of Wnt receptor-expressing cells and greater activation of the downstream Wnt-pathway. Our results identify DDB2 as both a partner and regulator of Wnt signaling with an important role in suppressing colon cancer development.

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Distinct angiogenic changes during carcinogenesis defined by novel label-free dark field imaging in a hamster cheek pouch model

There remain gaps in knowledge concerning how vascular morphology evolves during carcinogenesis. In this study, we imaged neovascularization by label-free dark field microscopy of a DMBA-induced hamster cheek pouch model of oral squamous cell carcinoma (SCC). Wavelength-dependent imaging revealed distinct vascular features at different imaging depths and vessel sizes. Vascular tortuosity increased significantly in high-risk lesions, while diameter decreased significantly in hyperplastic and SCC lesions. Large vessels preserved the same trends seen in the original images, whereas small vessels displayed different trends, with length and diameter increasing during carcinogenesis. Based on these data we developed and validated a classification algorithm incorporating vascular features from different vessel masks. Receiver operator curves generated from the classification results demonstrated high accuracies in discriminating normal and hyperplasia from high-grade lesions (area under the curve>0.95). Overall, these results provided automated imaging of vasculature in the earliest stages of carcinogenesis from which one can extract robust endpoints. The optical toolbox described here is simple, low-cost and portable and can be used in a variety of health care and research settings for cancer prevention and pharmacology research.

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Histone acetyltransferase KAT6A upregulates PI3K/Akt signaling through TRIM24 binding

Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM) where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis. Overexpressing activated AKT or PIK3CA rescued the growth inhibition due to KAT6A silencing. Conversely, the pan-PI3K inhibitor LY294002 abrogated the growth-promoting effect of KAT6A. Overexpression of KAT6A or TRIM24, but not KAT6A acetyltransferase activity- deficient mutants or TRIM24 mutants lacking H3K23ac binding sites promoted PIK3CA expression, AKT phosphorylation and cell proliferation. Taken together, our results define an essential role of KAT6A in glioma formation, rationalizing its candidacy as a therapeutic target for GBM treatment.

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Transcriptomic Analysis of Octanoic Acid Response in Drosophila sechellia Using RNA-Sequencing

The dietary specialist fruit fly Drosophila sechellia has evolved to specialize on the toxic fruit of its host plant Morinda citrifolia. Toxicity of Morinda fruit is primarily due to high levels of octanoic acid (OA). Using RNA interference (RNAi), prior work found that knockdown of Osiris family genes Osiris 6 (Osi6), Osi7, and Osi8 led to increased susceptibility to OA in adult D. melanogaster flies, likely representing genes underlying a Quantitative Trait Locus (QTL) for OA resistance in D. sechellia. While genes in this major effect locus are beginning to be revealed, prior work has shown at least five regions of the genome contribute to OA resistance. Here, we identify new candidate OA resistance genes by performing differential gene expression analysis using RNA sequencing (RNA-seq) on control and OA-exposed D. sechellia flies. We found 104 significantly differentially expressed genes with annotated orthologs in D. melanogaster, including six Osiris gene family members, consistent with previous functional studies and gene expression analyses. Gene ontology (GO) term enrichment showed significant enrichment for cuticle development in upregulated genes and significant enrichment of immune and defense responses in downregulated genes suggesting important aspects of the physiology of D. sechellia that may play a role in OA resistance. In addition, we identified 5 candidate OA resistance genes that potentially underlie QTL peaks outside of the major effect region, representing promising new candidate genes for future functional studies.



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Experimental Evidence From Newborn Chicks Enriches Our Knowledge on Human Spatial–Numerical Associations

Abstract

Núñez and Fias raised concerns on whether our results demonstrate a linear number-space mapping. Patro and Nuerk urge caution on the use of animal models to understand the origin (cultural vs. biological) of the orientation of spatial–numerical association. Here, we discuss why both objections are unfounded.



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Down-regulation of KLF5 in cancer-associated fibroblasts inhibit gastric cancer cells progression by CCL5/CCR5 axis

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Atrial fibrillation and central nervous complications in liver transplanted hereditary transthyretin amyloidosis patients.

Background: Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesised mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients. Methods: The medical records of all LTx ATTRm amyloidosis patients in the county of Vasterbotten, Sweden were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status. Results: Sixty-three patients that had survived for three years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P

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Management of Patients who Receive an Organ Transplant Abroad and Return Home for Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.

Eradicating transplant tourism depends upon complex solutions that include efforts to progress towards self-sufficiency in transplantation. Meanwhile, professionals and authorities are faced with medical, legal, and ethical problems raised by patients who return home after receiving an organ transplant abroad, particularly when the organ has been obtained through illegitimate means. In 2016, the Declaration of Istanbul Custodian Group convened an international, multidisciplinary workshop in Madrid, Spain, to address these challenges and provide recommendations for the management of these patients, which are presented in this paper. The core recommendations are grounded in the belief that principles of transparency, traceability and continuity of care applied to patients who receive an organ domestically should also apply to patients who receive an organ abroad. Governments and professionals are urged to ensure that, upon return, patients are promptly referred to a transplant center for evaluation and care; not cover the costs of transplants resulting from organ or human trafficking; register standardized information at official registries on patients who travel for transplantation; promote international exchange of data for traceability; and develop a framework for the notification of identified or suspected cases of transnational transplant-related crimes by health professionals to law enforcement agencies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in Children.

No abstract available

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Venous Thromboembolism After Adult Lung Transplantation: A Frequent Event Associated with Lower Survival.

Background: The incidence of venous thromboembolism (VTE) after lung transplantation (LTX) varies significantly across studies. Two studies have suggested that these thrombotic events are associated with a lower posttransplant survival. Herein, we sought to determine the incidence, predictors and impact of VTE on survival after LTX at a quaternary referral center. Methods: This was a large cohort study of LTX recipients. Key outcome parameters were time to VTE after transplant and survival. Deep vein thrombosis (DVT) diagnosis required a positive ultrasound. Pulmonary embolism diagnosis required either a positive chest computed tomography angiogram or a high-probability ventilation/perfusion scan. Results: The overall incidence of VTE among 701 LTX recipients was 43.8%, of which 97.7% were DVT episodes, of which 71.3% were in the upper extremities. Predictors of VTE were prior history of DVT (HR 2.82, 95% CI 1.49 - 5.37), days in intensive care (HR 1.01, 95% CI 1.01 - 1.02), and the use of extracorporeal membrane oxygenation (HR 2.22, 95% CI 1.43 - 3.45). Importantly, VTE predicted a lower posttransplant survival (HR 1.70, 95% CI 1.28 - 2.26), when occurring within or after the first 30 days. The location of the DVT, either upper extremity or below the knee, also predicted a poor survival. Conclusions: VTE was frequent in LTX recipients and predicted a poor survival even when located in the upper extremities or below the knee. Post LTX factors were the major predictors of VTE. These data suggest that aggressive VTE screening/treatment protocols be implemented in post LTX population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Contemporary Policies Regarding Alcohol and Marijuana use Among Liver Transplant Programs in the United States.

BACKGROUND: Alcoholic liver disease is a common indication for liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period prior to OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. METHODS: A questionnaire was distributed to 100 UNOS-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. RESULTS: Forty-nine programs responded. Only 43% of programs required a specific period of abstinence prior to transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors such as family support, patient's motivation or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of programs. CONCLUSIONS: Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The Optimization of the Prevascularization Procedures for Improving Subcutaneous Islet Engraftment.

Background: Subcutaneous islet transplantation (SC Tx) is associated with minimal invasiveness, but poor vascularization. Thus, the optimization of the prevascularization procedures is crucial for improving the outcomes. Although the effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal procedures remain unclear. We sought to optimize the prevascularization procedures including the use of a novel scaffold, recombinant peptide (RCP). Methods: Devices containing various amount of bFGF with/without heparin, or RCP were implanted into the subcutaneous space of diabetic C57BL/6 mice. Syngeneic islets were transplanted into the prevascularized space. Blood glucose, intra-peritoneal glucose tolerance, and immunohistochemistry were evaluated. Results: The cure rates in all the device groups irrespective of bFGF doses were considerably higher than in the nondevice group. The cure rate in the bFGF0 group was unexpectedly higher than that in the subcutaneous islet transplant alone group (the None group) (57.1 vs. 28.6%). Glucose tolerance was ameliorated in the bFGF10(-), 10(+) and 15(-) groups. The number of vWF-positive vessels in the bFGF10(+) group was significantly higher than that in the None and bFGF0 groups (P

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Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database

Abstract

Background

Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly.

Objective

This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life.

Patients and Methods

An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups.

Results

There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56–71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only.

Conclusions

ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies.



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Acute Asthma in the Pediatric Emergency Department: Infections Are the Main Triggers of Exacerbations

Background. Asthma exacerbations are a common reason for Emergency Department (ED) visits in children. Aim. To analyze differences among age groups in terms of triggering factors and seasonality and to identify those with higher risk of severe exacerbations. Methods. We retrospectively revised the files of children admitted for acute asthma in 2016 in our Pediatric ED. Results. Visits for acute asthma were 603/23197 (2.6%). 76% of the patients were

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Effects of Variety and Postharvest Handling Practices on Microbial Population at Different Stages of the Value Chain of Fresh Tomato (Solanum lycopersicum) in Western Terai of Nepal

Background. Fresh vegetables such as tomato should have low microbial population for safe consumption and long storage life. The aerobic bacterial count (ABC) and coliform bacterial count (CBC), yeast, and mold population are the most widely used microbial indicators in fresh vegetables which should be lower than 4 log CFU g−1 for safe consumption. The stages of the supply chain, postharvest handling methods, and crop varieties had significant effects on microbial population. ABC, CBC, yeast, and mold population were significantly highest () at retail market (5.59, 4.38, 2.60, and 3.14 log CFU g−1, resp.), followed by wholesale market (4.72, 4.71, 2.43, and 2.44 log CFU g−1, resp.), and were least at farm gate (3.89, 3.63, 2.38, and 2.03 log CFU g−1, resp.). Improved postharvest practices (washing in clean water and grading and packaging in clean plastic crate) helped to reduce ABC, CBC, and mold population by 2.51, 32.70, and 29.86 percentage as compared to the conventional method (no washing and no grading and packaging in mud plastered bamboo baskets). Among varieties, Pusa ruby had the lowest microbial load of 2.58, 4.53, 0.96, and 1.77 log CFU g−1 for ABC, CBC, yeast, and mold count, respectively. Significantly negative correlation () was observed between fruit pH & ABC and pH & mold count. Although the microbial quality of fresh tomato is safe in the local market of western Terai of Nepal both in conventional and in improved practices however still it is essential to follow improved postharvest handling practices in production and marketing of newly introduced tomato cultivars (high-pH cultivars) for ensuring the safe availability of fresh tomato in the market.

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Ear-EEG detects ictal and interictal abnormalities in focal and generalized epilepsy -A comparison with scalp EEG monitoring

The incidence of temporal lobe epilepsy (TLE) has been estimated to 10.4/100.000 (Landino et al., 2014). It is the most common type of epilepsy among patients with refractory epilepsy referred to tertiary centers (Semah et al., 1998) and TLE represents the majority of cases considered for epilepsy surgery (Téllez-Zenteno and Hernández-Ronquillo, 2011). The delay from first seizure to referral to epilepsy surgery is generally more than a decade (Benbadis et al., 2003). It has been estimated that 5-23% of patients with TLE are misdiagnosed (van Donselaar et al., 2006), which may contribute to the delay.

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NEURONOPATHY AND NEUROPATHY IN AUTOSOMAL DOMINANT SPINO-CEREBELLAR ATAXIA (SCA): A PRELIMINARY PERIPHERAL NERVE ULTRASOUND STUDY

Somatosensory or sensorimotor impairment is not uncommon in autosomal dominant spino-cerebellar ataxia (SCA) (Linnemann et al., 2015; Schöls et al., 2004), but it is unclear to what extent this is a primary peripheral nerve pathology, as typically seen in length-dependent neuropathy, or neuronopathy from neuron degeneration in dorsal root ganglia and/or anterior horn cells (van de Warrenburg et al., 2004). It is also unclear if neuropathy and neuronopathy are differently represented in the SCA subtypes.

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The View from Puerto Rico — Hurricane Maria and Its Aftermath

Hurricane Maria hit Puerto Rico on September 20 and caused unprecedented damage affecting the island's 3.4 million inhabitants (see Figure 1). Though no one in Puerto Rico was spared at least some impact, the poor and vulnerable were disproportionately affected. Loss of communication and…

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Creating Healthy Communities after Disasters

Recently, our country's heart was broken by the devastation wrought by three hurricanes affecting several U.S. states and territories. These tragedies remind us that natural disasters happen frequently and that no community is immune to them. Each year, the United States experiences approximately…

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Preparing for the Next Harvey, Irma, or Maria — Addressing Research Gaps

Extreme events often cast in bold relief what we do and don't know about medicine and public health. In recent weeks, three hurricanes, each characterized by "unprecedented" features, have illuminated our knowledge gaps regarding the consequences of disasters and their mitigation. Hurricanes…

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Exam 1: Association Between Endoscopist and Center Endoscopic Retrograde Cholangiopancreatography Volume With Procedure Success and Adverse Outcomes: A Systematic Review and Meta-analysis



http://ift.tt/2i7PsSp

The View from Puerto Rico — Hurricane Maria and Its Aftermath

Hurricane Maria hit Puerto Rico on September 20 and caused unprecedented damage affecting the island's 3.4 million inhabitants (see Figure 1). Though no one in Puerto Rico was spared at least some impact, the poor and vulnerable were disproportionately affected. Loss of communication and…

http://ift.tt/2gxusAL

Bringing the Medical Home back Home in the Context of Population Health - Home-Based Primary Care and Home-Based Palliative Care

With the growth of value-based care, payers and health systems have begun to appreciate the need to provide enhanced services to homebound adults. Recent studies have shown that home-based medical services for this high-cost, high-need population reduce costs and improve outcomes. Home-based medical care services have two flavors that are related to historical context and specialty background—home-based primary care and home-based palliative care. While the type of services provided by home-based primary care and home-based palliative care (together termed "home-based medical care") overlap, home-based primary care tends to encompass longitudinal and preventive care, while home-based palliative care often provides services for shorter durations focused more on distress management and goals of care clarification.

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High LC3/Beclin Expression Correlates with Poor Survival in Glioma: a Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux

Abstract

Recent studies suggest the role of autophagy, an evolutionarily conserved catabolic process, in determining the response of gliomas to treatment either positively or negatively. The study attempts to characterize autophagy in low and high-grade glioma by investigating the autophagic flux and clinical significance of autophagy proteins (LC3 and beclin 1) in a group of glioma patients. We evaluated the expression of autophagic markers in resected specimens of low-grade glioma (LGG) and high-grade glioma (HGG) tissues, by immunohistochemistry and Western blotting. Our results show that expression of autophagy proteins were more prominent in HGG than in LGG. Increased level of autophagic proteins in HGG can be due to an increased rate of autophagy or can be because of blockage in the final degradation step of autophagy (defective autophagy). To distinguish these possibilities, the autophagic flux assay which helps to determine the rate of degradation/synthesis of autophagic proteins (LC3-II and p62) over a period of time by blocking the final degradation step of autophagy using bafilomycin A1 was used . The assessment of autophagic flux in ex vivo culture of primary glioma cells revealed for the first time increased turnover of autophagy in high grade compared to low grade-glioma. Though autophagic markers were reduced in LGG, functionally autophagy was non defective in both grades of glioma. We then investigated whether autophagy in gliomas is regulated by nutrient sensing pathways including mTOR and promote cell survival by providing an alternate energy source in response to metabolic stress. The results depicted that the role of autophagy during stress varies with tissue and has a negative correlation with mTOR substrate phosphorylation. We also evaluated the expression of LC3 and beclin 1 with progression free survival (PFS) using Kaplan-Meier survival analysis and have found that patients with low LC3/beclin 1 expression had better PFS than those with high expression of LC3/beclin 1 in their tumors. Together, we provide evidence that autophagy is non-defective in glioma and also show that high LC3/beclin 1 expression correlates with poor PFS in both LGG and HGG.



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Does Prolonged Enteral Feeding With Supplemental Omega-3 Fatty Acids Impact on Recovery Post-esophagectomy: Results of a Randomized Double-Blind Trial

imageObjective: This randomized controlled trial (RCT) hypothesized that prolonged enteral nutrition (EN) with supplemental eicosapentanoic acid (EPA), an omega-3 fatty acid with immune and anabolic properties, may impact on clinical and nutritional outcomes. Background: Esophagectomy is associated with significant weight loss and catabolism, and negatively impacts quality of life (QL). Strategies to counter sustained catabolism have therapeutic rationale. Methods: This multicenter, double-blind, placebo-controlled RCT was powered on a 5% difference in lean body mass (LBM) at 1 month. Patients were randomly assigned to receive either EN-EPA (2.2 g EPA/day) (n = 97) or isocaloric isonitrogenous standard EN (EN-S) (n = 94), preoperatively (5 days orally), and postoperatively via a jejunostomy until 1 month postdischarge. Assessments perioperatively, and at 1, 3, and 6 months included weight, body mass index (BMI), body composition, muscle strength, cytokines, complications, and QL. Results: The median (range) nutrition support was for 51 (36 to 78) days, and overall compliance was 96%. For the entire cohort, a significant (P

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Prospective phase II trial of permanent seed implantation prostate brachytherapy for intermediate-risk localized prostate cancer: efficacy, toxicity, and quality of life outcomes

We report efficacy, toxicity and quality of life after prostate brachytherapy monotherapy for favorable intermediate risk cancer.Out of 300 patients, after a median follow-up of 5.1 years, only 10 recurrences were reported, yielding a 5-year freedom from biochemical failure rate of 97.3% and a 5-year biochemical progression-free survival rate of 94.9%.Four patients had late grade 3 genitourinary toxicity and two late grade 3 rectal toxicity; no grade 4 or 5 toxicity was observed.

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Multiplex proximity ligation assay to identify potential prognostic biomarkers for improved survival in locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy

In locally advanced pancreatic cancer (LAPC), the role of stereotactic body radiotherapy (SBRT) is evolving. Non-invasive seromarkers are needed to define prognosis. A proximity ligation assay (PLA) can evaluate expression levels of proteins that may correlate with outcomes. Herein, seromarker levels were explored for associations with outcomes in LAPC patients who received chemotherapy and SBRT.

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A particle filter-based target tracking algorithm for MR-guided respiratory compensation: robustness and accuracy assessment

A modified particle filter based algorithm allows tracking of abdominal and thoracic anatomies of interest. A total of 5 healthy volunteers and 8 patients were scanned with various image contrasts and resolutions. The results demonstrate an accurate and robust technique with promising clinical potential.

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Letter from Puerto Rico: The State of Radiation Oncology 1 Week After Maria’s Landfall



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Defining Benchmarks for Transthoracic Esophagectomy: A Multicenter Analysis of Total Minimally Invasive Esophagectomy in Low Risk Patients

imageObjective: To define "best possible" outcomes in total minimally invasive transthoracic esophagectomy (ttMIE). Background: TtMIE, performed by experts in patients with low comorbidity, may serve as a benchmark procedure for esophagectomy. Patients and Methods: From a cohort of 1057 ttMIE, performed over a 5-year period in 13 high-volume centers for esophageal surgery, we selected a study group of 334 patients (31.6%) that fulfilled criteria of low comorbidity (American Society of Anesthesiologists score ≤2, WHO/ECOG score ≤1, age ≤65 years, body mass index 19–29 kg/m2). Endpoints included postoperative morbidity measured by the Clavien-Dindo classification and the comprehensive complication index. Benchmark values were defined as the 75th percentile of the median outcome parameters of the participating centers to represent best achievable results. Results: Benchmark patients were predominantly male (82.9%) with a median age of 58 years (53–62). High intrathoracic (Ivor Lewis) and cervical esophagogastrostomy (McKeown) were performed in 188 (56.3%) and 146 (43.7%) patients, respectively. Median (IQR) ICU and hospital stay was 0 (0–2) and 12 (9–18) days, respectively. 56.0% of patients developed at least 1 complication, and 26.9% experienced major morbidity (≥grade III), mostly related to pulmonary complications (25.7%), anastomotic leakage (15.9%), and cardiac events (13.5%). Benchmark values at 30 days after hospital discharge were ≤55.7% and ≤30.8% for overall and major complications, ≤18.0% for readmission, ≤3.1% for positive resection margins, and ≥23 for lymph node yield. Benchmarks at 30 and 90 days were ≤1.0% and ≤4.6% for mortality, and ≤40.8 and ≤42.8 for the comprehensive complication index, respectively. Conclusion: This outcome analysis of patients with low comorbidity undergoing ttMIE may serve as a reference to evaluate surgical performance in major esophageal resection.

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Modern Surgeons: Still Masters of Their Trade or Just Operators of Medical Equipment?

No abstract available

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Transanal Versus Transabdominal Minimally Invasive (Completion) Proctectomy With Ileal Pouch-anal Anastomosis in Ulcerative Colitis: A Comparative Study

imageObjective: This study aims to compare surgical outcome of transanal ileal pouch-anal anastomosis (ta-IPAA) with transabdominal minimal invasive approach in ulcerative colitis (UC), using the comprehensive complication index (CCI). Background: Recent evolutions in rectal cancer surgery led to transanal dissection of the rectum resulting in a better exposure of the distal rectum and presumed better outcome. The same approach was introduced for patients with UC, resulting in decreased invasiveness. Methods: All patients, undergoing minimally invasive restorative proctocolectomy in 1, 2, or 3 stages between January 2011 and September 2016 in 3 referral centers were included. Only patients who underwent either multiport, single port, single port with 1 additional port, hand-assisted, or robotic (R) laparoscopy were included in the analysis. CCI, registered during 90 days after pouch construction, was compared between the transanal and the transabdominal approach. Results: Ninety-seven patients (male: 52%) with ta-IPAA were compared to 119 (male: 53%) with transabdominal IPAA. Ninety-nine (46%) patients had a defunctioning ileostomy at time of pouch construction. A 2-step model showed that the odds for postoperative morbidity were 0.52 times lower in the ta-IPAA group (95% confidence interval [0.29; 0.92] P = 0.026). In patients with morbidity, mean CCI of the transanal approach was 2.23 points lower than the transabdominal approach (95% confidence interval: [−6.64–3.36] P = 0.13), which was not significant. Conclusions: Ta-IPAA for UC is a safe procedure, resulting in fewer patients with morbidity, but comparable CCI when morbidity is present. Overall, ta-IPAA led to lower CCI scores.

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Mixed Reality in Visceral Surgery: Development of a Suitable Workflow and Evaluation of Intraoperative Use-cases

imageObjective: The paper evaluates the application of a mixed reality (MR) headmounted display (HMD) for the visualization of anatomical structures in complex visceral-surgical interventions. A workflow was developed and technical feasibility was evaluated. Summary of Background Data: Medical images are still not seamlessly integrated into surgical interventions and, thus, remain separated from the surgical procedure. Surgeons need to cognitively relate 2-dimensional sectional images to the 3-dimensional (3D) during the actual intervention. MR applications simulate 3D images and reduce the offset between working space and visualization allowing for improved spatial-visual approximation of patient and image. Methods: The surgeon's field of vision was superimposed with a 3D-model of the patient's relevant liver structures displayed on a MR-HMD. This set-up was evaluated during open hepatic surgery. Results: A suitable workflow for segmenting image masks and texture mapping of tumors, hepatic artery, portal vein, and the hepatic veins was developed. The 3D model was positioned above the surgical site. Anatomical reassurance was possible simply by looking up. Positioning in the room was stable without drift and minimal jittering. Users reported satisfactory comfort wearing the device without significant impairment of movement. Conclusion: MR technology has a high potential to improve the surgeon's action and perception in open visceral surgery by displaying 3D anatomical models close to the surgical site. Superimposing anatomical structures directly onto the organs within the surgical site remains challenging, as the abdominal organs undergo major deformations due to manipulation, respiratory motion, and the interaction with the surgical instruments during the intervention. A further application scenario would be intraoperative ultrasound examination displaying the image directly next to the transducer. Displays and sensor-technologies as well as biomechanical modeling and object-recognition algorithms will facilitate the application of MR-HMD in surgery in the near future.

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Effect of Esophageal Cancer Surgeon Volume on Management and Mortality From Emergency Upper Gastrointestinal Conditions: Population-based Cohort Study

imageObjective: To study the influence of esophageal cancer surgeon volume upon mortality from upper gastrointestinal emergencies. Background: Volume-outcome relationships led to the centralization of esophageal cancer surgery. Methods: Hospital Episode Statistics data were used to identify patients admitted to hospitals within England (1997–2012). The influence of esophageal high-volume (HV) cancer surgeon status (≥5 resections per year) upon 30-day and 90-day mortality from esophageal perforation (EP), paraesophageal hernia causing obstruction or gangrene (PEH) and perforated peptic ulcer (PPU) was analyzed, independent of HV esophageal cancer center status and patient and disease-specific confounding factors. Results: A total of 3707, 12,411, and 57,164 patients with EP, PEH, and PPU, respectively, were included. The observed 90-day mortality was 36.5%, 11.5%, and 29.0% for EP, PEH, and PPU, respectively. Management by HV cancer surgeon was independently associated with significant reductions in 30-day and 90-day mortality from EP (odds ratio, OR 0.51, 95% confidence interval, CI, 0.40–0.66), PEH (OR=0.70, 95% CI 0.53–0.91), and PPU (OR=0.85, 95% CI 0.7–0.95). Subset analysis of those patients receiving primary surgery as treatment showed no change in mortality when performed by HV cancer surgeons. However HV cancer surgeons performed surgery as primary treatment more commonly for EP (OR=2.38, 95% CI 1.87–3.04) and PEH (OR=2.12, 95% CI 1.79–2.51). Furthermore surgery was independently associated with reduced mortality for all 3 conditions. Conclusion: The complex elective workload of HV esophageal cancer surgeons appears to lower the threshold for surgical intervention in specific upper gastrointestinal emergencies such as EP and PEH, which in turn reduces mortality.

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Endovascular Repair of Abdominal Aortic Aneurysm in Patients Physically Ineligible for Open Repair: Very Long-term Follow-up in the EVAR-2 Randomized Controlled Trial

imageObjective: The aim of the study was to compare long-term total and aneurysm-related mortality in physically frail patients with abdominal aortic aneurysm (AAA) randomized to either early endovascular aneurysm repair (EVAR) or no-intervention. Summary Background Data: EVAR-2 remains the sole randomized trial to identify whether EVAR reduces mortality in patients physically ineligible for open repair. Methods: Between September 1999 and August 2004, 404 patients from 33 centers in the United Kingdom aged ≥60 years with AAA >5.5 cm in diameter were randomized 1:1 using computer-generated sequences of randomly permuted blocks stratified by center to receive either EVAR (197) or no-intervention (207). The primary analysis compared total and aneurysm-related deaths in groups until June 30, 2015 (mean, 12.0 yrs; maximum 14.1 yrs). Results: Mean follow-up until death or censoring was 4.2 years. There were 187 deaths (22.6 per 100 person-yrs) in the EVAR group and 194 (22.1 per 100 person-yrs) in the no-intervention group. By 12 years of follow-up the estimated survival was 5.3% [95% confidence interval (CI), 2.6–9.2] in the EVAR group and 8.5% (95% CI, 5.2–12.9) in the no-intervention group; there was no significant difference in life expectancy between the groups (both 4.2 yrs; P = 0.97). However, overall aneurysm-related mortality was significantly lower in the EVAR group [3.3 deaths per 100 person-yrs compared with 6.5 deaths per 100 person-yrs in the no-intervention group, adjusted hazard ratio 0.55 (95% CI, 0.34–0.91; P = 0.019)]. Patients surviving beyond 8 years were younger, with higher body mass index, estimated glomerular filtration rate, and forced expiratory volume in 1 second. Conclusions: EVAR does not increase overall life expectancy in patients ineligible for open repair, but can reduce aneurysm-related mortality.

