Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study.

Background: Carbapenem-Resistant Gram-Negative Bacteria, including Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA), are common causes of infections in intensive care units (ICUs) in Italy.

Objective: This prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy.

Methods: The study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023.

Proof of Concept for Genome Profiling of the Neurofibroma/Sarcoma Sequence in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues.

Reassessment of the NF1 variants of unknown significance found during the 20-year activity of a genetics diagnostic laboratory.

The finding of variants of uncertain significance (VUS) in the activity of a diagnostic genetic laboratory is a common issue, which is however provisional and needs to be periodically re-evaluated, due to the continuous advancements in our knowledge of the genetic diseases. Neurofibromatosis type 1, caused by the occurrence of heterozygous pathogenic NF1 variants, is a good model for studying the evolution of VUS, due to the widespread use of genetic testing for the disease, the constant enrichment of the international databases with NF1 variants and the full adult penetrance of the disease, which makes genotyping the parents a crucial step in the diagnostic workflow. The present study retrospectively reviewed and reinterpreted the genetic test results of NF1 in a diagnostic genetic laboratory in the period from January 1, 2000 to December 31, 2020.

Success and Pitfalls of Genetic Testing in Undiagnosed Diseases: Whole Exome Sequencing and Beyond.

Novel approaches to uncover the molecular etiology of neurodevelopmental disorders (NDD) are highly needed. Even using a powerful tool such as whole exome sequencing (WES), the diagnostic process may still prove long and arduous due to the high clinical and genetic heterogeneity of these conditions. The main strategies to improve the diagnostic rate are based on family segregation, re-evaluation of the clinical features by reverse-phenotyping, re-analysis of unsolved NGS-based cases and epigenetic functional studies.

Predominant VH1-69 IgBCR Clones Show Higher Expression of CD5 in Heterogeneous Chronic Lymphocytic Leukemia Populations.

The immunoglobulin B cell receptor (IgBCR) expressed by chronic lymphocytic leukemia (CLL) B cells plays a pivotal role in tumorigenesis, supporting neoplastic transformation, survival, and expansion of tumor clones. We demonstrated that in the same patient, two or more CLL clones could coexist, recognized by the expression of different variable regions of the heavy chain of IgBCR, composing the antigen-binding site. In this regard, phage display screening could be considered the easier and most advantageous methodology for the identification of small peptide molecules able to mimic the natural antigen of the tumor IgBCRs.

Feasibility of Testing of Formalin-Fixed and Paraffin-Embedded Pancreatic Tumor Samples: A Consecutive Clinical Series.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, with most patients diagnosed at advanced stages. First-line treatment based on a combined chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) provides limited benefits. Olaparib, a PARP inhibitor, has been approved as maintenance for PDAC patients harboring germline /2 pathogenic mutations and previously treated with a platinum-based chemotherapy.

When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that is responsible for coronavirus disease 2019 (COVID-19), which has rapidly spread across the world, becoming a pandemic. The "cytokine storm" (CS) in COVID-19 leads to the worst stage of illness, and its timely control through immunomodulators, corticosteroids, and cytokine antagonists may be the key to reducing mortality. After reviewing published studies, we proposed a Cytokine Storm Score (CSs) to identify patients who were in this hyperinflammation state, and at risk of progression and poorer outcomes.

Antimicrobial Stewardship Program, COVID-19, and Infection Control: Spread of Carbapenem-Resistant Klebsiella Pneumoniae Colonization in ICU COVID-19 Patients. What Did Not Work?

The Italian burden of disease associated with infections due to antibiotic-resistant bacteria has been very high, largely attributed to (). The implementation of infection control measures and antimicrobial stewardship programs (ASP) has been shown to reduce healthcare-related infections caused by multidrug resistance (MDR) germs. Since 2016, in our teaching hospital of Terni, an ASP has been implemented in an intensive care unit (ICU) setting, with the "daily-ICU round strategy" and particular attention to infection control measures.

Impact of Antimicrobial Stewardship Interventions on Appropriateness of Surgical Antibiotic Prophylaxis: How to Improve.

Surgical site infections (SSIs) are the most common healthcare-associated infections. The appropriate use of Surgical Antibiotic Prophylaxis (SAP) is a key component to reduce SSIs, while its inappropriate application is a major cause of some emerging infections and selects for antibiotic resistance. We describe an Antimicrobial Stewardship (AMS) intervention on SAP appropriateness.

Immune Profiling of Deficient Mismatch Repair Colorectal Cancer Tumor Microenvironment Reveals Different Levels of Immune System Activation.

To understand the immune landscape of deficient mismatch repair colorectal cancer (dMMR CRC) tumor microenvironment, gene expression profiling was performed by the nCounter PanCancer Immune Profiling Panel. This study was conducted retrospectively on 89 dMMR-CRC samples. The expression of CD3, CD8, programmed death-1, and programmed death ligand-1 protein was evaluated on a subset of samples by immunohistochemistry, and lymphocyte density was calculated.

The Molecular Signature More Than the Site of Localization Defines the Origin of the Malignancy.

The diagnosis of the primary origin of metastases to the thyroid gland is not easy, in particular in case of concomitant lung adenocarcinoma which shares several immunophenotypical features. Although rare, these tumors should be completely characterized in order to set up specific therapies. This is the case of a 64-years-old woman referred to our institution for a very advanced neoplastic disease diagnosed both as poorly differentiated/anaplastic thyroid cancer (PDTC/ATC) for the huge involvement of the neck and concomitant lung adenocarcinoma (LA).

Educational ICU Antimicrobial Stewardship model: the daily activities of the AMS team over a 10-month period.

The emergence of antibiotic resistance as a consequence of inappropriate use results in higher mortality rates and has become a major public health challenge worldwide. Antimicrobial stewardship programs (ASPs) aim to ensure proper use of antimicrobials and reduce health care costs. We assessed the impact of using a behavioral approach during a persuasive ASP on antibiotic appropriateness, consumption and costs.

Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial.

Background: Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer.

Phase II randomised study of maintenance treatment with bevacizumab or bevacizumab plus metronomic chemotherapy after first-line induction with FOLFOXIRI plus Bevacizumab for metastatic colorectal cancer patients: the MOMA trial.

Background: Alternating induction and maintenance phases is a common strategy in metastatic colorectal cancer (mCRC). Metronomic chemotherapy (metroCT) may represent a well-tolerated chemotherapy backbone for maximising bevacizumab effect during maintenance. The MOMA trial was designed to compare metroCT plus bevacizumab versus bevacizumab alone as maintenance following 4 months of induction with FOLFOXIRI plus bevacizumab.

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO.

Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status.

Patients And Methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab.

Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR monoclonal antibodies: the PRESSING case-control study.

Background: Refining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies.

Patients And Methods: We conducted this multicentre, prospective, case-control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations.

Inhibition of the platelet-derived growth factor receptor beta (PDGFRB) using gene silencing, crenolanib besylate, or imatinib mesylate hampers the malignant phenotype of mesothelioma cell lines.

Malignant pleural mesothelioma (MPM) is a cancer of the pleural cavity resistant to chemotherapy. The identification of novel therapeutic targets is needed to improve its poor prognosis. Following a review of literature and a screening of specimens we found that platelet-derived growth factor receptor beta () is over-expressed, but not somatically mutated, in MPM tissues.

Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months.

Background: The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs.

Case Presentation: A female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation.

Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest.

Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors.

Papillary Thyroid Carcinoma With Rare Exon 15 BRAF Mutation Has Indolent Behavior: A Single-Institution Experience.

Context: Approximately 40% of papillary thyroid carcinomas (PTCs) harbor the BRAF V600E mutation, which is significantly associated with the advanced clinicopathological features of PTC at diagnosis, a higher recurrence rate, and disease-related mortality. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established.

Objective: The aim of the study was to describe a large cohort of rare exon 15 BRAF alterations (r-BRAF) and the clinicopathological features of PTC harboring these alterations and to clarify their clinical significance.

EGFR and KRAS mutational analysis in a large series of Italian non-small cell lung cancer patients: 2,387 cases from a single center.

Activating EGFR mutations are important genetic alterations that have strong therapeutic implications for non-small cell lung cancer (NSCLC) patients. However, the role of KRAS mutations in this process is still under evaluation. Here, we report on the feasibility of a large‑scale EGFR and KRAS mutation analysis in the daily routine of a single center.

Role of gene expression profiling in defining indeterminate thyroid nodules in addition to BRAF analysis.

Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules. However, 15% to 30% of aspirations yield indeterminate cytologic findings. Because the assessment of BRAF mutations seems to improve the diagnostic accuracy, this study evaluated BRAF mutations with Sanger sequencing and real-time methods in 650 consecutive thyroid aspirates.

Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer.

Background: The enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking.

Methods: 119 primary CRCs were analyzed.