Editorial board

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7





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Effets paradoxaux des biothérapies — Une dénomination erronée ?

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7
Author(s): D. Jullien




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Le phénomène de la langue verte, ou le diagnostic par Google

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7
Author(s): C. Godillot, A. Laprie, C. Eid, J.-C. Fricain, S. Boulinguez, E. Casassa, E. Vigarios, V. Sibaud
IntroductionLa consommation régulière de cannabis peut s'associer à certaines toxicités endobuccales, souvent mal connues du clinicien : xérostomie, caries, maladie parodontale, leucoedème, hyperplasie gingivale, colonisation à Candida albicans, leucoplasie ou gingivite…ObservationNous rapportons ici l'apparition d'une coloration verte de la langue chez un patient, consécutive à l'inhalation intensive de marijuana.DiscussionCette complication n'a qu'exceptionnellement été rapportée dans la littérature médicale. Paradoxalement, elle est clairement identifiée sur différents moteurs de recherche sur internet, notamment Google.BackgroundRegular cannabis use may be associated with several oral changes not usually identified by dermatologists: xerostomia, increased risk of caries, periodontitis, leukoedema, gingival hyperplasia, and higher prevalence and density of Candida albicans, leukoplakia or gingivitis.Patients and methodsWe report herein the appearance of a characteristic green tongue in a patient following intensive marijuana inhalation.DiscussionThis complication has rarely been reported in the medical literature. Paradoxically, it is clearly described in different Internet search engines, particularly Google.



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Lymphome T cutané et systémique traité avec succès par greffe haplo-identique

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7
Author(s): M. Méchineaud, M. Mercier, Y. Le Corre, A. Croué, N. Ifrah, L. Martin
IntroductionNous rapportons un cas de lymphome T cutané et systémique ayant résisté au traitement conventionnel et dont l'évolution a conduit à réaliser une greffe de moelle haplo-identique.ObservationUne femme de 53 ans consultait pour un érythème infiltré du visage, des lésions kératosiques du tronc et des adénopathies centimétriques axillaires et inguinales. Le diagnostic de syndrome de Sézary (SS), forme leucémique d'un lymphome T cutané épidermotrope, était retenu. Après 3 ans de traitement par méthotrexate, la patiente développait un SS transformé avec atteinte viscérale. Le fort risque de rechute et l'absence de donneur HLA-compatible amenait à la réalisation d'une greffe haplo-identique de moelle osseuse. La patiente était en rémission complète à 2 ans et demi. L'évolution était cependant marquée par l'apparition, un an après la greffe, d'une éruption lichénoïde blaschko-distribuée dont l'aspect histologique était compatible avec une réaction du greffon contre l'hôte (GVH) chronique ; elle était traitée efficacement par bétaméthasone topique.DiscussionNous rapportons, à notre connaissance, la première greffe haplo-identique réalisée pour un lymphome cutané T transformé et systémique. Ce traitement pourrait désormais être une option pour les patients nécessitant une allogreffe mais n'ayant pas de donneur compatible. Les lésions lichénoïdes blaschko-distribuées attribuées à une GVH chronique pourraient être la conséquence d'une perte d'immunotolérance vis-à-vis de clones embryologiques anormaux, provoquant ainsi une réaction inflammatoire médiée par les lymphocytes T.BackgroundHerein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting.Patients and methodsA 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma. After three years of treatment with methotrexate, the patient developed transformed SS with visceral involvement. Given the high risk of relapse and the absence of an HLA-compatible donor, haploidentical bone marrow grafting was performed. The patient was still in complete remission two and a half years later. The disease course was nevertheless marked by the emergence one year after grafting of a Blaschko-distributed lichenoid eruption having histological features consistent with chronic graft-versus-host disease (GVHD); treatment with topical betamethasone proved efficacious.DiscussionTo our knowledge, this is the first reported case of haploidentical grafting for systemic and transformed cutaneous T-cell lymphoma. This approach could henceforth represent a therapeutic option for patients requiring an allograft in the absence of compatible donors. The Blaschko-distributed lichenoid lesions attributed to chronic GVHD could be the result of reduced immune tolerance to abnormal embryological clones leading to a T-lymphocyte-mediated inflammatory reaction.



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Ichtyoses congénitales : les biothérapies aussi ?

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7
Author(s): O. Dereure




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Calendrier

Publication date: June–July 2018
Source:Annales de Dermatologie et de Vénéréologie, Volume 145, Issues 6–7





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Carcinoma Cuniculatum of the Alveolar Mucosa: A Rare Variant of Squamous Cell Carcinoma

Abstract

Carcinoma cuniculatum is one of the variants of squamous cell carcinoma. It is significantly rare with an incidence rate < 1% compared to other histological variants of squamous cell carcinoma. Various etiologic factors implicated are trauma, HPV, chronic inflammation and alcohol consumption but real causative agent still remains unclear. Initially it resembles plantar wart which slowly progress to bulky exophytic mass in the sole of the foot, where cases have been reported first. In the oral cavity it presents clinically as an exophytic growth and slowly invades the jaw and destroys the underlying bone. Microscopically it exhibits as both exophytic and endophytic epithelial masses along with well differentiated and pronounced hyperkeratosis. Treatment includes surgical resection alone unlike other variants which are treated by radiation with or without chemotherapy. Here we present a case of carcinoma cuniculatum occurred in alveolar mucosa of a 47 years old female. It presented as an exophytic growth in mandibular alveolar region, with histological features consistent with carcinoma cuniculatum.

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The role of surgical margins in chondrosarcoma

Publication date: Available online 8 June 2018
Source:European Journal of Surgical Oncology
Author(s): Jonathan D. Stevenson, Minna K. Laitinen, Michael C. Parry, Vaiyapuri Sumathi, Robert J. Grimer, Lee M. Jeys
IntroductionChondrosarcoma (CS) is the second most common primary bone sarcoma with no clear role for adjuvant therapy. The purpose of this study was to investigate (1) the relationship between surgical excision margins and local recurrence free survival (LRFS), and (2) the role of local recurrence (LR) in disease specific survival (DSS) in CS of the extremity and pelvis.Material and methods341 pelvic and extremity CS diagnosed between 2003 and 2015 were studied retrospectively.ResultsLR developed in 23% of cases. Pelvic location, pathologic fracture, margin and grade were significant factors for LR after univariate analysis. Multivariate analysis revealed surgical margin and pelvic location as positive factors for LR, and grade-1 and 2 CS as negative factors for LR. Pathologic fracture, central versus peripheral, grade, and LR were significant factors with univariate analysis for DSS; and grade was significant after multivariate analysis for all patients for DSS. After competing risk analysis, LR was statistically significant for DSS in grade-2 and grade-3 tumours.ConclusionSurgical margins determine LR in all CS grades, but LR affects DSS only in grade-2 and grade-3 tumours. Although narrow margins are acceptable in grade-1 tumours, since biopsy is unreliable in predicting final grade, a minimum 4-mm margin should be the aim in all cases.



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Prostate sparing cystectomy for bladder cancer: A two-center study

Publication date: Available online 8 June 2018
Source:European Journal of Surgical Oncology
Author(s): Charlotte S. Voskuilen, Elisabeth E. Fransen van de Putte, Jose I. Pérez-Reggeti, Erik van Werkhoven, Laura S. Mertens, Bas WG. van Rhijn, Mohamed Saad, Axel Bex, Xavier Cathelineau, Henk G. van der Poel, Simon Horenblas, Rafael Sanchez-Salas, Richard P. Meijer
PurposeTo assess long-term functional and oncologic outcomes of prostate sparing cystectomy (PSC) as a sexuality-preserving alternative to radical cystectomy in a selected group of bladder cancer (BC) patients.Materials and MethodsBetween 1995 and 2014, 185 BC patients underwent PSC according to one of two standardized procedures at two centers. All patients had received extensive evaluation to rule out prostate cancer and BC at the bladder neck and prostatic urethra (PU), including prostate specific antigen blood analysis, transrectal ultrasound and/or prostate biopsies, PU biopsies and/or PU frozen section analysis. All patients received an orthotopic ileal neobladder. Overall survival (OS) was assessed by Kaplan–Meier estimates. Cumulative incidence of cancer specific mortality, any recurrence and loco-regional recurrence were calculated using competing-risk methods. Finally, functional outcomes (voiding, continence and erectile function) were evaluated.Results185 patients (cTa-3N0M0) with a mean age of 57 years (SD: 9) were included. Median follow-up was 7.5 years (IQR: 5.6-10.8). Five-year OS was 71% and 5-year cumulative incidence of recurrence was 31%. Twenty patients (10.8%) had a loco-regional recurrence, two recurrences were in the PU. During follow-up, prostate cancer was detected in six patients (3.2%). Erectile function was preserved in 86.1% of patients, complete daytime and nighttime continence in 95.6% and 70.2%, respectively.ConclusionThis two-center study shows that in men with BC in whom the prostate and PU were proven free of malignancy, PSC would represent a valid treatment option with excellent functional outcome. Oncologic outcomes were comparable to what is known from radical cystoprostatectomy series.



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Reply to: Management of locally recurrent rectal cancer

Publication date: Available online 7 June 2018
Source:European Journal of Surgical Oncology
Author(s): Karin Westberg, Anna Martling




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“Location of the Internal Mammary Vessels for Microvascular Autologous Breast Reconstruction: The “1–2–3 Rule”

Background: Postmastectomy breast reconstruction provides psychosocial benefits in self-esteem, sexuality, and quality of life. Autologous procedures yield the highest overall patient satisfaction compared to implant-based breast reconstruction as the gold standard. The internal mammary vessels (IMA/V) are the preferred recipient vessels for free flap breast reconstruction. The study's purpose is to provide surgeons with a reliable method to locate the vessels intraoperatively. Methods: The IMA/V were dissected bilaterally on 30 cadaveric specimens. Distances from the lateral sternal borders (LSBs) and the costochondral junctions (CCJs) to the IMA/V at the 2nd, 3rd and 4th costal levels were recorded. Descriptive bifurcation patterns were recorded. Initial dissection practicums were performed utilizing the proposed safer dissection zone per quantitative data. Results: 60 IMAs and 120 IMVs were studied at 3 costal levels resulting in 180 sets of measurements. Distances from LSB to medial IMV were 6.12 mm, 9.04 mm, and 10.45 mm at costal levels two, three, and four, respectively. Mean distances between CCJs and IMAs were 12.80 mm, 24.78 mm, and 33.28 mm at costal levels two, three, and four, respectively. Most IMV bifurcated at 3rd costal level, and left side bifurcated higher than right. Dissection practicums revealed that the proposed dissection zone was consistently reliable in locating the vessels. Conclusions: This study provides mean measurements from common bony landmarks to the IMA/V, equipping surgeons with a reliable zone of dissection for recipient vessel exposure. This may decrease morbidity and improve outcomes in autologous breast reconstructions. Financial Disclosure Statement: None of the authors has a financial interest to declare in relation to the content of this manuscript. Acknowledgements: The authors would like to thank the Kansas City University of Medicine and Biosciences Division of Clinical Anatomy and the University of Nebraska Medical Center for faculties, equipment, and specimens for this study. Corresponding Author: Christina Dami Lee, MS, 1750 Independence Avenue, Kansas City, MO 64106, Dami.lee4@gmail.com ©2018American Society of Plastic Surgeons

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Role of Fractionated Fat (FractoFat) in Blending the Lid-Cheek Junction

Introduction: Fat grafting is extensively used in plastic surgery in last 2 decades. Here, we report the retrospective comparison of patients who underwent fractionated fat injection to blend the lid-cheek junction with those who had regular fat injection. Method: After obtaining institutional review board approval, a retrospective review of patients who underwent lower blepharoplasty with fractionated fat injection for blending lid-cheek junction from January 2014 through October 2015 was performed. The results were compared to lower blepharoplasty patients who didn't have fractionated fat injected prior to January 2014.Twelve prospectively selected patients underwent histopathological and gene expression comparisons. Results: A comparison of complications between 2 groups revealed no significant difference. Furthermore, there was no significant difference between 2 groups for sequelae of fractionated fat injection and regular fat injection. The gene expression analysis of the fractionated and regular fat didn't have any difference with both undifferentiated and differentiated cells. Additionally, Oil Red O staining of the fractionated and regular fat after differentiation shows that cells from both kinds of fat groups differentiated equally well. Conclusion: Fractionated fat injection appears to be safe addition in blending the lid-cheek junction in the five step lower blepharoplasty. There is no fat nodule formation with injection of fractionated fat injection in comparison to injection of regular fat done superficially in the tear trough area. Contrary to what has previously been shown, the presence of viable cells in fractionated fat was noted. Disclosure: The authors have no financial interest to declare in relation to the content of this article. Dr. Rohrich receives instrument royalties from Micrins Instruments and book royalties from Thieme Publishers Corresponding author: Rod J. Rohrich, MD, Dallas Plastic Surgery Institute, 1901 North Central Expressway; Suite 600, Dallas, Texas 75230, Rod.rohrich@dpsi.org ©2018American Society of Plastic Surgeons

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Prepectoral Implant-Based Breast Reconstruction with Post-Mastectomy Radiation Therapy

Background: Two-stage subpectoral implant-based breast reconstruction (IBBR) is the most common method for breast reconstruction. Recent advances in surgical techniques and technology have made prepectoral IBBR feasible. There is limited data on outcomes after prepectoral IBBR and post-mastectomy radiation therapy (PMRT). Methods: A retrospective review of consecutive patients undergoing immediate two-stage prepectoral IBBR with PMRT was performed. Outcomes of radiated breasts were compared with non-radiated breasts in bilateral cases. Results: Ninety-three cases of prepectoral IBBR in 54 women who underwent immediate two-stage prepectoral IBBR (39 bilateral and 15 unilateral) and unilateral PMRT were identified. Mean follow-up was 19 months from mastectomy and tissue expander reconstruction and nine months from implant placement. Crude complication rates in radiated versus non-radiated sides were as follows: surgical site infection (SSI) 18.5% vs 7.7%, seroma 5.6% vs 5.1%, mastectomy skin flap necrosis 1.9% vs 2.6%, wound dehiscence 1.9% vs 7.7%, capsular contracture 1.9% vs 0%, hematoma 1.9% vs 2.6%, and extrusion 1.9% vs 0%. On univariate analysis there were no risk factors, including radiation, associated with any complication, SSI, unplanned readmissions, and unplanned return to the operating room. To date, reconstruction has been completed in 96% of patients, with successful IBBR in 81 breasts (45 radiated breasts and 36 non-radiated breasts). Conclusion: Early data of prepectoral IBBR in patients with PMRT show promising results. PMRT should not be an absolute contraindication to prepectoral IBBR. Financial Disclosure Statement: Dr. Jacobson is a Consultant to Allergan, Mentor, Sientra, LifeCell and Novadaq. Dr. Lemaine is a Consultant for LifeCell and Bonti. The remaining authors have no financial interest to declare in relation to the content of this article. REDCap database at our institution is funded through the Center for Clinical and Translational Science grant support (UL1 TR000135). IRB approval was obtained from Mayo Clinic Rochester. Authors' role: All authors made substantial contributions to the conception of the work, revised it critically for important intellectual content, approved of the submission of the final version to be reviewed for publication, and agree to be accountable for all aspects of the work. Corresponding author: Valerie Lemaine, MD, MPH, 200 First St SW, Rochester, MN 55905, Lemaine.Valerie@mayo.edu, Phone: 507-284-2736, Fax: 507-284-5994 ©2018American Society of Plastic Surgeons

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Nipple-sparing mastectomy Incisions for Cancer Extirpation (NICE) Prospective Cohort Trial: Perfusion, Complications, and Patient Outcomes

Background: Nipple-sparing mastectomy (NSM) offers several advantages for women seeking post-mastectomy breast reconstruction, but compromised skin and nipple perfusion may lead to skin and nipple necrosis. It is unclear if the incisional approach contributes to these complications; therefore, the purpose of this study was to compare the impact of incision type on outcomes in patients undergoing NSM. Methods: This is a prospective cohort study of patients undergoing NSM with prosthetic breast reconstruction through an inframammary fold (IMF) versus a lateral radial (LR) incision. Skin and nipple perfusion as represented by fluorescent intensity, mammometric parameters, patient-reported outcomes, and clinical outcomes were analyzed and compared for the two cohorts and multivariable logistic regression models were performed to evaluate effects of covariates on outcomes. Results: 79 patients were studied: 55 in the IMF cohort and 24 in the LR cohort. The IMF group had significantly less fluorescent intensity to the inferior (21.9% vs 36.9%, p=0.001) and lateral portions of breast skin (23.1% vs 40.7%, p=0.003) after reconstruction. Decreased fluorescent intensity was associated with smoking, decreased mean arterial pressure, and greater specimen weight. Post-reconstruction breast volumes were increased over preoperative volumes in the IMF group (38.3%) versus the LR (31.2%) group; however patients with a LR incision had a greater increase in satisfaction with their breasts and psychosocial well-being. Conclusions: There are significant differences in patient-reported outcomes and final breast volumes based on the incisional approach to NSM. These data can be used to guide providers and counsel patients considering NSM with prosthetic reconstruction. Meeting Presentation: These data were presented in part at Plastic Surgery The Meeting, American Society of Plastic Surgeons, October 2016, Los Angeles, California, USA Financial Disclosure: Dr. Myckatyn is a consultant for Acelity and Allergan. Acelity initially provided Spy kits for perfusion assessment to Dr. Tenenbaum for this study. No other funds or resources were provided for this study. None of the other authors have relevant financial disclosures. Acknowledgements: The authors would like to thank from the Department of Surgery at Washington University School of Medicine in Saint Louis, Ms. Colleen Kilbourne-Glynn for assistance with patient enrollment and data organization. They would like to thank Ms. Annette Irving for assistance with IRB preparation and Ms. Tracey Guthrie for administrative assistance. Corresponding Author: Terence M. Myckatyn, MD, Professor, Plastic and Reconstructive Surgery, West County Plastic Surgeons, Washington University School of Medicine, 1020 N. Mason, Suite 110, Saint Louis, MO 63141, E-mail: myckatyn@wudosis.wustl.edu, Phone: (314) 996-8800, Fax: (314) 367-0225 ©2018American Society of Plastic Surgeons

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Use of Roof-Shaped Costochondral Cartilage for Correction of Saddle Nose Deformity

Background: Cartilage grafts are routinely used in secondary and post-traumatic rhinoplasty. However, in most cases, there are weak areas in the nasal bones and upper lateral cartilages. The purpose of this study was to seek a solution for keystone area and dorsum of the nose in revision and post-traumatic rhinoplasty cases, and reconstruction of saddle nose deformity including upper lateral cartilage with roof shaped graft. Methods: A retrospective review of reconstructive rhinoplasties performed for saddle nose deformities was conducted. A part of the costochondral graft was carved and thinned (roof graft) for reconstruction of the keystone area and upper lateral cartilages, while another portion was used for making a neo-septal (reconstructed septum) graft and strut graft. Roof graft was capped onto the neo-septal graft with sutures, and this cartilage framework was adapted with fitting the cranial edge of neo-septal cartilage between the nasal bones. Finally strut graft was fixed to the cartilage framework. Results: A significant improvement in nasal shape and overall appearance was achieved in all cases, and 71.42% of patients recovered from nasal obstruction. No gross absorption, graft exposure or recurrence of deformities was observed. Conclusions: Surgical correction of a saddle-shaped nose should be an acceptable and uncomplicated technique, and the cosmetic result should be totally acceptable. There are many management options for a saddle-shaped nose. Use of roof grafts (shrunk gull wing grafts) with neo-septal and strut grafts enables simulation of the internal nasal valve and results in a natural nasal position. The authors has nothing to disclose. Presented at: Rhinoplasty Society Annual Meeting 2017, in San Diego, Califormia Corresponding author: Fatih Irmak; MD, Saglik Bilimleri Universitesi, Sisli Hamidiye Etfal Arastirma ve Uygulama Merkezi; Plastik, Rekonstruktif ve Estetik Cerrahi Klinigi, Halaskargazi cad. Etfal Sokak, Istanbul, Turkiye, dr.fatihirmak@gmail.com ©2018American Society of Plastic Surgeons

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When is Teenage Plastic Surgery vs Cosmetic Surgery OK - Reality vs Hype? – A Systematic Review

