Real-World Efficacy and Safety of First-Line Nivolumab Plus Chemotherapy in Patients with Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Nationwide Observational Turkish Oncology Group (TOG) Study.

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023.

Efficacy of Systemic Treatments in Patients With Metastatic Lung Invasive Mucinous Adenocarcinoma.

Background: Invasive mucinous adenocarcinoma (IMA) is a rare histological subtype of lung invasive adenocarcinoma with unique clinical, radiological, histopathological, and genomic characteristics. There have been limited studies on the effectiveness of systemic therapy for lung IMA, with conflicting results reported.

Methods: We retrospectively investigated the medical records of patients diagnosed with lung IMA.

3D-Printed Medical-Grade Polycaprolactone (mPCL) Scaffold for the Surgical Treatment of Vaginal Prolapse and Abdominal Hernias.

The expected outcome after a scaffold augmented hernia repair is the regeneration of a tissue composition strong enough to sustain biomechanical function over long periods. It is hypothesised that melt electrowriting (MEW) medical-grade polycaprolactone (mPCL) scaffolds loaded with platelet-rich plasma (PRP) will enhance soft tissue regeneration in fascial defects in abdominal and vaginal sheep models. A pre-clinical evaluation of vaginal and abdominal hernia reconstruction using mPCL mesh scaffolds and polypropylene (PP) meshes was undertaken using an ovine model.

Microporous/Macroporous Polycaprolactone Scaffolds for Dental Applications.

This study leverages the advantages of two fabrication techniques, namely, melt-extrusion-based 3D printing and porogen leaching, to develop multiphasic scaffolds with controllable properties essential for scaffold-guided dental tissue regeneration. Polycaprolactone-salt composites are 3D-printed and salt microparticles within the scaffold struts are leached out, revealing a network of microporosity. Extensive characterization confirms that multiscale scaffolds are highly tuneable in terms of their mechanical properties, degradation kinetics, and surface morphology.

Infectious complications of cyclin-dependent kinases 4 and 6 inhibitors in patients with hormone-receptor-positive metastatic breast cancer: a systematic review and meta-analysis.

Aim: The combination of cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors plus endocrine therapy (ET) improved the survival outcomes and became the standard of care in the treatment of metastatic hormone-positive breast cancer. However, these combinations increased the risk of neutropenia compared with ET alone. While the infection-related mortalities did not seem to be increased, the exact risk of infections with CDK 4/6 inhibitor and ET combinations is relatively understudied.

Adjuvant treatment with paclitaxel plus trastuzumab for node-negative breast cancer: real-life experience.

In node-negative -overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab.

Sarcopenia and anthracycline cardiotoxicity in patients with cancer.

Background: Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity.

Methods: Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included.

Engineering a 3D bone marrow adipose composite tissue loading model suitable for studying mechanobiological questions.

Tissue engineering strategies are widely used to model and study the bone marrow microenvironment in healthy and pathological conditions. Yet, while bone function highly depends on mechanical stimulation, the effects of biomechanical stimuli on the bone marrow niche, specifically on bone marrow adipose tissue (BMAT) is poorly understood due to a lack of representative in vitro loading models. Here, we engineered a BMAT analog made of a GelMA (gelatin methacryloyl) hydrogel/medical-grade polycaprolactone (mPCL) scaffold composite to structurally and biologically mimic key aspects of the bone marrow microenvironment, and exploited an innovative bioreactor to study the effects of mechanical loading.

A humanised rat model of osteosarcoma reveals ultrastructural differences between bone and mineralised tumour tissue.

Current xenograft animal models fail to accurately replicate the complexity of human bone disease. To gain translatable and clinically valuable data from animal models, new in vivo models need to be developed that mimic pivotal aspects of human bone physiology as well as its diseased state. Above all, an advanced bone disease model should promote the development of new treatment strategies and facilitate the conduction of common clinical interventional procedures.

Personalized, Mechanically Strong, and Biodegradable Coronary Artery Stents via Melt Electrowriting.

Biodegradable coronary artery stents are sought-after alternatives to permanent stents. These devices are designed to degrade after the blood vessel heals, leaving behind a regenerated artery. The original generation of clinically available biodegradable stents required significantly thicker struts (∼150 μm) than nondegradable ones to ensure sufficient mechanical strength.

Chemoimmunotherapy for the salvage treatment of Ewing sarcoma: A case report.

Introduction: Although, immune check-point inhibitors changed the course of many cancers, the outcomes in sarcomas were rather disappointing with less than 10% response rates. Ewing sarcoma is a poorly differentiated and aggressive tumor mostly seen in the children and adolescents. It's a distinct type of sarcoma with prominent chemosensitivity in the early stages.

A 3D-printed biomaterials-based platform to advance established therapy avenues against primary bone cancers.

In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγ (NSG) mice.

Melt Electrowriting of Complex 3D Anatomically Relevant Scaffolds.

The manufacture of fibrous scaffolds with tailored micrometric features and anatomically relevant three-dimensional (3D) geometries for soft tissue engineering applications remains a great challenge. Melt electrowriting (MEW) is an advanced additive manufacturing technique capable of depositing predefined micrometric fibers. However, it has been so far inherently limited to simple planar and tubular scaffold geometries because of the need to avoid polymer jet instabilities.

