Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager.

Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8 T cells.

Cost-effectiveness of a randomized controlled trial comparing low-dose aspirin to placebo for the prevention of recurrent preterm birth.

To assess the cost-effectiveness of low-dose aspirin compared to placebo for the prevention of recurrent preterm birth from a healthcare perspective. This was a cost-effectiveness analysis alongside a multicenter, randomized, double-blinded, placebo-controlled trial. We included women with a singleton pregnancy and a previous spontaneous preterm birth <37 weeks of gestation of a singleton.

Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

An organotypic human melanoma-in-skin model as an tool for testing Vγ9Vδ2-T cell-based immunotherapy.

Background: Despite considerable advancements in cancer immunotherapy, advanced melanoma still presents a substantial clinical challenge. In an effort to explore treatment options, we examined the immunotherapeutic potential of effector Vγ9Vδ2-T cells in a three-dimensional (3D) human organotypic melanoma-in-skin (Mel-RhS) model.

Materials And Methods: Vγ9Vδ2-T cells were introduced into Mel-RhS via intradermal injection and cultured within the tissue microenvironment for up to 3 days.

Same-day discharge after laparoscopic hysterectomy for benign/premalignant disease: A multicentre randomised controlled trial.

Objective: To evaluate whether physical function and quality of life was influenced by discharge on the same-day after a total laparoscopic hysterectomy.

Design: Multicentre non-inferiority randomised controlled trial.

Setting: Five teaching hospitals and two university hospitals in the Netherlands.

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer.

Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood.

Vaccination with DC-SIGN-Targeting αGC Liposomes Leads to Tumor Control, Irrespective of Suboptimally Activated T-Cells.

Cancer vaccines have emerged as a potent strategy to improve cancer immunity, with or without the combination of checkpoint blockade. In our investigation, liposomal formulations containing synthetic long peptides and α-Galactosylceramide, along with a DC-SIGN-targeting ligand, Lewis Y (Le), were studied for their anti-tumor potential. The formulated liposomes boosted with anti-CD40 adjuvant demonstrated robust invariant natural killer (iNKT), CD4, and CD8 T-cell activation in vivo.

A vertebra of a small species of from the North Sea and its inner structure and vascularity compared with other basilosaurid vertebrae from the same site.

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of (Morphotype 1b), a not-elongated vertebra of a large 'dorudontid' basilosaurid (Morphotype 2) and 'shortened' vertebrae of a new, unnamed taxon (Morphotype 3).

Reproductive and obstetrical outcomes after treatment of retained products of conception: hysteroscopic removal vs ultrasound-guided electric vacuum aspiration, a prospective follow-up study.

Background: Traditionally, curettage has been the most widely performed surgical intervention for removing retained products of conception. However, hysteroscopic removal is increasingly performed as an alternative because of the potentially lower risk of intrauterine adhesions and higher rates of complete removal. Until recently, studies comparing curettage with hysteroscopic removal regarding reproductive and obstetrical outcomes were limited, and data conflicting.

Manually driven versus motor driven hysteroscopic tissue removal system for polypectomy: Long-term results.

Objective: The aim of this follow-up study is to compare a manually driven hysteroscopic tissue removal system (Resectr 9 Fr) with a motor driven system (Truclear) in terms of long-term clinical outcomes such as abnormal uterine bleeding and polyp recurrence.

Study Design: This is a follow-up of a multicenter randomized controlled trial comparing a manually and motor driven hysteroscopic tissue removal system for polypectomy. This prospective cohort study was performed at Ghent University Hospital (Ghent, Belgium) and Catharina Hospital Eindhoven (Eindhoven, the Netherlands).

Allogeneic NK cells induce the in vitro activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions.

Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the ability of these cells to mediate tumor kill has been extensively studied, less is known about their capacity to influence the activity of other immune cells that may contribute to a concerted anti-tumor response in the tumor microenvironment (TME).

Quantitative ultrasound measurement of uterine contractility in adenomyotic vs. normal uteri: a multicenter prospective study.

Objective: To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method.

Design: A multicenter prospective observational study took place in three European centers between 2014 and 2023.

Setting: One university teaching hospital, 1 teaching hospital and 1 specialised clinic.

Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

Background: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia.

Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer.

