Publications by authors named "Najib Ben-Khaled"

Background And Aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)-based systemic therapies is unclear.

Approach And Results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.

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Article Synopsis
  • Immunotherapy combinations are the standard treatment for advanced hepatocellular carcinoma (HCC), with growing evidence supporting lenvatinib as a strong first-line option.
  • A retrospective study analyzed 412 patients treated with either atezolizumab/bevacizumab (AZ/BV) or lenvatinib (LEN) across 18 European hospitals, revealing that those on AZ/BV experienced longer progression-free survival.
  • Despite comparable survival rates between the two treatments overall, AZ/BV posed a higher risk of liver issues in patients with pre-existing liver function impairment, highlighting the need for careful patient monitoring.
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Immune checkpoint inhibitors (ICI) represent a breakthrough in cancer therapy. They are effective in various tumor entities and can be used in more and more treatment settings. This leads to an increase in the number and complexity of cases with immune-related adverse events (irAE).

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Article Synopsis
  • A study evaluated the efficacy and safety of first-line therapies for hepatocellular carcinoma (HCC), specifically comparing atezolizumab/bevacizumab (atezo/bev) and lenvatinib, focusing on bleeding and thromboembolic events.
  • A total of 464 patients from seven centers in Germany and Austria were analyzed, revealing that bleeding and thromboembolic events occurred in similar rates for both treatments within 6 months.
  • The findings suggest that safety concerns regarding bleeding and thromboembolic events might not significantly influence clinical decisions when selecting between atezo/bev and lenvatinib for HCC treatment.*
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Neutrophils rapidly respond to inflammation and infection, but to which degree their functional trajectories after mobilization from the bone marrow are shaped within the circulation remains vague. Experimental limitations have so far hampered neutrophil research in human disease. Here, using innovative fixation and single-cell-based toolsets, we profile human and murine neutrophil transcriptomes and proteomes during steady state and bacterial infection.

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Background & Aims: Herein we used data derived from the SORAMIC trial to explore the predictive value of systemic inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib monotherapy or the combination of selective internal radiation therapy (SIRT)/sorafenib.

Methods: Patients randomized to sorafenib monotherapy or SIRT/sorafenib within the per-protocol population of the SORAMIC trial were evaluated in this exploratory analysis. The median baseline values of NLR and PLR were used as cut-off values to describe subgroups.

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Background And Purpose: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC).

Materials And Methods: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation.

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Background: Combined hepatocellular-cholangiocarcinoma (cHCC-iCCA) is a rare type of primary liver cancer displaying characteristics of both hepatocytic and cholangiocytic differentiation.

Summary: Because of its aggressive nature, patients with cHCC-iCCA exhibit a poorer prognosis than those with HCC. Surgical resection and liver transplantation may be considered curative treatment approaches; however, only a minority of patients are eligible at the time of diagnosis, and postoperative recurrence rates are high.

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Background: Chest radiographs (CXRs) are still of crucial importance in primary diagnostics, but their interpretation poses difficulties at times.

Research Question: Can a convolutional neural network-based artificial intelligence (AI) system that interprets CXRs add value in an emergency unit setting?

Study Design And Methods: A total of 563 CXRs acquired in the emergency unit of a major university hospital were retrospectively assessed twice by three board-certified radiologists, three radiology residents, and three emergency unit-experienced nonradiology residents (NRRs). They used a two-step reading process: (1) without AI support; and (2) with AI support providing additional images with AI overlays.

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Article Synopsis
  • Immunotherapy is the primary treatment for advanced hepatocellular carcinoma (aHCC), but many patients still face disease progression despite initial responses, which has led to exploring combination therapies, including radiotherapy.
  • The study analyzed patients who received immune checkpoint inhibitors (ICIs) alongside radiotherapy to assess both effectiveness and adverse effects, focusing on those treated between 2016 and 2021.
  • Out of six patients, different radiotherapy techniques were employed with no severe adverse effects noted, and five of the six patients achieved long-term tumor control.
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Purpose: To investigate prognostic value of baseline MRI features for time-to-recurrence (TTR) and local recurrence in patients with early hepatocellular carcinoma (HCC).

Method: Baseline and follow-up images of 88 patients treated with thermal ablation followed by adjuvant sorafenib or matching placebo due to HCC within the phase II prospective randomized trial (SORAMIC) were included. Baseline MRI images were evaluated in terms of atypical enhancement (lack of wash-in or wash-out), lesion diameter, tumor capsule, peritumoral enhancement on arterial phase, intratumoral fat, irregular margin, satellite lesions, and peritumoral hypointensity on hepatobiliary phase.

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Background And Aims: The treatment of hepatocellular carcinoma (HCC) is undergoing a historic transformation with the approval of several new systemic therapies in the last few years. This study aimed to examine the impact of this changing landscape on survival and costs in a Western nationwide, real-world cohort.

Methods: A nationwide representative claims database (InGef) was screened for HCC cases between 2015 and 2020.

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Background And Aims: Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT).

Materials And Methods: 24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study.

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Gastric neuroendocrine carcinomas (G-NEC) are aggressive malignancies with poorly understood biology and a lack of disease models. Here, we use genome sequencing to characterize the genomic landscapes of human G-NEC and its histologic variants. We identify global and subtype-specific alterations and expose hitherto unappreciated gains of MYC family members in a large part of cases.

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Primary sclerosing cholangitis (PSC) represents a chronic liver disease characterized by poor prognosis and lacking causal treatment options. Yes-associated protein (YAP) functions as a critical mediator of fibrogenesis; however, its therapeutic potential in chronic biliary diseases such as PSC remains unestablished. The objective of this study is to elucidate the possible significance of YAP inhibition in biliary fibrosis by examining the pathophysiology of hepatic stellate cells (HSC) and biliary epithelial cells (BEC).

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Article Synopsis
  • Pseudoprogression (PsPD) is a rare response to immune checkpoint inhibitor therapy in cancer patients, characterized by initial signs of tumor progression without immediate confirmation.* -
  • In a study of 32 patients, 81.3% exhibited PsPD during their first follow-up, with various patterns of tumor progression observed, including increases in target lesions and the appearance of new lesions.* -
  • Most instances of PsPD were recorded shortly after treatment initiation, suggesting that close monitoring is essential, as significant changes in tumor size and serologic markers were noted, along with some immune-related adverse events.*
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Introduction: Immune checkpoint inhibitor-mediated colitis (IMC) is commonly managed with steroids and biologics. We evaluated the efficacy of ustekinumab (UST) in treating IMC refractory to steroids plus infliximab and/or vedolizumab.

Results: Nineteen patients were treated with UST for IMC refractory to steroids plus infliximab (57.

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Purpose: Identification of patients at risk of complicated or more severe COVID-19 is of pivotal importance, since these patients might require monitoring, antiviral treatment, and hospitalization. In this study, we prospectively evaluated the SACOV-19 score for its ability to predict complicated or more severe COVID-19.

Methods: In this prospective multicenter study, we included 124 adult patients with acute COVID-19 in three German hospitals, who were diagnosed in an early, uncomplicated stage of COVID-19 within 72 h of inclusion.

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Purpose: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS).

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Background & Aims: The aim of the study was to evaluate the efficacy and safety of adjuvant sorafenib treatment compared with placebo in patients with hepatocellular carcinoma who underwent local ablation.

Methods: The SORAMIC trial is a randomised controlled trial with diagnostic, local ablation, and palliative sub-study arms. After initial imaging within the diagnostic study, patients were assigned to local ablation or palliative arms.

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Atezolizumab plus bevacizumab is the standard of care for first-line systemic therapy for advanced hepatocellular carcinoma (aHCC). Data on the efficacy and safety of atezolizumab plus bevacizumab in patients with aHCC who have received prior systemic therapy are not available. Patients with aHCC who received atezolizumab plus bevacizumab after at least one systemic treatment between December 2018 and March 2022 were retrospectively identified in 13 centers in Germany and Austria.

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Hepatic ischemia-reperfusion injury (IRI) represents a major challenge during liver surgery, liver preservation for transplantation, and can cause hemorrhagic shock with severe hypoxemia and trauma. The reduction of blood supply with a concomitant deficit in oxygen delivery initiates various molecular mechanisms involving the innate and adaptive immune response, alterations in gene transcription, induction of cell death programs, and changes in metabolic state and vascular function. Hepatic IRI is a major cause of morbidity and mortality, and is associated with an increased risk for tumor growth and recurrence after oncologic surgery for primary and secondary hepatobiliary malignancies.

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