Gain-of-function SNPs in NLRP3 and IL1B genes confer protection against obesity and T2D: undiscovered role of inflammasome genetics in metabolic homeostasis?

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The associations of metabolic syndrome with incident hypertension, type 2 diabetes mellitus and chronic kidney disease: a cohort study

Abstract

Purpose

Metabolic syndrome (MetS) has been extensively studied for its long-term health effects, typically through conventional Cox proportional hazards regression modeling of the overall association of MetS with a single outcome. Such an approach neglects the inherent links between MetS-related disease outcomes and fails to provide sufficient insights into the impact of each component of MetS over time.

Methods

We therefore conducted a retrospective cohort study of 63,680 individuals who received health check-ups at the MJ Health Screening Center in Taiwan from 1997–2005 to study the subsequent risks of hypertension, type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) simultaneously for MetS and its components. Multivariate-adjusted hazard ratios (HRs) were calculated using Cox models for multiple failure outcomes.

Results

At baseline, MetS was identified in 7835 participants. Over a median follow-up of 3 years, 8252, 1634, and 6714 participants developed hypertension, T2DM and CKD, respectively. The HR for MetS was 2.41 (95% CI 2.29–2.53) for hypertension, 5.17 (95% CI 4.68–5.71) for T2DM and 1.22 (95% CI 1.15–1.31) for CKD. Three MetS components showed the strongest association with each of the outcomes: elevated blood pressure with hypertension (HR = 3.62, 95% CI 3.46–3.79), raised fasting plasma glucose with T2DM (HR = 8.89, 95% CI 7.86–10.06) and elevated triglycerides with CKD (HR = 1.14, 95% CI 1.08–1.21).

Conclusions

MetS may help identify individuals with metabolic profiles that confer incremental risks for multiple diseases. Additionally, several components of the syndrome should be considered by clinicians, as they show stronger associations with specific diseases than MetS.

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Pancreatic neuroendocrine tumors in MEN1 disease: a mono-centric longitudinal and prognostic study

Abstract

Purpose

Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine neoplastic syndrome associated with a greater risk of endocrine tumor development like pancreatic neuroendocrine tumors (p-NET), with different clinical characteristics from sporadic ones. This paper aims to compare clinical, hystological and morphological aspects of p-NET in patients affected from MEN1 (MEN1+) and not-affected ones (MEN1−).

Methods

We performed a retrospective observational study. Data was collected between December 2010 and December 2015, including patients with a histological diagnosis of p-NET and radiological imaging. We compared clinical, histological, radiological, and prognostic aspects of MEN+ p-NET with MEN−1 p-NET.

Results

Of the 45 patients enrolled, 13 MEN1+ and 21 MEN1− cases were analyzed. Frequency of not secreting p-NETs and insulin secreting p-NETs, histopathological grades and Ki67 expression were superimposable between MEN1+ and MEN1− patients. MEN1+ pNETs are more often multicentric compared to MEN1− pNETs. Frequency of liver and nodes metastatic spread was higher in MEN1− p-NET compared to MEN1+ p-NET. Analyzing p-NET according to the disease outcome, we found that recovered and stable p-NETs in MEN1+ patients, compared to MEN1− cases, are diagnosed at lower age (p = 0.04/p = 0.002) and that are more frequently multifocal lesions (p = 0.009/p = 0.002).

Conclusions

In our study pNETs in MEN1+ and pNETs in MEN1− don't significantly differ for prognosis but only for clinical features. p-NET stage disease and prognosis can be positively influenced by early diagnosis and screening in index patients' first-degree relatives

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Morphologic and molecular pathway of cushing syndrome cardiomyopathy

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Complete evaluation of pituitary tumours in a single tertiary care institution

Abstract

Introduction

We retrospectively evaluated all patients with pituitary tumours treated in our department from 1/1/1997 to 01/11/2014.

Patients and methods

Two hundred and fifteen patients (124 females, 91 males, mean age 50.9 years) were treated because of pituitary tumours. All patients underwent basal hormonal analysis and when required dynamic testing in order to check for hormonal activity. Pituitary masses were divided into groups concerning their hormonal status and were further classified according to gender, age at diagnosis, tumour size, and the development of postoperative pituitary insufficiency when neurosurgical intervention was conducted.

Results

One hundred and twenty-one patients had hormonally inactive tumours (non-functional adenomas; 56.3%), 57 prolactinomas (26.5%), 17 growth hormone secreting adenomas (7.9%), 16 Cushing's disease (7.4%), and 4 craniopharyngiomas (1.9%). Tumours with maximum size <1 cm (microadenomas) were detected in 62 patients (28.8%) and ≥1 cm (macroadenomas) in 153 (71.2%) of all cases (rate 1:2.5). Ninty eight patients (45.6%) had surgery (87 transsphenoidal and 11 transcranial), of this group 34 with hormonally active tumours (37.8% of the 90 patients of this subcohort). Indications for surgery were an increased risk or manifestation of chiasma syndrome and clinical symptoms due to hormonal hypersecretion. Complete [32 cases (32.6%)] or partial [33 cases (33.7%)] postoperative insufficiency in minimum one pituitary axis was present in 65/98 (66.3%) of the operated patients.

Conclusions

Pituitary adenoma prevalence is rising due to widely available imaging procedures. The majority of the tumours in our cohort were macroadenomas and hormonally inactive. Tumour extirpation via the transsphenoidal or transcranial route resulted in functional pituitary impairment of variable extent in 2/3 of the patients.

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Low-dose Synachten test with measurement of salivary cortisol in adult patients with β-thalassemia major

Abstract

Purpose

Beta-thalassemia major is a severe, congenital hematological disorder and, if untreated, leads to early mortality. Progress in therapeutical strategies improved clinical outcomes and life expectancy; however, increased survival led to the development of new disorders, including endocrinopathies. Little is known on the possible impairment of adrenocortical function, a potentially life-threatening condition, in long-term thalassaemic survivors. We therefore decided to assess adrenal reserve and the value of salivary cortisol during ACTH stimulation in the diagnosis of adrenocortical insufficiency in adult patients with β-thalassemia major.

Methods

Cross-sectional study including 72 adults with β-thalassemia major. Patients were tested with 1 µg ACTH for serum and salivary cortisol.

Results

Subnormal serum cortisol responses to ACTH stimulation (i.e., <500 nmol/l) were registered in 15 out of 72 patients. Salivary cortisol increased in parallel with serum cortisol and a clear-cut positive correlation was detected at each timepoint. Moreover, peak salivary cortisol values after ACTH stimulation were significantly lower in patients with impaired adrenal reserve (513.6 ± 52.33 vs. 914.1 ± 44.04 nmol/l p < 0.0001).

Conclusions

Our results attest to the need for testing for adrenal insufficiency among adult thalassaemic patients, as up to 20% presented impaired adrenal reserve. Salivary and serum cortisol levels during stimulation with ACTH were closely correlated and the use of salivary cortisol sampling during ACTH testing may represent a surrogate to serum cortisol in these patients.

