Physiologically Based Pharmacokinetic Model of Tyrosine Kinase Inhibitors to Predict Target Site Penetration, with PET-Guided Verification.

Osimertinib, a tyrosine kinase inhibitor (TKI), treats non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. However, its efficacy may vary due to heterogeneous drug distribution, assessable through microdosed radiolabeled drugs and positron emission tomography (PET). Precision dosing using microdosed TKI-PET encounters challenges due to pharmacokinetic (PK) variations between micro- and therapeutic doses.

Genome-wide association study on chronic postsurgical pain in the UK Biobank.

Background: Chronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP.

Genome-wide association study on chronic postsurgical pain after abdominal surgeries in the UK Biobank.

Introduction: Chronic pain is one of the most common and severe complications after surgery, affecting quality of life and overall wellbeing of patients. Several risk factors have been identified but the mechanisms of chronic postsurgical pain development remain unclear. This study aimed to identify single-nucleotide polymorphisms associated with developing chronic postsurgical pain after abdominal surgery, one of the most common types of surgery.

QSPRpred: a Flexible Open-Source Quantitative Structure-Property Relationship Modelling Tool.

Building reliable and robust quantitative structure-property relationship (QSPR) models is a challenging task. First, the experimental data needs to be obtained, analyzed and curated. Second, the number of available methods is continuously growing and evaluating different algorithms and methodologies can be arduous.

Memprot.GPCR-ModSim: modelling and simulation of membrane proteins in a nutshell.

Summary: Memprot.GPCR-ModSim leverages our previous web-based protocol, which was limited to class-A G protein-coupled receptors, to become the first one-stop web server for the modelling and simulation of any membrane protein system. Motivated by the exponential growth of experimental structures and the breakthrough of deep-learning-based structural modelling, the server accepts as input either a membrane-protein sequence, in which case it reports the associated AlphaFold model, or a 3D (experimental, modelled) structure, including quaternary complexes with associated proteins and/or ligands of any kind.

The Combined Effect of Western Diet Consumption and Diclofenac Administration Alters the Gut Microbiota and Promotes Anastomotic Leakage in the Distal Colon.

Background: Obesity, Western diet (WD) consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are co-occurring and modifiable factors associated with microbiome dysbiosis and anastomotic leakage. We studied the combined effect of a Western-type diet (WD) and diclofenac, a standard NSAID used in surgical patients, on anastomotic healing and gut microbiota composition following distal colon resection.

Methods: Forty-two rats were fed a WD for 6 weeks, after which they were randomized to either parenteral diclofenac 3 mg/kg/day or saline started on the day of surgery and continued for three days.

Global recommendations on adhesion prophylaxis in gynaecological laparoscopic surgery.

Adhesions are recognised as one of the most common complications of abdominal surgery; their diagnosis and prevention remains a significant unmet need in surgical therapy, affecting negatively a patient's quality of life and healthcare budgets. In addition, postoperative pelvic adhesions pose a high risk of reduced fertility in women of childbearing age. These 2023 Global Recommendations on Adhesion Prevention in Gynaecological Laparoscopic Surgery provide agreed-upon statements to guide clinical practice, with the ultimate goal of improving patient outcomes.

Animal models for preventing seroma after surgery: a systematic review and meta-analysis.

Novel interventions for seroma prevention are urgently needed in clinical practice. Animal models are pivotal tools for testing these interventions; however, a significant translational gap persists between clinical and animal model outcomes. This systematic review aims to assess the methodological characteristics and quality of animal models utilized for seroma prevention.

Proof-of-principle of a lung sealant based on functionalized polyoxazolines: experiments in an ovine acute aerostasis model.

Objectives: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury.

[Placebo procedures in the operating room: necessary or an unnecessary risk for the patient?].

Sham surgeries, surgical procedures without actually carrying out the intended surgical intervention, are rarely used in research concerning a new surgical or invasive technique. The conflicting needs of minimizing operational risks and maximizing simulation present challenges in designing placebo-controlled surgical trials. It is important to thoroughly consider ethical considerations in the design of studies involving sham surgeries, including the importance of a transparent research design, objective reporting of results, challenges related to the informed consent procedure, and the inherent risks associated with surgical procedures.

CAVE: Cerebral artery-vein segmentation in digital subtraction angiography.

Cerebral X-ray digital subtraction angiography (DSA) is a widely used imaging technique in patients with neurovascular disease, allowing for vessel and flow visualization with high spatio-temporal resolution. Automatic artery-vein segmentation in DSA plays a fundamental role in vascular analysis with quantitative biomarker extraction, facilitating a wide range of clinical applications. The widely adopted U-Net applied on static DSA frames often struggles with disentangling vessels from subtraction artifacts.

A new species of the genus Becker, 1923 and the first records of this genus for Europe (Diptera, Asilidae).

A new species of Becker, 1923, Álvarez Fidalgo & van den Broek, , is described from Spain, representing the first record of this genus for Europe. It is illustrated in high-resolution photographs and the first ecological information is provided, as well as a key to all species tentatively placed in this genus.

Home-based management of hypoxaemic COVID-19 patients: design of the Therapy@Home pilot study.

Introduction: During the COVID-19 pandemic, hospital capacity was strained. Home-based care could relieve the hospital care system and improve patient well-being if safely organised.We designed an intervention embedded in a regional collaborative healthcare network for the home-based management of acutely ill COVID-19 patients requiring oxygen treatment.

Continuous erector spinae plane block versus thoracic epidural analgesia in video-assisted thoracoscopic surgery: a prospective randomized open-label non-inferiority trial.

Background And Objectives: The evolving surgical techniques in thoracoscopic surgery necessitate the exploration of anesthesiological techniques. This study aimed to investigate whether incorporating a continuous erector spinae plane (ESP) block into a multimodal analgesia regimen is non-inferior to continuous thoracic epidural analgesia (TEA) in terms of quality of postoperative recovery for patients undergoing elective unilateral video-assisted thoracoscopic surgery.

Methods: We conducted a multicenter, prospective, randomized, open-label non-inferiority trial between July 2020 and December 2022.

Reproducibility and predictive value of three grading systems for intraoperative adverse events in a cohort of abdominal surgery.

Introduction: Intraoperative adverse events (iAEs) are increasingly recognized for their impact on patient outcomes. The Kaafarani classification and Surgical Apgar Score (SAS) were developed to assess the intraoperative course; however, both have their drawbacks. ClassIntra was validated for iAEs of any origin.

Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing.

Abdominal pain in patients with inflammatory bowel disease in remission: A prospective study on contributing factors.

Background: Abdominal pain is highly prevalent in patients with inflammatory bowel disease (IBD) in remission, but the aetiology is incompletely understood.

Aim: To investigate the association of clinical, lifestyle and psychosocial factors with abdominal pain in patients with IBD in remission.

Methods: We performed a prospective multicentre study enrolling consecutive patients with IBD.

Erector spinae plane block improves postoperative recovery after laminectomy and discectomy surgery: a retrospective cohort study.

Background: There is still room for improvement of pain management after spinal surgery. The goal of this study was to evaluate adding the erector spinae block to the standard analgesia regimen. Our hypothesis was that the erector spinae plane block will decrease length of hospital stay, reduce opioid need and improve numeric rating scale pain scores.

3DDPDs: describing protein dynamics for proteochemometric bioactivity prediction. A case for (mutant) G protein-coupled receptors.

Proteochemometric (PCM) modelling is a powerful computational drug discovery tool used in bioactivity prediction of potential drug candidates relying on both chemical and protein information. In PCM features are computed to describe small molecules and proteins, which directly impact the quality of the predictive models. State-of-the-art protein descriptors, however, are calculated from the protein sequence and neglect the dynamic nature of proteins.

Voices of society: the emergence of civil-society practices aiming to engage in the management of the COVID-19 pandemic in the Netherlands.

During the COVID-19 pandemic, public groups mobilised themselves in civil-society engagement practices (CSEPs) aiming to improve or suggest alternative epidemic management. This study explores the motivation to establish CSEPs and their perceived contributions to epidemic management, to gain insight whether integrating views of CSEPs could add value. A systematic online search was executed to identify CSEPs focused on COVID-19 management between January 2020 and January 2022 in the Netherlands.