The First Reported Case of Primary Intestinal-type Adenocarcinoma of the Middle Ear and Review of the Literature.

Objective: Adenocarcinoma of the middle ear is a rare entity that must be distinguished from other adenomatous tumors of the temporal bone. We present the first patient of an intestinal-type adenocarcinoma originating from the middle ear. Patients: A 58-year-old woman presented with an 8-year history of left otorrhea. Her middle ear effusions were quite thick and gummy. She underwent eight sets of pressure-equalization tubes within 3 years. In 2011, her physical examination identified a middle ear mass, and she underwent mastoidectomy. A middle ear adenoma was resected. She underwent an additional three mastoidectomies for recurrence, with pathology from the 4th mastoidectomy revealing a diagnosis of adenocarcinoma. Imaging, at that time, showed an extensive temporal bone and Eustachian tube tumor. Interventions: She underwent a left subtotal temporal bone resection, parotidectomy, infratemporal fossa resection, dural resection, and microvascular free flap reconstruction followed by postoperative proton beam radiotherapy. Main Outcome Measures: The final pathology report revealed intestinal-type adenocarcinoma. Results: Treatment was successful and the patient remains disease free 4 years later. Conclusion: This is the first report of an intestinal-type adenocarcinoma of the middle ear and temporal bone. This patient also illustrates the difficulty of accurate histologic diagnosis of adenomatous tumors of the middle ear. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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A New Slim Modiolar Electrode Array for Cochlear Implantation: A Radiological and Histological Study.

Hypothesis: To explore the results of a new slim modiolar electrode array (SMA) with respect to intracochlear placement and trauma evaluated by detailed radiologic imaging and histology. Background: Hearing and structure preservation is the goal of cochlear implantation for advanced hearing outcomes. Currently, this is most consistently achieved with thin lateral wall electrodes. Modiolar electrodes are located nearer the modiolus and may provide some electrophysiological advantages, but have a greater tendency for causing insertion trauma. Methods: The SMA was implanted in 20 fresh-frozen human temporal bones (TB). All TBs were scanned pre- and postoperatively with cone beam computed tomography. For atraumatic insertion, the round window approach was preferred. Scalar localization and trauma were analyzed by three-dimensional image fusion reconstructions of the pre- and postimplant scans. The TBs underwent histologic examination to validate the radiologic findings. Results: Insertion through the round window was performed in 19 TBs and through a cochleostomy in one TB. In one TB trauma in the form of scala translocation was identified radiologically and histologically. In the remaining TBs there was no insertion trauma. Adequate modiolar localization of the SMA was found in 19 of 20 TBs. The mean angular insertion depth was 400 degrees without correlation to cochlea size. There was no significant statistical difference between the radiological and histological measurements of electrode localization. Conclusion: The SMA showed consistent and atraumatic insertion results in TBs. Pre- and postimplant cone beam computed tomography with image fusion was shown to be very accurate for the assessment of electrode position and insertion trauma. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Surgery With or Without Postoperative Radiation Therapy for Early-stage External Auditory Canal Squamous Cell Carcinoma: A Meta-analysis.

Objective: External auditory canal squamous cell carcinoma (EACSCC) is a rare disease with no standard treatment supported by high-level evidence. The aim of this study was to investigate EACSCC prognoses according to treatment modality and thus determine the optimal intervention for early-stage disease. Data Sources: PubMed, Scopus, and Ichushi-Web searches of the English and Japanese-language literature published between January 1, 2006 and December 31, 2016 were performed using the key words "external auditory canal cancer" and "temporal bone cancer." Study Selection: Articles related to EACSCC that include the 5-year overall survival rate or individual patient data for histological types, follow-up periods, and final outcomes were enrolled. Data Extraction: Sex, age, Moody's modified Pittsburgh stage, type of treatment modality, type of operation, follow-up period, and 5-year survival rates were extracted. Data Synthesis: Twenty articles were used for the aggregate meta-analysis using a random-effects model, and 18 articles that reported 99 patients with early-stage EACSCC were used for the individual patient data meta-analysis. Conclusion: The 5-year overall survival rate of early-stage EACSCC was 77%. Postoperative radiation therapy (PORT) was performed in 45% of stage I patients and 68% of stage II patients. Survival analysis of all patients showed no differences between the surgery-only and PORT groups; however, PORT exhibited a better prognosis than surgery alone among patients with stage I disease (p = 0.003, log-rank test). This result indicated that PORT can be the standard therapy for stages I and II EACSCC. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Hearing Preservation During Cochlear Implantation and Electroacoustic Stimulation in Patients With SLC26A4 Mutations.

Background and Objectives: Patients with SCL26A4 mutations presenting with Mondini deformity and enlarged vestibular aqueduct (EVA) tend to have comparable residual hearing. Although cochlear implantation (CI) produces good results in this group, deterioration of residual hearing can be an adverse event after surgery due to accompanying cochlear malformation and perilymph leakage during cochleostomy. The purpose of this study was to investigate if CI in patients with SCL26A4 mutations via the round window (RW) approach could achieve preservation of residual hearing, and to evaluate their speech reception with electroacoustic stimulation (EAS). Subjects and Methods: This is a retrospective chart review of eight patients with bilateral EVA, who were bi-allelic patients with SCL26A4 mutations. CI was performed in all patients by a single surgeon using the RW approach. Audiological results were compared before and after implantation. Results: Additional hearing loss after CI was less than 10 dBHL in five out of eight patients. Average hearing deterioration after CI was 8.75 dB (range, 0-26). Six out of eight patients used EAS mode after CI. The acoustic stimulation frequency ranged from 271 to 438 Hz. Patients showed better speech recognition in quiet and in noise using EAS mode compared with electrical stimulation alone. Conclusions: Preservation of residual hearing could be achieved after CI in patients with the SLC26A4 mutation via the RW approach. For successful preservation of residual hearing, application of newly-developed soft electrode and meticulous surgical is necessary. Our study showed that patients with the SLC26A4 mutation can be good candidates for EAS surgery. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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The Effect of Citalopram Versus a Placebo on Central Auditory Processing in the Elderly.

Objective: Evaluate the effects of therapy with citalopram on the central auditory processing in the elderly measured by central auditory tests. Study Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Tertiary referral center. Patients: Thirty-nine patients older than 60 years with normal hearing thresholds or symmetrical sensorineural hearing loss up to 70 dBHL, word-recognition score equal to or better than 70%, and diagnosed with central auditory processing disorders completed the study. They underwent the mini-mental state examination, as a way to screen those with the possibility of dementia; they also underwent the Beck depression inventory, for screening individuals with depression. Intervention: Citalopram 20 mg/d or placebo for 6 months. Main Outcome Measure: The central auditory tests were applied to the selection of individuals with auditory processing disorders and repeated after 6 months' treatment. The tests were sound localization, speech in noise, dichotic digits test, pitch pattern sequence, duration pattern test, and gaps-in-noise. Results: Comparisons of central auditory tests pre- and posttreatment in groups showed: sound localization (p = 0.022), pitch pattern sequence humming (p = 0.110), pitch pattern sequence nomination (p = 0.355), duration pattern test humming (p = 0.801), duration pattern test nomination (p = 0.614), and gaps-in-noise (p = 0.230). Dichotic tests in right and left ears respectively: speech in noise (p = 0.949; p = 0.722), dichotic digits test (p = 0.943; p = 0.513). Conclusion: There was no clinical effect with the use of citalopram in central auditory processing tests of the subjects. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Oral Administration of Clinical Stage Drug Candidate SENS-401 Effectively Reduces Cisplatin-induced Hearing Loss in Rats.

Hypothesis: SENS-401, an oral clinical-stage drug, may reduce cisplatin-induced hearing loss and cochlear damage in an in vivo model. Background: Cisplatin is commonly associated with hearing loss, causing significant learning and behavioral difficulties in the pediatric cancer population, and for which there are currently no clinical solutions. SENS-401 has previously been shown to improve acoustic trauma-induced hearing loss in vivo. Methods: The effect of SENS-401 (R-azasetron besylate) on cisplatin IC50 values was evaluated in a panel of cisplatin-sensitive cell lines (NIH:OVCAR-3, SK-N-AS, NCI-H460, FaDu). Auditory brainstem response and distortion product otoacoustic emission tests were performed in a rat model of cisplatin-induced hearing-loss (8 mg/kg, day 1) at baseline, and after 14 days of SENS-401 (6.6, 13.2, 26.4 mg/kg/d). Cochlear outer hair cells were counted after immunolabeling for myosin-VIIa. Results: Cisplatin cytotoxicity was not impacted by the addition of SENS-401 (up to 10 [mu]M) in any of the cell types evaluated. In vivo, all SENS-401 doses significantly improved auditory brainstem response threshold shift (up to 30 dB) and distortion product otoacoustic emission amplitude loss (up to 19 dB) over placebo. Body weight and survival were not significantly different between rats receiving placebo and those receiving 26.4 mg/kg SENS-401. Significantly more surviving outer hair cells were present after SENS-401 treatment compared with placebo (p

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Duration of Eligibility Prior to Cochlear Implantation: Have We Made Any Progress?.

Objective: The objective is to determine if eligibility (as defined as the duration of severe to profound hearing loss before cochlear implantation [CI]) has changed over the 30 years since Food and Drug Administration approval. Data Sources: English-language, peer-reviewed articles, theses, and trial data available through PubMed and Cochrane Library databases up until and including May 31, 2016. Study Selection: One thousand six unique articles were identified. Prospective studies that reported duration of severe/profound hearing loss before CI in adult patients were included. Retrospective studies, reviews, meta-analyses, articles reporting pediatric or mixed data, hybrid/electroacoustic CI, and articles from centers outside the United States were excluded. Seventy-one studies met inclusion criteria and were included for analysis. Data Extraction: Contributing authors independently reviewed included studies for data validity and applicability. Data Synthesis: Metaregression was used to assess the relationship between the year of publication and duration of hearing loss. To account for a possible age effect, a second model was estimated including mean age at the time of study as a covariate. Conclusion: A positive association between study year and the duration of hearing loss before implantation was found showing a 0.28-year increase in the duration of hearing loss for every increasing study year. Contrary to conventional assumption, duration of eligibility for CI appears to be increasing. Though the reasons for this are not clear, current strategies to increase both awareness and access to CI seem to be falling short. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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The Seasonal Variation of Benign Paroxysmal Positional Vertigo.

Objective: Benign paroxysmal positional vertigo (BPPV) is characterized by recurrent episodes of positional vertigo due to dislodged otoconia debris within the semicircular canals. Many studies have proposed a correlation between Vitamin-D deficiency and recurrent BPPV. In the UK, serum Vitamin-D falls during the winter, reaching its lowest level in May and it is highest level in September. We hypothesize that if there is a relationship between BPPV and Vitamin-D levels, one would expect to see a seasonal variation in the incidence of BPPV among UK residents. Methods: A retrospective review of clinic letters and general practitioner referrals for patients presenting to a University Otolaryngology department over a 4-year period. Patients were divided into two groups: those presenting during the months associated with low serum Vitamin-D levels, and those presenting during the months associated with high serum Vitamin-D levels. Results: Three hundred thirty-nine patients were identified with posterior canal BPPV as a consequence of having had a positive Dix-Hallpike maneuver recorded in the clinical notes between October 2012 and October 2016. A Wilcoxon rank-sum test demonstrated there to be a statistically significant difference between the low serum Vitamin-D group and the high serum Vitamin-D group (p = 0.0367). Conclusion: The results confirm that there is a seasonal variation in the incidence of BPPV. This study is important as it adds to the mounting literature suggesting an association between serum Vitamin-D levels and BPPV. Second, it suggests a therapeutic strategy to improve outcomes in affected patients. Third, it adds significance to the hypothesized role of calcium metabolism for the development of inner ear disease. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Patulous Eustachian Tube Dysfunction: Patient Demographics and Comorbidities.

Objective: The objective is to describe a large cohort of patients presenting with patulous Eustachian tube (pET) dysfunction. Study Design: Retrospective patient series. Setting: Tertiary referral center. Patients: All outpatient visits (2004-2016) that were assigned ICD9 code (381.7-Patulous Eustachian tube) were screened. Only patients with observed tympanic membrane movements during ipsilateral nasal breathing or acoustic reflex decay testing demonstrating transmitted nasal breathing were included (n = 190, n = 239 ears). Main Outcome Measures: Demographics and nasopharyngoscopy/otomicroscopy findings by comorbidities. Results: The majority (54%) was female and mean age of symptom onset was 38.0 (SD 20.0) years. Common symptoms included voice autophony (93%), breath autophony (92%), aural fullness (57%), pulsatile tinnitus (17%), and crackling or rumbling sounds (14%). Symptoms increased in frequency and duration with time (65%), were exacerbated with exercise (27%), and improved with placing the head in a dependent position (65%), sniffing (28%), upper respiratory infection (8%), and ipsilateral internal jugular vein compression (12%). In 52% pET was bilateral. Common comorbidities include environmental allergy (49%), weight loss (35%), laryngopharyngeal reflux (33%), anxiety (31%), autoimmunity (13%), and neuromuscular disease (8%). Allergy and anxiety patients were younger and more likely to have tonic contraction of the tensor veli palatini on exam (p

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Intracanalicular Vestibular Schwannomas: Initial Clinical Manifestation, Imaging Classification, and Risk Stratification for Management Proposal.

Introduction: There is no consensus about the use of observation as a therapeutic modality for intracanalicular vestibular schwannoma (ICVS). The objective of this study was to describe tumor evolution, its correlation with initial size, stage of vestibular schwannoma, clinical presentation and to propose a risk classification for tumor growth with a therapeutic decision algorithm. Methods: Fifty-three patients with ICVS were followed prospectively from 2010 to 2015. The mean follow-up was 32 months. Patients underwent clinical examination, audiogram, magnetic resonance imaging at 6, 12, and then 12 months intervals within the first 5 years of initial diagnosis. We analyzed the patient's clinical course, audiologic changes, initial tumor location, and correlation of different parameters with ICVS growth. Results: Fourteen patients (26%) deteriorated their hearing level and 17 patients (27%) showed tumor growth during the follow-up period. Growth was noted during the first year of observation in 13 patients (76.5%). Considering initial presentation: tumor size, intracanalicular staging, and hearing level, patients with larger vestibular schwannoma, extension to the fundus regardless of tumor size, higher initial pure-tone average, and speech recognition test showed a significantly higher rate of tumor growth. ICVS evolution was not correlated with hearing deterioration with time. Discussion: We should consider observation a therapeutic modality. We valid the intrameatal staging as prognostic factor and propose a stratification of patients into low, moderate, or high risk for potential tumor growth to guide the initial management of ICVS. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Outcome of delayed miniplate osteosynthesis of maxillofacial fractures in a Nigerian tertiary institution

Olufemi K Ogundipe, Gabriel Elekwachi, Odunayo Babatola

African Journal of Trauma 2016 5(2):31-35

Background: This report describes treatment outcome following delayed miniplate osteosynthesis (MPO) of maxillofacial fractures. Materials and Methods: The records of patients who underwent delayed MPO of facial fractures from January 2011 to December 2014 at the Oral and Maxillofacial surgery Unit of the Federal Medical Centre, Owo, Nigeria were retrospectively reviewed. Data retrieved were age, gender, etiology of trauma, site of fractures, and time lapse from injury to treatment. Follow-up at postoperative intervals consisted of clinical and radiographic examinations. Outcome variables such as wound infection, wound dehiscence, malocclusion, hardware failure, fracture stability, and neurosensory disturbance were recorded. Results: Thirty-one patients with 52 facial fractures were treated. There were 18 (58.1%) mandibular, 8 (25.8%) maxillary fracture while 5 (16.1%) fractures occurred in both jaws. All patients had a stable fixation and normal healing. Thirteen complications occurred in 11 patients representing 35.5% of the total. Malocclusion and wound infection were the most common complication. More complications occurred in late treatment group. Conclusion: MPO with or without postoperative intermaxillary fixation is effective in the delayed facial fracture. Treatment delay may increase the incidence of complications.

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Fatal traumatic slicing injuries of the chest: An industrial death and safety concerns

Sunday S Soyemi, John O Obafunwa, Francis A Faduyile, Oluseun O Williams, Festus E Emiogun, Fadesewa O Osuolale, Oluwayemisi O Kila

African Journal of Trauma 2016 5(2):54-57

A 36-year-old male truck driver of a mattress manufacturing company in Lagos was allegedly found dead on the rotary conveyor belt of a foam slicing machine in the factory. A visit to the scene of the event including examination of the conveyor belt and interrogation of the industrial nurse and chief security officer was made. Postmortem examination revealed single transverse incised wound on the chest, left and the right arms. Internal examination revealed incision on the 6th rib anteriorly, right hemothorax and a linear incision on the base of the left ventricle. Other findings included incision on the liver, the left hemidiaphragm, and hemoperitoneum. Death was ascribed to multiple injuries following sharp force trauma to the chest and abdomen in an industrial accident. Due to lack of toxicological facilities, blood level analysis of alcohol, other intoxicants, or substance abuse could not be checked for. This would have ruled out alcohol intoxication, substance abuse, or drug overdose. Suicide was ruled out judging from the decedent's medical and social history. The manner of death, in this case, was in our opinion accidental. This case has brought to the fore one of many occurrences of industrial deaths following inadequacy of safety measures and equipment in the company. There has never been a situation where culpable individual in charge of safety is brought to book in this environment. It has also highlighted the problems that could be faced by forensic pathologist in deciding manner of death in this type of situation.

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Changing pattern in the treatment of mandibular fractures in North-Western Nigeria

Adebayo Aremu Ibikunle, Abdurrazaq Olanrewaju Taiwo, Ramat Oyebunmi Braimah, Olalekan Micah Gbotolorun

African Journal of Trauma 2016 5(2):36-42

Background: Maxillofacial fractures constitute a significant proportion of fractures seen at tertiary hospitals. Management of maxillofacial fractures is challenging and often associated with reduced quality of life among patients if not properly managed. This study was designed to analyze the trend in management of maxillofacial fractures at Usmanu Danfodiyo University Teaching Hospital, Sokoto, Northwest Nigeria between 2011 and 2016. Materials and Methods: Data on the sociodemographic characteristics, etiology, type of fracture, and treatment done were retrieved. Data analysis was done with SPSS and comparisons were made using Chi-square and t-test. Statistical significance was set at P < 0.05. Results: A total of 341 fracture sites were observed in 201 patients, the majority were males giving a male to female ratio of 6.2:1. The overall modal age group at presentation was the 21–30 year age group accounting for 78 (36.3%) of all cases seen. Road traffic accident (RTA) was the principal etiological factor accounting for 137 (63.7%) of the fracture cases seen. The mandibular body and dentoalveolar sites were the most frequently occurring fracture sites on the mandible accounting for 69 (20.2%) and 42 (12.3%) of all fractures. A comparison of the etiological factors among groups of patients based on the year of presentation and gender was statistically significant (P = 0.02). A comparison of the mode of treatment (open reduction and internal fixation [ORIF] or closed reduction) among patients based on the year of treatment was statistically significant (P < 0.001). Conclusion: RTA remains the foremost cause of maxillofacial fractures in our environment. Despite a variety of challenges, ORIF is gradually being embraced as a viable mode of treatment in our center.

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Community-based study of road traffic accident among Almajirai in Zaria

Jerry Godfrey Makama, Tukur Dahiru, Alaji A Aliyu

African Journal of Trauma 2016 5(2):48-53

Background: Trauma is a leading cause of morbidity and mortality among people of age <45 years. Almajiri is a boy of age 5–15 years that has left his parents to a distanced place in search of Islamic knowledge. They are often left on their own to cater for themselves, roaming on roads and streets from one place to another searching for alms and food. Therefore, we aim to assess the characteristics of road traffic injury among the Almajirai in Zaria. Materials and Methods: This was a cross-sectional, descriptive study, conducted in Zaria metropolis from June to December 2012. A multistage sampling technique was used to sample clusters of Almajirai. A structured interviewer-administered questionnaire was used to obtain the data. The information obtained from the respondents included the biodata, basic understanding of the use of roads, application of traffic rules and regulations, involvement in road traffic crash (RTC), the frequency and severity of RTC, where the Almajiri was managed and the outcome of each episode. The analysis was done using SPSS version 20 for the purpose of generating frequency tables, pie and bar charts including mean and Chi-square where applicable. Results: A total of 417 Almajirai participated in the study. Of this number, three hundred and sixteen (75.8%) admitted being involved in at least one form of RTC while 101 (24.2%) were not. Most accidents (23.5%) occurred in their neighborhoods and during rush hours (25%). Only 1%–2% had basic knowledge of road signs and proper use of busy roads. The majority (41.5%) were involved as pedestrian with injury, commonly, affecting the lower extremity. Conclusion: RTC was a significant cause of injury among the Almajirai in Zaria. The most common injury was trauma to the lower extremity. Special attention needs to be paid to this group of children in our society by all road users.

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Motorcycle accident mortality in Lagos, Nigeria: Impact of a traffic law

Festus Edobor Emiogun, Francis Adedayo Faduyile, Sunday Sokunle Soyemi, Olugbenga Olaide Oyewole

African Journal of Trauma 2016 5(2):43-47

Introduction: The use of the motorcycles for commercial purposes has been associated with a high rate of road traffic injuries and mortality in Nigeria. This study is to examine the effects of newly introduced traffic laws on the mortality rate as well as pattern of injury following the enforcement of the laws. Methodology: This is a 4-year retrospective autopsy study of motorcycle accident deaths in Lagos State University Teaching Hospital, Ikeja. The study period was divided into two parts; 2 years before the law, August 2010–July 2012 and 2 years after the law, August 2012–July 2014. The anatomical location of the injuries as well as the cause of death of the patients was extracted from the register and the data were analyzed using SPSS version 20. Test for statistical significance was set as P < 0.05. Results: There were 128 motorcycle death autopsies recorded during the period of study with 96 cases (75%) before the law and 32 cases (25%) after the law. The frequency of head injury was 39.8% before the law and 43.6% after the law. The proportion of road traffic accident deaths due to motorcycle crashes was from 23.4% before the law to 11.2% after the law. Conclusion: Head injury is the most frequent anatomical region of injury in both periods. There is a 3-fold decrease in the proportion of death from motorcycle crashes following the enforcement of the traffic law.

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Closed circuit refeeding biliary drainage in a complex blunt hepatobiliary trauma: A novel technique

Harish Jayaram, Preetham Poddutoor, Jyoti M Bothra, K Lalatendu Kumar

African Journal of Trauma 2016 5(2):58-61

Blunt trauma to the abdomen is common in children causing injuries of varying severity. We present a complex case of hepatobiliary, gastrointestinal, and renal artery injuries needing a tailored management strategy and a novel technique of nutrition for the best possible outcome for the patient. Our patient in this case report had extensive hepatobiliary trauma with complete biliary duct and duodenal transection and renal artery thrombosis. He was managed by staged surgeries comprising biliary diversion and duodenal repair in the first stage and undiversion of the system in the second surgery. This is a novel technique as the nutrition was maintained by a closed circuit of bile redrainage into the jejunostomy tube achieving a physiological drainage pattern and circumventing the need of parental nutrition.

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Otosclerosis and complications of stapedectomy: CT and MRI correlation

Publication date: Available online 10 August 2017
Source:Alexandria Journal of Medicine
Author(s): Heba Ibrahim Ali, Nivan Hany Khater




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Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars

Abstract

Colorectal cancer (CRC) is a leading cause of tumor-related morbidity and mortality worldwide, with mortality most often attributable to metastatic disease. Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, has a significant role in the treatment of metastatic CRC (mCRC). However, patient access to bevacizumab may be limited in some regions or circumstances, owing to factors related to insurance coverage, reimbursement, patient out-of-pocket costs, or availability. As a result, outcomes for patients with mCRC may be worsened. Additionally, counterfeit bevacizumab has infiltrated legitimate supply chains, exposing patients to risk. Oncologists may also be affected detrimentally, since resolving access issues can be time-consuming and demoralizing. The imminent expiry of patents protecting bevacizumab provides other manufacturers with the opportunity to produce highly similar versions known as biosimilars. High-quality, safe, and effective biosimilars have the potential to expand access to bevacizumab. Most of the bevacizumab biosimilars currently in development are in clinical trials in patients with non-small-cell lung cancer, and future authorization for mCRC indications will, therefore, be based on extrapolation. This article reviews the current role of bevacizumab in the management of mCRC, the possible barriers associated with diminished access to bevacizumab, and the potential bevacizumab biosimilars in development. How biosimilars may impact the treatment of mCRC is also discussed.

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Soft-diet feeding impairs neural transmission between mitral cells and interneurons in the mouse olfactory bulb

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Tomohiro Noguchi, Chizuru Utsugi, Makoto Kashiwayanagi
(Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors. Release of GABA from inhibitory interneurons at the olfactory bulb induces inhibitory currents at the mitral cells, which are output neurons from the olfactory bulb. (Design) In the present study, we measured spontaneous inhibitory postsynaptic currents (sIPSCs) at the mitral cells of mice fed a soft diet in order to explore the effects of changes in texture of diets on neural function at the olfactory bulb. (Results) The soft-diet feeding extended the intervals between sIPSCs and reduced their peak amplitudes. (Conclusions) The present results suggest that soft-diet feeding in mice attenuates the neural functions of inhibitory interneurons at the olfactory bulb.

Graphical abstract

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The Vascular Niche Regulates Hematopoietic Stem and Progenitor Cell Lodgment and Expansion via klf6a-ccl25b

Publication date: Available online 10 August 2017
Source:Developmental Cell
Author(s): Yuanyuan Xue, Junhua Lv, Chunxia Zhang, Lu Wang, Dongyuan Ma, Feng Liu
In mammals, hematopoietic stem and progenitor cells (HSPCs) rapidly expand in the fetal liver (FL), but the underlying mechanism remains unclear. Here, we characterize zebrafish caudal hematopoietic tissue (CHT) and identify an important cellular and molecular mechanism of HSPC expansion. Time-lapse imaging showed that HSPCs localize adjacent to vascular endothelial cells (ECs), and their migration and expansion display caudal vein-specific orientation in the CHT. RNA sequencing and functional analysis identified that an EC-expressed transcription factor, Krüppel-like factor 6a (Klf6a), is essential for the CHT niche. We further demonstrated that Klf6a directly regulates the expression of the chemokine (C-C motif) ligand 25b to modulate HSPC lodgment and proliferation. Ex vivo culture results support the conserved role of Ccl21/Ccr7 signaling in promoting HSPC expansion in mammals. Together, we identify the Klf6a-Ccl25b/Ccr7 axis in controlling the complex HSPC-CHT niche interaction, which may be applicable to in vitro expansion or engraftment of HSPCs after transplantation.

Graphical abstract

Teaser

The molecular mechanisms underlying hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Xue et al. reveal that vascular niche-derived chemokine signals are required for HSPC lodgment and expansion in the zebrafish caudal hematopoietic tissue.


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Aims and Scope & Editorial Board

Publication date: July 2017
Source:Bioactive Carbohydrates and Dietary Fibre, Volume 11





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Treatment of Patients With Hepatitis C Virus infection (Genotype 4) With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

Background: Hepatitis C virus infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir-sofosbuvir (LDV/SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. Methods: This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (Cohort A) and a cohort of postliver transplantation patients (Cohort B). Patients received LDV/SOF (90 mg-400 mg) once daily for 12-24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. Results: A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in KFSH&RC; 55% cohort A and 44% cohort B received ribavirin. Sustained virological response SVR12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, p value=0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. Conclusions: Ledipasvir-sofosbuvir without ribavirin is an effective and safe treatment option for patients with HCV genotype 4 infection in pre and postliver transplant setting. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Temperature-dependent performance of competitive native and alien invasive plant species

Publication date: October 2017
Source:Acta Oecologica, Volume 84
Author(s): Uhram Song
To assess the likely impacts of environmental change, the responses of two well-known invasive plant species, native Pueraria lobata and alien Humulus japonicus, to differences in growth temperature were studied in South Korea. Habitat preferences, physiological responses such as photosynthetic rates and chlorophyll contents, growth rates, and nutrient contents were quantified for each species. A competition experiment was conducted to evaluate the temperature preferences of the two species. All results indicated that the alien species H. japonicus can take advantage of elevated temperatures (35 °C) to enhance its competitive advantage against the native species P. lobata. While H. japonicus took advantage of elevated temperatures and preferred high-temperature areas, P. lobata showed reduced performance and dominance in high-temperature areas. Therefore, in future, due to global warming and urbanization, there are possibilities that H. japonicus takes advantage of elevated temperature against P. lobata that could lead to increased H. japonicus coverage over time. Therefore, consistent monitoring of both species especially where P. lobata is dominated are required because both species are found in every continents in the world. Controlling P. lobata requires thorough inspection of H. japonicus presence of the habitat in advance to prevent post P. lobata management invasion of H. japonicus.



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November 3, 2017 – AuD Open House for Prospective Students

The Doctor of Audiology program is hosting an open house for prospective students on Friday, November 3, 2017, at the SDSU and UCSD campuses.

Space is limited – Don't miss this opportunity to learn more about the AuD program and the application process.

• See the AuD Open House event details>>

 

 

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In Reply

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Disparities of Trastuzumab Use in Resource‐Limited or Resource‐Abundant Regions and Its Survival Benefit on HER2 Positive Breast Cancer: A Real‐World Study from China

AbstractBackground.Trastuzumab is a key component of therapy for human epidermal growth receptor 2 (HER2) positive breast cancer. Because real‐world data are lacking, the present research was conducted to evaluate the the actual use of and the effectiveness of trastuzumab in the real world in China.Methods.Inpatients with HER2 positive invasive breast cancer from 13 hospitals in Eastern China (2010–2015, n = 1,139) were included in this study. We aimed to assess the actual use of trastuzumab and to evaluate potential efficacy from trastuzumab in real‐world research.Results.Of 1,017 patients with early stage breast cancer (EBC), 40.5% (412/1,017) received trastuzumab therapy. Patients with EBC in resource‐abundant regions (gross domestic product per capita >$15,000 and trastuzumab included in Medicare) are more likely to receive trastuzumab than those in resource‐limited regions (37.3% vs. 13.0%, p < .05). After metastasis, 50.8% (366/720) patients received trastuzumab as their first‐line therapy. More than 10% of patients with metastatic breast cancer (MBC) continued trastuzumab therapy after twice progression in resource‐abundant regions, whereas more than 40% of patients never received any trastuzumab therapy during the whole course of therapy in resource‐limited regions. Overall, the improvement in survival for trastuzumab versus non‐trastuzumab was substantial in EBC (hazard ratio [HR] = 0.609, 95% confidence interval [CI]: 0.505–0.744) and in MBC (HR = 0.541, 95% CI: 0.418–0.606). This association was greater for patients with MBC who had never received trastuzumab (HR = 0.493, 95% CI: 0.372–0.576) than for those who had received adequate trastuzumab therapy in EBC stage (HR = 0.878, 95% CI: 0.506–1.431).Conclusion.This study showed great disparities in trastuzumab use in different regions and different treatment stages. Both EBC and MBC patients can benefit from trastuzumab, as the survival data show; however, when trastuzumab is adequate in the early stage, a further trastuzumab‐based therapy in first‐line treatment of MBC will be ineffective, especially for those with short disease‐free survival, and a second line of anti‐HER2 therapy will be recommended. (Research number: CSCO‐BC RWS 15001).Implications for Practice.This article shows there are huge disparities in the rates of trastuzumab use due to the unreasonable allocation of medical resources in China. The irrational use can be found both in resource‐abundant regions and in resource‐limited regions. Although trastuzumab‐based therapy improved survival, the actual use of trastuzumab in the early stage of breast cancer would influence the subsequent therapeutic effect after metastasis. This finding in real‐world research could give us a chance to consider the optimized scheme of anti‐HER2 therapy after metastasis especially in these regions with limited access to these expensive target drugs.

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Perspectives of Screening‐Eligible Women and Male Partners on Benefits of and Barriers to Treatment for Precancerous Lesions and Cervical Cancer in Kenya

AbstractBackground.Cervical cancer is the leading cause of female cancer mortality in Kenya. Kenya's National Cervical Cancer Prevention Program Strategic Plan outlines efforts to reduce the burden; however, treatment services remain limited. This study identified male and female perspectives regarding benefits, facilitators, and barriers to treatment for precancerous lesions and cervical cancer.Materials and Methods.Ten focus groups were conducted in Nairobi and Nyanza in 2014 with females aged 25–49 years (n = 60) and male partners (n = 40). Participants were divided into groups dependent on screening status, sex, language, and geographic location. Qualitative analytic software was used to analyze transcribed and translated data.Results.Treatment was endorsed as beneficial for the prevention of death and the improvement of wellness, quality of life, symptoms, and family life. Barriers reported by males and females included the following: (a) concerns about side effects; (b) treatment‐related fear and stigma; (c) marital discord; (d) financial and access issues; (e) religious and cultural beliefs; and (f) limited knowledge. Male endorsement of wanting to improve knowledge and communication with their partners, in spite of stigmatizing beliefs and misperceptions regarding females with abnormal screening results or those who have been diagnosed with cancer, was novel.Conclusion.Incorporating qualitative data on benefits of and barriers to treatment for precancerous lesions and cervical cancer into Kenya's national priorities and activities is important. Our findings can be used to inform the development and successful implementation of targeted, region‐specific community outreach and health messaging campaigns focused on alleviating the country's cervical cancer burden.Implications for Practice.This article provides important insight into female and male partner perspectives regarding benefits, facilitators, and barriers to treatment for precancerous lesions and cervical cancer. Our novel research findings can inform the development of targeted community health interventions, educational messages, and resources and aid stakeholders in strengthening strategic plans regarding treatment coverage and cervical cancer prevention. Because several treatment barriers identified in this study are similar to barriers associated with cervical cancer screening in low‐ and middle‐resourced countries, effective messaging interventions could address barriers to receipt of both screening and treatment.

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The Search for Surrogate Endpoints in Trials in Diffuse Large B‐Cell Lymphoma: The Surrogate Endpoints for Aggressive Lymphoma Project

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Regarding “Survival Outcomes in Asymptomatic Patients with Normal Conventional Imaging but Raised Carcinoembryonic Antigen Levels in Colorectal Cancer Following Positron Emission Tomography‐Computed Tomography Imaging”

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Radiotherapy and Smoking History Are Significant Independent Predictors for Osteosynthesis-Associated Late Complications in Vascular Free Fibula Reconstruction of Mandible.

Background: The vascular fibula flap is an ideal choice for function and appearance reconstruction of mandible. Despite the high success rate, "late complications" such as Ti plate exposure and local infection related to osteosynthesis are not uncommon. Patients and Method: A retrospective cohort of patients who received vascular fibula reconstruction for mandible from January 2011 to December 2013 from the Department of Oral and Maxillofacial Oncology in a tertiary hospital were charted: clinical, pathological, and therapeutic factors were analyzed for late complications in univariate and multivariate analyses. Results: One hundred forty-two patients were finally analyzed with median follow-up time of 47 months; 19 of them had "late complications," which occurred at a median of 8 months. Preoperative or postoperative radiotherapy (P = 0.02), type of Ti plate (P = 0.019), and the disease characteristics (P = 0.02) were significant factors on univariate. Cox regression suggested postoperative radiation (P = 0.009) and smoking history (P = 0.037) were independent significant factors for late complications. Secondary reconstruction (P = 0.069) and preoperative radiotherapy (P = 0.086) were borderline significant. Conclusion: Postoperative radiation and smoking history are associated with late complications. Mini Ti plate should be less used. Patients with risk factors need to be observed for at least 6 to 16 months before further management. (C) 2017 by Mutaz B. Habal, MD.

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Single-Stage Reconstruction of Eyebrow Defect Using a V-Y Advancement Pedicle Flap Based on the Orbicularis Oculi Muscle.

Eyebrows play an important role in face expression and facial mimics by virtue of muscle contraction. Defects or deformity of the eyebrows result in abnormal facial expressions, and may lead to aesthetic issues for patients. The objective of this study is to report the case of a patient, with a congenital skin pigmented nevus at the right side of the eyebrow treated with direct surgical resection and followed by immediate reconstruction of the eyebrow with a V-Y advancement pedicle flap based on the orbicularis oculi muscle. (C) 2017 by Mutaz B. Habal, MD.

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Comparison of Two Different Grafts in Nasal Framework Reconstruction of Binder Syndrome: Cartilage and Silicone.

Background: Binder syndrome is a rare congenital malformation with a flat facial profile especially a depressed nose. Rhinoplasty plays an important part in the multidisciplinary surgical protocol. Different materials have been proposed to reconstruct nasal framework. But fewer evidence concerns which graft can achieve more stable and appreciated nasal contour. In this article, the authors reported surgical details and experience of nasal framework reconstruction of Binder syndrome, compare the esthetic outcomes of 2 grafts: autologous costal cartilage and L-shaped silicone covered with auricular cartilage. Methods: A retrospective study of 25 Binder syndrome patients (9 with silicone and 16 with costal cartilage) was managed. Anthropometric method was used to evaluate nasal profiles preoperatively and postoperatively. Surgical techniques, complications were reviewed. Statistics analysis was managed. Probability (P) of

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Use of the Ipsilateral Anteromedial Thigh Flap for Immediate Rescue of Nonviable Anterolateral Thigh Flaps in Head and Neck Cancer Reconstruction.

Background: It is not always possible to use the anatomically variable free anterolateral thigh (ALT) flap for reconstructive surgery. An anteromedial thigh (AMT) flap serves as a good alternative, and shares the same vascular pedicle as the ALT flap. Methods: Of 698 reconstructions performed in 2006 to 2013 following head and neck tumor ablation surgery, ALT flaps were used in 653 patients. Eighteen free AMT flaps were harvested to replace variant nonviable ALT flaps. Results: The lack of a sizable perforator in the ALT flap territory was the main reason for changing the reconstruction plan. Anteromedial thigh flap size ranged from 10 x 4 to 30 x 8 cm. The flap survival rate was 100%. The follow-up period ranged from 3 to 56 months. Conclusion: During head and neck reconstruction, when no sizable perforator is available during harvest of the ALT flap, successful reconstruction can be achieved using the ipsilateral AMT flap without additional donor-site morbidity. (C) 2017 by Mutaz B. Habal, MD.

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Does Idiopathic Bone Cavity Involving Mandibular Condyle Need Surgical Intervention of Bone Cavity Filling?.

Idiopathic bone cavity (IBC) is a rare, asymptomatic, unilateral, oval-shaped radiolucent defect in the mandible. It is extremely rare that IBC occurs in the mandibular branch and condylar process. This article presents a 16-year-old male with IBC occuring in the mandibular branch. (C) 2017 by Mutaz B. Habal, MD.

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Seizure After Cranioplasty: Incidence and Risk Factors.

Background: To investigate clinical characteristics of postcranioplasty seizures (PCS) first observed after cranioplasty after decompressive craniectomy (DC) to treat traumatic brain injury and to define factors that increase PCS risk. Methods: This retrospective study, covering the period between January 2008 and July 2015, compared PCS in postcranioplasty patients. Postcranioplasty seizures risk factors included diabetes mellitus, hypertension, time between DC and cranioplasty, duraplasty material, cranioplasty contusion location, electrocautery method, PCS type, and infection. Multivariate logistic regression analysis was performed and confidence intervals (CIs) were calculated (95% CI). Results: Of 270 patients, 32 exhibited initial PCS onset postcranioplasty with 11.9% incidence (32/270). Patients fell into immediate (within 24 hours), early (from 1 to 7 days), and late (after 7 days) PCS groups with frequencies of 12, 5, and 15 patients, respectively. Generalized, partial, and mixed seizure types were observed in 13, 13, and 6 patients, respectively. Multivariate logistic regression analysis showed increased risk with increasing age (>50 years). Cranioplasty contusion location, precranioplasty deficits, duraplasty material, and monopolar electrocautery were predictive of PCS onset (P

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Overexpression of Glypican 3 Promotes Proliferation, Regulates Cell Cycle Progression, and Inhibits Apoptosis of Human Fetal Osteoblastic Cell Line 1.19

Craniosynostosis is a complex disease condition, which involves premature fusion of cranial vault sutures and lacks desirable treatment. Previous studies have demonstrated decreased proliferation rate of osteoblasts and downregulated expression of glypican 3 (GPC3) in syndromic craniosynostosis patients. In this study, quantitative and qualitative analysis were utilized to assess the effect of GPC3 in human fetal osteoblastic cell line, hFOB 1.19. Lentiviral transfection efficiency with green fluorescent protein images was obtained after 72 hours. Western Blot and quantitative real-time polymerase chain reaction analysis results indicated that GPC3 was overexpressed in hFOB 1.19 cells transfected with recombinant lentivirus LV-GPC3-GFP. Cell proliferation was assessed by CCK-8 assay and cell cycle progression and apoptosis were analyzed by flow cytometric assay. Results revealed that GPC3 promoted cell viability, induced cell cycle entry into S phase, and inhibited cell apoptosis. These findings provide novel ideas in understanding the pathogenesis of craniosynostosis. It also provides novel insights in the treatment of craniosynostosis by targeting GPC3. (C) 2017 by Mutaz B. Habal, MD.

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Surgical Treatment of Hemifacial Spasm Caused by the Compression of Internal Auditory Canal of Facial Nerve.

Objective: To make out the way to distinguish the offending vessels compressed the internal auditory canal part of the facial nerve. Methods: The hemifacial spasm patients were treated of microvascular decompression surgery with neurophysiologic monitoring. The patients were found that the internal auditory canal of the facial nerves was fully compressed, and the records of surgery monitoring were analyzed. Results: All the patients were recorded the delay incubation period in electromyography monitoring, and all patients were hemifacial spasm free finally. Conclusion: Some hemifacial spasms were caused by internal auditory canal compression, so during the operation, the authors should explore the whole course of the facial nerve and compress the internal auditory canal part with the aid of neurophysiologic monitoring. (C) 2017 by Mutaz B. Habal, MD.

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Research and Clinical Application of Three-Dimensional Location of Amygdaloid Body.

Accurately representing the spatial location of the amygdaloid body can lay an anatomical basis for the neurosurgery operation for amputation of the amygdaloid body through lateral fissure approach. As we know, there are a number of nerve nucleuses and essential structures locating around amygdaloid body in our brain, especially optic tract. However, only few research had been done to protect these tissues or nerve nucleuses. Thus, we reconstructed the three-dimensional images of the amygdaloid body of the human brain and established a coordinate system. The morphological parameters of the amygdaloid body and the three-dimensional coordinate data were measured. The spherical coordinates (R, [theta], [script phi]) were constructed by calculating the azimuth angle, elevation angle, and the distance from the coordinates origin to each amygdaloid body centroid. Sixty people brain MRI images without any visible organic disease were used in our research to investigate the average level of related parameters. The authors selected a proper coordinate origin and measured the value of anteroposterior diameter, right-and-left diameter, vertical diameter of the amygdaloid body, and the distance from the optic tract to amygdaloid body. The authors also measured the three-dimensional coordinate data of each centroid of the amygdaloid body in order to provide anatomical suggestion for surgery. The authors confirmed the nearest point from the foremost edge of the brain ventricle temporal horn to the lateral fissure, then viewed it as the coordinate origin. By means of coordinate translation, the authors got various morphological parameters and the coordinate values of each centroid of the amygdaloid body. Spherical coordinates were calculated from the three-dimensional coordinate values. The distances between the different layers of the amygdaloid body and the optic tract were also measured. The reconstruction of the three-dimensional coordinates of amygdaloid body is part of the digital engineering of the human body. The measurement of the parameters provides an important theoretical basis for the clinical amygdaloid body destruction surgery. Finally, the authors get conclusions as follows. There are no significant differences in the measured values of r1, r2, and r3 between the upper and lower diameters, the left and right diameters, the anteroposterior diameter of the amygdaloid body. The measured values of men and women are not statistically significant (P > 0.05). Spherical coordinates (R, [theta], [script phi]) calculated from the three-dimensional coordinate values and values from different sexes of the amygdaloid body are not statistically significant, either (P > 0.05). The distance between the different levels of the amygdaloid body and the optic tract (h1, h2, h3, h4, h5, h6, and h7) are not statistically significant (P > 0.05). (C) 2017 by Mutaz B. Habal, MD.

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Resurfacing of the Mid and Lower Faces by Preexpanded Supraclavicular Flap.

Extensive scarring and giant nevi on the mid and lower faces places further demands on scar resurfacing in terms of match, size, and thickness. The area of supraclavicular cervical flap is rather limited, but the expansion could expand its utility in facial resurfacing. Rectangular expanders were inserted via the incisions at the upper fringes of clavicles, and implanted under supraclavicular flap areas. After full expansion, the flap based on supraclavicular artery was elevated to cover the defects left by surgical removal of scar or tumor. Pedicle division was performed on the 10 to 14 days postoperatively. A total of 17 patients were treated with the described technique between 2005 and 2015. The dimensions of the flap ranged from 17 cm x 8.5 cm to 22 cm x 12 cm. The average size was 197 cm2. Twenty-one flaps (with 4 patients in bilateral fashion) survived completely. Epidermolysis occurred to 2 flaps, which healed by conservative management. These flaps matched well with the face in terms of the color, thickness, and texture. No obvious flap shrinkage occurred in the follow-up. The donor sites were closed primarily without loss of function or breast deformity. It is an efficient and safe method to obtain preexpanded supraclavicular flap, applying to patients with extensive scarring on mid and lower faces, especially female ones. Excellent aesthetics can be achieved without compromising function and aesthetics of donor sites. (C) 2017 by Mutaz B. Habal, MD.

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Surgery Navigation in Treating Congenital Midfacial Dysplasia of Patients With Facial Cleft.

Aim: To explore a new accurate way for the treatment of congenital midfacial dysplasia in facial cleft patients. Materials and Methods: Between November 2015 and November 2016, 8 patients with nasal deformity and midfacial dysplasia (Tessier Nos. 3-11 cleft) were collected (median age, years; range = 15-20 years). Expanded frontal flap for nasal reconstruction and image-guided navigation-assisted surgery for modified nasal-maxillary-hard palatine osteotomy to advance the peri-pyriform bone structure were performed in all the patients. After 6 to 12 months of follow-up, the authors analyzed the differences between preoperative planning and postoperative results through computed tomography data. Results: Patients were satisfied with surgery, and computed tomography data showed that there was little difference between preoperative planning and postoperative results with the navigation-assisted surgery. Conclusion: Using expanded frontal flap with navigation-assisted surgery for peri-pyriform advancement, the authors could treat congenital nasal deformity and midfacial dysplasia effectively, accurately, and safely in craniofacial cleft patients. (C) 2017 by Mutaz B. Habal, MD.

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Review of "Assessing the Magnitude of a Surgical Career Through His Trainees: The John L. Cameron Legacy Factor" by Cerullo M, Lipsett PA in Ann Surg 265:866-868, 2017.

No abstract available

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Review of "Negative and Positive Online Patient Reviews of Physicians-1 vs. 5 Stars" by Shemirani NL and Castrillon J in JAMA Facial Plast Surg [published online ahead of print January 26, 2017] doi: 10.1001/jamafacial.2016.2039

No abstract available

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Review of "Accreditation Council for Graduate Medical Education (ACGME) Surgery Resident Operative Logs" by Drake FT, Aarabi S, Garland BT, Huntington CR, McAteer JP, Richards MK, Zern NK, Gow KW in Ann Surg 265: 923-929, 2017.

No abstract available

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Review of "Trauma Recidivism Predicts Long-term Mortality" by Strong BL, Greene CR, Smith GS in Ann Surg 265: 847-853, 2017.

No abstract available

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Ocular surface lubricants.

Purpose of review: The purpose of this article is to provide an overview of the ocular lubricants currently available, consider the components of the various formulations and highlight the status of preservative use in the treatment of anterior ocular surface diseases. Recent findings: The primary components of ocular surface lubrication have been, in the past, based on various cellulose formulations that increase hydration. Advances in lubrication have come from areas of the human body requiring lubrication such as the skeletal joints as well as examining the use of natural components of the tear fluid. These have resulted in novel modifications of existing tear components, for example, thiolated carboxymethyl hyaluronic acid which creates crosslinking to mechanically increase retention time for ocular surface hydration. Other proteoglycans such as lubricin, having one of the lowest coefficients of friction in nature, to a lipopolysaccharide derivative of tamarind seed, may provide a unique delivery system for lubricants and medications. Summary: The present state of ocular surface lubrication is slowly advancing from the routine use of cellulose-based solutions and gels to more advanced replacement with natural tear components. The advances that are occurring on other lubricating surfaces of the musculoskeletal system are also providing some insights into potential use on the ocular surface. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Hymenoptera-induced anaphylaxis: is it a mast cell driven hematological disorder?.

Purpose of review: Hymenoptera-induced allergy (HVA) is a common cause of anaphylaxis and may be fatal. It is associated with systemic mastocytosis in about 7% of adult patients. Systemic mastocytosis is a proliferative disorder of hematopoietic mast cell progenitors. There is recent data on the association between systemic mastocytosis and HVA. Recent findings: Hymenoptera venoms are the most common immunoglobulin E-mediated elicitors of anaphylaxis in patients with mastocytosis. Some patients with systemic mastocytosis do not have cutaneous involvement and have only been identified because of HVA. These patients do have distinct demographic, clinical, and laboratory features as compared with patients with mastocytosis with skin lesions. They show a male predominance, more severe (cardiovascular) as compared to skin symptoms, lower baseline serum tryptase, less bone marrow mast cell aggregates, and KIT mutations restricted to mast cell lineage. Summary: Although hymenoptera-induced anaphylaxis is not primarily a mast cell-driven hematological disorder, the latter is present in a significant proportion of patients and has to be excluded by basal serum tryptase determination, skin inspection as well as exclusion of systemic mastocytosis by D816V mutation analysis in peripheral blood and/or bone marrow examination in selected patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Climate changes and Hymenoptera venom allergy: are there some connections?.

Purpose of review: This review aims to update the world status of the main allergenic stinging Hymenoptera. Recent findings: In this review, we consider the problems that social Hymenoptera (bees, wasps and ants) could represent in the nearest future for human health in different parts of the world. Summary: Distribution and consistency of allergenic species including venomous insects are interested by accelerated dynamics caused by climate changes and globalization. Owing to the expansion of ranges of native species and colonization of invasive ones, even in the uncertainty of present available models, new challenges presented by stinging Hymenoptera should be expected in the future. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Relevance of the nucleus of the solitary tract, gelatinous part, in learned preferences induced by intragastric nutrient administration

Publication date: 1 November 2017
Source:Appetite, Volume 118
Author(s): María A. Zafra, Antonio D. Agüera, Filomena Molina, Amadeo Puerto
Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task. Results show that unlike neurologically intact animals, which learn this task correctly, animals lesioned in the gelatinous part of NST manifest a disruption of discrimination learning. Thus, intakes of the flavored stimulus paired with predigested liquid diet and of the flavored stimulus paired with physiological saline were virtually identical. However, SolG- and sham-lesioned groups consumed similar total amounts of both flavors. These findings suggest that SolG, as a relay of the vagus nerve, along with its anatomical projection, the external lateral parabrachial subnucleus (LPBe), may constitute an anatomical axis that is important in the induction of concurrent flavor/side preferences. It also appears to be relevant in other behavioral processes that require rapid processing of information from the upper gastrointestinal tract.



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The prevalence of food addiction in a large sample of adolescents and its association with addictive substances

Publication date: 1 November 2017
Source:Appetite, Volume 118
Author(s): Gabry W. Mies, Jorien L. Treur, Junilla K. Larsen, Jutka Halberstadt, Joëlle A. Pasman, Jacqueline M. Vink
The prevalence of overweight and obesity is increasing, due to, among other factors, increased availability of highly palatable food (food high in fat, salt and/or sugar). It has been proposed that certain foods and/or eating behaviours may be addictive, to a degree comparable to substances of abuse. The Yale Food Addiction Scale (YFAS) measures 'food addiction' by translating the diagnostic criteria for substance use disorder to eating behaviour. So far, only a few studies have examined the prevalence of food addiction in children with the YFAS for children (YFAS-C). Large-scale studies, especially among adolescents, are lacking. Adolescence is of particular interest because it is a period wherein unhealthy eating behaviours or addictive tendencies are likely to develop. The current study examines the prevalence of food addiction using the YFAS-C in a large group of Dutch adolescents (N = 2653) aged 14–21 years. With Generalized Estimation Equation (GEE) analysis we tested the relationship between food addiction symptoms and smoking, cannabis use, alcohol use, and sugar intake through drinks, while controlling for gender, age, educational level and weight class. In the total sample 2.6% met the criteria for a food addiction 'diagnosis', and the average symptom count was 1.0 (SD = 1.3, range 0–7). Symptoms of food addiction were positively associated with smoking, alcohol use, cannabis use and sugar intake. We propose that future studies focus on possible genetic/(neuro)biological mechanisms involved in both food addiction and substance use and that longitudinal designs are needed to examine possible causal pathways.



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Chemometric authentication of the organic status of milk on the basis of trace element content

Publication date: 1 February 2018
Source:Food Chemistry, Volume 240
Author(s): R. Rodríguez-Bermúdez, M. López-Alonso, M. Miranda, R. Fouz, I. Orjales, C. Herrero-Latorre
The objective of this study was to develop a method for authenticating organic milk samples in North Spain on the basis of its trace mineral composition. Fourteen elements in 98 samples were determined by inductively coupled plasma mass spectrometry. Although concentrations of Co, Cr, Cu, I, Se and Zn where statistically higher in conventional milk and As in organic, none of these elements by itself was able to discriminate between organic and conventional milk. The chemical data was examined by principal component analysis and cluster analysis, revealing a natural separation between organic and conventional milk. In a second step, several supervised pattern recognition techniques were used to construct mathematical models for predicting the type of milk (organic or conventional) based on the metal content. The results proved that the model constructed using the artificial neural network is capable of correctly identifying the type of milk in almost 95% of cases.



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Effect of solvent on the electronic absorption spectral properties of some mixed β-octasubstituted Zn(II)-tetraphenylporphyrins

Publication date: 15 January 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 189
Author(s): P. Bhyrappa, M. Sankar
A series of mixed β-octasubstituted Zn(II)-porphyrins, 2,3,12,13-tetra(chloro/cyano/methyl)-5,7,8,10,15,17,18,20-octaphenylporphinato zinc(II), ZnTPP(Ph)4X4 (X=CN, Cl and CH3) have been examined by electronic absorption spectroscopy in various solvents. These Zn(II)-porphyrins exhibited varying degree of red-shift of absorption bands as high as 20–30nm in 'B' band and 50–60nm in longest wavelength band, 'Q(0,0)' band in polar solvents relative to that found in nonpolar solvents. The red-shift of B and Q(0,0) bands showed an unusual trend, ZnTPP(Ph)4(CN)4>ZnTPP(Ph)4(CH3)4>ZnTPP(Ph)4Cl4 but fails to follow an anticipated anodic shift in first porphyrin ring oxidation (vs Ag/AgCl) potential: ZnTPP(Ph)4(CN)4 (1.02V)>ZnTPP(Ph)4Cl4 (0.74V)>ZnTPP(Ph)4(CH3)4 (0.38V). Such a trend suggests the combined effect of non-planarity of the macrocycle and electronic effect of the peripheral substituents. The equilibrium constants for the binding of nitrogenous bases with the Zn(II)-porphyrins showed as high as twenty fold increase for ZnTPP(Ph)4X4 (X=Br and CN) relative to ZnTPP(Ph)4(CH3)4 and follow the order: ZnTPP(Ph)4(CN)4>ZnTPP(Ph)4Br4>ZnTPP(Ph)4(CH3)4≤ZnTPP which is approximately in line with an increase in anodic shift of their first ring redox potentials (ZnTPP(Ph)4(CN)4 (1.02V)>ZnTPP(Ph)4Br4 (0.72V)>ZnTPP (0.84V)>ZnTPP(Ph)4(CH3)4) (0.38V).

Graphical abstract

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Learning and combining image neighborhoods using random forests for neonatal brain disease classification

Publication date: Available online 9 August 2017
Source:Medical Image Analysis
Author(s): Veronika A. Zimmer, Ben Glocker, Nadine Hahner, Elisenda Eixarch, Gerard Sanroma, Eduard Gratacós, Daniel Rueckert, Miguel Ángel González Ballester, Gemma Piella
It is challenging to characterize and classify normal and abnormal brain development during early childhood. To reduce the complexity of heterogeneous data population, manifold learning techniques are increasingly applied, which find a low-dimensional representation of the data, while preserving all relevant information. The neighborhood definition used for constructing manifold representations of the population is crucial for preserving the similarity structure and it is highly application dependent. The recently proposed neighborhood approximation forests learn a neighborhood structure in a dataset based on a user-defined distance. We propose a framework to learn multiple pairwise distances in a population of brain images and to combine them in an unsupervised manner optimally in a manifold learning step. Unlike other methods that only use a univariate distance measure, our method allows for a natural combination of multiple distances from heterogeneous sources. As a result, it yields a representation of the population that preserves the multiple distances. Furthermore, our method also selects the most predictive features associated with the distances. We evaluate our method in neonatal magnetic resonance images of three groups (term controls, patients affected by intrauterine growth restriction and mild isolated ventriculomegaly). We show that combining multiple distances related to the condition improves the overall characterization and classification of the three clinical groups compared to the use of single distances and classical unsupervised manifold learning.

Graphical abstract

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MiR-let-7a regulates anti-citrullinated protein antibody-induced macrophage activation and correlates with the development of experimental rheumatoid arthritis

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Wei Zhu, Jianbo Yu, Shou Qiu, Haifeng Liu, Yan Wang, Xiaoyan Xu, Lili Shao, Lingling Zhu, Yan Jiao, Fan Liu, Xiaodong Zhu
Anti-citrullinated protein antibodies (ACPAs) are a key serological marker of rheumatoid arthritis (RA). To investigate whether miR-let7a downregulated ACPA-induced macrophage activation and arthritis, miR-let7a levels were assessed in the synovial fluid from patients with RA or osteoarthritis (OA). In addition, expression of the pro-inflammatory genes HMGA2, PI3K, and IRF5 was examined in ACPA-induced macrophages and a collagen antibody-induced mouse model of arthritis. As expected, miR-let7a expression in synovial fluid macrophages was substantially lower in patients with RA than in those with OA. Moreover, ACPAs treatment (160IU/mL) suppressed miR-let7a expression in macrophages isolated from patients with RA. Mechanistic studies revealed that miR-let7a directly targets HMGA2 to suppress ACPA-induced IRF5 expression through PI3K in macrophages. Further, miR-let7a expression was markedly decreased in swollen ankle tissue and splenocytes isolated from arthritic mice, whereas HMGA2, PI3K, and IRF5 expression positively correlated with disease severity. However, injection miR-let7a agomir was unable to mitigate the development of experimental arthritis in model mice. Collectively, these data demonstrated that miR-let7a directly targets HMGA2 to downregulate ACPAs-induced macrophage activation, and correlated with experimental RA severity.



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Sodium butyrate inhibits the NF-kappa B signaling pathway and histone deacetylation, and attenuates experimental colitis in an IL-10 independent manner

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Changhyun Lee, Byeong Gwan Kim, Jee Hyun Kim, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Butyrate is a bacterial metabolite of dietary fiber in the colon that has been used to treat inflammatory disease. However, the effect of oral supplementation with butyrate on colitis has not been fully explored. We evaluated the effects of and mechanisms underlying oral supplementation with butyrate on experimental murine colitis. In an in vitro study, we found that LPS induced the secretion of cytokines (i.e., IL-8 in COLO 205; TNF-α, IL-6, IL-12, and IL-10 in RAW 264.7; and TNF-α, IL-6 and IL-12 in peritoneal macrophages obtained from IL-10-deficient [IL-10^−/−] mice). Butyrate (100μM and 500μM) inhibited pro-inflammatory cytokine production (i.e., IL-8 in COLO205 and TNF-α, IL-6 and IL-12 in macrophages) but promoted anti-inflammatory cytokine (i.e., IL-10) production in RAW264.7 cells. Butyrate attenuated both the LPS-induced degradation/phosphorylation of IκBα and DNA binding of NF-κB and enhanced histone H3 acetylation. To confirm that butyrate played a protective role in colitis, an acute colitis model was induced using dextran sulfate sodium (DSS) and a chronic colitis model was induced in IL-10^−/− mice. The administration of oral butyrate (100mg/kg) significantly improved histological scores in both colitis models, including the IL-10^−/− mice. In immunohistochemical staining, IκBα phosphorylation was attenuated, and histone H3 acetylation was reversed in the treated colons of both colitis models. Our results indicate that oral supplementation with butyrate attenuates experimental murine colitis by blocking NF-κB signaling and reverses histone acetylation. These anti-colitic effects of butyrate were IL-10-independent. Butyrate may therefore be a therapeutic agent for colitis.

Graphical abstract

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Pseudomonas aeruginosa-mannose sensitive hemagglutinin injection treated cytokine-induced killer cells combined with chemotherapy in the treatment of malignancies

Publication date: October 2017
Source:International Immunopharmacology, Volume 51
Author(s): Chaoqi Zhang, Zhen Zhang, Liping Wang, Jiaoling Han, Feng Li, Chunyi Shen, Hong Li, Lan Huang, Xuan Zhao, Dongli Yue, Jianmin Huang, Yan Yan, Yi Zhang
Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) injection serves as immunological adjuvant in clinical treatment of cancer patients. In present study, we investigated whether PA-MSHA injection enhanced the anti-tumor efficacy of CIK cells. Twenty patients with malignancies were enrolled in this retrospective clinical trial. They were divided into two groups: 10 patients received PA-MSHA treated CIK cells transfusion combined with chemotherapy, and other patients accepted CIK cells and chemotherapy. The efficacy of PA-MSHA treated CIK cells was also observed in vitro and in vivo. With PA-MSHA treatment CIK cells exhibited enhanced proliferation but decreased expression of inhibitory cell surface markers such as Tim-3 and PD-1. Particularly in CIK cells, PA-MSHA promoted the extrusion of pro-inflammatory cytokines like IFN-γ. Of 10 patients with PA-MSHA treated CIK cells and chemotherapy, two patients reached partial remissions, 7 patients had stable disease and the other one had progressive disease. Some of these patients experienced fever after cell infusion. 8 patients with CIK cells showed stable disease and 2 patients had progressive disease. Moreover, the side effects were small in patients with CIK treatment. Our data indicated that PA-MSHA improves the functions of CIK cells and shed new light on developing more potent therapeutic approaches for malignancies.



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Organoid culture systems to study host–pathogen interactions

Devanjali Dutta | Hans Clevers

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Comparison of Pharmacokinetics and Safety of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects

Publication date: Available online 10 August 2017
Source:Clinical Therapeutics
Author(s): Kyoung Lok Min, Min Soo Park, Jina Jung, Min Jung Chang, Choon Ok Kim
PurposeRosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers.MethodsThis trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study.FindingsSixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of Cmax and AUC0–last were 101.54% (94.03–109.65) and 97.71% (91.86–103.93) for rosuvastatin, 108.93% (98.55–120.40) and 102.90% (96.72–109.47) for free ezetimibe, and 106.74% (98.18–116.05) and 104.24 % (99.53–109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study.ImplicationsThe FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848.



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Pulmonary function in patients with eosinophilic chronic rhinosinusitis

Publication date: Available online 10 August 2017
Source:Auris Nasus Larynx
Author(s): Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki
ObjectiveThere is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients.MethodsPulmonary function was measured in 53 patients with eosinophilic chronic rhinosinusitis with asthma, 58 patients with eosinophilic chronic rhinosinusitis without asthma, and 30 patients with non-eosinophilic chronic rhinosinusitis. The diagnosis of chronic rhinosinusitis was based on the definition in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012. Eosinophilic chronic rhinosinusitis was diagnosed based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system. The relationship between pulmonary function and clinical parameters was assessed. These parameters included radiographic severity of chronic rhinosinusitis, peripheral blood eosinophil percentage, serum total immunoglobulin E level, and eosinophilic infiltration in nasal polyps.ResultsThe pulmonary function of the patients with eosinophilic chronic rhinosinusitis was significantly affected. The eosinophilic chronic rhinosinusitis patients had more peripheral airway obstruction as compared to the patients with non-eosinophilic chronic rhinosinusitis.ConclusionOur findings indicated latent obstructive lung function changes in the eosinophilic chronic rhinosinusitis patients. The patients with eosinophilic chronic rhinosinusitis should be carefully monitored in order to detect lung diseases.



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Variations in the labyrinthine segment of facial nerve canal revealed by high-resolution computed tomography

Publication date: Available online 10 August 2017
Source:Auris Nasus Larynx
Author(s): Aiyan Jin, Peng Xu, Fengqin Qu
ObjectiveTo study variations in the labyrinthine segment of fallopian canal and the associated middle and inner ear malformations.MethodThe high-resolution computed tomography (HRCT) images of the temporal bone in 24 patients with congenital variations in the labyrinthine segment of fallopian canal were analyzed retrospectively. The length of labyrinthine segment of the facial nerve and angle of the first genu of 10 normal subjects were also measured. Based on the original axial images, multi-planar reformation (MPR) and curved-planar reformation (CPR) images of bilateral ossicular chains, inner ear structure and fallopian canal were reconstructed. HRCT features of congenital variations in the labyrinthine segment of the facial nerve were analyzed, including its beginning site, dehiscence, length, angle of the first genu and the associated middle and inner ear malformations.ResultsAmong the normal subjects, the length of labyrinthine segment of the facial nerve was 3.56±0.41mm, and angle of the first genu was 71.87±8.09°. Five types of variations in the labyrinthine segment of the facial nerve were found in 45 ears of 24 cases, including dehiscence in geniculate fossa in 25 ears, anteromedial displacement at the beginning site in 27 ears (widening of Bill's bar in 7 cases), enlargement of the angle of the first genu in 30 ears with an average value of 107.2° (96.0–126.0°), increase of length in 30 ears with an average length of 6.8mm (5.2–8.3mm) and bifurcation in one ear. Associated middle ear malformation in 6 ears and inner ear malformation in 36 ears were also found.ConclusionA variety of congenital variations may occur in the labyrinthine segment of the facial nerve and they are often associated with middle or inner ear malformations, which can be clearly displayed by HRCT with MPR or CPR images.



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Can electromagnetic-navigated maxillary positioning replace occlusional splints in orthognathic surgery? A clinical pilot study

Because of the inaccuracy of intermaxillary splints in orthognathic surgery, intraoperative guidance via a real time navigation system might represent a suitable method for enhancing the precision of maxillary positioning. Therefore, in this clinical trial, maxillary repositioning after Le Fort I osteotomy was guided splintless by an electromagnetic navigation system.

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Clinical prognostic factors of salivary adenoid cystic carcinoma: A single-center analysis of 61 patients

Adenoid cystic carcinomas are rare malignant tumors of the salivary glands. They are characterized by a high rate of local recurrence, late distant metastasis and a poor disease-free survival. In this study, we analysed a series of 61 patients who were all treated at the University of Göttingen over a period of 21.0 years.

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Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Melissa McDougall, Jaewoo Choi, Kathy Magnusson, Lisa Truong, Robert Tanguay, Maret G. Traber
Zebrafish (Danio rerio) are a recognized model for studying the pathogenesis of cognitive deficits and the mechanisms underlying behavioral impairments, including the consequences of increased oxidative stress within the brain. The lipophilic antioxidant vitamin E (α-tocopherol; VitE) has an established role in neurological health and cognitive function, but the biological rationale for this action remains unknown. In the present study, we investigated behavioral perturbations due to chronic VitE deficiency in adult zebrafish fed from 45 days to 18-months of age diets that were either VitE-deficient (E–) or VitE-sufficient (E+). We hypothesized that E– zebrafish would display cognitive impairments associated with elevated lipid peroxidation and metabolic disruptions in the brain. Quantified VitE levels at 18-months in E– brains (5.7 ± 0.1 nmol/g tissue) were ~20-times lower than in E+ (122.8 ± 1.1; n = 10/group). Using assays of both associative (avoidance conditioning) and non-associative (habituation) learning, we found E– vs E+ fish were learning impaired. These functional deficits occurred concomitantly with the following observations in adult E– brains: decreased concentrations of and increased peroxidation of polyunsaturated fatty acids (especially docosahexaenoic acid, DHA), altered brain phospholipid and lysophospholipid composition, as well as perturbed energy (glucose/ketone), phosphatidylcholine and choline/methyl-donor metabolism. Collectively, these data suggest that chronic VitE deficiency leads to neurological dysfunction through multiple mechanisms that become dysregulated secondary to VitE deficiency. Apparently, the E– animals alter their metabolism to compensate for the VitE deficiency, but these compensatory mechanisms are insufficient to maintain cognitive function.

Graphical abstract

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Shared Medical Appointments for Adolescent Breast Reduction

Abstract: Adolescents with macromastia face serious physical, emotional, and social burdens because of their large breast size. Studies have shown that reduction mammoplasty results in improvement in physical symptoms and quality of life for these patients. Shared medical appointments (SMAs), defined as individual patient-physician encounters that occur in a group setting, have been successfully applied to clinics for adult patients seeking breast reduction for this condition. We decided to apply the SMA model to our clinic for preoperative evaluation of adolescent patients with macromastia. The purpose of this article is to describe how our clinic implemented SMAs, evaluate changes in clinic efficiency, measure patient quality of life before surgery, and assess patient and provider satisfaction with the SMA model. From February to June 2016, our department instituted SMAs for preoperative evaluation of female adolescent patients with macromastia. We measured days from referral to appointment for 25 patients who attended SMAs and compared this with a retrospective cohort of 21 patients who attended traditional visits from 2013 to 2015. Clinic efficiency was measured in new patients per hour. During SMAs, we also administered the BREAST-Q, Pediatric Quality of Life Inventory, and patient and provider satisfaction surveys. Mean days between referral and office visit was reduced from 75.3 with traditional visits to 40.3 with shared appointments, although this finding was not statistically significant (P = 0.69). New patients per hour increased from 1.33 with traditional visits to 3 with SMAs, without reducing time spent on education or with the surgeon. The mean preoperative BREAST-Q scores were less than 40 for the 4 tested domains, and the mean (SD) total Pediatric Quality of Life Inventory score was 56.7 (14.8). Patients and the provider reported high satisfaction with SMAs, and the provider wishes to continue using SMAs in the clinic. In conclusion, SMAs resulted in high patient and provider satisfaction and increased clinic efficiency, without sacrificing time spent on education or with the surgeon. Low quality-of-life scores demonstrate a need for these patients to be evaluated and treated for their condition. Measuring patient-reported outcomes with validated surveys and improving clinic efficiency without sacrificing patient care have the potential to increase value at our institution.

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Breast Cancer Recurrence Is not Increased With Lipofilling Reconstruction: A Case-Controlled Study

Background: Lipofilling use has become a revolutionary technique for the correction of breast defect including breast cancer sequelae. The potential risk that progenitor cells included in fat graft tissue may contribute to disease progression by stimulation of residuary breast cancer cells in a tumor bed has set alarms regarding its safety. The aim of this study was to identify lipofilling interference over breast recurrence in patients with cancer history. Methods: We reviewed 205 patients with fat grafting reconstruction after breast cancer surgery performed in our institution between the years 2007 and 2015. For comparative analysis, we selected 2 matched control patients with similar characteristics who did not undergo any lipofilling procedure. Results: No significant differences in recurrence were observed in patients who had lipofilling compared with controls, local (2.4% vs 3.2%, P = 0. 485), regional (1.0 vs 0.7, P = 0.968), and distant (3.4% vs 3.9%, P = 0.590) recurrence. An increased risk of locoregional recurrence (P = 0.014) was detected when lipofilling took place within the first 36 months after cancer surgery. Conclusions: This study provides patients and surgeons with the confidence to keep using lipofilling reconstruction in women with breast cancer history when it is performed in a hospital setting by trained surgeons.

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The Impact of Physician Assistants on a Breast Reconstruction Practice: Outcomes and Cost Analysis

Background: Physician assistants (PAs) are commonly employed in plastic surgery. However, limited data exist on their impact, which may guide decisions regarding how best to integrate them into practice. Methods: A review of the practices of 2 breast reconstructive surgeons was performed. A comparison was made between a 1-year period before to a 1-year period after the addition of a PA into practice. The practice model was a one-to-one pairing of a plastic surgeon and a PA. Results: A total of 4141 clinic encounters and 1356 surgical cases were reviewed. After the addition of PAs, there was a significant increase in relative value units (1057 vs 1323 per month per surgeon, P

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Structural, tribological, and mechanical properties of the hind leg joint of a jumping insect: Using katydids to inform bioinspired lubrication systems

Publication date: Available online 9 August 2017
Source:Acta Biomaterialia
Author(s): Jun Kyun Oh, Spencer T. Behmer, Richelle Marquess, Cengiz Yegin, Ethan A. Scholar, Mustafa Akbulut
This study investigates the structural properties of the hind leg femur-tibia joint in adult katydids (Orthoptera: Tettigoniidae), including its tribological and mechanical properties. It is of particular interest because the orthopteran (e.g., grasshoppers, crickets, and katydids) hind leg is highly specialized for jumping. We show that the katydid hind leg femur-tibia joint had unique surfaces and textures, with a friction coefficient (μ) at its coupling surface of 0.053 ± 0.001. Importantly, the sheared surfaces at this joint showed no sign of wear or damage, even though it had undergone thousands of external shearing cycles. We attribute its resiliency to a synergistic interaction between the hierarchical surface texture/pattern on the femoral surfaces, a nanograded internal nanostructure of articulating joints, and the presence of lubricating lipids on the surface at the joint interface. The micro/nanopatterned surface of the katydid hind leg femur-tibia joint enables a reduction in the total contact area, and this significantly reduces the adhesive forces between the coupling surfaces. In our katydids, the femur and tibia joint surfaces had a maximum effective elastic modulus (Eeff) value of 2.6 GPa and 3.9 GPa, respectively. Presumably, the decreased adhesion through the reduction of van der Waals forces prevented adhesive wear, while the contact between the softer textured surface and harder smooth surface avoided abrasive wear. The results from our bioinspired study offer valuable insights that can inform the development of innovative coatings and lubrication systems that are both energy efficient and durable.Statement of SignificanceRelative to body length, insects can outjump most animals. They also accelerate their bodies at a much faster rate. Orthopterans (e.g., grasshoppers, crickets, and katydids) have hind legs that are specialized for jumping. Over an individual's lifetime, the hind leg joint endures repeated cycles of flexing and extending, including jumping, and its efficiency and durability easily surpass that of most mechanical devices. Although the efficient functioning of insect joints has long been recognized, the mechanism by which insect joints experience friction/adhesion/wear, and operate efficiently/reliably is still largely unknown. Our study on the structural, tribological, and mechanical properties of the orthopteran hind leg joints reveals the potential of katydid bioinspired research leading to more effective coatings and lubrication systems.

Graphical abstract

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Comment to “Orange Peel Excision of Gland: A Novel Surgical Technique for Treatment of Gynecomastia”

No abstract available

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Self-defensive antibiotic-loaded layer-by-layer coatings: imaging of localized bacterial acidification and pH-triggering of antibiotic release

Publication date: Available online 9 August 2017
Source:Acta Biomaterialia
Author(s): Victoria Albright, Iryna Zhuk, Yuhao Wang, Victor Selin, Betsy van de Belt-Gritter, Henk J. Busscher, Henny C. van der Mei, Svetlana Sukhishvili
Self-defensive antibiotic-loaded coatings have shown promise in inhibiting growth of pathogenic bacteria adhering to biomaterial implants and devices, but direct proof that their antibacterial release is triggered by bacterially-induced acidification of the immediate environment under buffered conditions remained elusive. Here, we demonstrate that Staphylococcus aureus and Escherichia coli adhering to such coatings generate highly localized acidification, even in buffered conditions, to activate pH-triggered, self-defensive antibiotic release. To this end, we utilized chemically crosslinked layer-by-layer hydrogel coatings of poly(methacrylic acid) with a covalently attached pH-sensitive SNARF-1 fluorescent label for imaging, and unlabeled-antibiotic (gentamicin or polymyxin B) loaded coatings for antibacterial studies. Local acidification of the coatings induced by S. aureus and E. coli adhering to the coatings was demonstrated by confocal-laser-scanning-microscopy via wavelength-resolved imaging. pH-triggered antibiotic release under static, small volume conditions, yielded high bacterial killing efficiencies for S. aureus and E. coli. Gentamicin-loaded films retained their antibacterial activity against S. aureus under fluid flow in buffered conditions. Antibacterial activity increased with the number of polymer layers in the films. Altogether, pH-triggered, self-defensive antibiotic-loaded coatings become activated by highly localized acidification in the immediate environment of an adhering bacterium, offering potential for clinical application with minimized side-effects.Statement of significancePolymeric coatings that are able to uptake and selectively release antibiotics upon stimulus by adhering bacteria, as a potential way to prevent biomaterial-associated infections, were created in order to understand the fundamental mechanisms behind pH-triggered antibiotic release. Through fluorescent imaging studies, this work importantly shows that adhering bacteria produce highly localized pH changes even in buffer. Accordingly such coatings only demonstrate antibacterial activity by antibiotic release in the presence of adhering bacteria. This is clinically important, because ad libitum releasing antibiotic coatings usually show a burst release and have often lost their antibiotic content when bacteria adhere.

Graphical abstract

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The “Sandwich Therapy”: A Microsurgical Integrated Approach for Presternal Keloid Treatment

Background: Keloid therapy remains a great challenge for plastic surgeons, especially when the defect cannot be closed primarily, necessitating tissue transplantation. Here, we introduce a new treatment modality, called the sandwich therapy, for presternal keloids; the sandwich therapy incorporates preradiotherapy, superficial circumflex iliac artery perforator (SCIP) flap transplantation, and postradiotherapy. Methods: From December 2012 to October 2013, 12 patients received the "sandwich therapy." For the protocol, all patients went through 5 days of specific events: the precut procedure, preradiotherapy, resection and SCIP flap transplantation, donor site radiotherapy, and final presternal radiotherapy. Results: All the flaps survived completely. No complication was observed during the perioperative period. With a mean follow-up of 12 months, only 1 case was reported with an incisional hypertrophic scar. In all patients, the main discomfort complaints were resolved postoperatively. Conclusions: A low-tension or without-tension closure could be achieved with SCIP flap transplantation. The perioperative radiotherapy could further lower the risk of keloid recurrence. The sandwich therapy provides a new surgical approach to presternal keloid treatment.

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Complications After Body Contouring Surgery in Postbariatric Patients

Introduction: Over recent years, body contouring procedures in postbariatric patients have been in exponentially growing demand resulting in high complication rates rendering a variety of ciphers in the literature. Objective: The purpose of this study is to determine the complication rate in patients who have undergone body contouring surgery after bariatric surgery between June 2012 and March 2015 at Hospital de San José. Methods: A cohort study including 153 individuals who underwent a total of 198 body contouring procedures after massive weight loss following bariatric surgery was conducted. Data on variables, such as complication rate according to the type of body contouring surgery, major and minor complications, weight of resected tissue, or intraoperation time, among other variables, were analyzed. Results: A total of 198 procedures were performed in 153 patients. The mean (SD) age of the patients was 43.93 years (9.4 years). Of 198 procedures, 110 (55.5%) had complications. The rate for major complications was 13%, and for minor complications, 87%. Complication rates according to the type of operation were as follows: circumferential abdominal lipectomy, 55.7%; extended abdominal lipectomy, 53.7%; cruroplasty, 69%; breast surgery, 57%; and brachioplasty, 40%. Patients who presented with bleeding enough to require transfusion (P = 0.000) and with weight of the resected tissue greater than 2700 g in abdominoplasty (odds ratio, 3.26; 95% confidence interval, 1.48–7.1) had a higher complication rate. There were no thromboembolic events among this population. Conclusions: The overall complication rate was 55.5%. The great majority were minor complications. The thromboprophylaxis regimen used was 100% effective.

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A Biomimetic Alternative to Synthetic Hydroxyapatite: “Boron-Containing Bone-Like Hydroxyapatite” Precipitated From Simulated Body Fluid

Background: Biological hydroxyapatite (HA), has several mechanical and physical advantages over the commercially available synthetic apatite (CAP-HA). The aim of this in vivo study was to investigate the effect of osteoinductive "bone-like hydroxyapatite" obtained from simulated body fluid (SBF) combined with osteoinductive "boron" (B) on bone healing. Materials: Bone like nanohydroxyapatite (SBF-HA) was precipitated from 10× simulated body fluid (10×SBF). Thirty Sprague-Dawley rats were randomly divided into 5 experimental groups (n = 6 each). The groups were involving blank defect, chitosan, SBF-HA, SBF-HA/B, and CAP-HA. Two biparietal round critical sized bone defect was created using a dental burr. The rats were sacrificed respectively at the end of second and fourth months after surgery and their calvarium were harvested for further macroscopic, microtomographic, and histologic evaluation. Results: The SBF-HA/B group demonstrated the highest mineralized matrix formation rates (30.69 ± 3.73 for the second month, 62.68 ± 7.03 for the fourth month) and was significantly higher than SBF-HA and the CAP-HA groups. The SBF-HA/B group demonstrated the highest mineralized matrix formation rates (30.69 ± 3.73 for the second month, 62.68 ± 7.03 for the fourth month) and was significantly higher than SBF-HA and the CAP-HA groups. In means of bone defect repair histologically, the highest result was observed in the SBF-HA/B group (P

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