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A Prospective Randomized Comparative Clinical Trial to Analyze Pain and Surgical Outcomes Between Frontal Nerve Blocks and Subconjunctival Anesthesia for Conjunctival Mullerectomy Resection

Purpose: Conjunctival Muller's muscle resection (CMMR) is a posterior approach surgical technique to correct blepharoptosis. The purpose of this study is to compare patient-reported pain scores and surgical outcomes for patients who received 2 different anesthetic techniques during CMMR, frontal nerve block and subconjunctival injection. Methods: A prospective randomized comparative clinical trial enrolled 33 CMMR subjects from one tertiary eye center. Patients undergoing unilateral CMMR were randomized to receive either frontal nerve block or subconjunctival injection. For patients undergoing bilateral CMMR, each side was randomized to one of the injection techniques. Upper eyelid margin reflex distance was measured and recorded for each eye before and after surgery. Patients' pain scores were quantified using the Wong Baker Pain Scale. Subjects quantified their pain during, immediately after, 12 and 24 hours after surgery. Results: Twenty-four bilateral and 9 unilateral cases were enrolled in the study. Twenty-two (92%) subjects were female, and the mean patient age was 69 ± 12 years. The mean margin reflex distance was 1.1 mm preoperatively, which increased to 3.5 and 3.6 mm 2 months postoperatively in frontal nerve block and subconjunctival injection groups, respectively (p value

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Distribution of Adrenergic Receptor Subtypes and Responses to Topical 0.5% Apraclonidine in Patients With Blepharoptosis

Purpose: To determine the relationship between the distribution of adrenergic receptors in the human eyelid and the eyelid elevation after topically instilling 0.5% apraclonidine in blepharoptosis patients. Methods: A total of 26 blepharoptotic patients (30 eyelids) were included in the experimental study. Marginal reflex distance 1 was measured before and after topical instillation of 0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine were classified as group A and those that negatively responded to it were classified as group B. Müller's muscle was obtained during the blepharoptotic surgery, followed by immunohistochemical staining and scoring. This study was approved by the Institutional Review Board of Kim's Eye Hospital and the study protocol adhered to the tenets of the Declaration of Helsinki. Results: α-1D staining intensity was significantly higher in group A than in B (p

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An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat Grafting for Complex Sockets

Purpose: To introduce a novel technique to design individually customized conformers for postenucleation sockets with dermis fat implants. Methods: We use a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an individualized conformer. This polymethylmetacrylate printed conformer is adapted to patients' socket, palpebral fissures, horizontal eyelid aperture, curvature of the eyelids, and mean diameter of patients' contralateral eye. Sutures through holes in the inferior part of the conformer and in the extension can be placed to fixate the conformer and anchor fornix deepening sutures. Results: A correct fitting conformer can be printed and attached to the socket and eyelids. The shape of this conformer can be used subsequently postsurgically to design the ocular prosthesis. Conclusion: Presurgical planning is important to anticipate for a functional socket to adequately fit an artificial eye. The presented technique using 3-dimensional imaging, designing, and printing promises to prevent conformer extrusion and forniceal shortening. Accepted for publication February 15, 2018. Supported by ODAS Foundation, Delft, The Netherlands. The sponsor or funding organization had no role in the design or conduct of this research. The authors have no financial or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.op-rs.com.). Ms. Mourits and Mr. Remmers contributed equally to this article. Address correspondence and reprint requests to Department of Ophthalmology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. E-mail: D.mourits@vumc.nl © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Amniotic Band Syndrome: A Review of 2 Cases

Amniotic band syndrome is a rare congenital disorder caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero that presents with complex multisystem anomalies. The authors report 2 children with amniotic band syndrome who presented to the ophthalmic unit of the authors' pediatric hospital. One of them presented with telecanthus, syndactyly, amputated toes, and unilateral epiphora diagnosed as congenital nasolacrimal duct obstruction. She was managed conservatively with lacrimal sac massage and provided with refractive correction while she simultaneously underwent multiple surgeries for correction of clubfoot and craniosynostosis. The second patient presented with cleft lip, cleft palate, multiple constriction bands in upper limbs and fingers with unilateral microphthalmos, microcornea, typical iris coloboma, and retinochoroidal coloboma, very similar to a case reported in literature. These 2 cases provide an overview of the clinical spectrum of ophthalmic manifestations along with their staged optimum rehabilitation. Accepted for publication February 6, 2018. Consent for photographs: Obtained and archived from the parents of the patients for printing identifiable photographs of their children. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Zia Chaudhuri, M.S., F.R.C.S. (Glasg), F.I.C.O., Department of Ophthalmology, Lady Hardinge Medical College, University of Delhi, PGIMER, Dr RML Hospital, New Delhi, India. E-mail: ziachaudhuri2@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Herpes Zoster Ophthalmicus With Orbital Findings Preceding Skin Rash

The authors describe 2 patients who presented with orbital findings and later developed vesicular lesions that were positive for varicella zoster virus and consistent with Herpes Zoster ophthalmicus. One case is the first to involve dacryoadenitis and orbital myositis preceding disseminated Herpes Zoster. In the other case, a patient developed zoster orbital syndrome leading to elevated intraocular pressure, loss of vision, and afferent pupillary defect. Canthotomy and cantholysis were required to restore vision. In both cases, the orbital syndrome developed prior to the vesicular rash. These cases highlight the need to consider Herpes Zoster ophthalmicus in patients with orbital syndrome not responding to conventional treatment. Accepted for publication February 14, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Elizabeth Chiang, M.D., Ph.D., Southside Eye Care, 3206 Churchland Blvd., Chesapeake, VA 23321. E-mail: echiangmdphd@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Ophthalmic Pyogenic Granulomas Treated With Topical Timolol—Clinical Features of 17 Cases

Purpose: Topical timolol has been increasingly demonstrated to be an effective treatment for pyogenic granulomas (PG). The authors review the treatment outcomes of 17 patients with ocular PG treated with topical timolol. Methods: Retrospective interventional study of 17 patients with ocular PGs treated with timolol 0.5% solution. Patient demographics, clinical features, treatment response, and recurrence were noted. Results: Nine females and 8 males with a mean age of 23 years (range, 3–67 years) were included. Mean duration of disease prior to treatment was 3.81 months (range, 0.25–11 months). Etiologies included chalazia (12 cases, 71%), postsurgical (4, 24%) and trauma (1, 6%). Five patients (29%) had treatment with topical steroids prior to presentation. Fifteen patients (88%) had PG located on the palpebral conjunctiva and 2 (12%) involving the bulbar conjunctiva. Mean lesion size was 5.06 × 6.06 mm (range, 3–8 × 3–18 mm). Fifteen patients (88%) had complete lesion resolution with a mean treatment duration of 3.07 weeks (range, 2–5 weeks) and no adverse events or recurrences with a mean follow up of 9.47 months (range, 6–27 months). Two patients (12%) underwent lesion excision after 6 weeks of timolol failed to yield resolution. Conclusion: Topical timolol appears to be a well-tolerated nonsurgical treatment of ocular PG in both children and adults. Clinicians may wish to consider topical timolol to treat PG as opposed to topical steroids, given the inherent risk of steroid response ocular hypertension and the difficulty to measure intraocular pressure in younger children who require general anesthesia for excision. Accepted for publication February 15, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Roman Shinder, M.D., F.A.C.S., Department of Ophthalmology, SUNY Downstate Medical Center, 451 Clarkson Ave, E bldg, 8th Fl, Suite C, Brooklyn, NY 11203. E-mail: shinder.roman@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Eye-Preserving Surgery Followed by Adjuvant Radiotherapy for Lacrimal Gland Carcinoma: Outcomes in 37 Patients

Purpose: To describe the clinical outcomes of eye-preserving surgery followed by adjuvant radiotherapy in patients with lacrimal gland carcinoma. Methods: Thirty-seven patients with lacrimal gland carcinoma who underwent eye-preserving surgery were studied. Results: At last follow up, 32 patients were alive without disease, 3 patients were alive with disease with distant metastasis, 1 patient had died of disease, and 1 patient had died of other cause. The 5-year recurrence-free survival rate was worse in patients without than in patients with adjuvant radiotherapy (p = 0.001) and worse in patients with T3-T4 tumors than in patients with T1-T2 tumors (p = 0.027). At last follow up, 25 patients (68%) had visual acuity of 20/40 or better. Conclusions: In patients with lacrimal gland carcinoma, eye-preserving surgery and adjuvant radiotherapy is associated with reasonable local control rates and visual and ocular function. Postoperative adjuvant radiotherapy seems to enhance local control rates. Accepted for publication February 7, 2018. Presentation at the American Academy of Ophthalmology Annual Meeting, October 2016, Chicago, IL. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Bita Esmaeli, M.D., Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1488, Houston, TX 77030. E-mail: besmaeli@mdanderson.org and Yoon-Duck Kim, MD, Department of Ophthalmology, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea. E-mail: ydkimoph@skku.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Why Aren't There More Female Pain Medicine Physicians?

