Physical Medicine & Rehabilitation

Energy Cost of Slow and Normal Gait Speeds in Low and Normally Functioning Adults Objective Slow walking speed paired with increased energy cost is a strong predictor for mortality and disability in older adults but has yet to be examined in a heterogenous sample (i.e. age, gender, disease status). The purpose of this study was to examine energy cost of slow and normal walking speeds among low- and normal-functioning adults. Design Adults 20-90 years old were recruited for this study. Participants completed a 10-m functional walk test at a self-selected normal walking speed, and were categorized as low-functioning (LF) or normal-functioning (NF) based upon expected age and gender adjusted average gait speed. Participants completed two successive 3-minute walking stages, at slower than normal and normal walking speeds, respectively. Gas exchange was measured, and energy cost per meter (ml.kg-1.m-1) was calculated for both walking speeds. Results Energy cost per meter was higher (p<0.0001) in the LF group (n=76; female=59.21%; age 61.13±14.68 years (mean±SD)) during the slower than normal and normal (p<0.0001) walking speed bouts compared with the NF group (n=42; female=54.76%; age 51.55±19.51 years). Conclusion Low-functioning adults rely on greater energy cost per meter of walking at slower and normal speeds. This has implications for total daily energy expenditure in low-functioning, adult populations. Corresponding Author: Scott J. Strath; sstrath@uwm.edu Author Disclosures: The authors have no competing interests. This work was supported by funding from the NIH 1R21HD080828. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The Feasibility and Effects of Acupuncture on Muscle Soreness and Sense of Well-being in an Adolescent Football Population Objective To assess the feasibility of performing acupuncture on multiple adolescent athletes in a warm weather, high intensity training environment. To measure perceived effects of acupuncture on delayed-onset muscle soreness (DOMS) and sense of well-being. Design Prospective feasibility study, registered clinical trial (NCT03478800). 42 healthy male participants, ages 13-18 years, were involved in at least one of five treatment days for a total of 147 individual treatment sessions. Fifteen-minute treatments of traditional needle acupuncture were administered at the football field. Time, cost, side effects, and participant to provider ratio were observed. Effect on DOMS and sense of well-being were measured via pre- and posttreatment VAS (0-10) rating analyses. Results Time required by research staff on treatment days, 75 minutes; total cost, $700 temperature range, 21-28°C; largest participant to acupuncturist ratio, 7-10:1. No major side effects occurred; 55% reported minimal side effects such as mild focal numbness or tingling. Overall pre- to posttreatment effect on DOMS (average over 5 days) demonstrated significantly improved posttreatment scores (pre 4.6 ± 2.0; post 2.9 ± 2.2, p<.001). There was no significant effect on sense of well-being (p=0.12). Conclusion Effectively providing acupuncture to multiple adolescent football players in their training environment is feasible with appropriate staff and resources. Despite mild side-effects, treatment was well tolerated. This study provides guidance on acupuncture delivery to other athletes in their training environments. Please address correspondence to: Edward Laskowski M.D. Department of Sports Medicine Mayo Clinic 200 1st Street SW Rochester, MN 55905 Email: Laskowski.Edward@mayo.edu Disclosures: The authors have nothing to disclose. This study was funded by the Department of Integrative Medicine and Health at Mayo Clinic, Rochester, MN. Acknowledgements: We thank acupuncturists Molly J. Mallory L.Ac. and Sarah E. Bublitz L.Ac. for helping to make this study possible. We thank the Department of Integrative Medicine and Health for their financial and secretarial support, volunteers for assisting with treatment station set-up, and coaching staff for their collaboration and cooperation. We also thank biostatistician Tina Wood-Wentz M.S. for her statistical support and Dr. Kristin L. Garlanger D.O. for contributions from the previous study design. May 9, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Traumatic Dislocation Of The Tibialis Posterior Tendon No abstract available

Hyperbaric oxygen improves functional recovery of the injured spinal cord by inhibiting inflammation and glial scar formation Background Inflammation and glial scar formation determine the recovery process after spinal cord injury (SCI). Hyperbaric oxygen (HBO) is used as a rehabilitation therapy for various clinical diseases, including SCI. However, the relationship between HBO therapy and inflammation or glial scar is not fully understood. Objective The aim of this study was to investigate the therapeutic effect and molecular mechanism of HBO on SCI. Methods A total of 54 developing female Sprague-Dawley (SD) rats were randomly divided into sham group, SCI group and HBO group, with 18 rats in each group. The model of SCI was established using Allen's method. HBO therapy was administered once a day until the rats were sacrificed. Results The results demonstrated inflammation and glial scar formation are involved in secondary SCI. After HBO treatment, there was a notable improvement of the locomotor function in rats. HBO reduced the inflammatory reaction and glial scar formation by inhibiting inflammation-related factors iNOS and COX-2, and glial scar-related components GFAP and NG2. This process may be achieved by inhibiting AKT and NF-kB pathways. Conclusion HBO effectively promotes the recovery of SCI by inhibiting inflammation and glial scar formation. To whom correspondence should be addressed: Dong Liu, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang road, Suzhou (China). Tel. 13451604878. E-Mail: 32982950@qq.com; Yongming Sun, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang road, Suzhou (China). Tel. 13182605276. E-Mail: sun-ym@21cn.com. Yue Zhou and Qirong Dong The authors contributed to this work equally. Author Disclosures: This study was supported by three Planned Science and Technology Project of Suzhou city (SS201611) (SYSD2016066) (2017Q010). The authors declare no conflict of interesting and no competing financial interests. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cognitive characteristics associated with device adoption, skill retention, and early withdrawal from a study of an advanced upper limb prosthesis Objective To examine the role of cognition in device adoption, skill retention, and withdrawal from a study of an advanced upper limb prosthesis (the DEKA Arm). Design T-tests and Wilcoxon rank-sum tests were used to compare test performance among study completers and non-completers. Multivariable regression analyses were used to predict study withdrawal and DEKA Arm skill retention. Results Compared to self-withdrawn participants, those who were withdrawn by study staff performed significantly worse on tests indexing processing speed, set-shifting, and memory encoding. DEKA Arm configuration (transradial, transhumeral, shoulder – based on amputation level), was a stronger predictor of skill retention than neuropsychological test performance. Conclusion Frontally-mediated cognitive skills may influence the successful adoption of the DEKA Arm. DEKA arm configurations at higher amputation levels (e.g., shoulder) appear to be more strongly associated with prosthetic skill retention than users' cognitive status. This may be due to non-cognitive user demands (e.g., device weight) statistically masking the discrete influence of cognitive status on skill retention at higher configuration levels. Neuropsychological assessment warrants consideration as a valuable tool in rehabilitation settings to assist in functional device candidacy evaluations. Corresponding Author: Jacob Lafo, PhD - Providence Veterans Affairs Medical Center, 830 Chalkstone Ave., Providence, RI 02908; Phone: 401-273-7100; Email: jacob_lafo@brown.edu Funding Sources: VA RR&D A9226, VA RR&D A9264A-S, VA RR&D, A9280-N Financial Disclosure Statement: None Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Trunk and Head Control During Walking in Patients with Unilateral Vestibular Hypofunction: Effect of Lower Limb Somatosensory Input Objectives To investigate (1) postural control, especially trunk and head control, in patients with unilateral vestibular hypofunction (UVH) and healthy controls (HCs) during walking on firm and foam surface; (2) the difference between the impact of left and right-side UVH, and correlation between trunk/head control and vestibular function in the patients. Design 13 patients and 13 HCs were recruited. Vestibular function was examined based on the canal paresis value. Participants walked on a treadmill on firm and foam surface. Peak-to-peak trunk (Troll and Tpitch) and head roll and pitch angle (Hroll and Hpitch) were calculated as primary outcome measures. Results In the UVH group but not HCs, Troll was significantly higher on foam than firm surface (p=0.03). Tpitch was significantly higher on foam than firm surface in both groups (p=0.02). Patients had significantly lower Hroll (p=0.03), Hpitch (p=0.02) and lower head-trunk correlation in both medio-lateral (p=0.05) and antero-posterior direction (p=0.03) than those in the HC group. Conclusion Patients with UVH appeared to rely more on lower limb somatosensory input for trunk control especially in the medio-lateral direction compared to HCs. Lower head sway and head-trunk correlation may suggest a more independent and successful head control strategy in patients. The two authors contributed equally to this study, Fang Zhang, Peng Liu All correspondence should be addressed to Dr Zulin Dou and Dr Yiqing Zheng. Corresponding authors: Zulin Dou, Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Yianhe Road, Guangzhou, People's Republic of China, Tel: +8602085252357, E-mail: douzul@163.com; Yiqing Zheng, Department of Otolaryngology-HNS, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, People's Republic of China. Tel: +8602034070287, E-mail: zhengyiq@mail.sysu.edu.cn Disclosure: The author(s) declared no potential conflicts of interest related to this work. Funding: This study was financially supported by Technology Program of Guangdong Province (No.2014A020212097), National Natural Science Foundation of China (No. 81771018), Guangdong Science and Technology Planning Project (Grant Nos. 2014B090901056 and 2015B020214003), Guangzhou Research Collaborative Innovation Projects (Grant No. 201604020108) and National Science & Technology Pillar Program during the 12th Five-year Plan Period of China (No. 2012BAI12B02). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Bilateral Quadriceps Muscle Strength and Pain Correlate with Gait Speed and Gait Endurance Early after Unilateral Total Knee Arthroplasty : A Cross-Sectional Study Objective The objective of this study was to determine the correlations between objective performance-based physical function, self-reported physical function, quality of life, and gait function at 1 month after unilateral total knee arthroplasty (TKA). Design Cross-sectional data from 195 patients who underwent unilateral primary TKA were analyzed. The isometric knee extensor and flexor strength of both knees, gait parameters, 6 minute walk test (6MWT), timed up-and-go (TUG) test, timed stair climbing test (SCT), knee flexion and extension range of motion (ROM) of surgical knee, Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and functional levels, EuroQol five-dimensions (EQ-5D) questionnaire and visual analog scale (VAS) for knee pain were assessed. Results In bivariate analyses, both postoperative gait speed and gait endurance hadsignificant positive correlations with postoperative peak torque (PT) of the extensor and flexor of both knees, cadence, stride length, and significant negative correlation with TUG, SCT-ascent, SCT-descent, VAS, WOMAC pain, stiffness, and function levels.In the linear regression analyses, postoperative PT of the extensors of both knees and VAS for knee pain were factors correlated with postoperative gait speed and gait endurance. Conclusion Quadriceps muscle strength of both knees and knee pain were important factors correlated with gait function early after TKA. Please address all correspondence to: Bo Ryun Kim, MD. Ph. D., Department of Rehabilitation Medicine, Jeju National University School of Medicine, Regional Rheumatoid and Degenerative Arthritis Center, Jeju National University Hospital, Aran 13 gil 15, Jeju 63241, Republic of Korea, Phone: +82-64-717-2711, FAX: +82-64-717-1131, E-mail: brkim08@gmail.com Author disclosures Competing Interests: The aurthors certify that no party having a direct interest in the results of the research supporting this article has or will confer a benefit on them or on any organization with which they are associated Funding or grants or equipment provided for the project from any source: The authors received no funding for this work. Financial benefits to the authors; Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Making patients fit for surgery: introducing a four pillar multimodal prehabilitation program in colorectal cancer Background Considering the relation between preoperative functional capacity and postoperative complications, enhancing a patients functional capacity prior to surgery with a prehabilitation program may facilitate faster recovery and improve quality of life. However, time before surgery is short, mandating a multimodal and high-intensity training approach. This study investigated feasibility and safety of a prehabilitation program for colorectal cancer. Methods Multimodal prehabilitation was offered to patients eligible for participation. They were assigned to an intervention or control group by block randomisation. The prehabilitation program consisted of four interventions: in-hospital high-intensity endurance and strength training, high-protein nutrition, smoking cessation and psychological support. Program attendance, patient satisfaction, adverse events and functional capacity were determined. Results Fifty patients participated in this study (prehabiilitaiton 20, control 30). Program evaluation revealed a high (90%) attendance rate and high level of patient satisfaction. No adverse events occurred. Endurance and/or strength were improved. 86% of patients with prehabilitation recovered to their baseline functional capacity 4 weeks post-operatively, 40% in the control group (p<0.01). Conclusions Multimodal prehabilitation including high-intensity training for colorectal cancer patients is feasible, safe and effective. A randomized controlled trial (NTR5947) was initiated to determine whether prehabilitation may lower morbidity and mortality rates in colorectal surgery. Corresponding author + request for reprints: S.J. van Rooijen MD PhD, Máxima Medical Center, Department of Surgery, P.O. Box 7777, Veldhoven, the Netherlands, stefanvanrooijen@msn.com / prehab.resurge@mmc.nl This pilot was financially supported (MMC2620) by the National Foundation against Cancer (Nationaal Fonds tegen Kanker). FrieslandCampina provided the Refit®TMP 90 Shakes. The funding sources had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Evaluating Physician Knowledge of Commonly Prescribed Inpatient Rehabilitation Unit Discharge Medication's Costs: An Observational Study The objective of this study was to assess physiatrists' knowledge of the cost of medications commonly prescribed at discharge from inpatient rehabilitation units across the spectrum of practice experience from residents to attending physicians. Investigators contacted 92 pharmacies across 4 major regions of the United States (U.S.) and averaged the cash price of each medication. An electronic survey was created highlighting 17 medications in which physicians estimated the cost of a medication per pill and per month for a 30-day supply. Surveys were sent to all ACGME-accredited programs across the U.S.; 43 participants responded to the survey. Most respondents overestimated the cost of the medications chosen for the survey. There was no significant difference between medication cost knowledge and practice experience (p = 0.497) or post-graduate year of training (p = 0.593). This raises awareness that physiatrists may not know the cost of medications they commonly prescribe at discharge, which may have implications on patient medication compliance, quality of care and patient satisfaction. Correspondence: Allison Capizzi, MD, University of Utah, 30 North 1900 East, Salt Lake City, UT, 84132. Office Phone: 801-585-2589. Mobile: 805-403-1763. Fax: 801-587-5757 Author Disclosures: No authors involved in this study have any competing interests, financial benefits, funding, grants or equipment to disclose. This material has not been presented at an AAPM&R Annual Assembly. Funding: No funding was acquired in completion of this project Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Clinical Practice Guidelines for the Rehabilitation of Lower Limb Amputation: An Update from the Department of Veterans Affairs and Department of Defense Between 2015 and 2017, the US Department of Veterans Affairs (VA) and the US Department of Defense (DoD) developed a Clinical Practice Guideline (CPG) for Rehabilitation of Lower Limb Amputation to address key clinical questions. A multidisciplinary workgroup of VA and DoD amputation care subject-matter-experts was formed and an extensive literature search was performed which identified 3,685 citations published from January 2007 through July 2016. Articles were excluded based upon established review criteria resulting in 74 studies being considered as evidence addressing one or more of the identified key issues. The identified literature was evaluated and graded utilizing the National Academies of Science GRADE criteria. Recommendations were formulated following extensive review. Eighteen recommendations were confirmed with four having strong evidence and workgroup confidence in the recommendation. Key recommendations address patient and caregiver education, consideration for the use of rigid and semi-rigid dressings, consideration for the use of microprocessor knees, and managed lifetime care that includes annual transdisciplinary assessments. In conclusion, this CPG utilized the best available evidence from the past 10 years to provide key management recommendations to enhance the quality and consistency of rehabilitation care for persons with lower limb amputation. Corresponding Author: Joseph B. Webster, M.D.; 1201 Broad Rock Boulevard, Richmond, VA 23112, 804-675-7036, joseph.webster@va.gov Disclosure: This work represents the opinions of the authors and not necessarily those of any government agency, academic institution or healthcare agency. This work was fully funded by the Departments of Defense and Veterans Affairs. No funding was received from any commercial entity. Material was presented at the 2018 AAPM&R Annual Assembly on October 26, 2018. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

