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Aim To evaluate tunnel positioning on radiographs in singlebundle (SB) and double-bundle (DB) anterior cruciate ligament (ACL) reconstruction, to evaluate if measurement is accurate and reproducible. Methods Radiographs of 30 SB and 30 DB ACL reconstruction were reviewed by two examiners who measured tunnel positioning with the quadrant method on the femur (a=depth, b=height) and the Amis and Jakob method on the tibia. Intra- and inter-observer reliability were evaluated with intra-class correlation coefficient (ICC). Results A radiographic analysis was completed in all patients in a SB-group and in 27 in a DB-group (p0.05). Intra-observer reliability was almost perfect on femoral (ICC: a=0.85, b=0.83) and tibial (ICC=0.87) side in the SB-group. In the DB-group, it was almost perfect for tibial anteromedial (AM) and posterolateral (PL) bundles (ICC: AM=0.84, PL=0.81) and for femoral PL bundle (ICC: a=0.83, b=0.82), and substantial for femoral AM bundle (ICC: a=0.78, b=0.74). Inter-observer reliability was almost perfect on tibial (ICC=0.81) and femoral (ICC: a=0.81, b=0.87) side in the SB-group, and substantial on tibial (ICC: AM=0.71, PL=0.77) and femoral (ICC: AM a=0.73, b=0.78; PL a=0.74, b=0.76) side in the DB-group. Standard deviation (SD) was low (±9%) with respect to the centre of tunnel(s). Conclusion The quadrant method and the Amis and Jakob method are accurate and reproducible measurement methods. Also, as SD was low, an outside-in approach with a front-entry guide, which is free-hand positioned, can be postulated as a reliable method to locate the femoral tunnel in SB reconstruction and the AM bundle in DB reconstruction.

Contains fulltext : 208133.pdf (Publisher’s version ) (Closed access) Background: Localized-type tenosynovial giant cell tumor (TGCT) is a rare, neoplastic disease with only limited data supporting treatment protocols. We describe treatment protocols and evaluate their oncological outcome, complications, and functional results in a large multicenter cohort of patients. A secondary study aim was to identify factors associated with local recurrence after surgical treatment. Methods: Patients with histologically proven localized TGCT of a large joint were included if they had been treated between 1990 and 2017 in 1 of 31 tertiary sarcoma centers. Of 941 patients with localized TGCT, 62% were female. The median age at initial treatment was 39 years, and the median duration of follow-up was 34 months. Sixty-seven percent of the tumors affected the knee, and the primary treatment at the tertiary center was 1-stage open resection in 73% of the patients. Proposed factors for predicting a first local recurrence after treatment in the tertiary center were tested in a univariate analysis, and those that demonstrated significance were subsequently included in a multivariate analysis. Results: The localized TGCT recurred in 12% of all cases, with local-recurrence-free rates at 3, 5, and 10 years of 88%, 83%, and 79%, respectively. The strongest factor for predicting recurrent disease was a prior recurrence (p < 0.001). Surgical treatment decreased pain and swelling in 71% and 85% of the patients, respectively, and such treatment was associated with complications in 4% of the patients. Univariate and multivariate analyses of the patients who had not undergone therapy previously yielded positive associations between local recurrence and a tumor size of >= 5 cm versus

Although multidisciplinary therapies have improved local control and overall survival in Ewing sarcoma (ES), the prognosis of pelvic lesions remains markedly worse than that of limb ES.We retrospectively evaluated the influence of the type of local treatment, margins, necrosis and sacrum involvement on overall survival (OS) and disease-free survival (DFS) in a series of 21 non-metastatic pelvic ES.The average follow-up was 46.3 months (range 3-156). Only one patient had recurrence, at 11 months after surgery. Eight patients showed pulmonary metastasis and five showed bone metastases. Necrosis was the only significant prognostic factor for overall survival at 5 years (p=0.0132) and disease-free survival (p=0.0086). Overall survival at 5 years was 40.1%.Local control in pelvic Ewing sarcoma is comparable for patients treated with surgery (S), surgery plus radiotherapy (S/RT), or definitive radiotherapy (RT). The combination of surgery plus radiotherapy could be indicated in cases of large tumor, a poor necrosis response (90%), or an inadequate margin with involvement of the sacrum. A poor response to neoadjuvant therapy is a significant risk factor for both local control and overall survival.

The Toll-interleukin 1 receptor superfamily includes the genes interleukin 1 receptor-like 1 (IL1RL1), Toll like receptors (TLRs), myeloid differentiation primary-response 88 (MyD88), and MyD88 adaptor-like (TIRAP). This study describes the interaction between MyD88, TIRAP and IL1RL1 against Helicobacter pylori infection. Cases and controls were genotyped at the polymorphic sites MyD88 rs6853, TIRAP rs8177374 and IL1RL1 rs11123923. The results show that specific combinations of IL1RL1-TIRAP (AA-CT; P: 2,8 × 10–17) and MyD88-TIRAP-IL1RL1 (AA-CT-AA; P: 1,4 × 10–8) – but not MyD88 alone—act synergistically against Helicobacter pylori. Nuclear magnetic resonance (NMR) clearly discriminates cases from controls by highlighting significantly different expression levels of several metabolites (tyrosine, tryptophan, phenylalanine, branched-chain amino acids, short chain fatty acids, glucose, sucrose, urea, etc.). NMR also identifies the following dysregulated metabolic pathways associated to Helicobacter pylori infection: phenylalanine and tyrosine metabolism, pterine biosynthesis, starch and sucrose metabolism, and galactose metabolism. Furthermore, NMR discriminates between the cases heterozygous at the IL1RL1 locus from those homozygous at the same locus. Heterozygous patients are characterized by high levels of lactate, and IL1RL1—both associated with anti-inflammatory activity—and low levels of the pro-inflammatory molecules IL-1β, TNF-α, COX-2, and IL-6.

Formyl peptide receptors (FPRs) are cell surface pattern recognition receptors (PRRs), belonging to the chemoattractant G protein-coupled receptors (GPCRs) family. They play a key role in the innate immune system, regulating both the initiation and the resolution of the inflammatory response. FPRs were originally identified as receptors with high binding affinity for bacteria or mitochondria N-formylated peptides. However, they can also bind a variety of structurally different ligands. Among FPRs, formyl peptide receptor-like 1 (FPRL1) is the most versatile, recognizing N-formyl peptides, non-formylated peptides, and synthetic molecules. In addition, according to the ligand nature, FPRL1 can mediate either pro- or anti-inflammatory responses. Hp(2-20), a Helicobacter pylori-derived, non-formylated peptide, is a potent FPRL1 agonist, participating in Helicobacter pylori-induced gastric inflammation, thus contributing to the related site or not-site specific diseases. The aim of this review is to provide insights into the role of FPRs in H. pylori-associated chronic inflammation, which suggests this receptor as potential target to mitigate both microbial and sterile inflammatory diseases.

Urea cycle disorders (UCD) are inherited defects in clearance of waste nitrogen with high morbidity and mortality. Novel and more effective therapies for UCD are needed. Studies in mice with constitutive activation of autophagy unravelled Beclin‐1 as druggable candidate for therapy of hyperammonemia. Next, we investigated efficacy of cell‐penetrating autophagy‐inducing Tat‐Beclin‐1 (TB‐1) peptide for therapy of the two most common UCD, namely ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL) deficiencies. TB‐1 reduced urinary orotic acid and improved survival under protein‐rich diet in spf‐ash mice, a model of OTC deficiency (proximal UCD). In AslNeo/Neo mice, a model of ASL deficiency (distal UCD), TB‐1 increased ureagenesis, reduced argininosuccinate, and improved survival. Moreover, it alleviated hepatocellular injury and decreased both cytoplasmic and nuclear glycogen accumulation in AslNeo/Neo mice. In conclusion, Beclin‐1‐dependent activation of autophagy improved biochemical and clinical phenotypes of proximal and distal defects of the urea cycle., Using mice with constitutive activation of autophagy and treating mice deficient for ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL) with the autophagy inducing Tat‐Beclin‐1 (TB‐1), this study shows that Beclin‐1‐dependent activation of autophagy improves the phenotypes of proximal and distal defects of the urea cycle.

Branched-chain amino acids (BCAAs) include leucine, isoleucine, and valine. Mammalians cannot synthesize these amino acids de novo and must acquire them through their diet. High levels of BCAAs are associated with insulin resistance; type 2 diabetes; obesity; and non-metabolic diseases, including several forms of cancer. BCAAs—in particular leucine—activate the rapamycin complex1 mTORC1, which regulates cell growth and metabolism, glucose metabolism and several more essential physiological processes. Diets rich in BCAAs are associated with metabolic diseases (listed above), while diets low in BCAAs are generally reported to promote metabolic health. As for the dysregulation of the metabolism caused by high levels of BCAAs, recent studies propose that the accumulation of acyl-carnitine and diacyl-CoA in muscles alters lipid metabolism. However, this suggestion is not broadly accepted. On clinical grounds, pre- and post-operative metabolic profiles of candidate patients for bariatric surgery are being used to select the optimal procedure for each individual patient.

Bacterial biofilm provides bacteria with resistance and protection against conventional antimicrobial agents and the host immune system. Bacteriophages are known to move across the biofilm to make it permeable to antimicrobials. Mineral hydroxyapatite (HA) can improve the lytic activity of bacteriophages, and, together with eicosanoic acid (C20:0), can destroy the biofilm structure. Here, we demonstrate the efficacy of the combined use of phage, HA and C20:0 against Xanthomonas campestris pv campestris (Xcc) biofilm. We used nuclear magnetic resonance (NMR)-based metabolomics to investigate the molecular determinants related to the lytic action, aiming at identifying the metabolic pathways dysregulated by phage treatment. Furthermore, we identified specific markers (amino acids, lactate and galactomannan) which are involved in the control of biofilm stability. Our data show that Xccφ1, alone or in combination with HA and C20:0, interferes with the metabolic pathways involved in biofilm formation. The approach described here might be extended to other biofilm-producing bacteria.