Despite a growing awareness about the importance of gender equity and the rising number of women in medicine, women remain persistently underrepresented in pain medicine and anesthesiology. Pain medicine ranks among the bottom quartile of medical specialties in terms of female applicants, female trainees, and proportion of female practitioners. Female pain medicine physicians are also notably disadvantaged compared with their male colleagues in most objective metrics of gender equity, which include financial compensation, career advancement, public recognition, and leadership positions. Increased gender diversity among pain medicine physicians is vital to fostering excellence in pain research, education, and clinical care, as well as creating a high-quality work environment. Pain medicine stands at a crossroads as a specialty, and must examine reasons for its current gender gap and consider a call to action to address this important issue. Accepted for publication December 24, 2017. Address correspondence to: Tina L. Doshi, MD, Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 550 N Broadway, Suite 309C, Baltimore, MD 21205 (e-mail: tina.doshi@jhmi.edu). The authors have no sources of funding to declare for this article. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Transgenerational consequences of prepregnancy chronic morphine use on spatial learning and hippocampal Mecp2 and Hdac2 expression

There has recently been increasing interest in the transgenerational effects of opioids. Herein, transgenerational consequences of maternal chronic morphine consumption before gestation were investigated at the behavioral and molecular levels of next two generations. Twelve female Wistar rats were randomly divided into two groups: pregestation morphine-consuming and control mothers. Morphine-consuming mothers had access to morphine solution ad libitum for 2 months, whereas the control mothers received only tap water. One month after stopping morphine consumption, rats were mated. After parturition, male and female offspring and later grandoffspring of morphine-consuming and control mothers were divided and used as the study groups. Behavioral testing comprised spatial memory assessment using Morris water maze. Hippocampal expressions of Mecp2 and Hdac2 were investigated through real-time PCR. Spatial memory was significantly diminished in male but not female offspring and grandoffspring of morphine-consuming mothers versus control (P

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Altered whole-brain gray matter volume in high myopia patients: a voxel-based morphometry study

High myopia (HM) was associated with impaired long-distance vision. Previous neuroimaging studies showed that abnormal visual experience leads to dysfunction in brain activity in HM even corrected. However, whether alterations in brain structure occur in HM remains unknown. In this study, we analyzed the difference in the whole-brain gray matter volume (GMV) and white matter volume between HM patients and healthy controls (HCs) using a voxel-based morphology method. A total of 82 HM patients (52 men and 30 women) and 58 HCs (28 men and 30 women), matched closely in terms of age and education, were enrolled in this study. All participants underwent MRI scans. The MRI data were processed using the SPM8 software. The relationship between the mean GMV values of the brain regions and clinical features, including refractive diopter and the mean retinal nerve fiber layer thickness, in the HM group were analyzed using Pearson's correlation. Compared with HCs, HM patients showed significantly decreased GMV values in the right cuneus/lingual gyrus and the right thalamus. In contrast, HM groups showed higher GMV values in the brain stem, right parahippocampal gyrus/thalamus, left parahippocampal gyrus/thalamus, as well as the right and the left putamen. No significantly different white matter volume values were found between the two groups. Moreover, in the HM group, the mean retinal nerve fiber layer of the left eye showed a negative correlation with the mean GMV values of the brain stem (r=−0.218; P=0.049), right parahippocampal gyrus/thalamus (r=−0.262; P=0.017), left parahippocampal gyrus/thalamus (r=−0.249; P=0.024), and left putamen (r=−0.232; P=0.036). We found that HM patients showed an altered brain structure in the visual pathway regions and the limbic system, which may provide useful information to explore the neural mechanisms of impaired long-distance vision in HM. *Xin Huang and Yuxiang Hu contributed equally to the writing of this article. Correspondence to Xiaorong Wu, PhD, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China Tel: +86 136 1709 3259; fax: +86 791 8869 2520; e-mail: wxr98021@126.com Received March 5, 2018 Accepted March 19, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Clinicopathological significance of tumor-infiltrating lymphocytes and programmed death-1 expression in cutaneous melanoma: a comparative study on clinical subtypes

Interactions between immune cells and tumor cells play an important role in tumor progression. We evaluated patterns of tumor-infiltrating lymphocytes (TILs) and programmed death-1 (PD-1) expression in acral and nonacral cutaneous melanoma, and determined their effects on clinicopathological characteristics and biologic responses. We identified 122 cases of cutaneous melanoma, of which 39 were cases of non-nail unit acral melanoma (NNUAM), 35 were cases of nail unit melanoma (NUM), and 48 were cases of nonacral melanoma. Clinicopathological features and survival outcomes were analyzed according to the scores for TILs and PD-1 expression in intratumoral and peritumoral compartments. The effects of the presence of TILs and PD-1 expression on various clinicopathological factors differed according to the clinical subtypes of cutaneous melanoma. The frequency of intratumoral TILs and PD-1 expression were lower in NUM than in the other two subtypes. The density of peritumoral PD-1 was significantly higher in NNUAM. In NUM and nonacral melanoma, a low density of intratumoral TILs and PD-1 was associated with a deeper Breslow thickness and the presence of a vertical growth phase. In NNUAM, a high density of peritumoral TILs and PD-1 was associated with a shallower Breslow thickness and less frequent extracutaneous dissemination. In NNUAM, a high density of peritumoral PD-1 was associated with a better prognosis. This study suggests that the effects of PD-1+ TILs on biological activity differ according to the clinical subtypes of cutaneous melanoma. Correspondence to Mi W. Lee, MD, PhD, Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 Gil, Songpa-gu, Seoul 05505, Korea Tel: +82 230 103 460; fax: +82 248 67831; e-mail: miumiu@amc.seoul.kr Received December 8, 2017 Accepted March 12, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Immune privilege: failure of immunotherapy in controlling metastatic cutaneous melanoma to the eye

This report concerns a 49-year-old female with cutaneous malignant melanoma and systemic metastases. These resolved following combination immunotherapy with ipilimumab and nivolumab. She subsequently experienced unilateral floaters, an increase in iris pigmentation and pigmentary glaucoma. The eye progressively lost vision and became painful due to iris neovascularization. The clinical diagnosis was of cutaneous melanoma metastatic to the vitreous, ciliary body and iris. Enucleation was performed for symptom control, with histopathology confirming the clinical diagnosis. The immune privilege of the eye may preclude ocular metastasis control with immunotherapy. Ocular symptoms in such patients merit referral to an ophthalmologist. Correspondence to David I.T. Sia, MBChB, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK Tel: +44 77 2980 2148; fax: +44 20 7566 2972; e-mail: david.sia@me.com Received November 21, 2017 Accepted February 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Comment on “Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma”

The authors of this study¹ should be commended on the important and complex undertaking of identifying multiple antigens for chimeric antigen receptor (CAR) T-cell therapy, which is one of several key limitations to the field. There are 2 levels of antigenic heterogeneity at play that require consideration—intrapatient variability, in which the existence of antigen-negative tumor cells may result in eventual recurrence, and interpatient variability, in which different expression patterns across all patients make identification of a single or "universal" therapeutic for treatment difficult, if not impossible. The authors state that by targeting 3 antigens: human epidermal growth factor receptor 2 (HER2), interleukin-13 receptor alpha 2 (IL13Rα2), and ephrin-A2 (EphA2) using a trivalent UCAR, they can "overcome intrapatient and interpatient variability" and that "trivalent T cells were able to approach killing in 100% of tumor cells in nearly all patients modeled." As investigators working in the field of immuno-oncology, we very much wish this to be the case; however, these conclusions are not supported by the data presented in the manuscript.

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Corrigendum to “Dopaminergic involvement in a drummer with focal dystonia: A case study” [Clin. Neurol. Neurosurg. (2018) 166 (March) 54–55]

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168
Author(s): T. Schirinzi, S. Scalise, G. Di Lazzaro, R. Cerroni, A. Chiaravalloti, P. Lavorenti Figueras, M. Pierantozzi, A. Pisani, A Stefani




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Comparison of operative outcomes of eloquent glioma resection performed under awake versus general anesthesia: A systematic review and meta-analysis

Publication date: Available online 9 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Victor M. Lu, Kevin Phan, Richard A. Rovin
Surgical resection of eloquent glioma can be achieved under general anesthesia (GA) or awake anesthesia (AA). The appeal of AA is that it facilitates intraoperative identification and avoidance of eloquent areas, which has the potential to minimize functional compromise. The aim of this meta-analysis was to compare the operative outcomes of eloquent glioma resection performed under GA compared to AA to assist in optimizing the decision algorithm between the two approaches. Searches of seven electronic databases from inception to December 2017 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. There were 1037 articles identified for screening. Data were extracted and analyzed using meta-analysis of proportions. A total of 9 comparative studies were included for analysis. Resection of glioma involving eloquent areas achieved under AA is mostly comparable in terms of operative and functional outcomes to that of GA. AA did demonstrate significantly lower incidence of postoperative nausea and vomiting (PONV, OR, 0.17; p < 0.001) and shorter length of stay (LOS, MD, -1.76 days; p = 0.02) when compared to GA. Future studies that are larger, prospective, randomized, and include long term quality of life metrics will assist in elucidating the true clinical benefit of AA in resecting glioma involving eloquent areas. This will assist in further developing management protocol of these glioma.



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Editorial Board

Publication date: May 2018
Source:Clinical Neurology and Neurosurgery, Volume 168





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Impact of frailty on complications in patients with thoracic and thoracolumbar spinal fracture

Publication date: Available online 9 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Remi A. Kessler, Rafael De la Garza Ramos, Taylor E. Purvis, A. Karim Ahmed, C. Rory Goodwin, Daniel M. Sciubba, Muhammad Abd-El-Barr
ObjectivesIt is well-documented that geriatric patients are at risk for serious injuries after fracture due to pre-existing medical conditions, physical changes of aging, and medication effects. Frailty has been demonstrated to be a predictor of morbidity and mortality in inpatient head and neck surgery, and for surgical intervention for adult spinal deformity and degenerative spine disease. However, the impact of frailty on complications following thoracolumbar/thoracic fracture is unknown and has not been previously assessed in the literature, particularly in a nationwide setting.Patients and MethodsThis was a retrospective study of the prospectively-collected American College of Surgeons National Surgical Quality Improvement database for the years 2007 through 2012. Patients who underwent spinal decompression (+/- fusion) or an alternative intervention, defined as vertebroplasty or kyphoplasty (VP/KP) for thoracic or thoracolumbar fracture were identified. Frailty status was determined using a modified frailty index from the Canadian Study of Health and Aging Frailty Index, with frailty defined as a score = 0.27. 30-day morbidity and mortality were compared between frail and non-frail patients in each treatment group.ResultsA total of 303 patients were included in this study. Of these, 38% of patients had VP/KP and 62% underwent surgery. Within the VP/KP cohort, 26% were frail. The proportion of these patients who developed at least one complication was 3.3% versus 3.6% for non-frail patients (p = 1.0). The 30-day mortality for frail versus not frail patients in this cohort was 0% versus 2.4% (p = 1.0). Among the surgical group, 13% were frail. In contrast, the likelihood of complications was 33.3% among frail patients and 4.2% for non-frail patients (p < 0.001). Frail patients also had a 16.7% 30-day mortality rate as compared to 0.6% in the non-frail group (p = 0.001). When comparing the frail versus non-frail patients overall, frail patients had a complication rate of 16.7%, as opposed to 4.0% in non-frail patients.ConclusionFrailty and surgical intervention are correlated with a higher 30-day complication rate in patients with thoracic and thoracolumbar fracture. This finding is an important consideration for surgical decision-making and patient counseling on treatment options.



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Relations Between Psychosocial Job Characteristics and Work Ability in Employees with Chronic Headaches

Abstract

Purpose The aim of the study was to determine (a) to which extent job demands and job resources predict work ability in employees with chronic headaches, and (b) whether work ability in these employees is more hampered by high demands and more enhanced by resources than in employees without chronic disease. Methods All employees with chronic headaches (n = 593) and without chronic disease (n = 13,742) were selected from The Netherlands Working Conditions Survey conducted in 2013. This survey assessed amongst others job characteristics and various indicators of work ability, i.e. sick leave, employability, work engagement, and emotional exhaustion. Hierarchical regression analyses were conducted for employees with chronic headaches and compared to employees without chronic disease, controlling for age, gender and educational level. Results In employees with chronic headaches higher quantitative and emotional demands contributed to higher emotional exhaustion, and higher emotional demands to higher sick leave. Higher cognitive demands were however associated with higher work engagement. Higher autonomy was related to higher employability and lower emotional exhaustion. Higher supervisor and colleague support was associated with higher employability, higher engagement and lower emotional exhaustion. Higher supervisor support was associated with lower sick leave. Supervisor support emerged as a stronger predictor for emotional exhaustion in the employees with chronic headaches than in the employees without chronic disease. Conclusions Job demands and job resources are important for work ability in employees with chronic headaches. Furthermore, results suggest that these employees benefit more strongly from supervisor support than employees without chronic disease.

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Spasmodic Dysphonia in Multiple Sclerosis Treatment With Botulin Toxin A: A Pilot Study

Publication date: Available online 9 April 2018
Source:Journal of Voice
Author(s): Arianna Di Stadio, Evanthia Bernitsas, Domenico Antonio Restivo, Enrico Alfonsi, Rosario Marchese-Ragona
ObjectivesThis study aims to evaluate the effect of botulin toxin A in patients with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the safety and effectiveness of this treatment in long-term observation.Materials and methodsThis is a pilot study on three relapsing-remitting MS patients with SD and their response to botulin toxin A.ResultsNone of the patients reported dysphagia or other adverse events. Significant improvement was observed in terms of both voice quality and laryngostroboscopy results. The treatment effect was durable for 6–8 months.ConclusionsBotulin toxin A is a safe treatment that can be successfully used to treat SD in patients with MS. Larger studies are necessary to confirm our results.



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Registers in Infant Phonation

Publication date: Available online 9 April 2018
Source:Journal of Voice
Author(s): Eugene H. Buder, Valerie F. McDaniel, Edina R. Bene, Jennifer Ladmirault, D. Kimbrough Oller
The primary vocal registers of modal, falsetto, and fry have been studied in adults but not per se in infancy. The vocal ligament is thought to play a critical role in the modal-falsetto contrast but is still developing during infancy (Tateya and Tateya, 2015). Cover tissues are also implicated in the modal-fry contrast, but the low fundamental frequency (fo) cutoff of 70 Hz, shared between genders, suggests a psychoacoustic basis for the contrast. Buder, Chorna, Oller, and Robinson (2008)⁶ used the labels of "loft," "modal," and "pulse" for distinct vibratory regimes that appear to be identifiable based on spectrographic inspection of harmonic structure and auditory judgments in infants, but this work did not supply acoustic measurements to verify which of these nominally labeled regimes resembled adult registers. In this report, we identify clear transitions between registers within infant vocalizations and measure these registers and their transitions for fo and relative harmonic amplitudes (H1-H2). By selectively sampling first-year vocalizations, this manuscript quantifies acoustic patterns that correspond to vocal fold vibration types not previously cataloged in infancy. Results support a developmental basis for vocal registers, revealing that a well-developed ligament is not needed for loft-modal quality shifts as seen in harmonic amplitude measures. Results also reveal that a distinctively pulsatile register can occur in infants at a much higher fo than expected on psychoacoustic grounds. Overall results are consistent with cover tissues in infancy that are, for vibratory purposes, highly compliant and readily detached.



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Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18 F-FDG and 18 F-FLT PET/CT imaging

Abstract

Background

Despite the significant upgrading in recent years of the role of ¹⁸F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3′-Deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate ¹⁸F-FLT PET/CT in imaging of MM patients, in the context of its combined use with ¹⁸F-FDG PET/CT.

Results

Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent ¹⁸F-FDG PET/CT and ¹⁸F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. ¹⁸F-FDG PET/CT demonstrated focal, ¹⁸F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, ¹⁸F-FLT PET/CT showed focal, ¹⁸F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 ¹⁸F-FDG avid, focal, MM-indicative lesions were detected with ¹⁸F-FDG PET/CT, while 17 ¹⁸F-FLT avid, focal, MM-indicative lesions were detected with ¹⁸F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for ¹⁸F-FDG PET/CT than for ¹⁸F-FLT PET/CT. A common finding was a mismatch of focally increased ¹⁸F-FDG uptake and reduced ¹⁸F-FLT uptake (lower than the surrounding bone marrow). Moreover, ¹⁸F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV_mean and SUV_max were significantly higher for ¹⁸F-FLT than for ¹⁸F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers.

Conclusions

Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that ¹⁸F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

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Why does chemotherapy stop affecting the cells of ovarian and breast tumors?

Future Oncology, Ahead of Print.


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The effect of Glut1 and c-myc on prognosis in esophageal squamous cell carcinoma of Kazakh and Han patients

Future Oncology, Ahead of Print.


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Use of lymphoscintigraphy to differentiate primary versus secondary lower extremity lymphedema after surgical lymphadenectomy: a retrospective analysis

Abstract

Background

When managing patients with cancer, lymphedema of the lower limbs (LLL) is commonly reported as secondary to the surgical excision and/or irradiation of lymph nodes (LNs). In the framework of lymphoscintigraphic imaging performed to evaluate secondary LLL, some lympho-nodal presentations have been observed that could not be explained by the applied treatments, suggesting that these LLL might be primary. Therefore, all our lymphoscintigraphic examinations that were performed in patients for LLL after surgery for gynecological or urological cancer were retrospectively analyzed in order to evaluate the frequency in which these LLL might not be secondary (either completely or partially) but primary in origin.

Methods

Lymphoscintigraphies performed in 33 patients who underwent LN dissection (limited to the intra-abdominal LN) with or without radiotherapy for histologically confirmed ovarian cancer (n = 6), uterine cancer (n = 14 with cervical cancer and n = 7 with endometrial cancer), or prostate cancer (n = 6) were compared to lymphoscintigraphies obtained in primary LLL.

Results

In 12 (33% of the) patients (3 men plus 9 women, 4 with cervical cancer and 5 with endometrial cancer), scintigraphy of the lower limbs revealed lympho-nodal presentation that did not match with the expected consequences of the surgical and/or radiological treatments and were either suggestive or typical of primary lymphedema.

Conclusions

This retrospective analysis of a limited but well-defined series of patients suggests that the appearance of LLL might not be related to cancer treatment(s) but that these LLL may represent the development of a primary lymphatic disease latent prior to the therapeutic interventions.

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Transbronchial Cryobiopsy for Interstitial Lung Disease: Is it too Late to Put the Toothpaste Back in the Tube?

No abstract available

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Utility of a 25- Versus 22-G EBUS Needle in Difficult-to-Access 2R Lymph Nodes

No abstract available

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Identification and validation of a 3-gene methylation classifier for HPV-based cervical screening on self-samples

Purpose: Offering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples. Experimental Design: We determined genome-wide DNA methylation profiles of 72 hrHPV-positive self-samples, using the Infinium Methylation 450K Array. The selected DNA methylation markers were evaluated by multiplex quantitative methylation-specific PCR (qMSP) in both hrHPV-positive lavage (n=245) and brush (n=246) self-samples from screening cohorts. Subsequently, logistic regression analysis was performed to build a DNA methylation classifier for CIN3 detection applicable to self-samples of both devices. For validation, an independent set of hrHPV-positive lavage (n=199) and brush (n=287) self-samples was analyzed. Results: Genome-wide DNA methylation profiling revealed 12 DNA methylation markers for CIN3 detection. Multiplex qMSP analysis of these markers in large series of lavage and brush self-samples yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5). This classifier showed a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. Importantly, all self-samples from women with cervical cancer scored DNA methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on hrHPV-positive self-samples, which is superior to currently available methods.

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Complete and durable responses in Primary Central Nervous System Post-Transplant Lymphoproliferative Disorder with Zidovudine, Ganciclovir, Rituximab and Dexamethasone

Purpose:  Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a complication of solid organ transplantation with a poor prognosis and typically associated with Epstein-Barr virus (EBV). We hypothesized EBV lytic-phase protein expression would allow successful treatment with antiviral therapy. Experimental Design:  Thirteen patients were treated with zidovudine (AZT), ganciclovir (GCV), dexamethasone, and rituximab in EBV+ PCNS-PTLD.  Twice-daily, intravenous AZT 1500 mg, GCV 5 mg/kg, and dexamethasone 10 mg were given for 14-days. Weekly Rituximab 375 mg/m2 was delivered for the first four weeks. Twice-daily Valganciclovir 450 mg and AZT 300 mg started day 15. Lytic and latent protein expression was assessed using in situ hybridization and immunohistochemistry. Immunoblot assay assessed lytic gene activation.  Cells transfected with lytic kinase vectors were assessed for sensitivity to our therapy using MTS tetrazolium and flow cytometry. Results:  The median time to response was 2 months. Median therapy duration was 26.5 months.  Median follow-up was 52 months. The estimated two-year overall survival (OS) was 76.9% (95% CI: 44.2-91.9%). Overall response rate (ORR) was 92% (95% CI: 64-100%). BXLF1/vTK and BGLF4 expression was found in the seven tumor biopsies evaluated. Lytic gene expression was induced in vitro using the four-drug regimen. Transfection with viral kinase cDNA increased cellular sensitivity to antiviral therapy. Conclusions:  EBV+ PCNS-PTLD expressed lytic kinases and therapy with AZT, GCV, rituximab and dexamethasone provided durable responses. Induction of the lytic protein expression and increased cellular sensitivity to antiviral therapy after transfection with viral kinase cDNA provides a mechanistic rationale for our approach.

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Announcements

Dear Colleagues,

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EACMFS Awards

The Council of EACMFS wishes to ensure that all members of the Association are aware of the current awards and prizes that are available. These are designed to provide educational support and also to allow the opportunity for trainees and those who have recently achieved specialist status to visit units outside their own departments.

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An Unexpected Donor Site Complication after Aesthetic Rhinoplasty: Arteriovenous Fistula of the Superficial Temporal Artery

Facial plast Surg 2018; 34: 235-236
DOI: 10.1055/s-0038-1636934

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Surgical Anatomy of the Upper Face and Forehead

Facial plast Surg 2018; 34: 109-113
DOI: 10.1055/s-0038-1637727

Aesthetic ideals regarding proportion and balance of the face have existed for centuries. The upper third of the face, including the brow, forehead, and temple, provides an important contribution to the overall facial aesthetic. This is especially true given how the brow frames the eyes, and the eyes serve as the key focal point in our interactions with others. There exists a variety of surgical and nonsurgical procedures aimed at improving the aesthetic of the upper portion of the face, and a thorough knowledge of the surgical anatomy of the upper face and forehead is critical to their successful execution.
[...]

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Halos and Asymmetric Triangles: Designing the Eyelids with Volume Using Fillers and/or Fat

Facial plast Surg 2018; 34: 173-177
DOI: 10.1055/s-0038-1636902

Periorbital aging is mainly a product of volume loss, which can be addressed with fillers and/or fat grafting. This stands in contrast to the lower face where a lifting procedure can be the principal method to improve moderate-to-significant aging. New models to explain these concepts of periorbital rejuvenation to both the surgeon and the prospective patient are outlined herein, namely, three facial halos (around the eyes, around the perimeter of the face, and around the mouth) and asymmetric triangles around the eyes. Specific techniques for fillers and fat grafting are also covered separately in detail in this article.
[...]

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The Aesthetics of the Upper Face and Brow: Male and Female Differences

Facial plast Surg 2018; 34: 114-118
DOI: 10.1055/s-0038-1636935

A hallmark of the modern era of facial plastic surgery is the increasing demand for upper facial rejuvenation by both genders and the growing variety of such options, including both surgical and non-surgical modalities. Thus, now more than ever, differentiating these aesthetic ideals between the two genders and understanding their nuances has become a necessity for the facial cosmetics community. In this article, a detailed comparison of the the pertinent anatomical and topographical differences is presented, followed by a review of the historical evolution of these aesthetic trends.
[...]

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Aesthetics and Rejuvenation of the Temple

Facial plast Surg 2018; 34: 159-163
DOI: 10.1055/s-0038-1636921

The temples are an often overlooked, but important element of facial rejuvenation. The anatomy of the temple should be understood prior to any intervention in this location. Multimodal treatment to re-establish youthful convexity, proper hairline position, and correct actinic damage is recommended for optimal results. Important anatomy, aesthetic goals, and methods of rejuvenation are reviewed in detail.
[...]

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Rejuvenation of the Upper Face and Brow: Neuromodulators and Fillers

Facial plast Surg 2018; 34: 119-127
DOI: 10.1055/s-0038-1637004

Facial aging involves a combination of volume loss and descent, loss of skin elasticity, dynamic lines due to facial mimetic muscle action, and development of static rhytids. Although surgery remains an option for treatment, minimally invasive aesthetic procedures continue to gain popularity with the use of neuromodulators and soft tissue fillers being the most sought-after procedures. Although these may be used in isolation to treat specific concerns, they are often combined to address multiple facets of aging. Multiple different neuromodulators and fillers are commercially available. Although relatively effective and safe, a thorough understanding of their indications, compositions, and potential adverse effects is paramount. This article will review the available aesthetic products for minimally invasive periorbital rejuvenation with botulinum toxin and injectable fillers. Although it will not focus on other therapies aimed at facial rejuvenation, such as resurfacing techniques or surgical interventions, it is important to note that an individualized treatment plan may combine multiple therapies to optimize patient outcomes and satisfaction.
[...]

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Upper Blepharoplasty: Management of the Upper Eyelid and Brow Complex via Transblepharoplasty Approach

Facial plast Surg 2018; 34: 183-193
DOI: 10.1055/s-0038-1636918

Upper blepharoplasty is one of the more common facial plastic procedures. The upper lid and brow complex are managed together. Whether upper blepharoplasty is performed for medical or cosmetic reasons, the aim is to improve appearance while retaining natural shape and maintaining (or improving) function. For optimal results, it is important to understand relevant eyelid anatomy and the concept of maintaining youthful volume and position of the eyelid brow orbit complex. Management of patient expectations, meticulous planning, and a degree of surgical finesse all contribute to the desired outcome. The article will focus on the assessment, techniques, and complications of upper blepharoplasty, which involve management of the skin, orbicularis oculi, preaponeurotic fat, levator aponeurosis and muscle as related to concomitant ptosis, and lateral brow complex via transblepharoplasty (internal) brow lift and fixation.
[...]

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Endoscopic Browplasty

Facial plast Surg 2018; 34: 139-144
DOI: 10.1055/s-0038-1637728

The endoscopic brow lift has become an established procedure that can safely and reliably rejuvenate the upper third of the face. The authors discuss relevant anatomy and considerations for patient selection to optimize surgical outcomes. A detailed review of surgical technique is presented, and the potential complications and means to reduce them are discussed.
[...]

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The Open Browlift

Facial plast Surg 2018; 34: 128-138
DOI: 10.1055/s-0038-1637003

The eyes and periorbital areas are critical components for the harmonious treatment of the aging face. The authors prefer the open browlift for rejuvenation of the forehead area. The open browlift is the most versatile, effective, and long-lasting method for the treatment of the forehead. The analysis of the forehead area, alternative treatments, variations in incisions, and key components of the surgical procedure are to be reviewed.
[...]

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Hairline Restoration: Difference in Men and Woman—Length and Shape

Facial plast Surg 2018; 34: 155-158
DOI: 10.1055/s-0038-1636905

Hair restoration has become increasingly popular in recent years with both men and women. New technologies such as follicular unit extraction and grafting have made it possible for patients to get a natural looking result with minimal downtime. Men usually experience hairline recession as a result of androgenic alopecia, while women most commonly experience thinning of the crown and vertex, with the preservation of the hairline. However, there is a growing population of women who wish to advance their hairline forward because of congenital high hairline, traction alopecia, or previous facial cosmetic surgery. There are several key differences between the female and male hairline. Understanding such differences and following certain guidelines will help the facial plastic surgeon to obtain beautiful and natural appearing results.
[...]

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Fat Grafting Volume Restoration to the Brow and Temporal Regions

Facial plast Surg 2018; 34: 164-172
DOI: 10.1055/s-0038-1636922

Primary manifestations of facial aging are the reduction in subcutaneous tissue volume, especially the atrophy of fat as well as bone volume depletion which directly contribute to loss of support and laxity of the skin. Depressions and hollows develop with a visible disruption of the cosmetic facial aesthetic units resulting in harsh shadows. This is especially evident in the eyebrow and temporal regions which accentuate the appearance of brow ptosis and a hollow, almost cadaveric look to the temple. Restoration of volume to these areas has been shown to rejuvenate the upper face creating a softer, fuller, and more youthful appearance. Fat grafting by itself or in combination with upper facial surgical procedures plays a major role in the restoration of youthful facial qualities in this region.
[...]

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Scalp Advancement and the Pretrichial Brow Lift

Facial plast Surg 2018; 34: 145-149
DOI: 10.1055/s-0038-1636920

This article will review considerations for scalp advancement, or forehead shortening, when done in combination with a brow lift. The author's technique for anterior hairline reshaping is presented with particular focus on simultaneous reduction of temporal recession.
[...]

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Effect of Orbicularis Muscle Resection during Blepharoplasty on the Position of the Eyebrow

Facial plast Surg 2018; 34: 178-182
DOI: 10.1055/s-0038-1636904

Dermatochalasis is a skin excess in the upper eyelid which may be associated with either an aesthetic and functional defect, blocking the peripheral vision. Upper blepharoplasty is the gold standard procedure for correction of dermatochalasis and to restore youthful contours to the periorbita. It is one of the most commonly performed procedures in aesthetic plastic surgery; however, there is still a lack of consensus about this procedure. The excess skin is sometimes removed alone or in conjunction with a strip of orbicularis oculi muscle. The rationale for both muscle and skin resection or skin alone preserving the muscle is uncertain. Some authors have studied the aging influence in brow position, and a few studies pointed out the influence of the upper blepharoplasty on brow height. The true effects, regarding the position of the eyebrow, of both techniques, with or without resection of the preseptal orbicularis oculi muscle, are unclear. The authors present a review of the literature to find the rationale for resecting or preserving the orbicularis oculi muscle in upper eyelid blepharoplasty and its relation to eyebrow position.
[...]

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The Trichophytic and Lateral Temporal Lifts: Application to the Focal Elevation of the Aging Lateral Eyebrow

Facial plast Surg 2018; 34: 150-154
DOI: 10.1055/s-0038-1636928

Rejuvenation of the upper face is a key component of overall facial rejuvenation. The upper face is probably the most important purveyor of our sense of well-being and our primary transmittal of nonverbal social interaction. There are many aspects to the aging changes in the area. Central to these concerns is the level and shape of the eyebrow. Ptosis of the lateral brow begins at a relatively young age and tends to worsen over time. This article describes an adaptation of modifiable techniques to address focal issues of the lateral eyebrow.
[...]

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The Aesthetics of the Upper Face: Forehead, Brow, and Upper Eyelid

Facial plast Surg 2018; 34: 107-108
DOI: 10.1055/s-0038-1636923

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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Manipulation of the Periorbital Musculature

Facial plast Surg 2018; 34: 194-200
DOI: 10.1055/s-0038-1636919

The resting and expressive states of the periorbital region contribute to perceived age, emotion, gender, race, and countenance. A thorough understanding of the periorbital musculature is essential for comprehensive facial rejuvenation. Surgical and nonsurgical manipulation of these muscles can lead to alterations in brow elevation, resting brow position, and dynamic periorbital rhytids. Both surgical and nonsurgical techniques can produce desired effects, and they are often used concomitantly to obtain optimal results.
[...]

