Summary: Columella is an important structure in the center of the face, and its structural integrity has an important functional, social, and psychological role. Columella reconstruction can be very challenging for surgeons and the ideal technique remains elusive. This article describes a reconstruction technique in a young woman with columella necrosis due to nasal continuous positive airway pressure treatment. The method of reconstruction described here, with a V-shaped internal nasal vestibular flap and a cartilage grafts from lateral crura, is simple and easily reproducible, providing an optimal aesthetic result and in addition the donor site does not create a secondary deformity by disrupting normal anatomy. 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 12 January 2018. Received for publication July 20, 2017; accepted October 18, 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. Giulia Lo Russo, MD, Department of Surgery and Translational Medicine, Plastic and Reconstructive Microsurgery, Careggi University Hospital, Florence, Italy, E-mail: giulialorusso70@gmail.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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Σάββατο 20 Ιανουαρίου 2018
The Use of Vibrational Energy to Isolate Adipose-Derived Stem Cells
Background: Adipose-derived stem cell (ADSC)–based treatments have the potential to treat numerous soft-tissue pathologies. It would be beneficial to develop an efficient and reliable intraoperative, nonenzymatic method of isolating ADSCs for clinical use. This study aims to determine the (1) viability and proliferative capacity of ADSCs after exposure to vibrational energies and (2) efficacy of vibrational energy as a method of ADSC isolation from surgically harvested infrapatellar fat pad (IFP). Methods: Cultured ADSCs were exposed to 15 minutes of vibration (60 Hz) with displacements ranging from 0 to 2.5 mm to assess cell viability and proliferation. Then, arthroscopically harvested adipose tissue (IFP; n = 5 patients) was filtered and centrifuged to separate the stromal vascular fraction, which was exposed to 15 minutes of vibration (60 Hz; 1.3 mm or 2.5 mm displacement). A viability analysis was then performed along with proliferation and apoptosis assays. Results: Vibration treatment at all displacements had no effect on the viability or proliferation of the cultured ADSCs compared with controls. There was an increased apoptosis rate between the 2.5 mm displacement group (7.53%) and controls (5.17%; P
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An Enhanced Recovery after Surgery Pathway for Microvascular Breast Reconstruction Is Safe and Effective
Background: The aim of this study was to develop, implement, and evaluate a standardized perioperative enhanced recovery after surgery (ERAS) clinical care pathway in microsurgical abdominal-based breast reconstruction. Methods: Development of a clinical care pathway was informed by the latest ERAS guideline for breast reconstruction. Key features included shortened preoperative fasting, judicious fluids, multimodal analgesics, early oral nutrition, early Foley catheter removal, and early ambulation. There were 3 groups of women in this cohort study: (1) traditional historical control; (2) transition group with partial implementation; and (3) ERAS. Narcotic use, patient-reported pain scores, antiemetic use, time to regular diet, time to first walk, hospital length of stay, and 30-day postoperative complications were compared between the groups. Results: After implementation of the pathway, the use of parenteral narcotics was reduced by 88% (traditional, 112 mg; transition, 58 mg; ERAS, 13 mg; P
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SSET Project: Cost-effectiveness Analysis of Surgical Specialty Emergency Trays in the Emergency Department
Background: We hypothesize that reusable, on-site specialty instrument trays available to plastic surgery residents in the emergency department (ED) for bedside procedures are more cost-effective than disposable on-site and remote re-usable operating room (OR) instruments at our institution. Methods: We completed a cost-effectiveness analysis comparing the use of disposable on-site kits and remote OR trays to a hypothetical, custom, reusable tray for ED procedures completed by PRS residents. Material costs of existing OR trays were used to estimate the purchasing and use-cost of a custom on-site tray for the same procedures. Cost of per procedure 'consult time' was estimated using procedure and resident salary. Results: Sixteen bedside procedures were completed over a 4.5 month period. A mean of 2.14 disposable kits were used per-procedure. Mean consultation time was 1.66 hours. Procedures that used OR trays took 3 times as long as procedures that used on-site kits (4 vs. 1.1 hours). Necessary, additional instruments were unavailable for 75% of procedures. Mean cost of using disposable kits and OR trays was $115.03/procedure versus an estimated $26.67/procedure cost of using a custom tray, yielding $88.36/procedure cost-savings. Purchase of a single custom tray ($1,421.55) would be redeemed after 2.3 weeks at 1 procedure/day. Purchasing 4 trays has projected annual cost-savings of $26,565.20. Conclusion: The purchase of specialized procedure trays will yield valuable time and cost-savings while providing quality patient care. Improving time efficiency will help achieve the Accreditation Council of Graduate Medical Education (ACGME) goals of maintaining resident well-being and developing quality improvement competency. 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 11 January 2018. Received for publication August 22, 2017; accepted October 17,2017. Presented at the 56th Annual Scientific Meeting of the Midwestern Association of Plastic Surgeons, Chicago, IL, on April 15, 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. David H. Song, MD, MBA, Department of Plastic Surgery, MedStar Georgetown University Hospital, 1 PHC, 3800 Reservoir Rd. NW, Washington, D.C. 20007, E-mail: David.H.Song@MedStar.net 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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Clinical Significance of Venous Anomalies in Syndromic Craniosynostosis
Background: The pattern of cranial venous drainage in syndromic craniosynostosis is unpredictable and not adequately understood. Collateral channels substitute for stenotic venous sinuses and pose potential risk for surgical intervention. The purpose of this study was to analyze the patterns of venous drainage in patients with syndromic craniosynostosis and their influence on operative planning and morbidity. Methods: A retrospective study of patients with syndromic craniosynostosis from 2000 to 2013 was performed. Demographic data were collected including phenotype and associated pathologies. Pre- and/or postoperative venous imaging was reviewed for venous sinus stenosis, collateral emissaries, and persistent fetal sinuses. Categorization of anomalous venous drainage was performed, and the relationship with surgical morbidity was assessed. Results: Forty-one patients were identified. Anomalies were present in 31 patients (76%) consisting of dural sinus stenosis in 28 (68%), dilated emissaries in 26 (63%), and fetal sinuses in 7 (17%). Pfeiffer syndrome was most commonly associated with anomalous drainage (100%). Venous anomalies were associated with elevated intracranial pressure (ICP), shunted hydrocephalus, Chiari malformations, and sleep apnea. In 5 cases, the surgical plan was adjusted based on anomalous anatomy. No mortalities occurred. Intraoperative complication rate was 7.3%, all with anomalous drainage. Median estimated blood loss was 1,100 cc for patients with anomalies versus 400 cc without anomalies (P = 0.181). Conclusion: Cranial venous anomalies are commonly detected in patients with syndromic craniosynostosis and may affect surgical morbidity and outcome with a higher estimated blood loss, alteration of procedure, and postoperative morbidity. Detailed preoperative imaging of the venous drainage is therefore recommended in cases of syndromic synostosis. 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 18 January 2018. Received for publication September 6, 2016; accepted November 7,2017. 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. Christopher R. Forrest, MD, Division of Plastic and Reconstructive Surgery, Department of Surgery, The Hospital for Sick Children, Suite 5430 – 555 University Avenue, Toronto, ON, Canada, M5G 1X8, E-mail: christopher.forrest@sickkids.ca 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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Complications following Nipple-Sparing Mastectomy and Immediate Acellular Dermal Matrix Implant-based Breast Reconstruction—A Systematic Review and Meta-analysis
Background: Acellular dermal matrix was introduced in breast reconstruction in 2001 and is gradually becoming a standard component for immediate breast reconstruction and nipple-sparing mastectomy. The reconstructive technique allows for improved aesthetic outcomes. However, there seems to be uncertainty regarding complication rates. The aim of this review was to systematically evaluate complication rates related to this method. Methods: This systematic review was conducted according to the recommendations outlined in the Cochrane Handbook for reviews and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Relevant databases were searched for in the literature concerning the use of acellular dermal matrix in implant-based nipple-sparing mastectomy and immediate breast reconstruction. All studies underwent detailed quality assessment. Summarized outcome rates were computed using meta-analysis. Results: Nine of 1,039 studies were eligible for inclusion yielding 778 procedures. The quality was acceptable for all included studies. The meta-analysis found the rate of skin necrosis to be 11%, nipple necrosis 5%, infection in 12%, hematoma in 1%, treated seroma in 5%, explantation 4%, and unplanned return to the operating room in 9%. Conclusion: The use of acellular dermal matrix in nipple-sparing mastectomy and implant-based breast reconstruction can be done with acceptable complication rates in selected patients. We recommend future studies to include specific definitions when reporting complication rates. Furthermore, future studies should elaborate on demographic characteristics of the included study samples and include predictor analysis to enhance knowledge of high risk patients. 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 12 January 2018. Received for publication April 5, 2017; accepted November 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 Research Unit at the Department of Plastic and Reconstructive Surgery, Odense University Hospital, Denmark. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Lene Nyhøj Heidemann, MD, Department of Plastic- and Reconstructive Surgery, Odense University Hospital, Denmark, E-mail: lenenyhoj@gmail.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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Structural and Mechanical Comparison of Human Ear, Alar, and Septal Cartilage
Background: In the human ear and nose, cartilage plays a key role in establishing its form and function. Interestingly, there is a noticeable paucity on biochemical, structural, and mechanical studies focused on facial cartilage. Such studies are needed to provide elementary knowledge that is fundamental to tissue engineering of cartilage. Therefore, in this study, a comparison is made of the biochemical, structural, and mechanical differences between ear, ala nasi, and septum on the extracellular matrix (ECM) level. Methods: Cartilage samples were harvested from 10 cadaveric donors. Each sample was indented 10 times with a nanoindenter to determine the effective Young's modulus. Structural information of the cartilage was obtained by multiple-photon laser scanning microscopy capable of revealing matrix components at subcellular resolution. Biochemistry was performed to measure glycosaminoglycan (GAG), DNA, elastin, and collagen content. Results: Significant differences were seen in stiffness between ear and septal cartilage (P = 0.011) and between ala nasi and septal cartilage (P = 0.005). Elastin content was significantly higher in ear cartilage. Per cartilage subtype, effective Young's modulus was not significantly correlated with cell density, GAG, or collagen content. However, in septal cartilage, low elastin content was associated with higher stiffness. Laser microscopy showed a distinct difference between ear cartilage and cartilage of nasal origin. Conclusion: Proposed methods to investigate cartilage on the ECM level provided good results. Significant differences were seen not only between ear and nasal cartilage but also between the ala nasi and septal cartilage. Albeit its structural similarity to septal cartilage, the ala nasi has a matrix stiffness comparable to ear cartilage. 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 18 January 2018. Received for publication May 21, 2017; accepted October 25, 2017. Disclosure: The research by Mieke Pluemeekers was financially supported by SenterNovem in the framework of EuroNanoMed (EAREG-406340-131009/1). The research of Ernst Jan Bos was supported by the Dutch Burns Foundation. Neither of the other authors has any financial disclosures. 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. Paul van Zuijlen, MD, PhD, Burn Center Department, Red Cross Hospital, Vondellaan 13, Beverwijk 1942 LE, The Netherlands, E-mail: p.vanzuijlen@vumc.nl 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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Superficial Inferior Epigastric Artery Flap Salvage Technique Using Deep Inferior Epigastric Artery Graft
Summary: Superficial inferior epigastric artery (SIEA) flap salvage remains challenging, particularly in cases of arterial insufficiency due to vessel spasm, pedicle kinking, or thrombosis. The already small, short SIEA pedicle, in addition to its inherent tendency toward spasm, renders the SIEA flap more difficult to manage when anastomotic revision is required. Furthermore, arterial thrombosis will cause dilation of the internal mammary artery, exacerbating vessel mismatch. In our previously published experience with 145 SIEA flaps, no flap with postoperative arterial thrombosis was salvageable. Following this experience, a new salvage technique using deep inferior epigastric artery grafts has been utilized and is described here. 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 12 January 2018. Received for publication June 29, 2017; accepted August 23,2017. 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. Julie E. Park, MD, Section of Plastic and Reconstructive Surgery, Department of Surgery, University of Chicago Hospitals, 5841 S. Maryland Avenue, MC 6035, Chicago, IL 60637, E-mail: jpark@surgery.bsd.uchicago.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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Successful Hand Replantation in a Case of Total Avulsion without Vein Graft
Summary: Replantation is the reattachment of a severed body part, with attempts to restore neurovascular and musculoskeletal integrity, function, and aesthetics. On September 7, 1964, the first extremity replantation—a completely amputated hand—by vascular anastomosis technique was successfully performed.1 Soon after, the first replantation of a complete thumb amputation using microvascular anastomosis in a human was successfully conducted by Komatsu et al.2 in 1968. The overall success rate of limb replantation surgery is around 83.2%.3 The mechanism of injury plays a role in the outcome; guillotine amputations—for example—carry a better prognosis than crush amputations.4 We present a case report of a 36-year-old male patient who presented with a total avulsion of the right hand with multiple fracture levels at the level of trans-carpal, distal radius extra-articulation fracture, and total avulsion of the hand. The patient was managed by a multidisciplinary team who were able to reattach his hand successfully with good functional outcome. 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. Received for publication September 17, 2017; accepted November 29,2017. The patient provided written consent for the use of his images. 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. Shatha M. Sulaiman, MD, Riyadh, Saudi Arabia, E-mail: shatha6677@hotmail.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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Single-Stage Breast Reconstruction Using an All-In-One Adjustable Expander/Implant
Background: When tissue expansion is necessary in breast reconstruction, a single-stage approach is possible using adjustable expander/implants, with or without the use of acellular dermal matrix. We aimed to present the senior author's single-stage experience over a period of 12 years using combined expander/implants in breast reconstruction. Methods: This is a Single-institution, retrospective review of breast reconstruction with combined expander/implants from 2002 to 2014. Logistic regression was performed to evaluate the impact of multiple variables on long-term outcomes. Results: A total of 162 implants in 105 patients were included in this study. Mean follow-up time was 81.7 months (SD, ± 39.2; range, 15–151). Complication rates were as follows: 0.62% extrusion, 1.2% mastectomy flap necrosis, 1.2% hematoma, 1.9% dehiscence, 2.5% seroma, 4.9% infection, and 15.4% deflation. The following associations were identified by logistic regression: adjuvant radiotherapy and capsular contracture (P = 0.034), tumor size and deflation (P = 0014), and smoking history and infection (P = 0.013). Conclusions: Overall, 81% of breasts were successfully reconstructed in a single stage. Single-stage reconstruction using all-in-one expander/implants reduces costs by eliminating the need for a second procedure under general anesthesia and can achieve results comparable with other alloplastic reconstructions reported in the literature. 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 11 January 2018. Received for publication September 19, 2017; accepted October 25, 2017. We have received ethical approval by our institution's ethics committee. We have followed the World Medical Association's Declaration of Helsinki. Presented at the Canadian Society of Plastic and Reconstructive Surgeons (CSPS) Annual Meeting, June 2016, Ottawa, ON; L'Association des Spécialistes en Chirurgie Plastique et Esthétique du Québec (ASCPEQ) annual meeting, February 2017, Montreal, QC; Fraser Gurd Surgical Research Forum, McGill University, May 2016, Montreal, QC; American Society of Plastic Surgeons (ASPS) Annual Meeting, October 2017, Orlando, FL. Disclosure: The video was financed by Mentor. The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid by the authors. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Lucie Lessard, MD, FRCSC, FACS, Division of Plastic and Reconstructive Surgery, McGill University Health Center, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, E-mail: lucie.lessard@mcgill.ca 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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Virtual Surgical Planning: The Pearls and Pitfalls
Objective: Over the past few years, virtual surgical planning (VSP) has evolved into a useful tool for the craniofacial surgeon. Virtual planning and computer-aided design and manufacturing (CAD/CAM) may assist in orthognathic, cranio-orbital, traumatic, and microsurgery of the craniofacial skeleton. Despite its increasing popularity, little emphasis has been placed on the learning curve. Methods: A retrospective analysis of consecutive virtual surgeries was done from July 2012 to October 2016 at the University of Montreal Teaching Hospitals. Orthognathic surgeries and free vascularized bone flap surgeries were included in the analysis. Results: Fifty-four virtual surgeries were done in the time period analyzed. Forty-six orthognathic surgeries and 8 free bone transfers were done. An analysis of errors was done. Eighty-five percentage of the orthognathic virtual plans were adhered to completely, 4% of the plans were abandoned, and 11% were partially adhered to. Seventy-five percentage of the virtual surgeries for free tissue transfers were adhered to, whereas 25% were partially adhered to. The reasons for abandoning the plans were (1) poor communication between surgeon and engineer, (2) poor appreciation for condyle placement on preoperative scans, (3) soft-tissue impedance to bony movement, (4) rapid tumor progression, (5) poor preoperative assessment of anatomy. Conclusion: Virtual surgical planning is a useful tool for craniofacial surgery but has inherent issues that the surgeon must be aware of. With time and experience, these surgical plans can be used as powerful adjuvants to good clinical judgement. 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 17 January 2018. Presented at the Annual meeting of the Canadian Society of Plastic Surgeons, June 2016, Ottawa, Canada. Received for publication May 31, 2017; accepted June 20, 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. Daniel Borsuk, MD, MBA, FRCSC, FACS, Plastic and Reconstructive Surgery Service, Centre Hospitalier Universitaire Sainte-Justine, 3175 Ch. Cote-Ste-Catherine, Montreal, Quebec, Canada, H3T1C5, E-mail: info@drborsuk.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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Treatment Strategies for Hypopigmentation in the Context of Burn Hypertrophic Scars
Dyspigmentation in burn scars can contribute to the development of psychosocial complications after injury and can be detrimental to social reintegration and quality of life for burn survivors. Although treatments for skin lightening to treat hyperpigmentation have been well reviewed in the literature, skin-darkening strategies to treat hypopigmentation have not. The following potential treatment options in the context of burn hypertrophic scar will be discussed: use of the melanocyte-keratinocyte transplantation procedure, use of ectopic synthetic analogues of alpha-melanocyte stimulating hormone to initiate melanogenesis, and use of FK506 to induce melanogenesis. A proposed future direction of research in laser-assisted drug delivery of inducers of local melanin production, with the hope of developing a targeted, effective approach to dyspigmentation in hypertrophic scar is also discussed. 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 18 January 2018. Received for publication November 8, 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. Jeffrey W. Shupp, MD, The Burn Center, 110 Irving Street, NW, Suite 3B-55, Washington, DC 20010, E-mail: jeffrey.w.shupp@medstar.net 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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Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency
Summary: Most cases of severely contracted nose require revision rhinoplasty and septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft tissue is necessary for tension-free revision surgery. The present study aimed to evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide (PDRN) and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF) for revision surgery of a contracted nose. In total, 30 patients were treated with 16 sessions (8 preoperative sessions and 8 postoperative sessions) of intralesional injection of PDRN and invasive RF treatment using microneedle electrodes at 1-week intervals. One week after the final combined pretreatment using PDRN and invasive bipolar RF, the skin of contracted noses was sufficiently softened, and nasal skin mobility was notably improved in all the patients. During revision rhinoplasty and septoplasty, the contracted nasal skin in each patient was adequately released for proper covering of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy elicited marked clinical improvements in persistent nasal tip dimpling and contracture, septal deviation, and warping from the incomplete recovery of nasal contracture after revision surgery. In conclusion, our pre- and postoperative adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin of the nose without major side effects. 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 16 January 2018. Received for publication August 22, 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. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Sung Bin Cho, MD, PhD, Department of Dermatology and Cutaneous Biology Research Center, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, 25 Simgok-ro, Seo-gu, 22711 Incheon, Republic of Korea, E-mail: drsbcho@gmail.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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The Pedicled LICAP Flap Combined with a Free Abdominal Flap In Autologous Breast Reconstructions
Background: Previous surgery or slim body configuration can limit the size of the available abdominal flap in autologous breast reconstruction. However, redundant skin and subcutaneous tissue lateral to the mastectomy site can be utilized as the pedicled lateral intercostal artery perforator (LICAP) flap. This study evaluates the combination of a free abdominal flap and a pedicled LICAP flap to achieve increased breast size and improved cosmetic outcome. Methods: Patients undergoing secondary autologous breast reconstruction were included in a prospective study. The combination with a LICAP flap was used for women with insufficient abdominal flap tissue in relation to the desired breast size. The authors also assessed their modification of the original lateral thoracodorsal flap design to improve the aesthetic outcome. Results: In 109 patients, 121 free abdominal flaps were performed. The combination with a pedicled LICAP flap was used in 82 free abdominal flap reconstructions (68%). The LICAP flap provided additional volume and resulted in better projection and ptosis of the neo-mamma. The overall complication rate for the LICAP flaps was 26 %; all minor complications. Despite combining flaps, the majority of patients needed additional surgery to improve breast symmetry. Breast reduction of the native breast was the most common symmetrizing procedure. Conclusion: In selected patients with insufficient abdominal flap tissue, a combination of a free abdominal flap and a pedicled LICAP flap is a valuable option to increase breast size and cosmetic outcome. Additional symmetrizing surgery might still be necessary. 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 12 January 2018. Received for publication June 24, 2017; accepted September 1,2017. Presented by the corresponding author at the 9th Congress for World Society for Reconstructive Microsurgery, June 14–17 2017, Seoul, Korea. 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 a grant from the publication fund of UiT, The Arctic University of Norway. Drs. Sjøberg and de Weerd have contributed equally to the conception and design, acquisition of data, analysis, and interpretation of data. Prepublishing revision and final approval was performed in agreement. Thomas Sjøberg, MD, Department of Plastic and Reconstructive surgery, University Hospital of North Norway, PO Box 100, N- 9038 Tromsø, Norway, E-mail: thomas.sjoberg@unn.no 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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Microsurgical Engineering: Bilateral Deep Inferior Epigastric Artery Perforator Flap with Flow-Through Intraflap Anastomosis
Squamous cell carcinoma (SCC) of the head and neck affects a significant number of people around the world every year. Treatment generally entails surgical resection, radiotherapy, chemotherapy, or some combination of the three. Following resection, microsurgical reconstruction can provide definitive coverage, replace many tissue types simultaneously, and bring healthy tissue to irradiated wound beds. Microsurgical engineering, the manipulation and reorganization of native vascular tissue, can further augment the adaptability of free tissue transfer to complex, compromised wound beds. We present one such case. The patient described in the following report was treated for a recurrent SCC of the left face, which required extensive resection resulting in a complex, composite tissue defect with compromised vascular supply. Using the principals of microsurgical engineering, definitive coverage of the defect, with accept- able aesthetic result, was achieved via bipedicle, DIEP flap with flow-through intraflap anastomosis. 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 16 January 2018. Received for publication May 31, 2017; accepted September 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. Hugo St. Hilaire, MD, DDS, FACS, Division of Plastic and Reconstructive Surgery, Department of Surgery, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, Room 741,, New Orleans, LA 70112 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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Hinge Flap with Triangular Extension for Reconstruction of Pharyngocutaneous and Laryngocutaneous Fistulas
Summary: Hinge flaps are commonly used for closure of a pharyngocutaneous fistula (PCF) or laryngocutaneous fistula. These flaps are employed to augment the wall of the pharynx or larynx, but the junction between the reconstructed and native lumens can eventually become narrow and irregular after reconstruction with standard hinge flaps. We devised a method of adding a triangular extension to the end of either or both flaps and used it to treat 3 patients. In 1 patient who developed a PCF (4 × 10 cm) after laryngectomy followed by radiotherapy, the fistula was closed with 2 hinge flaps. One flap had a caudal triangular extension. The residual skin defect was covered by a pedicled latissimus dorsi musculocutaneous flap. Another patient who developed a PCF (2.5 × 3 cm) after laryngectomy underwent 2-stage reconstruction using a buccal mucosal graft with a triangular extension, followed by 2 hinge flaps. A patient who developed an laryngocutaneous fistula (1 × 2 cm) after radiotherapy and subsequent partial laryngectomy underwent reconstruction using 2 hinge flaps, each of which had a triangular extension. The skin defect was covered by another flap. Postoperative CT or video fluoroscopic examination of swallowing showed a smooth lumen with no strictures in all 3 patients. The triangular extension of the hinge flap supplements the pharyngeal/laryngeal wall at the junction between the reconstructed and intact regions, thus avoiding postoperative stricture. Especially with PCF reconstruction, restoration of a smooth luminal surface minimizes dysphagia. 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 12 January 2018. Received for publication September 6, 2017; accepted November 10,2017. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid by JSPS KAKENHI Grant Number 16H05467. Supplemental digital content is available for this article. Clickable URL citations appear in the text. No specific products were used in this study. Presented at the 60th Annual meeting of Japan society of plastic and reconstructive surgery 2017 in Osaka, Japan. Ryuichi Azuma, MD, PhD, Department of Plastic Surgery, National Defense Medical College, 3-2 Namiki Tokorozawa, Saitama 359-0042 Japan, E-mail: azuma@ndmc.ac.jp 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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Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of Safety in 403 Patients
Background: The Earfold system, a new treatment for the correction of prominent ears, consists of 3 components: the Earfold implant, the Earfold introducer, and the Prefold positioner. Methods: This is an interim report based on an ongoing analysis of safety in a series of patients treated for prominent ears with the Earfold implant between February 2013 and September 2014. Safety was assessed based on adverse event reports and the need for implant revision; follow-up is ongoing. Results: Seven surgeons used 1,200 Earfold implants to treat 403 patients (ages, 7–70 years; 63% male); the time since the initial implant procedure now ranges from 30 to 48 months. To date, 145 patients (36%) have returned for a follow-up visit (mean, 7.7 months [range, 1–34 months]). Adverse events requiring intervention have affected 39 of 403 (9.7%) patients; these include implant revisions (n = 17 [4.2%], most often due to implant visibility), skin erosion over the implant (n = 15 [3.7%]), and infection (n = 7 [1.7%]). Bleeding, recurrence of prominence, hematoma, deformity, or adverse scarring did not occur. Conclusions: This interim analysis has shown that Earfold prominent ear correction system is associated with relatively few adverse events that require intervention; a small number of patients experienced infection, implant extrusion, or implant visibility that required revision. Most adverse events were related to either patient selection or technical errors at implantation. It is expected that with continued use of Earfold by surgeons experienced in otoplasty, the adverse event incidence will decrease. 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 12 January 2018. Received for publication June 8, 2017; accepted November 8, 2017. The opinions expressed in this article are those of the authors. The authors received no honoraria or other form of financial support related to the development of this article. Allergan plc, Dublin, Ireland funded editorial support for this article. Data collection and writing of the article were performed by the principal author with the assistance of his co-authors and without funding support. The decision to submit the article rests with the authors. Disclosure: Editorial support for this article was provided by Peloton Advantage, Parsippany, N.J., and was funded by Allergan plc, Dublin, Ireland. Norbert V. Kang is the inventor of the Earfold implant used for this investigation. He was formerly the chairman and chief technical officer for the company [Northwood Medical Innovations (NMI) Ltd] that supplied the Earfold implant. NMI Ltd has now been acquired by Allergan. None of the other authors listed have any conflicts of interest. The Article Processing Charge was paid for by Allergan plc, Dublin, Ireland. Supplemental digital content is available for this article.Clickable URL citations appear in the text. Norbert V. Kang, FRCS (Plast), Royal Free Hospital NHS Trust, Pond Street, London NW3 2QG, United Kingdom, E-mail: norbertkang@gmail.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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Reexploring the Anatomy of the Distal Humerus for its Role in Providing Vascularized Bone
Background: The lateral arm flap is used for composite defects in need of vascularized soft tissue, skin, and bone. From its original description, the distal humeral metaphysis can be included with the flap, supplied by the periosteal extensions of the posterior branch of the radial collateral artery. We sought to reexplore the anatomy of the lateral arm to determine its utility as a donor site for vascularized bone. Methods: Twelve fresh, silicone-injected cadaver dissections were performed. Arteriovenous anatomy, pedicle length and diameter, and anatomic variability as well as photo documentation was recorded. Results: The distal extent of the deltoid, lateral intermuscular septum and lateral humeral epicondyle were identified before the dissection. A septocutaneous perforator was consistently located 10 cm proximal to the lateral humeral epicondyle, which could be used for a skin paddle to monitor. Harvest of a 1.5 cm × 2 cm corticocancellous bone graft was performed. Average pedicle length was 9.1 ± 1.1 cm, and average pedicle diameter was 1.74 ± 0.52 mm. The inferior lateral cutaneous nerve of the arm and the posterior cutaneous nerve of the forearm were consistently identified and preserved. Conclusion: The predictable anatomy of the lateral distal humerus make it an ideal donor site for small segments of vascularized bone. 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 12 January 2018. Received for publication September 14, 2017; accepted November 17,2017. Presented at the Annual meeting of the American Association for Hand Surgery, Nassau, Bahamas, January 2015. Supported by DePuy-Synthes research grant. 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. T. Shane Johnson, MD, Division of Plastic Surgery, Department of Surgery, The Pennsylvania State University, College of Medicine, H071, 500 University Drive, Hershey, PA 17033, E-mail: tjohnson2@pennstatehealth.psu.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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Innovative Use of Thighplasty to Improve Prosthesis Fit and Function in a Transfemoral Amputee
