L'anatomia endodontica dei secondi molari superiori: ricerca ex vivo

Aim: of the present study was to deter- mine anatomic complexities which can be seen in maxillary second molars, with a specific attention to the presence of MB2 (second mesio-buccal) canals. Methodology: 50 maxillary second molars, which had been extracted for periodontal reasons, were selected for the study, following strict exclusion cri- teria. After determining the different roots, only the mesio-buccal one was examined. Location and number of canals were determined (i) after a normal access cavity, (ii) after a wider removal of dentine from the chamber floor, and (iii) after sectioning the root 4 mm be- low the cementum-enamel junction. Data were collected and analyzed. Results: MB2 canals were present in 44% of the examined teeth (20% of ca- ses showed Weine 2 configuration, while the remaining 24% showed Weine 3 configuration). It was possible to estabilish patency in MB2 canals only in 28% of cases. Conclusions: MB2 canals are often present in maxillary second molars, being individuated in nearly half cases. This possibility and the presence of an indipendent apex make the research of MB2 canals mandatory during the endodontic treatment

SAT0166 BIOMARKERS OF B-CELL DEPLETION AND RESPONSE IN A RANDOMIZED, CONTROLLED TRIAL OF OBINUTUZUMAB FOR PROLIFERATIVE LUPUS NEPHRITIS

Background:Incomplete B-cell and plasmablast depletion, as measured using highly sensitive flow cytometry (HSFC), is associated with lower response rates following rituximab in SLE [1]. Enhanced B-cell depletion with the type II anti-CD20 mAb obinutuzumab resulted in increased renal responses in proliferative lupus nephritis (LN) in the NOBILITY trial (NCT02550652) and will be further evaluated in the Phase 3 REGENCY trial (NCT04221477).Objectives:To measure peripheral B-cells, B-cell subsets (naïve, memory and plasmablast) and B-cell activating factor (BAFF) levels and to assess associations between B-cell depletion and renal response in LN patients in a clinical trial of obinutuzumab.Methods:126 patients with active Class III/IV LN were randomized to obinutuzumab or placebo infusions in combination with mycophenolate and glucocorticoids. Peripheral B-cells were measured using a HSFC method with a lower limit of quantitation of 0.441 cells/μL. Serum levels of BAFF were evaluated using ELISA. Sustained depletion was defined by total B-cells below the limit of detection at both weeks 24 and 52. Renal response definitions from Phase 2 NOBILITY and Phase 3 REGENCY trials were used.Results:Obinutuzumab resulted in rapid and complete depletion of total B-cells, memory and naïve B-cells, and plasmablasts from peripheral blood, with 88% of obinutuzumab patients depleted to 15% from baseline SCr, and 15% from baseline and urinary RBCs not increased > 50% from baseline66%***45%*29%REGENCY complete responseUPCR 25% from baseline SCr69%**45%31%REGENCY overall responseCRR or ≥ 50% reduction in UPCRb with SCr not increased > 25% from baseline84%***55%50%* P < 0.2 vs. placebo group.** P < 0.05 vs. placebo group.*** P < 0.001 vs. placebo group.aEleven patients in the obinutuzumab group with insufficient data to determine depletion status were excluded.b≥ 50% reduction in UPCR to a value < 1 (< 3 if the baseline UPCR was ≥ 3).Acknowledgments :This study was funded by F. Hoffmann-La Roche.Disclosure of Interests: :Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Philippe Rémy: None declared, Luis Fernando Quintana Porras: None declared, Laurent Chiche: None declared, Dominique Chauveau: None declared, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Thomas Schindler Employee of: F. Hoffmann-La Roche, Jay Garg Employee of: Genentech, Matthew D. Cascino Employee of: Genentech, Zahir Amoura Grant/research support from: GSK, Roche, Consultant of: GSK, Astra Zeneca, Amgen, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Cary Michael Donna Looney Employee of: Genentech, Dario Roccatello: None declare

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

sem informaçãoThe epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant91sem informaçãosem informaçãosem informaçã

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis

BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (CPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6,12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression >= 0.01 expression units (termed FCRL5(hi)) exhibited significantly higher CR rates at 6,12, and 18 months as compared with FCRL5(lo) subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study

Purpose: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. Methods: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. Results: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends’ relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. Conclusions: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. Level of evidence IV: Evidence obtained from multiple time series analysis such as case studies

Lateralizing Value of Interictal Spikes on Overnight Sleep-EEG Studies in Temporal Lobe Epilepsy

Purpose: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. Methods: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free ≤24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. Results: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (<95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. Conclusions: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66154/1/j.1528-1157.1999.tb02044.x.pd

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study

Purpose: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. Methods: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. Results: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends\u2019 relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. Conclusions: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as\ua0prevention strategies for EDs. Level of evidence IV: Evidence obtained from multiple time series analysis such as case studies

Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Since 1999, patients presenting with brain metastases (BM) from breast cancer (BC) are treated in our institution with a carmustine (BCNU) - methotrexate (MTX) combination. We report here our clinical experience regarding this combination.</p> <p>Patients and Methods</p> <p>Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity.</p> <p>Results</p> <p>50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5). Median number of cycles was 3 (1-20). There were 11 objective responses (23% [95%CI 12-37]) among 48 evaluable patients. Median progression-free survival and overall survival (OS) were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis.</p> <p>Conclusions</p> <p>This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.</p