Amplification of FRS2 in atypical lipomatous tumour/well -differentiated liposarcoma and dedifferentiated liposarcoma: a clinicopathological and genetic study of 146 cases

Abstract

Aims

Fibroblast growth factor receptor substrate 2 (FRS2) is located within the 12q13-15 band. The aim of this study was to evaluate the frequency of FRS2 amplification and its relationship with the clinicopathological features of atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL)/dedifferentiated liposarcoma (DDL).

Methods and results

FRS2 and MDM2 fluorescence in situ hybridization (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs). One hundred and eight control samples were included for FRS2 analysis. FRS2 amplification was detected in 136 of 146 (93.2%) ALT/WDL/DDLs, including 63 ALT/WDLs and 73 DDLs. A higher FRS2/CEP12 ratio was observed in DDLs than in ALT/WDLs (p=0.0005). The FRS2/CEP12 ratio of peripheral tumours was lower than that of central tumours (p=0.00004). All of the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2+/FRS2- series included 7 ALT/WDLs and 3 DDLs. Four of 7 (57.1%) MDM2+/FRS2- ALT/WDLs occurred in peripheral sites, slightly higher than the percentage of MDM2+/FRS2+ ALT/WDLs (28/63, 44.4%). All of the 3 MDM2+/FRS2- DDLs (100%) were peripheral tumours, a much higher proportion than that of MDM2+/FRS2+ DDLs (10/73, 13.7%). A high percentage of homologous pleomorphic liposarcoma-like DDLs (2/3) were observed in the MDM2+/FRS2- group. In the control group, all of the parosteal osteosarcomas (5/5, 100%) were FRS2-amplified, whereas the remaining 103 samples were FRS2-nonamplified.

Conclusions

These findings suggest that FRS2 is consistently amplified in ALT/WDL/DDLs and offer another avenue for the investigation of the biology of this tumour group. MDM2+/FRS2- cases seem to be associated with certain clinicopathological features, and further investigation is needed.

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Contribution of the α5 GABAA receptor to the discriminative stimulus effects of propofol in rat

Propofol as an agonist of GABAA receptor has a rewarding and discriminative stimulus effect. However, which subtype of the GABAA receptor is involved in the discriminative stimulus effects of propofol is still not clear. We observed the effects of an agonist or an antagonist of the subtype-selective GABAA receptor on discriminative stimulus effects of propofol. Male Sprague-Dawley rats were trained to discriminate 10 mg/kg (intraperitoneal) propofol from intralipid under a fixed-ratio 10 schedule of food reinforcement. We found that propofol produced dose-dependent substitution for propofol at 10 mg/kg, with response rate reduction only at a dose above those producing the complete substitution. CL218,872 (1–3 mg/kg, intraperitoneal), an α1 subunit-selective GABAA receptor agonist, and SL651,498 (0.3–3 mg/kg, intraperitoneal), an α2/3 GABAA receptor selective agonist, could partially substitute for the discriminative stimulus effects of propofol (40–80% propofol-appropriate responding). Meanwhile, L838,417 (0.2–0.6 mg/kg, intravenous), a α2/3/5 GABAA receptor selective agonist, could produce near 100% propofol-appropriate responding and completely substitute for propofol effects. Moreover, the administration of L655,708, the α5 GABAA receptor inverse agonist, could dose dependently attenuate the discriminative stimulus of propofol. In contrast, the α1 GABAA receptor antagonist β-CCt (1–3 mg/kg) combined with propofol (10 mg/kg) failed to block the propofol effect. The data showed that propofol produces discriminative stimulus effects in a dose-dependent manner and acts mainly on the α5 GABAA to produce the discriminative stimulus effect. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/1hexVwJ *Benfu Wang and Kun Lv contributed equally to the writing of this article. Correspondence to Qing-Quan Lian, MD, Department of Anesthesiology, Second Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325000, People's Republic China Tel:+86 139 577 13889; e-mail: lianqingquanmz@163.com or Correspondence to Wen-hua Zhou, PhD, Laboratory of Behavioral Neuroscience, Ningbo Addiction, Research and Treatment Center, School of Medicine, Ningbo University, Zhejiang Province 42 Xibei St, Ningbo 315010, People's Republic China Tel:+86 138 058 47235; e-mail: whzhou@vip.163.com Received October 4, 2017 Accepted November 28, 2017 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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The dysfunction of processing task-irrelevant emotional faces in pituitary patients: an evidence from expression-related visual mismatch negativity

Evidence showed impaired cognitive ability of patients with pituitary adenoma as an intracranial tumor. In the present study, we investigated the preattentive processing of emotional faces in pituitary adenoma patients by recording and analyzing the visual mismatch negativity elicited by deviant emotional faces. In the normal control group, deviant emotional faces elicited expression-related mismatch negativity (EMMN), with a more pronounced negative waveform for sad than happy face conditions. Compared with the normal group, EMMN related to sad faces was smaller in patients, whereas the EMMN related to happy faces remained the same. These data indicate the functional dysfunction of negative emotional processing at the preattentive stage of information processing in pituitary adenoma patients. * Jian Song and Chenglong Cao contributed equally to the writing of this article. Correspondence to Dr Guozheng Xu, Department of Neurosurgery, Wuhan General Hospital, 627 Wu Luo Road, Wuhan 430070, Hubei, China Tel: +86 027 0507 72471; fax:+86 027 8774 0350; e-mail: docxgz@163.com Received August 24, 2017 Accepted December 4, 2017 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Retinal Arterio-Arterial Collaterals in Susac Syndrome

Background: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. Methods: This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified. Results: A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months. Conclusions: The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals. Address correspondence to Robert A. Egan, MD, Department of Neurology, Rockwood Clinic, 910 W. 5th Avenue, Suite 1000, Spokane, WA 99204; E-mail: Eganr8@gmail.com The authors report no conflicts of interest. © 2018 by North American Neuro-Ophthalmology Society

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Literature Commentary

In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles: Nachev P, Rose GE, Verity DH, Manohar SG, MacKenzie K, Adams G, Theodorou M, Pankhurst QA, Kennard C. Magnetic oculomotor prosthetics for acquired nystagmus. Ophthalmology. 2017;124:1556–1564.Vestergaard N, Rosenberg T, Torp-Pedersen C, Vorum H, Andersen CU, Aasbjerg K. Increased mortality and comorbidity associated with Leber's hereditary optic neuropathy: a nationwide cohort study. Invest Ophthalmol Vis Sci. 2017;58:4586–4592.Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, Zhu X, Chimowitz MI, Antonucci MU. Effects of space flight on astronaut brain structure as indicated on MRI. N Engl J Med. 2017;377:1746–1753.Klawiter EC, Bove R, Elsone L, Alvarez E, Borisow N, Cortez M, Mateen F, Mealy MA, Sorum J, Mutch K, Tobyne SM, Ruprecht K, Buckle G, Levy M, Wingerchuk D, Paul F, Cross AH, Jacobs A, Chitnis T, Weinshenker B. High risk of postpartum relapses in neuromyelitis optica spectrum disorder. Neurology. 2017;89:2238–2244.Ahle G, Touitou V, Cassoux N, Bouyon M, Humbrecht C, Oesterlé H, Baraniskin A, Soussain C, Nguyen-Them L, Gaultier C, Hoang-Xuan K, Houillier C. Optic nerve infiltration in primary central nervous system lymphoma. JAMA Neurol. 2017;74:1368–1373.Gelfand JM, Bradshaw MJ, Stern BJ, Clifford DB, Wang Y, Cho TA, Koth LL, Hauser SL, Dierkhising J, Vu N, Sriram S, Moses H, Bagnato F, Kaufmann JA, Ammah DJ, Yohannes TH, Hamblin MJ, Venna N, Green AJ, Pawate S. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology. 2017;89:2092–2100. © 2018 by North American Neuro-Ophthalmology Society

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Risk of Acute Ischemic Stroke in Patients With Monocular Vision Loss of Vascular Etiology

