Anatomically reduced fixation should always be considered when treating B and C proximal epiphyseal humeral fractures

Background Proximal humeral fractures are commonly observed in elderly patients. Management of these injuries is controversial. Literature comparing locking plate fixation, arthroplasty, and conservative treatments show no clear advantages for any of these management strategies. Thus far, no study has considered anatomically reduced fractures obtained after locking plate treatment. To clarify the best surgical procedure in middle-aged patients, we considered outcomes and major complications leading to surgical revision following an anatomically reduced fracture fixed with locking plate and reverse shoulder arthroplasty (RSA) in the treatment of type B/C fractures in patients between 50 and 75 years of age. Methods This is a retrospective study including 59 patients between 50 and 75 years of age with type B/C proximal humeral fracture treated with RSA or with locking plate fixation (resulting in an anatomical reduction) between January 2010 and December 2018. Preoperative radiographs and computed tomography (CT) were evaluated in all patients. Clinical and radiologic follow-up was performed using range of motion (ROM), the Constant-Murley Score (CMS), the Oxford Shoulder Score (OSS), the Simple Shoulder Test (SST), the Subjective Shoulder Value (SSV), and visual analog scale (VAS). Major complications were considered. Results In the plate fixation group, ROM, CMS, SST, and VAS were higher than in the RSA group. Lower complication rates compared with the literature were observed in both groups. Anatomically reduced fracture fixed with plate and screw could outperform RSA in terms of outcome. In second-level centers where traumatology is performed by surgeons with great expertise in upper limb trauma, the choice between plate fixation and reverse arthroplasty should be made during surgery. Conclusion Anatomically reduced fractures showed better outcomes compared with RSA in type B/C fractures. Surgeons should always try to perform a reduction of the fracture in order to understand if a plate fixation could be feasible. If it is impossible to perform an anatomical reduction, we suggest to consider RSA. This is a retrospective observational study

Treatment with a GSK-3β/HDAC Dual Inhibitor Restores Neuronal Survival and Maturation in an In Vitro and In Vivo Model of CDKL5 Deficiency Disorder

open11noFunding: This research was funded by the Telethon foundation (grant number GGP19045, awarded to E.C.), and by the Italian parent association “CDKL5 insieme verso la cura” (to E.C.).Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a rare neurodevelopmental disorder characterized by early-onset seizures and severe cognitive, motor, and visual impairments. To date there are no therapies for CDKL5 deficiency disorder (CDD). In view of the severity of the neurological phenotype of CDD patients it is widely assumed that CDKL5 may influence the activity of a variety of cellular pathways, suggesting that an approach aimed at targeting multiple cellular pathways simultaneously might be more effective for CDD. Previous findings showed that a single-target therapy aimed at normalizing impaired GSK-3β or histone deacetylase (HDAC) activity improved neurodevelopmental and cognitive alterations in a mouse model of CDD. Here we tested the ability of a first-in-class GSK-3β/HDAC dual inhibitor, Compound 11 (C11), to rescue CDD-related phenotypes. We found that C11, through inhibition of GSK-3β and HDAC6 activity, not only restored maturation, but also significantly improved survival of both human CDKL5-deficient cells and hippocampal neurons from Cdkl5 KO mice. Importantly, in vivo treatment with C11 restored synapse development, neuronal survival, and microglia over-activation, and improved motor and cognitive abilities of Cdkl5 KO mice, suggesting that dual GSK-3β/HDAC6 inhibitor therapy may have a wider therapeutic benefit in CDD patients.openLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, ElisabettaLoi, Manuela; Gennaccaro, Laura; Fuchs, Claudia; Trazzi, Stefania; Medici, Giorgio; Galvani, Giuseppe; Mottolese, Nicola; Tassinari, Marianna; Giorgini, Roberto Rimondini; Milelli, Andrea; Ciani, Elisabett

Molecular profiling of single circulating tumor cells with diagnostic intention

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance

Molecular profiling of single circulating tumor cells with diagnostic intention

Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of >90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

PLANT FOR DISPOSING OF USED TYRES \ua0

A plant (1) for transforming into secondary raw material, or disposing of, used tyres (P), made of rubber or other carbon matrices, comprises at least one pyrolysis chamber (6), wherein said used tyres (P) are subjected to pyrolysis treatment, said tyres (P) being conveyed to said at least one pyrolysis chamber (6) by means of at least one supplying device (5) that receives the tyres (P) from a first conveying device (3), at least one hydraulic seal element (9) associated with said at least one supplying device (5) and heating means (16) for heating said at least one pyrolysis chamber (6). The at least one supplying device (5) comprises a second conveying device (7) that receives the tyres (P) from the first conveying device (3) and conveys the tyres (P) through said at least one hydraulic seal element (9) and along at least one supplying conduit (11) that extends prevalently vertically until it reaches an inlet zone (12) of the at least one pyrolysis chamber (6), where said tyres (P) are released by said second conveying device (7) and drop by gravity into said pyrolysis chamber (6) through an inlet opening (13). The inlet opening (13) is provided with a movable closing element (14), that can rotate around a hinge element (16) between a closed position and an open position and an end portion (15) of the at least one supplying conduit (11), in contact with the at least one pyrolysis chamber (6), is made of thermally insulating material. The movable closing element (14) and the end portion (15) in thermally insulating material minimise the transmission of heat to the hydraulic seal element. Below an openable bottom (28) of the pyrolysis chamber (6) a hopper (22) is arranged that is suitable for conveying solid residual materials of the pyrolysis treatment to a shredding device (23), said hopper (22) being provided with pushing means (32) arranged for pushing to the shredding device (23) solid residues that accumulate on the walls of the hopper (22)

PLANT FOR DISPOSING OF USED TYRES

A plant (1) for transforming into secondary raw material, or disposing of, used tyres (P), made of rubber or other carbon matrices, comprises at least one pyrolysis chamber (6), wherein said used tyres (P) are subjected to pyrolysis treatment, said tyres (P) being conveyed to said at least one pyrolysis chamber (6) by means of at least one supplying device (5) that receives the tyres (P) from a first conveying device (3), at least one hydraulic seal element (9) associated with said at least one supplying device (5) and heating means (16) for heating said at least one pyrolysis chamber (6). The at least one supplying device (5) comprises a second conveying device (7) that receives the tyres (P) from the first conveying device (3) and conveys the tyres (P) through said at least one hydraulic seal element (9) and along at least one supplying conduit (11) that extends prevalently vertically until it reaches an inlet zone (12) of the at least one pyrolysis chamber (6), where said tyres (P) are released by said second conveying device (7) and drop by gravity into said pyrolysis chamber (6) through an inlet opening (13). The inlet opening (13) is provided with a movable closing element (14), that can rotate around a hinge element (16) between a closed position and an open position and an end portion (15) of the at least one supplying conduit (11), in contact with the at least one pyrolysis chamber (6), is made of thermally insulating material. The movable closing element (14) and the end portion (15) in thermally insulating material minimise the transmission of heat to the hydraulic seal element. Below an openable bottom (28) of the pyrolysis chamber (6) a hopper (22) is arranged that is suitable for conveying solid residual materials of the pyrolysis treatment to a shredding device (23), said hopper (22) being provided with pushing means (32) arranged for pushing to the shredding device (23) solid residues that accumulate on the walls of the hopper (22)

Crop Systems, Quality and Protection of Diplotaxis tenuifolia

Perennial wall-rocket (Diplotaxis tenuifolia (L.) D.C.) is a herbaceous plant belonging to the Brassicaceae with a cosmopolitan distribution. Traditionally harvested as a spontaneous herb, today it is a crop species of increasing importance after the diffusion of the ready-to-use salads in the vegetable retail markets. Besides relevance as a food crop, its consumption is prompted by consideration in the traditional medicine of several peoples in the native areas of the Mediterranean and western Asia based on recognized health beneficial effects. In fact, the leaves have notable nutritional properties related to their contents of glucosinolates and some antioxidant compounds, such as vitamin C and flavonoids, which entitle their dietary inclusion for the prevention of cancer and cardiovascular diseases. This paper provides an overview on aspects concerning the biology, crop management, nutritional properties, industrial processing and uses of perennial wall-rocket

Crop Systems, Quality and Protection of Diplotaxis tenuifolia

Perennial wall-rocket (Diplotaxis tenuifolia (L.) D.C.) is a herbaceous plant belonging to the Brassicaceae with a cosmopolitan distribution. Traditionally harvested as a spontaneous herb, today it is a crop species of increasing importance after the diffusion of the ready-to-use salads in the vegetable retail markets. Besides relevance as a food crop, its consumption is prompted by consideration in the traditional medicine of several peoples in the native areas of the Mediterranean and western Asia based on recognized health beneficial effects. In fact, the leaves have notable nutritional properties related to their contents of glucosinolates and some antioxidant compounds, such as vitamin C and flavonoids, which entitle their dietary inclusion for the prevention of cancer and cardiovascular diseases. This paper provides an overview on aspects concerning the biology, crop management, nutritional properties, industrial processing and uses of perennial wall-rocke