Αρχειοθήκη ιστολογίου

Τρίτη 3 Απριλίου 2018

RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA mutated breast cancer

Abstract
Background
BRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) and enhanced sensitivity to DNA damaging agents or to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed in clinical trials. Numerous mechanisms of PARPi resistance have been described, whose clinical relevance in gBRCA-mutated breast cancer is unknown. This highlights the need to identify functional biomarkers to better predict PARPi sensitivity.
Patients and Methods
We investigated the in vivo mechanisms of PARPi resistance in gBRCA1 patient-derived tumor xenografts (PDXs) exhibiting differential response to PARPi. Analysis included exome sequencing and immunostaining of DNA damage response proteins to functionally evaluate HRR. Findings were validated in a retrospective sample set from gBRCA1/2-cancer patients treated with PARPi.
Results
RAD51 nuclear foci, a surrogate marker of HRR functionality, was the only common feature in PDX and patient samples with primary or acquired PARPi resistance. Consistently, low RAD51 was associated with objective response to PARPi. Evaluation of the RAD51 biomarker in untreated tumors was feasible due to endogenous DNA damage. In PARPi-resistant gBRCA1 PDXs, genetic analysis found no in-frame secondary mutations, but BRCA1 hypomorphic proteins in 60% of the models, TP53BP1-loss in 20% and RAD51-amplification in one sample, none mutually exclusive. Conversely, one of three PARPi-resistant gBRCA2 tumors displayed BRCA2 restoration by exome sequencing. In PDXs, PARPi resistance could be reverted upon combination of a PARPi with an ATM inhibitor.
Conclusion
Detection of RAD51 foci in gBRCA tumors correlates with PARPi resistance regardless of the underlying mechanism restoring HRR function. This is a promising biomarker to be used in the clinic to better select patients for PARPi therapy. Our study also supports the clinical development of PARPi combinations such as those with ATM inhibitors.

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Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Role, Controversy, and Future Directions

Abstract
Background
The value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet PF (cisplatin and fluorouracil). We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.
Design
We nonsystematically reviewed published phase 3 clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.
Results
TPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (ie, cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.
Conclusions
TPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists.

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Should decisions on adding adjuvant chemotherapy in early stage ER positive breast cancer be based on gene expression testing or clinicopathologic factors or both?



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Neo-adjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08)

Abstract
Background
This open-label, phase lll trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma.
Patients and Methods
Patients were randomly assigned (1:1) to 2 cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary endpoint was progression-free survival (PFS).
Results
In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years (95% CI, 2.0 to not reached) with cetuximab and 2.0 years (95% CI, 1.5 to 2.8) with control (HR, 0.79; 95% CI, 0.58 to 1.07; P = .13). Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2 to 4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52 to 1.01; P = .055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31 to 0.90; P = .017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64 to 1.59, P = .97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings.
Conclusion
Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma.
Clinical trial information
NCT01107639

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Circulating tumor DNA detection in hepatocellular carcinoma



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Eribulin in BRAF V600E mutant metastatic colorectal cancer: Case series and potential rationale



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Hyaluronic Acid-Based Matrix in Wound Bed Preparation

What benefits might the application of a hyaluronic acid-based matrix offer patients with complex surgical wounds?
ePlasty, Open Access Journal of Plastic Surgery

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Focus on People Awards Opens for Nominations

Oticon, Inc. is seeking nominations of outstanding individuals with any degree of hearing loss for the 2018 Oticon Focus on People Awards.  For 20 years, the Oticon Focus on People Awards have set the gold standard for recognizing the achievements and contributions of people with hearing loss.  Established in 1997, the national awards program honors students, adults, advocacy volunteers and hearing care professionals who show that hearing loss does not limit a person's ability to make a positive difference. 

FOP_20th.jpg"For more than 20 years, the Oticon Focus on People Awards has created the kind of awareness that changes attitudes and opens doors of opportunity for all people with hearing loss," said Nancy Palmere, Director of Consumer Marketing and Public Relations for Oticon, Inc., who heads the national program.  "Our approach is simple. By drawing national attention to everyday people doing amazing things, who also happened to have hearing loss, we aim to change negative perceptions of hearing loss and encourage those reluctant to address their own hearing health to seek professional care."

Easy to Nominate

Anyone may nominate.  Quick and easy nominations forms, available at www.Oticon.com/FOP, can be downloaded or completed online. People with all degrees of hearing loss – from mild to more severe - are eligible. There is also a special category for hearing care practitioners with or without hearing loss. Deadline for nominations is May 18, 2018.

Four Categories with Three Winners in Each

Categories include: Student, for full-time students with hearing loss, ages 6 – 25; Adult, for people with hearing loss, ages 21 and above; and Advocacy, for volunteers with hearing loss, who are actively involved in support efforts for the hard-of-hearing and deaf community. A special Practitioner category recognizes hearing care professionals who go "above and beyond" through humanitarian and public education efforts. Nominees in the Practitioner category are not required to have a hearing loss to qualify.

First place winners receive a $1,000 cash prize and a $1,000 donation to the charity of their choice.  First place winners in the Student, Adult and Advocacy categories also receive Oticon BrainHearing™ hearing devices.  Second place winners receive a $500 cash prize and third place winners, a $250 cash prize.

Following the close of nominations, the general public will be invited to vote online to determine first, second and third place winners in each category. 

Published: 4/3/2018 12:12:00 PM


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Smoking Increases Risk of Hearing Loss

Smokers are at a higher risk of developing hearing loss, concludes a recently published research.

cigarette-599485_1280.jpgIn an observational study using data from the yearly health checkups of 50,195 adults with no hearing loss at baseline, researchers found a solid evidence that links smoking with increased risk of hearing loss, especially high-frequency hearing loss. The study also reports that the excess risk disappears shortly after study participants quit smoking.
 
"Hearing loss is common in the adult population," said Huanhuan Hu, PhD, lead author of the study. "Identifying modifiable risk factors is important for hearing health care."
 
"Smoking has been associated with prevalent hearing loss in cross-sectional studies. However, few prospective cohort studies have examined the association between smoking and hearing loss, and their findings conflict," Hu told The Hearing Journal. "Our J-ECOH Study has high quality data on hearing and smoking. Thus, we examined the association between smoking and hearing loss."
 
During the follow-up sessions, which were conducted to a maximum of eight years, high-frequency hearing loss was seen in 3,532 participants and low-frequency hearing loss in 1,575. Researchers found that the risk of high- and low-frequency hearing loss increased with the number of cigarettes smoked per day. Smoking cessation led to decline in hearing loss risk, even among those who stopped smoking less than five years before baseline.
 
The Centers for Disease Control and Prevention (CDC) warns the public that cigarette smoking is the leading cause of preventable disease and death in the United states, responsible for more than one in five deaths every year. CDC also reports that in 2016, approximately 37.8 million adults  in the country are cigarette smokers and more than 16 million have smoking-related disease.
 
The study by Hu and his colleagues at the National Center for Global Health and Medicine in Japan contributes to the evidence that smoking causes preventable diseases.
 
"Our study provides reliable evidence that smoking may cause hearing loss and the excess risk can be eliminated through quitting smoking," Hu explained. "Smoking will be more widely acknowledged as a risk factor for hearing loss. In addition, these findings can motivate smokers to quit smoking." 
Published: 4/2/2018 5:32:00 PM


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Loyola Medicine Marks 500th Cochlear Implant

Loyola Medicine reached a landmark feat with its 500th cochlear implant surgery. A standard treatment for patients with hearing loss but do not benefit as much from hearing aids, cochlear implants (CIs) have been reported to improve the quality of life of recipients.

shutterstock_280677998.jpg"Loyola Medicine has an adult population of CI recipients, the vast majority of whom present with progressive hearing loss ranging from several years to decades," shared Candace R. Blank, AuD, audiologist chief at Loyola Medicine. "We see patients who range in age from their late teens through their 90s, with expected co-morbidities including anxiety, depression, and social isolation."
 
Over 37.5 million American adults have reported some form of hearing difficulty—an issue that worsens with age and gets aggravated by factors like occupational noise and excessive listening to recreational sounds.
 
Hearing loss is also associated with increased health risks like depression and cognitive impairment. However, a recent study based on a large-scale NHIS survey has pointed to the gap in audiology referral of many adults who could benefit from a hearing test, hearing aids, and CIs (Hearing Journal. 2018;71(3):6). In fact, only 22 percent of CI candidates actually get the device, the study found.
 
"There is a lack of information and awareness of current guidelines for implantable solutions among the public as well as with primary care physicians," explained Blank. "The survey underscores the importance of the primary care physician in taking an active role in understanding the significant implications of hearing loss.It is extremely unfortunate that majority of people who could benefit from a CI are not directed to the proper avenues necessary to be evaluated."
 
But Loyola offers a different scene, being one of the busiest hearing centers in the Midwest. It is also one of the first centers to implant a hybrid system—a combination of a CI and a hearing aid.
 
