Airway Remodeling in Cystic Fibrosis Is Heterogeneous.

RATIONALE+OBJECTIVE/ Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving towards obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis, is still poorly understood. METHOD/ On high-resolution computed tomography (HRCT, 600µm, CF=21, control=6) and micro-computed tomography (µCT, 150µm, CF=3, control=1) scans of inflated explant lungs, AV% (airway/total lung volume) was calculated as marker for bronchiectasis, while airway segmentation was used for generation analysis.

Clinico-pathological predictors of radiologic complete response to first-line anti-HER2 therapy in metastatic breast cancer.

This study aimed to identify the clinico-pathological variables predictive of radiologic complete response (rCR) to first-line anti-HER2 therapy in patients with HER2-positive metastatic breast cancer. Patients were selected from the database of the GIM14 study and classified according to the best radiologic response obtained to first-line anti-HER2 therapy and upon time-to-treatment-discontinuation (TTD). A total of 545 patients were included in the analysis.

Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: Long-term Results of a Prospective Phase II Study.

Aims: To analyze the long-term results of a prospective phase II trial testing intensified total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC).

Materials And Methods: Patients with histologically confirmed LARC adenocarcinoma were enrolled. Intensified TNT consisted of targeted agent (bevacizumab or panitumumab/cetuximab) plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified (oxaliplatin and 5-fluorouracil) chemoradiotherapy (CRT) and surgical resection.

Heterogeneous neutrophils in lung transplantation and proteolytic CXCL8 activation in COVID-19, influenza and lung transplant patient lungs.

Elevated neutrophil counts in broncho-alveolar lavage (BAL) fluids of lung transplant (LTx) patients with chronic lung allograft dysfunction (CLAD) are associated with disease pathology. However, phenotypical characteristics of these cells remained largely unknown. Moreover, despite enhanced levels of the most potent human neutrophil-attracting chemokine CXCL8 in BAL fluid, no discrimination had been made between natural NH-terminally truncated CXCL8 proteoforms, which exhibit up to 30-fold differences in biological activity.

Liver transplantation for organ failure following multiple locoregional treatments for breast cancer metastasis.

Patients with nonresectable breast cancer liver metastasis (BCLM) face a dismal prognosis. Despite liver transplantation (LT) for metastatic liver tumors having recently shown good results, BCLM represents an absolute contraindication. This study aimed to investigate the potential for long-term survival after LT for BCLMs in a patient experiencing end-stage liver disease, following multiple oncologic treatments.

Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

Background: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre.

Methods: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023.

Clinical impact of drug-drug interactions on abemaciclib in the real-world experience of AB-ITALY study.

Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2- advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs' impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting.

COVID-19 vaccination in cancer patients: Immune responses one year after the third dose.

Cancer patients (CPs), being immunosuppressed due to the treatment received or to the disease itself, are more susceptible to infections and their potential complications, showing therefore an increased risk of developing severe COVID-19 compared to the general population. We evaluated the immune responses to anti-SARS-CoV-2 vaccination in patients with solid tumors one year after the administration of the third dose and the effect of cancer treatment on vaccine immunogenicity was assessed. Healthy donors (HDs) were enrolled.

Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases.

Human diseases are characterized by intricate cellular dynamics. Single-cell sequencing provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in-silico drug interventions. Here, we introduce UNAGI, a deep generative neural network tailored to analyze time-series single-cell transcriptomic data.

TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer.

Purpose: TIPRL1 (target of rapamycin signaling pathway regulator-like 1) is a known interactor and inhibitor of protein phosphatases PP2A, PP4 and PP6 - all pleiotropic modulators of the DNA Damage Response (DDR). Here, we investigated the role of TIPRL1 in the radiotherapy (RT) response of Head and Neck Squamous Cell Carcinoma (HNSCC).

Methods: TIPRL1 mRNA (cBioportal) and protein expression (immunohistochemistry) in HNSCC samples were linked with clinical patient data.

Mucosal immune alterations at the early onset of tissue destruction in chronic obstructive pulmonary disease.

Rationale: COPD is characterized by chronic airway inflammation, small airways changes, with disappearance and obstruction, and also distal/alveolar destruction (emphysema). The chronology by which these three features evolve with altered mucosal immunity remains elusive. This study assessed the mucosal immune defense in human control and end-stage COPD lungs, by detailed microCT and RNA transcriptomic analysis of diversely affected zones.

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials.

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included.

A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss of .

Primary liver cancer (PLC) can be classified in hepatocellular (HCC), cholangiocarcinoma (CCA), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). The molecular mechanisms involved in PLC development and phenotype decision are still not well understood. Complete deletion of encoding the B56δ subunit of Protein Phosphatase 2A (PP2A) results in spontaneous HCC development in mice via a c-MYC-dependent mechanism.

Circulating Natural Killer Cells as Prognostic Value for Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Correlation with Sarcopenia.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of tumors. Natural killer (NK) cells can play an important role in cancer immune surveillance. The aim of this prospective observational study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICIs in order to identify predictive factors for better survival outcomes.

Evaluation of Efficacy of ALK Inhibitors According to Body Mass Index in ALK Rearranged NSCLC Patients-A Retrospective Observational Study.

No evidence exists as to whether body mass index (BMI) impairs clinical outcomes from ALK inhibitors (ALKi) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). Retrospective data of patients affected by metastatic ALK-rearranged NSCLC treated with ALKi were collected. We divided patients into "low- BMI" (≤25 kg/m) and "high- BMI" (>25 kg/m) categories and correlated them with overall survival (OS) and progression-free survival (PFS).

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from , a multicentric, observational study.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available.

Prognostic Role of Circulating Tumor Cell Trajectories in Metastatic Colorectal Cancer.

Background: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was to evaluate the clinical value of CTC dynamics in mCRC patients receiving first-line treatments.

Abscopal Effect on Bone Metastases from Solid Tumors: A Systematic Review and Retrospective Analysis of Challenge within a Challenge.

Background: Abscopal effect (AE) describes the ability of radiotherapy (RT) to induce immune-mediated responses in nonirradiated distant metastasis. Bone represents the third most frequent site of metastasis and an immunologically favorable environment for the proliferation of cancer cells. We revised the literature, searching documented cases of AE involving bone metastases (BMs) and evaluated the incidence of AE involving BMs in patients requiring palliative RT on BMs or non-BMs treated at our department.

Genomic landscape and survival analysis of ctDNA "neo- wild-type" patients with originally mutant metastatic colorectal cancer.

Background: The term "neo- wild-type" refers to the switch to wild-type disease in plasma circulating tumor DNA (ctDNA) from originally mutant colorectal cancers. Consistently, the hypothesis to re-determine mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of "neo- wild-type" is unknown.

The management of oligometastatic disease in colorectal cancer: Present strategies and future perspectives.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns.

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

Background: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development.

nmCRPC, a look in the continuous care of prostate cancer patients: state of art and future perspectives.

Non-metastatic castration resistant prostate cancer (nmCRPC) is a clinical setting defined as confirmed rising levels of PSA in patients treated with ADT but without detectable metastases on conventional imaging with computerized tomography (CT) and technetium-99 m scintigraphy. Men with nmCRPC and a PSA doubling time (PSADT) ≤ 10 months are considered at high risk of rapidly developing metastases with a consequent possible impact on survival. Three recent phase III trials have demonstrated, in this setting, the efficacy of adding a next-generation androgen receptor targeted agent (ARTA) to ADT in respect to ADT only, in delaying the development of metastases (metastasis-free survival, MFS) and prolong overall survival.

The value of the multidisciplinary team in metastatic renal cell carcinoma: Paving the way for precision medicine in toxicities management.

The new landscape of treatments for metastatic clear cell renal carcinoma (mRCC) is constantly expanding, but it is associated with the emergence of novel toxicities, adding to up to those observed in the tyrosine-kinase inhibitor (TKI) era. Indeed, the introduction of immune checkpoint inhibitors (ICIs) alone or in combination has been associated with the development of immune-related adverse events (irAEs) involving multiple-organ systems which, even if rarely, had led to fatal outcomes. Moreover, due to the relatively recent addition of ICIs to the previously available treatments, the potential additive adverse effects of these combinations are still unknown.

Lenvatinib Sorafenib in Advanced Hepatic Cell Carcinoma: A Double Center Retrospective Analysis.

Background/aim: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib.

Patients And Methods: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib).