Κυριακή 1 Απριλίου 2018

Evaluation of superior concha bullosa by computed tomography.

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Evaluation of superior concha bullosa by computed tomography.

Surg Radiol Anat. 2018 Mar 30;:

Authors: İla K, Yilmaz N, Öner S, Başaran E, Öner Z

Abstract
OBJECTIVE: Concha bullosa is generally regarded as pneumatisation of the middle turbinate in the nose. However, pneumatisation may also be seen in the superior and inferior turbinate. Computed tomography (CT) of paranasal sinuses is extremely helpful for the examination of this inaccessible area. Coronal CT sections of paranasal sinuses are particularly useful for surgical anatomy, as these images show nearly the same regions as the endoscopic examinations. The aim of this retrospective study was to evaluate the presence, incidence and unilaterality-bilaterality of superior turbinate pneumatisation and concomitant nasal pathologies.
METHODS: A total of 1000 patients who underwent CT of the paranasal sinuses because of headaches, nasal obstructions, anosmia, facial pain or facial trauma were evaluated retrospectively.
RESULTS: Among the 1000 patients, superior pneumatized turbinate was seen on CT images of the paranasal sinuses in 149 (14.9%) cases. Of these patients, 84 were female, 65 were male, and the mean age was 38.14 years. Among 149 patients, 58 patients had bilateral superior pneumatized turbinate and the remaining 91 patients had unilateral superior pneumatized turbinate. 60.4% of the patients with superior pneumatized turbinate also had middle pneumatized turbinate.
CONCLUSION: The superior pneumatized turbinate is an anatomical variation with an incidence ranging from 12.2 to 50%. The present study revealed that there is no relationship between volume size of the superior pneumatized turbinates and sinusitis, nasal septum deviation and paradoxical middle concha. It is very important to define anatomical variations in the preoperative CT evaluation of the paranasal sinuses.

PMID: 29602963 [PubMed - as supplied by publisher]



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Preoperative radiologic patent blue localization for intracorporeal laparoscopic resection of a terminal ileal submucosal lipoma: A case report.

Preoperative radiologic patent blue localization for intracorporeal laparoscopic resection of a terminal ileal submucosal lipoma: A case report.

Int J Surg Case Rep. 2018 Mar 15;45:91-95

Authors: Wu HY, Huang SF, Pan KT, Yu MC

Abstract
BACKGROUND: Ileal submucosal lipomas are rare cases and surgical intervention was necessary in case of abdominal pain and intussusception. Laparoscopic resection may be difficult for the intraluminal submucosal lesion. Herein, we report a case of terminal ileal submucosal lipoma resected by radiologic-assisted laparoscopic surgery.
CASE PRESENTATION: The 31-year-old female was admitted for intermittent abdominal pain. The colonoscopy showed a 1.5 cm diameter subepithelial lesion in terminal ileum and computed tomography showed a hypodense lesion in distal ileum. The diagnosis of terminal ileal submucosal lipoma without obstruction was impressed and surgical strategy of minimal invasive surgery was taken. Preoperative CT-guided patent blue dye injection near the terminal ileal submucosal lipoma for localization was performed by Radiologist. Then laparoscopic resection with intracorporeal suture was done smoothly without complications. The pathology proved lipoma and she had good recovery within one week.
CONCLUSIONS: There are many kinds of intervention methods to treat the small bowel lipoma. Our experience supports that laparoscopic surgery with radiologic localization assistance is feasible for terminal ileal nonintussusceptive submucosal lipoma resection.

PMID: 29604532 [PubMed - as supplied by publisher]



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The successful salvage of a thrombosed pancreatic graft at the early postoperative period of a simultaneous pancreas and kidney transplantation.

The successful salvage of a thrombosed pancreatic graft at the early postoperative period of a simultaneous pancreas and kidney transplantation.

Int J Surg Case Rep. 2018 Mar 16;45:116-120

Authors: Shahbazov R, Azari F, Whan PA, Wei L, Agarwal A, Brayman KL

Abstract
INTRODUCTION: Simultaneous kidney and pancreas transplant is the preferred treatment option for end-stage renal disease due to type 1 diabetic nephropathy. Vascular complications are detrimental to graft survival and can lead to graft loss in the early postoperative phase of transplantation. Generally, duplex Doppler ultrasound is used for vascular patency monitoring and pancreatectomy followed by re-transplantation is required in the majority of cases. Recently, pancreatic graft salvage with non-operative management, including medical anticoagulation and endovascular thrombectomy, in the early postoperative period has been described with success.
PRESENTATION OF CASE: We report a case of early detection of pancreas venous graft thrombosis via clinical suspicion and radiological methods, and early intervention with endovascular thrombolysis. As a result, the pancreatic graft was successfully salvaged.
DISCUSSION: A limited number of studies had showed successful graft salvage in only 30-45% of thrombosed pancreatic graft with surgical thrombectomy. Our patient also had bleeding from the vascular access site and ultimately required blood transfusion, however she recovered well after procedure.
CONCLUSION: Given the complexity and significance of PVGT, urgent and prompt treatment is necessary. Interpreting outcomes from our case and other small studies, it appears that endovascular pharmacomechanical thrombectomy can be a vital tool to salvage graft organs in those receiving SPK.

PMID: 29604531 [PubMed - as supplied by publisher]



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Double cross finger flaps from the middle to the index or ring finger: A case series of 4 patients with an emphasis on donor finger morbidity.

Double cross finger flaps from the middle to the index or ring finger: A case series of 4 patients with an emphasis on donor finger morbidity.

Int J Surg Case Rep. 2018 Mar 26;45:107-111

Authors: Al-Qattan OM, Almobarak AA, Al-Qattan MM

Abstract
INTRODUCTION: The use of two cross finger flaps from one digit has not been previously reported and the technique raises concerns regarding donor finger morbidity. In this paper, the authors report on a case series of double cross fingers flaps harvested from the middle finger to reconstruct large defects in the adjacent index or ring finger; with an emphasis on documenting morbidity in the donor middle finger.
METHODS: A total of four cases of double cross finger flaps were retrospectively reviewed. Demographic data, surgery, and postoperative complications were documented. Donor middle finger morbidity (stiffness, painful neuromas, skin graft instability, cold intolerance and cosmetic concerns) were also documented.
RESULTS: All patients were young male industrial workers. Two patients underwent reconstruction with de-epithelialized cross finger flaps and the other two patients had classic cross finger flaps. No postoperative complications were noted. Mild stiffness at the distal interphalangeal joints were noted in all patients. There were no painful neuromas and one donor site had occasional blistering at the site of the skin graft. Mild cold intolerance was seen in the two patients with electric burns. Hyperpigmentation of the skin grafts was noted in all patients.
CONCLUSIONS: Our paper introduces to the literature the technique of utilizing two cross finger flaps from the middle finger to reconstruct large dorsal or volar defects of the adjacent index or ring finger. The study shows that the technique is feasible and is easily executed. The results document an acceptable donor finger morbidity.

PMID: 29604530 [PubMed - as supplied by publisher]



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Renal cell metastasis to the thyroid gland: An emerging phenomenon.

Renal cell metastasis to the thyroid gland: An emerging phenomenon.

Int J Surg Case Rep. 2018 Mar 26;45:104-106

Authors: Connolly CE

Abstract
INTRODUCTION: Suspected thyroid malignancies are usually assumed to be primary in origin. Rarely, in 1-3% of cases, the tumour arises from a secondary source such as a melanoma or breast carcinoma. There is a growing body of research concerning metastatic spread of renal cell carcinoma to the thyroid gland.
PRESENTATION OF CASE: This case report describes the presentation and diagnostic work-up of an 84yr male presenting with a goitre and hoarse voice. Histopathological examination of the excised 95 × 65 × 55 mm tissue mass revealed metastatic clear cell renal cell carcinoma.
DISCUSSION: This disease pattern has become increasingly apparent in recent literature. A literature review of 150 documented cases worldwide showed that the mean interval for this spread to occur is 9 years.
CONCLUSION: There is a need for further investigation into the underlying pathophysiology of this phenomenon and increased awareness from clinicians of its existence.

PMID: 29604529 [PubMed - as supplied by publisher]



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Intraabdominal actinomycosis resulting in a difficult to diagnose intraperitoneal mass: A case report.

Intraabdominal actinomycosis resulting in a difficult to diagnose intraperitoneal mass: A case report.

Int J Surg Case Rep. 2018 Mar 21;45:101-103

Authors: Tsujimura N, Takemoto H, Nakahara Y, Wakasugi M, Matsumoto T, Nishioka K, Takachi K, Oshima S, Yoshida K

Abstract
INTRODUCTION: Actinomycosis is a chronic suppurative granulomatous disease caused by Actinomyces israelii. Preoperative confirmed diagnosis is very difficult, so most cases are diagnosed preoperatively as malignant tumors. We report a case of intraabdominal actinomycosis which was difficult to diagnose preoperatively.
PRESENTATION OF THE CASE: A woman, 60 years old, experienced discomfort in her lower right abdomen. She complained of nausea and anorexia and visited our hospital. Laboratory blood tests, abdominal CT, and abdominal MRI led to a diagnosis of a uterine sarcoma or primary intestinal mass, and she underwent surgery. Her histopathological diagnosis was intraabdominal actinomycosis.
DISCUSSION: Actinomycosis is a chronic purulent granulomatous inflammation caused by Actinomyces israelii. No clinical symptoms or laboratory findings are characteristic of abdominal actinomycosis, so this disorder is very difficult to diagnose preoperatively. Therefore, many cases are diagnosed as malignant tumors and undergo surgery. After surgery, long-term antibiotic treatment (penicillin) is usually administered.
CONCLUSIONS: We reported a case of intraabdominal actinomycosis that resulted in a difficult to diagnose intraperitoneal mass. When a large intraperitoneal mass is found, actinomycosis needs to be included as one of differential diagnoses.

PMID: 29604528 [PubMed - as supplied by publisher]



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Subcortical sources dominate the neuroelectric auditory frequency-following response to speech.

Subcortical sources dominate the neuroelectric auditory frequency-following response to speech.

Neuroimage. 2018 Mar 28;:

Authors: Bidelman GM

Abstract
Frequency-following responses (FFRs) are neurophonic potentials that provide a window into the encoding of complex sounds (e.g., speech/music), auditory disorders, and neuroplasticity. While the neural origins of the FFR remain debated, renewed controversy has reemerged after demonstration that FFRs recorded via magnetoencephalography (MEG) are dominated by cortical rather than brainstem structures as previously assumed. Here, we recorded high-density (64 ch) FFRs via EEG and applied state-of-the art source imaging techniques to multichannel data (discrete dipole modeling, distributed imaging, independent component analysis, computational simulations). Our data confirm a mixture of generators localized to bilateral auditory nerve (AN), brainstem inferior colliculus (BS), and bilateral primary auditory cortex (PAC). However, frequency-specific scrutiny of source waveforms showed the relative contribution of these nuclei to the aggregate FFR varied across stimulus frequencies. Whereas AN and BS sources produced robust FFRs up to ∼700 Hz, PAC showed weak phase-locking with little FFR energy above the speech fundamental (100 Hz). Notably, CLARA imaging further showed PAC activation was eradicated for FFRs >150 Hz, above which only subcortical sources remained active. Our results show (i) the site of FFR generation varies critically with stimulus frequency; and (ii) opposite the pattern observed in MEG, subcortical structures make the largest contribution to electrically recorded FFRs (AN ≥ BS > PAC). We infer that cortical dominance observed in previous neuromagnetic data is likely due to the bias of MEG to superficial brain tissue, underestimating subcortical structures that drive most of the speech-FFR. Cleanly separating subcortical from cortical FFRs can be achieved by ensuring stimulus frequencies are >150-200 Hz, above the phase-locking limit of cortical neurons.

PMID: 29604459 [PubMed - as supplied by publisher]



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Incidence of head and neck cancer in children: A Danish nationwide study from 1978 to 2014.

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Incidence of head and neck cancer in children: A Danish nationwide study from 1978 to 2014.

Pediatr Blood Cancer. 2018 Mar 30;:e27037

Authors: Grønhøj C, Hjalgrim L, Jakobsen KK, Charabi B, Mirian C, Laier GH, Kiss K, Rechnitzer C, Friborg J, von Buchwald C, Hjuler T

Abstract
BACKGROUND: Pediatric head and neck malignancies are rare and only a few descriptive epidemiological studies have been published. Using unique nationwide registries, we report age-specific incidence rates of head and neck cancer (HNC) among children during four decades.
METHODS: Data were obtained from the Danish Cancer Registry. We included children aged 0-14 years diagnosed between January 1, 1978 and December 31, 2014 with extra-orbital, nonskin and nonbone HNC. Patients were divided into nine groups in regard to tumor location: oral cavity, oropharynx, nasopharynx, hypopharynx, thyroid, major salivary glands, larynx, and middle ear. Based on the World Health Organization standard population and Danish age-specific population counts, age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) were calculated and examined for trends.
RESULTS: In total, 169 children (55.6% females) were registered with a malignant tumor in the head and neck region. The AAIR increased with an AAPC of 2.2% (95% CI, 0.8-3.7%). Females showed an AAIR of 0.54 per 100,000 person years compared to that of males, with 0.41 per 100,000 person years (P < 0.01). The AAIR was higher among children aged 10-14 years compared to 0-9-year-old children (P < 0.01). Based on morphology, a significant increase in AAIR was observed for sarcomas, with an increase of 0.16-0.27 per 100,000 person years (P < 0.05).
CONCLUSIONS: The incidence rate of pediatric HNC was higher among females and evidence of increasing rates was observed during 1978-2014, explained by an increase mainly in sarcomas.

PMID: 29603576 [PubMed - as supplied by publisher]



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Trend in otolaryngological surgeries in an era of super-aging: Descriptive statistics using a Japanese inpatient database.

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Trend in otolaryngological surgeries in an era of super-aging: Descriptive statistics using a Japanese inpatient database.

Auris Nasus Larynx. 2018 Mar 27;:

Authors: Suzuki S, Yasunaga H, Matsui H, Fushimi K, Yamasoba T

Abstract
OBJECTIVE: To reveal the age distribution and capture the longitudinal trend in otolaryngological surgeries performed in Japan, where society is rapidly aging.
METHODS: Using the Diagnosis Procedure Combination database, we extracted data on patients who were hospitalized and underwent any type of otolaryngological surgery in departments of otolaryngology or head and neck surgery from fiscal year 2007 to fiscal year 2013. Type of surgery, patient's age, and fiscal year were compared. We categorized >200 types of surgeries into eight specialties: ear surgery, functional endoscopic sinus surgery (FESS), other types of paranasal surgery (except for malignancy), head and neck cancer surgery, benign tumor surgery, upper airway surgery (including pharynx and larynx), removal of foreign body, and other.
RESULTS: In total, 558,732 patients were included. The proportions of patients in each age category formed two peaks in middle age and in children aged ≤9years. The proportion of all surgeries made up by FESS, other paranasal surgery, benign tumor surgery, and head and neck cancer surgery gradually increased with age, forming a peak in patients in their 60s. The proportion of ear surgery was highest in patients aged ≤9years (34.0% of all surgeries, mostly myringotomy and transtympanic ventilation tube insertion) and formed a gradual peak in patients in their 60s (mostly tympanoplasty). The proportion of upper airway surgery (tonsillectomy and adenoidectomy) was highest in patients aged ≤9years (25.3% of all surgeries). The proportion of foreign body removal was highest in patients aged ≤9years (52.2% of all surgeries) and increased slightly with age. In 2013, compared with 2007, those aged 65-74 years and ≥75years made up a larger percentage of patients undergoing each specific surgery, including tympanoplasty, stapedectomy/stapedotomy, FESS, head and neck cancer surgery, pharyngolaryngectomy, total/subtotal glossectomy, thyroid lobectomy, parotidectomy (for a benign tumor), submandibular gland resection, tonsillectomy, and vocal fold polypectomy.
CONCLUSION: The age distribution of otolaryngological surgeries varied by specialty. We found an increased proportion of patients aged 65-74 and ≥75years in most specific surgeries.

PMID: 29602585 [PubMed - as supplied by publisher]



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Pharyngocutaneous and tracheoesophageal fistula closure using supraclavicular artery island flap.

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Pharyngocutaneous and tracheoesophageal fistula closure using supraclavicular artery island flap.

Eur Arch Otorhinolaryngol. 2018 Mar 30;:

Authors: Teixeira S, Costa J, Monteiro D, Bartosch I, Ínsua-Pereira I, Correia B, Silva Á

Abstract
BACKGROUND: Pharyngocutaneous fistula is a common complication of laryngopharyngeal surgery, being associated with increased morbidity and mortality. Classical regional and free flaps, frequently used in the treatment of this complication, have several limitations, including bulking, donor site morbidity and long operative time. The supraclavicular artery island flap (SCAIF) is a fasciocutaneous flap and presents as an alternative option with good results and without the previously stated limitations. We describe our experience with SCAIF in pharyngocutaneous and tracheoesophageal fistula closure.
METHODS: Between April and December 2017, four patients with pharyngocutaneous and two patients with tracheoesophageal fistula underwent fistula closure with SCAIF. Clinical records were retrospectively reviewed.
RESULTS: Pharyngocutaneous fistulae were associated with anterior esophageal wall defects ranging from 4 to 13.5 cm2. Tracheoesophageal fistulae defects were smaller (approximately 2 cm2). Fistula closure was achieved in all patients, oral diet was started on the 14th day post-operative and there were no signs of recurrence during follow-up. The donor area was complicated with the formation of hematoma in two patients.
CONCLUSIONS: The SCAIF has unique features that makes it an ideal option for pharyngocutaneous and tracheoesophageal fistula closure, namely, reliable perfusion, quick and simple dissection, pliability and minor donor site morbidity. Local complications do not significantly affect long term morbidity of the donor area and can be avoided with simple measures.

PMID: 29602967 [PubMed - as supplied by publisher]



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Parent understanding of the risk of future limitations secondary to pediatric cancer treatment.

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Parent understanding of the risk of future limitations secondary to pediatric cancer treatment.

Pediatr Blood Cancer. 2018 Mar 30;:e27020

Authors: Greenzang KA, Cronin AM, Kang T, Mack JW

Abstract
BACKGROUND: Parents and physicians may have different understandings of a child's risk of future limitations due to cancer or cancer treatment. We evaluated alignment between parent- and physician-estimated risk of late effects.
METHODS: We surveyed 352 parents of children with cancer within 12 weeks of diagnosis, and the children's oncologists, at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Children's Hospital of Philadelphia. We assessed parent and physician estimations of the child's risk of future limitations in physical abilities, intelligence, or quality of life (QOL) due to cancer treatment. Physician-estimated risk of limitations ≥50% was considered high risk.
RESULTS: Physicians considered 22% of children at high risk of physical impairments, 9% at high risk for impaired intelligence, and 6% at high risk for impaired QOL. Among high-risk children, 38% of parents recognized this risk in physical abilities, 21% in intelligence, and 5% in QOL. In multivariable analysis, parental understanding of risk, defined as concordant parent and physician estimates, was greater among parents of children at lower risk of future limitations (odds ratio 2.59; 95% confidence interval 1.35-4.96). Regardless of risk, 92% of parents considered it very/extremely important to receive information about potential health implications of cancer treatment.
CONCLUSIONS: Although most parents want information about life after cancer, most parents of children at high risk of future impairment do not recognize this risk. Strategies to improve communication about late effects throughout pediatric cancer treatment should prioritize meeting information needs and improving parent understanding of the risk of impairment.

PMID: 29603610 [PubMed - as supplied by publisher]



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Hemoptysis After CardioMEMS Implantation: Case Report and Review.

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Hemoptysis After CardioMEMS Implantation: Case Report and Review.

Am J Case Rep. 2018 Mar 31;19:382-385

Authors: Rali AS, Shah Z, Sauer AJ, Gupta K

Abstract
BACKGROUND The CardioMEMS heart failure system is a small sensor that is placed in a branch pulmonary artery for ambulatory monitoring of pulmonary artery pressures. CardioMEMS has been approved for use in the United States in patients with New York Heart Association (NYHA) class III heart failure and frequent hospitalizations. In this report we describe a patient who had hemoptysis after CardioMEMS implantation. Further, we discuss possible etiologies for the occurrence of hemoptysis and suggest strategies to minimize this risk. CASE REPORT The patient was a 79-year-old female with NYHA class III heart failure with non-ischemic cardiomyopathy (LVEF 40%) and chronic atrial fibrillation who was referred for CardioMEMS implantation. The procedure was completed uneventfully. The patient was transferred out of the procedure suite to the recovery area where she developed a slight cough approximately 20 minutes after the implantation. Within a few coughs the patient started having hemoptysis. She was transferred to the cardiac intensive care unit for observation. She was kept off warfarin and aspirin and her hemoptysis resolved 3 days later. While the exact etiology of hemoptysis in this patient was unclear, we felt that it may have been precipitated by a minor wire-induced distal branch pulmonary artery injury. CONCLUSIONS Our report discusses hemoptysis as a potential life-threatening complication of CardioMEMS sensor implantation while suggesting possible etiologies and avoidance strategies. As the utilization of this technology expands in the years to come, a more comprehensive national registry for surveillance of device related complications will be crucial.

PMID: 29602943 [PubMed - in process]



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Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas.

Oncosis-like cell death is induced by berberine through ERK1/2-mediated impairment of mitochondrial aerobic respiration in gliomas.

Biomed Pharmacother. 2018 Mar 28;102:699-710

Authors: Sun Y, Yu J, Liu X, Zhang C, Cao J, Li G, Liu X, Chen Y, Huang H

Abstract
Gliomas, the most common primary malignant brain tumor, exhibit high metabolic activity. The targeting of metabolism alterations, particularly in mitochondria, is emerging as an efficient approach for curing cancers. Here, we showed that berberine, a natural compound that is used as an antibacterial agent, could reduce cellular viability and induce oncosis-like death, characterized by cell swelling, cytoplasmic vacuoles and plasma membrane blebbing, in gliomas, and that these effects were correlated with intracellular adenosine triphosphate (ATP) depletion. We also found that berberine induced autophagy as a protective effect and decreased the oxygen consumption rate (OCR), which could inhibit mitochondrial aerobic respiration by repressing phosphorylated extracellular regulated protein kinases (p-ERK1/2). Furthermore, the down-regulation of mitochondrial p-ERK1/2 by berberine inhibited aerobic respiration and led to glycolysis, an inefficient energy production pathway. In addition, berberine reduced tumor growth and inhibited Ki-67 and p-ERK1/2 expression in vivo. The results demonstrate that berberine, which represses aerobic oxidation in mitochondria and decreases their energy production efficiency, decreases metabolic activity by reducing ERK1/2 activity.

PMID: 29604589 [PubMed - as supplied by publisher]



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TRIM50 regulates Becli-1 proautophagic activity.

TRIM50 regulates Becli-1 proautophagic activity.

Biochim Biophys Acta. 2018 Mar 28;:

Authors: Fusco C, Mandriani B, Di Rienzo M, Micale L, Malerba N, Cocciadiferro D, Sjøttem E, Augello B, Squeo G, Pellico MT, Jain A, Johansen T, Fimia GM, Merla G

Abstract
Autophagy is a catabolic process needed for maintaining cell viability and homeostasis in response to numerous stress conditions. Emerging evidence indicates that the ubiquitin system has a major role in this process. TRIMs, an E3 ligase protein family, contribute to selective autophagy acting as receptors and regulators of the autophagy proteins recognizing endogenous or exogenous targets through intermediary autophagic tags, such as ubiquitin. Here we report that TRIM50 fosters the initiation phase of starvation-induced autophagy and associates with Beclin1, a central component of autophagy initiation complexes. We show that TRIM50, via the RING domain, ubiquitinates Beclin 1 in a K63-dependent manner enhancing its binding with ULK1 and autophagy activity. Finally, we found that the Lys-372 residue of TRIM50, critical for its own acetylation, is necessary for its E3 ligase activity that governs Beclin1 ubiquitination. Our study expands the roles of TRIMs in regulating selective autophagy, revealing an acetylation-ubiquitination dependent control for autophagy modulation.

PMID: 29604308 [PubMed - as supplied by publisher]



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Oral exposure to silver nanoparticles increases oxidative stress markers in the liver of male rats and deregulates the insulin signalling pathway and p53 and cleaved caspase 3 protein expression.

Oral exposure to silver nanoparticles increases oxidative stress markers in the liver of male rats and deregulates the insulin signalling pathway and p53 and cleaved caspase 3 protein expression.

Food Chem Toxicol. 2018 Mar 28;:

Authors: Blanco J, Tomás-Hernández S, García T, Mulero M, Gómez M, Domingo JL, Sánchez DJ

Abstract
The present study was aimed at assessing the impact of AgNPs on the liver of male rats orally exposed to 0, 50, 100 and 200 mg/kg/day of polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) for 90 days. The induction of apoptotic cell death -by measuring the protein levels of the active form of caspase 3- and the levels of the microtubule-associated protein 1A/1B-light chain (LC3) protein were measured as a marker of the induction of autophagy. PVP-AgNPs caused an increase of the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver of male rats. However, the activity decreased after exposure to high amounts of PVP-AgNPs. Increased protein levels of IRS-1, AKT, GSK3β and mTOR proteins were observed in a dose-dependent manner. However, these proteins showed a decrease at 200 mg/kg/day. The same pattern was observed for the p53, p21 and cleaved caspase 3 protein levels. The current results suggest that the increase of ROS production by PVP-AgNPs stimulated SOD and CAT activity, as well as IRS-1, AKT, mTOR, p53, p21 and caspase 3 as protective mechanisms of cell survival and preserve DNA fidelity. However, cellular damage by excessive ROS production might induce the depletion of these survival mechanisms at 200 mg/kg/day.

PMID: 29604305 [PubMed - as supplied by publisher]



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Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells.

Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells.

Biochem Biophys Res Commun. 2018 Mar 28;:

Authors: Ji ST, Kim YJ, Jung SY, Kim DY, Kang S, Park JH, Jang WB, Ha J, Yun J, Kwon SM

Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs. We found that short-term priming with OLP attenuated H2O2-induced apoptosis by regulating the pro-apoptotic marker Bax and the anti-apoptotic markers Bcl-2 and Mcl-1. Notably, OLP inhibits H2O2 -induced autophagic cell death by modulating autophagy-related death signals, including mTOR (mammalian target of rapamycin), ULK1 (unc-51 like autophagy activating kinase 1), Beclin-1, AMPK (AMP-activated protein kinase), and LC3 (microtubule-associated protein 1a/1b-light chain 3). Our data suggest that OLP might reduce H2O2-induced autophagy and cell apoptosis in MSCs by regulating both the AMPK-ULK axis and the Bcl-2-Mcl-1 axis. Consequently, short-term cell priming with OLP might enhance the therapeutic effect of MSCs against ischemic vascular diseases, which provides an important potential improvement for emerging therapeutic strategies.

PMID: 29604275 [PubMed - as supplied by publisher]



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Patulin induced ROS-dependent autophagic cell death in Human Hepatoma G2 cells.

Patulin induced ROS-dependent autophagic cell death in Human Hepatoma G2 cells.

Chem Biol Interact. 2018 Mar 28;:

Authors: Yang G, Bai Y, Wu X, Sun X, Sun M, Liu X, Yao X, Zhang C, Chu Q, Jiang L, Wang S

Abstract
Patulin (PAT) is a secondary metabolite produced by certain species of Penicillium, Byssochlamys and Aspergillus. It has been shown to induce liver toxicity, but the possible molecular mechanisms are not completely elucidated. In our study, we treated Human Hepatoma G2 (HepG2) cells by 3-methyladenine (3-MA), an autophagosome formation inhibitor, and rapamycin, an autophagosome formation stimulator. The results showed that 3-MA protected the HepG2 cells against PAT cytotoxicity, while rapamycin decreased the cell viability. Thus, autophagy may play an important role in PAT-induced toxicity. To uncover the mechanism by which cells decrease proliferation and activation of autophagy, we found that collapses of mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) level were increased under treatment with PAT. Further, we elucidated that the expression of p-Akt1 and p-MTOR was inhibited during this process. N-acetyl-l-cysteine (NAC), a ROS inhibitor, protected against PAT-induced cytotoxicity, decreased the protein expression of LC3-II, and up-regulated the level of p-Akt1 and p-MTOR. These findings suggested that PAT-induced autophagic cell death was ROS-dependent in HepG2 cells. In conclusion, it is possible that PAT elicited autophagy through ROS-Akt1-MTOR pathway in the HepG2 cells.

PMID: 29604266 [PubMed - as supplied by publisher]



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The Nem1/Spo7-Pah1/lipin axis is required for autophagy induction after TORC1 inactivation.

The Nem1/Spo7-Pah1/lipin axis is required for autophagy induction after TORC1 inactivation.

