Transumbilical laparoscopy for pneumoperitoneum establishment: a comprehensive multicentre evaluation affirming safety, feasibility, and a range of clinical benefits.

Introduction: Transumbilical laparoscopy (TUL) has emerged as a promising technique for establishing pneumoperitoneum in laparoscopic cholecystectomy, offering potential safety, feasibility, and clinical benefits. This retrospective multicentre study aims to evaluate the efficacy and outcomes of TUL in the management of gallbladder diseases.

Methods: A retrospective analysis was conducted on a cohort of 2,543 patients who underwent TUL between 2011 and 2021 across various medical institutions in Italy.

Stereotactic placement of dual lumen catheter system for continuous drainage, irrigation, and intraventricular antibiotic therapy for treatment of brain abscess with ventriculitis - A case report and literature review.

Background: Cerebral abscesses complicated by ventriculitis present significant treatment challenges, often associated with high morbidity and mortality. Traditional management approaches, including systemic antibiotic therapy and external ventricular drainage (EVD), face limitations due to the blood-brain barrier and risks of catheter-related complications. This report discusses a case where the dual-lumen catheter system, an innovative neurosurgical tool integrating continuous irrigation with drainage, was employed.

Assessment of Respiratory Function and Need for Noninvasive Ventilation in a Cohort of Patients with Myotonic Dystrophy Type 1 Followed at One Single Expert Center.

Introduction: Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus that these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia, and sleep disturbances, the prevalence of respiratory disease and indication for the effects of noninvasive ventilation (NIV) need to be further explored.

Objectives: To describe respiratory function and need for NIV at baseline and over time in a cohort of adult patients with DM1.

Acute acalculous cholecystitis and cardiovascular disease, which came first? After two hundred years still the classic chicken and eggs debate: A review of literature.

The existence of a close association between disease of the biliary tract and disease of the heart is known from the mists of time. Acute acalculous cholecystitis (AAC) can be defined as an acute necro inflammatory disease of the gallbladder in the absence of cholelithiasis. AAC is a challenging diagnosis.

Lift the curtain on long non-coding RNAs in hematological malignancies: Pathogenic elements and potential targets.

The Human Genome Project in 2001 has opened the Pandora's box on the complexity of DNA structure and transcriptional regulation. Only a small fraction of the 3 billion bases is part of the protein-coding genes, while approximately 98.5% is represented by non-coding sequences.

Novel Approaches for the Treatment of Patients with Richter's Syndrome.

In the last 10-15 years, the way to treat cancers has dramatically changed towards precision medicine approaches. These treatment options are mainly based on selective targeting against signaling pathways critical for or detrimentally activated in cancer cells in cancer cells, as well as exploiting molecules that are specifically expressed on neoplastic cells, also known as tumor-associated antigens. These considerations hold true also in the hematological field where a plethora of novel targeted agents have reached patients' bedside, significantly improving clinical responses.

Synergistic efficacy of the dual PI3K-δ/γ inhibitor duvelisib with the Bcl-2 inhibitor venetoclax in Richter syndrome PDX models.

A small subset of cases of chronic lymphocytic leukemia undergoes transformation to diffuse large B-cell lymphoma, Richter syndrome (RS), which is associated with a poor prognosis. Conventional chemotherapy results in limited responses, underlining the need for novel therapeutic strategies. Here, we investigate the ex vivo and in vivo efficacy of the dual phosphatidylinositol 3-kinase-δ/γ (PI3K-δ/γ) inhibitor duvelisib (Duv) and the Bcl-2 inhibitor venetoclax (Ven) using 4 different RS patient-derived xenograft (PDX) models.

ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient-derived xenograft mouse models.

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukemia (CLL), typically to an aggressive lymphoma. Treatment options for RS are limited and the disease is often fatal. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is expressed on CLL cells and other cancers but not on healthy adult tissues, making it an attractive, tumor-specific therapeutic target.

Rova-T enhances the anti-tumor activity of anti-PD1 in a murine model of small cell lung cancer with endogenous Dll3 expression.

Rovalpituzumab tesirine (Rova-T) offers a targeted therapy for ~85% of SCLC patients whose tumors express DLL3, but clinical dosing is limited due to off-target toxicities. We hypothesized that a sub-efficacious dose of Rova-T combined with anti-PD1, which alone shows a clinical benefit to ~15% of SCLC patients, might elicit a novel mechanism of action and extend clinical utility. Using a pre-clinical murine SCLC tumor model that expresses Dll3 and has an intact murine immune system, we found that sub-efficacious doses of Rova-T with anti-PD1 resulted in enhanced anti-tumor activity, compared to either monotherapy.

The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons (MNs) in the central nervous system. ALS etiology is highly multifactorial and multifarious, and an effective treatment is still lacking. Neuroinflammation is a hallmark of ALS and could be targeted to develop new therapeutic approaches.

Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions.

Representing the major cause of morbidity and mortality for chronic lymphocytic leukemia (CLL) patients, immunosuppression is a common feature of the disease. Effectors of the innate and the adaptive immune response show marked dysfunction and skewing towards the generation of a tolerant environment that favors disease expansion. Major deregulations are found in the T lymphocyte compartment, with inhibition of CD8 cytotoxic and CD4 activated effector T cells, replaced by exhausted and more tolerogenic subsets.

Activating Killer-cell Immunoglobulin-like Receptor genes confer risk for Crohn's disease in children and adults of the Western European descent: Findings based on case-control studies.

Background: Killer-cell Immunoglobulin-like Receptor (KIR) genes encode receptors, which are mainly expressed on, and control functional activities of, Natural Killer (NK) cells. There exist six distinct activating KIR genes in humans, who differ from one another with respect to the repertoire of these genes. Because activated NK cells can potentially cause tissue destruction, we hypothesized that variation in the inherited activating KIR genes in humans is associated with their innate susceptibility/resistance to developing Crohn disease (CD).

Pregnancy Epigenetic Signature in T Helper 17 and T Regulatory Cells in Multiple Sclerosis.

Increasing evidence supports the anti-inflammatory role of estrogens in Multiple Sclerosis (MS), originating from the observation of reduction in relapse rates among women with MS during pregnancy, but the molecular mechanisms are still not completely understood. Using an integrative data analysis, we identified T helper (Th) 17 and T regulatory (Treg) cell-type-specific regulatory regions (CSR) regulated by estrogen receptor alpha (ERα). These CSRs were validated in polarized Th17 from healthy donors (HD) and in peripheral blood mononuclear cells, Th17 and Treg cells from relapsing remitting (RR) MS patients and HD during pregnancy.

Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade.

Checkpoint blockade immunotherapy targeting the PD-1/PD-L1 inhibitory axis has produced remarkable results in the treatment of several types of cancer. Whereas cytotoxic T cells are known to provide important antitumor effects during checkpoint blockade, certain cancers with low MHC expression are responsive to therapy, suggesting that other immune cell types may also play a role. Here, we employed several mouse models of cancer to investigate the effect of PD-1/PD-L1 blockade on NK cells, a population of cytotoxic innate lymphocytes that also mediate antitumor immunity.

A novel field-based molecular assay to detect validated artemisinin-resistant k13 mutants.

Background: Given the risk of artemisinin resistance spreading from the Greater Mekong sub-region, prospective monitoring in sub-Saharan Africa should be expedited. Molecular biology techniques used for monitoring rely on the detection of k13 validated mutants by using PCR and Sanger sequencing approach, usually not available in malaria endemic areas.

Methods: A semi-automated workflow based on the easyMAG platform and the Argene Solution (bioMérieux, Marcy l'Etoile, France) as a field-based surveillance tool operable at national level was developed in four steps.

Depletion of tumor-associated macrophages switches the epigenetic profile of pancreatic cancer infiltrating T cells and restores their anti-tumor phenotype.

Pancreatic Ductal Adenocarcinoma (PDA) is characterized by a complex tumor microenvironment that supports its progression, aggressiveness and resistance to therapies. The delicate interplay between cancer and immune cells creates the conditions for PDA development, particularly due to the functional suppression of T cell anti-tumor effector activity. However, some of the mechanisms involved in this process are still poorly understood.

A Novel Functional Domain of Tab2 Involved in the Interaction with Estrogen Receptor Alpha in Breast Cancer Cells.

Tab2, originally described as a component of the inflammatory pathway, has been implicated in phenomena of gene de-repression in several contexts, due to its ability to interact with the NCoR corepressor. Tab2 interacts also with steroid receptors and dismisses NCoR from antagonist-bound Estrogen and Androgen Receptors on gene regulatory regions, thus modifying their transcriptional activity and leading to pharmacological resistance in breast and prostate cancer cells. We demonstrated previously that either Tab2 knock-down, or a peptide mimicking the Estrogen Receptor alpha domain interacting with Tab2, restore the antiproliferative response to Tamoxifen in Tamoxifen-resistant breast cancer cells.

A potentially protective role of IL-18 Binding Protein in HIV-infected Long-Term Non-Progressors.

An imbalance between IL-18 and its antagonist, IL-18 Binding Protein, occurs in the circulation of HIV-infected individuals. We show here for the first time that HIV-infected Long Term Non-Progressors (LTNPs) do not develop this imbalance, and maintain normal levels of IL-18BP in the circulation. Their circulating levels of the antagonist correlate negatively with viral loads and show a positive trend with CD4+ T cells counts.

E2 Regulates Epigenetic Signature on Neuroglobin Enhancer-Promoter in Neuronal Cells.

Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB) is one of the estrogen target genes involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERβ) that bind to specific regulatory genomic regions.

Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells.

Unlabelled: Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination.