Correlation Between Sagittal Balance and Mechanical Distal Junctional Failure in Degenerative Pathology of the Spine: A Retrospective Analysis

Study design Retrospective cohort study. Objectives This study aimed to investigate the failure of the caudal end of lumbar posterior fixation in terms of pre-operative and post-operative spinopelvic parameters, correction performed, demographic and clinical data. Methods The lumbar, thoraco-lumbar and lumbo-sacral posterior fixations performed with pedicle screws and rods in 2017-2019 were retrospectively analyzed. As 81% failures occurred within 4 years, an observational period of 4 years was chosen. The revision surgeries due to the failure in the caudal end were collected in the junctional group. Fixations which have not failed were gathered in the control group. The main spinopelvic parameters were measured for each patient on standing lateral radiographs with the software Surgimap. Demographic and clinical data were extracted for both groups. Results Among the 457 patients who met the inclusion criteria, the junctional group included 101 patients, who required a revision surgery. The control group collected 356 primary fixations. The two most common causes of revision surgeries were screws pullout (57 cases) and rod breakage (53 cases). SVA, PT, LL, PI-LL and TPA differed significantly between the two groups (P = .021 for LL, P < .0001 for all the others). The interaction between the two groups and the pre-operative and post-operative conditions was significant for PT, SS, LL, TK, PI-LL and TPA (P < .005). Sex and BMI did not affect the failure onset. Conclusions Mechanical failure is more likely to occur in patients older than 40 years with a thoraco-lumbar fixation where PT, PI-LL and TPA were not properly restored

RNAi-Based Strategies for Cyclooxygenase-2 Inhibition in Cancer

Cyclooxygenase-2 (COX-2) enzyme has been involved in the tumorigenesis and in the progression of colorectal cancer (CRC). The use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors has been proposed for the prevention and the treatment of this relevant neoplastic disease. In the light of an innovative alternative to these pharmacological approaches, we review here the possible strategies to achieve a strong and selective inhibition of COX-2 enzyme by using the mechanism of RNA Interference (RNAi) targeted against its mRNA. Anti-COX-2 siRNA molecules (siCOX-2) can be generated in CRC cells from short hairpin RNA (shRNA) precursors, delivered in vitro by a retroviral expression system, and induce a significant and stable silencing of overexpressed COX-2 in human colon cancer cells. As a safer alternative to viral approach, nonpathogenic bacteria (E. coli) can be engineered to invade eukaryotic cells and to generate siCOX-2 molecules in cancer cells. Moreover, the involvement of miRNAs in COX-2 posttranscriptional regulation opens up the possibility to exploit an endogenous silencing mechanism to knockdown overexpressed COX-2. Thus, these recent strategies disclose new challenging perspectives for the development of clinically compatible siRNA or miRNA capable of selectively inhibiting COX-2 enzyme

Cellular Prion Protein and Caveolin-1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

It has been reported that cellular prion protein (PrPc) is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1) participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST)-fusion proteins assay, we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11), by confocal microscopy analysis, flotation on density gradient, and coimmunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2) was triggered, suggesting that following translocations from rafts to caveolae or caveolaelike domains PrPc could interact with Cav-1 and induce signal transduction events

Adverse Events Capture Systems, Checklists and Teamwork as Relevant Tools to Reduce Complications and Increase Patients’ Safety in Spinal Surgery

Adverse events in Hospitals are often related to surgery and they represent a relevant problem in healthcare. Different approaches have been introduced during the last decade to address the problem of patient safety, especially in the surgical environment. The teamwork is crucial in all these actions which aim to decrease adverse events and improve clinical outcomes. We analyze in particular the use of adverse events capture systems in spinal surgery and the use of checklist systems, starting from the Surgical Safety Checklist introduced by the World Health Organization (WHO) in 2008

Spinal surgery complications: an unsolved problem—Is the World Health Organization Safety Surgical Checklist an useful tool to reduce them?

Abstract Purpose To investigate whether the World Health Organization Safety Surgical Checklist (SSC) is an effective tool to reduce complications in spinal surgery. Methods We retrospectively evaluated the clinical and radiological charts prospectively collected from patients who underwent a spinal surgery procedure from January 2010 to December 2012. The aim of this study was to compare the incidence of complications between two periods, from January to December 2010 (without checklist) and from January 2011 and December 2012 (with checklist), in order to assess the checklist's effectiveness. Results The sample size was 917 patients with an average of 30-month follow-up. The mean age was 52.88 years. The majority of procedures were performed for oncological diseases (54.4%) and degenerative diseases (39.8%). In total, 159 complications were detected (17.3%). The overall incidence of complications for trauma, infectious pathology, oncology, and degenerative disease was 22.2%, 19.2%, 18.4%, and 15.3%, respectively. No correlation was observed between the type of pathology and the complication incidence. We observed a reduction in the overall incidence of complications following the introduction of the SSC: In 2010 without checklist, the incidence of complications was 24.2%, while in 2011 and 2012, following the checklist introduction, the incidence of complications was 16.7% and 11.7%, respectively (mean 14.2%). Conclusions The SSC seems to be an effective tool to reduce complications in spinal surgery. We propose to extend the use of checklist system also to the preoperative and postoperative phases in order to further reduce the incidence of complications. Graphic abstract These slides can be retrieved under Electronic Supplementary Material

Carbon Fiber-Reinforced PolyEtherEtherKetone (CFR-PEEK) Instrumentation in Degenerative Disease of Lumbar Spine: A Pilot Study

: CFR-PEEK is gaining popularity in spinal oncological applications due to its reduction of imaging artifacts and radiation scattering compared with titanium, which allows for better oncological follow-up and efficacy of radiotherapy. We evaluated the use of these materials for the treatment of lumbar degenerative diseases (DDs) and considered the biomechanical potential of the carbon fiber in relation to its modulus of elasticity being similar to that of bone. Twenty-eight patients with DDs were treated using CRF-PEEK instrumentation. The clinical and radiographic outcomes were collected at a 12-month FU. Spinal fusion was evaluated in the CT scans using Brantigan scores, while the clinical outcomes were evaluated using VAS, SF-12, and EQ-5D scores. Out of the patients evaluated at the 12-month FU, 89% showed complete or almost certain fusion (Brantigan score D and E) and presented a significant improvement in all clinical parameters; the patients also presented VAS scores ranging from 6.81 ± 2.01 to 0.85 ± 1.32, EQ-5D scores ranging from 53.4 ± 19.3 to 85.0 ± 13.7, SF-12 physical component scores (PCSs) ranging from 29.35 ± 7.04 to 51.36 ± 9.75, and SF-12 mental component scores (MCSs) ranging from 39.89 ± 11.70 to 53.24 ± 9.24. No mechanical complications related to the implant were detected, and the patients reported a better tolerance of the instrumentation compared with titanium. No other series of patients affected by DD that was stabilized using carbon fiber implants have been reported in the literature. The results of this pilot study indicate the efficacy and safety of these implants and support their use also for spinal degenerative diseases

Impiego di oligonucleotidi antisenso diretti verso molecole coinvolte nella regolazione di processi fisio-patologici quali l'infiammazione e l'angiogenesi.

Dottorato di ricerca in biologia e fisiologia cellulare. A. a. 1998-99. Docente responsabile Vittorio Tomasi. Coordinatore Davide ZannoniConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Modification of proteins secreted by endothelial cells during modeled low gravity exposure

The exposure of the human body to microgravity, conditions that occurs during space flights, causes significant changes in the cardiovascular system. Many cell types have been involved in these changes, and the endothelium seems to play a major role. In endothelial cells (EC), it has been shown that modeled low gravity impairs nitric oxide synthesis, cell adhesion, extracellular matrix composition, cytoskeleton organization, cytokines, and growth factors secretion. Nevertheless, detailed analysis of EC physiological changes induced by microgravity exposure is still lacking. Secretome analysis is one of the most promising approaches for the identification of biomarkers directly related to the physiopathological cellular state. In this study, we analyzed in details the modifications of EC secretome by using umbilical vein endothelial (HUVE) cells exposed to modeled low gravity conditions. By adopting a two-dimensional (2-D) proteomic approach, in conjunction with a technique for the compression of the dynamic range of proteins, we observed that modeled low gravity exposure of HUVE cells affected the secretion of proteins involved in the regulation of cytoskeleton assembly. Moreover, by using Luminex® suspension array systems, we found that the low gravity condition decreased in ECs the secretion of some key pro-inflammatory cytokines, including IL-1α and IL-8, and of the pro-angiogenic factor bFGF. On the contrary, microgravity increase the secretion of two chemokines (Rantes and Eotaxin), involved in leukocytes recruitment