Organ Transplantation

Caring for the patient with a failing allograft: challenges and opportunities Purpose of review The population of kidney transplant recipients with advanced chronic kidney disease is growing but their outcomes are poor and care is not standardized. There has been wide variety of research in recent years on different aspects of care in failing allografts, and these research findings may help the providers in optimizing care. The purpose of the review is to outline the challenges and opportunities in management of failing allograft, and provide tools for improvement. Recent findings This review summarizes the recent research in field of failing allograft including outcomes, immunosuppression, risk factor management, multidisciplinary CKD care, dialysis initiation, nephrectomy and re-transplantation. Summary Kidney allograft failure is a period of higher risk of mortality compared with other transition periods for patients with ESRD. Risk mitigation is a complex challenge for patients and their care teams. In addition to summarizing the recent literature, we propose a checklist approach to the various issues, medical, surgical, psychological and nutritional as patients approach kidney transplant failure while they consider initiation of dialysis and possible repeat transplantation. Once standard algorithms are instituted, studies can be conducted to identify those high-value interventions that actually reduce morbidity and mortality risk during this transition period. Correspondence to Nikhil Agrawal, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA. Tel: +617 632 9700; e-mail: nagrawa2@bidmc.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A diagnostic 'C' saw: the Ups and downs of C1q testing Purpose of review The present review will focus on recently published data of solid organ allograft recipients reporting that patients with de-novo donor-specific HLA antibodies (DSA) that fix complement in vitro have a significantly higher risk for antibody-mediated rejection (AMR) and/or graft loss compared to patients whose de-novo DSA do not fix complement or patients who present with preexisting complement fixing DSA. Recent findings HLA DSAs that fix complement in vitro appear to be a key indicator for rejection and failure of kidney, heart, and lung allografts from studies performed around the world. The majority of these studies are population based and retrospective in nature. Although these studies seemingly indicate that in-vitro complement activating DSAs represent a higher clinical risk than noncomplement fixing DSAs, the majority have not accounted for false-negative reactions attributable to the so-called prozone/interference phenomenon. In the limited number of published studies addressing that concern, high mean fluorescence intensity (MFI) value noncomplement fixing DSAs correlate as well as complement fixing DSAs with AMR and graft loss. Combined with the cost of additional testing, these observations bring into question whether there is sufficient clinical applicability to warrant routine testing for complement fixing antibodies. Summary Complement fixing DSAs are clearly associated with AMR and/or loss of transplanted allografts. However, under appropriate testing conditions, complement fixing capability typically correlates with MFI values of the DSAs. As such, the routine implementation of in-vitro assays to determine whether DSAs fix complement is of questionable value especially when considering additional issues such as cost of testing, logistics, and whether the test results factor into individualized patient care. Correspondence to Howard M. Gebel, PhD, Department of Pathology, Room HB53, 1364 Clifton Road NE, Atlanta, GA 30322, USA. Tel: +404 712 8199; fax: +404 712 4717; e-mail: hgebel@emory.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Epitope matching in kidney transplantation: recent advances and current limitations Purpose of review Evolution of human leukocyte antigen (HLA) molecular typing techniques has progressively enabled more accurate determination of the three-dimensional building blocks that form the antibody accessibility and binding sites of each HLA allele. These immunogenic HLA regions known as epitopes are composed of polymorphic sequences of amino acid residues termed eplets. This review provides a critical appraisal of the current understanding of epitope compatibility in kidney transplantation. Recent findings There is a tendency to suggest that epitope matching is likely to be superior to broad antigen HLA matching such that the allocation of donor kidneys to patients with a more favorable epitope compatibility profile may lead to better allograft outcomes. A growing body of work has highlighted the association between a greater number of eplet mismatches and adverse allograft outcomes, and approaches using eplet matching have been successfully implemented in organ allocation programs. However, our understanding of epitope compatibility remains in its infancy, requiring further and more in-depth evaluation. Critically, it remains unclear how best to translate findings derived at the population level to the care of individual patients. Questions that need to be answered include a lack of consensus in the definition and interpretation of epitope compatibility, are class I and II compatibility of similar clinical importance, how best to define predetermined mismatch thresholds for utilization in organ allocation, and whether other properties such as differences in electrostatic potential between donor and recipient HLA alleles are also important in determining immunological compatibility. Summary Epitope matching likely represents a valid progression in understanding donor–recipient HLA compatibility. However, more clinical data and a better understanding about differences in methods to determine epitope compatibility are required before the approach can be widely applied in clinical practice. Corresponding to Nicholas G. Larkins, MBBS (Hons), FRACP MMed (Clin Epi), PhD, Department of Nephrology, Perth Children's Hospital, 15 Hospital Ave., Nedlands, Perth, Western Australia 6009, Australia. Tel: +61 08 6456 0216; e-mail: nicholas.larkins@health.wa.gov.au Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-transplantation.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

ALEXANDROS SFAKIANAKIS ANAPAFSEOS 5 AGIOS NIKOLAOS CRETE 72100 GREECE +306932607174 +302841026182

Cancer Immunology, Immunotherapy

Correction to: Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial In the original publication of the article the following abstract and keywords were inadvertently omitted.

Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients Abstract Bevacizumab (Bv) remains frequently prescribed in glioblastoma (GBM) patients, especially at recurrence. We conducted a prospective clinical trial with 29 recurrent GBM patients treated with Bv alone with a longitudinal follow-up of different circulating immune cells [complete blood count, myeloid-derived suppressor cells (MDSCs), classical, intermediate, non-classical and Tie2 monocytes, VEGFR1+ and regulatory T cells (Treg)]. We observed a significant increase for leucocytes, neutrophils, eosinophils and classical monocytes and a decrease for the fraction of Treg during the treatment. The best prognostic values for survival under Bv were obtained for basal neutrophils and Treg. Counts below 3.9 G/L for neutrophils and above 0.011 G/L for Treg were associated with an overall survival of 17.5 and 19.9 months, respectively, as compared with 5.4 and 5.6 months, respectively, for counts above and below these cutoffs (p = 0.004 and p < 0.001). No prognostic impact was observed for neutrophils in a retrospective cohort of 26 patients treated with nitrosoureas alone. In another retrospective validation cohort of 61 GBM patients treated at recurrence with a Bv-containing regimen, an interaction was observed between neutrophils and corticosteroid intake. The predictive value of neutrophils on survival under Bv was lost in patients treated with corticosteroids, when steroid-free patients with a low neutrophil count had a particularly long median survival of 3.4 years. These two simply accessible criteria (basal neutrophils and steroid intake) could be used to reserve this relatively costly treatment for patients likely to be the most responsive to Bv and prevent unnecessary side effects in others.

Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile Abstract Objective As the development and progression of colorectal cancer (CRC) are known to be affected by the immune system, cell subsets such as T cells, natural killer (NK) cells, and natural killer T (NKT) cells are considered interesting targets for immunotherapy and clinical biomarker research. Until now, the role of systemic immune profiles in tumor progression remains unclear. In this study, we aimed to characterize the immunophenotype of circulating T cells, NK cells, and NKT-like cells in patients with CRC, and to subsequently correlate these immunophenotypes to clinical follow-up data. Methods Using multiparameter flow cytometry, the subset distribution and immunophenotype of T cells (CD3+CD56−), CD56dim NK cells (CD3−CD56dim), CD56bright NK cells (CD3−CD56bright), and NKT-like (CD3+CD56+) cells were investigated in peripheral blood mononuclear cell (PBMC) samples from 71 CRC patients and 19 healthy donors. Results CRC patients showed profound differences in immune cell subset distribution and their immunophenotype compared to healthy donors, as characterized by increased percentage of regulatory T cells, and reduced expression level of the natural cytotoxicity receptors NKp44 and NKp46 on both CD56dim NK cells and NKT-like cells. Finally, we showed in a multivariate analysis that above-median percentage of CD16+ NKT-like cells was independently associated with shorter disease-free survival in CRC patients. Conclusion The altered phenotype of circulating immune cell subsets in CRC and its association with clinical outcome highlight the potential use of PBMC subsets as prognostic biomarkers in CRC, thereby contributing to better insight into the role of systemic immune profiles in tumor progression.

Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy Abstract Background Pleomorphic dermal sarcomas (PDS) are sarcomas of the skin with local recurrences in up to 28% of cases, and distant metastases in up to 20%. Although recent evidence provides a strong rational to explore immunotherapeutics in solid tumors, nothing is known about the immune environment of PDS. Methods In the current study, a comprehensive immune-phenotyping of 14 PDS using RNA and protein expression analyses, as well as quantitative assessment of immune cells using an image-analysis tool was performed. Results Three out of 14 PDS revealed high levels of CD8-positive tumor-infiltrating T-lymphocytes (TILs), also showing elevated levels of immune-related cytokines such as IL1A, IL2, as well as markers that were very recently linked to enhanced response of immunotherapy in malignant melanoma, including CD27, and CD40L. Using a multivariate analysis, we found a number of differentially expressed genes in the CD8-high group including: CD74, LYZ and HLA-B, while the remaining cases revealed enhanced levels of immune-suppressive cytokines including CXCL14. The "CD8-high" PDS showed strong MHC-I expression and revealed infiltration by PD-L1-, PD-1- and LAG-3-expressing immune cells. Tumor-associated macrophages (TAMs) predominantly consisted of CD68 + , CD163 + , and CD204 + M2 macrophages showing an accentuation at the tumor invasion front. Conclusions Together, we provide first explorative evidence about the immune-environment of PDS tumors that may guide future decisions whether individuals presenting with advanced PDS could qualify for immunotherapeutic options.