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In the Next Issue

No abstract available

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Postoperative Outcomes of Minimally Invasive Gastrectomy Versus Open Gastrectomy During the Early Introduction of Minimally Invasive Gastrectomy in the Netherlands: A Population-based Cohort Study

imageObjective: To compare postoperative outcomes of minimally invasive gastrectomy (MIG) to open gastrectomy (OG) for cancer during the introduction of MIG in the Netherlands. Background: Between 2011 and 2015, the use of MIG increased from 4% to 53% in the Netherlands. Methods: This population-based cohort study included all patients with curable gastric adenocarcinoma that underwent gastrectomy between 2011 and 2015, registered in the Dutch Upper GI Cancer Audit. Patients with missing preoperative data, and patients in whom no lymphadenectomy or reconstruction was performed were excluded. Propensity score matching was applied to create comparable groups between patients receiving MIG or OG, using year of surgery and other potential confounders. Morbidity, mortality, and hospital stay were evaluated. Results: Of the 1697 eligible patients, 813 were discarded after propensity score matching; 442 and 442 patients who underwent MIG and OG, respectively, remained. Conversions occurred in 10% of the patients during MIG. Although the overall postoperative morbidity (37% vs 40%, P = 0.489) and mortality rates (6% vs 4%, P = 0.214) were comparable between the 2 groups, patients who underwent MIG experienced less wound complications (2% vs 5%, P = 0.006). Anastomotic leakage occurred in 8% of the patients after MIG, and in 7% after OG (P = 0.525). The median hospital stay declined over the years for both procedures (11 to 8 days, P

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Does a Combination of Laparoscopic Approach and Full Fast Track Multimodal Management Decrease Postoperative Morbidity?: A Multicenter Randomized Controlled Trial

imageObjective: The aim of this study was to assess whether association of laparoscopic approach and full fast track multimodal (FFT) management can reduce postoperative morbidity after colorectal cancer surgery, as compared to laparoscopic approach with limited fast-track program (LFT). Summary of Background Data: Recent advances in colorectal cancer surgery are introduction of laparoscopy and FFT implementation. Methods: Patients eligible for elective laparoscopic colorectal cancer surgery were randomized into 2 groups: FFT or LFT care (with only early oral intake and mobilization starting on Day 1). Primary outcome was postoperative 30-day morbidity, according to Clavien-Dindo classification. Results: Two hundred seventy patients were randomized and 263 were analyzed: 130 in FFT group and 133 in LFT group, including 106 colon (FFT: n = 52 and LFT: n = 54) and 157 rectal cancer (FFT: n = 78 and LFT: n = 79). Postoperative 30-day mortality was nil. Overall postoperative 30-day morbidity did not show any difference between the groups (FFT: 35% vs LFT: 29%, P = 0.290), neither regarding the overall population, nor in the colon (FFT: 23% vs LFT: 19%, P = 0.636) or rectal (FFT: 44% vs LFT: 35%, P = 0.330) cancer subgroups. Severe postoperative morbidity was also not different between groups (FFT: 12% vs LFT: 8%, P = 0.266). After multivariate regression analysis, only early intravenous catheter removal (on day 2) [odds ratio: 0.390; 95% confidence interval: (95% CI 0.181–0.842); P = 0.017] and the absence of intraoperative lidocaine intravenous perfusion (odds ratio: 0.182, 95% CI 0.042–0.788; P = 0.019) were identified as independent predictive factors of reduced postoperative morbidity. Conclusion: Addition of FFT multimodal management to laparoscopic approach with early oral intake and mobilization does not reduce postoperative morbidity after colorectal cancer surgery.

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Impact of Lymph Node Yield on Overall Survival in Patients Treated With Neoadjuvant Chemoradiotherapy Followed by Esophagectomy for Cancer: A Population-based Cohort Study in the Netherlands

imageObjective: To evaluate the impact of lymph node yield (LNY) on survival in patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy for cancer. Background: The value of an extended lymphadenectomy after nCRT for esophageal cancer is debated. Recent reports demonstrate no association between LNY and survival. This association has not yet been evaluated in larger cohorts. Methods: All patients who underwent nCRT followed by esophagectomy between 2005 and 2014 were identified from the Netherlands Cancer Registry. The association between LNY and overall survival was analyzed using multivariable Cox regression analyses, adjusting for diagnosis year, referral, hospital volume, age, sex, malignancy history, tumor location, histology, cTN-stage, surgical approach, radicality, and ypTN-stage. Analyses were performed with LNY as categorized predictor (

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Liver Function in Patients With Nonalcoholic Fatty Liver Disease Randomized to Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: A Secondary Analysis of a Randomized Clinical Trial

imageObjectives: The aim of the study was to compare the influence of sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB) on liver function in bariatric patients with non-alcoholic fatty liver disease (NAFLD) in a randomized clinical trial (NCT01806506). Background: Rapid weight loss and malabsorption after bariatric surgery in patients with NAFLD or steatohepatitis (NASH) may impair liver function. Methods: Sixty-six morbidly obese patients randomized to SG or RYGB were included in a secondary outcome analysis. Intraoperative liver biopsies were categorized with NAFLD Activity Score (NAS) and liver function tests were done before surgery and after 1, 6 and 12 months. Results: NASH was present in 54.5% RYGB and 51.5% SG patients (P > 0.05). At 12 months excess weight loss was 68.7 ± 19.7% after SG and 62.8 ± 18.5% after RYGB (P > 0.05). At 1 month international normalized ratio (INR) increased after RYGB (0.98 ± 0.05 vs 1.14 ± 0.11; P

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Prospective Evaluation of Precision Multimodal Gallbladder Surgery Navigation: Virtual Reality, Near-infrared Fluorescence, and X-ray-based Intraoperative Cholangiography

imageObjective: We aimed to prospectively evaluate NIR-C, VR-AR, and x-ray intraoperative cholangiography (IOC) during robotic cholecystectomy. Background: Near-infrared cholangiography (NIR-C) provides real-time, radiation-free biliary anatomy enhancement. Three-dimensional virtual reality (VR) biliary anatomy models can be obtained via software manipulation of magnetic resonance cholangiopancreatography, enabling preoperative VR exploration, and intraoperative augmented reality (AR) navigation. Methods: Fifty-eight patients were scheduled for cholecystectomy for gallbladder lithiasis. VR surgical planning was performed on virtual models. At anesthesia induction, indocyanine green was injected intravenously. AR navigation was obtained by overlaying the virtual model onto real-time images. Before and after Calot triangle dissection, NIR-C was obtained by turning the camera to NIR mode. Finally, an IOC was performed. The 3 modality performances were evaluated and image quality was assessed with a Likert-scale questionnaire. Results: The three-dimensional VR planning enabled the identification of 12 anatomical variants in 8 patients, of which only 7 were correctly reported by the radiologists (P = 0.037). A dangerous variant identified at VR induced a "fundus first" approach. The cystic-common bile duct junction was visualized before Calot triangle dissection at VR in 100% of cases, at NIR-C in 98.15%, and in 96.15% at IOC. Mean time to obtain relevant images was shorter with NIR-C versus AR (P = 0.008) and versus IOC (P = 0.00000003). Image quality scores were lower with NIR-C versus AR (P = 0.018) and versus IOC (P

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The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice

imageObjective: To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer. Background: Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown. Methods: ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements. Results: ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d). Conclusions: Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.