Introduction: Natural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly lyse tumor cells without inducing graft-versus-host disease. As NK cells are also able to influence the function of other immune cells (most notably dendritic cells (DC)), a better understanding of the effects of allogeneic NK cell products on the host immune system is required.

Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions.

Background: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach.

Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography.

Operative hysteroscopy versus ultrasound-guided electric vacuum aspiration for removal of retained products of conception: A prospective cohort study.

Objectives: To compare intrauterine adhesion (IUA) formation after hysteroscopic removal (HR) of retained products of conception (RPOC) with IUA formation after ultrasound-guided electric vacuum aspiration (EVA) and externally validate the outcomes of an RCT.

Study Design: This prospective cohort study was conducted from April 2015 until June 2022 in 2 Dutch teaching hospitals and one Belgian university hospital. Women opting for EVA underwent the procedure as soon as possible.

Hysteroscopic morcellation vs. curettage for removal of retained products of conception: a multicenter randomized controlled trial.

Objective: To study the comparison between hysteroscopic morcellation (HM) of retained products of conception (RPOC) with ultrasound (US)-guided electric vacuum aspiration in terms of intrauterine adhesion (IUA) formation, efficacy, and complications.

Design: A randomized controlled, nonblinded trial.

Setting: Three teaching hospitals and one university hospital from April 2015 to June 2022.

A Bispecific γδ T-cell Engager Targeting EGFR Activates a Potent Vγ9Vδ2 T cell-Mediated Immune Response against EGFR-Expressing Tumors.

Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models.

Clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr 5fr, for the resection of endometrial polyps in an office setting.

Purpose: A first clinical evaluation of a new hand-driven hysteroscopic tissue removal device, Resectr 5fr, for office polypectomy without any anesthesia.

Methods: Women with at least one small endometrial polyp were eligible. Hysteroscopic polypectomy was performed using the Resectr 5fr in an office setting, without any anesthesia.

A bispecific T cell engager recruits both type 1 NKT and Vγ9Vδ2-T cells for the treatment of CD1d-expressing hematological malignancies.

Bispecific T cell engagers (bsTCEs) hold great promise for cancer treatment but face challenges due to the induction of cytokine release syndrome (CRS), on-target off-tumor toxicity, and the engagement of immunosuppressive regulatory T cells that limit efficacy. The development of Vγ9Vδ2-T cell engagers may overcome these challenges by combining high therapeutic efficacy with limited toxicity. By linking a CD1d-specific single-domain antibody (VHH) to a Vδ2-TCR-specific VHH, we create a bsTCE with trispecific properties, which engages not only Vγ9Vδ2-T cells but also type 1 NKT cells to CD1d tumors and triggers robust proinflammatory cytokine production, effector cell expansion, and target cell lysis in vitro.

Manual morcellation (Resectrâ„¢ 9Fr) vs electromechanical morcellation (TruClearâ„¢) for hysteroscopic polypectomy: A randomized controlled non-inferiority trial.

Introduction: Meta-analyses comparing hysteroscopic electromechanical morcellation with electrosurgical resection showed a shorter operating time for electromechanical morcellation, mainly for polypectomy. The Resectrâ„¢ 9Fr is a new hysteroscopic manual morcellator, designed to simplify this procedure. We aimed to compare manual with electromechanical morcellation for hysteroscopic polypectomy.

The ADENO study: ADenomyosis and its Effect on Neonatal and Obstetric outcomes: a retrospective population-based study.

Background: Adenomyosis is a benign gynecologic condition arising from the uterine junctional zone. Recent studies suggest a relationship between adenomyosis and adverse obstetrical outcomes, but evidence remains conflicting. There is no large-scale study investigating obstetrical outcomes in women with adenomyosis using the gold standard of histopathologic diagnosis.

Systemic Therapy for Patients with HER2-Positive Breast Cancer and Brain Metastases: A Systematic Review and Meta-Analysis.

Aim: Patients with HER2-positive (HER2+) metastatic breast cancer (mBC) develop brain metastases (BM) in up to 30% of cases. Treatment of patients with BM can consist of local treatment (surgery and/or radiotherapy) and/or systemic treatment. We undertook a systematic review and meta-analysis to determine the effect of different systemic therapies in patients with HER2+ mBC and BM.