An immunosuppressive macrophage profile attenuates the prognostic impact of CD20-positive B cells in human soft tissue sarcoma Abstract Background Immune cells can regulate disease progression and response to treatment in multiple tumor types, but their activities in human soft tissue sarcoma are poorly characterized. Methods Marker-defined immune cell subsets were characterized from a tumor microenvironmental perspective in two independent cohorts of human soft tissue sarcoma by multiplex IHC, quantitative PCR and/or bioinformatics. Results B cell profiling revealed a prognostic role for CD20 protein (cohort 1, 33 patients) and MS4A1 gene expression (cohort 2, 265 patients). Multiplex IHC and gene correlation analysis supported a role in antigen presentation, immune cell differentiation and T cell activation. The prognostic role of MS4A1 expressing B cells was only observed in an IL10low, PTGS2low or CD163low tumor microenvironment according to the transcriptomic data. IL10 levels consistently correlated with the M2-like macrophage marker CD163, which also defined the majority of macrophages. A polarization of these cells toward a pro-tumoral phenotype was further supported by lack of correlation between CD163 and M1 markers like NOS2, as well as by low abundance of CD80 positive cells in tissue. Conclusions Analysis of CD20/MS4A1 expression in soft tissue sarcoma merits further attention as a promising candidate prognostic tool for survival, but not in patients with a pronounced immunosuppressive tumor microenvironment. Macrophages are ubiquitous and polarized toward a protumoral phenotype. This provides a rationale for further studies on B cell function and immunotherapy targeting M2-polarized macrophages.

Autologous tumor cell vaccination combined with systemic CpG-B and IFN-α promotes immune activation and induces clinical responses in patients with metastatic renal cell carcinoma: a phase II trial

Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas Abstract Background Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors. Aim of the study To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution. Materials and methods Eighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were analyzed semi-quantitatively. Results Among the 60 sweat gland, 18 sebaceous and 5 trichoblastic carcinomas, 11% expressed PD-L1 in ≥ 1% tumor cells, more frequently sweat gland carcinomas (13%, 8/60) including apocrine carcinoma (40%, 2/5) and invasive extramammary Paget disease (57%, 4/7). Immune cells expressed significantly more PD-L1 than tumor cells (p < 0.01). Dense CD8+ TILs were present in 60% trichoblastic, 43% sweat gland, and 39% sebaceous carcinomas. CD8+ TILs were associated with PD-L1 expression by tumor cells (p < 0.01). Thirteen patients out of 47 developed metastases (27%) with a median follow-up of 30.5 months (range 7–36). Expression of PD-L1 by tumor cells was associated with the development of metastasis in univariate analysis (HR 4.0, 95% CI 1.1–15, p = 0.0377) but not in multivariate analysis (HR 4.1, 95% CI 0.6–29, p = 0.15). Conclusion PD-L1 expression is highly heterogeneous among adnexal carcinoma subtypes, higher in apocrine carcinoma and invasive extramammary Paget disease, and associated with CD8+ TILs. Our data suggest the interest of evaluating anti-PD1 immunotherapy in advanced or metastatic cutaneous adnexal carcinoma.

MHC class-I downregulation in PD-1/PD-L1 inhibitor refractory Merkel cell carcinoma and its potential reversal by histone deacetylase inhibition: a case series Abstract Background Merkel cell carcinoma (MCC) is an aggressive skin cancer in which PD-1/PD-L1 blockade has shown remarkable response rates. However, a significant proportion of patients shows primary or secondary resistance against PD-1/PD-L1 inhibition, with HLA class-I downregulation and insufficient influx of CD8+ T cells into the tumor as possible immune escape mechanisms. Histone deacetylase inhibitors (HDACi) have been demonstrated to reverse low HLA class-I expression caused by epigenetic downregulation of the antigen machinery (APM) in vitro and in pre-clinical models in vivo. Case presentations We report four cases of patients with metastatic MCC who did not respond to immunotherapy by PD-1/PD-L1 blockade. Two of the patients received, subsequently, the HDACi panobinostat in combination with PD-1/PD-L1 blockade. Tumor biopsies of the patients were analyzed for cellular and molecular markers of antigen processing and presentation as well as the degree of T-cell infiltration. Results and conclusion Low expression of APM-related genes associated with low HLA class-I surface expression was observed in all MCC patients, progressing on PD-1/PD-L1 blockade. In one evaluable patient, of the two treated with the combination therapy of the HDACi, panobinostat and PD-1/PD-L1 blockade, reintroduction of HLA class-I-related genes, enhanced HLA class-I surface expression, and elevated CD8+ T-cell infiltration into the MCC tumor tissue were observed; however, these changes did not translate into a clinical benefit. Our findings suggest that HDACi may be useful to overcome HLA class-I downregulation as a resistance mechanism against anti-PD-1/PD-L1 antibodies in MCC patients. Prospective clinical trials are needed to evaluate this notion.

Expression profiling of immune inhibitory Siglecs and their ligands in patients with glioma Abstract Gliomas appear to be highly immunosuppressive tumors, with a strong myeloid component. This includes MDSCs, which are a heterogeneous, immature myeloid cell population expressing myeloid markers Siglec-3 (CD33) and CD11b and lacking markers of mature myeloid cells including MHC II. Siglec-3 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family and has been suggested to promote MDSC expansion and suppression. Siglecs form a recently defined family of receptors with potential immunoregulatory functions but only limited insight in their expression on immune regulatory cell subsets, prompting us to investigate Siglec expression on MDSCs. We determined the expression of different Siglec family members on monocytic-MDSCs (M-MDSCs) and polymorphnuclear-MDSCs (PMN-MDSCs) from blood of glioma patients and healthy donors, as well as from patient-derived tumor material. Furthermore, we investigated the presence of sialic acid ligands for these Siglecs on MDSCs and in the glioma tumor microenvironment. Both MDSC subsets express Siglec-3, -5, -7 and -9, with higher levels of Siglec-3, -7 and -9 on M-MDSCs and higher Siglec-5 levels on PMN-MDSCs. Similar Siglec expression profiles were found on MDSCs from healthy donors. Furthermore, the presence of Siglec-5 and -9 was also confirmed on PMN-MDSCs from glioma tissue. Interestingly, freshly isolated glioma cells predominantly expressed sialic acid ligands for Siglec-7 and -9, which was confirmed in situ. In conclusion, our data show a distinct Siglec expression profile for M- and PMN-MDSCs and propose possible sialic acid–Siglec interactions between glioma cells and MDSCs in the tumor microenvironment.

Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition Abstract Immune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, > 60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line ICI or combination treatment, we tested 25 SNPs, associated with > 2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568—a risk variant for allergy, colitis and type 1 diabetes—was associated with increased anti-PD-1 response, with significance surpassing multiple testing adjustments (OR 0.26; 95% CI 0.12–0.53; p = 0.0002). This variant maps to a locus of established immune-related genes: IL2 and IL21. Our study provides first evidence that autoimmune genetic susceptibility may modulate ICI efficacy, suggesting that systematic testing of autoimmune risk loci could reveal personalized biomarkers of ICI response.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

OtoRhinoLaryngology

RETRACTED ARTICLE: Commentary on safety of outpatient admission and comparison of different surgical techniques in adult tonsillectomy

Response to "Drop attacks, hydrops severity and disease duration in hydropic ear disease (Menière's)"

Whose nose does not know? Demographical characterization of people unaware of anosmia Abstract Purpose For functionally anosmic subjects, the sense of smell is basically useless in daily activities—they are unlikely to detect the threatening smell of rotten food, gas or smoke, or to enjoy the flavor of food or the smell of perfumes. Although this appears very distressing, functionally anosmic subjects in our sample seemed not to be aware or bothered with impaired olfaction and enrolled for the study targeted to people with a normal sense of smell. Methods In the large sample of 9139 subjects who declared themselves to have a normal sense of smell, we have retrospectively found a notable proportion of scores indicating functional anosmia. Results When we look at the overall Sniffin' Sticks score, 0.45% of the sample was functionally anosmic and this fraction increased to 3.4% when the identification score of 8 points and below was used. We present demographical information of those subjects, who despite their inability to use smell in daily life, consider themselves healthy. Conclusions Data offer a new perspective on the importance of olfaction in daily life and supports the notion about the importance of using screening tools in clinical practice.