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Survival Benefit of Neoadjuvant Treatment in Clinical T3N0M0 Esophageal Cancer: Results From a Retrospective Multicenter European Study

imageBackground: Based on current guidelines, clinical T3N0M0 esophageal tumors may or may not receive neoadjuvant treatment, according to their perception as locally advanced (cT3) or early-stage tumors (stage II). The study aim was to assess the impact of neoadjuvant treatment upon survival for cT3N0M0 esophageal cancer patients, with subgroup analyses by histological type (squamous cell carcinoma vs adenocarcinoma) and type of neoadjuvant treatment (chemotherapy vs radiochemotherapy). Methods: Data from patients operated on for esophageal cancer in 30 European centers were collected. Among the 382 of 2944 patients with clinical T3N0M0 stage at initial diagnosis (13.0%), we compared those treated with primary surgery (S, n = 193) versus with neoadjuvant treatment plus surgery (NS, n = 189). Results: The S and NS groups were similar regarding their demographic and surgical characteristics. In-hospital postoperative morbidity and mortality rates were comparable between groups. Patients were found to be pN+ in 64.2% versus 42.9% in the S and NS groups respectively (P

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Bioengineering a Human Face Graft: The Matrix of Identity

imageObjective: During the last decade, face allotransplantation has been shown to be a revolutionary reconstructive procedure for severe disfigurements. However, offer to patients remains limited due to lifelong immunosuppression. To move forward in the field, a new pathway in tissue engineering is proposed. Background: Our previously reported technique of matrix production of a porcine auricular subunit graft has been translated to a human face model. Methods: 5 partial and 1 total face grafts were procured from human fresh cadavers. After arterial cannulation, the specimens were perfused using a combined detergent/polar solvent decellularization protocol. Preservation of vascular patency was assessed by imaging, cell and antigen removal by DNA quantification and histology. The main extracellular matrix proteins and associated cytokines were evaluated. Lip scaffolds were cultivated with dermal, muscle progenitor and endothelial cells, either on discs or in a bioreactor. Results: Decellularization was successful in all facial grafts within 12 days revealing acellular scaffolds with full preservation of innate morphology. Imaging demonstrated a preservation of the entire vascular tree patency. Removal of cells and antigens was confirmed by reduction of DNA and antigen markers negativation. Microscopic evaluation revealed preservation of tissue structures as well as of major proteins. Seeded cells were viable and well distributed within all scaffolds. Conclusions: Complex acellular facial scaffolds were obtained, preserving simultaneously a cell-friendly extracellular matrix and a perfusable vascular tree. This step will enable further engineering of postmortem facial grafts, thereby offering new perspectives in composite tissue allotransplantation.

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EMCrit Wee – Dissemination and Information Transfer (Questions not Answers)

I need help...

EMCrit by Scott Weingart.



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Littoral cell angioma of spleen



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Hepatic cystic echinococcosis in Australia: an update on diagnosis and management

Background

Echinococcosis is an uncommonly encountered zoonotic disease caused by the taeniid Echinococcus. The only endemic species in Australia, Echinococcus granulosus, forms cysts in the liver in 70% of cases. The aim of this study was to review the literature to provide an evidence-based narrative update on the diagnosis and management of hepatic cystic echinococcosis in Australia.

Methods

We reviewed the literature, utilizing multiple research databases and citation tracking. Original research and review articles examining the diagnosis and management of hydatid disease in adults, published prior to 2016 and in the English language were included in our review.

Results

Ultrasound is the gold-standard screening test, whilst computed tomography has a role in emergency presentations and screening for multi-organ involvement. Magnetic resonance imaging is the preferred second-line imaging and better demonstrates biliary involvement. Medical therapy or PAIR (percutaneous aspiration, irrigation with scolicide and re-aspiration) may be appropriate in selected cases; however, surgery remains the definitive treatment for active, large (>5 cm), symptomatic or complicated cysts. A variety of surgical techniques have been described, including conservative, radical and minimally invasive procedures. There is currently no consensus approach; surgical modality should be tailored to patient factors, relevant anatomy, local facilities and surgeons' expertise.

Conclusion

Diagnosis and therapy in hepatic hydatid cysts have been significantly advanced by imaging, interventional radiology and surgical approaches in recent years. Surgery remains the mainstay of treatment for large, active, complicated or symptomatic hepatic hydatid cysts.



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Revision gastric bypass after laparoscopic adjustable gastric band: a 10-year experience at a public teaching hospital

Background

In Australia, there is limited access to public revisional bariatric procedures. However, the need for such procedures is rising. We investigated the safety and efficacy of band-to-bypass procedures in our experience at a public teaching hospital over a period of 10 years.

Methods

Using a prospectively maintained bariatric surgical database, we analysed 91 consecutive planned band-to-bypass procedures from 2007 to November 2016. All patients had prior laparoscopic adjustable gastric bands removed and formation of Roux-en-Y gastric bypass, in one or two stages. Primary outcomes were 30-day complication rate and excess weight loss from 12 months. The impact of fellows as primary operators on these outcomes was assessed.

Results

Eighty-two patients met the inclusion criteria. Seventy-one (84.5%) were females. Mean age was 48.8 years (SD: 8.85). Immediate post-operative complications included six (7.3%) patients with gastrojejunostomy leak, three of whom required conversion to laparotomy, with one mortality (1.22%). Fifty-two patients had follow-up of 1 year or more (median: 2.36, range: 1–9.24). Mean excess weight loss at the end of follow-up was 52.79% (SD: 46.46). Twenty-eight (34.14%) cases were performed primarily by a fellow under the guidance of an experienced bariatric surgeon, with equivalent results.

Conclusion

Revisional band-to-bypass in the public setting is an effective but complex procedure associated with morbidity. Some risk may be ameliorated by development of selection criteria to exclude certain high-risk groups. We hope discussion amongst other bariatric groups will further refine this approach.



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Effect of a See and Treat clinic on skin cancer treatment time

Background

Many plastic surgery departments in Australasia have experienced increasing referrals for management of skin lesions. This has driven a demand for new strategies to decrease patient waiting time and administrative costs. The aim of this study was to determine if a purpose-built See and Treat skin cancer clinic could provide a faster skin cancer treatment pathway with comparable clinical outcomes and acceptability to patients.

Methods

This was a prospective observational study of patients treated through the See and Treat clinic with a retrospective control cohort. The prospective 'See and Treat' cohort included a consecutive series of 106 patients, while the retrospective cohort included a consecutive series of 200 patients. Patient demographics, time from referral to surgery and operative measures were analysed. One hundred patients in the prospective cohort completed an anonymous satisfaction survey regarding their treatment.

Results

The average time from referral to surgery was reduced from 121 days in the retrospective cohort to 60 days in the See and Treat cohort (P < 0.001). Rates of complete excision of malignant and premalignant lesions were not different between the two groups, being 93% (178/191) and 91% (76/84), respectively (P = 0.609). Ninety-five percent (95/100) of patients were satisfied with their See and Treat experience overall.

Conclusion

We show that a considerable reduction in the time between referral and surgery can be achieved through a See and Treat clinic without compromise of the success of surgical treatment. Moreover, such a treatment pathway has been shown to be acceptable, and largely preferable, to patients.



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Laparoscopic pancreaticoduodenectomy in Brisbane, Australia: an initial experience

Background

The role of minimally invasive approach for pancreaticoduodenectomy has not yet been well defined in Australia. We present our early experience with laparoscopic pancreaticoduodenectomy (LPD) from Brisbane, Australia.

Methods

Retrospective review in a prospectively collected database of patients undergoing LPD between 2006 and 2016 was performed. Patients who underwent a hybrid LPD (HLPD) mobilization approach and resection followed by open reconstruction and totally LPD (TLPD) approach were included in this study. Operative characteristics, perioperative outcomes, pathological and survival data were collected.

Results

Twenty-seven patients underwent LPD including 17 HLPD (63%) and 10 TLPD (37%) patients. HLPD patients were mostly converted to open for planned reconstruction or vascular resection. With increasing experience, more TLPDs were performed, including laparoscopic anastomoses. Median operating time was 462 min (504 min for TLPD). Median length of hospital stay was 10 days. Histology showed 21 invasive malignancies, two neuroendocrine tumours, two intraductal papillary mucinous neoplasms and two benign lesions. Median nodal harvest was 22. Margin negative resection was achieved in 84% of patients. Twenty-two percent of patients developed a Grade 3/4 complication, including 19% clinically significant pancreatic fistula. There was one perioperative mortality (4%) due to pancreatic fistula, post-operative haemorrhage and sepsis.

Conclusions

LPD is a technically challenging operation with a steep learning curve. The early oncological outcomes appear satisfactory. It remains to be determined whether the minimally invasive approach to pancreaticoduodenectomy offers benefits to patients



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Ex Situ Hepatectomy and Liver Autotransplantation for Cholangiocarcinoma

Abstract

Background

Hepatic resection of tumors invading the retrohepatic vena cava and hepatic veins are a challenge for surgeons, who consider them unresectable most of the time.1 ,2 Ex situ hepatectomy and liver autotransplantation has developed to improve resectability of these malignancies.3,4

Methods

The patient was a 51-year-old man who had jaundice secondary to a intrahepatic cholangiocarcinoma 7 cm in diameter in the right lobe of the liver and the caudate lobe. A volumetric scan showed a future liver remnant (segments 2 and 3) not sufficient according to the body weight. The patient was considered to be unresectable by conventional resection due to the critical invasion to the retrohepatic vena cava together with the three hepatic veins. Therefore, an ex vivo extended right hepatectomy and autotransplantation were indicated.

Results

The patient underwent biliary decompression through a percutaneous transhepatic catheter and right portal vein embolization for left lobe hypertrophy. During the surgery, the liver was removed with the retrohepatic vena cava, which was replaced by a prosthetic graft without a veno-venous bypass. Ex vivo extended right hepatectomy was performed, and a prosthetic graft was used to replace the vena cava where the remaining left hepatic vein was anastomosed. The surgery duration was 9 h, and the anhepatic time was 4.5 h. The postoperative hospital stay was 19 days, and at this writing, 3 years later, the patient is disease-free.

Conclusion

Ex vivo hepatectomy without veno-venous bypass should be considered a valid therapeutic option for selected patients with cholangiocarcinoma invading the retrohepatic vena cava.



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Actinomyces turicensis Bacteremia Secondary to a Decubitus Ulcer: A Case Report and Review of the Literature.

We present a rare case of Actinomyces turicensis bacteremia secondary to a polymicrobial sacral decubitus ulcer infection in an elderly male patient. A PubMed search revealed only 9 previously reported cases of bacteremia due to A. turicensis, mostly in female patients. Because Actinomyces species are commensal organisms of the gastrointestinal tract, sacral decubitus ulcers may have an increased propensity of becoming infected and consequently cause a bacteremia. Our patient was successfully treated with debridement and intravenous antibiotic therapy; however, the optimal antibiotic treatment and length of therapy remain unclear because only a few case reports exist in the literature. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Releasing the “GENI”: Integrating authentic microbial genomics research into the classroom through GENI-ACT.

Abstract
The integration of genomics research into the undergraduate biology curriculum provides students with the opportunity to become familiar with bioinformatics tools and answer original research questions. Our purpose with this research project was to upscale the research experience through integration with classroom experience giving students access to authentic research projects. Students annotated 60 predicted ABC genes of Methanothermobacter thermautotrophicus and Methanobacterium sp. SWAN-1 and they were required to present a research poster to demonstrate their understanding of the project. During this research project a number of tests, assessments and surveys were conducted to assess familiarity with technical and conceptual understanding of genome annotation, satisfaction with annotation instruction, gain in bioinformatics research skills, scientific communications skills and increased student interest in research. We found that students gained significant skills in bioinformatics, specifically genome annotation skills and also gained confidence in their abilities to carry out scientific research. As a result of this authentic undergraduate research experience underrepresented students were motivated to pursue future careers in STEM fields.

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A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy

Abstract
Recent studies have identified various bacterial groups that are altered in dogs with chronic inflammatory enteropathies (CE) compared to healthy dogs. The study aim was to use quantitative PCR (qPCR) assays to confirm these findings in a larger number of dogs, and to build a mathematical algorithm to report these microbiota changes as a dysbiosis index (DI). Fecal DNA from 95 healthy dogs and 106 dogs with histologically confirmed CE was analyzed. Samples were grouped into a training set and a validation set. Various mathematical models and combination of qPCR assays were evaluated to find a model with highest discriminatory power. The final qPCR panel consisted of eight bacterial groups: total bacteria, Faecalibacterium, Turicibacter, E. coli, Streptococcus, Blautia, Fusobacterium, and C. hiranonis. The qPCR based dysbiosis index (DI) was built based on the nearest centroid classifier, and reports the degree of dysbiosis in a single numerical value that measures the closeness in the$\ {l_2} - norm$ of the test sample to the mean prototype of each class. A negative DI indicates normobiosis, whereas a positive DI indicates dysbiosis. For a threshold of 0, the DI based on the combined dataset achieved 74% sensitivity and 95% specificity to separate healthy and CE dogs.

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High-throughput sequencing revealed novel Dehalococcoidia in dechlorinating microbial enrichments from PCB contaminated marine sediments

Abstract
In this study six PCE-to-ethene dechlorinating cultures, fed with a fermentable substrate (lactate) or hydrogen as electron donor, were obtained from PCB and PCE dechlorinating microcosms constructed with PCB contaminated marine sediments.A novel Chloroflexi member (OTU-DIS1) affiliated to Dehalococcoidales Incertae Sedis, only distantly related to known dechlorinating bacteria, dominated the enrichment cultures (up to 86% of total OTUs). Sulfate-, thiosulfate- and sulfur-reducing bacteria affiliated to genera Desulfobacter, Dethiosulfatibacter and Desulfuromusa were also found to lesser extent.Remarkably, tceA, vcrA and the bifunctional PCE/PCB dehalogenase genes pcbA1, pcbA4 and pcbA5 were found in all dechlorinating microbial enrichments indicating the coexistence of different Dehalococcoides mccartyi strains.The reductive dechlorination rate in each culture remained unvaried over long-term operation (≈ 30 months) and ranged between 0.85 and 0.97 mmol Cl−1 released L−1 d−1 in the lactate fed microbial enrichments and between 0.66 and 0.85 mmol Cl−1 released L−1 d−1 in the H2 fed microbial enrichments.Overall, this study highlights the presence of yet unexplored biodiversity in PCBs contaminated marine sediments and indicates these environments as promising sources of novel organohalide respiring bacteria.

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Tissue damage induced midgut stem cell proliferation and microbial dysbiosis in Spodoptera litura

Abstract
In the past decade, gut microbiota has come to the fore in search for the cause of disregulation in intestinal homeostasis. Here, we report a possible link between gut microbial dynamics and stress inducing factors using the leaf worm moth Spodoptera litura as a model organism. Investigation reveals that S. litura exhibits dysbiosis i.e. alteration in the gut microbiota composition that might induce or suppress inflammation upon exposure to dextran sulfate, sodium salt, a tissue damaging agent (DSS, 40kD). It primarily corresponds to an expansion of the bacterial phylotypes Enterobacter sp., Pseudomonas sp., Escherichia sp. and Acinetobacter sp. belonging to subclass Gammaproteobacteria. To assess the role played by gut residents in midgut inflammation, we recolonized the axenic insects with Pseudomonas, Enterobacter and Acinetobacter individually. We observed that Pseudomonas and Enterobacter monoassociated insects exhibits inflammatory effects like damage to gut epithelium and hyperproliferation of stem cells under stress conditions. Conversely, Acinetobacter promotes fitness in larvae and reduces inflammatory effects of DSS. However, we failed to detect phenotypic inflammatory changes like midgut epithelium damage and stem cell proliferation in axenic insects reared on DSS supplemented diet. Our results highlights that gut commensals which apparently remain low in abundance and benign under typical conditions can exert modulatory (positive or negative) effects on host fitness in the presence of stimulator.

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Comparative genomics of the genus Desulfitobacterium

Abstract
The Desulfitobacterium genus comprises anaerobic Gram-positive bacteria, of which the majority are facultative organohalide-respirers. We here present the genomes of eight strains of Desulfitobacterium spp., including five strains of D. hafniense, one strain each from D. dichloroeliminans and D. metallireducens, and one strain that had not been assigned to any species prior to this study. The newly sequenced genomes were compared with four previously published desulfitobacterial genomes. The average genome sizes are 5.5, 4.3 and 3.4 Mbp for D. hafniense, D. dehalogenans and D. dichloroeliminans/metallireducens, respectively. The genomes encode up to seven reductive dehalogenases, the genomes of both D. hafniense DP7 and D. metallireducens 853–15AT did not encode any reductive dehalogenase. The latter result was a surprise as D. metallireducens 853–15AT has been reported to carry out organohalide respiration. Unlike reported for the pceABCT gene cluster, the other reductive dehalogenase gene clusters do not show any signs of being genetically mobile. All analyzed desulfitobacterial genomes encode a complete cobalamin synthesis pathway. A menaquinone synthesis pathway was found in all strains except D. dichloroeliminans DCA1T. The detailed analysis of the genome sequence of twelve desulfitobacteria from four different species, confirmed that this genus has an extremely large metabolic repertoire.

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A Millimeter Scale Flexural Testing System for Measuring the Mechanical Properties of Marine Sponge Spicules

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We present a protocol for performing three-point bending tests on sub-millimeter scale fibers using a custom-built mechanical testing device. The device can measure forces ranging from 20 µN up to 10 N and can therefore accommodate a variety of fiber sizes.

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Initial evaluation of the Celesteion large-bore PET/CT scanner in accordance with the NEMA NU2-2012 standard and the Japanese guideline for oncology FDG PET/CT data acquisition protocol version 2.0

Abstract

Background

The goal of this study was to evaluate the performance of the Celesteion positron emission tomography/computed tomography (PET/CT) scanner, which is characterized by a large-bore and time-of-flight (TOF) function, in accordance with the NEMA NU-2 2012 standard and version 2.0 of the Japanese guideline for oncology fluorodeoxyglucose PET/CT data acquisition protocol. Spatial resolution, sensitivity, count rate characteristic, scatter fraction, energy resolution, TOF timing resolution, and image quality were evaluated according to the NEMA NU-2 2012 standard. Phantom experiments were performed using 18F-solution and an IEC body phantom of the type described in the NEMA NU-2 2012 standard. The minimum scanning time required for the detection of a 10-mm hot sphere with a 4:1 target-to-background ratio, the phantom noise equivalent count (NECphantom), % background variability (N 10mm), % contrast (Q H,10mm), and recovery coefficient (RC) were calculated according to the Japanese guideline.

Results

The measured spatial resolution ranged from 4.5- to 5-mm full width at half maximum (FWHM). The sensitivity and scatter fraction were 3.8 cps/kBq and 37.3%, respectively. The peak noise-equivalent count rate was 70 kcps in the presence of 29.6 kBq mL−1 in the phantom. The system energy resolution was 12.4% and the TOF timing resolution was 411 ps at FWHM. Minimum scanning times of 2, 7, 6, and 2 min per bed position, respectively, are recommended for visual score, noise-equivalent count (NEC)phantom, N 10mm, and the Q H,10mm to N 10mm ratio (QNR) by the Japanese guideline. The RC of a 10-mm-diameter sphere was 0.49, which exceeded the minimum recommended value.

Conclusions

The Celesteion large-bore PET/CT system had low sensitivity and NEC, but good spatial and time resolution when compared to other PET/CT scanners. The QNR met the recommended values of the Japanese guideline even at 2 min. The Celesteion is therefore thought to provide acceptable image quality with 2 min/bed position acquisition, which is the most common scan protocol in Japan.



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