Background: To evaluate the risk of concurrent acute ischemic stroke and monocular vision loss (MVL) of vascular etiology. Design: Retrospective, cross-sectional study. Subjects: Patients aged 18 or older diagnosed with MVL of suspected or confirmed vascular etiology who had no other neurologic deficits and who received brain MRI within 7 days of onset of visual symptoms were included. Methods: A medical record review was performed from 2013 to 2016 at Yale New Haven Hospital. Patients were included if vision loss was unilateral and due to transient monocular vision loss (TMVL), central retinal artery occlusion (CRAO), or branch retinal artery occlusion (BRAO). Any patients with neurologic deficits other than vision loss were excluded. Other exclusion criteria were positive visual phenomena, nonvascular intraocular pathology, and intracranial pathology other than ischemic stroke. Main Outcome Measures: The presence or absence of acute stroke on diffusion-weighted imaging (DWI) on brain MRI. Results: A total of 641 records were reviewed, with 293 patients found to have MVL. After excluding those with focal neurologic deficits, there were 41 patients who met the inclusion criteria and received a brain MRI. Eight of the 41 subjects (19.5%) were found to have findings on brain MRI positive for acute cortical strokes. The proportion of lesion positive MRI was 1/23 (4.3%) in TMVL subjects, 4/12 (33.3%) in CRAO subjects, and 2/5 (40%) in BRAO subjects. Brain computed tomography (CT) scans were not able to identify the majority of acute stroke lesions in this study. Conclusions: Patients with MVL of vascular etiology such as TMVL, CRAO, or BRAO may have up to 19.5% risk of concurrent ischemic stroke, even when there are no other neurologic deficits. These strokes were detected acutely with brain MRI using DWI but were missed on CT. Address correspondence to Jason Zhang, MD, Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, 40 Temple Street, Suite 3D, New Haven, CT 06510; E-mail: jason.zhang@yale.edu Presented at the American Academy of Ophthalmology Annual Meeting, November 14–17, 2015, Las Vegas, NV. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2018 by North American Neuro-Ophthalmology Society

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Retinal Arterio-Arterial Collaterals in Susac Syndrome

Background: The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals. Methods: This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified. Results: A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months. Conclusions: The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals. Address correspondence to Robert A. Egan, MD, Department of Neurology, Rockwood Clinic, 910 W. 5th Avenue, Suite 1000, Spokane, WA 99204; E-mail: Eganr8@gmail.com The authors report no conflicts of interest. © 2018 by North American Neuro-Ophthalmology Society

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Literature Commentary

In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD will discuss the following 6 articles: Nachev P, Rose GE, Verity DH, Manohar SG, MacKenzie K, Adams G, Theodorou M, Pankhurst QA, Kennard C. Magnetic oculomotor prosthetics for acquired nystagmus. Ophthalmology. 2017;124:1556–1564.Vestergaard N, Rosenberg T, Torp-Pedersen C, Vorum H, Andersen CU, Aasbjerg K. Increased mortality and comorbidity associated with Leber's hereditary optic neuropathy: a nationwide cohort study. Invest Ophthalmol Vis Sci. 2017;58:4586–4592.Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, Zhu X, Chimowitz MI, Antonucci MU. Effects of space flight on astronaut brain structure as indicated on MRI. N Engl J Med. 2017;377:1746–1753.Klawiter EC, Bove R, Elsone L, Alvarez E, Borisow N, Cortez M, Mateen F, Mealy MA, Sorum J, Mutch K, Tobyne SM, Ruprecht K, Buckle G, Levy M, Wingerchuk D, Paul F, Cross AH, Jacobs A, Chitnis T, Weinshenker B. High risk of postpartum relapses in neuromyelitis optica spectrum disorder. Neurology. 2017;89:2238–2244.Ahle G, Touitou V, Cassoux N, Bouyon M, Humbrecht C, Oesterlé H, Baraniskin A, Soussain C, Nguyen-Them L, Gaultier C, Hoang-Xuan K, Houillier C. Optic nerve infiltration in primary central nervous system lymphoma. JAMA Neurol. 2017;74:1368–1373.Gelfand JM, Bradshaw MJ, Stern BJ, Clifford DB, Wang Y, Cho TA, Koth LL, Hauser SL, Dierkhising J, Vu N, Sriram S, Moses H, Bagnato F, Kaufmann JA, Ammah DJ, Yohannes TH, Hamblin MJ, Venna N, Green AJ, Pawate S. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology. 2017;89:2092–2100. © 2018 by North American Neuro-Ophthalmology Society

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Risk of Acute Ischemic Stroke in Patients With Monocular Vision Loss of Vascular Etiology

Background: To evaluate the risk of concurrent acute ischemic stroke and monocular vision loss (MVL) of vascular etiology. Design: Retrospective, cross-sectional study. Subjects: Patients aged 18 or older diagnosed with MVL of suspected or confirmed vascular etiology who had no other neurologic deficits and who received brain MRI within 7 days of onset of visual symptoms were included. Methods: A medical record review was performed from 2013 to 2016 at Yale New Haven Hospital. Patients were included if vision loss was unilateral and due to transient monocular vision loss (TMVL), central retinal artery occlusion (CRAO), or branch retinal artery occlusion (BRAO). Any patients with neurologic deficits other than vision loss were excluded. Other exclusion criteria were positive visual phenomena, nonvascular intraocular pathology, and intracranial pathology other than ischemic stroke. Main Outcome Measures: The presence or absence of acute stroke on diffusion-weighted imaging (DWI) on brain MRI. Results: A total of 641 records were reviewed, with 293 patients found to have MVL. After excluding those with focal neurologic deficits, there were 41 patients who met the inclusion criteria and received a brain MRI. Eight of the 41 subjects (19.5%) were found to have findings on brain MRI positive for acute cortical strokes. The proportion of lesion positive MRI was 1/23 (4.3%) in TMVL subjects, 4/12 (33.3%) in CRAO subjects, and 2/5 (40%) in BRAO subjects. Brain computed tomography (CT) scans were not able to identify the majority of acute stroke lesions in this study. Conclusions: Patients with MVL of vascular etiology such as TMVL, CRAO, or BRAO may have up to 19.5% risk of concurrent ischemic stroke, even when there are no other neurologic deficits. These strokes were detected acutely with brain MRI using DWI but were missed on CT. Address correspondence to Jason Zhang, MD, Department of Ophthalmology and Visual Sciences, Yale University School of Medicine, 40 Temple Street, Suite 3D, New Haven, CT 06510; E-mail: jason.zhang@yale.edu Presented at the American Academy of Ophthalmology Annual Meeting, November 14–17, 2015, Las Vegas, NV. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2018 by North American Neuro-Ophthalmology Society

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Temporomandibular Joint Septic Arthritis

Summary: Infection of the temporomandibular joint (TMJ) is a rare pediatric condition resulting from the introduction of pathogens into the joint by hematogenous seeding, local extension, or trauma. Early recognition of the typical signs and symptoms including fever, trismus, preauricular swelling, and TMJ region tenderness are critical in order to initiate further evaluation and prevent feared complications of fibrosis, ankylosis, abnormal facial structure, or persistence of symptoms. Contrast-enhanced computed tomography with ancillary laboratory analysis including erythrocyte sedimentation rate, C-reactive protein, and white blood cell count are beneficial in confirming the suspected diagnosis and monitoring response to therapy. Initial intervention should include empiric parenteral antibiotics, early mandibular mobilization, and joint decompression to provide synovial fluid for analysis including cultures. This report describes a case of TMJ bacterial arthritis in a healthy 6-year-old male who was promptly treated nonsurgically with intravenous antibiotics and localized needle joint decompression with return to normal function after completion of oral antibiotics and physical therapy. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 23 January 2018. Received for publication July 23, 2017; accepted December 4, 2017. The article was created in accordance without violation of ethical standards. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Alexander Y. Lin, MD, FACS, St. Louis Cleft-Craniofacial Center, Division of Plastic Surgery, SSM Health Cardinal Glennon Children's Hospital, Saint Louis University School of Medicine, 1465 South Grand Boulevard, St. Louis, MO 63104-1095, E-mail: AYLin@SLU.edu Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Quality Improvement in Facial Transplantation: Standard Approach for Novel Procedures

No abstract available

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Enhanced Preoperative Deep Inferior Epigastric Artery Perforator Flap Planning with a 3D-Printed Perforasome Template: Technique and Case Report

Summary: Optimizing preoperative planning is widely sought in deep inferior epigastric artery perforator (DIEP) flap surgery. One reason for this is that rates of fat necrosis remain relatively high (up to 35%), and that adjusting flap design by an improved understanding of individual perforasomes and perfusion characteristics may be useful in reducing the risk of fat necrosis. Imaging techniques have substantially improved over the past decade, and with recent advances in 3D printing, an improved demonstration of imaged anatomy has become available. We describe a 3D-printed template that can be used preoperatively to mark out a patient's individualized perforasome for flap planning in DIEP flap surgery. We describe this "perforasome template" technique in a case of a 46-year-old woman undergoing immediate unilateral breast reconstruction with a DIEP flap. Routine preoperative computed tomographic angiography was performed, with open-source software (3D Slicer, Autodesk MeshMixer and Cura) and a desktop 3D printer (Ultimaker 3E) used to create a template used to mark intra-flap, subcutaneous branches of deep inferior epigastric artery (DIEA) perforators on the abdomen. An individualized 3D printed template was used to estimate the size and boundaries of a perforasome and perfusion map. The information was used to aid flap design. We describe a new technique of 3D printing a patient-specific perforasome template that can be used preoperatively to infer perforasomes and aid flap design. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 23 January 2018. Received for publication August 10, 2017; accepted November 29, 2017. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. The content of this article has not been submitted or published elsewhere. The article has been seen and approved by all authors. No color reproduction is required in this publication. Michael P. Chae, MBBS, BMedSc, Department of Plastic and Reconstructive Surgery, Frankston Hospital, Peninsula Health, 2 Hastings Road, Frankston, Victoria 3199 Australia, E-mail: mpc25@me.com Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Latissimus Dorsi and Immediate Fat Transfer (LIFT) for Complete Autologous Breast Reconstruction

Background: Despite the popularity of latissimus dorsi (LD) flap in breast reconstruction, a breast implant is often necessary to achieve sufficient volume. Prior reports describe fat grafting to the LD flap as a secondary procedure to correct contour deformities and improve volume. Our institution has instituted autologous breast reconstruction with an LD flap and immediate fat transfer (LIFT). Methods: A retrospective review of all patients undergoing the LIFT procedure was undertaken. Patient age, total volume of fat transfer, length of follow-up, need for adjuvant therapy, and complications were recorded. The procedure begins with harvest of the LD flap and fat. Prior to disorigination of the latissimus muscle, fat is injected into the flap. Flap harvest is then completed and inset to create a breast mound. Results: Eighteen patients underwent LIFT procedures over 3 years with an average follow-up of 8.7 months (range, 2–24). Four breasts (22.2%) had previously received adjuvant radiation therapy. The mean total fat grafting volume was 515.5 mL (range, 325–730) per breast. The average estimated fat graft take was 66.8% (range, 50–80%). Four patients (22.2%) experienced complications. Conclusion: Autologous augmentation of the LD flap with lipotransfer has been used to avoid placement of an implant. We improve the technique by performing lipotransfer during index reconstruction. Furthermore, we perform lipotransfer prior to disorigination of the LD muscle to minimize trauma to the flap and increase the efficiency of fat grafting. Our experience demonstrates that this technique is a viable autologous alternative to microsurgical breast reconstruction. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 23 January 2018. Received for publication August 30, 2017; accepted December 8, 2017. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Supplemental digital content is available for this article. Clickable URL citations appear in the text. David H. Song, MD, MBA, Regional Chief MedStar Health, Professor and Chairman, Department of Plastic Surgery, Georgetown University School of Medicine, 3800 Reservoir Road NW, 1-PHC, Washington, DC 20007, Email: David.H.Song@gunet.georgetown.edu Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Stromal tiny black dots, like “sugar-coated”, of von Kossa stain is a diagnostic clue to hyalinizing trabecular tumor of the thyroid gland

Hyalinizing trabecular tumor (HTT) is a rare low-grade tumor, and a prominent feature is the basement membranous stroma. We assume that such characteristic stromal findings of HTT are related to calcium deposition, and examined HTT samples by von Kossa special staining. There has been no report describing von Kossa special staining for such stroma. We collected 12 cases of HTT and 30 cases of papillary thyroid carcinoma (PTC) that had matched age, gender, tumor size, and surgical procedure characteristics as a control group. We compared the staining pattern and degree of von Kossa positivity between HTT and PTC, and a grading system of von Kossa stain was adopted to highlight differences between them. On von Kossa staining, all HTT revealed many tiny black dots around vessels in the hyalinized stroma, like "sugar-coated", and a high degree of calcium deposition in most cases, whereas PTC showed sparse stromal calcification in some cases. The degree of von Kossa staining was significantly different between the two groups. This is the first report describing abundant tiny black dots, like a "sugar-coated" appearance, of von Kossa stain in HTT. Here, we propose this finding can be a useful diagnostic clue to HTT.

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JNA Journal Club

No abstract available

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Correction to: Ionizing radiation from computed tomography versus anesthesia for magnetic resonance imaging in infants and children: patient safety considerations

Abstract

The published version of this article incorrectly lists Dr. Joseph P. Cravero in the Department of Radiology at Boston Children's Hospital. Dr. Cravero's correct affiliation is given below.

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In ineffective esophageal motility, failed swallows are more functionally relevant than weak swallows

Abstract

Background

Esophageal pressure topography (EPT) diagnosis of ineffective esophageal motility (IEM) can be non-specific with unclear clinical significance.

Aims

To determine whether peristaltic vigor or lower esophageal sphincter (LES) integrity is associated with poor clearance and acid reflux in IEM.

Methods

Bolus clearance on high-resolution impedance manometry (HRIM) and available reflux studies in patients with IEM were retrospectively reviewed. Bolus clearance was assessed using both line tracing and colored contour methods on HRIM. EPT parameters, bolus clearance, and acid reflux variables were explored.

Key Results

Eighty-eight patients with IEM were included. Bolus clearance occurred in 71% of all swallows, and 55.7% of patients had complete bolus transit (CBT, bolus clearance in ≥80% of swallows). Bolus clearance was impaired in swallows with distal contractile integral (DCI) <100 mmHg•cm•s compared to DCI 100-450 (0.43 vs 0.79, P < .0001). A cutoff at DCI 100 mmHg•cm•s was associated with clearance with an accuracy of 76% compared to 49% at DCI 450 (P = .0001 for both). A median DCI <100 was associated with a higher Eckardt score (9 vs 3, P = .03), and on reflux testing available in 47 patients, with abnormal acid exposure time (P = .002). Peristaltic reserve (PR) defined as (DCI of multiple rapid swallow/median DCI of wet swallows), integrated relaxation pressure, and resting lower esophageal sphincter pressure were not associated with clearance or acid exposure.

Conclusions & Inferences

Failed peristalsis, as defined by DCI <100 mmHg•cm•s, is associated with impaired bolus clearance and more severe dysphagia in IEM, and likely abnormal acid exposure.

Ineffective esophageal motility (IEM) is an esophageal motility disorder with unclear clinical implications. We assess bolus transit, acid exposure, and symptoms in IEM. IEM with a distal contractile integral <100 mmHg•cm•s is associated with impaired bolus clearance and a higher degree of dysphagia .

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Effect of membrane exposure on guided bone regeneration: A systematic review and meta-analysis

Abstract

Aims

This review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at peri-implant sites and edentulous ridges.

Material and Methods

Electronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A random-effects meta-analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported.

Results

Overall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was −76.24% (95% CI = −137.52% to −14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at peri-implant sites was −27.27% (95% CI of −45.87% to −8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure.

Conclusion

Based on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For peri-implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure.

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Reviewers do matter

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Effect of preoperative immunonutrition on postoperative short-term outcomes of patients with head and neck squamous cell carcinoma

Abstract

Background

Patients with head and neck squamous cell carcinoma (HNSCC) often acquire an impaired nutritional status resulting in compromised outcomes. Perioperative immunonutrition may have a positive effect on outcomes after elective surgery.

Methods

Short-term outcomes before and after implementation of preoperative immunonutrition were retrospectively assessed. Regression models adjusted for outcome predictors were used to compare the length of stay (LOS) in the hospital, local infections, and general complications.

Results

Four hundred eleven patients were included (control group = 209 and the intervention group = 202). With immunonutrition, hospital LOS was significantly lower (median 6 vs 8 days; adjusted mean difference of −5.65 days; P < .001) and local infections were significantly reduced (7.4% vs 15.3%; adjusted odds ratio [OR] 0.30; P = .006). Subgroup analysis showed more pronounced effects in patients with previous radiotherapy and extensive surgery.

Conclusion

Patients receiving preoperative immunonutrition had a shorter hospital LOS and a lower rate for wound infections and local complications. These effects remained robust after a multivariate adjustment.

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Prevalence of human papillomavirus infection among Iranian women using COBAS HPV DNA testing

Abstract

Background

Persistent infection with High Risk Human Papillomavirus (HR HPV) typesplaysamajor role in the development of cervical cancer. Therefore, the detection of HR HPV types is an essential part of cervical cancer screening. The aim of this study was to estimate the prevalence of HR HPV infection among healthy women undergoing routine cervical cancer screening in Iran.

Methods

In this cross-sectional study,the results of HPV DNA typing in 2453 normal Iranian womenwhowere referred for routine cervical cancer screening from September 2015 to March 2017 were analyzed. Participants were screened using COBAS assay for HPV DNA typing and liquid based cytology.

Results

A total of 2453 healthy sexually active women were included in this study. The mean age was 35.1 ± 8.08 years. The overall prevalence of HR HPV infection was 10.3%. HPV16 was found in 73 (3%) women. The prevalence of HPV18 and other HR HPV typeswere 16(0.7%) and166 (8.2%),respectively. Approximately, 5% of the study population had an abnormal cervical cytology (ASCUS or worse), of whom 34% were infected by HR HPV.

Conclusion

The prevalence of HR HPV infection among Iranian women has increased in the recent years which indicates the need for public education and health planning toprevent this cancer through vaccination and early diagnosis using screening tests.HPV DNA typing, diagnosisand the distribution of prevalent genotypes should be considered in the development of comprehensive cervical cancer prevention programs in Iran.

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Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort

Abstract

Introduction

To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).

Methods

Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.

Results

A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [−], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2− group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2− groups (Gp1–3 vs. anti-CCP2−: P < 0.0001 for left and right hands). DXR–BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR–BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).

Conclusion

Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.

Funding

Bristol-Myers Squibb.

Trial Registration

Clinicaltrials.gov identifier, NCT01793103.

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The Novel Oncolytic Adenoviral Mutant Ad5-3{Delta}-A20T Retargeted to {alpha}v{beta}6 Integrins Efficiently Eliminates Pancreatic Cancer Cells

Metastatic pancreatic ductal adenocarcinomas (PDAC) are incurable due to the rapid development of resistance to all current therapeutics. Oncolytic adenoviral mutants have emerged as a promising new strategy that negates such resistance. In contrast to normal tissue, the majority of PDACs express the αvβ6 integrin receptor. To exploit this feature, we modified our previously reported oncolytic adenovirus, Ad, to selectively target αvβ6 integrins to facilitate systemic delivery. Structural modifications to Ad include the expression of the small but potent αvβ6-binding peptide, A20FMDV2, and ablation of binding to the native coxsackie and adenovirus receptor (CAR) within the fiber knob region. The resultant mutant, Ad5-3-A20T, infected and killed αvβ6 integrin–expressing cells more effectively than the parental wild-type (Ad5wt) virus and Ad. Viral uptake through αvβ6 integrins rather than native viral receptors (CAR, αvβ3 and αvβ5 integrins) promoted viral propagation and spread. Superior efficacy of Ad5-3-A20T compared with Ad5wt was demonstrated in 3D organotypic cocultures, and similar potency between the two viruses was observed in Suit-2 in vivo models. Importantly, Ad5-3-A20T infected pancreatic stellate cells at low levels, which may further facilitate viral spread and cancer cell elimination either as a single agent or in combination with the chemotherapy drug, gemcitabine. We demonstrate that Ad5-3-A20T is highly selective for αvβ6 integrin–expressing pancreatic cancer cells, and with further development, this new and exciting strategy can potentially be extended to improve the systemic delivery of adenoviruses to pancreatic cancer patients. Mol Cancer Ther; 17(2); 1–13. ©2018 AACR.

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Correction to: Effect of 1064-nm Q-switched Nd:YAG laser on invasiveness and innate immune response in keratinocytes infected with Candida albicans

Abstract

In the published online version of the article, the authors' given and family names were incorrectly captured. The corrected names are shown in the author group section above.

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A profile of Propionibacterium acnes resistance and sensitivity at a tertiary dermatological centre in Singapore

Propionibacterium acnes (P. acnes) is a key component in the pathogenesis of acne. Both topical and oral antibiotics are key therapeutic options. Unfortunately, antibiotic resistance is rapidly increasing globally. Many countries have reported greater than 50% of P.acnes strains acquiring resistance to topical macrolides^1-3. In Singapore, antibiotic resistance rates of 8% in 1999⁴ rising to 14.9%⁵ in 2007 were reported. We aimed to update the local prevalence of antibiotic resistance and identify features which may distinguish patients demonstrating antibiotic resistance from those who are pan-sensitive.

This article is protected by copyright. All rights reserved.

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Pulsed-dye laser therapy for carcinoma in situ of the penis

Carcinoma in situ (CIS) of the penis is a precancerous condition with a 5 to 10% risk for progression into an invasive penile squamous cell carcinoma (SCC)¹. Clinical variants of genital CIS encompass bowenoid papulosis, erythroplasia of Queyrat and Bowen's disease. Treatment options of penile CIS include topical application of 5-fluorouracil (5-FU) or imiquimod, photodynamic therapy (PDT), ablative laser therapy, cryotherapy and surgery² .

This article is protected by copyright. All rights reserved.

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Omalizumab updosing allows disease activity control in refractory patients with chronic spontaneous urticaria

Omalizumab has been shown to be a very effective drug in chronic spontaneous urticaria (CSU) improving patients' quality of life.¹ Phase III clinical trials ASTERIA I/II and GLACIAL showed respectively 58.8-52.4% of patients achieving a twice daily average Urticaria Activity Score 7 (UAS7td)≤6 at week 12.² Outside of clinical trials, the response varies between 77-83%.³ However, some patients do not achieve well-controlled activity of the disease with the licensed dose of omalizumab (300mg/4 weeks).

This article is protected by copyright. All rights reserved.

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Dermoscopic features of pilar leiomyomas

Cutaneous pilar leiomyomas are benign smooth muscle neoplasms that usually present as painful firm erythematous to brown coloured papules and nodules.¹ Dermoscopy has been used as an auxiliary tool in the diagnosis of various cutaneous tumors. Herein we report the various dermoscopic features of 48 cutaneous pilar leiomyomas in five patients.

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Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges and Recommendations

Purpose: Immune checkpoint inhibition has been shown to generate profound and durable responses in MMR-D solid tumors and has elicited interest in detection tools and strategies to guide therapeutic decision-making. Herein we address questions on the appropriate screening, detection methods, patient selection, and initiation of therapy for MMR-D PDAC and assess the utility of NGS in providing additional prognostic and predictive information for MMR-D PDAC. Experimental Design: Archival and prospectively acquired samples and matched normal DNA from N= 833 PDAC cases were analyzed using a hybridization capture based, NGS assay designed to perform targeted deep sequencing of all exons and selected introns of 341- 468 cancer-associated genes. A computational program using NGS data derived the MSI status from the tumor-normal paired genome sequencing data. Review of available germline testing, IHC, and MSI PCR results were performed to assess and confirm MMR-D and MSI status. Results: MMR-D in PDAC is a rare event among PDAC patients (7/833) occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high mutational load and elevated MSIsensor scores were correlated with MMR-D PDAC. All 7 MMR-D PDAC patients in the study were found to have Lynch Syndrome. Four (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment benefit (1 complete response; 2 partial responses; 1 stable disease). Conclusions: An integrated approach of germline testing and somatic analyses of tumor tissues in advanced PDAC using NGS may help guide future development of immune and molecularly directed therapies in PDAC patients.

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Molecular markers increase precision of the European Association of Urology non-muscle invasive bladder cancer progression risk groups

Purpose: The European Association of Urology (EAU) guidelines for non-muscle invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathological parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1239 patients in follow-up for NMIBC in six European countries. Fresh frozen tumor samples were analyzed for GATA2, TBX2, TBX3 and ZIC4 methylation and FGFR3, TERT, PIK3CA and RAS mutation status. Cox-regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR=rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared to older studies is likely due to improved treatment in the last two decades. Overall, wild type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR 0.34, 2.53 and 2.64, respectively). The PIR for EAU high risk patients was 4.25. Based on FGFR3 mutation status and methylation of GATA2 this cohort could be reclassified into a good class (PIR=0.86, 26.2% of patients), a moderate class (PIR=4.32, 49.7%) and a poor class (PIR=7.66, 24.0%). Conclusions: We conclude that addition of selected biomarkers to the EAU risk stratification, increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression.

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Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial-Mesenchymal Transition

Purpose: Cancers with aberrant expression of Serine/threonine kinase 33 (STK33) is particularly aggressive. However, its expression, clinical significance and biological functions in gastric cancer remain largely unknown. In the present study, we determined the expression and function of STK33 in gastric cancer and delineated the clinical significance of Krüppel-like factor 4 (KLF4) /STK33 signaling pathway. Experimental Design: STK33 expression and its association with multiple clinicopathologic characteristics were analyzed immunohistochemically in human gastric cancer specimens. STK33 knockdown and overexpression were used to dissect the underlying mechanism of its functions in gastric cancer cells. Regulation and underlying mechanisms of STK33 expression by KLF4 in gastric cancer cells were studied using cell and molecular biological methods. Results: Drastically higher expression of STK33 was observed in gastric cancer and gastric intraepithelial neoplasia tissues compared to adjacent normal gastric tissues. Increased STK33 expression correlated directly with tumor size, lymph node and distant metastasis; and patients with low STK33 expression gastric cancer were predicted to have a favorable prognosis. Enforced expression of STK33 promoted gastric cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas reduced STK33 did the opposite. Moreover, STK33 promoted epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, KLF4 transcriptionally inhibited STK33 expression in gastric cancer cells. KLF4-mediated inhibition of gastric cancer cell invasion was reversed by upregulation of STK33 expression. Conclusions: STK33 has pro-tumor function and is a critical downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential prognostic marker and therapeutic target for gastric cancer.

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Flt-3L expansion of recipient CD8{alpha}+ dendritic cells deletes alloreactive donor T cells and represents an alternative to post-transplant cyclophosphamide for the prevention of GVHD

Purpose: Allogeneic bone marrow transplantation (BMT) provides curative therapy for leukemia via immunological graft-versus-leukemia (GVL) effects. In practice, this must be balanced against life threatening pathology induced by graft-versus-host disease (GVHD). Recipient dendritic cells (DC) are thought to be important in the induction of GVL and GVHD. Experimental Design: We have utilized preclinical models of allogeneic BMT to dissect the role and modulation of recipient DC in controlling donor T cell mediated GVHD and GVL. Results: We demonstrate that recipient CD8a+ DC promote activation-induced clonal deletion of allospecific donor T cells after BMT. We compared pre-transplant fms-like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy of post-transplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate superior protection from GVHD with the immunomodulatory Flt-3L approach, and similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L treatment permitted maintenance of the donor polyclonal T cell pool, where PT-Cy did not. Conclusions: These data highlight pre-transplant Flt-3L therapy as a potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD, which appears particularly well suited to haploidentical BMT where the control of infection and the prevention of GVHD are paramount.

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Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond

Abstract

Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.

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Lateral Skull Base Approaches in Pediatric Skull Base Surgery

J Neurol Surg B
DOI: 10.1055/s-0038-1624572

Lateral skull base pathology is rare in children. Awareness of the potential for lateral skull base lesions in children is imperative for timely identification and appropriate management. Some of the common presentations and pathologies shall be presented, as well as a variety of approaches that may be utilized to access the lateral skull base in the pediatric patient. Although the lateral skull base approaches utilized in adults may also be considered for management of pediatric lesions, some special considerations given the small developing anatomy need to be kept in mind.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm

J Neurol Surg B
DOI: 10.1055/s-0038-1625984

Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3–581), nine remained with recurrent/persistent disease (23%).Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0–240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Open Approaches to the Anterior Skull Base in Children: Review of the Literature

J Neurol Surg B
DOI: 10.1055/s-0037-1621739

Introduction Skull base lesions in children and adolescents are rare, and comprise only 5.6% of all skull base surgery. Anterior skull base lesions dominate, averaging slightly more than 50% of the cases. Until recently, surgery of the anterior skull base was dominated by open procedures and endoscopic skull base surgery was reserved for benign pathologies. Endoscopic skull base surgery is gradually gaining popularity. In spite of that, open skull base surgery is still considered the "gold standard" for the treatment of anterior skull base lesions, and it is the preferred approach in selected cases. Objective This article reviews current concepts and open approaches to the anterior skull base in children in the era of endoscopic surgery. Materials and Methods Comprehensive literature review. Results Extensive intracranial–intradural invasion, extensive orbital invasion, encasement of the optic nerve or the internal carotid artery, lateral supraorbital dural involvement and involvement of the anterior table of the frontal sinus or lateral portion of the frontal sinus precludes endoscopic surgery, and mandates open skull base surgery. The open approaches which are used most frequently for surgical resection of anterior skull base tumors are the transfacial/transmaxillary, subcranial, and subfrontal approaches. Reconstruction of anterior skull base defects is discussed in a separate article in this supplement. Discussion Although endoscopic skull base surgery in children is gaining popularity in developed countries, in many cases open surgery is still required. In addition, in developing countries, which accounts for more than 80% of the world's population, limited access to expensive equipment precludes the use of endoscopic surgery. Several open surgical approaches are still employed to resect anterior skull base lesions in the pediatric population. With this large armamentarium of surgical approaches, tailoring the most suitable approach to a specific lesion in regard to its nature, location, and extent is of utmost importance.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Technical aspects of abdominal ultrasound and color Doppler assessment of bowel viability in necrotizing enterocolitis

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Bioaccumulation of Trace and Non-trace Elements in Blood and Fibers of Alpacas ( Vicugna pacos ) that Graze in Italian Pastures

Abstract

The concentrations of trace and non-trace elements were determined in blood and fibers of alpacas (Vicugna pacos) from a north Italian area, as well as in their pasture forages. This is the first investigation regarding this species in Italy, and the first considering alpaca's fiber as bioindicator worldwide. Metal contents in blood were in the decreasing order: copper > zinc > aluminum > selenium > lead > nickel > manganese > chromium > arsenic and cadmium, while in fiber, metal levels were in the following order: aluminum > zinc > copper > manganese > chromium > nickel > selenium > lead > arsenic and cadmium. Antimony, beryllium, mercury, tin, and thallium were below the limit of quantification (0.010 mg kg⁻¹). The analysis of the alpacas' forage confirmed the same trend found in fiber, suggesting that metal bioaccumulation was affected by diet. These preliminary results have shown that all the trace elements studied bioaccumulated to a greater extent in the fibers of the alpaca than in the blood. Accordingly, we may suggest that alpaca fibers could be used for monitoring exposure especially to non-essential metals like aluminum, cadmium, and lead, and could constitute a suitable non-invasive method for measuring trace and non-trace element exposure in camelids.

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Adaptation and micro-structure of Co-Cr alloy maxillary complete denture base plates fabricated by selective laser melting technique

Abstract

The purpose of the study was to evaluate the adaptation and micro-structure of Co-Cr alloy maxillary complete denture base plates fabricated by the selective laser melting (SLM) technique. Twenty pairs of edentulous casts were randomly and evenly divided into two groups, and manufacturing of the Co-Cr alloy maxillary complete denture base was conducted either by the SLM technique or by the conventional method. The base-cast sets were transversally sectioned into three sections at the distal canines, mesial of the first molars and the posterior palatal zone. The gap between the metal base and cast was measured in these three sections with a stereoscopic microscope, and the data were analysed using t tests. A total of five specimens of 5 mm diameter were fabricated with the Co-Cr alloy by SLM and the traditional casting technology. A scanning electron microscope (SEM) was used to evaluate the differences in microstructure between these specimens. There was no statistical difference between the three sections in all four groups (P > 0.05). At the region of the canines, the clearance value for the SLM Co-Cr alloy group was larger than that of the conventional method group (P < 0.05). At the mesial of the first molar region and the posterior palatal zone, there was no statistical difference between the gaps observed in the two groups (P > 0.05). The SLM Co-Cr alloy has a denser microstructure behaviour and less casting defect than the cast Co-Cr alloy. The SLM technique showed initial feasibility for the manufacture of dental bases of complete dentures, but large sample studies are needed to prove its reliability in clinical applications. The mechanical properties and microstructure of the denture frameworks prepared by selective laser melting indicate that these dentures are appropriate for clinical use.

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Effects of Coenzyme Q10 Supplementation on Serum Values of Gamma-glutamyl transferase, Pseudocholinesterase, Bilirubin, Ferritin, and High-Sensitivity C-Reactive Protein in Women with Type 2 Diabetes

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-124183

Background Type 2 diabetes mellitus (T2DM) is a disease associated with increased oxidative stress which results from mitochondrial dysfunction. Coenzyme Q10 (CoQ10) is an essential antioxidant for energy production in mitochondria. The purpose of this randomized double-blind clinical trial study was to evaluate the effects of CoQ10 supplementation on serum values of gamma-glutamyl transferase (GGT), pseudocholinesterase (PchE), bilirubin, ferritin, and high-sensitivity c-reactive protein (hs-CRP) and metabolic syndrome biomarkers in women with T2DM. Material & Methods Eighty women with T2DM enrolled in this study. Thirty six of them were randomized in the drug group (receiving 100 mg/day of CoQ10) and 44 women were randomized in placebo group. Intervention was continued for 12 weeks. In both groups 35 subjects finished the study and were included in the analysis. Serum levels of the variables were measured before and after supplementation. Results Serum values of FBS (P=0.039), HOMA-IR (P=0.01), ferritin (P<0.001), total cholesterol (TC) (P=0.006), LDL-C (P=0.007) decreased and HDL-C (P=0.02) increased significantly in the drug group after intervention. Serum levels of triglyceride (P=0.09) decreased marginally in CoQ10 group. Conclusions The results of the current study had shown that after supplementation with 100 mg/day of CoQ10 for 12 weeks, serum values of FBS, HOMA-IR, TC, LDL-C and ferritin were decreased and values of HDL-C were increased in women with T2DM.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Cardiovascular Risk Factors in Acromegaly: What's the Impact of Disease Control?

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-124668

Objective Cardiovascular disease is one of the most important causes of death in acromegalic patients. The aim of this study is to compare the prevalence of cardiovascular risk factors among acromegalic patients and to evaluate the impact of disease control on these factors. Material and Methods 11 acromegalic patients with active disease and 12 controlled patients were evaluated for blood pressure, body mass index, glucose, coagulation status, and lipid profile. A group of 11 patients with non-functioning pituitary adenomas was used as control population. Results Significant differences were found in lipid profile, glucose and coagulation status in both active and controlled patients. Higher levels of fasting glucose (151.2±102.5 mg/dL, p=0.05 and 108.3±23.4 mg/dL, p=0.02 for active and controlled patients respectively) and fibrinogen (427.1±61.9 mg/dL, p=0.02 and 437.3±106.6 mg/dL, p=0.04 for active and controlled patients respectively) were present in both acromegalic groups. Active patients had higher levels of antithrombin III (1.1±0.1 U/mL, p=0.005) and the controlled ones had higher levels of high density lipoprotein cholesterol (56.1±12.5 mg/dL, p=0.05), compared with the non-functioning group. The differences between active and controlled acromegalic patients are that the latter have reduced total cholesterol (170.4±31.7 vs 201.7±34.6 mg/dL, p=0.02), lower density lipoprotein cholesterol (96,8±25,2 vs 130.8±31.5 mg/dL, p=0.01) and antithrombin III (1.0±0.2 vs 1.1±0.1 U/mL, p=0.05). Conclusion There is some reduction in cardiovascular risk factors with control of the disease, but possibly without the return to basal levels.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-125066

Berberine, a natural compound extracted from several Chinese herbs including Coptis chinensis, has been shown to have anti-obesity effects and prevents insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut microbiota; however, the molecular mechanisms underlying these activities remain unknown. We investigated the effects of berberine on obesity and insulin resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4)/tumor necrosis factor (TNF)-α signaling pathway in livers of HFD-fed obese rats. Our results showed that 8-week berberine (200 mg/kg) treatment significantly reduced fasting blood glucose, triglyceride, low-density lipoprotein-cholesterol and insulin resistance in HFD-fed obese rats. However, berberine had no significant effects on body weight, visceral fat mass or the visceral fat to body weight ratio. Berberine also attenuated HFD-induced hepatic steatosis. A prolonged HFD altered the gut microbiota composition by reducing protective bacteria like Bifidobacterium and increasing gram negative bacteria like Escherichia coli, which resulted in increased LPS release into plasma. Berberine reversed these effects and inhibited LPS-induced TLR4/TNF-α activation, resulting in increased insulin receptor and insulin receptor substrate-1 expression in the liver. These findings suggested that berberine may reduce insulin resistance, at least in part by modulating the gut microbiota along with inhibiting LPS/TLR4/TNF-α signaling in the liver.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Screening for Hypogonadism in Primary Healthcare: How to do this Effectively

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-114866

Background Testosterone, the most important androgen produced by the testes, plays an integral role in male health. Testosterone levels are increasingly being checked in primary healthcare as awareness of the risks of male hypogonadism grows. Aim To investigate what tests are performed to screen for hypogonadism and to exclude secondary hypogonadism. Design and Setting All participants attended general practices in the UK. Methods Data search was performed using the EMIS® clinical database (provider of the majority of GP operating systems in Cheshire). The anonymised records of male patients aged 18–98 years who had undergone a check of serum testosterone during a 10-year period were analysed. Results Overall screening rate was 4.3%. Of 8 788 men with a testosterone result, 1 924 men (21.9%) had a total testosterone level <10 nmol/L. Just 689 of 8 788 men (7.8%) had a sex hormone-binding globulin (SHBG) result, corresponding to 30.5% of those potentially hypogonadal. Estimated free testosterone was negatively associated with BMI (Spearman's rho -0.2, p<0.001) as was total testosterone in the over 50 s. Of 1 924 potentially hypogonadal men with a serum testosterone <10 nmol/L, 588 of 1 924 (30.6%) had a check of serum prolactin. 46.3% and 41.7% had LH and FSH measured, respectively. Only 19.1% of 1 924 men with a hypogonadal total testosterone level were subsequently put on testosterone replacement. The percentage of men in the relatively socially disadvantaged category was similar for both eugonadal and hypogonadal men with a much higher rate of screening for hypogonadism in more socially advantaged men. Conclusions Screening in primary healthcare identified a significant minority of men who had potential hypogonadism. Interpretation of a low serum testosterone requires measurement of serum prolactin, LH and FSH in order to rule out secondary hypogonadism. We suggest that this becomes part of routine screening with a balanced screening approach across the socioeconomic spectrum.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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A Big Thank You to Our Reviewers in The Past Year!

Exp Clin Endocrinol Diabetes 2018; 126: 4-6
DOI: 10.1055/s-0043-124476

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Young Adult Female Cancer Survivors' Concerns About Future Children's Health and Genetic Risk

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Autologous Fat Graft for the Treatment of Sighted Posttraumatic Enophthalmos and Sunken Upper Eyelid

Purpose: The treatment of enophthalmos and sunken upper eyelid is challenging. Although autologous fat graft has been widely used in breast augmentation, buttock contouring, and facial rejuvenation, its application in enophthalmos and sunken upper eyelid is not yet widely utilized. The clinical safety and value of autologous fat graft in sighted patients with enophthalmos and sunken upper eyelid are unclear. This study retrospectively analyzed the cosmetic results and safety of autologous fat graft in the correction of sighted traumatic enophthalmos and sunken upper eyelid. Methods: Autologous fat graft was performed in 9 patients with posttraumatic enophthalmos and sunken upper eyelid. The visual acuity, orbital swelling, eye movement, enophthalmos, and sunken upper eyelid were observed. Results: Eight to 24 months after autologous fat graft, enophthalmos and sunken upper eyelid in 9 patients improved significantly. Although orbital swelling occurred in the early postoperative period, no vision loss, eye movement limitation, or fat embolism had occurred. Conclusion: Autologous fat graft is an effective, predictable, scarless, and minimally invasive surgery for the correction of the sighted posttraumatic enophthalmos and sunken upper eyelid. The possible risk of fat embolization and blindness from the compression of the optic nerve should not be neglected. Further studies and more cases must be performed. Accepted for publication October 14, 2017. Supported by the National Basic Research Program of China (973 Program, No. 2015CB554100), National Natural Science Foundation of China (No. 81271035/H1205), and Foundation for Returned Personals Studying Abroad from Human Resources Department of Sichuan Province in 2015, People's Republic of China. HC, QZ, and QQ are co-first authors. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Hui Chen, M.D., Ophthalmology Department, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: 540685790@qq.com; Zhenglin Yang, Ph.D., Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: zliny@yahoo.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Paracanthal “One-Snip” Decompression in a Cadaver Model of Retrobulbar Hemorrhage

Purpose: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. Methods: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. Results: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11–18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. Conclusions: Compared with traditional lateral canthotomy and inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression. Accepted for publication September 28, 2017. Supported in part by the NIH-NEI P30 Core Grant (IP30EY025585-01A1) and Unrestricted Grant from The Research to Prevent Blindness, Inc., awarded to the Cole Eye Institute. The authors have no conflicts of interest to disclose. Correspondence address and reprint requests to Alexander D. Blandford, M.D., Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk i-13, Cleveland, OH 44195. E-mail: blandfa@ccf.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Deep Orbital Sub-Q Hyaluronic Acid Filler Injection for Enophthalmic Sighted Eyes in Parry–Romberg Syndrome

Purpose: The authors present a consecutive series of deep orbital Sub-Q injections to treat enophthalmic sighted eyes in Parry–Romberg syndrome patients. Methods: Retrospective, interventional case series in 2 centers. Data were collected on patient demographics, Parry–Romberg syndrome onset age, previous orbital and eyelid surgeries, diplopia, ocular movement restriction before and after the injection, number of injections, interval between injections, indication for any top-up or dissolution of filler, and any other complications. In all cases, the hyaluronic acid gel used was Restylane Sub-Q + Lidocaine. Results: A total of 8 injections on 3 patients with Parry–Romberg syndrome, and significant enophthalmos is reported. All injections were with deep orbital Sub-Q filler. All patients were females, aged 32, 24, and 52 years old while their symptoms started at 15, 16, and 30 years old, respectively. None had orbital surgery prior to the injection. Follow up period was 2, 7, and 5 years respectively. All presented a significant enophthalmos of 4 mm which reduced to 1 mm after the injection, and duration effect was 18, 24, and 20 months, respectively. We observed a significant improvement in enophthalmos, lagophthalmos, exposure keratopathy, and even ocular motility. Lagophthalmos improved from 1, 4, and 7 mm to 0, 1, and 2 mm post injection. Ocular motility improved with no onset of new limitation or diplopia. Lower eyelid retraction increased in 1 patient after orbital injection. No other complications occurred. Conclusions: Deep orbital Sub-Q hyaluronic injection for treatment of enophthalmos in Parry–Romberg syndrome is an useful option in sighted eyes. Accepted for publication November 16, 2017. Case 1 was presented at DOG (German Ophthalmological Society), Berlin, 2015. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Improving Outcomes of Posterior Approach Levatorpexy for Congenital Ptosis With Reduced Levator Function

Purpose: The authors present a new series of our experience using posterior approach levatorpexy for congenital ptosis with poorer levator function (LF) in comparison with our first published report. This technique avoids a skin incision or any resection in addition to no excision of tissue. Methods: A consecutive series of 16 patients. Retrospective review of levatorpexy for congenital ptosis. Data included eyelid margin reflex distance 1, pretarsal show, contour, and complications, including nocturnal lagophthalmos, eyelid lag on downgaze, and dry eye. Surgery was considered successful if the following 4 criteria were simultaneously met: a postoperative margin reflex distance 1 of ≥2 mm and ≤4.5 mm, intereyelid height asymmetry of ≤1 mm, no overcorrection compare to opposite eye, and satisfactory eyelid contour. Results: Mean age was 10.3 years (range 1–26 years). Mean LF was 7.3 mm (2–14 mm), while 66% (12) had LF ≤7 mm. Preoperative phenylephrine test was positive in 87.5% of patients. Mean preoperative and postoperative margin reflex distance 1 was 1.34 mm and 3.2 mm, respectively. Fourteen patients (87%) achieved the desired eyelid height and fulfilled our criteria set of success. Among 10 patients with LF ≤7 mm, 9 (90%) achieved the desired eyelid height and fulfilled our criteria set of success. Ninety-four percent did not report nocturnal lagophthalmos. Three patients needed a further levatorpexy procedure due to undercorrection. Mean postoperative follow up was up 11.2 (range 6–36) months. Conclusions: Posterior approach levatorpexy is an useful first-line choice for congenital ptosis for all ranges of LF. It is popular among parents due to its avoidance of a skin incision or any resection or excision of tissue. Accepted for publication November 18, 2017. Presented at European Society of Ophthalmic Plastic and Reconstructive Surgery in Athens, Greece, September 15, 2016. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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No Physician Shortage Despite Dire Warnings: Zeke Emanuel

Dr Eric Topol discusses factors behind a predicted physician shortage (or lack thereof) with policy expert and ethicist Dr Ezekiel Emanuel.
Medscape

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A Time Limit for Initiating Anti-Inflammatory Treatment for Improved Olfactory Function after Head Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Rat Model of Brain Injury to Occupants of Vehicles Targeted by Land Mines: Mitigation by Elastomeric Frame Designs

Journal of Neurotrauma , Vol. 0, No. 0.


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A Time Limit for Initiating Anti-Inflammatory Treatment for Improved Olfactory Function after Head Injury

Journal of Neurotrauma , Vol. 0, No. 0.


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Rat Model of Brain Injury to Occupants of Vehicles Targeted by Land Mines: Mitigation by Elastomeric Frame Designs

Journal of Neurotrauma , Vol. 0, No. 0.


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Autologous Fat Graft for the Treatment of Sighted Posttraumatic Enophthalmos and Sunken Upper Eyelid

Purpose: The treatment of enophthalmos and sunken upper eyelid is challenging. Although autologous fat graft has been widely used in breast augmentation, buttock contouring, and facial rejuvenation, its application in enophthalmos and sunken upper eyelid is not yet widely utilized. The clinical safety and value of autologous fat graft in sighted patients with enophthalmos and sunken upper eyelid are unclear. This study retrospectively analyzed the cosmetic results and safety of autologous fat graft in the correction of sighted traumatic enophthalmos and sunken upper eyelid. Methods: Autologous fat graft was performed in 9 patients with posttraumatic enophthalmos and sunken upper eyelid. The visual acuity, orbital swelling, eye movement, enophthalmos, and sunken upper eyelid were observed. Results: Eight to 24 months after autologous fat graft, enophthalmos and sunken upper eyelid in 9 patients improved significantly. Although orbital swelling occurred in the early postoperative period, no vision loss, eye movement limitation, or fat embolism had occurred. Conclusion: Autologous fat graft is an effective, predictable, scarless, and minimally invasive surgery for the correction of the sighted posttraumatic enophthalmos and sunken upper eyelid. The possible risk of fat embolization and blindness from the compression of the optic nerve should not be neglected. Further studies and more cases must be performed. Accepted for publication October 14, 2017. Supported by the National Basic Research Program of China (973 Program, No. 2015CB554100), National Natural Science Foundation of China (No. 81271035/H1205), and Foundation for Returned Personals Studying Abroad from Human Resources Department of Sichuan Province in 2015, People's Republic of China. HC, QZ, and QQ are co-first authors. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Hui Chen, M.D., Ophthalmology Department, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: 540685790@qq.com; Zhenglin Yang, Ph.D., Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: zliny@yahoo.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Paracanthal “One-Snip” Decompression in a Cadaver Model of Retrobulbar Hemorrhage

Purpose: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. Methods: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. Results: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11–18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. Conclusions: Compared with traditional lateral canthotomy and inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression. Accepted for publication September 28, 2017. Supported in part by the NIH-NEI P30 Core Grant (IP30EY025585-01A1) and Unrestricted Grant from The Research to Prevent Blindness, Inc., awarded to the Cole Eye Institute. The authors have no conflicts of interest to disclose. Correspondence address and reprint requests to Alexander D. Blandford, M.D., Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk i-13, Cleveland, OH 44195. E-mail: blandfa@ccf.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Deep Orbital Sub-Q Hyaluronic Acid Filler Injection for Enophthalmic Sighted Eyes in Parry–Romberg Syndrome

Purpose: The authors present a consecutive series of deep orbital Sub-Q injections to treat enophthalmic sighted eyes in Parry–Romberg syndrome patients. Methods: Retrospective, interventional case series in 2 centers. Data were collected on patient demographics, Parry–Romberg syndrome onset age, previous orbital and eyelid surgeries, diplopia, ocular movement restriction before and after the injection, number of injections, interval between injections, indication for any top-up or dissolution of filler, and any other complications. In all cases, the hyaluronic acid gel used was Restylane Sub-Q + Lidocaine. Results: A total of 8 injections on 3 patients with Parry–Romberg syndrome, and significant enophthalmos is reported. All injections were with deep orbital Sub-Q filler. All patients were females, aged 32, 24, and 52 years old while their symptoms started at 15, 16, and 30 years old, respectively. None had orbital surgery prior to the injection. Follow up period was 2, 7, and 5 years respectively. All presented a significant enophthalmos of 4 mm which reduced to 1 mm after the injection, and duration effect was 18, 24, and 20 months, respectively. We observed a significant improvement in enophthalmos, lagophthalmos, exposure keratopathy, and even ocular motility. Lagophthalmos improved from 1, 4, and 7 mm to 0, 1, and 2 mm post injection. Ocular motility improved with no onset of new limitation or diplopia. Lower eyelid retraction increased in 1 patient after orbital injection. No other complications occurred. Conclusions: Deep orbital Sub-Q hyaluronic injection for treatment of enophthalmos in Parry–Romberg syndrome is an useful option in sighted eyes. Accepted for publication November 16, 2017. Case 1 was presented at DOG (German Ophthalmological Society), Berlin, 2015. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Improving Outcomes of Posterior Approach Levatorpexy for Congenital Ptosis With Reduced Levator Function

Purpose: The authors present a new series of our experience using posterior approach levatorpexy for congenital ptosis with poorer levator function (LF) in comparison with our first published report. This technique avoids a skin incision or any resection in addition to no excision of tissue. Methods: A consecutive series of 16 patients. Retrospective review of levatorpexy for congenital ptosis. Data included eyelid margin reflex distance 1, pretarsal show, contour, and complications, including nocturnal lagophthalmos, eyelid lag on downgaze, and dry eye. Surgery was considered successful if the following 4 criteria were simultaneously met: a postoperative margin reflex distance 1 of ≥2 mm and ≤4.5 mm, intereyelid height asymmetry of ≤1 mm, no overcorrection compare to opposite eye, and satisfactory eyelid contour. Results: Mean age was 10.3 years (range 1–26 years). Mean LF was 7.3 mm (2–14 mm), while 66% (12) had LF ≤7 mm. Preoperative phenylephrine test was positive in 87.5% of patients. Mean preoperative and postoperative margin reflex distance 1 was 1.34 mm and 3.2 mm, respectively. Fourteen patients (87%) achieved the desired eyelid height and fulfilled our criteria set of success. Among 10 patients with LF ≤7 mm, 9 (90%) achieved the desired eyelid height and fulfilled our criteria set of success. Ninety-four percent did not report nocturnal lagophthalmos. Three patients needed a further levatorpexy procedure due to undercorrection. Mean postoperative follow up was up 11.2 (range 6–36) months. Conclusions: Posterior approach levatorpexy is an useful first-line choice for congenital ptosis for all ranges of LF. It is popular among parents due to its avoidance of a skin incision or any resection or excision of tissue. Accepted for publication November 18, 2017. Presented at European Society of Ophthalmic Plastic and Reconstructive Surgery in Athens, Greece, September 15, 2016. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Issue Information - TOC

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Annals of Neurology: Volume 83, Number 1, January 2018

Antibodies against contactin associated protein-like 2 (Caspr2) are found in some patients with autoimmune encephalitis. To see how these antibodies interact with Caspr2, cultured rat hippocampal neurons were stained with antibodies against the Caspr2 protein on the cell surface (red) and with antibodies against the Caspr2 protein that can penetrate the cell (green). Nearly all of the stained protein is golden colored (overlap of red and green), indicating that it was stained with both antibodies because it was on the surface of the cell. Caspr2 antibodies may cause encephalitis by binding to nerve cells in the brain and blocking their cell surface interactions with other cells. See Patterson et al., pages 40–51, this issue.

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Issue Information - Copyright

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Issue Information - Masthead

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Importance of whole-body imaging with complete coverage of hands and feet in alveolar rhabdomyosarcoma staging

Abstract

Background

Alveolar rhabdomyosarcoma commonly arises in the extremities and is characterized by aggressive biology and high frequency of metastases. Whole-body imaging is increasingly employed in pediatric oncology but not recommended as standard in the staging of soft-tissue sarcomas.

Objective

After observing patients with a large symptomatic alveolar rhabdomyosarcoma lesion and a smaller silent lesion in the more distal part of an extremity we sought to estimate the frequency of this constellation.

Materials and Methods

We retrospectively evaluated the data of prospectively registered paediatric patients (age <21 years) with alveolar rhabdomyosarcoma in the SoTiSaR (Soft Tissue Sarcoma Registry) of the Cooperative Weichteilsarkom Studiengruppe (CWS) 09/2011–04/2015 with regard to whole-body imaging.

Results

Seventy-five patients were eligible. Images of 57 patients had been submitted for reference consultation, including 80 whole-body examinations in 36 patients. Among them were 5 patients (14%, 95% confidence interval 3–25%) who had been diagnosed because of a symptomatic lesion while an additional silent lesion in the distal part of an extremity had remained unnoticed and had only been detected by later whole-body imaging. It is noteworthy that in 42 (53%) of all 80 whole-body examinations, the hands and feet had been only partially covered or completely excluded.

Conclusion

In alveolar rhabdomyosarcoma silent lesions can be overlooked when the distal parts of the limbs are not thoroughly examined and not completely covered by imaging. Missing them influences treatment decisions and prognosis. Our results should be considered when evaluating the potential role of whole-body imaging in rhabdomyosarcoma.

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