Background: Excess residual limb fat is a common problem that can impair prosthesis control and negatively impact gait. In the general population, thighplasty and liposuction are commonly performed for cosmetic reasons but not specifically to improve function in amputees. The objective of this study was to determine if these procedures could enhance prosthesis fit and function in an overweight above-knee amputee. Methods: We evaluated the use of these techniques on a 50-year-old transfemoral amputee who was overweight. The patient underwent presurgical imaging and tests to measure her residual limb tissue distribution, socket-limb interface stiffness, residual femur orientation, lower-extremity function, and prosthesis satisfaction. A medial thighplasty procedure with circumferential liposuction was performed, during which 2,812 g (6.2 lbs.) of subcutaneous fat and skin was removed from her residual limb. Imaging was repeated 5 months postsurgery; functional assessments were repeated 9 months postsurgery. Results: The patient demonstrated notable improvements in socket fit and in performing most functional and walking tests. Her comfortable walking speed increased 13.3%, and her scores for the Sit-to-Stand and Four Square Step tests improved over 20%. Femur alignment in her socket changed from 8.13 to 4.14 degrees, and analysis showed a marked increase in the socket-limb interface stiffness. Conclusions: This study demonstrates the potential of using a routine plastic surgery procedure to modify the intrinsic properties of the limb and to improve functional outcomes in overweight or obese transfemoral amputees. This technique is a potentially attractive option compared with multiple reiterations of sockets, which can be time-consuming and costly. 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 12 January 2018. Received for publication June 12, 2017; accepted November 15, 2017. A part of this research was presented at the First International Symposium on Innovations in Amputation Surgery and Prosthetic Technologies, May 12–13, 2016, Chicago, Ill. Supported by numerous philanthropic grants awarded to the Center for Bionic Medicine, primarily those from the George Link, Jr. Foundation and the RIC Women's Board. 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 research protocol for this study was approved by the Northwestern University Institutional Review Board (STU00090292). Further documentation supporting our informed consent procedures can be provided upon request. Clinical Trial registration number/identifier: ClinicalTrials.gov Identifier NCT02346019. Registered January 9, 2015. Supplemental digital content is available for this article. Clickable URL citations appear in the text. Todd Kuiken, MD, PhD, Center for Bionic Medicine Shirley Ryan AbilityLab, 355 East Erie, Floor 11, Room 1414, Chicago, IL 60611 312-238-2080, E-mail: tkuiken@sralab.org 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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Hyperbaric Oxygen for Ischemia due to Injection of Cosmetic Fillers: Case Report and Issues
Summary: Natural and synthetic fillers have revolutionized aesthetic facial rejuvenation and soft-tissue augmentation. We present a case highlighting the dangers of filler self-injection. A 37-year-old woman self-injected a dermal filler around both temples. She immediately experienced left--side hearing loss, blanching over the left face, and pain. Prompt treatment with hyaluronidase, topical nitro paste, and warm compresses ensued. An emergency computed tomography angiogram showed occlusion of a superficial temporal artery branch. We treated her with enoxaparin, aspirin, dexamethasone, piperacillin-tazobactam, and intradermal lidocaine. After 6 hyperbaric oxygen therapy (HBO2) treatments in 3 days, the patient showed improvement in appearance with markedly decreased ischemic discoloration and her hearing returned to baseline. Algorithms for treating such injuries generally neglect HBO2. HBO2 is thought to be efficacious in these situations by a variety of mechanisms: oxygenation of ischemic tissues, reduction of edema, amelioration of ischemic/reperfusion injury, promotion of angiogenesis and collagen maturation. Her resolved hearing highlights the utility of HBO2 in sudden hearing loss as well. Injectors should have guidelines for using product, not only on patients but staff as well. Filler courses should include handling complications and include HBO2 in their guidelines. Clinicians should remind patients to seek treatment from qualified clinicians. The goal of a bargain price using self-injection may quickly become expensive and disfiguring. 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 11 January 2018. Received for publication August 18, 2017; accepted November 8,2017. Abstract presented as poster at Undersea and Hyperbaric Medicine Society, Annual Scientific Meeting 2017, Naples, FL. 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 Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, Neb. Jeffrey S. Cooper, MD, Department of Emergency Medicine, University of Nebraska Medical Center, 981150 NMC, Omaha, NE 68198, E-mail: Jeffrey.cooper@unmc.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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Effect of the carbon dioxide 10,600-nm laser and topical fluoride gel application on enamel microstructure and microhardness after acid challenge: an in vitro study
Abstract
The aim of this in-vitro study was to evaluate positive effects of the carbon dioxide laser (CO2, 10,600 nm) with acidulated phosphate fluoride (APF) gel on enamel acid resistance. Twenty extracted human third molars (40 surfaces) were randomly assigned into four groups: group C, untreated control; group L, CO2 laser alone group; group F, APF 1.23% fluoride gel; and group FL, APF 1.23% gel and laser. Samples from group L were irradiated with a CO2 laser for 30s. The parameter settings used were average power, 0.73 W; time on, 100 μs; time off, 40 ms; tip-to-tissue distance, 20 mm; tip diameter 700 μm; and energy density with movements, 5 J/cm2. Samples from group F were treated with the APF gel for 4 min, and the gel was washed off with distilled water. The enamel samples from group FL were treated with APF gel for 4 min and then irradiated with the CO2 laser for 30s without removing the gel. Each enamel sample was placed in 50 ml soft drink (pH = 2.75) for 10 min then rinsed with deionized water and stored in artificial saliva at 37 °C for 1 h. Samples were assessed for Vickers hardness number (VHN) before and after treatments and subjected to SEM analysis. Data were analyzed using a one-way analysis of variance (ANOVA) and Tukey's test (α < 0.05). After the acid challenge, the untreated C group was demineralized to a great extent and the enamel surface was with the lowest mean score of microhardness. The observed VHN in the control (C group) had a mean value of 176.13, the scores in the CO2 laser group (L group) were with mean value of 238.40, the F group with a mean value of 218.45, and the fluoride-treated and laser-irradiated FL group—with a mean of 268.28 VHN. Paired t test performed to compare groups C, L, F, and FL has shown that group FL has greater resistance to decrease in microhardness of dental enamel (P ≤ 0.05) on exposure to acidic protocol. After the acid challenge, the fluoride-treated and laser-irradiated samples (group FL) showed the least diminution in enamel surface microhardness. The sub-ablative carbon dioxide laser irradiation in combination with fluoride treatment is more effective in protecting enamel surface and resisting demineralization than CO2 laser irradiation or fluoride alone.
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Prevalence of technical errors and periapical lesions in a sample of endodontically treated teeth: a CBCT analysis
Abstract
Objectives
The aims of this study are to identify the most frequent technical errors in endodontically treated teeth and to determine which root canals were most often associated with those errors, as well as to relate endodontic technical errors and the presence of coronal restorations with periapical status by means of cone-beam computed tomography images.
Methods
Six hundred eighteen endodontically treated teeth (1146 root canals) were evaluated for the quality of their endodontic treatment and for the presence of coronal restorations and periapical lesions. Each root canal was classified according to dental groups, and the endodontic technical errors were recorded. Chi-square's test and descriptive analyses were performed.
Results
Six hundred eighty root canals (59.3%) had periapical lesions. Maxillary molars and anterior teeth showed higher prevalence of periapical lesions (p < 0.05). Endodontic treatment quality and coronal restoration were associated with periapical status (p < 0.05). Underfilling was the most frequent technical error in all root canals, except for the second mesiobuccal root canal of maxillary molars and the distobuccal root canal of mandibular molars, which were non-filled in 78.4 and 30% of the cases, respectively.
Conclusions
There is a high prevalence of apical radiolucencies, which increased in the presence of poor coronal restorations, endodontic technical errors, and when both conditions were concomitant. Underfilling was the most frequent technical error, followed by non-homogeneous and non-filled canals.
Clinical relevance
Evaluation of endodontic treatment quality that considers every single root canal aims on warning dental practitioners of the prevalence of technical errors that could be avoided with careful treatment planning and execution.