Summary: Plastic surgery in teenagers has become popular in past decades due to an increase in self-awareness and desire to "fit in" with their peers. In 2016, over 229,551 cosmetic procedures were performed in patients who are under the age of 19 years old 1. The trend of plastic surgery in adolescents is increasing, and it is important for plastic surgeons to perform safe and appropriate procedures in this group. To this date, there is a myriad of literature on the psychological and ethical issues concerning plastic surgery in teenagers. However, studies regarding the safety of performing plastic surgery in this population are scare 2. The rationale for this review is to study this issue in depth via a systematic review. We will discuss the current indications, safety, patient satisfaction, and ethical considerations of teenage plastic surgery as well as make recommendations for future studies on this important area in plastic surgery. Financial Disclosure and Products: Rod J. Rohrich, MD receives instrument royalties from Eriem Surgical, Inc and book royalties from Thieme Medical Publishing. No funding was received for this article. Min-Jeong Cho, M.D., has no financial interest to declare in relation to the content of this article. Acknowledgements: None Corresponding Author Contact Information: Address correspondence to: Rod J. Rohrich M.D., Dallas Plastic Surgery Institute, 9101 North Central Expressway, Suite 600, Dallas, TX 75231, Rod.Rohrich@UTSouthwestern.edu ©2018American Society of Plastic Surgeons

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A report of 736 high definition lipoabdominoplasties performed in conjunction with circumferential Vaser liposuction

Background: Several innovations and modifications to abdominal lipectomy procedure have been performed through the years. Despite the recent improvements, the lack of natural results, including high scars, navel deformities and "tense" abdomen are still challenging. The objective is to present an alternative technique of combined 360-degree truncal liposuction with abdominal definition, abdominoplasty and neoumbilicoplasty. Methods: From January 2005 to June 2017, 736 VASER assisted lipoabdominoplasties were performed. Only healthy women with body mass index below 33 were included. A 3-step procedure was done: 1. Truncal Liposculpture. 2. dermolipectomy and plication of the rectus abdominis muscle. 3. Neo-umbilicoplasty through a butterfly technique. The following included photos and medical assessment with a mean of 2 years (up to 5 years). A non-standardized survey was performed to self-evaluate the results. Results: 670 patients answered the survey (91%). 615 patients were satisfied with the procedure (91.79%). Minor complications were reported: seroma (7.3%), prolonged bruising (10%) and swelling (18%). Neither flap necrosis nor infections were reported. Neo umbilicoplasty was performed in all patients. Additional procedures were required in 4.6%. Conclusions: The Ultrasonic-assisted assisted Lipoabdominoplasty is an alternative lipectomy technique that prevents stigmata of the procedure. The abdominal definition improves the shape and recreate the superficial anatomy. Neoumbilicoplasty shape, form and choice of its position over the abdominal wall gives significant improvements in results. Financial Disclosure Statement: The authors received no financial support for the research, authorship, and publication of this article. Statement of financial interest:Dr. Hoyos was an unpaid speaker and advisor for the product development team of Sound Surgical, (now Valeant Pharmaceuticals International) up to May 2013. Since May 2013 he receives royalties for the liposuction kits named after him. During the time of the study the authors did not have financial interest nor receive any financial support of the products or devices mentioned in this article Corresponding author: Alfredo Hoyos, MD., Address: Carrera 15 # 83 – 33, Suite 304, Bogotá, Colombia. alhoyos@gmail.com ©2018American Society of Plastic Surgeons

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Human Acellular Dermis as Spacer for Small Joint Arthroplasty: Analysis of Revascularization in a Rabbit Trapeziectomy Model

BACKGROUND: Carpometacarpal (CMC) osteoarthritis affects 8-12% of the general population. Surgical management provides symptomatic relief for 78% of patients who fail conservative therapy, but little consensus exists regarding which surgical procedure provides superior patient outcomes. Recent human trials substituted exogenous acellular dermal matrices (ADMs) in the bone space, but there is no quantitative histological data on the outcome of ADMs in this environment. We aimed to quantify the revascularization and recellularization of ADMs in the joint space using a rabbit model. METHODS: Bilateral lunate carpal bones were surgically removed in New Zealand rabbits. ADM and autologous tissue were implanted in place of the lunate of the right and left wrists, respectively. ADM was also implanted subcutaneously as a non-joint control. Histological and immunofluorescence analysis was performed after collection at zero, six, and twelve weeks. RESULTS: Quantitative analysis of anti- α- smooth muscle actin (SMA) and CD31 immunofluorescence revealed a sequential and comparable increase of vascular lumens in joint space and subcutaneous ADMs. In contrast, autologous tissue implanted in the joint space did not have a similar increase in SMA- or CD31-positive lumens. Semi-quantitative analysis revealed increased cellularity in both autologous and ADM wrist implants at each time point, while average cellularity of subcutaneous ADM peaked at six weeks and regressed by twelve. Trichrome and Sirius Red staining revealed abundant collagen at all time points. CONCLUSIONS: The trapeziectomy joint space supports both cellular and vascular ingrowth into human ADM. * Authors contributed equally Disclosures: This work was funded in part by a grant from the Musculoskeletal Transplant Foundation/Plastic Surgery Foundation. AKW is supported by NIH 1K08HL132110-01. All procedures were approved by the Keck School of Medicine of USC Institutional Animal Care and Use Committee (IACUC #20099) and animals were housed according to recommendations from the USC Department of Animal Resources (DAR) Corresponding Author: Alex K. Wong, Division of Plastic and Reconstructive Surgery, Department of Surgery, Keck School of Medicine of USC, 1510 San Pablo St. Suite 415, Los Angeles, CA 90033 USA. Alex.Wong@med.usc.edu ©2018American Society of Plastic Surgeons

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Commentary for A report of 736 high definition lipoabdominoplasties performed in conjunction with circumferential Vaser liposuction

No abstract available

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Changes in Cutaneous Gene Expression after Microvascular Free Tissue Transfer in Parry Romberg Disease

Purpose: Parry Romberg's Disease (PRD) is an enigmatic craniofacial disorder characterized by progressive facial atrophy. The pathogenesis and molecular mechanisms governing PRD have never before been described. The purpose of our current study was two fold; 1) to begin to elucidate the pathophysiology of this disease using next gen RNA sequencing and 2) evaluate the effect of surgical treatment on gene expression. Methods: Patients with PRD underwent microvascular free tissue transfer (MVFF) to the face to address contour deformity in both active and burned out disease. Tissue samples were collected for analysis at the time of initial MVFF, and 6 months later at a scheduled revision surgery. Patients presenting for rhytidectomy had tissue samples taken as control tissue. Patients with disease were compared to control samples. Results: Twenty two subjects were evaluated. (Six control and Sixteen Parry Romberg patients) All patients with PRD underwent MVFF to the face. Thirteen patients underwent scheduled six month revision surgery. Disease samples were distinct from healthy controls, and postoperative patient samples were more similar to healthy control samples. Parry Romberg patients had a unique proinflammatory gene expression profile including upregulation of: IL24, ADAMTS4, and GFCSF3. Postoperatively, more than 3,400 genes were changed (p

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Seasonal Impact on Surgical Site Infections in Body Contouring Surgery: A Retrospective Cohort Study of 602 Patients Over a Period of 6 Years

Purpose: Postoperative Surgical Site Infections (SSI) are severe complications following body-contouring-surgery (BCS). Here we evaluate if SSI rates are influenced by higher temperatures during the summer season. Patients and Methods: We enrolled 602 patients who underwent BCS between 2009 and 2015 in a retrospective cohort study. Data collected included demographics, surgical data and postoperative outcome. BCS procedures included lower and upper-bodylift, abdominoplasty, breast-reduction, mastopexy, brachioplasty and thigh-lift. Infection rates were calculated on a seasonal basis and compared using Fisher's-exact test and logistic-regression-analysis. Results: There were 136 patients (125 women; 11 men) in the warm season (June-August; with an average temperature of 67.622°F (19.79°C) and 466 patients (438 women; 28 men) in the cold seasons group (September-May; with an average temperature of 45.45 °F (7.47°C)). The composition of the study cohorts was comparable. Average age was 40 years and average body mass index was 27. From a total of 602 patients we observed 33 SSIs, representing a rate of 5.48%. A statistically significant rise of postoperative SSIs could be detected during summer (10.29% vs. 4.08%, p=0.0071) representing an increase of 150%. Additionally, a logistic regression analysis determined 'season' as the strongest predictor for SSIs with a risk exaltation of 2.693 times in the warm season. Conclusion: BCS are elective procedures making careful risk consideration an absolute prerequisite. We demonstrate a significantly increased infection risk during summer and establish a causal link between the warm season and SSI accumulation. Consequently, preoperative patient information and operative planning should be adjusted accordingly. * These authors contributed equally to this work None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. CORRESPONDING AUTHOR: DR. GEORG M HUEMER, M.SC. MBA, Section of Plastic and Reconstructive Surgery- Kepler University Hospital Linz, Krankenhausstrasse 9, 4020 Linz- Austria. Conflict of Interest:The authors have no financial interest to declare in relation to the content of this article. ©2018American Society of Plastic Surgeons

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Novel approach for risk-reducing mastectomy - first stage implant placement and subsequent second stage mastectomy.

Background: Risk-reducing mastectomy (RRM) with tissue expander then implant-based breast reconstruction conventionally involved immediate submuscular placement of tissue expanders during mastectomy, then after expansion, replacement of expanders for permanent implants in a second stage operation. Use of acellular dermal matrix (ADM) can achieve a single staged operation but ADMs are costly and may have potential complications. We aim to assess the feasibility of placement of implants as a first stage before RRM as a novel technique of reconstruction which avoids the need for serial outpatient expansion and ADM. Methods: Patients for RRM were offered first stage dual plane placement of fixed volume silicone gel permanent implants via inframammary fold incisions. RRM was undertaken several months later as the second operation, leaving the implants in place protected by the muscle and capsule pocket. Nipples were preserved or reconstructed according to patient's choice. Results: Eight patients with 15 operated breasts were recruited. Anatomically shaped implants were used in all patients and complete coverage of each implant was achieved. Mean implant volume was 433ml (range: 290-545ml). There were no complications and good aesthetic outcomes were achieved. Conclusions: This proof of principle finds that placement of implants before RRM is a novel technique for women at high breast cancer risk that could reduce the use of tissue expanders and ADMs and their associated problems. Two-staged RRM with first stage implant placement and subsequent RRM leaving the implants in place is feasible with no complications and can produce a good cosmetic outcome. Novel reconstruction of risk-reducing mastectomy The authors declare no conflict of interest and do not have any financial disclosure. Corresponding author: Dr Geok-Hoon Lim, Address: KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Republic of Singapore. Tel: (65) 6225 5554, Fax: (65) 6394 5817, Email: ghlimsg@yahoo.com.sg ©2018American Society of Plastic Surgeons

https://ift.tt/2JDLHzS

Opioid Usage Following Outpatient Breast Surgery: Are Physicians Part of the Problem?