FEBS J. 2018 Mar 31;:

Authors: Arifur MR, Golam MM, Ushimaru T

Abstract
Autophagy is a process that requires intense membrane remodeling and consumption. The nutrient-responsive TORC1 (target of rapamycin complex 1) kinase regulates autophagy. However, how TORC1 controls autophagy via lipid/membrane biogenesis is unknown. TORC1 regulates the function of yeast phosphatidate phosphatase lipin Pah1 via the Nem1/Spo7 phosphatase complex. Here, we show that the Nem1/Spo7-Pah1 axis is required for autophagy induction after TORC1 inactivation and survival during starvation. Furthermore, this axis was critical for nucleophagy (both micronucleophagy and macronucleophagy) and was required for proper localization of micronucleophagy factor Nvj1 and macronucleophagy receptor Atg39. This study indicated that the Nem1/Spo7-Pah1 axis controlled by TORC1 is a critical branch for autophagy induction in nutrient starvation conditions. This article is protected by copyright. All rights reserved.

PMID: 29604183 [PubMed - as supplied by publisher]



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Metabolic Regulation of Methionine Restriction in Diabetes.

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Metabolic Regulation of Methionine Restriction in Diabetes.

Mol Nutr Food Res. 2018 Mar 30;:e1700951

Authors: Yin J, Ren W, Chen S, Li Y, Han H, Gao J, Liu G, Wu X, Li T, Kim SW, Yin Y

Abstract
Although the effects of dietary methionine restriction have been investigated in the physiology of aging and diseases related to oxidative stress, the relationship between methionine restriction and the development of metabolic disorders has not been explored extensively. This review summarizes studies of the possible involvement of dietary methionine restriction in improving insulin resistance, glucose homeostasis, oxidative stress, lipid metabolism, the pentose phosphate pathway, and inflammation, with an emphasis on the fibroblast growth factor 21 and protein phosphatase 2A signals and autophagy in diabetes. Diets deficient in methionine may be a useful nutritional strategy in patients with diabetes. This article is protected by copyright. All rights reserved.

PMID: 29603632 [PubMed - as supplied by publisher]



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Demarcation of Viral Shelters Results in Destruction by Membranolytic GTPases: Antiviral Function of Autophagy Proteins and Interferon-Inducible GTPases.

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Demarcation of Viral Shelters Results in Destruction by Membranolytic GTPases: Antiviral Function of Autophagy Proteins and Interferon-Inducible GTPases.

Bioessays. 2018 Mar 30;:e1700231

Authors: Brown HM, Biering SB, Zhu A, Choi J, Hwang S

Abstract
A hallmark of positive-sense RNA viruses is the formation of membranous shelters for safe replication in the cytoplasm. Once considered invisible to the immune system, these viral shelters are now found to be antagonized through the cooperation of autophagy proteins and anti-microbial GTPases. This coordinated effort of autophagy proteins guiding GTPases functions against not only the shelters of viruses but also cytoplasmic vacuoles containing bacteria or protozoa, suggesting a broad immune-defense mechanism against disparate vacuolar pathogens. Fundamental questions regarding this process remain: how the host recognizes these membranous structures as a target, how the autophagy proteins bring the GTPases to the shelters, and how the recruited GTPases disrupt these shelters. In this review, these questions are discussed, the answers to which will significantly advance our understanding of the response to vacuole-like structures of pathogens, thereby paving the way for the development of broadly effective anti-microbial strategies for public health.

PMID: 29603284 [PubMed - as supplied by publisher]



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Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation.

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Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation.

Br J Surg. 2018 Mar 30;:

Authors: De Deken J, Rex S, Lerut E, Martinet W, Monbaliu D, Pirenne J, Jochmans I

Abstract
BACKGROUND: Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Preconditioning, reconditioning and postconditioning with argon and xenon protects against renal ischaemia-reperfusion injury in rodent models. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function in a porcine renal autotransplant model was tested.
METHODS: Pigs (n = 6 per group) underwent left nephrectomy after 60 min of warm ischaemia (renal artery and vein clamping). The procured kidney was autotransplanted in a separate procedure after 18 h of cold storage, immediately after a right nephrectomy. Upon reperfusion, pigs were randomized to inhalation of control gas (70 per cent nitrogen and 30 per cent oxygen), argon (70 per cent and 30 per cent oxygen) or xenon (70 per cent and 30 per cent oxygen) for 2 h. The primary outcome parameter was peak plasma creatinine; secondary outcome parameters included further markers of graft function (creatinine course, urine output), graft injury (aspartate aminotransferase, heart-type fatty acid-binding protein, histology), apoptosis and autophagy (western blot, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining), inflammatory mediators and markers of cell survival/growth (mRNA and tissue protein quantification), and animal survival. Results are presented as median (i.q.r.). ANOVA and Kruskal-Wallis tests were used where indicated.
RESULTS: Peak plasma creatinine levels were similar between the groups: control 20·8 (16·4-23·1) mg/dl, argon 21·4 (17·1-24·9) mg/dl and xenon 19·4 (17·5-21·0) mg/dl (P = 0·607). Xenon was associated with an increase in autophagy and proapoptotic markers. Creatinine course, urine output, injury markers, histology, survival and inflammatory mediators were not affected by the intervention.
CONCLUSION: Postconditioning with argon or xenon did not improve kidney graft function in this experimental model. Surgical relevance Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Based on mainly small animal experiments, noble gases (argon and xenon) have been proposed to minimize this ischaemia-reperfusion injury and improve outcomes after transplantation. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function was tested in a porcine kidney autotransplantation model. The peak plasma creatinine concentration was similar in the control, argon and xenon groups. No other secondary outcome parameters, including animal survival, were affected by the intervention. Xenon was associated with an increase in autophagy and proapoptotic markers. Despite promising results in small animal models, postconditioning with argon or xenon in a translational model of kidney autotransplantation was not beneficial. Clinical trials would require better results.

PMID: 29603122 [PubMed - as supplied by publisher]



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Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling.

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Low-level laser irradiation at a high power intensity increased human endothelial cell exosome secretion via Wnt signaling.

Lasers Med Sci. 2018 Mar 30;:

Authors: Bagheri HS, Mousavi M, Rezabakhsh A, Rezaie J, Rasta SH, Nourazarian A, Avci ÇB, Tajalli H, Talebi M, Oryan A, Khaksar M, Kazemi M, Nassiri SM, Ghaderi S, Bagca BG, Rahbarghazi R, Sokullu E

Abstract
The distinct role of low-level laser irradiation (LLLI) on endothelial exosome biogenesis remains unclear. We hypothesize that laser irradiation of high dose in human endothelial cells (ECs) contributes to the modulation of exosome biogenesis via Wnt signaling pathway. When human ECs were treated with LLLI at a power density of 80 J/cm2, the survival rate reduced. The potential of irradiated cells to release exosomes was increased significantly by expressing genes CD63, Alix, Rab27a, and b. This occurrence coincided with an enhanced acetylcholine esterase activity, pseudopodia formation, and reduced zeta potential value 24 h post-irradiation. Western blotting showed the induction of LC3 and reduced level of P62, confirming autophagy response. Flow cytometry and electron microscopy analyses revealed the health status of the mitochondrial function indicated by normal ΔΨ activity without any changes in the transcription level of PINK1 and Optineurin. When cells exposed to high power laser irradiation, p-Akt/Akt ratio and in vitro tubulogenesis capacity were blunted. PCR array and bioinformatics analyses showed the induction of transcription factors promoting Wnt signaling pathways and GTPase activity. Thus, LLLI at high power intensity increased exosome biogenesis by the induction of autophagy and Wnt signaling. LLLI at high power intensity increases exosome biogenesis by engaging the transcription factors related to Wnt signaling and autophagy stimulate.

PMID: 29603107 [PubMed - as supplied by publisher]



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Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics.

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Secretome of Differentiated PC12 Cells Restores the Monocrotophos-Induced Damages in Human Mesenchymal Stem Cells and SHSY-5Y Cells: Role of Autophagy and Mitochondrial Dynamics.

Neuromolecular Med. 2018 Mar 30;:

Authors: Srivastava A, Singh S, Rajpurohit CS, Srivastava P, Pandey A, Kumar D, Khanna VK, Pant AB

Abstract
A perturbed cellular homeostasis is a key factor associated with xenobiotic exposure resulting in various ailments. The local cellular microenvironment enriched with secretory components aids in cell-cell communication that restores this homeostasis. Deciphering the underlying mechanism behind this restorative potential of secretome could serve as a possible solution to many health hazards. We, therefore, explored the protective efficacy of the secretome of differentiated PC12 cells with emphasis on induction of autophagy and mitochondrial biogenesis. Monocrotophos (MCP), a widely used neurotoxic organophosphate, was used as the test compound at sublethal concentration. The conditioned medium (CM) of differentiated PC12 cells comprising of their secretome restored the cell viability, oxidative stress and apoptotic cell death in MCP-challenged human mesenchymal stem cells and SHSY-5Y, a human neuroblastoma cell line. Delving further to identify the underlying mechanism of this restorative effect we observed a marked increase in the expression of autophagy markers LC3, Beclin-1, Atg5 and Atg7. Exposure to autophagy inhibitor, 3-methyladenine, led to a reduced expression of these markers with a concomitant increase in the expression of pro-apoptotic caspase-3. Besides that, the increased mitochondrial fission in MCP-exposed cells was balanced with increased fusion in the presence of CM facilitated by AMPK/SIRT1/PGC-1α signaling cascade. Mitochondrial dysfunctions are strongly associated with autophagy activation and as per our findings, cellular secretome too induces autophagy. Therefore, connecting these three potential apices can be a major breakthrough in repair and rescue of xenobiotic-damaged tissues and cells.

PMID: 29603067 [PubMed - as supplied by publisher]



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Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.

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Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.

Arch Toxicol. 2018 Mar 30;:

Authors: Müller SM, Finke H, Ebert F, Kopp JF, Schumacher F, Kleuser B, Francesconi KA, Raber G, Schwerdtle T

Abstract
Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.

PMID: 29602950 [PubMed - as supplied by publisher]



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SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy.

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SMAD4 gene mutation renders pancreatic cancer resistance to radiotherapy through promotion of autophagy.

Clin Cancer Res. 2018 Mar 30;:

Authors: Wang F, Xia X, Yang C, Shen J, Mai J, Kim HC, Kirui D, Kang Y, Fleming JB, Koay EJ, Mitra S, Ferrari M, Shen H

Abstract
PURPOSE: Understanding the mechanism of radioresistance could help develop strategies to improve therapeutic response of patients with PDAC. The SMAD4 gene is frequently mutated in pancreatic cancer. In this study, we investigated the role of SMAD4 deficiency in pancreatic cancer cells' response to radiotherapy.
EXPERIMENTAL DESIGN: We downregulated SMAD4 expression with SMAD4 siRNA or SMAD4 shRNA and overexpressed SMAD4 in SMAD4 mutant pancreatic cancer cells followed by clonogenic survival assay to evaluate their effects on cell radioresistance. To study the mechanism of radioresistance, the effects of SMAD4 loss on reactive oxygen species (ROS) and autophagy were determined by Flow Cytometry and immunoblot analysis, respectively. Furthermore, we measured radioresistance by clonogenic survival assay after treatment with autophagy inhibitor (Chloroquine) and ROS inhibitor (N-acetyl-L-cysteine) in SMAD4-depleted pancreatic cancer cells. Finally, the effects of SMAD4 on radioresistance were also confirmed in an orthotopic tumor model derived from SMAD4-depleted Panc-1 cells.
RESULTS: SMAD4-depleted pancreatic cancer cells were more resistant to radiotherapy based on clonogenic survival assay. Overexpression of wild type SMAD4 in SMAD4-mutant cells rescued their radiosensitivity. Radioresistance mediated by SMAD4 depletion was associated with persistently higher levels of ROS and radiation-induced autophagy. Finally, SMAD4 depletion induced in vivo radioresistance in Panc-1-derived orthotopic tumor model (P = 0.038). More interestingly, we observed that the protein level of SMAD4 is inversely correlated with autophagy in orthotopic tumor tissue samples.
CONCLUSIONS: Our results demonstrate that defective SMAD4 is responsible for radioresistance in pancreatic cancer through induction of ROS and increased level of radiation-induced autophagy.

PMID: 29602802 [PubMed - as supplied by publisher]



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Parent understanding of the risk of future limitations secondary to pediatric cancer treatment.

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Parent understanding of the risk of future limitations secondary to pediatric cancer treatment.

Pediatr Blood Cancer. 2018 Mar 30;:e27020

Authors: Greenzang KA, Cronin AM, Kang T, Mack JW

Abstract
BACKGROUND: Parents and physicians may have different understandings of a child's risk of future limitations due to cancer or cancer treatment. We evaluated alignment between parent- and physician-estimated risk of late effects.
METHODS: We surveyed 352 parents of children with cancer within 12 weeks of diagnosis, and the children's oncologists, at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Children's Hospital of Philadelphia. We assessed parent and physician estimations of the child's risk of future limitations in physical abilities, intelligence, or quality of life (QOL) due to cancer treatment. Physician-estimated risk of limitations ≥50% was considered high risk.
RESULTS: Physicians considered 22% of children at high risk of physical impairments, 9% at high risk for impaired intelligence, and 6% at high risk for impaired QOL. Among high-risk children, 38% of parents recognized this risk in physical abilities, 21% in intelligence, and 5% in QOL. In multivariable analysis, parental understanding of risk, defined as concordant parent and physician estimates, was greater among parents of children at lower risk of future limitations (odds ratio 2.59; 95% confidence interval 1.35-4.96). Regardless of risk, 92% of parents considered it very/extremely important to receive information about potential health implications of cancer treatment.
CONCLUSIONS: Although most parents want information about life after cancer, most parents of children at high risk of future impairment do not recognize this risk. Strategies to improve communication about late effects throughout pediatric cancer treatment should prioritize meeting information needs and improving parent understanding of the risk of impairment.

PMID: 29603610 [PubMed - as supplied by publisher]



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Procalcitonin monitoring as a guide for antimicrobial therapy: a review of current literature.

Procalcitonin monitoring as a guide for antimicrobial therapy: a review of current literature.

Pharmacotherapy. 2018 Mar 31;:

Authors: Covington EW, Roberts MZ, Dong J

Abstract
Effective antimicrobial stewardship practices are increasingly essential to best utilize the current arsenal of antimicrobials for the shortest necessary duration to minimize the development of antimicrobial resistance, secondary infections, and health care costs. Monitoring of serum procalcitonin (PCT) levels represents an effective antimicrobial stewardship strategy to differentiate bacterial infections from viral infections and noninfectious inflammatory conditions. Current literature illustrates the merits of PCT monitoring in reducing duration of antibiotic therapy without detrimental effects on mortality or infection relapses. However, the interpretation of PCT levels can be challenging, especially in light of comorbid disease states that can elevate PCT levels. This review will shed light on the utility of PCT monitoring, as well as provide insight into the practical interpretation of PCT levels. Much of the current literature surrounding PCT monitoring consists of use among patients with lower respiratory tract infections or in the critically ill. Overall, studies have demonstrated shorter antibiotic therapy durations when PCT monitoring is utilized. No studies to date have found increased rates of mortality or infection relapses, suggesting that PCT monitoring is not only effective, but also safe when used as a guide for antimicrobial therapy. Nonetheless, many conditions have been shown to elevate PCT serum concentrations, even in the absence of bacterial infections, which can make interpretation of PCT concentrations challenging. Two common conditions that affect the accurate interpretation of PCT levels are renal dysfunction and congestive heart failure. Limited studies have been performed in these populations, but current available data proposes the need for higher PCT thresholds in those with renal dysfunction or congestive heart failure and supports utilizing PCT trends to monitor clinical improvement from bacterial infections. Evidence also suggests that PCT monitoring is cost effective, as long as the test is ordered judiciously. In summary, PCT monitoring represents a promising antimicrobial stewardship strategy to limit exposure to unnecessary antimicrobial therapy. This article is protected by copyright. All rights reserved.

PMID: 29604109 [PubMed - as supplied by publisher]



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Reductions in otitis and other respiratory tract infections following childhood pneumococcal vaccination.

Reductions in otitis and other respiratory tract infections following childhood pneumococcal vaccination.

Acta Paediatr. 2018 Mar 30;:

Authors: Johansson Kostenniemi U, Palm J, Silfverdal SA

Abstract
AIM: Streptococcus pneumoniae commonly causes respiratory tract infections including acute otitis media and pneumonia. In this study, we evaluated the impact of general infant pneumococcal vaccination, introduced in Sweden in 2009, on respiratory tract infections.
METHODS: We studied the incidence of respiratory tract infections and antibiotic consumption in Västerbotten County, Sweden, during 2005-2014 by using the County Council's diagnosis register.
RESULTS: Comparing the pre-vaccination period of 2005-2008 to 2014, the incidences of all-cause acute otitis media decreased significantly in children aged 0-4 and 5-17 years, by 41.5% and 20.9% respectively. In addition, we also noted significant reductions for sinusitis and other upper respiratory tract infections, and some reductions in adults. Antibiotic consumption for upper respiratory tract infections decreased by 37.1%, with the largest decrease occurring in children aged 0-4 years. For pneumonia, the incidence significantly decreased by 28.6% for children aged 0-4 years, with no significant changes in older children or adults.
CONCLUSION: Pneumococcal vaccination was followed by reduced incidence of upper respiratory tract infections and antibiotic consumption in vaccinated children, with some indications of possible herd immunity. For pneumonia a major reduction was noted limited to the youngest children. This article is protected by copyright. All rights reserved.

PMID: 29603797 [PubMed - as supplied by publisher]



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Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.

Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.

Biomed Pharmacother. 2018 Mar 28;102:681-688

Authors: Hu WJ, Liu J, Zhong LK, Wang J

Abstract
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancers with poor prognosis. Despite that platinum-based chemotherapy concurrent with radiotherapy have made great achievements for the treatment of NPC, the therapeutic reaction and toxicity varies dramatically among individuals. Apigenin (API), a naturally occurring plant flavone, is considered to have anti-cancer effect. Cetuximab (CET), a well known epidermal growth factor receptor (EGFR) inhibitor, is widely used in various cancers, especially head and neck cancers. The aim of our study was to measure the combination of API and CET for the treatment of NPC in vitro and in vivo. Results demonstrated that combining API and CET could better suppress the viability of the human nasopharyngeal carcinoma cell lines (HONE1 and CNE2) and inhibit the growth of NPC than API or CET used alone. Besides, the combination of API with CET produced greater pro-apoptosis effect. Moreover, the increased G2/M phase arrest caused by CET could be remarkably enhanced by adding API in HONE1 and CNE2 cells. Although, both API and CET could decrease the expressions of p-EGFR, p-Akt, p-STAT3 and Cyclin D1. Combining them produced greater inhibition effect. These results suggested that the combination of API and CET may be a promising therapeutic approach for the treatment of NPC.

PMID: 29604587 [PubMed - as supplied by publisher]



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Resistin upregulates MUC5AC/B mucin gene expression in human airway epithelial cells.

Resistin upregulates MUC5AC/B mucin gene expression in human airway epithelial cells.

Biochem Biophys Res Commun. 2018 Mar 28;:

Authors: Kwak S, Kim YD, Na HG, Bae CH, Song SY, Choi YS

Abstract
Adipokines, a group of proteins including leptin, visfatin, resistin, and adiponectin, are produced by adipocytes. Among adipokines, resistin is implicated in insulin resistance and inflammatory response modulation. Mucus hypersecretion has been greatly linked to airway diseases, such as asthma, chronic obstructive pulmonary disease, and rhinosinusitis. Increasing evidence has indicated that adipokines, such as leptin and visfatin, play important regulatory roles in various biological processes involved in mucus secretion. However, the effects of resistin on mucin expression in human airway epithelial cells, as well as the underlying mechanisms, have not been investigated yet. We showed that resistin affected mucin expression in human airway epithelial cells via the mitogen-activated protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Resistin increased MUC5AC and MUC5B expression in NCI-H292 and primary human nasal epithelial cells. Additionally, it significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and NF-κB. ERK1/2 and p38 specific inhibitors significantly attenuated resistin-induced MUC5AC/5B expression; however, NF-κB inhibitor reduced resistin-induced MUC5AC, but not MUC5B, expression. Knockdown of ERK1, ERK2, and p38 by ERK1, ERK2, and p38 small interfering RNA (siRNA), respectively, significantly blocked resistin-induced MUC5AC and MUC5B mRNA expression. In addition, NF-κB siRNA attenuated resistin-induced MUC5AC, but not MUC5B, expression. These results suggested that resistin induced MUC5AC and MUC5B expression via activation of different signaling pathways in human airway epithelial cells.

PMID: 29604272 [PubMed - as supplied by publisher]



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Salivary flow and xerostomia in patients with type 2 diabetes.

Salivary flow and xerostomia in patients with type 2 diabetes.

J Oral Pathol Med. 2018 Mar 31;:

Authors: Carramolino-Cuéllar E, Lauritano D, Silvestre FJ, Carinci F, Lucchese A, Silvestre-Rangil J

Abstract
BACKGROUND: Saliva is secreted by the major and minor salivary glands. There are a number of physiological factors that can reduce this secretion such as age, sex, body weight, number of teeth present in the mouth, or time of day. This decrease may also be caused by the use of certain drugs, radiotherapy for head and neck cancer, chronic rheumatic diseases such as Sjögren's syndrome, and other systemic disorders such as diabetes mellitus (DM). Objective of this study was to investigate the effect of type 2 DM on salivary secretion and its relation to the sensation of xerostomia.
METHODS: 47 patients with type 2 DM and 46 healthy individuals, aged 40-80, participated in the study. Samples of saliva were collected, at rest and after stimulation, at baseline and after the administration of a meal. A questionnaire of 10 items was used to define the patients' sensations of xerostomia. For statistical analysis, the Mann-Whitney test was used to assess the difference in salivary flow between the two groups and the relationship between the response to each of the questions and salivary flow levels. The degree of the patients' sensation of xerostomia was analysed by the Fisher test.
RESULTS AND CONCLUSIONS: There was a significant decrease in total saliva levels at rest in patients with type 2 DM compared to the control group. The study group also experienced higher levels of dryness at night and on waking as well as a greater sensation of lingual burning compared to the control group. This article is protected by copyright. All rights reserved.

PMID: 29604122 [PubMed - as supplied by publisher]



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Out of balance: how a binaural coincidence detection circuit responds to unilateral deafferentation.

Out of balance: how a binaural coincidence detection circuit responds to unilateral deafferentation.

J Physiol. 2018 Mar 31;:

Authors: Roberts MT

Abstract
Coincidence detection is a fundamental computation used by neurons to determine when two or more sources of input are active within a brief time window. Optimal coincidence detection generally requires a delicate balance of synaptic strengths, so that no single source of input dominates the computation. This article is protected by copyright. All rights reserved.

PMID: 29604080 [PubMed - as supplied by publisher]



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Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: Results from a prospective cohort study.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: Results from a prospective cohort study.

Int J Cancer. 2018 Mar 31;:

Authors: Arthur AE, Goss AM, Demark-Wahnefried W, Mondul AM, Fontaine KR, Chen YT, Carroll WR, Spencer SA, Rogers LQ, Rozek LS, Wolf GT, Gower BA, and The University of Michigan Head and Neck SPORE Program

Abstract
No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC- specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23 - 4.25), total sugar (HR: 3.03; 95% CI: 1.12 - 3.68), glycemic load (HR: 2.10; 95% CI: 1.15, 3.83), and simple carbohydrates (HR 2.26; 95% CI 1.19 - 4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45 (1.23 - 4.25) and total sugar (HR 3.03; 95% CI 1.12 - 3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01 - 0.69) and all-cause mortality (HR 0.27; 95% CI 0.07 - 0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted. This article is protected by copyright. All rights reserved.

PMID: 29604042 [PubMed - as supplied by publisher]



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Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

Int J Cancer. 2018 Mar 31;:

Authors: Annunziata C, Pezzuto F, Greggi S, Ionna F, Losito S, Botti G, Buonaguro L, Buonaguro FM, Tornesello ML

Abstract
Two recurrent mutations (-124 G>A and -146 G>A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral SCC and 16.8% of cervical squamous cell carcinoma (SCC) harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G>A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124 G>A or -146 G>A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. This article is protected by copyright. All rights reserved.

PMID: 29603728 [PubMed - as supplied by publisher]



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A Retrospective Study to Compare the Use of the Mean Apnea-Hypopnea Duration and the Apnea-Hypopnea Index with Blood Oxygenation and Sleep Patterns in Patients with Obstructive Sleep Apnea Diagnosed by Polysomnography.

A Retrospective Study to Compare the Use of the Mean Apnea-Hypopnea Duration and the Apnea-Hypopnea Index with Blood Oxygenation and Sleep Patterns in Patients with Obstructive Sleep Apnea Diagnosed by Polysomnography.

Med Sci Monit. 2018 Mar 31;24:1887-1893

Authors: Zhan X, Fang F, Wu C, Pinto JM, Wei Y

Abstract
BACKGROUND The apnea-hypopnea index (AHI) and the mean apnea-hypopnea duration (MAD) are used to measure the severity of the symptoms of obstructive sleep apnea (OSA). The aim of this study was to compare the use of the MAD with the AHI as indicators of clinical and demographic parameters, blood oxygenation, and sleep parameters in patients diagnosed with OSA by polysomnography (PSG). MATERIAL AND METHODS A retrospective study included 511 patients with OSA diagnosed by PSG and who had the AHI and the MAD measured according to the guidelines from the American Academy of Sleep Medicine (AASM). The patients were divided into two groups: patients with a short MAD and with a long MAD, according to median duration, and using the inter-quartile range (IQR), as the data were not normally distributed. Clinical and demographic parameters were recorded. Pulse oximetry was used to measure blood oxygen saturation during sleep, sleep structure was recorded, and the Epworth Sleepiness Scale (ESS) questionnaire was used to measure daytime sleepiness. RESULTS In all 511 patients with OSA, the MAD was significantly, but weakly, correlated with the AHI (r=0.17, P<0.01), but showed no significant associations with patient age (r=0.08, P=0.06), body weight (r=0.014, P=0.75), and height (r=0.06, P=0.16). Patients with a long MAD or severe OSA (n=260) had significantly worse blood oxygen levels and sleep parameters. CONCLUSIONS For patients with severe OSA, this study showed that the MAD was a useful indicator of blood oxygenation and sleep parameters.

PMID: 29603712 [PubMed - in process]



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Management of a Severe Cervicofacial Odontogenic Infection.

Management of a Severe Cervicofacial Odontogenic Infection.

J Contemp Dent Pract. 2018 Mar 01;19(3):352-355

Authors: Tormes AK, De Bortoli MM, Júnior RM, Andrade ES

Abstract
INTRODUCTION: Odontogenic infections originate from a tooth or from its supporting structures, generally secondary to a pulp necrosis, periodontal disease, pericoronitis, apical lesions, or complications of dental procedures, which can be restricted to the alveolus or can reach the jaws and face through maxillofacial spaces. These are the most common conditions which affect the head and neck regions.
AIM: The aim of this study is to report a severe case of a cervicofacial odontogenic infection while discussing the most relevant aspects.
CASE REPORT: A 47-year-old female patient with a background of diabetes mellitus (DM) had a cervicofacial infection presenting edema and erythema in the left hemiface extending from the frontoparietal to cervical region and was submitted to extensive surgical treatment combined with antibiotic therapy.
CONCLUSION: Although the prevalence and complication rates of odontogenic infections had decreased with the advancement of diagnostic techniques, availability of effective antibiotics, and improvement in oral hygiene, still there are conditions that require attention and accurate treatment to prevent the progression of the pathology to deeper fascial spaces.
CLINICAL SIGNIFICANCE: Odontogenic infections can be treated with fewer complications if approached earlier when diagnosed while their premature clinical manifestations. However, if the treatment is postponed and the infection spreads into deeper fascial spaces, it can damage vital structures, and, consequently, threaten the patient's life. In these cases, extensive and aggressive therapy should be performed.

PMID: 29603711 [PubMed - in process]



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Practice patterns and outcomes of chemoradiotherapy versus radiotherapy alone for older patients with nasopharyngeal cancer.

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Practice patterns and outcomes of chemoradiotherapy versus radiotherapy alone for older patients with nasopharyngeal cancer.

Cancer Med. 2018 Mar 30;:

Authors: Verma V, Surkar SM, Moreno AC, Lin C, Simone CB

Abstract
Older patients are at increased risk of toxicities from aggressive oncologic therapy and of nononcologic death. A meta-analysis of non-nasopharyngeal head and neck cancers showed no statistical benefit in adding chemotherapy to radiotherapy (RT) in older patients; another meta-analysis of RT versus chemoradiotherapy (CRT) in NPC found advantages to CRT, but vastly under-represented patients ≥70 years old. This is the largest study to date evaluating outcomes of CRT versus RT alone in this population. The National Cancer Data Base (NCDB) was queried for primary nasopharyngeal cancer cases (2004-2013) in patients ≥70 years old receiving RT alone or CRT. Patients with unknown RT/chemotherapy and T1N0 or M1 disease were excluded. Logistic regression analysis ascertained factors associated with CRT delivery. Kaplan-Meier analysis evaluated overall survival (OS) between both cohorts. Cox proportional hazards modeling determined variables associated with OS. In total, 930 patients were analyzed (n = 713 (77%) CRT, n = 217 (23%) RT). Groups were relatively balanced; CRT was less frequently delivered in patients with advancing age, lower nodal burden, and females (P < 0.05 for all). Median OS in the CRT and RT groups were 35.3 versus 20.0 months, respectively (P = 0.002). On multivariate analysis, independent predictors of OS included age, comorbidities, income and insurance status, tumor grade, and stage (P < 0.05 for all). Notably, receipt of chemotherapy independently predicted for improved OS (P = 0.036). CRT, compared to RT alone, was independently associated with improved survival in NPC patients ≥70 years old. CRT appears to be a promising approach in this population, but treatment-related toxicity risks should continue to be weighed against potential oncologic benefits.

PMID: 29603669 [PubMed - as supplied by publisher]



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Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review.

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Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review.

Autism Res. 2018 Mar 30;:

Authors: Talge NM, Tudor BM, Kileny PR

Abstract
Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click-evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well-characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta-analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically-developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedges's g) for at least one ABR latency component (I, III, V, I-III, III-V, I-V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random-effects regressions to generate component-specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I-III (g = 0.7, 95% CI 0.2, 1.2), and I-V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium-to-large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co-occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
LAY SUMMARY: Auditory brainstem responses (ABR) may be associated with ASD, but participant characteristics and assessment protocols vary considerably across individual studies. Our goal is to combine the results across these studies to facilitate clarity on the topic. Doing so represents a first step in evaluating whether ABRs yield potential for informing the etiology of ASD risk and/or ASD symptom profiles.

PMID: 29603654 [PubMed - as supplied by publisher]



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Simultaneous targeting of EGFR, HER2 and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines.

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Simultaneous targeting of EGFR, HER2 and HER4 by afatinib overcomes intrinsic and acquired cetuximab resistance in head and neck squamous cell carcinoma cell lines.

Mol Oncol. 2018 Mar 30;:

Authors: De Pauw I, Lardon F, Van den Bossche J, Baysal H, Fransen E, Deschoolmeester V, Pauwels P, Peeters M, Vermorken JB, Wouters A

Abstract
The epidermal growth factor receptor (EGFR, HER1) is a therapeutic target in head and neck squamous cell carcinoma (HNSCC). After initial promising results with EGFR-targeted therapies such as cetuximab, therapeutic resistance has become a major clinical problem, and new treatment options are therefore necessary. Moreover, the relationship between HER receptors, anti-EGFR therapies and the human papillomavirus (HPV) status in HNSCC is not fully understood. In contrast to first generation EGFR inhibitors, afatinib irreversibly inhibits multiple HER receptors simultaneously. Therefore, treatment with afatinib might result in a more pronounced therapeutic benefit, even in patients experiencing cetuximab resistance. In this study, the cytotoxic effect of afatinib as single agent and in combination with cisplatin was investigated in cetuximab sensitive, intrinsically and acquired resistant HNSCC cell lines with different HPV status under normoxia and hypoxia. Furthermore, the influence of cetuximab resistance, HPV and hypoxia on the expression of HER receptors was investigated. Our results demonstrated that afatinib was able to establish cytotoxicity in cetuximab sensitive, intrinsically and acquired resistant HNSCC cell lines, independent of the HPV status. However, cross-resistance between cetuximab and afatinib might be possible. Treatment with afatinib caused a G0 /G1 cell cycle arrest as well as induction of apoptotic cell death. Additive to antagonistic interactions between afatinib and cisplatin could be observed. Neither cetuximab resistance nor HPV status significantly influenced the expression of HER receptors in HNSCC cell lines. In contrast, the expression of EGFR, HER2 and HER3 was significantly altered under hypoxia. Oxygen deficiency is a common characteristic of HNSCC tumors and these hypoxic tumor regions often contain cells that are more resistant to treatment. However, we observed that afatinib maintained its cytotoxic effect under hypoxia. In conclusion, our preclinical data support the hypothesis that afatinib might be a promising therapeutic strategy to treat HNSCC patients experiencing intrinsic or acquired cetuximab resistance.

PMID: 29603584 [PubMed - as supplied by publisher]



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Incidence of head and neck cancer in children: A Danish nationwide study from 1978 to 2014.

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Incidence of head and neck cancer in children: A Danish nationwide study from 1978 to 2014.

Pediatr Blood Cancer. 2018 Mar 30;:e27037

Authors: Grønhøj C, Hjalgrim L, Jakobsen KK, Charabi B, Mirian C, Laier GH, Kiss K, Rechnitzer C, Friborg J, von Buchwald C, Hjuler T

Abstract
BACKGROUND: Pediatric head and neck malignancies are rare and only a few descriptive epidemiological studies have been published. Using unique nationwide registries, we report age-specific incidence rates of head and neck cancer (HNC) among children during four decades.
METHODS: Data were obtained from the Danish Cancer Registry. We included children aged 0-14 years diagnosed between January 1, 1978 and December 31, 2014 with extra-orbital, nonskin and nonbone HNC. Patients were divided into nine groups in regard to tumor location: oral cavity, oropharynx, nasopharynx, hypopharynx, thyroid, major salivary glands, larynx, and middle ear. Based on the World Health Organization standard population and Danish age-specific population counts, age-adjusted incidence rates (AAIR) and average annual percentage change (AAPC) were calculated and examined for trends.
RESULTS: In total, 169 children (55.6% females) were registered with a malignant tumor in the head and neck region. The AAIR increased with an AAPC of 2.2% (95% CI, 0.8-3.7%). Females showed an AAIR of 0.54 per 100,000 person years compared to that of males, with 0.41 per 100,000 person years (P < 0.01). The AAIR was higher among children aged 10-14 years compared to 0-9-year-old children (P < 0.01). Based on morphology, a significant increase in AAIR was observed for sarcomas, with an increase of 0.16-0.27 per 100,000 person years (P < 0.05).
CONCLUSIONS: The incidence rate of pediatric HNC was higher among females and evidence of increasing rates was observed during 1978-2014, explained by an increase mainly in sarcomas.

PMID: 29603576 [PubMed - as supplied by publisher]



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Transoral endoscopic thyroid surgery via the tri-vestibular approach with a hybrid space-maintaining method: A preliminary report.

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Transoral endoscopic thyroid surgery via the tri-vestibular approach with a hybrid space-maintaining method: A preliminary report.

Head Neck. 2018 Mar 30;:

Authors: Wang Y, Zhang Z, Zhao Q, Xie Q, Yan H, Yu X, Xiang C, Zhang M, Wang P

Abstract
BACKGROUND: Transoral endoscopic thyroid surgery has been introduced in a few institutions. The purpose of this study was to present an innovative hybrid space-maintaining method for the tri-vestibular approach.
METHODS: Eighteen consecutive patients underwent transoral endoscopic thyroidectomy. Three incisions were made in the vestibule. The surgical space was maintained with CO2 insufflation along with a suspension device. Thyroidectomy and central neck dissection (CND) were performed safely and effectively.
RESULTS: The mean operation time was 124 minutes for a simple lobectomy, subtotal thyroidectomy, and isthmectomy in 8 patients, 172 minutes for hemithyroidectomy with ipsilateral CND in 8 patients, and 205 minutes for total thyroidectomy with ipsilateral CND in 7 patients. Transient superior laryngeal nerve (SLN) injury occurred in 3 patients and transient mental nerve injury was found in 1 patient. No evidence of recurrence or metastasis was found at follow-up.
CONCLUSION: This approach brings satisfactory cosmetic effect along with minimal invasion. Further study is needed to verify its validity.

PMID: 29603475 [PubMed - as supplied by publisher]



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Systematic review evaluating randomized controlled trials of smoking and alcohol cessation interventions in people with head and neck cancer and oral dysplasia.

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Systematic review evaluating randomized controlled trials of smoking and alcohol cessation interventions in people with head and neck cancer and oral dysplasia.

Head Neck. 2018 Mar 30;:

Authors: Shingler E, Robles LA, Perry R, Penfold C, Ness AR, Thomas S, Lane JA, Martin RM

Abstract
BACKGROUND: Smoking and alcohol increase the risk of head and neck cancer and affect treatment outcomes. Interventions modifying these behaviors may improve posttreatment outcomes and survival. We systematically reviewed evidence of the effectiveness of smoking/alcohol interventions in head and neck cancer and oral dysplasia.
METHODS: The AMED, CINAHL, Embase, MEDLINE, and Web of Science databases were searched for randomized controlled trials (RCTs) of smoking/alcohol interventions in people with head and neck cancer. A qualitative synthesis of the studies was conducted.
RESULTS: Three RCTs were identified: 2 smoking interventions and 1 smoking and alcohol intervention. One intervention, which was comprised of a smoking intervention based on Cognitive Behavioral Therapy and pharmacologic management compared to usual care, reduced smoking prevalence.
CONCLUSION: Further research is required into the underlying mechanisms that lead to cessation and interventions that include both pharmacological and behavioral therapy. Future RCTs should include suitable control conditions and sufficient power to assess clinical outcomes.

PMID: 29603464 [PubMed - as supplied by publisher]



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Frontline Science: IL-18 primes murine NK cells for proliferation by promoting protein synthesis, survival, and autophagy.

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Frontline Science: IL-18 primes murine NK cells for proliferation by promoting protein synthesis, survival, and autophagy.