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Breaking paradigms in severe epistaxis: the importance of looking for the S-point
Publication date: Available online 20 January 2018
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Eduardo Macoto Kosugi, Leonardo Balsalobre, João Mangussi Gomes, Miguel Soares Tepedino, Daniel Marcus San da Silva, Erika Mucciolo Cabernite, Diego Hermann, Aldo Cassol Stamm
IntroductionSince the introduction of nasal endoscopy into the field of Otorhinolaryngology, the treatment paradigm for cases of severe epistaxis has shifted toward early and precise identification of the bleeding site. Although severe epistaxis is usually considered to arise from posterior bleeding, an arterial vascular pedicle in the superior portion of the nasal septum, around the middle turbinate axilla projection, frequently has been observed. That vascular pedicle was named the S-point.ObjectiveThe aim of this study was to describe the S-point and report cases of severe epistaxis originating from it.MethodsA retrospective case series study was conducted. Nine patients with spontaneous severe epistaxis, where the S-point was identified as the source of bleeding, were treated between March 2016 and March 2017.ResultsMale predominance (77.8%) with age average of 59.3 years old were reported. Most cases presented comorbidities (88.9%) and were not taking acetylsalicylic acid (66.7%). A predominance of left sided involvement (55.6%) anteroposterior bleeding being the principal initial presentation (77.8%) was seen. Six patients (66.7%) presented with hemoglobin levels below 10g/dL, and four (44.4%) required blood transfusion. Cauterization of S-point was performed in all patients, with complete resolution of bleeding. No patient experienced recurrence of severe epistaxis.ConclusionThe S-point, a novel source of spontaneous severe epistaxis, is reported, and its cauterization was effective and safe. Otolaryngologists must actively seek this site of bleeding in cases of severe epistaxis.
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Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells
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Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo
Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer. * Ye Wei and Fangzheng Zhou contributed equally to the writing of this article. Correspondence to Dandan Yu, MD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: yudan7088@hotmail.com or Correspondence to Gang Wu, PhD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: xhzlwg@163.com Received August 29, 2017 Accepted January 3, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Intratidal Analysis of Intraoperative Respiratory System Mechanics: Keep it Simple
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MicroRNAs as Clinical Biomarkers and Therapeutic Tools in Perioperative Medicine
Over the past decade, evolutionarily conserved, noncoding small RNAs—so-called microRNAs (miRNAs)—have emerged as important regulators of virtually all cellular processes. miRNAs influence gene expression by binding to the 3′-untranslated region of protein-coding RNA, leading to its degradation and translational repression. In medicine, miRNAs have been revealed as novel, highly promising biomarkers and as attractive tools and targets for novel therapeutic approaches. miRNAs are currently entering the field of perioperative medicine, and they may open up new perspectives in anesthesia, critical care, and pain medicine. In this review, we provide an overview of the biology of miRNAs and their potential role in human disease. We highlight current paradigms of miRNA-mediated effects in perioperative medicine and provide a survey of miRNA biomarkers in the field known so far. Finally, we provide a perspective on miRNA-based therapeutic opportunities and perspectives.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2F18Wy1
A Tale of Two Solutions: High vs Low-Chloride Intravenous Fluids
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Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial
BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting 90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightlyfrom #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2F17QCf
“Mirror, Mirror on the Wall”: Learning From Reflections on Quality
The Syringe Driver: Continuous Subcutaneous Infusions in Palliative Care, 4th ed.
A Novel Approach to Synthesize the Evidence on Analgesic Adjuvants for Postoperative Pain
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Sugammadex and Oral Contraceptives: Is It Time for a Revision of the Anesthesia Informed Consent?
Learning From Human Factors Can Make Anesthesia Even Safer
Pediatric Anesthesiology Fellows’ Perception of Quality of Attending Supervision and Medical Errors
BACKGROUND: Appropriate supervision has been shown to reduce medical errors in anesthesiology residents and other trainees across various specialties. Nonetheless, supervision of pediatric anesthesiology fellows has yet to be evaluated. The main objective of this survey investigation was to evaluate supervision of pediatric anesthesiology fellows in the United States. We hypothesized that there was an indirect association between perceived quality of faculty supervision of pediatric anesthesiology fellow trainees and the frequency of medical errors reported. METHODS: A survey of pediatric fellows from 53 pediatric anesthesiology fellowship programs in the United States was performed. The primary outcome was the frequency of self-reported errors by fellows, and the primary independent variable was supervision scores. Questions also assessed barriers for effective faculty supervision. RESULTS: One hundred seventy-six pediatric anesthesiology fellows were invited to participate, and 104 (59%) responded to the survey. Nine of 103 (9%, 95% confidence interval [CI], 4%–16%) respondents reported performing procedures, on >1 occasion, for which they were not properly trained for. Thirteen of 101 (13%, 95% CI, 7%–21%) reported making >1 mistake with negative consequence to patients, and 23 of 104 (22%, 95% CI, 15%–31%) reported >1 medication error in the last year. There were no differences in median (interquartile range) supervision scores between fellows who reported >1 medication error compared to those reporting ≤1 errors (3.4 [3.0–3.7] vs 3.4 [3.1–3.7]; median difference, 0; 99% CI, −0.3 to 0.3; P = .96). Similarly, there were no differences in those who reported >1 mistake with negative patient consequences, 3.3 (3.0–3.7), compared with those who did not report mistakes with negative patient consequences (3.4 [3.3–3.7]; median difference, 0.1; 99% CI, −0.2 to 0.6; P = .35). CONCLUSIONS: We detected a high rate of self-reported medication errors in pediatric anesthesiology fellows in the United States. Interestingly, fellows' perception of quality of faculty supervision was not associated with the frequency of reported errors. The current results with a narrow CI suggest the need to evaluate other potential factors that can be associated with the high frequency of reported errors by pediatric fellows (eg, fatigue, burnout). The identification of factors that lead to medical errors by pediatric anesthesiology fellows should be a main research priority to improve both trainee education and best practices of pediatric anesthesia.from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2F17HPd
Ischemic Preconditioning and the Role of Antifibrinolytic Drugs: Translation From Bench to Bedside
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Brain Monitoring and the Depth of Anesthesia: Another Goldilocks Dilemma
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Emergency General Surgery: Time for Anesthesiology and Surgery to Work Together to Drive Improvement in Outcomes
Developing Reflective Practice: A Guide for Medical Students, Doctors, and Teachers
New Diabetes Medications Raise New Perioperative Concerns for the Anesthesiologist
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Not All Calcium Formulations Are Alike
“That’s Not What I Said”: Seeking Fidelity in Citations
From Foundation to Demolition: The Influence of Perioperative Tranexamic Acid
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Disparities in Anesthesia Care
Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly
Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%–15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.