"Loyola Medicine's successful CI program is directly related to the close relationship between our excellent audiology and neurotology team," Blank told The Hearing Journal. The 500th CI surgery was done by John Leonetti, MD, one of Loyola's four otolaryngologists with expertise in this procedure. "Together we determine if someone is medically, audiologically, and holistically a candidate—even if the patient is 96 years old… We treat both the patient's body and soul."
Published: 3/30/2018 10:15:00 AM


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Hearing Loss May Increase Accident Risks

People with hearing problems may have a higher risk of getting into accidents, says a recent study published in JAMA Otolaryngology-Head and Neck Surgery. Data from the National Health Interview Survey (NHIS), collected from 232.2 million U.S. adults from 2007 to 2015, showed that respondents who had "a lot of trouble" hearing were twice as likely to be hurt.

accident.JPGAccidental or unintentional injuries have led to 30.6 million emergency department visits in the United States, according to the CDC National Center for Health Statistics. Meanwhile, over 37.5 million American aged 18 and over suffer from different forms of hearing difficulty. Understanding the link between the accidental injury and hearing loss is key to reduce risks and incidences, including deaths.

In the NHIS survey, respondents were asked to describe their hearing status and were given the following options: excellent, good, a little trouble, moderate trouble, a lot of trouble, and deaf. The researchers did a cross-sectional analysis of the responses and tracked injuries that were related to work, leisure, and activities like sports and driving. Accidental injuries were found in 2.8 percent of survey respondents; the most prevalent injuries were work- and leisure-related.

With the observational study's design, the researchers could not intervene nor control natural differences that could further explain the findings. The researchers noted that self-reporting was admittedly one of the study limitations. Nonetheless, they concluded that improved public awareness of hearing health and proper screening is important to reduce the risk of accidental injuries. 

Notably, study author Hossein Mahboubi, MD, MPH, of University of California, Irvine, wrote about the gaps in hearing loss referral and evaluation in the March 2018 issue of The Hearing Journal​, and stressed the need for increased hearing health awareness. ​
Published: 3/28/2018 11:53:00 AM


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Hearing Loss is Higher in Children with Post-Cardiac Surgery

Researchers at the Children's Hospital of Philadelphia found out that hearing loss in preschoolers who have undergone cardiac surgery during infancy could be 20 times more than in the one percent incidence in the general population.
 
Three hundred forty-eight children, who had surgery for their congenital heart disease (CHD), underwent audiologic and neurodevelopmental evaluations as part of a prospective study on neurodevelopmental progress at the age of 4. Researchers looked into the possible contributing factors of hearing loss and the impact of the hearing impairment on neurodevelopmental outcomes.
 
Senior author Nancy B. Burnham, RN, MSN, CRNP explained that the parent study was inspired by the increasing evidence of impaired neurodevelopmental outcomes in children with CHD who require surgery as infants. These outcomes have so many inter-individual variations.
 
"Audiological testing at the time of the National Institutes of Health (NIH) funded evaluation was primarily done because of the cognitive and speech evaluation to make sure they did not have associated hearing loss," Burnham told The Hearing Journal. "I don't know if we knew we would discover such a high prevalence of hearing loss."
 
The study reported that the prevalence of hearing loss was 21.6 percent. Specifically, the prevalence of conductive hearing loss was 12.4 percent; the incidence of sensorineural hearing loss was 6.9 percent, and the indeterminate hearing loss was 2.3 percent. Only 18 preschoolers out of the 348 subjects were tested for hearing loss prior to the study. Ten subjects were already using hearing aids. The study suggested that hearing loss was associated with longer postoperative duration of stay, the presence of a genetic anomaly, and younger gestational age. Effects of the hearing loss included worse neurodevelopmental outcomes in language, cognition, and attention.
 
Burnham said that the impact of the findings of the study is "without a doubt, the importance of early screening and early testing."
 
When asked about possible measures to prevent the unintended hearing loss from cardiac surgery in infancy, given that younger gestational age, genetic anomaly, and longer postoperative duration of stay are the risk factors, Burnham explained: "There might be modifiable factors but additional research would be required.  Duration of stay is a potential area of research. What about the longer length of stay increases the risk for hearing impairment? Perhaps the many ototoxic drugs they receive during their hospital stay (a potential mechanism for future study). Research has shown babies with CHD brains are more immature than their associated GA at birth. If there were measures that would reduce preterm or near-term births that might have an impact."
Published: 3/27/2018 9:00:00 AM


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Knockdown of Sox2 Inhibits OS Cells Invasion and Migration via Modulating Wnt/β-Catenin Signaling Pathway

Abstract

Osteosarcoma (OS) was a prevalent malignant bone tumor which threatens people's health worldwide. Wnt/β catenin signaling pathway had been proved significant in various cancers, indicating its possible function in OS as well. Sox2, a crucial member among SOX family could regulate cells biologically. How Sox2 modulated Wnt/β catenin signaling pathway in OS remained to be discussed. The study aimed to investigate the effects of Sox2 on the invasion and migration of OS cells and the related molecular mechanisms. Twenty-four human OS and adjacent tissue samples were involved in this study. Human OS cell lines MG63 and HOS were selected for further investigation. The liposome carrier si-Sox2 which could interfere with the expression of Sox2 gene was built to transfect MG63 and HOS cells). QRT-PCR assay and western blot were utilized to analyze the expression of mRNA and proteins of Sox2. Transwell assay and wound healing assay were conducted to test the invasion and migration level of cells. The expression of GSK3, β-catenin, cyclin D1 and c-myc proteins were detected by western blot assay after transfection with si-Sox2. Compared with normal tissues and cells, the expression of Sox2 in OS tissues and cells was significantly higher. The mRNA and protein levels of Sox2 significantly decreased after transfection with si-Sox2. The invasion and migration of OS cells were down-regulated significantly through the inhibition of Sox2 by inactivating Wnt/β-catenin signaling pathway related proteins. Knockdown of Sox2 could inhibit invasion and migration of OS cells via modulating Wnt/β-catenin signaling pathway.



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Exhibition of stochastic resonance in vestibular tilt motion perception

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Publication date: Available online 3 April 2018
Source:Brain Stimulation
Author(s): R.C. Galvan-Garza, T.K. Clark, A.P. Mulavara, C.M. Oman
BackgroundStochastic Resonance (SR) is a phenomenon broadly described as "noise benefit". The application of subsensory electrical Stochastic Vestibular Stimulation (SVS) via electrodes behind each ear has been used to improve human balance and gait, but its effect on motion perception thresholds has not been examined.ObjectiveThis study investigated the capability of subsensory SVS to reduce vestibular motion perception thresholds in a manner consistent with a characteristic bell-shaped SR curve.MethodsWe measured upright, head-centered, roll tilt Direction Recognition (DR) thresholds in the dark in 12 human subjects with the application of wideband 0–30 Hz SVS ranging from ±0–700 μA. To conservatively assess if SR was exhibited, we compared the proportions of both subjective and statistical SR exhibition in our experimental data to proportions of SR exhibition in multiple simulation cases with varying underlying SR behavior. Analysis included individual and group statistics.ResultsAs there is not an established mathematical definition, three humans subjectively judged that SR was exhibited in 78% of subjects. "Statistically significant SR exhibition", which additionally required that a subject's DR threshold with SVS be significantly lower than baseline (no SVS), was present in 50% of subjects. Both percentages were higher than simulations suggested could occur simply by chance. For SR exhibitors, defined by subjective or statistically significant criteria, the mean DR threshold improved by −30% and −39%, respectively. The largest individual improvement was −47%.ConclusionAt least half of the subjects were better able to perceive passive body motion with the application of subsensory SVS. This study presents the first conclusive demonstration of SR in vestibular motion perception.



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Does postoperative PI-LL mismatching affect surgical outcomes in thoracolumbar kyphosis associated with ankylosing spondylitis patients?

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Zhuo-jie Liu, Bang-ping Qian, Yong Qiu, Sai-hu Mao, Jun Jiang, Bin Wang
ObjectiveTo investigate if pelvic incidence (PI) and lumbar lordosis (LL) mismatching affects surgical outcomes for ankylosing spondylitis (AS) related kyphosis following 1-level lumbar pedicle subtraction osteotomy (PSO).Patients and MethodsAS patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO from March 2006 and February 2014 in our institution, were retrospectively reviewed. The radiographic measurements and health-related quality of life (HRQoL) scores, including Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) for pain, were recorded at baseline and the last follow-up. Patients were divided into 2 groups according to PI-LL matching or not postoperatively (Match Group, Mismatch Group), and comparison of the aforementioned parameters between the two groups was performed.ResultsSeventy patients were enrolled with a mean age of 34.60 ± 9.45 years (range, 17 yrs. to 59 yrs.). Among them, 44 were included in the Match Group and 26 in the Mismatch Group. At baseline, patients in the Match Group had larger LL (p = 0.014) and smaller pelvic tilt (PT, p < 0.001) than patients in the Mismatch Group. At the last follow-up, along with larger LL (p = 0.004) and smaller PT (p = 0.001), Match Group patients also had significantly smaller sagittal vertical axis (SVA, 3.31 cm vs 6.27 cm, p = 0.001) than those in the Mismatch Group. Seventy-five percent (33/44) of the patients in the Match Group had a SVA < 5 cm at the last follow-up, while in the Mismatch Group, only 35% (9/26) of the patients did. However, no significant difference was found between the two groups regarding HRQoL scores.ConclusionPatients with postoperative PI-LL matching were more likely to have a better correction of SVA; they also tended to have a smaller preoperative PT. However, PI-LL mismatching didn't affect HRQoL scores at the last follow-up, which was different from the results of previous studies in the settings of ASD.