Response to the Letter to the Editor: "Pediatric otogenic lateral sinus thrombosis: focus on the prognostic role of contralateral venous drainage"

Bilateral nasal septal chemical cautery: a safe and effective outpatient procedure for control of recurrent epistaxis, our experience in 134 patients Abstract Purpose To assess the effectiveness and complications of bilateral nasal septal cautery using silver nitrate in anterior nasal epistaxis. Methods This prospective study was carried out on 180 consecutive patients presenting with epistaxis to a general ENT clinic. Local anaesthetic cautery was performed using 5% lidocaine hydrochloride and 0.5% phenylephrine hydrochloride spray in all the patients except eight children that were 4 years or younger that were done under general anaesthetic. Visible vessels in Little's areas were cauterised using two silver nitrate sticks each side. Patients were prescribed naseptin cream and followed-up. We classified re-bleeds as follow: 0–1 episodes: significant improvement, 2–3 episodes: moderate improvement, 4 + episodes: no improvement. Results We analysed 134 (74%) patients who were seen at follow-up. Age range was 5–88 years (mean 25, median 15), there were 89 (67%) males. Children made up 60% (81) of the study population (aged 16 years and under), of these 56 (69%) were male. Significant improvement was seen in 93% (124) of the study population, but there were relapses in two children (1.5%) and only moderate improvement in eight patients (6%). There was no significant complication in the study population, but 11 patients had crusting at the sites of cautery at follow-up. Conclusions Bilateral silver nitrate cauterisation is an effective method of treating recurrent epistaxis with low risk of complications.

Impact of bilateral nasal polyposis on the interoptic and interzygomatic distance Abstract Purpose To identify and determine variations on eye distance in patients with bilateral nasal polyposis (BNP) compared to a healthy control group. Methods This is a case–control study that included 20 BNP patients and 40 healthy controls. We included all patients with BNP confirmed by pathology and a computed tomography scan. A healthy control group was admitted, filtered by the exclusion criteria of nasal polyposis, craniofacial malformations, and encephalocele. Paranasal sinus CT scans were performed in all participants, and two measures were evaluated, the interoptic (soft tissue) and the interzygomatic (bone structure) distances. Results A total of 20 BNP subjects, 13 (65%) male and 7 (35%) female, with a mean age of 38.8 years, and 40 healthy controls, 16 (40%) male and 24 (60%) female with a mean age of 43.2 years, were included. The mean interoptic distance was 69.7 mm (71.9 mm men, 66.4 mm women) and interzygomatic distance was 103.1 mm (104.5 mm men, 100.6 mm women). A significant increase of the interoptic (p < 0.001) and interzygomatic (p < 0.002) measurements was found in patients with polyposis compared to the controls. In the receptor operative curve analysis, the interoptic distance had an area under a curve of 96% and the threshold that maximizes the sensitivity and specificity was 59.85 mm (sensitivity 90%, specificity 95%, PPV 90%, NPV 95%). Conclusions An increase in ocular and orbital distances was identified in patients with BNP. Polyposis may be identified by measuring eye separation. The established cut point distance identifies patients that may benefit from follow-up. Further research in this study line is suggested.

Endoscopic versus conventional septoplasty: objective/subjective data on 276 patients Abstract Purpose Endoscopic approach represents a valid alternative to conventional septoplasty. The aim of this study is to analyze the objective and subjective data on 276 patients, who underwent traditional (147) or endoscopic (129) septoplasty. Methods This is a prospective observational study on 276 consecutive patients affected by deviated nasal septum (DNS), who underwent isolated septoplasty between 2011 and 2018. 147 of them were treated using an "open" approach, while 129 were treated with an endoscopic approach. The two groups were compared 3 months after surgery: the objective results (complications such as bleeding, hematoma, pain, synechiae, septal tears and incomplete correction), objective (rhinomanometric data) and subjective measurements (NOSE questionnaires). Results Both techniques are effective in decreasing nasal obstruction and discharge. Complications such as pain, synechiae, early postoperative bleeding, septal tears and incomplete correction are less frequent in the endoscopic group (p < 0.05). The rhinomanometric analysis reveal improvement in both groups without statistical differences. Subjective questionnaires show a good symptoms relief with an improved quality of life in all 276 patients without statistical difference between the two gropus. Conclusions Both techniques are effective in reducing nasal obstruction and related symptoms with fewer overall complications in the endoscopic approach. The endoscope provides improved field of view, less mucosal damages and a more anatomic dissection. Finally, such approach can be a valuable teaching tool for assistants, residents and students.

Increased TSLP, IL-33, IL-25, IL-19, IL 21 and amphiregulin (AREG) levels in chronic rhinosinusitis with nasal polyp Abstract Objective Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease. The surrogate indicating biomarkers in patients with CRSwNP need further evaluation. The aim of this study was to investigate the association of thymic stromal lymphopoietin (TSLP) and amphiregulin (AREG) cytokines in patients with CRSwNP. Methods Sinonasal tissue samples were collected from 33 patients with CRSwNP and 29 controls. Levels of AREG, IL-19, IL-21, IL-25, IL-33 and TSLP in nasal polyp and control sinonasal tissues were determined following the enzyme-linked immunosorbent assay method. Results We found that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP levels were significantly higher in the CRSwNP group compared to the control group (p < 0.000; p < 0.000; p < 0.000; p < 0.000; p < 0.003; p < 0.021, respectively). Conclusions Our findings indicated that AREG, IL-19, IL-21, IL-25, IL-33 and TSLP were significantly increased in tissue samples of CRSwNP patients and may be considered as molecular indicators and targets for therapeutic developments for patients with CRSwNP.

Vestibular function in panic disorder patients: a vestibular-evoked myogenic potentials and video head impulse test study Abstract Purpose To evaluate the function of the utriculus and sacculus and their central connections by ocular and cervical vestibular-evoked myogenic potentials (oVEMPs and cVEMPs), and the function of high-frequency VOR of the semicircular canals by video head impulse test (vHIT) in patients with panic disorder (PD). Methods Forty-eight patients with PD (21 with agoraphobia) and 20 sex- and age-matched healthy controls took part in the investigation. The vestibulo-ocular reflex (VOR) gains and latencies and peak-to-peak amplitudes of sound-induced VEMPs were measured and compared with those of healthy controls. Results Any statistical differences in the parameters of cVEMP and oVEMP responses between both PD patients groups and between patients and healthy controls were not observed. Also, significant differences between VOR in patients and healthy controls were not found. The VOR gain, bilaterally in the three semicircular canals was within normal limits (0.8–1.2) for 67%, and higher for 33% of the patients with PD. Overt and covert saccades were not observed. The relationship between higher VOR gains and the increase of postural instability when a sensory conflict exists (standing on foam pad with eyes closed) for patients with PD was established. Conclusion The VEMPs and vHIT tests demonstrated that there is no evidence of hypofunction of the semicircular canals in the high-frequency spectrum of VOR functioning. Nor are there any indications of impairment of the otolith system in patients with PD, regardless of their subjective vestibular sensations. The findings of the current study confirm the proposed link between anxiety, panic symptoms and postural instability in PD patients.

Exploring the feasibility of the combination of acoustic voice quality index and glottal function index for voice pathology screening Abstract Purpose The aim of this study was to explore the diagnostic value of the combination of Acoustic Voice Quality Index (AVQI) and Glottal Function Index (GFI) as a screening tool for voice disorders, and to compare the AVQI measurements obtained using oral and smartphone (SP) microphones. Methods A study group consisted of 183 adult individuals including 86 subjects with normal voice and 97 patients with pathological voice. Voice recordings were performed simultaneously with an oral AKG Perception 220 and SP iPhone 6s microphones. To evaluate the diagnostic accuracy differentiating normal and pathological voice, the receiver-operating characteristic statistics [area under curve (AUC), positive and negative likelihood ratios (LR+ and LR−)], and correct classification rate (CCR) were used. Results The AVQI cut-off scores of 3.31 for oral and 3.32 for SP microphones were associated with very good test accuracy (AUC = 0.857 and AUC = 0.818), resulting in balance between sensitivity and specificity (70.0% vs 86.0% and 70% vs 87.0%). The CCR reached 78%. The combined AVQI and GFI cut-off scores of 6.65 for oral and 7.1 for SP microphones corresponded with excellent test accuracy (AUC = 0.976 and AUC = 0.965) and sensitivity and specificity (93.0% vs 93.0% and 91.0% vs 94%). Very respectable levels of LR+ and LR− both for oral microphone (13.3 and 0.08) and for SP microphone (15.6 and 0.10) voice recordings were achieved. CCRs of 93% and 92% confirmed the results of ROC statistics. Conclusions Combination of AVQI and GFI measurements significantly improved diagnostic accuracy in differentiating normal vs pathological voice.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Craniofacial Surgery