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Morbidity and Volumetric Progression in Juvenile Nasopharyngeal Angiofibroma in a Long-Term Follow-Up

J Neurol Surg B
DOI: 10.1055/s-0038-1635255

Objective We compare the open and transnasal approaches for the excision of juvenile nasopharyngeal angiofibromas regarding the rate of morbidity, and residual tumor and its symptomatic recurrence over time. In addition, we present volumetric measurements of juvenile nasopharyngeal angiofibromas over time. Methods All surgically treated patients of our institution were reviewed back to 1969 for type of surgery, residual tumor by magnetic resonance imaging (MRI)-based volumetry, recurrence, and morbidity. We performed a prospective clinical and radiological follow-up on reachable patients. Results In total, 40 patients were retrievable from our records. We were able to follow up on 13 patients after a mean of 15.7 years since surgery (range: 1–47 years). Patients operated by the open approach had a higher rate of postoperative complications and thus a higher morbidity than endoscopic patients (4/4 vs 3/9; p = 0.007), although tumor sizes were equal among groups (p = 0.12). Persisting tumor was noted in 3/4 and 4/9 (p = 0.56) patients, respectively. The corresponding mean volumes of residual tumors were 16.2 ± 14.4 cm3 and 10.8 ± 6.6 cm3 (p = 0.27). No progression could be noted in endoscopically treated patients (p = 0.24, mean time between scans 2 years). Conclusions Our analysis shows that the endoscopic approach results in less morbidity. The open approach does not guarantee freedom from persisting tumor tissue. Age seems to be a most important risk factor for the conversion of an asymptomatic persistence into a symptomatic recurrence.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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Revision Surgery for Vestibular Schwannomas

J Neurol Surg B
DOI: 10.1055/s-0038-1635256

Objectives To describe clinical outcomes of patients undergoing revision surgery for vestibular schwannomas. Design Retrospective case series. Setting Tertiary private neurotologic practice. Participants Patients who underwent revision surgeries for recurrent/residual vestibular schwannomas between 1985 and 2015. Main Outcome Measures Degree of resection, facial nerve function, cerebrospinal fluid (CSF) leak. Results A total of 234 patients underwent 250 revision surgeries for recurrent/residual vestibular schwannomas. Of these, 86 carried a diagnosis of neurofibromatosis type 2 (NF2). The mean number of prior surgeries was 1.26, and 197 (85%) prior surgeries had been performed elsewhere. The average age at surgery was 43. The most common approach employed at the time of revision surgery was translabyrinthine (87%), followed by transcochlear (6%), middle fossa (5%), and retrosigmoid (2%). Gross total resection was achieved in 212 revision surgeries (85%). Preoperative House–Brackmann facial nerve function was similar in non-NF2 and NF2 groups (mean: 2.7). Mean postoperative facial nerve function at last follow-up was 3.8 in the non-NF2 group and 3.9 in the NF2 group. History of radiation and the extent of resection were not associated with differences in facial nerve function preoperatively or postoperatively. CSF leaks occurred after 21 surgeries (8%), and six (2%) patients required reoperation. Conclusions This is the largest series of revision surgery for vestibular schwannomas to date. Our preferred approach is the translabyrinthine craniotomy, which can be readily modified to include the transcochlear approach for improved access. CSF leak rate slightly exceeds that of primary surgery, and gross total resection is achievable in the vast majority of patients.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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More Rules, Still Exceptions: Understanding Immunomodulatory Antibody Activity In Vivo

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Andrea Ipsen-Escobedo, Falk Nimmerjahn
Understanding how agonistic and checkpoint control antibodies mediate their activity in vivo is essential for further development of these promising anti-cancer therapies. In this issue of Cancer Cell, studies by Vargas et al. and Yu et al. provide insights into the mode of action of CTLA-4- and CD40-specific antibodies.

Teaser

Understanding how agonistic and checkpoint control antibodies mediate their activity in vivo is essential for further development of these promising anti-cancer therapies. In this issue of Cancer Cell, studies by Vargas et al. and Yu et al. provide insights into the mode of action of CTLA-4- and CD40-specific antibodies.


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T Cell Dysfunction in Cancer

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Daniela S. Thommen, Ton N. Schumacher
Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.

Teaser

Therapeutic reinvigoration of tumor-specific T cells has greatly improved clinical outcome in cancer. Nevertheless, many patients still do not achieve durable benefit. Recent evidence from studies in murine and human cancer suggest that intratumoral T cells display a broad spectrum of (dys-)functional states, shaped by the multifaceted suppressive signals that occur within the tumor microenvironment. Here we discuss the current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how our emerging understanding of T cell dysfunction may be utilized to develop personalized strategies to restore antitumor immunity.


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The Immune Revolution: A Case for Priming, Not Checkpoint

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Robert H. Vonderheide
Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.

Teaser

Most tumors are unresponsive to immune checkpoint blockade, especially if deep immunosuppression in the tumor develops prior to and prevents T cell immunosurveillance. Failed or frustrated T cell priming often needs repair before successful sensitization to PD-1/PD-L1 blockade. CD40 activation plays a critical role in generating T cell immunity, by activating dendritic cells, and converting cold tumors to hot. In preclinical studies, agonistic CD40 antibodies demonstrate T cell-dependent anti-tumor activity, especially in combination with chemotherapy, checkpoint inhibitory antibodies, and other immune modulators. With the advent of multiple CD40 agonists with acceptable single-agent toxicity, clinical evaluation of CD40 combinations has accelerated.


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The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Vancheswaran Gopalakrishnan, Beth A. Helmink, Christine N. Spencer, Alexandre Reuben, Jennifer A. Wargo
The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.

Teaser

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.


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Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Roberta Zappasodi, Taha Merghoub, Jedd D. Wolchok
Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.

Teaser

Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from "self," generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization.


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Mechanistic Insights into Transmissible Cancers of Mammals

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Susan Bullman, Tao Zou, Matthew Meyerson
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz et al. and Frampton et al. present novel insights into the potential mechanisms underlying the propagation of naturally occurring transmissible cancers in mammals.

Teaser

Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. In this issue of Cancer Cell, two articles by Stammnitz et al. and Frampton et al. present novel insights into the potential mechanisms underlying the propagation of naturally occurring transmissible cancers in mammals.


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Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Stephen J. Russell, Glen N. Barber
Selective destruction of neoplastic tissues by oncolytic viruses (OVs) leads to antigen-agnostic boosting of neoantigen-specific cytotoxic T lymphocyte (CTL) responses, making OVs ideal companions for checkpoint blockade therapy. Here we discuss the mechanisms whereby OVs modulate both adjuvanticity and antigenicity of tumor cells. Suppression of antitumor immunity after OV therapy has not been observed, possibly because viral antigen expression diminishes as the antiviral response matures, thereby progressively honing the CTL response to tumor neoantigens. By combining direct in situ tumor destruction with the ability to boost antitumor immunity, OVs also have the potential to be powerful standalone cancer therapies.



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The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Maximilian R. Stammnitz, Tim H.H. Coorens, Kevin C. Gori, Dane Hayes, Beiyuan Fu, Jinhong Wang, Daniel E. Martin-Herranz, Ludmil B. Alexandrov, Adrian Baez-Ortega, Syd Barthorpe, Alexandra Beck, Francesca Giordano, Graeme W. Knowles, Young Mi Kwon, George Hall, Stacey Price, Ruth J. Pye, Jose M.C. Tubio, Hannah V.T. Siddle, Sukhwinder Singh Sohal, Gregory M. Woods, Ultan McDermott, Fengtang Yang, Mathew J. Garnett, Zemin Ning, Elizabeth P. Murchison
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.

Graphical abstract

Teaser

Stammnitz et al. show that the two transmissible cancer clones that affect Tasmanian devils are very similar in their tissues-of-origin, mutational patterns and driver gene candidates. Importantly, these cancers are both highly sensitive to inhibitors of some receptor tyrosine kinases as well as to inhibitors of DNA repair.


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Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Dan Frampton, Hagen Schwenzer, Gabriele Marino, Lee M. Butcher, Gabriele Pollara, Janos Kriston-Vizi, Cristina Venturini, Rachel Austin, Karina Ferreira de Castro, Robin Ketteler, Benjamin Chain, Richard A. Goldstein, Robin A. Weiss, Stephan Beck, Ariberto Fassati
The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression.

Graphical abstract

Teaser

By analyzing serial biopsies of vincristine-treated canine transmissible venereal tumors, Frampton et al. show that tumor regression occurs in sequential steps involving the activation of the innate immune system and immune infiltration of the tumor, and they identify CCL5 as a possible driver of regression.


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Dysregulated IL-18 Is a Key Driver of Immunosuppression and a Possible Therapeutic Target in the Multiple Myeloma Microenvironment

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Kyohei Nakamura, Sahar Kassem, Alice Cleynen, Marie-Lorraine Chrétien, Camille Guillerey, Eva Maria Putz, Tobias Bald, Irmgard Förster, Slavica Vuckovic, Geoffrey R. Hill, Seth L. Masters, Marta Chesi, P. Leif Bergsagel, Hervé Avet-Loiseau, Ludovic Martinet, Mark J. Smyth
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk^∗MYC MM progression in a CD8⁺ T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses. Strikingly, high levels of bone marrow plasma IL-18 were associated with poor overall survival in MM patients. Furthermore, our preclinical studies suggested that IL-18 could be a potential therapeutic target in MM.

Graphical abstract

Teaser

Nakamura et al. show that IL-18 produced by the multiple myeloma (MM) niche promotes MM progression in a CD8⁺ T cell-dependent manner in a mouse model and that IL-18 could be a potential therapeutic target in MM. High levels of bone marrow plasma IL-18 are associated with poor overall survival in MM patients.


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Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Jianfeng Huang, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Elias A. Castilla, Timo D. Müller, Matthias H. Tschöp, Jorge Moscat, Maria T. Diaz-Meco
Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.

Graphical abstract

Teaser

Huang et al. show in a prostate cancer mouse model that p62 loss in adipocytes leads to aggressive disease by increasing osteopontin secretion, which mediates tumor fatty acid oxidation and invasion. P62 deficiency also represses energy-consuming pathways in adipocytes, increasing nutrient availability for tumors.


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Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Yong Yu, Kolja Schleich, Bin Yue, Sujuan Ji, Philipp Lohneis, Kristel Kemper, Mark R. Silvis, Nouar Qutob, Ellen van Rooijen, Melanie Werner-Klein, Lianjie Li, Dhriti Dhawan, Svenja Meierjohann, Maurice Reimann, Abdel Elkahloun, Steffi Treitschke, Bernd Dörken, Christian Speck, Frédérick A. Mallette, Leonard I. Zon, Sheri L. Holmen, Daniel S. Peeper, Yardena Samuels, Clemens A. Schmitt, Soyoung Lee




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Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Maria Kleppe, Richard Koche, Lihua Zou, Peter van Galen, Corinne E. Hill, Lauren Dong, Sofie De Groote, Efthymia Papalexi, Amritha V. Hanasoge Somasundara, Keith Cordner, Matthew Keller, Noushin Farnoud, Juan Medina, Erin McGovern, Jaime Reyes, Justin Roberts, Matthew Witkin, Franck Rapaport, Julie Teruya-Feldstein, Jun Qi, Raajit Rampal, Bradley E. Bernstein, James E. Bradner, Ross L. Levine




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Modelling Motor Neuron Disease in Fruit Flies: Lessons from Spinal Muscular Atrophy

Publication date: Available online 9 April 2018
Source:Journal of Neuroscience Methods
Author(s): Beppe Aquilina, Ruben J. Cauchi
Motor neuron disease (MND) is characterised by muscle weakness and paralysis downstream of motor neuron degeneration. Genetic factors play a major role in disease pathogenesis and progression. This is best underscored by spinal muscular atrophy (SMA), the most common MND affecting children. Although SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene, partial compensation by the paralogous SMN2 gene and/or genetic modifiers influence age of onset and disease severity. SMA is also the first MND that is treatable thanks to the recent development of a molecular-based therapy. This key milestone was possible following an intense research campaign in which animal models had a starring role. In this review, we specifically focus on the fruit fly Drosophila melanogaster and highlight its sterling contributions aimed at furthering our understanding of SMA pathogenesis. Methods of gene disruption utilised to generate SMA fly models are discussed and ways through which neuromuscular defects have been characterised are elaborated on. A phenotypic overlap with patients and mammalian models, allowed the use of SMA fly models to identify genetic modifiers, hence spurring investigators to discover pathways that are perturbed in disease. Targeting these can potentially lead to complimentary therapies for SMA. The same output is expected from the use of SMA fly models to identify therapeutic compounds that have an ameliorative effect. We believe that lessons gained from SMA will allow researchers to eagerly exploit Drosophila to confirm novel genes linked to MND, reveal disease mechanisms and ultimately identify therapeutics.



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Hiding in Plain Sight: Rediscovering the Importance of Noncoding RNA in Human Malignancy

At the time of its construction in the 1950s, the central dogma of molecular biology was a useful model that represented the current state of knowledge for the flow of genetic information after a period of prolific scientific discovery. Unknowingly, it also biased many of our assumptions going forward. Whether intentional or not, genomic elements not fitting into this paradigm were deemed unimportant and emphasis on the study of protein-coding genes prevailed for decades. The phrase "Junk DNA," first popularized in the 1960s, is still used with alarming frequency to describe the entirety of noncoding DNA. It has since become apparent that RNA molecules not coding for protein are vitally important in both normal development and human malignancy. Cancer researchers have been pioneers in determining noncoding RNA function and developing new technologies to study these molecules. In this review, we will discuss well known and newly emerging species of noncoding RNAs, their functions in cancer, and new technologies being utilized to understand their mechanisms of action in cancer. Cancer Res; 1–10. ©2018 AACR.

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Could exercise improve mental health and cognitive skills for surgeons and other healthcare professionals?

Publication date: Available online 9 April 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): D.A. Parry, R.S. Oeppen, M.S.A. Amin, P.A. Brennan
Workplace-related illness is common in the UK, and in healthcare more than five million working days over 10years have been lost as a result. Occupational stress is well known and can affect clinicians at any stage, yet many healthcare professionals continue to work with this or other psychological problems (including anxiety, chronic fatigue, and burnout) as they do not wish to let their colleagues down. Mental health issues might be dismissed, particularly in surgery, because there is a misconception that surgeons can cope better with stress than those working in other specialties, and are better protected from clinical burnout. The benefit of exercise on physical health is clear, but its role in the maintenance of good mental health and well-being should not be underestimated. As society adopts an increasingly sedentary lifestyle, exercise for many has a lower priority than other activities. In this article we give an overview of the mental health issues that might affect doctors and surgeons, and explore how exercise can benefit our well-being and clinical performance.



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Metoidioplasty

Publication date: Available online 9 April 2018
Source:Clinics in Plastic Surgery
Author(s): Rados P. Djinovic

Teaser

Transmasculine gender confirmation surgery remains challenging and demanding. As there is no perfect or standard procedure for creating male genitalia, practitioners continue to strive for better solutions. There are 2 goals in the surgical treatment of transgender persons: removal of the native genitalia and secondary sexual characteristics and creation of the desired genitalia and secondary sexual characteristics. In transmen, this often means removal of the uterus, fallopian tubes, ovaries, and vagina and creation of the external genitalia. This article highlights metoidioplasty. Metoidioplasty with simultaneous removal of the internal genitalia may be performed in a single procedure.


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