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Are older patients with solitary spinal metastases fit for total en-bloc surgery?

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Peng Liu, Libo Jiang, Yun Liang, Houlei Wang, Hao Zhou, Xilei Li, Hong Lin, Xiaogang Zhou, Jian Dong
ObjectiveDue to radical resection, total en-bloc spondylectomy (TES) is associated with significant levels of surgical injury and spinal instability, particularly in elderly patients with solitary spinal metastases (SM), whether the possible benefits outweigh the risk requires intense consideration. Our aim was to compare and analyze the impact of age on patient prognosis.Patients and MethodsThis study investigated TES in 78 consecutive patients with solitary SM, who were divided into Group A (>65 years, n = 32) and group B (<60 years of age, n = 46). Surgical outcomes were assessed according to survival time, local recurrence, neurological function, pain, and quality of life before and after surgery. Differences between groups were statistically compared using analysis of variance (ANOVA) or chi-square tests.ResultsThere was no significant difference between the two groups in terms of surgery duration, blood loss, blood transfusion or the duration of hospital stay (p > 0.05). Furthermore, there was no significant difference in the median survival time between the two groups (p > 0.05). However, the perioperative complication rate in group A was higher than that in group B (p < 0.05). There was no significant difference in terms of local recurrence rate when compared between group A and group B (p > 0.05), and there were no significant differences in terms of improvements in neurological function, Visual Analogue Scale and Karnofsky scores of patients between the two groups (p > 0.05).ConclusionOlder patients can experience survival and local recurrence rates that were similar to those of younger patients. Although older patients are at increased risk of perioperative complications, this factor does not appear to lead to serious adverse outcomes. Older patients are still good candidates to receive TES to cure solitary SM after careful preparation and strict selection.



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Occiput-axis crossing translaminar screw fixation technique using offset connectors: An in vitro biomechanical study

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Jiyong Gu, Weiwei Lei, Zong Xin, Yi Wu, Lin Peng, Zhibin Li, Zize Feng, Minchan Zhao, Songtao Qi, Yuntao Lu
ObjectiveFixation with the axis vertebra (C2) using pedicle screws is commonly used to treat an unstable occipitocervical junction; however, it is accompanied by a risk of vertebral artery injury. The occiput-C2 (OC2) crossing translaminar screw fixation technique may avoid this risk, but rod implantation is difficult. Offset connectors can help facilitate this construct. This study aimed to evaluate the stability of a technique for OC2 crossing translaminar screw fixation using offset connectors (C2LAM + OF) in comparison with other methods.Patients and methodsSix fresh-frozen human cadaveric occipital–cervical spines were tested intact under flexion, extension, lateral bending, and axial rotation. These were then made into a type II odontoid fracture model, instrumented with an occipital plate, and tested in the following modes: C2 bilateral pedicle screws (C2P), a single C2 pedicle screw and bilateral C3 lateral mass screws (C2P + C3M), C2 crossing translaminar screws (C2LAM), and C2LAM + OF. The OC2 range of motion (ROM) for each construct was obtained and compared using a repeated-measures analysis.ResultsThe ROM of the C2LAM + OF construct was found not to be significantly different from that of the C2P and C2P + C3M fixations in every direction (p > 0.05). However, the C2LAM + OF construct was superior to the C2LAM construct in axial rotation (p < 0.05).ConclusionsOC2 crossing translaminar screw fixation using offset connectors offers similar stability to C2 pedicle screw fixation and is an effective alternative method for treating an unstable occipitocervical junction.



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CPEB4 regulates glioblastoma cell proliferation and predicts poor outcome of patients

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Hong-xiang Wang, Rong Qin, Jian Mao, Qi-lin Huang, Fan Hong, Feng Li, Zhen-yu Gong, Tao Xu, Yong Yan, Shao-hui Chao, Shi-kun Zhang, Ju-xiang Chen
ObjectiveCytoplasmic polyadenylation element binding protein 4 (CPEB4) is a regulator of gene expression at transcriptional level and has been reported to be associated with biological malignancy in cancers. However, little was known about the correlation between CPEB4 and glioblastoma cell proliferation and the prognostic significance in patients. Our aim was to investigate the functional role and prognostic value of CPEB4 in glioblastoma.Patients and methodsWe determined the expression of CPEB4 protein using immunohistochemistry in tissue microarrays containing 278 glioma patients (including 98 primary glioblastomas) and evaluated its association with pathological grades and clinical outcome by univariate and multivariate analyses. And then, lentiviral-mediated RNAi targeting CPEB4 was utilized to study the role of CPEB4 in glioblastoma cell proliferation.ResultsIn our cohort, CPEB4 expression was positively related to glioma pathological grade (p < 0.01) and elevated in glioblastoma (p < 0.01). High expression of CPEB4 was associated with significantly poor prognosis, and could be identified as an independent risk factor for overall survival (OS) and progression-free survival (PFS) of glioblastoma patients (hazard ratio (HR) = 1.730, p = 0.014 and HR = 1.877, p = 0.004, respectively). In vitro studies further showed that downregulation of CPEB4 significantly reduced the growth rate of T98G and U251 cells comparing with the controls.ConclusionOur study indicated that increased expression of CPEB4 in primary glioblastoma is a novel biomarker for predicting poor outcome of patients and suppression of CPEB4 inhibit tumor cell proliferation, suggesting a potential therapeutic target for glioblastoma.



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Issue Information

Pathology International, Volume 68, Issue 4, Page i-iv, April 2018.


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Characteristics and sources of nitrous acid in an urban atmosphere of northern China: Results from 1-yr continuous observations

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Dandan Li, Likun Xue, Liang Wen, Xinfeng Wang, Tianshu Chen, Abdelwahid Mellouki, Jianmin Chen, Wenxing Wang
Nitrous acid (HONO) is a key reservoir of the hydroxyl radical (OH) and plays a central role in the atmospheric chemistry. To understand the sources and impact of HONO in the polluted atmosphere of northern China, continuous measurements of HONO and related parameters were conducted from September 2015 to August 2016 at an urban site in Ji'nan, the capital city of Shandong province. HONO showed well-defined seasonal and diurnal variation patterns with clear wintertime and nighttime concentration peaks. Elevated HONO concentrations (e.g., over 5 ppbv) were frequently observed with a maximum value of 8.36 ppbv. The HONO/NOX ratios of direct vehicle emissions varied in the range of 0.29%–0.87%, with a mean value of 0.53%. An average NO2-to-HONO nighttime conversion frequency (khet) was derived to be 0.0068 ± 0.0045 h−1 from 107 HONO formation cases. A detailed HONO budget analysis suggests an unexplained daytime missing source of 2.95 ppb h−1 in summer, which is about seven times larger than the homogeneous reaction of NO with OH. The effect of HONO on OH production was also quantified. HONO photolysis was the uppermost source of local OH radical throughout the daytime. This study provides the year-round continuous record of ambient HONO in the North China Plain, and offers some insights into the characteristics, sources and impacts of HONO in the polluted atmospheres of China.



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Lower expression of bone marrow miR-122 is an independent risk factor for overall survival in cytogenetically normal acute myeloid leukemia

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Ting-juan Zhang, Zhen Qian, Xiang-mei Wen, Jing-dong Zhou, Xi-xi Li, Zi-jun Xu, Ji-chun Ma, Zhi-hui Zhang, Jiang Lin, Jun Qian
BackgroundThe liver-enriched microRNA-122 (miR-122) plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) with prognostic value. Recently, miR-122 was also found to be related to many other cancers besides HCC. However, less study determined miR-122 expression and its clinical significance in acute myeloid leukemia (AML).MethodsReal-time quantitative PCR was performed to detect the level of bone marrow (BM) miR-122 in de novo AML patients. The clinical significance of miR-122 expression in AML was further investigated.ResultsAmong whole-cohort AML, lower expression of BM miR-122 was associated with male patients, higher hemoglobin and favorable-karyotypes (P = 0.038, 0.006, and 0.038, respectively). Among cytogenetically normal AML (CN-AML), lower expression of BM miR-122 was correlated with DNMT3A wild type (P = 0.043). Moreover, patients with lower expression of BM miR-122 presented lower complete remission (CR) rate and shorter overall survival (OS) than those with higher expression of BM miR-122 in CN-AML (P = 0.025 and 0.013, respectively). Cox regression analyses further confirmed the prognostic value of BM miR-122 expression in CN-AML (P = 0.024). In follow-up patients, BM miR-122 expression level in CR time was increased compared to diagnosis time, and was returned to primary level when in relapse time again (P = 0.062 and 0.049, respectively).ConclusionsOur findings indicated that lower expression of BM miR-122 acted as an independent risk factor for OS in CN-AML.



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Histopathology of Locally Advanced Colorectal Carcinoma, With Emphasis on Tumor Invasion of Adherent Peritoneal Membranes

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Jey-Hsin Chen
Locally advanced colorectal carcinomas are characterized by neoplastic cells that invade beyond the colon and directly into surrounding organs and structures that include the retroperitoneum and abdominopelvic sidewall. These aggressive tumors are prognostically adverse and are categorized with highest possible tumor stage in current cancer staging systems. Recognizing colorectal carcinoma with extensive locoregional invasion is typically straightforward, but some cases can be diagnostically challenging. These include tumors with limited invasion of extracolonic tissue such as the subserosa in which there are no cells or structures that are histologically or architecturally distinct from the colonic primary. Tumor-associated injury of the colonic peritoneum often precedes invasion by the neoplastic cells and can cause the peritoneal membrane of the colon to adhere and subsequently fuse to the peritoneal membrane of a neighboring organ or structure, thereby creating a trans-peritoneal bridge through which a tumor can directly invade the adherent extracolonic tissue. Hence, locally advanced colorectal carcinoma can be narrowly defined by neoplastic cells that completely invade through the fused peritoneal membrane and into the subserosa of the adherent extracolonic tissue. The evaluation of tumor invasion of the fused peritoneal membrane, which is enhanced by the combined use of an elastic stain and an immunostain for pan-keratin, is essential for the proper staging of locally advanced colorectal carcinoma and its clinical management.



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Editorial Board

Publication date: April 2018
Source:Pathology - Research and Practice, Volume 214, Issue 4





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Peroxiredoxin 1 promoted tumor metastasis and angiogenesis in colorectal cancer

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Huan-Xi Li, Xiang-Yu Sun, Shi-Ming Yang, Qing Wang, Zhen-Yu Wang
Peroxiredoxin1 (Prdx1) is a member of the PrdxS family, and it regulates cellular signaling and differentiation. The role of Prdx1in colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of Prdx1 in the metastasis and angiogenesis of CRC. The expression of Prdx1 in 60 cases human CRC tissues was detected through immunohistochemistry. The tumors that highly expressed Prdx1 (42/60) exhibited higher tumor grade and lymph node metastasis than those with low expression of Prdx1 (18/60) (p < 0.05). Kaplan–Meier survival analysis showed that the survival time of thePrdx1-positive group was shorter than that of thePrdx1-negative group (p = 0.046).Moreover, a statistically significant correlation was observed between the Prdx1 expression and microvessel density (p = 0.004). Transwell migration assay revealed that Prdx1 was down-regulated in the CRC cell line HCT116, thereby suppressing the invasion and migration capacities of tumor cells, whereas Prdx1was up-regulated in HT29 cells, thereby increasing the invasion and migration capacities of tumor cells. The tube formation capacity of human umbilical vein endothelial cells cultured in 3D medium was increased after conditioned medium from overexpressed Prdx1cancer cells was added relative to that when down-regulated Prdx1 cell medium was added(p < 0.05). In addition, up-regulated Prdx1 increased the protein expression of MMP2, MMP9, and VEGFA. These data suggested that Prdx1 expression predicted poor prognosis by regulating the tumor metastasis and angiogenesis of CRC. Therefore, Prdx1 may serve as a potential therapeutic target.



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Issue Information

International Forum of Allergy &Rhinology, Volume 8, Issue 4, Page 453-455, April 2018.


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International Forum of Allergy &Rhinology, Volume 8, Issue 4, Page 553-553, April 2018.


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Clinical and pathological characteristics of KEAP1- and NFE2L2- mutated non-small cell lung carcinoma (NSCLC)

Background: KEAP1 and NFE2L2 mutations are associated with impaired prognosis in many cancers and with squamous cell carcinoma formation in non-small cell lung cancer (NSCLC). However, few is known about frequency, histology-dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Patients and methods: Tumor tissue of 1391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival and treatment outcome of patients with KEAP1 or NFE2L2 mutations were assessed. Results: KEAP1 mutations occurred with a frequency of 11.3% (n=157) and NFE2L2 mutations with a frequency of 3.5% (n=49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. KEAP1 mutations were found mainly in adenocarcinoma (AD) (72%), while NFE2L2 mutations were more common in squamous cell carcinoma (LSCC) (59%). KEAP1 mutations were spread over the whole protein, whereas NFE2L2 mutations were clustered in hot-spot regions. In over 80% of patients both mutations co-occurred with other cancer-related mutations, among them targetable aberrations like activating EGFR mutations or MET amplification. Both patient groups showed different patterns of metastases, stage and performance state. No patient with KEAP1 mutation had a response on systemic treatment in 1st-, 2nd- or 3rd-line setting. Of NFE2L2 mutated patients, none responded to 2nd- or 3rd-line therapy. Conclusion: KEAP1 and NFE2L2 mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and are found together with other cancer-related, partly targetable, aberrations. Both markers seem to be predictive for chemotherapy resistance. 



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An Effective Epigenetic-PARP inhibitor Combination Therapy for Breast and Ovarian Cancers Independent of BRCA-mutations

Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are primarily effective against BRCA1/2-mutated breast and ovarian cancers but resistance due to reversion of mutated BRCA1/2 and other mechanisms is common. Based on previous reports demonstrating a functional role for DNMT1 in DNA repair (DDR) and our previous studies demonstrating DNMTis ability to resensitize tumors to primary therapies, we hypothesized that combining a DNMTi with PARPi would sensitize PARPi resistant breast and ovarian cancers to PARPi therapy, independent of BRCA status. Experimental Design: Breast and ovarian cancer cell lines (BRCA- wildtype/-mutant) were treated with PARPi talazoparib and DNMTi guadecitabine. Effects on cell survival, reactive oxygen species (ROS) accumulation, and cAMP levels were examined. In vivo, mice bearing either BRCA-proficient breast or ovarian cancer cells were treated with talazoparib and guadecitabine, alone or in combination. Tumor progression, gene expression and overall survival were analyzed. Results: Combination guadecitabine and talazoparib synergized to enhance PARPi efficacy, irrespective of BRCA mutation status. Co-administration of guadecitabine with talazoparib increased accumulation of ROS, promoted PARP activation and further sensitized, in a cAMP/PKA-dependent manner, breast and ovarian cancer cells to PARPi. In addition, DNMTi enhanced PARP 'trapping' by talazoparib. Guadecitabine plus talazoparib decreased xenograft tumor growth and increased overall survival in BRCA-proficient high-grade serous ovarian and triple negative breast cancer models. Conclusions: The novel combination of the next generation DNMTi guadecitabine and the first-in-class PARPi talazoparib inhibited breast and ovarian cancers harboring either wildtype- or mutant-BRCA, supporting further clinical exploration of this drug combination in PARPi-resistant cancers.



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Molecular diagnosis of diffuse gliomas through sequencing of cell-free circulating tumour DNA from cerebrospinal fluid

Purpose: Diffuse gliomas are the most common primary tumour of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumour specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumour DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies. Experimental Design: Diffuse gliomas are the most common primary tumour of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumour specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumour DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies. Results: Analysis of the mutational status of the IDH1, IDH2, TP53, TERT, ATRX, H3F3A and HIST1H3B genes allowed the classification of 79% of the 648 diffuse gliomas analysed, into IDH-wildtype glioblastoma, IDH-mutant glioblastoma/diffuse astrocytoma and oligodendroglioma, each subtype exhibiting diverse median overall survival (1.1, 6.7, 11.2 respectively). We developed a sequencing platform to simultaneously and rapidly genotype these seven genes in CSF ctDNA allowing the sub-classification of diffuse gliomas. Conclusions:The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients.



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Cell-free DNA modification dynamics in abiraterone acetate-treated prostate cancer patients

Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20-40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance. Experimental Design: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients. Results: Thirty cytosines showed significant modification differences (FDR q < 0.05) between the AA-sensitive and AA-resistant patients during the treatment, of which 21 cytosines were differentially modified prior to treatment. In addition, the AA-sensitive patients, but not AA-resistant patients, lost inter-individual variation of cfDNA modification shortly after starting AA-treatment, but such variation returned to initial levels in the later phases of treatment. Conclusions: Our findings provide a list of potential biomarkers for prediction of AA-treatment response, highlight the prognostic value of using cytosine modification variance as biomarkers, and shed new insights into the mechanisms of prostate cancer relapse in AA-sensitive patients.



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Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers.

Purpose: To define the genetic landscape of advanced differentiated and anaplastic thyroid cancer and identify genetic alterations of potential diagnostic, prognostic and therapeutic significance. Experimental design: The genetic profiles of 583 advanced differentiated and 196 anaplastic thyroid cancers (ATC) generated with targeted next-generation sequencing cancer-associated gene panels MSK-IMPACT and FoundationOne were analyzed. Results: ATC had more genetic alterations per tumor, and pediatric papillary thyroid cancer had fewer genetic alterations per tumor when compared to other thyroid cancer types. DNA mismatch repair deficit and activity of APOBEC cytidine deaminases were identified as mechanisms associated with high mutational burden in a subset of differentiated and anaplastic thyroid cancers. Copy number losses and mutations of CDKN2A and CDKN2B, amplification of CCNE1, amplification of receptor tyrosine kinase genes KDR, KIT and PDGFRA, amplification of immune evasion genes CD274, PDCD1LG2 and JAK2 and activating point mutations in small GTPase RAC1 were associated with ATC. An association of KDR, KIT and PDGFRA amplification with the sensitivity of thyroid cancer cells to lenvatinib was shown in vitro. Three genetically distinct types of ATC are proposed. Conclusions: This large-scale analysis describes genetic alterations in a cohort of thyroid cancers enriched in advanced cases. Many novel genetic events previously not seen in thyroid cancer were found. Genetic alterations associated with anaplastic transformation were identified. An updated schematic of thyroid cancer genetic evolution is proposed.