Adding Depth to Cephalometric Analysis: Comparing Two- and Three-Dimensional Angular Cephalometric Measurements Introduction: Lateral cephalometric radiographs (LCR) have been the standard tool used for cephalometric analysis in craniofacial surgery. Over the past decade, a three-dimensional (3D) revolution in cephalometric analysis and surgical planning has been underway. To date, research has not validated whether cephalometric measurements taken from two-dimensional (2D) and 3D data sources are equivalent and interchangeable. The authors sought to compare angular cephalometric measurements taken with 2D and 3D modalities. Methods: Sixty-two head CT scans (36 females, 26 males) with an average age of 63 ± 20 years were studied. Twelve cephalometric angular measurements were taken from 3D reconstructed skulls using the software package Mimics 19.0 (Materialize; Leuven, Belgium). These same facial angles were measured from 2D lateral cephalograms reconstructed from the original CT scans using Dolphin 11.9. Measurements taken with both techniques were compared for agreement using a paired t test. Intra-class correlation coefficient assessment was used to determine inter-rater reliability. Statistical significance was set at P < 0.05. Results: Five of the 12 angular measurements (SNA, SNB, MP-FH, U1-SN, and U1-L1) demonstrated statistically significant differences (P < 0.05) between the 2D and 3D analyses. All of these differences were less than the standard deviations for the respective measure. Conclusion: The differences between angular cephalometric values obtained from 2D LCRs and 3D CT reconstructions are small. This supports the practices of using 2D and 3D cephalometric data interchangeably in most applications. Clinicians must be selective in which measures they employ to maximize accuracy and care must be taken when measuring dental inclination with lateral cephalograms. Address correspondence and reprint requests to S. Alex Rottgers, MD, Assistant Professor of Plastic Reconstructive Surgery, Johns Hopkins All Children's Hospital, Division of Plastic and Reconstructive Surgery, 601 Fifth Street South, Suite 306, St. Petersburg, FL 33701; E-mail: srottge1@jhmi.edu Received 28 November, 2018 Accepted 12 March, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Risk Factors for Adult Postintubation Tracheal Stenosis Background: To identify risk factors for developing adult postintubation tracheal stenosis (TS) and determine if there were patient characteristics that could serve as prognostic indicators of clinical outcomes in this patient population. Methods: A total of 55 patients with postintubation TS admitted to our institution between February 2009 and March 2017 (TS group) and randomly selected 86 patients admitted to the intensive care unit and intubated over the same period in whom TS was ruled out (control group) were compared. Causal factors of intubation were noted. Patient-, treatment-, and procedure/cuff site-related risk factors of TS were compared. Results: Both groups did not differ from each other by means of age and gender (P = 0.640, and P = 0.724, respectively). Compared to controls, patients with TS had a significantly higher BMI (32.8 ± 7.64 kg/m2 versus 25.9 ± 6.68 kg/m2; p = 0.002) and were more likely to have diabetes (28.4% vs 9.82%; p = 0.0011). Patients who were previously intubated for more than 48 hours (P = 0.016) and patients treated with irradiation (P = 0.028) were significantly more likely to develop TS than control patients. Conclusion: Patients with TS had a significantly higher BMI, and were more likely to have diabetes compared to controls. Patients who were previously intubated for more than 48 hours and patients treated with irradiation were more likely to develop TS than control patients. Address correspondence and reprint requests to Murat Songu, MD, Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey; E-mail: songumurat@yahoo.com Received 16 January, 2019 Accepted 27 February, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Transnasal Endoscopic Retrieval of a Metallic Intraorbital Intraconal Foreign Body Facilitated by an Intraoperative Magnetic Stick Here, we report the case of an intraorbital intraconal foreign body that was successfully retrieved by a transnasal endoscopic approach facilitated intraoperatively by a magnetic stick. A 36-year-old man was admitted to our unit with a left-sided intraorbital intraconal metallic foreign body. Following 2 failed attempts via a transconjunctiva approach, we finally recovered the foreign body using transnasal endoscopic surgery. During this procedure, a magnetic stick was used to help us locate and successfully remove the foreign body, grapeshot measuring approximately 0.5 cm in diameter. Visual acuity in the injured eye increased from 0.01 preoperatively to 0.04 6 days after surgical intervention. There were no complications. We therefore propose that in selected patients, the endoscopic transnasal approach is an effective, safe and minimally invasive approach for the removal of intraorbital intraconal foreign bodies. The intraoperative use of a magnet can facilitate the successful location and removal of magnetic metallic foreign bodies. Address correspondence and reprint requests to Jianfeng Liu, MD, Department of Otolaryngology, China-Japan Friendship Hospital, Yinghuadong Street, Chaoyang District, Beijing, China 100029; e-mail: mmconfucius@163.com Received 19 February, 2019 Accepted 31 March, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Unusual Cause of Facial Asymmetry: Sturge-Weber Syndrome Sturge-Weber syndrome is a rare neurocutaneous disease, also called encephalotrigeminal angiomatosis. In this study, we aimed to present a patient with Sturge-Weber syndrome who had atypical radiological findings and with dural arteriovenous fistula. The patient presented with hemifacial asymmetry. Sturge-Weber syndrome may present with atypical radiological findings and additional pathologies. Address correspondence and reprint requests to Hayri Ogul, MD, Department of Radiology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey; E-mail: drhogul@gmail.com Received 21 February, 2019 Accepted 20 March, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Removal of Foreign Bodies in Orbit-Zygomatic-Maxillary Complex Trauma is one of the leading causes of death worldwide. Due to its anatomy and position in the facial skeleton, the orbit becomes a region susceptible to trauma which may also involve the penetration of foreign bodies (FBs). These events can have serious repercussions depending on their extent due to the proximity of the orbit with other noble structures of the face and skull. Because of this, a system of prehospital management of traumas must be established, in order to promote a better prognosis for patients. The present study aims to report the case of a patient suffering from a motorcycle accident with multiple fragments of FBs in the region of orbit-zygomatic-maxillary complex. The emergency surgical removal of the fragments was performed by a multidisciplinary team, involving Ophthalmology and Oral and Maxillofacial Surgery and Traumatology (OMST). Wound cleansing and debridement were performed with subsequent removal of the foreign bodies by the OMST team, in addition to the reduction and fixation of related fractures. As for Ophthalmology, the evisceration of the affected eye was performed due to its anatomical and functional impairment. The patient is 12 months postoperatively, with no aesthetic or functional complaints regarding OMST. The anatomical knowledge of the traumatized region, besides the establishment of the conduct regarding the removal of possible associated foreign bodies are required so that the success of the treatment can be obtained, aiming to minimize the damages to the patient. Address correspondence and reprint requests to Edson Luiz Cetira Filho, DDS, MSc, Rua Monsenhor Furtado, 1273, Rodolfo Teófilo, Fortaleza, CE 60430-355, Brazil; E-mail: edson.cetira@hotmail.com Received 3 March, 2019 Accepted 28 March, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Head Shape Retention Following Helmet Therapy for Deformational Plagiocephaly Background: The aim of the present study was to evaluate whether any change can be expected in the 6-month period after completing treatment with a molding helmet for deformational plagiocephaly. A retrospective review of helmeted patients from a deformational plagiocephaly clinic from May 2010 to June 2011. Methods: A total of 71 individuals with 6-month follow-up after completion of molding helmet treatment were identified. About 51 males and 20 females ranged in age from 2 to 10 months at initial treatment. The main outcome measure was the amount of change in head shape in the 6-month period following molding helmet therapy. Results: During the course of helmet treatment cephalic index and cranial vault asymmetry both decreased significantly (P < 0.001). Posthelmet follow-ups revealed a further decrease in cephalic index (P < 0.001). Although the cranial vault asymmetry decreased slightly between the final helmeting visit and the follow-up visit, this change was not statistically significant (P = 0.292). Controlling for other factors, continued normalization was not significantly related to helmeting duration. Conclusion: Findings revealed both cephalic index and cranial vault asymmetry improved while in the helmet. During the 6 months following helmet treatment, cephalic index continued to improve; cranial vault asymmetry changed only insignificantly in this same period. Address correspondence and reprint requests to Sybill D. Naidoo, PhD, CPNP, 660 S Euclid, Campus Box 8238, St Louis, MO 63110; E-mail: naidoos@wustl.edu Received 4 March, 2019 Accepted 24 March, 2019 Dr Naidoo is a speaker for Hanger Clinic and Orthomerica. Dr Patel is a speaker for Hanger Clinic and a consultant for Stryker. The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Coexistence of Antrochoanal Polyp and Fibrous Dysplasia in the Maxilla The authors report an unusual case of coexistence of antrochoanal polyp (ACP) and fibrous dysplasia (FD) in the maxilla. To the best of our knowledge, this condition has never been reported in the literature. The complete removal of the ACP through endoscopic sinus surgery was attained and FD was ultimately diagnosed by histopathological examination. It is hypothesized that chronic inflammation or irritation due to FD has an effect on the occurrence of ACP. Address correspondence and reprint requests to Sang Chul Lim, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 322, Seoyang-ro, Hwasun, Jeonnam, South Korea 58128; E-mail: limsc@jnu.ac.kr Received 14 March, 2019 Accepted 10 April, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Controversy on the Age of Hypertelorism Correction Introduction: Orbital hypertelorism (HTO) is a challenging craniofacial problem seen in association with some congenital deformities. The age of HTO correction is a matter of debate. The Aim of the work: to evaluate the outcome of HTO correction and determine the optimal timing for intervention, striving for the earliest possible intervention with the lowest relapse. Patients and methods: A standard craniofacial approach with medial bone resection, 4 walls orbital box osteotomy and orbital medialization were done for all patients. Skeletal and soft tissue procedures were done as indicated. Results: there were 10 patients aging 6 to 19 years. Seven were associated with craniofacial clefts, and 3 with craniosynostosis syndromes. HTO was severe in 8 cases and moderate in 2 cases. It was asymmetric in 2 cases. Frontoorbital remodeling was done in 3 cases with craniosynostosis. Failed surgery was reported in 2 cases. A redo surgery was done for one of them with an excellent outcome, while refused by the other. Nine patients had an excellent outcome. The mean level of satisfaction was 93.37%. Three patients had ugly facial scars. No major complications were recorded. Conclusion: The time for surgical treatment of HTO is determined by the severity of the associated deformity. If there is an urgent factor indicating intervention, early correction can be performed exceptionally; otherwise, HTO correction should be performed after the age of 6 years. Address correspondence and reprint requests to Ahmed Gaber Hassanein, MD, Address: Maxillofacial Surgery Unit, General Surgery Department, Sohag Faculty of Medicine, Sohag, Egypt; E-mail: ahmedgaber_74@yahoo.com Received 2 August, 2018 Accepted 10 April, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Applications of Bone Morphogenetic Protein-2: Alternative Therapies in Craniofacial Reconstruction Large defects of the craniofacial skeleton can be exceedingly difficult to reconstruct since autologous bone grafts are limited by donor site morbidity and alloplastic implants have low biocompatibility. Bone morphogenetic proteins (BMPs) in craniofacial reconstruction have been used with mixed outcomes and complication concerns; however, results for specific indications have been promising. In alveolar clefts, cranial vault defects, mandibular defects, and rare Tessier craniofacial clefts, BMP-2 impregnated in collagen matrix was looked at as an alternative therapy for challenging cases. In cases where structural support was required, BMP-2 was used as part of a construct with bio-resorbable plates. Demineralized bone was added in certain cases. The authors described specific indications, detailed surgical techniques, and a review of the current literature regarding the use of BMP-2 in craniofacial reconstruction. BMP-2 is a viable option for craniofacial reconstruction to decrease donor-site morbidity or when alternatives are contraindicated. It is not recommended for routine use or in the oncologic setting but should currently be reserved as an alternative therapy for complex cases with limited options. Bone morphogenetic proteins are a promising, emerging option for complex craniofacial reconstruction. Future directions of BMP-2 therapies will become apparent as data from prospective randomized trials emerges. Address correspondence and reprint requests to James P. Bradley, MD, 1991 Marcus Avenue, #102, Lake Success, NY, 11042; E-mail: JPBradley4@mac.com Received 9 October, 2018 Accepted 20 March, 2019 The authors report no conflicts of interest. © 2019 by Mutaz B. Habal, MD.

