Decoding KRAS mutation in non-small cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review.

Introduction: KRAS mutation the most common molecular alteration in advanced non-small cell lung cancer (NSCLC) and is associated with an unfavourable prognosis, largely due to the lack of targeted therapeutic options for the majority of the KRAS mutated isoforms. The landscape of NSCLC treatment has expanded with the introduction of immune checkpoint inhibitors (ICIs). Nonetheless, data regarding the efficacy of ICI in NSCLC patients harbouring KRAS mutations are conflicting.

Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation.

Alterations in nuclear structure and function are hallmarks of cancer cells. Little is known about these changes in Cancer-Associated Fibroblasts (CAFs), crucial components of the tumor microenvironment. Loss of the androgen receptor (AR) in human dermal fibroblasts (HDFs), which triggers early steps of CAF activation, leads to nuclear membrane changes and micronuclei formation, independent of cellular senescence.

Unleashing precision: A review of targeted approaches in pleural mesothelioma.

This review delves into the intricate landscape of pleural mesothelioma (PM), emphasizing the need for nuanced therapeutic strategies. While platinum-based chemotherapy remains a cornerstone, the advent of immune checkpoint inhibitors (ICIs), notably through the Checkmate 743 trial, has reshaped treatment paradigms. Challenges persist due to patient heterogeneity and a lack of specific biomarkers.

Diabetic Foot Osteomyelitis in Patients with and without Peripheral Arterial Disease: Two Different Diseases?

The aim of the current study was to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO), comparing subjects with and without peripheral arterial disease (PAD). The study is a prospective study including a population of patients affected by a DFO located in the forefoot. All patients were managed by a surgical conservative approach defined by the removal of the infected bone, in association with the antibiotic therapy.

Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients.

Attitude to Co-Administration of Influenza and COVID-19 Vaccines among Pregnant Women Exploring the Health Action Process Approach Model.

Respiratory tract diseases caused by influenza virus and SARS-CoV-2 can represent a serious threat to the health of pregnant women. Immunological remodulation for fetus tolerance and physiological changes in the gestational chamber expose both mother and child to fearful complications and a high risk of hospitalization. Vaccines to protect pregnant women from influenza and COVID-19 are strongly recommended and vaccine co-administration could be advantageous to increase coverage of both vaccines.

The impact of decision tools during oncological consultation with lung cancer patients: A systematic review within the I3LUNG project.

Introduction: To date, lung cancer is one of the most lethal diagnoses worldwide. A variety of lung cancer treatments and modalities are available, which are generally presented during the patient and doctor consultation. The implementation of decision tools to facilitate patient's decision-making and the management of their healthcare process during medical consultation is fundamental.

Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited.

Response to lorlatinib rechallenge in a case of ALK-rearranged metastatic NSCLC with a resistance mutation to second generation TKIs.

Introduction: Several anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have been developed for the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged non-small cell lung cancer (NSCLC), with the newer generation agents brigatinib, alectinib and lorlatinib showing prolonged responses. With the increasing number of target therapies available, the optimal sequence is yet to be defined, as resistance profiles may evolve over time and in response to sequential ALK inhibitors. Therefore, ALK-targeted strategies may be personalized based upon the presence of specific ALK resistance mutations.

Nivolumab in pretreated pleural mesothelioma: Results from an observational real-world study of patients treated within the AIFA 5% Fund.

Background: Pleural mesothelioma is a rare cancer with a dismal prognosis and few therapeutic options, especially in the pretreated setting. Immunotherapy with checkpoint inhibitors as single agents yielded interesting results in refractory pleural mesothelioma, achieving a response rate between 10-20%, median progression-free survival of 2-5 months and median overall survival of 7-13 months.

Patients And Methods: A retrospective, multi-institutional study of pleural mesothelioma patients treated with nivolumab in second and further line was performed.

ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.

There are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development and progression are closely linked to fibroblast senescence and transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control in human dermal fibroblasts (HDFs) and a key driver of CAF conversion, independent of cellular senescence.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease.

Impact of Actively Offering Influenza Vaccination to Frail People during Hospitalisation: A Pilot Study in Italy.

Despite the worldwide recommendations for influenza immunisation, vaccination coverage for patients exposed to the highest risk of severe complications is still far from the optimal target. The need to take advantage of alternative methods to provide vaccination is essential. This study presents a hospital-based strategy which offers influenza vaccination to inpatients at discharge.

High bone tumor burden to identify advanced non-small cell lung cancer patients with survival benefit upon bone targeted agents and immune checkpoint inhibitors.

Background: Bone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown.

Exploring the Role of Immunotherapy-Based Treatments for Advanced Non-Small-Cell Lung Cancer With Novel Driver Alterations.

Background: Immunotherapy (IO) single agent or combined with chemotherapy (CT-IO) is the standard treatment for advanced non-small-cell lung cancer (aNSCLC) without driver alterations. IO efficacy in patients with novel driver alterations is not well reported.

Materials And Methods: Data of aNSCLC patients treated with IO or CT-IO in any line from January 2016 to September 2022 were retrospectively collected.

Higher rates of non-skeletal complications and greater healthcare needs in achondroplasia compared to the general UK population: a matched cohort study using the CPRD database.

Background: The natural history of skeletal complications in achondroplasia (ACH) is well-described. However, it remains unclear how the rates of non-skeletal complications, surgical procedures, healthcare needs and mortality differ between individuals with ACH and the general population. This study aimed to contextualise the extent of these outcomes by comparing event rates across the lifespan, between those with ACH and matched controls in a United Kingdom (UK) population.

Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation.

Alterations of nuclear structure and function, and associated impact on gene transcription, are a hallmark of cancer cells. Little is known of these alterations in Cancer-Associated Fibroblasts (CAFs), a key component of the tumor stroma. Here we show that loss of androgen receptor (AR), which triggers early steps of CAF activation in human dermal fibroblasts (HDFs), leads to nuclear membrane alterations and increased micronuclei formation, which are unlinked from induction of cellular senescence.

Modeling and Validation of an Ultra-Compact Regenerative Liver Dialysis Device.

The availability of a wearable artificial liver that facilitates extracorporeal dialysis outside of medical facilities would represent a significant advancement for patients requiring dialysis. The objective of this preliminary investigation is to explore, using validated mathematical models based on in vitro data, the feasibility of developing a novel, cost-effective, and highly compact extracorporeal liver support device that can be employed as a transitional therapy to transplantation outside of clinical settings. Such an innovation would offer substantial cost savings to the national healthcare system while significantly improving the patient's quality of life.

PEOPLE (NTC03447678), a phase II trial to test pembrolizumab as first-line treatment in patients with advanced NSCLC with PD-L1 <50%: a multiomics analysis.

Background: Chemoimmunotherapy represents the standard of care for patients with advanced non-small cell lung cancer (NSCLC) and programmed death-ligand 1 (PD-L1) <50%. Although single-agent pembrolizumab has also demonstrated some activity in this setting, no reliable biomarkers yet exist for selecting patients likely to respond to single-agent immunotherapy. The main purpose of the study was to identify potential new biomarkers associated with progression-free-survival (PFS) within a multiomics analysis.

The EU-funded ILUNG Project: Integrative Science, Intelligent Data Platform for Individualized LUNG Cancer Care With Immunotherapy.

Although immunotherapy (IO) has changed the paradigm for the treatment of patients with advanced non-small cell lung cancers (aNSCLC), only around 30% to 50% of treated patients experience a long-term benefit from IO. Furthermore, the identification of the 30 to 50% of patients who respond remains a major challenge, as programmed Death-Ligand 1 (PD-L1) is currently the only biomarker used to predict the outcome of IO in NSCLC patients despite its limited efficacy. Considering the dynamic complexity of the immune system-tumor microenvironment (TME) and its interaction with the host's and patient's behavior, it is unlikely that a single biomarker will accurately predict a patient's outcomes.