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ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and claudin-1 through a ZEB1-Dependent Transcriptional Mechanism.

Purpose: ZIP4 is overexpressed in human pancreatic cancer and promotes tumor growth. However, little is known about the role of ZIP4 in advanced stages of this dismal neoplasm. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by ZIP4 modulating pancreatic tumor metastasis. Experimental Design: The expression of ZIP4, ZO-1, claudin-1, and ZEB1 in human pancreatic cancer tissues, genetically engineered mouse model, xenograft tumor model and pancreatic cancer cell lines were examined, and the correlations between ZIP4 and those markers were also analyzed. Functional analysis of ZO-1, claudin-1, and ZEB1 was investigated in pancreatic cancer cell lines and orthotopic xenografts. Results: Genetic inactivation of ZIP4 inhibited migration and invasion in pancreatic cancer, and increased the expression of ZO-1 and claudin-1. Conversely, overexpression of ZIP4 promoted migration and invasion, and increased the expression of ZEB1 and downregulation of the aforementioned epithelial genes. ZIP4 downregulation of ZO-1 and claudin-1 requires the transcriptional repressor ZEB1. Further analysis demonstrated that ZIP4-mediated repression of ZO-1 and claudin-1 lead to upregulation of their targets FAK and Paxillin. Silencing of ZIP4 caused reduced phosphorylation of FAK and Paxillin, which was rescued by simultaneous blocking of ZO-1 or claudin-1. Clinically, we demonstrated that ZIP4 positively correlates with the levels of ZEB1 and inversely associates with the expression of ZO-1 and claudin-1. Conclusions: These findings suggest a novel pathway activated by ZIP4 controlling pancreatic cancer invasiveness and metastasis, which could serve as a new therapeutic target for this devastating disease.



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Mechanistic insights of an immunological adverse event induced by an anti-KIT antibody drug conjugate and mitigation strategies

Purpose: Hypersensitivity reactions (HSR) were observed in three patients dosed in a phase I clinical trial treated with LOP628, a KIT targeted antibody drug conjugate. Mast cell degranulation was implicated as the root cause for the HSR. Underlying mechanism of this reported HSR was investigated with an aim to identifying potential mitigation strategies. Experimental Design: Biomarkers for mast cell degranulation were evaluated in patient samples and in human peripheral blood cell-derived mast cell (PBC-MC) cultures treated with LOP628. Mitigation strategies interrogated include pretreatment of mast cells with small molecule inhibitors that target KIT or signaling pathways downstream of FcR1, FcR, and treatment with Fc silencing antibody formats. Results: Transient elevation of serum tryptase was observed in patients one hour post-treatment of LOP628. In agreement with the clinical observation, LOP628 and its parental antibody LMJ729 induced degranulation of human PBC-MCs. Unexpectedly, KIT small molecule inhibitors did not abrogate mast cell degranulation. By contrast, small molecule inhibitors that targeted pathways downstream of Fc receptors blunted degranulation. Furthermore, interference of the KIT antibody to engage Fc receptors by pre-incubation with IgG or using engineered Fc silencing mutations reduced or prevented degranulation.  Characterization of Fcg receptors revealed human PBC-MCs expressed both FcRII and low levels of FcRI. Interestingly, increasing the level of FcRI upon addition of IFN, significantly enhanced LOP628-mediated mast cell degranulation. Conclusions: Our data suggests LOP628-mediated mast cell degranulation is the likely cause of HSR observed in the clinic due to co-engagement of the FcR and KIT, resulting in mast cell activation.



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Mutation profiling of key cancer genes in primary breast cancers and their distant metastases

Although the repertoire of somatic genetic alterations of primary breast cancers has been extensively catalogued, the genetic differences between primary and metastatic tumors have been less studied. In this study, we compared somatic mutations and gene copy number alterations of primary breast cancers and their matched metastases from patients with estrogen receptor (ER)-negative disease, with higher incidence of brain metastases than ER-positive/HER2-negative cancers. DNA samples obtained from formalin-fixed paraffin-embedded ER-negative/HER2-positive (n=9) and ER-, progesterone receptor (PR-), HER2-negative (n=8) primary breast cancers and from paired brain or skin metastases and normal tissue were subjected to a hybridization capture-based massively parallel sequencing assay, targeting 341 key cancer genes. A large subset of non-synonymous somatic mutations (45%) and gene copy number alterations (55%) were shared between the primary tumors and paired metastases. However, mutations restricted to either a given primary tumor or its metastasis, the acquisition of loss of heterozygosity of the wild-type allele and clonal shifts of genes affected by somatic mutations such as TP53 and RB1 were observed in the progression from primary tumors to metastases. No metastasis location-specific alterations were identified, but synchronous metastases showed higher concordance with the paired primary tumor than metachronous metastases. Novel potentially targetable alterations were found in the metastases relative to their matched primary tumors. These data indicate that repertoires of somatic genetic alterations in ER-negative metastatic breast cancers may differ from those of their primary tumors, even by the presence of driver and targetable somatic genetic alterations.

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Adoptive immunotherapy using PRAME-specific T cells in medulloblastoma

Medulloblastoma is the most frequent malignant childhood brain tumor with a high morbidity. Identification of new therapeutic targets would be instrumental in improving patient outcomes. We evaluated the expression of the tumor-associated antigen PRAME in biopsies from 60 medulloblastoma patients. PRAME expression was detectable in 82% of tissues independent of molecular and histopathologic subgroups. High PRAME expression also correlated with worse overall survival. We next investigated the relevance of PRAME as a target for immunotherapy. Medulloblastoma cells were targeted using genetically modified T cells with a PRAME-specific TCR (SLL TCR T cells). SLL TCR T cells efficiently killed medulloblastoma HLA-A*02+ DAOY cells as well as primary HLA-A*02+ medulloblastoma cells. Moreover, SLL TCR T cells controlled tumor growth in an orthotopic mouse model of medulloblastoma. To prevent unexpected T cell-related toxicity,an inducible caspase 9 (iC9) gene was introduced in frame with the SLL TCR; this safety switch triggered prompt elimination of genetically-modified T cells. Altogether, these data indicate that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating HLA-A*02+ medulloblastoma patients.

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Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice

Journal of Anatomy, EarlyView.


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The effect of speech-language pathology students on clinician time use and activity

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MNE Scan: Software for Real-Time Processing of Electrophysiological Data

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Publication date: Available online 3 April 2018
Source:Journal of Neuroscience Methods
Author(s): Lorenz Esch, Limin Sun, Viktor Klüber, Seok Lew, Daniel Baumgarten, P. Ellen Grant, Yoshio Okada, Jens Haueisen, Matti S Hämäläinen, Christoph Dinh
BackgroundMagnetoencephalography (MEG) and Electroencephalography (EEG) are noninvasive techniques to study the electrophysiological activity of the human brain. Thus, they are well suited for real-time monitoring and analysis of neuronal activity. Real-time MEG/EEG data processing allows adjustment of the stimuli to the subject's responses for optimizing the acquired information especially by providing dynamically changing displays to enable neurofeedback.New MethodWe introduce MNE Scan, an acquisition and real-time analysis software based on the multipurpose software library MNE-CPP. MNE Scan allows the development and application of acquisition and novel real-time processing methods in both research and clinical studies. The MNE Scan development follows a strict software engineering process to enable approvals required for clinical software.ResultsWe tested the performance of MNE Scan in several device-independent use cases, including, a clinical epilepsy study, real-time source estimation, and Brain Computer Interface (BCI) application.Comparison with Existing Method(s)Compared to existing tools we propose a modular software considering clinical software requirements expected by certification authorities. At the same time the software is extendable and freely accessible.ConclusionWe conclude that MNE Scan is the first step in creating a device-independent open-source software to facilitate the transition from basic neuroscience research to both applied sciences and clinical applications.



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The rolling stones: an inappropriate surrogate for upper-abdominal image-guided radiotherapy

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Publication date: Available online 3 April 2018
Source:Practical Radiation Oncology
Author(s): Jasmine Chen, Louise Murray, Laura A. Dawson, Michael Velec




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Radiation retinopathy after external-beam irradiation for nasopharyngeal carcinoma: a case report and review of the literature.

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Publication date: Available online 3 April 2018
Source:Practical Radiation Oncology
Author(s): Pritam Bawankar, Manabjyoti Barman, Harsha Bhattacharjee, Ronel Soibam, Vivek Paulbuddhe




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Improving detection of patient deterioration in the general hospital ward environment

imagePatient monitoring on low acuity general hospital wards is currently based largely on intermittent observations and measurements of simple variables, such as blood pressure and temperature, by nursing staff. Often several hours can pass between such measurements and patient deterioration can go unnoticed. Moreover, the integration and interpretation of the information gleaned through these measurements remains highly dependent on clinical judgement. More intensive monitoring, which is commonly used in peri-operative and intensive care settings, is more likely to lead to the early identification of patients who are developing complications than is intermittent monitoring. Early identification can trigger appropriate management, thereby reducing the need for higher acuity care, reducing hospital lengths of stay and admission costs and even, at times, improving survival. However, this degree of monitoring has thus far been considered largely inappropriate for general hospital ward settings due to device costs and the need for staff expertise in data interpretation. In this review, we discuss some developing options to improve patient monitoring and thus detection of deterioration in low acuity general hospital wards.

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Free pre-operative clear fluids before day-surgery?: Challenging the dogma

No abstract available

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Reply to: what is more important, cost or effectiveness?

No abstract available

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Postoperative nausea and vomiting after unrestricted clear fluids before day surgery: A retrospective analysis

imageBACKGROUND Guidance on pre-operative fluids fasting policy continues to evolve. Current European guidelines encourage the intake of oral fluids up to 2 h before the induction of general anaesthesia. From October 2014, Torbay Hospital Day Surgery Unit commenced an unrestricted fluid policy, encouraging patients to drink clear fluids up until the time of transfer to theatre. OBJECTIVE The aim of this study was to assess the incidence of postoperative nausea and vomiting before and after the change to the unrestricted pre-operative clear oral fluids. DESIGN Retrospective, before and after study. SETTING Single district general hospital between November 2013 and February 2016. PATIENTS A total of 11 500 patients on the day case pathway who were receiving either sedation, general anaesthesia, regional anaesthesia or their combination. The data from these patients were collected routinely. This number of patients represents approximately 78% of all patients before the change in fluids policy and 74% after the change. Exclusions were patients undergoing a termination of pregnancy, or patients undergoing community dental procedures, from whom patient experience data are not collected. INTERVENTION Introduction of a change to the day surgery pathway policy permitting unrestricted clear oral fluids preoperatively until transfer to theatre (from October 2014). MAIN OUTCOME MEASURES Incidence of postoperative nausea and vomiting. RESULTS The rates of nausea within 24 h postoperatively were 270/5192 (5.2%) when patients could not drink within 2 h of surgery, and 179/4724 (3.8%) when patients could drink up until surgery, a relative rate (95% confidence interval) of 0.73 (0.61 to 0.88), P = 0.00074. The corresponding rates of vomiting were 146/5186 (2.8%) and 104/4716 (2.2%), a relative rate (95% confidence interval) of 0.78 (0.61 to 1.00), P = 0.053. CONCLUSION Our data suggest that the liberal consumption of clear fluids before the induction of scheduled day case anaesthesia reduced the rates of postoperative nausea and vomiting.

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Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial

imageBACKGROUND Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. OBJECTIVE The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. DESIGN A randomised, double-blind controlled trial. SETTING Single-centre, KK Women's and Children's Hospital, Singapore. PATIENTS Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. MAIN OUTCOME MEASURES The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. RESULTS The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P 

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Intra-operative lidocaine in the prevention of vomiting after elective tonsillectomy in children: A randomised controlled trial

imageBACKGROUND Postoperative vomiting (POV) is a frequent complication of tonsillectomy in children. In adult patients undergoing abdominal surgeries, the use of intravenous lidocaine infusion can prevent POV. OBJECTIVE To evaluate the anti-emetic effect of an intravenous lidocaine infusion used as an adjuvant to general anaesthesia, in children undergoing elective ear, nose and throat surgery. DESIGN Double-blind, randomised, controlled study. SETTING Hospital-based, single-centre study in Chile. PATIENTS ASA I-II children, aged 2 to 12 years, scheduled for elective tonsillectomy. INTERVENTION We standardised the induction and maintenance of anaesthesia. Patients were randomly allocated to lidocaine (1.5 mg kg−1 intravenous lidocaine over 5 min followed by 2 mg kg−1 h−1) or 0.9% saline (at the same rate and volume). Infusions were continued until the end of the surgery. MAIN OUTCOME MEASURES Presence of at least one episode of vomiting, retching or both in the first 24 h postoperatively (POV). SECONDARY OUTCOMES Plasma concentrations of lidocaine and postoperative pain. RESULTS Ninety-two children were enrolled. Primary outcome data were available for 91. In the Lidocaine group, 28 of 46 patients (60.8%) experienced POV, compared with 37 of 45 patients (82.2%) in the Saline group [difference in proportions 21.3% (95% confidence interval (CI) 2.8 to 38.8), P = 0.024]. The intention-to-treat analysis showed that when we assumed that the patient in the Saline group lost to follow-up did not have POV, the difference in proportions decreased to 19.6% (95% CI, 0.9 to 37.2), with an unadjusted odds ratio of 0.38 (95% CI, 0.15 to 0.97, P = 0.044). The odds of having POV were 62% less likely in those patients receiving lidocaine compared with patients in the Saline group. The mean lidocaine plasma concentration was 3.91 μg ml−1 (range: 0.87 to 4.88). CONCLUSION Using an intravenous lidocaine infusion as an adjuvant to general anaesthesia decreased POV in children undergoing elective tonsillectomy. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01986309.

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The trapezius plane block: a technique for regional anaesthesia of the superficial posterior thorax

imageNo abstract available

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Oesophageal or transgastric views for estimating mean pulmonary artery pressure with transoesophageal echocardiography: A prospective observational study

imageBACKGROUND Recent data suggest that in cardiac surgical patients, the pulmonary artery acceleration time (PAT) is useful for estimating mean pulmonary artery pressure (MPAP) noninvasively with transoesophageal echocardiography (TOE). The pulmonary valve can be visualised from multiple echocardiographic windows, but it is unclear which, if any, view correlates best with MPAP. OBJECTIVE(S) To compare the PAT measured with TOE from oesophageal and transgastric views with MPAP obtained invasively with a pulmonary artery catheter. DESIGN A prospective observational study. SETTING St. Vincent's Hospital, Melbourne, a university tertiary referral centre in Australia. PATIENTS Sixty-three patients having cardiac surgery were included in our study. All patients had insertion of both a TOE probe and pulmonary artery catheter; this is the routine standard of care in our centre. INTERVENTION(S) Nil. MAIN OUTCOME MEASURES During a period of haemodynamic stability, the PAT was measured first from an oesophageal view and then immediately after from a transgastric view. The results were then compared with the invasively measured MPAP. RESULTS Simultaneous measurements of MPAP and PAT were taken in 63 patients. In two patients, these measurements were not possible in the transgastric position due to an inability to visualise the right ventricular outflow tract and pulmonary valve. A Bland–Altman analysis of the PAT measured from the upper oesophageal and transgastric views showed a mean difference of 1 ms and limits of agreement of −18 to 16 ms. The area under the receiver operating curves for predicting pulmonary hypertension with PAT were upper oesophageal view 0.99 [95% confidence interval (CI), 0.98 to 1.00] and transgastric view 0.99 (95% CI, 0.97 to 1.00). The agreement between the results from these two views in the diagnosis of pulmonary hypertension (defined as PAT  25 mmHg) with a sensitivity of 94.7% and specificity of 97.6%. The transgastric view predicted pulmonary hypertension with a sensitivity of 89.4% and specificity of 95.2%. CONCLUSION Oesophageal and transgastric measurements of PAT have close agreement and a similar high ability to discriminate between people with and without pulmonary hypertension. The transgastric measurement was unobtainable in a small percentage of patients and required more probe manipulation. We would recommend PAT measurement in the upper oesophageal view.

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Ultrasound examination of the antrum to predict gastric content volume in the third trimester of pregnancy as assessed by MRI: A prospective cohort study

imageBACKGROUND Ultrasound examination of the gastric antrum allows reliable pre-operative assessment of gastric contents and volume in adult patients. However, during pregnancy, the change in the anatomical position of the stomach due to the gravid uterus leads to a change in the measured value of the antral area. Therefore, current mathematical models predicting gastric content volume (GCV) in the adult may not apply in term pregnant women. OBJECTIVE To propose a mathematical model which is predictive of GCV in pregnant women and to assess the performance of an ultrasound qualitative grading scale (0 to 2) for the diagnosis of clear fluid volumes more than 0.8 and 1.5 ml kg−1. DESIGN Prospective cohort study. SETTING Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Lyon and Assistance Publique – Hôpitaux de Marseille, Hôpital Nord, Marseille, France. PATIENTS Pregnant women in the third trimester of pregnancy. MAIN OUTCOME MEASURES Comparison of the GCV as measured by MRI and the ultrasound measured antral cross-sectional area, and an assessment of gastric contents according to a 0 to 2 qualitative grading scale. RESULTS Data from 34 women were analysed. A linear model predictive of GCV was constructed with a 95% agreement band of ±95 ml, with a mean polar angle of −8.7°. Performance of the qualitative grading scale to detect fluid volumes >0.8 and >1.5 ml kg−1 was improved when used in a composite scale including a 505 mm2 antral area cut-off value in the semirecumbent supine position. CONCLUSION We report a new mathematical model predictive of GCV in women in the third trimester of pregnancy. Furthermore, the combination of the qualitative and the quantitative ultrasound examination of the gastric antrum might be useful to assess gastric fluid volume in pregnant women. TRIAL REGISTRATION ANSM Register N°2015-A00800-49