Correlation Between Speech Outcomes and the Amount of Maxillary Advancement After Orthognathic Surgery (Le Fort I Conventional Osteotomy and Distraction Osteogenesis) in Patients With Cleft Lip and Palate Background: The purpose of this study is to evaluate the factors affecting the speech outcome following Le fort I conventional osteotomy(CO) or Le Fort I distraction osteogenesis(DO) in patients with cleft lip and palate at a single institution. Method: Records of cleft lip and palate patients who underwent orthognathic surgery between 2010 and 2015 were reviewed. Data included age at orthognathic surgery, sex, cleft lip and palate type, type of orthognathic surgery, the amount of maxillary advancement, and speech assessment. Speech outcomes were classified into 2 categories. Compared with the pre and post-operative Pittsburgh Weighted speech scale scores, in case that the post-operative total score is increased the authors define it as "Speech deterioration" and if not, the authors define it as "Speech preservation." Result: The 44 patients were identified, 33 patients underwent CO and 11 patients underwent DO. The mean age was 19.4 ± 1.4. The mean period time of speech evaluation after orthognathic surgery was 1.0 ± 0.46 year. The mean amount of maxillary advancement was 7.2 ± 3.2 mm and show significant correlation with speech outcomes. (P = 0.012) . In CO group, the patients who had the maxilla 1∼5 mm advancement maintained their speech completely and 44% of patients with 6∼8 mm deteriorated their speech. In DO group, patients with 9∼10 mm maintained their speech completely, 50% of patients with 11∼12 mm deteriorated their speech and 100% of patients with 13∼16 mm deteriorated their speech. According to the relationship between the amount of maxillary advancement and speech outcomes, there was a statistically significant correlation in both CO and DO groups. (P = 0.04, 0.029). Conclusion: It was found that speech of the patients with more amount of maxillary advancement tended to get worse. Also, it was observed that there exist some stable ranges of maxillary advancement for speech safety which does not effect on speech. (1∼5 mm in CO group and 9∼10 mm in DO group). Address correspondence and reprint requests to Yountaek Koo, MD, Wonjin Plastic Surgery, Seoul, Korea, 419, Gangnam-daero, Seocho-gu, Seoul, Korea; E-mail: kooyountaek@gmail.com; Sukwha Kim, MD, Department of Plastic Surgery, Seoul National University Hospital, 101 Daehak-ro Jongno-gu, Seoul 110–744, Korea; E-mail: kimsw@snu.ac.kr Received 20 October, 2018 Accepted 1 April, 2019 The authors report no conflicts of interest. Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcraniofacialsurgery.com). © 2019 by Mutaz B. Habal, MD.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Neurosurgical Anesthesiology

Defining a Taxonomy of Intracranial Hypertension: Is ICP More Than Just a Number? Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension. Supported by Department of Health and Human Services, National Institutes of Health, and National Institute of Neurological Disorders and Stroke, 1R01NS082309-01A1. W.A.K.: funded by 1R01NS082309-01A1. Legal consultant; multiple legal and health care entities. Royalty payments Oxford University Press and Elsevier. Honoraria NIH study sections. Editorial Board Neurocritical Care. Editorial Board J Neurosurg Anesth. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. R.B.: funded by 1R01NS082309-01A1. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. The remaining authors have no conflicts of interest to disclose. Address correspondence to: W. Andrew Kofke, MD, MBA. E-mail: kofkea@uphs.upenn.edu. Received November 26, 2018 Accepted April 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Subanesthetic Dose of Ketamine Improved CFA-induced Inflammatory Pain and Depression-like Behaviors Via Caveolin-1 in Mice Background: Ketamine, a commonly used nonbarbiturate anesthetic drug, possesses antidepressant properties at subanesthetic doses; however, the underlying mechanisms remain unclear. Materials and Methods: The analgesic and antidepressant effects of ketamine were explored using a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model in vivo. Mice were first divided into sham or CFA injection group randomly, and were observed for mechanical hyperalgesia, depression-like behavior, and mRNA expression of caveolin-1. Then ketamine was administered in CFA-treated mice at day 7. Results: The behavioral testing results revealed mechanical hyperalgesia and depression in mice from days 7 to 21 after CFA injection. Ketamine reversed depression-like behaviors induced by CFA injection. It also restored the brain-regional expression levels of caveolin-1 in CFA-treated mice. In addition, caveolin-1 mRNA and protein expression were increased in the prefrontal cortex and nucleus accumbens of CFA-treated mice. However, ketamine reversed the increase in caveolin-1 expression in the ipsilateral and contralateral prefrontal cortex and nucleus accumbens, supporting the distinct roles of specific brain regions in the regulation of pain and depression-like behaviors. Conclusions: In CFA-treated mice that exhibited pain behavior and depression-like behavior, ketamine reversed depression-like behavior. The prefrontal cortex and nucleus accumbens are the important brain regions in this regulation network. Despite these findings, other molecules and their mechanisms in the signal pathway, as well as other regions of the brain in the pain matrix, require further exploration. J.L. and R.H. contributed equally to this work. J.W. and Q.Z. are co-first authors. This work was funded by the Beijing Municipal Administration of Hospitals' Ascent Plan (code number DFL20180502) and Clinical Medicine Development of Special Funding Support (code number ZYLX201708). R.H. is a member of the Editorial Board of the Journal of Neurosurgical Anethesiology. The authors have no conflicts of interest to disclose. Address correspondence to: Ruquan Han, MD, PhD. E-mail: ruquan.han@ccmu.edu.cn. Received November 21, 2018 Accepted April 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Editorial No abstract available

Standardized Accreditation of Neuroanesthesiology Fellowship Programs Worldwide: The International Council on Perioperative Neuroscience Training (ICPNT) No abstract available