J Leukoc Biol. 2018 Mar 30;:

Authors: El-Darawish Y, Li W, Yamanishi K, Pencheva M, Oka N, Yamanishi H, Matsuyama T, Tanaka Y, Minato N, Okamura H

Abstract
Combined stimulation by IL-2 and IL-18 effectively promotes proliferation of NK cells, whereas singular stimulation does not. In this study, synergistic effects of these cytokines on NK cells proliferation was analyzed, focusing on the roles of IL-18. In splenic resting NK cells from IL-18KO mice, IL-18 rapidly activated NF-κB independently of IL-2, and activated or up-regulated various molecules downstream of PI3K/AKT and mTOR, including S6, Bcl-XL, ATG5, and LC3II, accompanying increases in cell growth and survival. Thus, IL-18 alone was revealed to augment various cellular processes (gene transcription, protein synthesis, survival) in the absence or presence of IL-2. Notably, combined IL-18 and IL-2 promoted autophagosome formation. In addition, priming NK cells with IL-18 augmented IL-2R, especially CD25, and enabled cells to respond to IL-2, resulting in activation of STAT3 and STAT5, followed by increase of cyclin B1 leading to proliferation. However, IL-2 alone failed to activate STAT3 or STAT5 in resting IL18KO NK cells. These results clarify the distinct roles of IL-2 and IL-18 in NK cell proliferation, and the intrinsic roles of IL-18 in various cellular processes, suggesting a range of functions of IL-18 expressed in an array of nonhematopoietic cells.

PMID: 29603367 [PubMed - as supplied by publisher]



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A Clinical Decision Support System Using Ultrasound Textures and Radiologic Features to Distinguish Metastasis From Tumor-Free Cervical Lymph Nodes in Patients With Papillary Thyroid Carcinoma.

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A Clinical Decision Support System Using Ultrasound Textures and Radiologic Features to Distinguish Metastasis From Tumor-Free Cervical Lymph Nodes in Patients With Papillary Thyroid Carcinoma.

J Ultrasound Med. 2018 Mar 30;:

Authors: Abbasian Ardakani A, Reiazi R, Mohammadi A

Abstract
OBJECTIVES: This study investigated the potential of a clinical decision support approach for the classification of metastatic and tumor-free cervical lymph nodes (LNs) in papillary thyroid carcinoma on the basis of radiologic and textural analysis through ultrasound (US) imaging.
METHODS: In this research, 170 metastatic and 170 tumor-free LNs were examined by the proposed clinical decision support method. To discover the difference between the groups, US imaging was used for the extraction of radiologic and textural features. The radiologic features in the B-mode scans included the echogenicity, margin, shape, and presence of microcalcification. To extract the textural features, a wavelet transform was applied. A support vector machine classifier was used to classify the LNs.
RESULTS: In the training set data, a combination of radiologic and textural features represented the best performance with sensitivity, specificity, accuracy, and area under the curve (AUC) values of 97.14%, 98.57%, 97.86%, and 0.994, respectively, whereas the classification based on radiologic and textural features alone yielded lower performance, with AUCs of 0.964 and 0.922. On testing the data set, the proposed model could classify the tumor-free and metastatic LNs with an AUC of 0.952, which corresponded to sensitivity, specificity, and accuracy of 93.33%, 96.66%, and 95.00%.
CONCLUSIONS: The clinical decision support method based on textural and radiologic features has the potential to characterize LNs via 2-dimensional US. Therefore, it can be used as a supplementary technique in daily clinical practice to improve radiologists' understanding of conventional US imaging for characterizing LNs.

PMID: 29603330 [PubMed - as supplied by publisher]



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In response to Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease.

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In response to Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease.

Laryngoscope. 2018 Mar 30;:

Authors: Lechien JR, Karkos PD, Harmegnies B, Saussez S

PMID: 29603239 [PubMed - as supplied by publisher]



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A novel technique for tracheal reconstruction using a resorbable synthetic mesh.

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A novel technique for tracheal reconstruction using a resorbable synthetic mesh.

Laryngoscope. 2018 Mar 30;:

Authors: Chen D, Britt CJ, Mydlarz W, Desai SC

PMID: 29603235 [PubMed - as supplied by publisher]



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Rendezvous endoscopic recanalization for complete esophageal obstruction.

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Rendezvous endoscopic recanalization for complete esophageal obstruction.

Surg Endosc. 2018 Mar 30;:

Authors: Fusco S, Kratt T, Gani C, Stueker D, Zips D, Malek NP, Goetz M

Abstract
BACKGROUND AND STUDY AIM: Complete esophageal obstruction after (chemo)radiation for head and neck cancers is rare. However, inability to swallow one's own saliva strongly inflicts upon quality of life. Techniques for endoscopic recanalization in complete obstruction are not well established. We assessed the efficacy and safety of rendezvous recanalization.
PATIENTS AND METHODS: We performed a retrospective review of all patients who underwent endoscopic recanalization of complete proximal esophageal obstruction after radiotherapy between January 2009 and June 2016. Technical success was defined as an ability to pass an endoscope across the recanalized lumen, clinical success by changes in the dysphagia score. Adverse events were recorded prospectively.
RESULTS: 19 patients with complete obstruction (dysphagia IV°), all of whom had failed at least one trial of conventional dilatation, underwent recanalization by endoscopic rendezvous, a combined approach through a gastrostomy and perorally under fluoroscopic control. Conscious sedation was used in all patients. In 18/19 patients (94.7%), recanalization was technically successful. In 14/18 patients (77.8%), the post-intervention dysphagia score changed to ≤ II. Three patients had their PEG removed. Factors negatively associated with success were obstruction length of 50 mm; and tumor recurrence for long-term success. No severe complications were recorded.
CONCLUSIONS: Rendezvous recanalization for complete esophageal obstruction is a reliable and safe method to re-establish luminal patency. Differences between technical and clinical success rates highlight the importance of additional functional factors associated with dysphagia. Given the lack of therapeutic alternatives, rendezvous recanalization is a valid option to improve dysphagia.

PMID: 29602985 [PubMed - as supplied by publisher]



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A Review of Promising Natural Chemopreventive Agents for Head and Neck Cancer.

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A Review of Promising Natural Chemopreventive Agents for Head and Neck Cancer.

Cancer Prev Res (Phila). 2018 Mar 30;:

Authors: Crooker K, Aliani R, Ananth M, Arnold L, Anant S, Thomas SM

Abstract
Head and neck squamous cell carcinoma (HNSCC) accounts for 300,000 deaths per year worldwide and overall survival rates have shown little improvement over the past three decades. Current treatment methods including surgery, chemotherapy, and radiotherapy leave patients with secondary morbidities. Thus, treatment of HNSCC may benefit from exploration of natural compounds as chemopreventive agents. With excellent safety profiles, reduced toxicities, antioxidant properties, and general acceptance for use as dietary supplements, natural compounds are viewed as a desirable area of investigation for chemoprevention. Though most of the field is early in development, numerous studies display the potential utility of natural compounds against HNSCC. These compounds face additional challenges such as low bioavailability for systemic delivery, potential toxicities when consumed in pharmacological doses, and acquired resistance. However, novel delivery vehicles and synthetic analogs have shown overcome some of these challenges. This review covers eleven promising natural compounds in the chemoprevention of HNSCC including vitamin A, curcumin, isothiocyanate, green tea, luteolin, resveratrol, genistein, lycopene, bitter melon, withaferin A, and guggulsterone. The review discusses the therapeutic potential and associated challenges of these agents in the chemopreventive efforts against HNSCC.

PMID: 29602908 [PubMed - as supplied by publisher]



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Pancreaticoduodenectomy is justified in a subset of elderly patients with pancreatic ductal adenocarcinoma: A population-based retrospective cohort study of 4,283 patients.

Pancreaticoduodenectomy is justified in a subset of elderly patients with pancreatic ductal adenocarcinoma: A population-based retrospective cohort study of 4,283 patients.

Int J Surg. 2018 Mar 28;:

Authors: Lu L, Zhang X, Tang G, Shang Y, Liu P, Wei Y, Gong P, Ma L

Abstract
BACKGROUND: The survival benefit of pancreaticoduodenectomy (PD) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) is still unclear.
METHODS: Data pertaining to elderly (age ≥75 years) and younger (age <75 years) patients with potentially curable PDAC who underwent pancreaticoduodenectomy in the period 2004-2013 were extracted from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards model and stratified Kaplan-Meier survival analyses were performed.
RESULTS: A total of 4283 patients (3256 younger patients and 1027 elderly patients) were included. On multivariate analysis, advanced age (age ≥75 years) was not found to be an independent risk factor for DSS (age ≥75 years vs. age <75 years, HR = 1.043, P = 0.418). Survival analysis disaggregated by gender, tumor size, American Joint Committee on Cancer stage, and tumor differentiation showed comparable DSS in younger and elderly patients (log-rank test). Among patients with poorly-differentiated or undifferentiated tumors, those in the elderly age-group experienced shorter DSS as compared to that of younger patients (poorly-differentiated: elderly vs. younger, 32.779 months vs. 42.198 months, P = 0.043; undifferentiated: elderly vs. younger, 17.500 months vs. 43.028 months, P = 0.210). However, PD was still warranted for elderly patients with poorly-differentiated tumors (surgery vs. without surgery, 32.779 months vs. 11.490 months, P < 0.001). Patients with undifferentiated tumors experienced only a minor survival benefit after PD (surgery vs. without surgery, 17.500 months vs. 11.699 months, P = 0.330).
CONCLUSIONS: Advanced age (age ≥75 years) is not an independent risk factor for DSS. PD is justified in a subset of elderly PDAC patients; however, it should be performed in a high-volume center to minimize the risk of post operative complications. Future studies should explore individualized treatment strategies for elderly patients with undifferentiated tumors.

PMID: 29604352 [PubMed - as supplied by publisher]



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