The Patenting and Technological Trends in Hernia Mesh Implants.

Described as a projection (prolapse) of tissue through a fascial defect in the abdominal wall, hernias are associated with significant rates of complications, recurrence, and reoperations. This literature review is aimed at providing an overview of the prosthetic surgical meshes used for the repairing of hernia defects. The review was carried out using two specialized online databases: Espacenet, from the European Patent Office (EPO), and WIPO from the World Intellectual Property Organization.

Effect of gelatin source and photoinitiator type on chondrocyte redifferentiation in gelatin methacryloyl-based tissue-engineered cartilage constructs.

Gelatin methacryloyl (GelMA) hydrogels are a mechanically and biochemically tuneable biomaterial, facilitating chondrocyte culture for tissue engineering applications. However, a lack of characterisation and standardisation of fabrication methodologies for GelMA restricts its utilisation in surgical interventions for articular cartilage repair. The purpose of this study was to determine the effects of gelatin source and photoinitiator type on the redifferentiation capacity of monolayer-expanded human articular chondrocytes encapsulated in GelMA/hyaluronic acid methacrylate (HAMA) hydrogels.

The Current Versatility of Polyurethane Three-Dimensional Printing for Biomedical Applications.

Reconstructive surgery aims to restore tissue defects by replacing them with similar autologous tissue to achieve good clinical outcomes. However, often the defect is too large or the tissue available is limited, requiring synthetic materials to restore the anatomical shape and partial function. The utilization of three-dimensional (3D) printing allows for the manufacture of implants with complex geometries and internal architecture that more closely matches the required clinical needs.

Type II Photoinitiator and Tuneable Poly(Ethylene Glycol)-Based Materials Library for Visible Light Photolithography.

Stereolithography (SL) has several advantages over traditional biomanufacturing techniques such as fused deposition modeling, including increased speed, accuracy, and efficiency. While SL has been broadly used in tissue engineering for the fabrication of three-dimensional scaffolds that can mimic the environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable, low-cost photoinitiator system that we used to establish a systematic library of crosslinked materials based on low molecular weight poly(ethylene glycol) diacrylate.

Pembrolizumab- and/or pazopanib-induced remitting seronegative symmetrical synovitis with pitting edema in a patient with renal cell carcinoma.

Introduction: Immune checkpoint inhibitors and angiogenesis inhibitors are novel treatment options for renal cell carcinoma and widely used in clinical practice. They are related with adverse events that occur as a consequence of immune system activation and inhibition of angiogenesis. Herein, we report a rare case of inflammatory arthritis seen in a patient treated with an anti Programmed cell death-1 pembrolizumab and an anti-vascular endothelial growth factor pazopanib.

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting.

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment.

Tuning mechanical reinforcement and bioactivity of 3D printed ternary nanocomposites by interfacial peptide-polymer conjugates.

We present a study on ternary nanocomposites consisting of medical grade poly(ε-caprolactone) (mPCL) matrix, hydroxyapatite nanopowder (nHA) and compatibilized magnesium fluoride nanoparticle (cMgF) fillers. MgF nanoparticles were compatibilized by following a design approach based on the material interfaces of natural bone. MgF-specific peptide-poly(ethylene glycol) conjugates were synthesized and used as surface modifiers for MgF nanoparticles similarly to the non-collagenous proteins (NPC) of bone which compatibilize hydroxyapatite nanocrystallites.

Printomics: the high-throughput analysis of printing parameters applied to melt electrowriting.

Melt electrowriting (MEW) combines the fundamental principles of electrospinning, a fibre forming technology, and 3D printing. The process, however, is highly complex and the quality of the fabricated structures strongly depends on the interplay of key printing parameter settings including processing temperature, applied voltage, collection speed, and applied pressure. These parameters act in unison, comprising the principal forces on the electrified jet: pushing the viscous polymer out of the nozzle and mechanically and electrostatically dragging it for deposition towards the collector.

The quest for mechanically and biologically functional soft biomaterials via soft network composites.

Developing multifunctional soft biomaterials capable of addressing all the requirements of the complex tissue regeneration process is a multifaceted problem. In order to tackle the current challenges, recent research efforts are increasingly being directed towards biomimetic design concepts that can be translated into soft biomaterials via advanced manufacturing technologies. Among those, soft network composites consisting of a continuous hydrogel matrix and a reinforcing fibrous network closely resemble native soft biological materials in terms of design and composition as well as physicochemical properties.

Humanization of bone and bone marrow in an orthotopic site reveals new potential therapeutic targets in osteosarcoma.

Background: Existing preclinical murine models often fail to predict effects of anti-cancer drugs. In order to minimize interspecies-differences between murine hosts and human bone tumors of in vivo xenograft platforms, we tissue-engineered a novel orthotopic humanized bone model.

Methods: Orthotopic humanized tissue engineered bone constructs (ohTEBC) were fabricated by 3D printing of medical-grade polycaprolactone scaffolds, which were seeded with human osteoblasts and embedded within polyethylene glycol-based hydrogels containing human umbilical vein endothelial cells (HUVECs).

Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures.

The additive manufacturing of highly ordered, micrometer-scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning-melt electrospinning writing (MEW)-is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures.