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Unconventional platelet activation in COVID-19 (DOI 10.1111/jth.15575)
No full textFILE "patients and controls data" correspond to the row data of patients and controls (figures 1 and 2 and tables 1-3)
FILE "in vitro exp" correspond to the row data of in vitro experiments (figures 3, 4 and 5
HIV-1 env does not enable the development of protective broadly neutralizing antibodies is an experimental autoimmune encephalomyelitis mouse model
No full textDOI for this work is: 10.3389/fimmu.2021.771359
Published in 2021 by Lucia Lopalco et al.
Recent studies showed that immunological tolerance may restrict the development of Env-specific autoreactive broadly neutralizing antibodies. This evidence is consistent with the finding that Env immunization of a systemic lupus erythematosus (SLE) murine model produced antibodies that neutralize tier 2 HIV-1 strains. In this study, we address the possibility of eliciting neutralizing anti-Env antibodies in other autoimmune diseases such as multiple sclerosis (MS). While, as reported for SLE, we showed for the first time that a small number of HIV-1 negative, relapsing remitting MS patients exhibited antibodies with neutralizing properties, our attempts at inducing those antibodies in a EAE mouse model of MS failed. The success in eliciting Env-specific neutralizing antibodies might be related to the specific characteristics of the autoimmune disease, or it might rely in improving the vaccination design. Studies using mouse models are useful to gain insight in how HIV-specific neutralizing antibody responses are regulated in order to develop a protective HIV-1 vaccine. The raw data of each figure reported in the manuscript is reported here. In total we have 6 different files
R Status is a Relevant Prognostic Factor for Recurrence and Survival After Pancreatic Head Resection for Ductal Adenocarcinoma
No full textData refer to the paper doi: 10.1245/s10434-020-09467-6
Data were collected in a prospective database maintained at the Division of Pancreatic Surgery, San Raffaele Scientific Institute, Milan, Italy. Patients with a histologic diagnosis of PDAC in the head of the pancreas who underwent pancreatoduodenectomy or total pancreatectomy were eligible for the study. Only patients with a minimum follow-up period of 12 months were included unless they had died within 1 year after surgery because of tumor recurrenc
Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency
No full textTITLE: Efficacy and safety of anti-CD45–saporin as conditioning agent for RAG deficiency
Maria Carmina Castiello, Marita Bosticardo, Nicolò Sacchetti, Enrica Calzoni, Elena Fontana, Yasuhiro Yamazaki, Elena Draghici, Cristina Corsino , Ileana Bortolomai, Lucia Sereni, Hsin-Hui Yu, Paolo Uva, Rahul Palchaudhuri, David T. Scadden, Anna Villa, Luigi D. Notarangelo.
PMID: 32387109
Background: Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation.
Objectives: Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP).
Methods: Rag1-KO and Rag1-F971L mice, which represent models of severe combined immune deficiency and combined immune deficiency with immune dysregulation, respectively, were conditioned with CD45-SAP, CD45-SAP plus 2 Gy of total body irradiation (TBI), 2 Gy of TBI, 8 Gy of TBI, or no conditioning and treated by using transplantation with lineage-negative bone marrow cells from wild-type mice. Flow cytometry and immunohistochemistry were used to assess engraftment and immune reconstitution. Antibody responses to 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin were measured by ELISA, and presence of autoantibody was detected by microarray.
Results: Conditioning with CD45-SAP enabled high levels of multilineage engraftment in both Rag1 mutant models, allowed overcoming of B- and T-cell differentiation blocks and thymic epithelial cell defects, and induced robust cellular and humoral immunity in the periphery.
Conclusions: Conditioning with CD45-SAP allows multilineage engraftment and robust immune reconstitution in mice with either null or hypomorphic Rag mutations while preserving thymic epithelial cell homeostasis
Therapeutic advantages of combined gene/cell therapy strategies in a murine model of GM2 gangliosidosis
No full textGenetic deficiency of β-N-acetylhexosaminidase (Hex) functionality leads to accumulation of GM2 ganglioside in Tay-Sachs disease and Sandhoff disease (SD), which presently lack approved therapies. Current experimental gene therapy (GT) approaches with adeno-associated viral vectors (AAVs) still pose safety and efficacy issues, supporting the search for alternative therapeutic strategies. Here we leveraged the lentiviral vector (LV)-mediated intracerebral (IC) GT platform to deliver Hex genes to the CNS and combined this strategy with bone marrow transplantation (BMT) to provide a timely, pervasive, and long-lasting source of the Hex enzyme in the CNS and periphery of SD mice. Combined therapy outperformed individual treatments in terms of lifespan extension and normalization of the neuroinflammatory/neurodegenerative phenotypes of SD mice. These benefits correlated with a time-dependent increase in Hex activity and a remarkable reduction in GM2 storage in brain tissues that single treatments failed to achieve. Our results highlight the synergic mode of action of LV-mediated IC GT and BMT, clarify the contribution of treatments to the therapeutic outcome, and inform on the realistic threshold of corrective enzymatic activity. These results have important implications for interpretation of ongoing experimental therapies and for design of more effective treatment strategies for GM2 gangliosidosis
Inhibiting glycolysis rescues memory impairment in an intellectual disability Gdi1-null mouse
No full textthe tables are the data to compute the graphs showed in the pubblication, doi: 10.1016/j.metabol.2020.15446
Blood neurofilament light chain and total tau levels at admission predict death in COVID-19 patients
No full textRaw data of the publication with the DOI 10.1007/s00415-021-10595-6
Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
No full textKinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular
cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children. Titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. doi: 10.3390/vaccines9030260
Efficacy of Endoscopic Ultrasound-Guided Ablation with the HybridTherm Probe in Locally Advanced or Borderline Resectable Pancreatic Cancer: A Phase II Randomized Controlled Trial.
No full textdoi: 10.3390/cancers13184512.
The National Comprehensive Cancer Network (NCCN) subclassified the “locallyadvanced” pancreatic ductal adenocarcinoma (PDAC) into borderline-resectable and locally-advanced categories and established the 4- or 6-months induction chemotherapy as standard of care to control and eventually downsize the locally advanced PDAC and select the borderline resectable PDAC at higher risk of non-radical resection. However, chemotherapy and radiotherapy regimens in locally advanced PDAC have only led to a marginal survival improvement, with a 5-year survival rate less than 8% only. Recently, tumour local thermal ablation has been investigated in PDAC, hypothesizing that it may add local efficacy to the chemotherapy systemic activity, inducing changes of the tumour microenvironment and increased intra-tumour drug uptake and efficacy. We recently demonstrated that endoscopic ultrasound-guided local thermal ablation with HybridTherm-Probe significantly reduced the tumour volume in locally advanced PDAC. In this phase II/III randomized controlled trial, originally designed as multicentric, we investigated the efficacy of local thermal ablation with the HybridTherm probe under endoscopic ultrasound-guidance (EUS) as first-line complement to chemotherapy (HTP-CT arm) versus standard first-line chemotherapy alone (CT arm), in locally advanced and borderline resectable PDAC. Evaluation of the 6-months progression-free survival (PFS) rate was the primary endpoint. A sample size of 33 patients per arm in the phase II trial was calculated to verify a 20% improved 6-months PFS rate adding the HybridTherm ablation. Up to three EUS-guided ablation could be performed. Restaging was planned at 2-months, 4-months and 6-months after chemotherapy onset, assessing the response to therapy using the Choi criteria and tumor volume at contrast-enhanced multidetector CT scan and magnetic resonance imaging, and the serum levels of CA19-9. Between November 2014 and June 2019, we randomized 17 patients and 20 patients to HTP-CT arm and CT arm, respectively. Because of unforeseen problems in patients’ enrolment in other centres and withdrawal of the HybridTherm probe by the manufacturer in 2020 as consequence, it was established to stop enrolment and perform the phase II trial analysis as monocentric despite the smaller sample size than required. Baseline and chemotherapy-related features were evenly balanced. Although not significantly, we found an improved 6-month PFS rate in the HTP-CT arm over CT arm (41.2% vs. 30%), as well as with regard to the decrease ≥50% of serum CA19.9 levels (75% vs. 64.3%) and reduction of tumor volume (64.3% vs. 47.1%). However, no impact on the resection rate has been observed and the overall survival was similar between the two arms. As the study, originally designed to be multi-centric, is underpowered these results suggest further investigation on EUS-guided thermal ablation in selected patients with localized disease
Long-Term Survivors after Upfront Resection for Pancreatic Ductal Adenocarcinoma: An Actual 5-Year Analysis of Disease-Specific and Post-Recurrence Survival
No full textData refer to the paper doi: 10.1245/s10434-021-10401-7
Data refer to patients who underwent upfront surgical resection for pancreatic ductal adenocarcinoma between 2009 and 201