Targeting Immunometabolism Mediated by CD73 Pathway in -Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance.

Despite the relevant antitumor efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC), the results in patients whose cancer harbors activating epidermal growth factor receptor () mutations are disappointing. The biological mechanisms underlying immune escape and both unresponsiveness and resistance to immunotherapy in -mutant NSCLC patients have been partially investigated. To this regard, lung cancer immune escape largely involves high amounts of adenosine within the tumor milieu with broad immunosuppressive effects.

New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials.

Introduction: The development of immune checkpoint inhibitors (ICI) has represented a revolution in the treatment of non-small cell lung cancer (NSCLC) and has established a new standard of care for different settings. However, through adaptive changes, cancer cells can develop resistance mechanisms to these drugs, hence the necessity for novel immunotherapeutic agents.

Areas Covered: This paper explores the immunotherapeutics currently under investigation in phase I clinical trials for the treatment of NSCLC as monotherapies and combination therapies.

Molecular and Genomic Profiling of Lung Cancer in the Era of Precision Medicine: A Position Paper from the Italian Association of Thoracic Oncology (AIOT).

The identification of the optimal cancer treatment has become progressively more intricate for non-small-cell lung cancer (NSCLC) patients due to the multitude of options available. The testing of biomarkers to predict clinical responses to therapies is pivotal to stratify the patients based on the molecular features of their tumors. The number of actionable genetic alterations to be tested is increasing together with the comprehension of the molecular mechanisms underlying tumor growth and development.

SARS-CoV-2 Infection and High-Risk Non-Muscle-Invasive Bladder Cancer: Are There Any Common Features?

Background: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death.

Summary: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction.

Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer: final results of a randomised phase 2 clinical trial.

Background: The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC).

Methods: A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS.

Effects of gender on cognitive and behavioral manifestations in multiple system atrophy.

Gender differences have been described in several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The effects of gender on cognitive and behavioral manifestations in multiple system atrophy and the changes of cognitive functions over time according to gender have not been investigated so far. Fifty-five patients with a diagnosis of multiple system atrophy underwent a comprehensive neuropsychological and neuropsychiatric battery at baseline and 26 of them could be re-evaluated at 1-year follow-up.

Beyond PSA: The Role of Prostate Health Index (phi).

Background: Widespread use of prostate specific antigen (PSA) in screening procedures allowed early identification of an increasing number of prostate cancers (PCas), mainly including indolent cancer. Availability of different therapeutic strategies which have a very different impact on the patient's quality of life suggested a strong need for tools able to identify clinically significant cancer at diagnosis. Multi-parametric magnetic resonance showed very good performance in pre-biopsy diagnosis.

The optional approach of oncogene-addicted non-small cell lung cancer with brain metastases in the new generation targeted therapies era.

In recent years, the study of the molecular characteristics of non-small cell lung cancer (NSCLC) has highlighted a specific role of some genes that represent important therapeutic targets, including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS-1) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). Patients with oncogene-addicted cancer benefit more from therapy with tyrosine kinase inhibitors (TKIs) than from chemotherapy. The brain is a preferred site for tumor spread in these patients.

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study.

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond.

Pharmacodynamics of current and emerging PD-1 and PD-L1 inhibitors for the treatment of non-small cell lung cancer.

: As of today, one of the cornerstones of NSCLC treatment is represented by Immune Checkpoint Inhibitors (ICI) treatment in the form of anti-PD-1/PD-L1 monoclonal antibodies. However, apart from currently approved, recommended and employed agents (nivolumab, pembrolizumab, atezolizumab, durvalumab), several new agents are currently under development and investigation both in monotherapy and in combinational settings.: This paper aims to discuss both the current state of the art and the most interesting emerging PD-1 and PD-L1 inhibitors and their present and future role in metastatic NSCLC treatment.

Vascular endothelial growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small cell lung cancer.

: Angiogenesis is the process by which the tumor develops its potential for growth and distant metastasis. The main proangiogenic switch is vascular endothelial growth factor (VEGF), which, along with its receptor VEGFR, is a target for biological drugs such as multi-targeted tyrosine kinase inhibitors used for many neoplasms, including non-small cell lung cancer (NSCLC).: The fact that angiokinase inhibitors act on several signaling molecules simultaneously means that the use of alternative transmission pathways, which nullifies the effect of drugs directed against a single target, is avoided.

Inferior vena cava agenesis in patients with lower limb deep vein thrombosis in the RIETE registry. When and why to suspect.

Background: Limited data exist about the clinical presentation and outcomes of patients with inferior vena cava agenesis (IVCA) who develop deep vein thrombosis (DVT).

Methods: We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry to compare clinical characteristics and outcomes of patients with lower limb DVT, according to the presence or absence of IVCA. Major outcomes included recurrent DVT, major bleeding and post-thrombotic syndrome (PTS).

Biomarkers of Prognosis and Efficacy of Anti-angiogenic Therapy in Metastatic Clear Cell Renal Cancer.

In the last decades, the prognosis of metastatic renal cell carcinoma (mRCC) has remarkably improved following the advent of the "targeted therapy" era. The expanding knowledge on the prominent role played by angiogenesis in RCC pathogenesis has led to approval of multiple anti-angiogenic agents such as sunitinib, pazopanib, axitinib, cabozantinib, sorafenib, and bevacizumab. These agents can induce radiological responses and delay cancer progression for months or years before onset of resistance, with a clinically meaningful activity.

New immunotherapy in the treatment of advanced renal cancer.

: Metastatic renal cell carcinoma (mRCC) in recent years has been one of the diseases in the oncology that has experienced the greatest development of targeted therapies.: On one hand, more and more refined acquisitions of molecular biology are allowing a better sub-classification of this tumor, identifying new and peculiar biological profiles of patients with metastatic renal cancer that will soon be destined for increasingly tailored treatments. On the other hand, immunotherapy has, in a short time, redesigned the perimeter of our knowledge, entering clinical practice in an overpowering and convincing way.

Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting.

Introduction: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified.

Methods: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy).

Knee septic arthritis caused by α-hemolytic Streptococcus in a patient with a recent history of knee arthroscopy: a case report.

Background: Arthroscopic partial meniscectomy is a common procedure in orthopedic practice. Infections are uncommon complications of this procedure with an incidence rate of 0,01% - 3,4%. Staphylococcus spp are the predominant causative agents in such cases.

The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives.

Background: In the recent years, immunotherapeutics and specifically immunecheckpoints inhibitors have marked a significant shift in the diagnostic and therapeutic algorithm of Non-Small Cell Lung Cancer (NSCLC), allowing us to use immunotherapeutics alone or combined with chemotherapy for a great subset of patients. However, new interesting approaches are being presently investigated, markedly immunotherapy combinations, that is, the use of two or more immunotherapeutics combined.

Methods: In particular, the combination of anti-PD-1 nivolumab and anti-CTLA-4 ipilimumab has already provided groundbreaking positive results in the advanced NSCLC and other combinations are currently under investigation.

The role of combination chemo-immunotherapy in advanced non-small cell lung cancer.

: Even with the currently recommended chemotherapeutic and immunotherapeutic treatment, the five year survival rate for advanced nonsquamous and squamous NSCLC without oncogenic drivers remains poor. However, several different chemo-immunotherapy combinations are presently being investigated - with favorable results- in order to increase the PFS and OS rates of these patients. : Therefore, this paper aims to discuss the most promising trials investigating chemo-immunotherapy combinations and their present and future impact on advanced NSCLC treatment paradigms.

Combining immunotherapies to treat non-small cell lung cancer.

: In recent years, immunotherapy has become an integral part of the treatment of many cancers, including non-small cell lung cancer (NSCLC). Precious therapeutic weapons impacting survival are monoclonal antibodies directed against the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) immune checkpoint. : Unfortunately, not all patients treated with checkpoint inhibitors have durable clinical responses.

First-line treatment of advanced non-small cell lung cancer with ALK rearrangement: state of the art and future development.

: Approximately 5% of all diagnosed non-small cell lung cancer (NSCLC) patients harbor a genetic rearrangement between the ALK and EML4 genes, representing a specific molecular, histological and clinical subgroup (ALK+ NSCLC). To date, upfront treatment with ALK-tyrosine-kinase inhibitors (ALK-TKIs) has replaced chemotherapy in the first line setting for this subset of patients with excellent results. However, all treated patients eventually develop acquired resistance mechanisms to these agents (mainly resistance mutations) and experience progression of the disease.