Purpose: The increasing rate of opioid abuse warrants standardization of postoperative pain management. The purpose of this study is to analyze the use of opioids in pain control and patient satisfaction following ambulatory breast surgery. Methods: This is a prospective study of a consecutive series of patients undergoing secondary breast reconstruction [SBR: n=60)] or breast reduction [BR:n=35]. All patients were given a pain questionnaire preoperatively. Postoperatively, women received 30 tablets of oxycodone 5.0mg/acetaminophen 325mg. Patients were contacted three times postoperatively: postoperative day [POD] 3-5, 8-10, and >/30. All patients were queried on narcotic usage, pain level (0-10), and satisfaction with pain control. Patients with allergies or taking narcotics preoperatively were excluded. Results: Most in SBR group (61.5%) had stopped taking opioids by POD5. Patients consumed a mean of 11.4 pills following SBR and 17.5 after BR. A majority reported feeling satisfied with their pain management. At POD>/30, most experienced very mild pain with an improvement of 3.74 points following BR. There were 18.6 and 12.5 pills per patient leftover for both SBR and BR, respectively. 1,551 unused pills were leftover entire cohort at POD>/30. There was not a significant difference in average pain scores and interference with enjoyment or activity between those that did or did not take pain medication. Conclusion: This commonly prescribed pain regimen provides adequate pain relief and satisfaction for breast surgery with a substantial number of leftover pills. We as prescribers should be aware of discrepancies. Thirty opioids after outpatient breast surgery appears unnecessary and excessive. This paper was previously presented at the Southeastern Society of Plastic and Reconstructive Surgeons in June of 2017. AH has nothing to disclose JB has nothing to disclose LK has nothing to disclose AL has nothing to disclose Corresponding Author: Albert Losken, M.D., 550 Peachtree Street NE, Suite 9000, Atlanta, GA 30308, 404-686-8143, alosken@emory.edu ©2018American Society of Plastic Surgeons

https://ift.tt/2LtzQlp

Optimizing Perforator Selection: A Multivariable Analysis of Predictors for Fat Necrosis and Abdominal Morbidity in DIEP Flap Breast Reconstruction

Introduction: This study aims to elucidate the important predicting factors for fat necrosis and abdominal morbidity in the patient undergoing DIEP flap reconstruction. Methods: Retrospective review of 866 free-flap breast reconstructions performed at one institution from 2010-2016. 28 potential predictors were included in multivariable analyses to control for possible confounding interactions. Results: 409 total DIEA perforator flaps were included in our statistical analysis. 14.4% had flap fat necrosis, 21.3% had an abdominal wound or complication, and 6% had an abdominal bulge or hernia. Analysis showed an increase in the odds of fat necrosis with increasing flap weight (OR 1.002 per 1g increase, p-value=. 0002). A decrease in the odds of fat necrosis was seen with lateral row (OR .29, p-value=. 001) and both-row perforator flaps (OR .21, p-value=. 001), if ICG angiography was utilized (OR .46, p-value=. 04), and with increasing total flow rate of the flap (OR .62 per 1 mm/s increase, p-value= .05). Increased odds of abdominal bulge or hernia were seen with lateral or both row perforators (OR 3.21, p-value=. 05) vs. medial row perforator based flaps, and with patients whom had an abdominal wound post-operatively (OR 2.59, p-value=. 05). Conclusions: Our results suggest that utilizing larger caliber perforators and perforators from the lateral row alone, or in addition to medial row perforators, can decrease fat necrosis rather than by simply harvesting more perforators alone. However, lateral and both row perforator flaps come at the cost of increasing abdominal bulge rates. Financial Disclosure: The authors have no commercial or financial associations related to the submitted manuscript, and no commercial or financial conflicts of interest. No funding was received for the performance of this research of production of the manuscript. Acknowledgements: We would like to thank the expedient and accurate work of Hong Zhu, Ph.D. and Jingsheng Yan of the Division of Biostatistics at the Department of Clinical Sciences & Simmons Comprehensive Cancer Center at UT Southwestern Medical Center Corresponding Author: Nicholas Haddock, M.D., UT Southwestern Medical Center, 1801 Inwood Road, Dallas, Texas, 75390, Phone: (214) 645-2353, Email: nicholas.haddock@utsouthwestern.edu ©2018American Society of Plastic Surgeons

https://ift.tt/2MaVPyD

“Transversus Abdominis Plane Blocks in Microsurgical Breast Reconstruction: Analysis of Pain, Narcotic Consumption, Length of Stay and Cost.”

Background: Transversus abdominis plane (TAP) blocks are increasingly being utilized in microvascular breast reconstruction. The implications of TAP blocks on specific reconstructive, patient and institutional outcomes remain to be fully elucidated. Methods: Patients undergoing abdominally-based microvascular breast reconstruction from 2015-2017 were reviewed. Length of stay, complications, narcotic consumption, donor-site pain and hospital expenses were compared between patients that did and those that did not receive TAP blocks with liposomal bupivacaine. Outcomes were subsequently compared in patients with elevated body mass index (BMI). Results: Fifty patients (43.9%) received TAP blocks (27 [54.0%] under ultrasound guidance) and 64 patients (56.1%) did not. Patients with TAP blocks had significantly decreased oral and total narcotic consumption (p=0.0001 and p

https://ift.tt/2LxYx02

Nitroglycerin Ointment for Reducing the Rate of Mastectomy Flap Necrosis in Immediate Implant Based Breast Reconstruction

Background: Mastectomy flap necrosis (MFN) remains a challenging complication in immediate tissue expander breast reconstruction (ITEBR). Nitroglycerin ointment has been shown to reduce the incidence of MFN in a randomized controlled study, using 45g per breast and treating one side only in bilateral cases. This study was conducted to determine the efficacy of 15g of nitroglycerin ointment per breast - therefore permitting application to both breasts in cases of bilateral mastectomy. Methods: A retrospective cohort study of patients undergoing ITEBR by a single reconstructive surgeon was conducted. The intervention cohort consisted of all patients between June 10, 2015 and June 9, 2016 (94 patients, 158 breasts), where 15g of nitroglycerin ointment was routinely applied per breast. The control cohort consisted of all patients from June 10, 2014 to June 9, 2015 (107 patients, 170 breasts) where nitroglycerin was not applied. All complications were tracked including minor wound healing problems. Results: There was an overall 22% decreased incidence of MFN in the nitroglycerin ointment cohort (47.5% vs. 60.6%, p=0.002), with a 44% reduction in full thickness MFN that trended towards statistical significance (9.5% vs. 16.5%, p=0.06). On multivariate analysis, nitroglycerin application was independently associated with a decrease in MFN or need for mastectomy flap debridement. There was no significant difference in the incidence of post-operative hypotension (3.8 vs. 2.9%) or headache among cohorts. Conclusion: Topical nitroglycerin ointment application to mastectomy skin flaps at 15g per breast is a cost-effective means to decrease the incidence of MFN in unilateral and bilateral ITEBR. Disclosures: The authors declare that they had no financial interests, commercial associations, or conflicts of interest during the course of this study. Grants: The authors have no external funding sources or grants to declare. Prior presentations: This work has been presented at the 2017 MAPS (Midwest Association of Plastic Surgeons) meeting taking place in Chicago, IL in April 2017 Corresponding Author: Sergey Y Turin, MD, Division of Plastic and Reconstructive Surgery, Northwestern University Feinberg School of Medicine, 675 N St Clair St., Suite 19-250, Chicago, IL, 60611, 312-695-6022, sergeyturin@gmail.com ©2018American Society of Plastic Surgeons

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Opioid Usage Following Outpatient Breast Surgery: Are Physicians Part of the Problem?

No abstract available

https://ift.tt/2LtzQ4T

Discussion: A Matter of Replication. Nitroglycerin Ointment for Reducing Rate of Mastectomy Flap Necrosis in Immediate Implant Based Breast Reconstruction

No abstract available

https://ift.tt/2JBulDX

The use of bone dust to correct the open roof deformity in rhinoplasty

Background: Hump removal frequently results in an open roof during rhinoplasty, which is conventionally closed with lateral osteotomies. However, if the patient has a narrow bony vault, then lateral osteotomies are problematic. Here, we present a new and practical approach to fix the open roof deformity. Methods: A total of 240 patients (female, 187; male, 53) were enrolled and operated with the presented technique. This approach has four steps as follows: complete submembranous dissection, the preparation of spreader flaps, harvesting the bone dust from the bony hump, and the placement of the bone dust. The patient's nasal dorsum was evaluated by ultrasonography (US). During the follow-up period, all patients were postoperatively photographed from standart views using a digital camera. Photos were inspected by two independent plastic surgeons. A palpation test for the nasal dorsum was conducted by a senior surgeon to identify any irregularities. A rhinoplasty outcomes evaluation (ROE) questionnaire was administered to all patients at a 1-year follow-up visit. Functional improvement was assessed with self-evaluation nasal patency. The chi-square test was used for statistical analysis. Results: Of the 240 patients, 182 completed the 1-year follow-up period and ROE questionnaire. Thirty-seven patients were evaluated by US at postoperative year 1. During the follow-up period, no resorption or displacement was detected. High patient satisfaction was achieved, and no complications were encountered. Conclusions: The presented four-step surgical concept was useful for rhinoplasty surgeons to successfully manage open roof deformity in selected patients. Foot Note: A part of this study was presented in Fifth Bergamo Open Rhinoplasty Course (March 15-19, 2016 in Bergamo, Italy) and selected for Best Presentation Award. Conflict of Interest: 'TAS 1' 'TAS 2' 'TAS 3' were designed by the author (S.T) and patented in the Turkish Patent Institute (No: 2016/05472). These instruments are not commericial avaible yet, however they can be produced by Elektron Medical Company (a Turkish instrument company) with a special order via their website (https://ift.tt/2JBuirL). The author does not receive any payment from the company and has no financial gain. Acknowledgement: The author thanks to Dr.Isil Yurdaisik for her valuable contributions in ultrasonographic evaluation. The use of bone dust to correct the open roof deformity in rhinoplasty Address for correspondence: Süleyman Taş, MD, Hakkı Yeten Cad, No: 11, Terrace Fulya, Center: 1, Apt: 97 Şişli, Istanbul 34349, Turkey. Tel: +90-532-0563693; Fax: +90 212 9793000,. E-mail: drsuleymantas@live.com ©2018American Society of Plastic Surgeons

https://ift.tt/2Lx9uij

“Not all breast implants are equal: a 13-year review of implant longevity and reasons for explantation”

Background: Augmentation mammoplasty is the most common aesthetic procedure. Textured implants control implant position and have improved capsular contracture rates; however, the impact of texturing on longevity and clinical findings at explantation is unclear. Methods: All cases of explantation between January 2005 – April 2017 from an aesthetic practice were reviewed retrospectively. Patient demographics, implant characteristics, time-to-explantation, and clinical presentation and intraoperative findings at explantation were analyzed. Results: 539 breast implants were explanted during the study period: 249 saline, 147 smooth gel, 123 Biocell®, and 20 other nonaggressively textured breast implants. Average time from placement to explantation was 7.5 years, 5.6 years, 4.9 years, and 4.0 years for saline, other textured, smooth gel, and Biocell® implants, respectively (p-value = 3.25e-08). The percentage of implants removed associated with implant performance failure was 50.3%, 57.5%, 75.0%, and 85.4% for smooth gel, saline, other textured, and Biocell® implants, respectively (p-value = 7.25e-09). 21.1% of Biocell® implants versus 1.5% of all other implants presented with pain (p-value = 2.71e-15). 45 Biocell® implants had double capsules; this phenomenon was not observed with any other implant type (p-value = 5.85e-37). Seven Biocell® implants had late seromas, compared to three late seromas with any other implant type (p-value = 0.0013). Conclusions: Here, we provide evidence that Biocell® implants have the shortest time-to-explantation and the highest proportion of implants associated with implant performance failure. This information should complement the informed consent process when selecting an appropriate implant. Financial Disclosure Statement: Nicholas J. Carr (consultant Allergan, Mentor) Aaron Van Slyke and Michael Carr have nothing to disclose. This article was funded by an academic research grant from the UBC Division of Plastic Surgery Presented at: UBC Division of Plastic Surgery Research Day 2017 in Vancouver, B.C. All authors have met the ICMJE guidelines for authorship credit as follows: Aaron C. Van Slyke: conception and design, acquisition of data, analysis and interpretation; drafting the article and revising the article critically for important intellectual content; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Michael Carr: acquisition of data, analysis and interpretation of data; revising the article critically for important intellectual content; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Nicholas J. Carr: conception and design of the study; interpretation of the data; revising the article critically for important intellectual content; final approval of the version to be submitted; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. AKNOWLEDGEMENTS: This study was funded by a 2016 UBC Division of Plastic Surgery Academic Research Grant. Statistical analysis was performed by Karey Shumansky from the Applied Statistics and Data Science Group through the UBC Department of Statistics. Corresponding author: Aaron C. Van Slyke, MD, MSc, Division of Plastic Surgery, Burn and Trauma Unit, University of British Columbia (UBC) and Vancouver General Hospital, 2nd Floor, JPP 899 West 12th Avenue, Vancouver, BC, Canada. V5Z 1M9, vanslykeaaron@gmail.com ©2018American Society of Plastic Surgeons

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Is there an optimal method for measuring baseline metabolic tumor volume in diffuse large B cell lymphoma?

https://ift.tt/2HtklYg

18 F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics

Abstract

Purpose

PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is ⁶⁸Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity, ¹⁸F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel ¹⁸F-labelled ligand PSMA-1007 at two different time points.

Methods

This retrospective analysis included 40 consecutive patients (mean age 68.7 ± 8.1 years) referred for PSMA PET/CT. ¹⁸F-PSMA-1007 PET/CT was performed for localization of biochemical relapse, primary staging or therapy follow-up. Circular regions of interest were placed on representative slices of the liver, spleen, kidney, abdominal aortic blood pool, bone marrow (fourth lumbar vertebral body), urinary bladder and gluteus muscle at 60 and 120 min after injection. In malignant lesions the maximum standardized uptake (SUV_max) was measured within volumes of interest at both time points. All SUVs at 60 min were compared with those at 120 min after injection.

Results

The activity in the blood pool, urinary bladder and gluteus muscle was very low and decreased significantly over time (P < 0.001). Uptake in the liver, spleen and kidney showed a significant increase over time and uptake in the bone marrow remained stable. Overall, 135 PCa lesions were detected at 60 min and 136 lesions at 120 min after injection. The median SUV_max increased significantly (P < 0.001) from 10.98 to 15.51 between 60 and 120 min.

Conclusion

PCa lesions show a significant increase in ¹⁸F-PSMA-1007 uptake at 120 min compared with 60 min after injection. In addition, accumulation of the tracer in the urinary bladder was very low leading to improved contrast of adjacent PCa lesions. Increasing accumulation in the liver may limit the sensitivity of the tracer in detecting liver metastases.

https://ift.tt/2sH2mZL

The role of interim 18 F-FDG PET/CT in prediction of response to ipilimumab treatment in metastatic melanoma

Abstract

Purpose

The aim of the present study was to assess the value of interim ¹⁸F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy.

Methods

The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body ¹⁸F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients' best clinical response, assessed at a median of 21.4 months (range 6.3–41.9 months) was used as reference.

Results

According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46).

Conclusion

The application of the recently proposed PERCIMT to interim ¹⁸F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.

https://ift.tt/2Hvd8qF

Correction to: 18 F-FDG PET in drug-resistant epilepsy due to focal cortical dysplasia type 2: additional value of electroclinical data and coregistration with MRI

The original version of this article has added numbers in the text which are unnecessary. Correct line should be: "We also performed PET/MRI based surgical resections in an increasing number of MRI negative/ doubtful cases with favourable outcome."

https://ift.tt/2JEdJLI

The impact of a Bayesian penalized-likelihood reconstruction algorithm on delayed-time-point Ga-68-PSMA PET for improved recurrent prostate cancer detection

https://ift.tt/2HsKMxp

Amyloid load but not regional glucose metabolism predicts conversion to Alzheimer’s dementia in a memory clinic population

Abstract

Purpose

The value of imaging regional glucose metabolism with [¹⁸F]FDG PET for the prediction of progression from mild cognitive impairment (MCI) to Alzheimer's dementia (AD) is controversial. The predictive value of imaging with [¹⁸F]FDG PET was therefore tested and compared with that of imaging beta-amyloid load with [¹¹C]PIB PET in the same memory clinic population of MCI patients.

Methods

Thirty-nine patients with MCI who had undergone [¹⁸F]FDG as well as [¹¹C]PIB PET were identified from a single-centre clinical registry. [¹⁸F]FDG and [¹¹C]PIB PET images were rated as positive or negative for the presence of regional hypometabolism typical of AD and beta-amyloid deposition, respectively. Raters were blinded to the clinical information. Patients were followed clinically for 2.7 ± 1.2 years after PET. Cox proportional hazards models, adjusted for age and sex, were used to test the predictive value of [¹⁸F]FDG PET, [¹¹C]PIB PET, and both in combination.

Results

[¹⁸F]FDG PET did not significantly predict conversion to AD (p > 0.1). By contrast, models including [¹¹C]PIB PET only (p < 0.05) or both [¹⁸F]FDG and [¹¹C]PIB PET (p < 0.05) significantly predicted conversion to AD. The hazard ratio for AD in patients with a positive [¹¹C]PIB scan was 10.2 (95% confidence interval 1.3–78.1). The results were confirmed by analysis of semiquantitative measures using normalized [¹⁸F]FDG uptake and [¹¹C]PIB standardized uptake value ratios in AD-typical regions as continuous predictors.

Conclusion

In contrast to [¹¹C]PIB PET, [¹⁸F]FDG PET did not predict conversion from MCI to AD in this clinical patient sample. Therefore, amyloid PET should be preferred for individual prediction and patient counselling in clinical practice.

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Alphatherapy, the new impetus to targeted radionuclide therapy?

https://ift.tt/2HsKFSv

The central zone has increased 68 Ga-PSMA-11 uptake: “Mickey Mouse ears” can be hot on 68 Ga-PSMA-11 PET

Abstract

Purpose

Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in ⁶⁸Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of ⁶⁸Ga-PSMA-11.

Methods

We retrospectively analysed all patients who underwent a staging ⁶⁸Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUV_max and SUV_mean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test.

Results

Of 283 consecutive patients scanned with ⁶⁸Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUV_max between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p < 0.001).

Conclusion

Our results suggest that higher ⁶⁸Ga-PSMA-11 accumulation in the central zone than in the transition and peripheral zones is normal, and leads to a pattern resembling "Mickey Mouse ears" on ⁶⁸Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans.

https://ift.tt/2sFRnjt

Preoperative [ 18 F]FDG PET/CT tumour heterogeneity index in patients with uterine leiomyosarcoma: a multicentre retrospective study

Abstract

Purpose

We investigated the prognostic value of the tumour heterogeneity index determined on preoperative [¹⁸F]FDG PET/CT in patients with uterine leiomyosarcoma (LMS).

Methods

We retrospectively reviewed patients with uterine LMS who underwent preoperative [¹⁸F]FDG PET/CT scans at three tertiary referral hospitals. The PET/CT parameters maximum standardized uptake value of the primary tumour (SUV_max), metabolic tumour volume (MTV) and total lesion glycolysis were assessed. The negative values of the MTV linear regression slope (nMLRS) according to the SUV thresholds of 2.5 and 3.0 were determined as the tumour heterogeneity index. The value of PET/CT-derived parameters in predicting progression-free survival (PFS) and overall survival (OS) were determined in regression analyses.

Results

Clinicopathological and PET/CT data from 16 patients were reviewed. The median postsurgical follow-up was 21 months (range 4–82 months), and 12 patients (75.0%) experienced recurrence. Tumour size (P = 0.017), SUV_max (P = 0.019), MTV (P = 0.016) and nMLRS (P = 0.008) were significant prognostic factors for recurrence. MTV (P = 0.048) and nMLRS (P = 0.045) were significant prognostic factors for patient survival. nMLRS was correlated with clinicopathological parameters including tumour size (Pearson's correlation coefficient γ = 0.825, P < 0.001) and lymph node metastasis (γ = 0.721, P = 0.004). Patient groups categorized according to the nMLRS cut-off value showed significant differences in PFS (P = 0.033) and OS (P = 0.044).

Conclusion

The preoperative tumour heterogeneity index obtained using the MTV linear regression slope may be a novel and useful prognostic marker in uterine LMS.

https://ift.tt/2HtJguS

Scratch induced thin film buckling for quantitative adhesion measurements

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): A. Kleinbichler, M.J. Pfeifenberger, J. Zechner, S. Wöhlert, M.J. Cordill
Adhesion of thin films is one of the most important factors determining reliability of microelectronic devices and semiconductor industry requires quantitative testing methods to effectively compare these interfaces. Several techniques have been developed over the last decades with scratch induced delamination being a rarely studied method. For compressively stressed films on rigid substrates scratching can cause buckling failure and by modeling the delaminations according to the Hutchinson and Suo model the adhesion can be determined quantitatively. Two different sample systems, a tungsten-titanium film on a silicate glass and a silicon nitride film on a silicate glass with a tungsten-titanium overlayer, have been tested using scratch loads in the range of 100–500 mN. This study demonstrates that the scratching resulted in buckles parallel to the scratch trace and triggered further spontaneous buckling. Using the dimensions of the induced buckles the interfacial adhesion energies were quantified. The adhesion energy of the tungsten‑titanium/silicate glass interface was measured to be 2.7 J/m² and of the silicon nitride/silicate glass interface was 1.5 J/m². The results illustrate that the scratch test can be utilized for quantitative adhesion testing of thin films and suggest that scratch induced delamination is a valuable addition to established adhesion measurement techniques.

Graphical abstract

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Inclusion evolution in additive manufactured 316L stainless steel by laser metal deposition process

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): Du-Rim Eo, Sun-Hong Park, Jung-Wook Cho
In laser metal deposition (LMD) process, meltpool oxidation is inevitable due to high working temperature, which results in finely dispersed non-metallic inclusions in the steel matrix. In this paper, characteristics of these inclusion, such as number density and mean radius, were controlled by means of changing process parameters, for instance, scan speed and laser power, using AISI 316L stainless steel powders. Subsequently, the yield stress of cast samples from each condition was measured in order to investigate the possibility of utilizing these inclusions in material strengthening. As oxygen contents varied from 306 ppm to 994 ppm, number densities of inclusion varied from 16,900/mm² to 34,000/mm². The yield stress of deposited material was proportional to inclusion number density ranging from 218 MPa to 269 MPa. Oxygen contents were governed by beam intensity and deoxidizer compositions in the powder, while faster scan speed gave smaller inclusion diameter due to shorter time for growth. The composition and viscosity of slag layer, which covered interface between superheated meltpool and atmosphere, brought in a large difference in oxidation kinetic. Compared with conventional casting process, a large number of inclusions were more finely distributed and possess smaller size, meaning that oxide metallurgy can be fully utilized in the LMD process.

Graphical abstract

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Effective design and simulation of surface-based lattice structures featuring volume fraction and cell type grading

Publication date: 5 October 2018
Source:Materials & Design, Volume 155
Author(s): I. Maskery, A.O. Aremu, L. Parry, R.D. Wildman, C.J. Tuck, I.A. Ashcroft
In this paper we present a numerical investigation into surface-based lattice structures with the aim of facilitating their design for additive manufacturing. We give the surface equations for these structures and show how they can be used to tailor their volume fractions. Finite element analysis is used to investigate the effect of cell type, orientation and volume fraction on the elastic moduli of the lattice structures, giving rise to a valuable set of numerical parameters which can be used to design a lattice to provide a specified stiffness. We find the I-WP lattice in the [001] orientation provides the highest stiffness along a single loading direction, but the diamond lattice may be more suitable for cases where lower mechanical anisotropy is important. Our stiffness models enable the construction of a powerful numerical tool for predicting the performance of graded structures. We highlight a particular problem which can arise when two lattice types are hybridised; an aberration leading to structural weakening and high stress concentrations. We put forward a novel solution to this problem and demonstrate its usage. The methods and results detailed in this paper enable the efficient design of lattice structures functionally graded by volume fraction and cell type.

Graphical abstract

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Genetic and nongenetic factors that may predispose individuals to allergic drug reactions

Purpose of review Defining predisposition to allergic drug reactions has largely focussed on HLA associations, but other genetic and nongenetic factors are also likely to be involved. Recent findings Polymorphic genetic variants in cytokine genes, including IL-10, and co-signalling pathways, including CTLA4, have been associated with allergic drug reactions, but the effect size is lower than with HLA alleles and most associations have not been replicated. Although TCR specificity seems to be important for CBZ-induced SJS/TEN in South East Asian patients, a distinct repertoire may not play a role in reactions to other drugs. New mass spectrometric techniques allowing for the identification of naturally eluted peptides from drug-exposed HLA alleles will allow for the antigenic source of T-cell activation to be defined and may shed light on the influence of disease. Indeed, preliminary data highlight the propensity of drug-responsive T cells to cross-react with T cells primed to viral antigens. Furthermore, the environment can epigenetically influence regulatory gene expression, suggesting that an individual's family exposure history may alter immune thresholds and tip the balance toward activation. Summary It is likely that predisposition to allergic drug reactions is multifaceted in most cases. This will require the study of large numbers of patients to detect genetic factors that have a lower effect size than HLA alleles. This should be accompanied by detailed clinical phenotyping of patients and the assessment of the immunological phenotype with respect to the presence and type of drug antigen-responsive T cells. Correspondence to Munir Pirmohamed, Institute of Translational Medicine, University of Liverpool, Block A: Waterhouse Building, 1–5 Brownlow Street, Liverpool L69 3GL, United Kingdom. E-mail: munirp@liverpool.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Interaction between foods and nonsteroidal anti-inflammatory drugs and exercise in the induction of anaphylaxis

Purpose of review To assess the studies that focus on the study of food-dependent exercise-induced anaphylaxis (FDEIA) and food-dependent NSAID-induced anaphylaxis (FDNIA). Recent findings Cofactors, as exercise and nonsteroidal anti-inflammatory drugs (NSAIDs), are relevant in up to 30% of episodes of anaphylaxis. Gliadin and lipid transfer proteins are the main allergens involved. The attempts to reproduce FDEIA and FDNIA in a controlled setting have an important failure rate. The cyclooxigenase (COX) pathway could play an important role in the underlying mechanisms: NSAIDs and exercise increase the permeability of the intestinal barrier. This effect is stronger with NSAID that inhibit both isoforms than with preferential COX-2 inhibitor. Basophils obtained from FDNIA patients, showed an increase of its activation with the food allergen with lysine–aspirin compared with the food allergen alone. This potentiating effect was not observed when basophils were stimulated with the food allergen with selective COX-2 inhibitor. Other mechanisms including transient receptor potential superamily, reactive oxygen species, altered B-cell pathway and increased neutrophil activation markers have been speculated. Summary The frequent implication of cofactors, as exercise and NSAID, in food-induced anaphylaxis highlights the importance of recognizing and including them into diagnostic workup. The understanding of the underlying mechanisms would help in the development of diagnostic and therapeutic strategies. Correspondence to Joan Bartra, Allergy Section, Pneumology Department, Hospital Clinic, Villarroel 170, Barcelona 08036, Spain. Tel: +34 627902503; e-mail: jbartra@clinic.ub.es Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Advances in hypersensitivity drug reactions

No abstract available

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Granulocyte Macrophage Colony-Stimulating Factor Alone Reduces Toxoplasma gondii Replication in Microglial Culture by Superoxide and Nitric Oxide, without IFN-γ production: A Preliminary Report

Publication date: Available online 7 June 2018
Source:Microbes and Infection
Author(s): Tamirys Simão Pimenta, Natalie Ferreira Chaves, Ana Paula Drummond Rodrigues, Cristovam Wanderley Picanço Diniz, Renato Augusto DaMatta, José Antônio Picanço Diniz Junior
In vitro studies have demonstrated that GM-CSF in combination with other stimulatory factors induces a microbicidal response that control T. gondii infection. We assessed whether GM-CSF alone can control T. gondiireplication in murine microglial cultures. Microglia were collected and cultured with or without GM-CSF and the half of each group was infected with T. gondii. We determined the T. gondii infectivity, cytokines levels, NO and superoxide detection.GM-CSF alone primes microglia, which after infection induces the production of TNF-α and IL-6, leading to NO and superoxide production, without any stimulus from IL-12p70 and IFN-γ.



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Nonstructural protein of severe fever with thrombocytopenia syndrome phlebovirus targets STAT2 and not STAT1 to inhibit type I interferon-stimulated JAK-STAT signaling

Publication date: Available online 7 June 2018
Source:Microbes and Infection
Author(s): Yoshinori Kitagawa, Madoka Sakai, Masayuki Shimojima, Masayuki Saijo, Masae Itoh, Bin Gotoh
The nonstructural protein NSs of severe fever with thrombocytopenia syndrome phlebovirus blocks type I interferon (IFN)-stimulated JAK-STAT signaling. However, there is continuing controversy as to whether NSs targets STAT1 or STAT2 or both for this blockade. The present study was designed to gain a further understanding of the blockade mechanism. Immunoprecipitation experiments revealed a stronger interaction of NSs with STAT2 than with any other component constituting the JAK-STAT pathway. Expression of NSs resulted in the formation of cytoplasmic inclusion bodies (IBs), and affected cytoplasmic distribution of STAT2. STAT2 was relocated to NSs-induced IBs. Consequently, NSs inhibited IFN-α-stimulated tyrosine phosphorylation and nuclear translocation of STAT2. These inhibitory effects as well as the signaling blockade activity were not observed in NSs mutant proteins lacking the STAT2-binding ability. In contrast, NSs affected neither subcellular distribution nor phosphorylation of STAT1 in response to IFN-α and IFN-γ, demonstrating that NSs has little physical and functional interactions with STAT1. Taken together, these results suggest that NSs sequesters STAT2 into NSs-induced IBs, thereby blocking type I IFN JAK-STAT signaling.



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Comparative Study of Nasal Symptoms and Pulmonary Function Tests Post FESS in Ethmoidal Polyposis

Abstract

The objective of this study were to assess the pulmonary function in patients with ethmoidal polyposis who did not respond to medical treatment; to evaluate the effect of Functional Endoscopic Sinus Surgery on the lung function of these patients and to compare the total nasal symptom score in these patients. A prospective observational study was conducted in Department of ENT, KMC Manipal on 50 subjects with ethmoidal polyposis who were unresponsive to medical treatment and hence underwent FESS. Pulmonary function tests were assessed using spirometry and nasal symptoms were scored as per TNSS system prior to surgery and 3 months post-surgery and compared with the pre-operative values and analysed. Pre operatively majority (35 patients) had TNSS value of 6–9 whereas post operatively the score was reduced to 2–3 in many patients (38 patients). The mean TNSS was 7.24 before surgery which declined to 2.82 after surgery with a p value < 0.0001 indicating a statistically significant improvement in the nasal symptoms post FESS. The mean pre-operative FVC, FEV1, MEFR were 2.94, 2.41 and 2.51 L respectively whereas the mean post-operative values were 2.95, 2.39 and 2.49 L respectively. There was no statistically significant change in lung function tests following FESS. Our study shows that FESS benefits patients with nasal polyposis by improving the symptoms and there by the quality of life without any adverse effects on the lower airways.

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Classification of Naso Septal Deviation Angle and its Clinical Implications: A CT Scan Imaging Study of Palakkad Population, India

Abstract

Computerized tomographic imaging of the nasal and paranasal regions has become an indispensable tool for the endoscopic sinonasal surgery. The case control study was carried out on 120 patients for pilot study and 800 patients for the main study. The cases were selected with a clinical diagnosis of chronic rhino sinusitis. They were referred for a sinus CT scan by otolaryngologists and controls from the normal population. The patients were separated into males and females and anatomical variations were assessed. Increased prevalence of left sided nasal septal deviation and type II nasal septal deviation was seen in males belonging to cases group in our study. Knowledge about the nasal septum anatomical variations provides understanding about the upper limit of surgical dissection and aids in road mapping the confident direction for the functional endoscopic surgeons.

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Little cigars and cigarillos: Affect and perceived relative harm among U.S. adults, 2015

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Ban A. Majeed, Amy Nyman, Kymberle L. Sterling, Paul Slovic
IntroductionSimilar to cigarette smoking, consumption of cigars delivers nicotine and byproducts of tobacco combustion and elevates the risk of addiction, illness, and premature death. This study examined the relationship of affect, perceived relative harm, and LCC smoking behavior among U.S. adults.MethodsData were from Tobacco Products and Risk Perceptions Survey conducted in 2015. The study included a probability based sample of 6051 adults (18+) drawn from an online research panel. A current LCC smoker was defined as having ever smoked LCCs and was currently smoking LCCs every day, somedays, or rarely. Participants were asked whether smoking LCCs was less harmful, had about the same level of harm, or was more harmful than smoking regular cigarettes. Feelings about LCCs were collected using word association technique. Descriptive and multinomial logistic regression analyses were conducted.ResultsAbout 7% of the study participants were current LCC smokers. Adults with positive feelings had four-fold the adjusted odds to be current LCC smokers. Perceiving LCCs to be less harmful had 2.7 higher adjusted odds of being current LCC smokers.ConclusionsCompared to cigarettes, LCCs evoked more positive feelings among adults and these positive feelings were strongly associated with both perceiving LCCs as less harmful than cigarettes and with current LCC smoking. Cessation and prevention interventions would benefit from applying the principles of social marketing in which information is provided not only to inform consumers but also to evoke negative feelings and associations with LCC smoking.



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Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study

Publication date: Available online 7 June 2018
Source:Autoimmunity Reviews
Author(s): Debora N. Setoue, Ana C. Pitta, Fernanda J. Fiorot, Mariana M. Nastri, Glaucia V. Novak, Beatriz C. Molinari, Juliana C. Oliveira, Natali W. Gormezano, Ana P. Sakamoto, Maria T. Terreri, Rosa M. Pereira, Claudia Saad-Magalhães, Adriana M. Sallum, Katia Kozu, Melissa M. Fraga, Daniela P. Piotto, Gleice Clemente, Roberto Marini, Hugo R. Gomes, Carlos N. Rabelo-Junior, Marta M. Felix, Maria C. Ribeiro, Rozana G. Almeida, Ana P. Assad, Silvana B. Sacchetti, Leandra C. Barros, Eloisa Bonfá, Clovis A. Silva
ObjectiveTo evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population.MethodsA multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated.ResultsAt cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001).ConclusionsApproximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.



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Polyautoimmunity - The missing ingredient

Publication date: Available online 7 June 2018
Source:Autoimmunity Reviews
Author(s): Gabriel Samasca, Ramesh Ajay, Daniel Sur, Cornel Aldea, Lucia Sur, Emanuela Floca, Genel Sur, Iulia Lupan, Matthias Torsten, Lerner Aaron




https://ift.tt/2sGfRcb

Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study

Publication date: Available online 7 June 2018
Source:Autoimmunity Reviews
Author(s): Debora N. Setoue, Ana C. Pitta, Fernanda J. Fiorot, Mariana M. Nastri, Glaucia V. Novak, Beatriz C. Molinari, Juliana C. Oliveira, Natali W. Gormezano, Ana P. Sakamoto, Maria T. Terreri, Rosa M. Pereira, Claudia Saad-Magalhães, Adriana M. Sallum, Katia Kozu, Melissa M. Fraga, Daniela P. Piotto, Gleice Clemente, Roberto Marini, Hugo R. Gomes, Carlos N. Rabelo-Junior, Marta M. Felix, Maria C. Ribeiro, Rozana G. Almeida, Ana P. Assad, Silvana B. Sacchetti, Leandra C. Barros, Eloisa Bonfá, Clovis A. Silva
ObjectiveTo evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population.MethodsA multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated.ResultsAt cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001).ConclusionsApproximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.



https://ift.tt/2JteaoO

Polyautoimmunity - The missing ingredient

Publication date: Available online 7 June 2018
Source:Autoimmunity Reviews
Author(s): Gabriel Samasca, Ramesh Ajay, Daniel Sur, Cornel Aldea, Lucia Sur, Emanuela Floca, Genel Sur, Iulia Lupan, Matthias Torsten, Lerner Aaron




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Acute O2 Sensing: Role of Coenzyme QH2/Q Ratio and Mitochondrial ROS Compartmentalization

Publication date: Available online 7 June 2018
Source:Cell Metabolism
Author(s): Ignacio Arias-Mayenco, Patricia González-Rodríguez, Hortensia Torres-Torrelo, Lin Gao, M. Carmen Fernández-Agüera, Victoria Bonilla-Henao, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O2-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O2-sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. We show that responsiveness to hypoxia progressively disappears after inducible deletion of the Ndufs2 gene, which encodes the 49 kDa subunit forming the coenzyme Q binding site in MCI, even in the presence of MCII substrates and chemical NAD⁺ regeneration. We also show contrasting effects of physiological hypoxia on mitochondrial ROS production (increased in the intermembrane space and decreased in the matrix) and a marked effect of succinate dehydrogenase activity on acute O2 sensing. Our results suggest that acute responsiveness to hypoxia depends on coenzyme QH2/Q ratio-controlled ROS production in MCI.

Graphical abstract

Teaser

Arias-Mayenco et al. observe that an inducible deficiency of mitochondrial complex I (MCI) leads to a parallel decrease of carotid body chemoreceptor cell responsiveness to hypoxia. Acute O2 sensing depends on a high CoQH2/CoQ ratio, NADH accumulation, and compartmentalized reactive oxygen species production at MCI to signal membrane ion channel activity.


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Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Publication date: Available online 7 June 2018
Source:Cell Metabolism
Author(s): Tsadik Habtetsion, Zhi-Chun Ding, Wenhu Pi, Tao Li, Chunwan Lu, Tingting Chen, Caixia Xi, Helena Spartz, Kebin Liu, Zhonglin Hao, Nahid Mivechi, Yuqing Huo, Bruce R. Blazar, David H. Munn, Gang Zhou
The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells. We further demonstrate that T cell-derived tumor necrosis factor alpha (TNF-α) can synergize with chemotherapy to intensify oxidative stress and tumor cell death in an NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase-dependent manner. Reduction of oxidative stress, by preventing TNF-α-signaling in tumor cells or scavenging ROS, antagonized the therapeutic effects of adoptive immunotherapy. Conversely, provision of pro-oxidants after chemotherapy can partially recapitulate the antitumor effects of T cell transfer. These findings imply that reinforcing tumor oxidative stress represents an important mechanism underlying the efficacy of adoptive immunotherapy.

Graphical abstract

Teaser

Using a preclinical model of colorectal tumors treated with CD4+ T cell-based adoptive immunotherapy, Habtetsion et al. show that profound metabolic changes occur in tumors before tumor regression. T cells shape tumor metabolism through TNF-α, which can synergize with chemotherapy, to increase tumor cell oxidative stress through an NOX-dependent mechanism.


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Chemical and ecotoxicological effects of the use of drinking-water treatment residuals for the remediation of soils degraded by mining activities

Publication date: 15 October 2018
Source:Ecotoxicology and Environmental Safety, Volume 161
Author(s): P. Alvarenga, C. Ferreira, C. Mourinha, P. Palma, A. de Varennes
The aim of this study was to evaluate the use of drinking-water treatment residuals (DWTR) in the amendment of a soil affected by mining activities (Aljustrel mine, Portuguese sector of the Iberian Pyrite Belt), considering the effects on its chemical, biochemical and ecotoxicological characteristics. The DWTR had neutral characteristics (pH 6.7) and an organic matter (OM) content of 575 g kg⁻¹ dry matter (DM), which makes them a potential amendment for the remediation of mine degraded soils, as they may correct soil acidity and reduce the extractable metal fraction. An incubation assay, with soil and DWTR, with or without lime, was carried out to test the doses to be used in the assisted-phytostabilization experiment. Based on the results obtained, the doses of DWTR used were the equivalent to 48, 96, and 144 t DM ha⁻¹, with and without lime application (CaCO3 11 t DM ha⁻¹). Agrostis tenuis Sibth was used as the test plant. Some amendments doses were able to improve soil characteristics (pH and OM content), to decrease metal extractability by 0.01 M CaCl2 (especially for Cu and Zn), and to allow plant growth, that did not occur in the non-amended soil. Copper, Pb and Zn concentrations in the plant material were lower than the maximum tolerable level for cattle feed, used as an indicator of risk of entry of those metals into the human food chain. The simultaneous application of DWTR (96 and 144 t ha⁻¹), with lime, allowed a reduction in the mine soil ecotoxicity, as evaluated by some lethal and sub-lethal bioassays, including luminescence inhibition of Vibrio fischeri, Daphnia magna acute immobilization test, mortality of Thamnocephalus platyurus, and 72-h growth inhibition of the green microalgae Pseudokirchneriella subcapitata. However, DWTR were unable to increase soil microbial activity, evaluated by dehydrogenase activity, an important soil-health indicator. Also, OM content and NKjeldahl, concentrations increased slightly but remained low or very low (P and K extractable concentrations were not affected). In general, the bioassays highlighted a decrease in soil ecotoxicity with the presence of lime and DWTR (144 t DM ha⁻¹). In conclusion, DWTR are recommended to amend acidic soils, with high concentrations of trace elements, but an additional application of organic or mineral fertilizers should be considered.



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An evaluation of an immunomodulatory feed ingredient in heat-stressed lactating Holstein cows: Effects on hormonal, physiological, and production responses

Publication date: Available online 7 June 2018
Source:Journal of Dairy Science
Author(s): L.W. Hall, F. Villar, J.D. Chapman, D.J. McLean, N.M. Long, Y. Xiao, J.L. Collier, R.J. Collier
Holstein cows (n = 30) were balanced by days in milk, milk production, and parity (91 ± 5.9 d in milk, 36.2 ± 2.5 kg/d, and 3.1 ± 1.4, respectively) and fed OmniGen-AF (OG; Phibro Animal Health, Teaneck, NJ), an immune stimulant, at 0 g/cow per d for control (CON) or 56 g/cow per d for OG for 52 d on a commercial dairy. At 52 d of the study cows were randomly selected (n = 12) from both groups (6 OG and 6 CON) and housed in environmentally controlled rooms at the Agricultural Research Complex for 21 d at the University of Arizona. Cows were subjected to 7 d of thermoneutral (TN) conditions, 10 d of heat stress (HS), and 4 d of recovery (REC) under TN conditions. Feed intake, milk production, and milk composition were measured daily. Rectal temperatures (RT) and respiration rates (RR) were recorded 3 times per day (600, 1400, and 1800 h). Blood samples were taken on d 7 (TN), 8 (HS), 10 (HS), 17 (HS), and 18 (TN) during the Agricultural Research Complex segment. Cows in HS had higher RR and RT and water intake and lower dry matter intake and milk yield than these measures in TN. There was a treatment × environment interaction with cows fed OG having lower RR and RT and higher dry matter intake during peak thermal loads than CON. However, milk yield did not differ between groups. Cows fed OG had lower milk fat percent than CON (3.7 vs 4.3%) during HS. The SCC content of milk did not differ between treatment groups but rose in both groups during the REC phase following HS. Plasma insulin and plasma glucose levels were not different between groups. However, plasma insulin in both groups was lower during acute HS, then rose across the HS period, and was highest during the REC phase. Plasma cortisol levels were highest in all cows on the first day of HS (d 8) but were lower in cows fed OG compared with CON. However, plasma ACTH concentrations were elevated in OG-fed animals at all times samples were collected. Plasma ACTH was also elevated in cows fed both OG and CON during HS. Feeding OG reduced plasma cortisol during acute but not chronic HS and increased basal plasma ACTH, suggesting that OG treatment may alter the hypothalamic pituitary adrenal axis.



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Short communication: Effects of body fat mobilization on macrophage infiltration in adipose tissue of early lactation dairy cows

Publication date: Available online 7 June 2018
Source:Journal of Dairy Science
Author(s): Jenne De Koster, Clarissa Strieder-Barboza, Jonas de Souza, Adam L. Lock, G. Andres Contreras
Intense lipolysis triggers an inflammatory response within adipose tissue characterized by adipose tissue macrophage (ATM) infiltration; however, the mechanisms triggering this process are poorly characterized in transition dairy cows. The aim of this study was to determine the association between ATM infiltration and body fat mobilization in the transition period, markers of excessive lipolysis, and adipose tissue expression of genes related to chemotactic and inflammatory responses. Subcutaneous adipose tissue samples were taken from the tailhead of 9 multiparous Holstein cows, 27 ± 2.2 d (far-off) and 10 ± 1.5 d (close-up) before and 9 ± 0.3 d after calving (fresh). Blood samples were collected by coccygeal venipuncture 2 h before adipose sample collections. Body condition score (BCS) was assessed independently by 3 experienced technicians at every time point. Based on BCS loss intensity between the close-up and fresh period, cows were divided into 2 groups: low BCS loss (LBCSL, change in BCS <0.25 units, n = 5) and high BCS loss (HBCSL, change in BCS >0.25 units, n = 4). Although none of the LBCSL cows had a health event, all cows in the HBCSL group suffered from one or more clinical disorder (retained placenta, milk fever, or ketosis) in the transition period. The number of ATM was determined by immunohistochemistry, and expression of selected chemotactic and inflammatory genes was determined by reverse-transcription quantitative real-time PCR in subcutaneous adipose tissue samples. The proportion of ATM in subcutaneous adipose tissue increased in HBCSL during the postpartum period. The proportion of ATM was not associated with serum β-hydroxybutyrate or free fatty acid concentrations on the day of adipose tissue collection. The ATM infiltration in the fresh period was associated with local expression of the chemotactic genes, C-C motif chemokine ligand 22 (CCL22), osteopontin (SPP1), and the receptor for SPP1, cluster of differentiation 44 (CD44). This supports a potential chemotactic role of CCL22 and SPP1 for ATM in bovine adipose tissue. None of the genes encoding pro- or anti-inflammatory mediators, tumor necrosis factor (TNF), IL6, and IL10 were associated with the proportion of ATM. Our results indicate that ATM infiltration of subcutaneous adipose tissue is associated with body fat mobilization in early-lactation dairy cows and supports a role for ATM in the adaptation of adipose tissues to the metabolic challenges of the transition period.



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Effects of level of dietary cation-anion difference and duration of prepartum feeding on performance and metabolism of dairy cows

Publication date: Available online 7 June 2018
Source:Journal of Dairy Science
Author(s): C. Lopera, R. Zimpel, A. Vieira-Neto, F.R. Lopes, W. Ortiz, M. Poindexter, B.N. Faria, M.L. Gambarini, E. Block, C.D. Nelson, J.E.P. Santos
The objectives were to evaluate the effects of feeding diets with 2 levels of negative dietary cation-anion differences (DCAD) during the last 42 or 21 d of gestation on performance and metabolism in dairy cows. The hypothesis was that extending feeding from 21 to 42 d and reducing the DCAD from −70 to −180 mEq/kg of dry matter (DM) would not be detrimental to performance. Holstein cows at 230 d of gestation were blocked by parity prepartum (48 entering their second lactation and 66 entering their third or greater lactation) and 305-d milk yield, and randomly assigned to 1 of 4 treatments arranged as a 2 × 2 factorial. The 2 levels of DCAD, −70 or −180 mEq/kg of DM, and 2 feeding durations, the last 21 d (short) or the last 42 d (long) prepartum resulted in 4 treatments, short −70 (n = 29), short −180 (n = 29), long −70 (n = 28) and long −180 (n = 28). Cows in the short treatments were fed a diet with DCAD of +110 mEq/kg of DM from −42 to −22 d relative to calving. After calving, cows were fed the same diet and production and disease incidence were evaluated for 42 d in milk, whereas reproduction and survival was evaluated for 305 d in milk. Blood was sampled pre- and postpartum for quantification of metabolites and minerals. Reducing the DCAD linearly decreased prepartum DM intake between −42 and −22 d relative to calving (+110 mEq/kg of DM = 11.5 vs. −70 mEq/kg of DM = 10.7 vs. −180 mEq/kg of DM = 10.2 ± 0.4), and a more acidogenic diet in the last 21 d of the dry period reduced intake by 1.1 kg/d (−70 mEq/kg of DM = 10.8 vs. −180 mEq/kg of DM = 9.7 ± 0.5 kg/d). Cows fed the −180 mEq/kg of DM diet had increased concentrations of ionized Ca in blood on the day of calving (−70 mEq/kg of DM = 1.063 vs. −180 mEq/kg of DM = 1.128 ± 0.020 mM). Extending the duration of feeding the diets with negative DCAD from 21 to 42 d reduced gestation length by 2 d (short = 277.2 vs. long = 275.3 d), milk yield by 2.5 kg/d (short = 40.4 vs. long = 37.9 ± 1.0 kg/d) and tended to increase days open because of reduced pregnancy per artificial insemination (short = 35.0 vs. long = 22.6%). Results suggest that increasing the duration of feeding diets with negative DCAD from 21 to 42 d prepartum might influence milk yield and reproduction of cows in the subsequent lactation, although yields of 3.5% fat- and energy-corrected milk did not differ with treatments. Reducing the DCAD from −70 to −180 mEq/kg of DM induced a more severe metabolic acidosis, increased ionized Ca concentrations prepartum and on the day of calving, and decreased colostrum yield in the first milking, but had no effects on performance in the subsequent lactation. Collectively, these data suggest that extending the feeding of an acidogenic diet beyond 21 d is unnecessary and might be detrimental to dairy cows, and a reduction in the DCAD from −70 to −180 mEq/kg of DM is not needed.



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