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1.
Luca Mazzone Ueli Moehrlen Nicole Ochsenbein‐Klble Luca Pontiggia Thomas Biedermann Ernst Reichmann Martin Meuli 《Journal of tissue engineering and regenerative medicine》2020,14(1):58-65
An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time‐mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo‐epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo‐epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available. 相似文献
2.
Elio Mazzone Felix Preisser Sebastiano Nazzani Zhe Tian Nicola Fossati Giorgio Gandaglia Andrea Gallina Denis Soulieres Derya Tilki Francesco Montorsi Shahrokh F. Shariat Fred Saad Alberto Briganti Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(2):105-113.e2
Background
Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM.Patients and Methods
Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs.Results
Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P < .001), and overall mortality–free survival was 12 versus 7 months (P < .001) for, respectively, RC and non-RC patients. In multivariable CRMs, lower CSM (hazard ratio = 0.48; P < .001) and lower overall mortality (hazard ratio = 0.49; P < .001) rates were recorded in RC patients. LND status did not affect CSM-free survival (13 vs. 10 months; P = .1). Cubic splines-derived cutoff of ≥ 13 number of removed nodes showed better CSM-free survival (20 vs. 11 months; P = .02) and reduced CSM in CRMs (hazard ratio = 0.67; P = .02).Conclusion
Our study validates the survival benefit of RC in mUCB and highlights the importance of more extensive LND. These findings may corroborate the hypothesis of potential cytoreductive effect of surgery in the context of metastatic disease. 相似文献3.
Silvia Morlino Annalucia Carbone Marco Ritelli Carmela Fusco Vincenzo Giambra Grazia Nardella Angelantonio Notarangelo Patrizio Panelli Gianluigi Mazzoccoli Nicoletta Zoppi Paola Grammatico Emma M Wade Marina Colombi Marco Castori Lucia Micale 《Human mutation》2019,40(10):1886-1898
Transforming growth factor β‐activated kinase 1 (TAK1) mediates multiple biological processes through the nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) and the mitogen‐activated protein kinase (MAPK) signaling pathways. TAK1 activation is tightly regulated by its binding partners (TABs). In particular, binding with TAB2 is crucial for cardiovascular development and extracellular matrix (ECM) homeostasis. In our previous work, we reported a novel multisystem disorder associated with the heterozygous TAB2 c.1398dup variant. Here, we dissect the functional effects of this variant in order to understand its molecular pathogenesis. We demonstrate that TAB2 c.1398dup considerably undergoes to nonsense‐mediated messenger RNA decay and encodes a truncated protein that loses its ability to bind TAK1. We also show an alteration of the TAK1 autophosphorylation status and of selected downstream signaling pathways in patients’ fibroblasts. Immunofluorescence analyses and ECM‐related polymerase chain reaction‐array panels highlight that patient fibroblasts display ECM disorganization and altered expression of selected ECM components and collagen‐related pathways. In conclusion, we deeply dissect the molecular pathogenesis of the TAB2 c.1398dup variant and show that the resulting phenotype is well explained by TAB2 loss‐of‐function. Our data also offer initial insights on the ECM homeostasis impairment as a molecular mechanism probably underlying a multisystem disorder linked to TAB2. 相似文献
4.
Stefan J. Cano Anna Mayhew Allan M. Glanzman Kristin J. Krosschell Kathryn J. Swoboda Marion Main Birgit F. Steffensen Carole Brard Franoise Girardot Christine A.M. Payan Eugenio Mercuri Elena Mazzone Bakri Elsheikh Julaine Florence Linda S. Hynan Susan T. Iannaccone Leslie L. Nelson Shree Pandya Michael Rose Charles Scott Reza Sadjadi Mackensie A. Yore Cynthia Joyce John T. Kissel 《Muscle & nerve》2014,49(3):422-430
Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49 :422–430, 2014 相似文献
5.
6.
Time‐varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: An EEG‐TMS study 下载免费PDF全文
7.
Jaume Tur Martínez Patrizio Petrone Alexander Axelrad Corrado P. Marini 《Cirugía espa?ola》2018,96(7):443-449
Introduction
TEG provides an in-vivo assessment of viscoelastic clot strength in whole blood compared with CCT, which may not reflect the influence of platelets. The aim of this study was to compare TEG vs. CCT in trauma patients stratified by mechanism of injury (MOI) and pre-existing coagulation status.Methods
A retrospective, observational study of 230 polytrauma patients admitted to a University Hospital Level 1 Trauma Center, with TEG and CCT on admission stratified by MOI: multiple trauma (MT), isolated traumatic brain injury (TBI) or MT+TBI. Statistical analysis included correlation between TEG and CCT in all groups and a subgroup analysis of anticoagulated patients. Data were analyzed with ANOVA, Spearman and lineal regression when appropriate. Statistical significance was accepted at P<0.05.Results
TEG was normal in 28.7%, hypercoagulable in 68.3%, hypocoagulable in 7%. There was no difference in TEG status among the groups. The coagulation status was not affected by age, ISS or shock. The CCT were abnormal in 63.6% of patients with normal TEG. Normal or hypercoagulable-TEG was found in 21/23 patients on Coumadin who had elevated INR and in 10/11 patients on NOAC. An analysis of the 23 patients on Coumadin stratified by INR showed a normal or hypercoagulable-TEG in 21/23 patients. Only 2 patients had a hypocoagulable-TEG. Mortality was 5.2% (58.3% severe TBI).Conclusions
TEG is more useful than CCT in polytrauma patients, including patients on anticoagulants. TBI could increase the incidence of hypercoagulability in trauma. CCT are not useful from the standpoint of treatment. 相似文献8.
Patrizio Petrone Cristina Magadán Álvarez D’Andrea Joseph Lee Cartagena Fahd Ali Collin E.M. Brathwaite 《Cirugía espa?ola》2018,96(5):250-259
Traumatic retroperitoneal injuries constitute a challenge for trauma surgeons. They usually occur in the context of a trauma patient with multiple associated injuries, in whom invasive procedures have an important role in the diagnosis of these injuries. The retroperitoneum is the anatomical region with the highest mortality rates, therefore early diagnosis and treatment of these lesions acquire special relevance. The aim of this study is to present current published scientific evidence regarding incidence, mechanism of injury, diagnostic methods and treatment through a review of the international literature from the last 70 years. In conclusion, this systematic review showed an increasing trend towards non-surgical management of retroperitoneal injuries. 相似文献
9.
Alessandro Nini Umberto Capitanio Alessandro Larcher Paolo Dell’Oglio Federico Dehò Nazareno Suardi Fabio Muttin Cristina Carenzi Massimo Freschi Roberta Lucianò Giovanni La Croce Alberto Briganti Renzo Colombo Andrea Salonia Alessandro Castiglioni Patrizio Rigatti Francesco Montorsi Roberto Bertini 《European urology》2018,73(5):793-799