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Microvascular reactivity, assessed by near-infrared spectroscopy and a vascular occlusion test, is associated with patient outcomes following cardiac surgery: A prospective observational study

imageBACKGROUND Microvascular dysfunction in patients admitted to the ICU following cardiac surgery may be related to perioperative complications and increased resource utilisation even in the presence of acceptable systemic haemodynamic variables. OBJECTIVES To assess the relationship between microvascular impairment using peripheral near-infrared spectroscopy at ICU admission and 6 h postadmission and the duration of mechanical ventilatory support, length of stay in ICU and in hospital. DESIGN Prospective, observational cohort study. SETTING Single-centre, tertiary-level cardiac ICU. PATIENTS Sixty-nine adult patients following elective cardiac surgery excluding patients with on-going extracorporeal support or in whom tissue haemoglobin oxygen saturation (StO2) measurements were not feasible. MAIN OUTCOME MEASURES Thenar and forearm StO2 in response to a vascular occlusion test to calculate desaturation and reperfusion slopes. A logistic regression model was used to ascertain the associations between StO2, desaturation and reperfusion slopes as well as cardiac index, mean arterial pressure, arterial lactate concentrations and prolonged (≥75th percentile) duration of mechanical ventilation, ICU length of stay and hospital length of stay. RESULTS A reduced reperfusion slope at ICU admission was associated independently with prolonged mechanical ventilation at thenar (OR 0.08; 95% CI [0.02 to 0.47], P = 0.003) and forearm [OR 0.2 (0.04 to 0.59), P = 0.006] sites. Similarly, a reduced Rres was associated with prolonged ICU LOS at both thenar [OR 0.3 (0.13 to 0.77), P = 0.007] and forearm [OR 0.2 (0.05 to 0.62), P = 0.007] sites at ICU0 h, as well as ICU6 h [OR 0.2 (0.05 to 0.66), P = 0.004 and OR 0.05 (0.008 to 0.34), P = 0.002]. An increased Rdes was associated with prolonged hospital LOS at the thenar eminence at ICU0 h [OR 1.9 (1.4 to 2.3), P = 0.004] and ICU6 h [OR 6.7 (2.0 to 23), P = 0.002] as well as the forearm at ICU0 h [OR 1.5 (1.3 to 1.9), P = 0.004] and ICU6 h [OR 1.6 (1.3 to 2.1), P = 0.004]. CONCLUSION In the early postoperative period following cardiac surgery, changes in thenar and forearm tissue oxygenation variables are associated with patient resource utilisation outcomes.

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What is more important, cost or effectiveness?

No abstract available

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Prediction of bilateral cerebral oxygen desaturations from a single sensor in adult cardiac surgery: A prospective observational study

imageBACKGROUND Monitoring regional cerebral oxygen saturation (rcSO2) with near-infrared spectroscopy is increasingly being performed in patients scheduled for cardiac surgery. It is sometimes difficult to monitor both frontal lobes due to anatomical or space compromises. However, it remains unclear whether the use of only one lateral or medial probe can provide adequate bilateral monitoring. OBJECTIVE To evaluate the efficacy of using a single lateral or medial probe to detect substantial desaturations on both sides. DESIGN A prospective observational study. SETTING Tertiary university teaching hospital. PATIENTS Seventeen adult patients undergoing elective cardiac surgery monitored with three near-infrared spectroscopy probes (two lateral and one medial) using an INVOS 5100C monitor. INTERVENTIONS The value of rcSO2 was recorded up to 19 times during each procedure. Substantial desaturation was defined as an absolute rcSO2 value of 50% or less or a decrease of more than 20% compared with baseline values on spontaneous ventilation with 21% oxygen. MAIN OUTCOME MEASURES The level of agreement between the three pairs of probes using the Bland–Altman method for repeated measures, and the grade of concordant and discordant results between the three pairs of probes by means of contingency tables and the κ coefficient. RESULTS We obtained 244 records per probe. Greater agreement was observed between the two lateral probes (mean ± SD of the differences between recordings was -0.9 ± 5.5); mean difference between left and medial, and right and medial probes was 2.4 ± 7.3 and 3.3 ± 6.7, respectively. The rate of discordant results between the two lateral probes was 5.7%, κ coefficient of 0.6 with 95% confidence interval (95% CI 0.4 to 0.8), and between the left and medial, and right and medial of 8.2 and 7.4%, with κ coefficients of 0.57 (95% CI 0.38 to 0.76) and 0.5 (95% CI 0.29 to 0.71), respectively. CONCLUSION In cardiac surgery patients in whom there is difficulty in accommodating two rcSO2 probes, a single lateral probe can effectively measure bilateral rcSO2 in specific scenarios.

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Intubation with cervical spine immobilisation: a comparison between the KingVision videolaryngoscope and the Macintosh laryngoscopeA randomised controlled trial

No abstract available

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Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: A randomised double-blinded trial

imageBACKGROUND During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN A randomised, double-blind, controlled study. SETTING Single University Hospital. PATIENTS Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 μg kg−1 over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 μg kg−1 h−1 dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION Administration of dexmedetomidine in doses 0.4 and 0.6 μg kg−1 h−1 was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org).

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Economic evaluation of bilateral sternal local anaesthetic infusions via multi-hole catheters after cardiac surgery

imageNo abstract available

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Insomnia symptoms and sleep duration and their combined effects in relation to associations with obesity and central obesity

Previous studies have shown that both sleep duration and insomnia have an impact on obesity and central obesity. However, studies of the joint effects of these sleep disorders are still sparse.

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A Computerized Tomography Study of Vocal Tract Setting in Hyperfunctional Dysphonia and in Belting

Vocal tract setting in hyperfunctional patients is characterized by a high larynx and narrowing of the epilaryngeal and pharyngeal region. Similar observations have been made for various singing styles, eg, belting. The voice quality in belting has been described to be loud, speech like, and high pitched. It is also often described as sounding "pressed" or "tense". The above mentioned has led to the hypothesis that belting may be strenuous to the vocal folds. However, singers and teachers of belting do not regard belting as particularly strenuous.

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Financial outcomes of transoral robotic surgery: A narrative review

To determine the current cost impact and financial outcomes of transoral robotic surgery in Otolaryngology.

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The Cochleural Alternating Acoustic Beam Therapy (CAABT): A pre-clinical trial

We intend to assess the effectiveness of a novel tinnitus treatment therapy, the Cochleural Alternating Acoustic Beam Therapy (CAABT) using the psychoacoustic measures, the questionnaires and rs-fMRI.

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A Computerized Tomography Study of Vocal Tract Setting in Hyperfunctional Dysphonia and in Belting

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Publication date: Available online 3 April 2018
Source:Journal of Voice
Author(s): Marcelo Saldias, Marco Guzman, Gonzalo Miranda, Anne-Maria Laukkanen
BackgroundVocal tract setting in hyperfunctional patients is characterized by a high larynx and narrowing of the epilaryngeal and pharyngeal region. Similar observations have been made for various singing styles, eg, belting. The voice quality in belting has been described to be loud, speech like, and high pitched. It is also often described as sounding "pressed" or "tense". The above mentioned has led to the hypothesis that belting may be strenuous to the vocal folds. However, singers and teachers of belting do not regard belting as particularly strenuous.PurposeThis study investigates possible similarities and differences between hyperfunctional voice production and belting. This study concerns vocal tract setting.MethodsFour male patients with hyperfunctional dysphonia and one male contemporary commercial music singer were registered with computerized tomography while phonating on [a:] in their habitual speaking pitch. Additionally, the singer used the pitch G4 in belting. The scannings were studied in sagittal and transversal dimensions by measuring lengths, widths, and areas.ResultsVarious similarities were found between belting and hyperfunction: high vertical larynx position, small hypopharyngeal width, and epilaryngeal outlet. On the other hand, belting differed from dysphonia (in addition to higher pitch) by a wider lip and jaw opening, and larger volumes of the oral cavity.ConclusionsBelting takes advantage of "megaphone shape" of the vocal tract. Future studies should focus on modeling and simulation to address sound energy transfer. Also, they should consider aerodynamic variables and vocal fold vibration to evaluate the "price of decibels" in these phonation types.



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Bicycle helmets are protective against facial injuries, including facial fractures: a meta-analysis

Publication date: Available online 3 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): D.G. Fitzpatrick, M. Goh, D.C. Howlett, M. Williams
Cycling is a popular activity. However there are risks associated with cycling, including facial injury. Helmets are often worn to prevent head injury. Evidence for their protection against facial injury is limited. This meta-analysis investigated the effect of bicycle helmets on the incidence of facial injury. The PubMed/MEDLINE, Google Scholar, and Cochrane Library databases were searched. Studies included were observational and involved adult participants. Paediatric studies, studies on helmet legislation, and those combining facial injuries with other injury types were excluded. The studies were evaluated by two reviewers. Risk of bias was assessed using the RevMan bias assessment tool. Odds ratios (OR) were extracted for facial injuries and facial fractures. Two meta-analyses were performed using these categories. Nine of the 102 studies identified were included. Helmets were protective against facial injury (OR 0.69, 95% confidence interval 0.63–0.75, P<0.0001). Five studies reported facial fracture rates; helmets were protective against these also (OR 0.79 95% confidence interval 0.70–0.90, P=0.0003). There are no randomized controlled trials on this topic and the number of studies available is small. Bicycle helmets offer protection against facial injuries and this should be considered by cyclists when deciding whether or not to use one.



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Clefts of the lip and palate: is the Internet a trustworthy source of information for patients?

Publication date: Available online 3 April 2018
Source:International Journal of Oral and Maxillofacial Surgery
Author(s): G.A. Karamitros, N.A. Kitsos
Great numbers of patients use the Internet to obtain information and familiarize themselves with medical conditions. However, the quality of Internet-based information on clefts of the lip and palate has not yet been examined. The goal of this study was to assess the quality of Internet-based patient information on orofacial clefts. Websites were evaluated based on the modified Ensuring Quality Information for Patients (EQIP) instrument (36 items). Three hundred websites were identified using the most popular search engines. Of these, 146 were assessed after the exclusion of duplicates, irrelevant sites, and web pages in languages other than English. Thirty-four (23.2%) web pages, designed mostly by academic centres and hospitals, covered more than 22 items and were classified as high-score websites. The EQIP score achieved by websites ranged between 4 and 30, out of a total possible 36 points; the median score was 19 points. The top five high-scoring web pages are highlighted. The overall quality of Internet-based patient information on orofacial clefts is low. Also, the majority of web pages created by medical practitioners have a marketing perspective and in order to attract more patients/customers avoid mentioning the risks of the reconstructive procedures needed.



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UW global oral health symposium set for July 31

Registration has opened for a University of Washington international symposium on global oral health scheduled for July 31.

The post UW global oral health symposium set for July 31 appeared first on UW School of Dentistry.



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Endocytoscopy for in situ real-time histology of oral mucosal lesions

This study investigated the utility of endocytoscopy, a novel emerging endoscopic system, for in situ real-time histology of oral mucosal lesions. Endocytoscopy involves the use of a contact light microscopy system with 380-fold magnification. With the development of endoscopic instruments, it has become possible to observe the abnormal microvascular and capillary patterns of tumour cells. The resolution of the endoscopic image is improved in situ, and a more detailed diagnosis is possible. In this study, endocytoscopy along with other diagnostic modalities was used in nine patients.

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Septal anchoring suture: a key suture to improve the nasolabial symmetry in unilateral cheiloplasty

Since 2008, a septal anchoring suture has been used in unilateral cleft lip repair at Chang Gung Memorial Hospital in order to stabilize the lateral lip centrally. This study compared the symmetry of two groups of patients: those treated with and without an anchoring suture. Multiple standardized direct and photographic facial measurements were performed on the faces of all patients pre-cheiloplasty and at 5 years post-cheiloplasty. The degree of nasolabial symmetry was evaluated by comparing the ratios of measurements of the cleft vs.

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The Cochleural Alternating Acoustic Beam Therapy (CAABT): A pre-clinical trial

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Publication date: Available online 3 April 2018
Source:American Journal of Otolaryngology
Author(s): Chunli Liu, Han Lv, Tao Jiang, Jing Xie, Lu He, Guopeng Wang, Jiao Liu, Zhenchang Wang, Shusheng Gong
PurposeWe intend to assess the effectiveness of a novel tinnitus treatment therapy, the Cochleural Alternating Acoustic Beam Therapy (CAABT) using the psychoacoustic measures, the questionnaires and rs-fMRI.Materials and methodsIn this study, we enrolled 11 older than 18 years old Chinese patients with normal hearing who had unilateral, chronic (longer than 6 months), sensorineural tinnitus, of frequencies between 125–8000 Hz, and an average loudness of 31 dB. The patients underwent the treatment with the CAABT method for 12 weeks and the outcomes were evaluated with tinnitus questionnaire scores, a set of psychoacoustic measures, and rs-fMRI testing before treatment and at 3 months. This was an earlier study of the controlled randomized clinical trial which was registered with ClinicalTrials.gov, number NCT02774122.ResultsAlmost all the patients reported reduced tinnitus annoyance after the three-month treatment. The THI and VAS scores showed decreased tinnitus severity. The rs-fMRI results indicated that the right middle frontal gyrus and the right superior temporal gyrus displayed noticeable decreases of the ReHo values for the subjects between the before and after treatment, supporting the clinical evidence of significant tinnitus reduction.ConclusionThe therapy seemed effective in patients of varying severities, and no side effects were observed in this trial. The CAABT can be an alternative for those who are suitable for sound therapy once a large scale of and better controlled clinical studies have validated the findings of this experiment.



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Financial outcomes of transoral robotic surgery: A narrative review

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Publication date: Available online 3 April 2018
Source:American Journal of Otolaryngology
Author(s): Sammy Othman, Brian J. McKinnon
ObjectiveTo determine the current cost impact and financial outcomes of transoral robotic surgery in Otolaryngology.Data sourcesA narrative review of the literature with a defined search strategy using Pubmed, MEDLINE, CINAHL, and Web of Science.Review methodsUsing keywords ENT or otolaryngology, cost or economic, transoral robotic surgery or TORs, searches were performed in Pubmed, MEDLINE, CINAHL, and Web of Science and reviewed by the authors for inclusion and analysis.ResultsSix total papers were deemed appropriate for analysis. All addressed cost impact of transoral robotic surgery (TORs) as compared to open surgical methods in treating oropharyngeal cancer and/or the identification of the primary tumor within unknown primary squamous cell carcinoma. Results showed TORs to be cost-effective.ConclusionTransoral robotic surgery is currently largely cost effective for both treatment and diagnostic procedures. However, further studies are needed to qualify long-term data.



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Does hearing in response to soft-tissue stimulation involve skull vibrations? A within-subject comparison between skull vibration magnitudes and hearing thresholds

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Publication date: Available online 3 April 2018
Source:Hearing Research
Author(s): Shai Chordekar, Ronen Perez, Cahtia Adelman, Haim Sohmer, Liat Kishon-Rabin
Hearing can be elicited in response to bone as well as soft-tissue stimulation. However, the underlying mechanism of soft-tissue stimulation is under debate. It has been hypothesized that if skull vibrations were the underlying mechanism of hearing in response to soft-tissue stimulation, then skull vibrations would be associated with hearing thresholds. However, if skull vibrations were not associated with hearing thresholds, an alternative mechanism is involved. In the present study, both skull vibrations and hearing thresholds were assessed in the same participants in response to bone (mastoid) and soft-tissue (neck) stimulation. The experimental group included five hearing-impaired adults in whom a bone-anchored hearing aid was implanted due to conductive or mixed hearing loss. Because the implant is exposed above the skin and has become an integral part of the temporal bone, vibration of the implant represented skull vibrations. To ensure that middle-ear pathologies of the experimental group did not affect overall results, hearing thresholds were also obtained in 10 participants with normal hearing in response to stimulation at the same sites. We found that the magnitude of the bone vibrations initiated by the stimulation at the two sites (neck and mastoid) detected by the laser Doppler vibrometer on the bone-anchored implant were linearly related to stimulus intensity. It was therefore possible to extrapolate the vibration magnitudes at low-intensity stimulation, where poor signal-to-noise ratio limited actual recordings. It was found that the vibration magnitude differences (between soft-tissue and bone stimulation) were not different then the hearing threshold differences at the tested frequencies. Results of the present study suggest that bone vibration magnitude differences can adequately explain hearing threshold differences and are likely to be responsible for the hearing sensation. Thus, the present results support the idea that bone and soft-tissue conduction could share the same underlying mechanism, namely the induction of bone vibrations. Studies with the present methodology should be continued in future work in order to obtain further insight into the underlying mechanism of activation of the hearing system.



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Vestibular and balance function is often impaired in children with profound unilateral sensorineural hearing loss

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Publication date: Available online 3 April 2018
Source:Hearing Research
Author(s): Meirav Sokolov, Karen A. Gordon, Melissa Polonenko, Susan I. Blaser, Blake C. Papsin, Sharon L. Cushing
RationaleChildren with unilateral deafness could have concurrent vestibular dysfunction which would be associated with balance deficits and potentially impair overall development. The prevalence of vestibular and balance deficits remains to be defined in these children.MethodsTwenty children with unilateral deafness underwent comprehensive vestibular and balance evaluation.ResultsRetrospective review revealed that more than half of the cohort demonstrated some abnormality of the vestibular end organs (otoliths and horizontal canal), with the prevalence of end organ specific dysfunction ranging from 17 to 48% depending on organ tested and method used. In most children, impairment occurred only on the deaf side. Children with unilateral deafness also displayed significantly poorer balance function than their normal hearing peers.ConclusionsThe prevalence of vestibular dysfunction in children with unilateral deafness is high and similar to that of children with bilateral deafness. Vestibular and balance evaluation should be routine and the functional impact of combined vestibulo-cochlear sensory deficits considered.



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