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"Ferrari, Davide"
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Star wars. Episode IV
\"Capturing the galaxy-spanning action of A New Hope, experience Episode IV as a beautiful graphic novel combining the epic wonder of Star Wars with streamlined, young-reader friendly designs. This all-ages graphic novel is a must-read for longtime fans and a great introduction for newcomers!\"-- Provided by publisher.
Book
Detection of COVID-19 Infection from Routine Blood Exams with Machine Learning: A Feasibility Study
The COVID-19 pandemia due to the SARS-CoV-2 coronavirus, in its first 4 months since its outbreak, has to date reached more than 200 countries worldwide with more than 2 million confirmed cases (probably a much higher number of infected), and almost 200,000 deaths. Amplification of viral RNA by (real time) reverse transcription polymerase chain reaction (rRT-PCR) is the current gold standard test for confirmation of infection, although it presents known shortcomings: long turnaround times (3-4 hours to generate results), potential shortage of reagents, false-negative rates as large as 15-20%, the need for certified laboratories, expensive equipment and trained personnel. Thus there is a need for alternative, faster, less expensive and more accessible tests. We developed two machine learning classification models using hematochemical values from routine blood exams (namely: white blood cells counts, and the platelets, CRP, AST, ALT, GGT, ALP, LDH plasma levels) drawn from 279 patients who, after being admitted to the San Raffaele Hospital (Milan, Italy) emergency-room with COVID-19 symptoms, were screened with the rRT-PCR test performed on respiratory tract specimens. Of these patients, 177 resulted positive, whereas 102 received a negative response. We have developed two machine learning models, to discriminate between patients who are either positive or negative to the SARS-CoV-2: their accuracy ranges between 82% and 86%, and sensitivity between 92% e 95%, so comparably well with respect to the gold standard. We also developed an interpretable Decision Tree model as a simple decision aid for clinician interpreting blood tests (even off-line) for COVID-19 suspect cases. This study demonstrated the feasibility and clinical soundness of using blood tests analysis and machine learning as an alternative to rRT-PCR for identifying COVID-19 positive patients. This is especially useful in those countries, like developing ones, suffering from shortages of rRT-PCR reagents and specialized laboratories. We made available a Web-based tool for clinical reference and evaluation (This tool is available at https://covid19-blood-ml.herokuapp.com/).
Journal Article
Esophageal Lipoma and Liposarcoma: A Systematic Review
Background
Esophageal lipomatous tumors, also reported as fibrovascular polyp, fibrolipoma, angiolipoma, and liposarcoma, account for less than 1% of all benign mesenchymal submucosal tumors of the esophagus. Clinical presentation and therapy may differ based on location, size, and morphology. A comprehensive and updated systematic review of the literature is lacking.
Methods
A systematic review of the literature was performed according to PRISMA guidelines. Pubmed, Embase, Cochrane, and Medline databases were consulted using MESH keywords. Non-English written articles and abstracts were excluded. Sex, age, symptoms at presentation, diagnosis, tumor location and size, surgical approach and technique of excision, pathology, and morphology were extracted and recorded in an electronic database.
Results
Sixty-seven studies for a total of 239 patients with esophageal lipoma or liposarcoma were included in the qualitative analysis. Among 176 patients with benign lipoma, the median age was 55. The main symptoms were dysphagia (64.2%), transoral polyp regurgitation (32.4%), and globus sensation (22.7%). The majority of lipomas (85.7%) were intraluminal polyps, with a stalk originating from the upper esophagus. Overall, 165 patients underwent excision of the mass through open surgery (65.5%), endoscopy (27.9%), or laparoscopy/thoracoscopy (3.6%). Only 5 (3%) of patients required esophagectomy. Of the 11 untreated patients with an intraluminal polyp, 7 died from asphyxia. Overall, liposarcoma was diagnosed in 63 patients, and 12 (19%) underwent esophagectomy.
Conclusion
Esophageal lipomatous tumors are rare but potentially lethal when are intraluminal and originate from the cervical esophagus. Modern radiological imaging has improved diagnostic accuracy. Minimally invasive transoral and laparoscopic/thoracoscopic techniques represent the therapeutic approach of choice.
Journal Article
Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis
Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments.
Journal Article
Six to 12-year outcomes of magnetic sphincter augmentation for gastroesophageal reflux disease
The magnetic sphincter augmentation (MSA) device has been proven safe and effective in controlling typical reflux symptoms and esophageal acid exposure for up to 6-year follow-up. Longer term outcomes have not been reported yet. A prospectively maintained database was reviewed to assess long-term safety and efficacy of the laparoscopic MSA procedure at a single referral center. Gastro-Esophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL), use of proton-pump inhibitors (PPI), and esophageal acid exposure were compared to baseline. Favorable outcomes were defined as ≥ 50% improvement of GERD-HRQL total score and PPI discontinuation. Between March 2007 and March 2020, 335 patients met the study inclusion criteria, and 124 of them were followed from 6 to 12 years after surgery (median 9 years, IQR 2). Mean total GERD-HRQL score significantly improved from 19.9 to 4.01 (
p
< 0.001), and PPI were discontinued by 79% of patients. The mean total percent time with pH < 4 decreased from 9.6% at baseline to 4.1% (
p
< 0.001), with 89% of patients achieving pH normalization. Independent predictors of a favorable outcome were age at intervention < 40 years (OR 4.17) and GERD-HRQL score > 15 (OR 4.09). We confirm long-term safety and efficacy of MSA in terms of symptom improvement, decreased drug dependency, and reduced esophageal acid exposure.
Journal Article
Assessing the impact of COVID-19 mass testing in South Tyrol using a semi-parametric growth model
Mass antigen testing has been proposed as a possible cost-effective tool to contain the COVID-19 pandemic. We test the impact of a voluntary mass testing campaign implemented in the Italian region of South Tyrol on the spread of the virus in the following months. We do so by using an innovative empirical approach which embeds a semi-parametric growth model—where COVID-19 transmission dynamics are allowed to vary across regions and to be impacted by the implementation of the mass testing campaign—into a synthetic control framework which creates an appropriate control group of other Italian regions. Our results suggest that mass testing campaigns are useful instruments for mitigating the pandemic.
Journal Article
Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination
Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling
in vivo
and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.
Adverse life events have been associated with reduced survival in cancer patients. Here, the authors explore the mechanism responsible and show that chronic stress in mice activates a signalling cascade in macrophages and tumour cells, which results in restructuring of the tumour lymphatic system, promoting metastasis.
Journal Article
Esophageal emergencies: WSES guidelines
The esophagus traverses three body compartments (neck, thorax, and abdomen) and is surrounded at each level by vital organs. Injuries to the esophagus may be classified as foreign body ingestion, caustic ingestion, esophageal perforation, and esophageal trauma. These lesions can be life-threatening either by digestive contamination of surrounding structures in case of esophageal wall breach or concomitant damage of surrounding organs. Early diagnosis and timely therapeutic intervention are the keys of successful management.
Journal Article
Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R
By acting on the P2X
7
receptor, ATP released upon cell damage functions as a danger signal to promote acute graft-versus-host disease after bone marrow transplantation in mice.
Danger signals released upon cell damage can cause excessive immune-mediated tissue destruction such as that found in acute graft-versus-host disease (GVHD), allograft rejection and systemic inflammatory response syndrome. Given that ATP is found in small concentrations in the extracellular space under physiological conditions
1
, and its receptor P2X
7
R is expressed on several immune cell types, ATP could function as a danger signal when released from dying cells. We observed increased ATP concentrations in the peritoneal fluid after total body irradiation, and during the development of GVHD in mice and in humans. Stimulation of antigen-presenting cells (APCs) with ATP led to increased expression of CD80 and CD86
in vitro
and
in vivo
and actuated a cascade of proinflammatory events, including signal transducer and activator of transcription-1 (STAT1) phosphorylation, interferon-γ (IFN-γ) production and donor T cell expansion, whereas regulatory T cell numbers were reduced. P2X
7
R expression increased when GVHD evolved, rendering APCs more responsive to the detrimental effects of ATP, thereby providing positive feedback signals. ATP neutralization, early P2X
7
R blockade or genetic deficiency of P2X
7
R during GVHD development improved survival without immune paralysis. These data have major implications for transplantation medicine, as pharmacological interference with danger signals that act via P2X
7
R could lead to the development of tolerance without the need for intensive immunosuppression.
Journal Article
The Potential of Purinergic Signaling to Thwart Viruses Including SARS-CoV-2
A long-shared evolutionary history is congruent with the multiple roles played by purinergic signaling in viral infection, replication and host responses that can assist or hinder viral functions. An overview of the involvement of purinergic signaling among a range of viruses is compared and contrasted with what is currently understood for SARS-CoV-2. In particular, we focus on the inflammatory and antiviral responses of infected cells mediated by purinergic receptor activation. Although there is considerable variation in a patient’s response to SARS-CoV-2 infection, a principle immediate concern in Coronavirus disease (COVID-19) is the possibility of an aberrant inflammatory activation causing diffuse lung oedema and respiratory failure. We discuss the most promising potential interventions modulating purinergic signaling that may attenuate the more serious repercussions of SARS-CoV-2 infection and aspects of their implementation.
Journal Article