Remifentanil Patient-controlled Analgesia in Awake Craniotomy: An Introduction of an Innovative Technique No abstract available

Effect of Daytime Versus Night-Time on Outcome in Patients Undergoing Emergent Neurosurgical Procedures Background: Timing of neurosurgical procedures is controversial. Challenges identified with night-time surgeries include physician fatigue and sleep deprivation, and fewer staff and resources compared with daytime surgery. These might contribute to medical errors and complications, and, hence, worse patient outcomes. Methods: This single center retrospective study of 304 patients who underwent emergent neurosurgical procedures between January 1, 2010 and December 31, 2016 included 2 groups based on the timing of surgery: daytime (7:00 AM to 6:59 PM) and night-time (7:00 PM to 6:59 AM) surgery groups. Patient demographics, diagnosis, surgical characteristics, complications, and neurological outcome were obtained from the medical records. Results: There was no difference in patient demographics, intraoperative complications, and length of surgery between the 2 groups. Although there was no statistically significant difference in neurological outcome between the 2 groups at hospital discharge and 1 month postdischarge, there was a higher proportion of patients in the night-time surgical group with unfavorable neurological outcome (Glasgow Outcome Score 1 to 3) at both these times. There were differences in hospital length of stay, location of postoperative management (postanesthesia care unit or intensive care unit), midline shift, baseline Glasgow Coma Scale score, and acuity of surgery between the 2 groups. Logistic regression analysis showed that age, baseline Glasgow Coma Scale score, surgery acuity status, procedure type, and intraoperative complications influenced neurological outcome. Conclusions: This study found no difference in the rate of unfavorable neurological outcome in patients undergoing emergent neurosurgical procedures during the daytime and night-time. However, our findings cannot exclude the possibility of an association between timing of surgery and outcome given its limitations, including small sample size and omission of potentially confounding variables. Further well-designed prospective trials are warranted to confirm our findings. This study is a part of Bachelor of Science (Medicine) project thesis of A.H.Q., and he received a stipend from the University of Manitoba to conduct this research project. This project is funded by Anesthesia Oversight Committee, Department of Anesthesiology, Perioperative and Pain Medicine, University of Manitoba, Winnipeg, Canada. T.C. (primary supervisor) received the above-mentioned grant. Support was provided solely from institutional and/or departmental sources. Presented at: Neuroanesthesia Rounds, August 15, 2018, University of Manitoba; Bachelor of Science (Medicine) Research Symposium, August 23, 2018, University of Manitoba. The authors have no conflicts of interest to disclose. Address correspondence to: Tumul Chowdhury, MD, DM, FRCPC. E-mail: tumul.chowdhury@umanitoba.ca. Received September 9, 2018 Accepted March 12, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Language Monitoring in Brain Surgery Under General Anesthesia Background: Awake surgeries for cerebral lesion resection have several limitations including patient fear, discomfort, or pain. This study aimed to determine whether components of language function could be measured under general anesthesia. In this study, the occurrence of mismatch negativity (MMN) was searched in evoked potentials for phonological sounds. Materials and Methods: Five normal hearing, French native speaker, awake volunteers participated in evaluating the phonological task (4 females and 1 male). Eleven normal-hearing, French native speaker patients (6 left and 5 right hemisphere lesions) participated at the time of their tumor neurosurgery (3 females and 8 males). Repetitions of the standard syllable /pa/ with the insertion of 1 deviant /po/ were presented through earphones. The difference between averaged epochs of standards and deviants syllables determined the MMN. During surgery, total intravenous anesthesia was performed with propofol and synthetic opioid sufentanil. The bispectral index was targeted (40 to 60). Results: The MMN was found in all awake volunteers and validated by an N250 component. In the patient group, the electroencephalogram analysis was not possible in 4 of 11 patients because of anesthesia being too deep, burst suppression, or a high level of noise (>40 μV). Significant N250 response was obtained in 5 of 7 (71.4%) patients under general anesthesia. The 2 other patients also showed MMN which did not reach significance. Conclusions: To our knowledge, this is the first demonstration that phonological processing can be measured during brain surgery under general anesthesia, suggesting that some language processing persists under the condition of unconsciousness. These results encourage further study of language processing under general anesthesia with the goal of making intraoperative neuromonitoring. Supported by the University Hospital of Geneva (in particular with the fund PRD no. 10-2015-I "Advanced electrophysiological monitoring in neurosurgery"). The authors have no conflicts of interest to disclose. Address correspondence to: Colette Boëx, PhD. E-mail: colette.boex@hcuge.ch. Received December 7, 2018 Accepted March 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

The Role of Near-infrared Spectroscopy in Cerebral Autoregulation Monitoring No abstract available

Comparison of 2 Automated Pupillometry Devices in Critically Ill Patients Background: Automated pupillometry may help detect early cerebral disturbances in critically ill patients. It remains unclear whether different automated pupillometry devices can detect pupillary abnormalities with similar accuracy. The aim of this study was to compare the performance of 2 commercially available automated pupillometry devices—Neurolight Algiscan (NL) and NPi-200 (NP) versus standard pupillary light reflex (PLR) examination in an unselected cohort of critically ill patients. Materials and Methods: This prospective study included all adult (>18 y) patients admitted to the intensive care unit of a university hospital over a 20-day period. Measurements were made consecutively with each method once during the intensive care unit stay in each patient. To assess sensitivity and specificity, we calculated areas under the curve of the receiver operating characteristic curve. Results: A total of 112 patients were included in the study. There was a significant correlation between the 2 automated pupillometry devices for pupil size, constriction to light stimulation, and constriction velocity but not for pupillary latency. The mean bias for pupil size measured by the NL and the NP devices was −0.12 (limit of agreement [LoA], −1.29 to 1.06) mm, for pupil constriction −1.0% (LoA, −9.3% to 7.2%), and for latency 0.02 (LoA, −0.22 to 0.25) ms. There was a significant correlation between pupil size evaluated by clinical examination and that using the NL or NP. The areas under the curves for pupil constriction measured by NL and NP were 0.93 and 0.91, respectively, to detect clinically reactive pupils. Conclusions: Although there was a significant correlation between NL and NP values as well as with clinical examination of the PLR, the 2 devices were not always interchangeable, especially for the evaluation of pupillary latency. F.S.T., B.M.S., and S.P.: conceived and designed the study. F.S.T., B.M.S., S.P., and J.C.: selected the population. B.M.S., F.S.T., S.P., J.C., and J.L.V.: screened and collected data from the population. F.S.T., M.O., and C.R.: conduced the statistical analysis. F.S.T., M.O., and C.R.: wrote the first draft of the manuscript. J.L.V., J.C., B.M.S., and S.P.: revised the text for intellectual content. All the coauthors read and approved the final text. M.O. has received lectures fees from Neuroptics. The remaining authors have no funding or conflicts of interest to disclose. Address correspondence to: Fabio S. Taccone, MD, PhD. E-mail: ftaccone@ulb.ac.be. Received November 17, 2018 Accepted March 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Bilateral Ultrasound-guided Erector Spinae Plane Block for Postoperative Analgesia in Lumbar Spine Surgery: A Randomized Control Trial Background: Major lumbar spine surgery causes severe postoperative pain. The primary objective of this randomized controlled study was to compare the effect of ultrasound (US)-guided erector spinae plane (ESP) block on 24-hour postoperative cumulative opioid requirements with standard (opioid-based) analgesia. Postoperative pain control and patient satisfaction were also assessed. Materials and Methods: Adults scheduled for elective lumbar spine surgery under general anesthesia were randomly assigned to the following (and they are): Control group-no preoperative ESP block, or ESP block group-preoperative bilateral US-guided ESP block. Both groups received standard general anesthesia during surgery. Postoperative pain score, number of patients requiring rescue analgesia, and total morphine consumption during the first 24 postoperative hours were recorded. Patient satisfaction was assessed 24 hours after surgery. Results: Postoperative morphine consumption was significantly lower in patients in the ESP group compared with those in the control group (1.4±1.5 vs. 7.2±2.0 mg, respectively; P<0.001). All patients in the control group required supplemental morphine compared with only 9 (45%) in the ESP block group (P=0.002). Pain scores immediately after surgery (P=0.002) and at 6 hours after surgery (P=0.040) were lower in the ESP block group compared with the control group. Patient satisfaction scores were more favorable in the block group (P<0.0001). Conclusions: US-guided ESP block reduces postoperative opioid requirement and improves patient satisfaction compared with standard analgesia in lumbar spine surgery patients. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Swati Singh, MD. E-mail: deepakswat@yahoo.com. Received November 24, 2018 Accepted March 13, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com