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Home Hearing Test: Within-Subjects Threshold Variability
Background: The Home Hearing Test (HHT) is an automated pure-tone threshold test that obtains an air conduction audiogram at five test frequencies. It was developed to provide increased access to hearing testing and support home telehealth programs. Purpose: Test and retest thresholds for 1000-Hz stimuli were analyzed to determine intrasubject variability from two independent data sets. Research Design: Prospective, repeated measures. Study Sample: In the Veterans Affairs (VA) study, results from 26 subjects 44 to 88 years of age (mean = 65) recruited from the Nashville VA audiology clinic were analyzed. Subjects were required to have a Windows PC in the home and were self-reported to be comfortable with using computers. Two subjects had normal hearing, and 24 had hearing losses of various severities and configurations. The National Center for Rehabilitative Auditory Research (NCRAR) sample included 100 subjects (68 males; 32 females) with a complaint of hearing difficulty recruited from the local community and Veteran population. Subjects ranged in age from 32 to 87 years (mean = 63.7 years). They were tested in a quiet room at the NCRAR. Data Collection and Analysis: Subjects in the VA study were provided kits for installing HHT on their home computers. HHT was installed on a computer at NCRAR to test subjects in the NCRAR study. HHT obtains a five-frequency air conduction audiogram with a retest of 1000 Hz in both ears. Only the 1000-Hz test–retest results are analyzed in this report. Six statistical measures of test–retest variability are reported. Results: Test and retest thresholds were highly correlated in both studies (r ≥ 0.96). Test–retest differences were within ±5 dB ≥92% of the time in the two studies. Standard deviations of absolute test–retest difference were ≤3.5 dB in the two studies. Conclusions: Intrasubject variability is comparable to that obtained with manual testing by audiologists in sound-treated test rooms. ACKNOWLEDGMENTS: The authors thank Drs. Josephine Helmbrecht, Rachel Tomasek, and Jay Vachhani for their valuable assistance. R.H.M., M.C.K., and G.L.S. have commercial interests in the Home Hearing Test. This work was supported by contract nos. VA-14-0005253 and VA118-12-C-0029 from the U.S. Department of Veterans Affairs and grant nos. R33DC011769 and 4R33DC011769 from the National Institute on Deafness and Other Communication Disorders. The Home Hearing Test was developed in response to the recommendations from the Workshop on Accessible and Affordable Hearing Health Care for Adults with Mild to Moderate Hearing Loss, Bethesda, Maryland, August 25–27, 2009, sponsored by the National Institute on Deafness and Other Communications Disorders. See Donahue et al. (2010) for a report of the workshop. The content of this report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Veterans Affairs. Address for correspondence: Robert H. Margolis, Audiology Incorporated, 4410 Dellwood Street, Arden Hills, MN 55112, USA. E-mail: rhmargo001@gmail.com Received August 22, 2017; accepted November 29, 2017. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Psychometric properties of outcome measures evaluating decline in gait in cerebellar ataxia: A systematic review
Source:Gait & Posture, Volume 61
Author(s): Sarah C. Milne, Anna Murphy, Nellie Georgiou-Karistianis, Eppie M. Yiu, Martin B. Delatycki, Louise A. Corben
Cerebellar ataxia often results in impairment in ambulation secondary to gait pattern dysfunction and compensatory gait adjustments. Pharmaceutical and therapy-based interventions with potential benefit for gait in ataxia are starting to emerge, however evaluation of such interventions is hampered by the lack of outcome measures that are responsive, valid and reliable for measurement of gait decline in cerebellar ataxia. This systematic review aimed for the first time to evaluate the psychometric properties of gait and walking outcomes applicable to individuals with cerebellar ataxia. Only studies evaluating straight walking were included. A comprehensive search of three databases (MEDLINE, CINAHL and EMBASE) identified 53 studies meeting inclusion criteria. Forty-nine were rated as 'poor' as assessed by the COnsensus-based Standards for the selection of health Measurement INstruments checklist. The primary objective of most studies was to explore changes in gait related to ataxia, rather than to examine psychometric properties of outcomes. This resulted in methodologies not specific for psychometric assessment. Thirty-nine studies examined validity, 11 examined responsiveness and 12 measured reliability. Review of the data identified double and single support and swing percentage of the gait cycle, velocity, step length and the Scale for Assessment and Rating of Ataxia (SARA) gait item as the most valid and responsive measures of gait in cerebellar ataxia. However, further evaluation to establish their reliability and applicability for use in clinical trials is clearly warranted. We recommend that inter-session reliability of gait outcomes should be evaluated to ensure changes are reflective of intervention effectiveness in cerebellar ataxia.
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Temporal-spatial gait parameter models of very slow walking
Source:Gait & Posture, Volume 61
Author(s): Andrew J.J. Smith, Edward D. Lemaire
This study assessed the relationship between walking speed and common temporal-spatial stride-parameters to determine if a change in gait strategy occurs at extremely slow walking speeds. Stride-parameter models that represent slow walking can act as a reference for lower extremity exoskeleton and powered orthosis controls since these devices typically operate at walking speeds less than 0.4 m/s. Full-body motion capture data were collected from 30 health adults while walking on a self-paced treadmill, within a CAREN-Extended virtual reality environment. Kinematic data were collected for 0.2–0.8 m/s, and self-selected walking speed. Eight temporal stride-parameters were determined and their relationship to walking speed was assessed using linear and quadratic regression. Stride-length, step-length, and step-frequency were linearly related to walking speed, even at speeds below 0.4 m/s. An inflection point at 0.5 m/s was found for stride-time, step-time, stance-time, and double support time. Equations were defined for each stride-parameter, with equation outputs producing correlations greater than 0.91 with the test data. This inflection point suggests a change in gait strategy at very slow walking speeds favouring greater ground contact time.
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Reported balance confidence and movement reinvestment of younger knee replacement patients are more like younger healthy individuals, than older patients
Source:Gait & Posture, Volume 61
Author(s): Brian D. Street, Allan Adkin, William Gage
This study focused on differences between the rapidly growing younger (<65 years old) and older (>65 years old) total knee replacement (TKR) patients for measures of balance confidence, movement reinvestment, and functional mobility. Fifty-nine participants, including twenty-nine primary unilateral TKR patients (six months post-TKR) formed the four experimental groups: 1) Younger TKR Patient (YP), 2) Younger Control (YC), 3) Older TKR Patient (OP), and 4) Older Control (OC). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Oxford Knee Score (OKS), Activities-specific Balance Confidence scale (ABC), the Movement-Specific Reinvestment Scale (MSRS), and the Timed Up and Go (TUG) test were measured. The YP group reported a significantly lower WOMAC score (p < 0.001), and higher perceived knee joint function (p = 0.001), compared to the OP group. The YP group also reported significantly higher balance confidence (p < 0.001) and less movement reinvestment (p = 0.001) than the OP group. TUG durations revealed that the YP group had significantly higher functional mobility compared to the OP group (p = 0.001). The YP group did not differ from the YC group across any of these measures (p > 0.05). These results identify a clear distinction between younger and older TKR patients for fall risk and TKR outcome, which argues that age should be a factor clinicians take into account when addressing the management and care of individuals recovering from TKR.
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Distal upper limb kinematics during functional everyday tasks
Source:Gait & Posture, Volume 61
Author(s): Ben Stansfield, Scott Rooney, Lisa Brown, Matthew Kay, Lisa Spoettl, Shivaramkumar Shanmugam
Quantitative characterisation of upper limb motion allows the evaluation of the effect of pathology on functional task performance, potentially directing rehabilitation strategies. Movement patterns of the distal upper limb in healthy adults during functional tasks have not been extensively characterised. During five loaded functional tasks (drinking from a glass, pouring from a kettle, turning a handle, lifting a bag to a shelf, turning a key) the movement patterns were characterised using three-dimensional motion analysis with a minimal marker set in 16 healthy adults (10 M,6F, 27 (IQR:25–43)years). Joint angles reported include flexion/extension at the elbow and wrist, forearm supination/pronation and digits 2–5 metacarpophalangeal (MCP) joint flexion/extension. Additionally for the thumb the angle between the metacarpal of the thumb and the 2nd digit (Thumb base), the thumb MCP (Thumb MCP) and interphalangeal (Thumb IP) joint angles are presented. Durations of activities performed at self-selected comfortable speeds (3.36 (IQR:3.07,3.66)s turning a key to 6.20 (IQR:5.44,6.38)s drinking from a glass) are reported. The maximum joint angles used (median of participants' maxima) were 141° of elbow flexion, 116° forearm supination, 36° wrist extension, 56° Thumb base, 14° Thumb MCP flexion, 18° Thumb IP flexion, 85° MCP2-5 flexion. The tasks of drinking from a glass, lifting a bag to a shelf and turning a key appeared to have the least variation in performance, suggesting that these activities are better suited to be selected as standardized tasks for assessing the impact of pathology on movement than pouring from a kettle and turning a handle.
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NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors
NUT midline carcinoma is an aggressive tumor that occurs mainly in the head and neck and, less frequently, the mediastinum and lung. Following identification of an index case of a NUTM1 fusion positive undifferentiated soft tissue tumor, we interrogated additional cases of primary undifferentiated soft tissue and visceral tumors for NUTM1 abnormalities. Targeted next-generation sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue, and results validated by fluorescence in situ hybridization using custom bacterial artificial chromosome probes. Six patients were identified: mean age of 42 years (range, 3 to 71 y); equal sex distribution; and, tumors involved the extremity soft tissues (N=2), kidney (N=2), stomach, and brain. On systemic work-up at presentation all patients lacked a distant primary tumor. Morphologically, the tumors were heterogenous, with undifferentiated round-epithelioid-rhabdoid cells arranged in solid sheets, nests, and cords. Mitotic activity was generally brisk. Four cases expressed pancytokeratin, but in only 2 cases was this diffuse. Next-generation sequencing demonstrated the following fusions: BRD4-NUTM1 (3 cases), BRD3-NUTM1, MXD1-NUTM1, and BCORL1-NUTM1. Independent testing by fluorescence in situ hybridization confirmed the presence of NUTM1 and partner gene rearrangement. This study establishes that NUT-associated tumors transgress the midline and account for a subset of primitive neoplasms occurring in soft tissue and viscera. Tumors harboring NUTM1 gene fusions are presumably underrecognized, and the extent to which they account for undifferentiated mesenchymal, neuroendocrine, and/or epithelial neoplasms is unclear. Moreover, the relationship, if any, between NUT-associated tumors in soft tissue and/or viscera, and conventional NUT carcinoma, remains to be elucidated. Conflicts of Interest and Source of Funding: Supported in part by: P50 CA140146-01 (CRA); P30-CA008748 (CRA); Kristen Ann Carr Foundation (CRA); Cycle for Survival (CRA). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Brendan C. Dickson, MD, Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, ON, Canada M5G 1×5 (e-mail: brendan.dickson@sinaihealthsystem.ca). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Architectural Patterns are a Relevant Morphologic Grading System for Clear Cell Renal Cell Carcinoma Prognosis Assessment: Comparisons With WHO/ISUP Grade and Integrated Staging Systems
We developed and validated an architecture-based grading for clear cell renal cell carcinoma (ccRCC) in an observational retrospective cohort study including 506 tumors (principal cohort, n=254; validation cohort, n=252). Study endpoints were disease-free survival (DFS) and cancer-specific survival (CSS). Relationships with outcome were analyzed using Harrell concordance index, time-dependent receiver operating characteristic curve, area under curve, and Cox regression model. An architecture-based grading was devised on positive likelihood ratio (LR+) for DFS at 50 months as follows: grade 1 (LR+
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Patterns of age-specific socioeconomic inequalities in net survival for common cancers in Taiwan, a country with universal health coverage
Source:Cancer Epidemiology, Volume 53
Author(s): Li-Hsin Chien, Tzu-Jui Tseng, Fang-Yu Tsai, Jie-Huei Wang, Chao A. Hsiung, Tsang-Wu Liu, I-Shou Chang
IntroductionIn high-income countries, advances in early diagnosis and treatment have improved cancer survival. However, socioeconomic inequalities in survival have persisted or increased for some adult cancers.Materials and methodsWe assessed net survival for the 20 most common adult cancers in Taiwan. They were stratified into six age groups and three socioeconomic groups.ResultsOut of 120 cancer site and age group combinations, 49 showed improvements in 5-year net survival from 2000–2004 to 2005–2010. Only cervix uteri cancer in the 35–49-year age group showed a deterioration. During 2000–2010, 13 of the 20 cancer cases experienced socioeconomic inequalities for all age groups combined, and the deprivation gaps varied with cancer site and age at diagnosis. For the five most common cancers – liver, colon and rectum, lung, breast, and oral – there were socioeconomic inequalities, and 5-year net survival improved for most or all of the six age groups from 2000–2004 to 2005–2010.ConclusionReducing socioeconomic inequality in survival may lead to improvements in survival overall. We should focus on the age groups with large deprivation gaps. Our results are useful for prioritizing cancer sites and age groups for in-depth socioeconomic disparity studies and for proposing interventions for health disparity reductions and net cancer survival improvements.
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Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma
Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2–6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8–15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9–13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6–6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30–0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2–8.5), 5.7 months (95% CI: 3.0–8.4) for dabrafenib, and 3.6 months (95% CI: 3.5–3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT. Correspondence to Dieta Brandsma, MD, PhD, Department of Neuro-Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Tel: +31 20 512 2570; fax: +31 20 512 2572; e-mail: d.brandsma@nki.nl Received August 13, 2017 Accepted December 15, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases
Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P
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Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report
The mitogen-activated protein kinase pathway regulates cell growth and differentiation and is activated by BRAF mutations. BRAF mutations are present in about 40–50% of cutaneous melanomas. More than 90% of BRAF mutations are the V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant advanced melanomas. A variety of side effects have been observed with combination therapy including pyrexia, fatigue, nausea, and vomiting. Rhabdomyolysis is one of the most severe adverse events, but it is very rare. Only two cases of rhabdomyolysis have been reported in clinical trials. A 41-year-old Japanese woman with cutaneous melanoma was started on a combination of dabrafenib and trametinib therapy after failure of immune checkpoint therapy. One month later, she complained of myalgia and fatigue and was shifted to our hospital. She was diagnosed with trametinib-induced rhabdomyolysis and showed improvement only with a high volume of fluid infusion. We stopped combination therapy, but there were no useful treatment options for her. After resuming dabrafenib, followed by trametinib, she did not have any problems. This is the first case of a patient with metastatic cutaneous melanoma who could recommence combination therapy after trametinib-associated rhabdomyolysis. We assume that not all patients experience recurrence of rhabdomyolysis in trametinib-induced rhabdomyolysis. As few cases have been reported, more information is needed. We have to evaluate safety carefully if rechallenging combination therapy. Correspondence to Yusuke Muto, MD, Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan Tel: +81 033 542 2511; fax: +81 033 545 3567; e-mail: ymuto@ncc.go.jp Received May 8, 2017 Accepted November 19, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Cardiopulmonary Aerobic Fitness Assessment During Maximal and Submaximal Exercise Testing in Pediatric Oncology Patients After Chemotherapy
Purpose: The cardiopulmonary exercise test (CPET) is a valuable tool to assess cardiopulmonary exercise capacity in pediatric oncology patients after chemotherapy. In addition, few studies on the utility of submaximal testing have been performed, which could be important as some patients are unable to complete a maximal effort test secondary to deconditioning by both disease and treatment. Materials and Methods: We performed a retrospective chart review of pediatric cancer patients exposed to chemotherapy from 1992 to 2013 who underwent CPET with cycle ergometry (n=27). The study patients were compared with age-matched, sex-matched, and size-matched normal controls. The submaximal measure recorded was the oxygen consumption (VO2)@respiratory exchange ratio (RER) 1.0 during a maximal effort test. Results: The chemotherapy group demonstrated significantly lower exercise time (9.2±3.6 vs. 11.4±3.8; P=0.008), total work capacity (4914.4±3290.3 vs. 7664.4±4289.5; P=0.004), systolic blood pressure at peak exercise (162.9±23.2 vs. 177.3±23.8; P=0.01), indexed peak VO2 (33.9±6.9 vs. 40.0±6.3; P=0.001), and indexed peak oxygen pulse (6.1±1.3 vs. 7.0±1.5; P=0.004)). For the submaximal outcome measured, 11/27 of the chemotherapy patients had VO2@RER 1.0 values
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