A non-randomised open-label exploratory 'window of opportunity' study of TG02 treatment in patients with locally advanced primary and recurrent mutant colorectal cancer.

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with -mutant colorectal cancer.

Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF.

Use of patient-derived explants as a preclinical model for precision medicine in colorectal cancer: A scoping review.

Purpose: Whilst the treatment paradigm for colorectal cancer has evolved significantly over time, there is still a lack of reliable biomarkers of treatment response. Treatment decisions are based on high-risk features such as advanced TNM stage and histology. The role of the tumour microenvironment, which can influence tumour progression and treatment response, has generated considerable interest.

Technological advances define shifting pathway signaling from normal to primary and metastatic colorectal cancer.

Adoption of organoid/tumoroid propagation of normal and malignant intestinal epithelia has provided unparalleled opportunities to compare cell growth factor and signaling dependencies. These 3D structures recapitulate tumours in terms of gene expression regarding the tumor cells but also allow deeper insights into the contribution of the tumour microenvironment (TME). Elements of the TME can be manipulated or added back in the form of infiltrating cytotoxic lymphocytes and/or cancer associated fibroblasts.

Acute Abortive Therapies for Seizure Clusters in Long-Term Care.

Objectives: To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures and seizure clusters.

Design: Narrative review.

Setting And Participants: People with seizures in long-term care, including group residences.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

Aim: Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective.

Cell signaling activation and extracellular matrix remodeling underpin glioma tumor microenvironment heterogeneity and organization.

Purpose: Tumor cells thrive by adapting to the signals in their microenvironment. To adapt, cancer cells activate signaling and transcriptional programs and migrate to establish micro-niches, in response to signals from neighboring cells and non-cellular stromal factors. Understanding how the tumor microenvironment evolves during disease progression is crucial to deciphering the mechanisms underlying the functional behavior of cancer cells.

MAO Visible Spectroscopy for Ligand Interactions, Redox Chemistry, and Kinetics of Irreversible Inhibition.

The covalently bound FAD cofactor in monoamine oxidase (MAO) is reduced by the amine substrate and reoxidized by oxygen. Visible spectroscopy provides a convenient tool to study the interaction of ligands and the kinetics of the half-reactions for mechanistic investigations. Equilibrium redox titrations allow measurement of redox potentials, while rapid mixing experiments allow determination of the rate of reduction by different substrates and of covalent adduct formation by irreversible inactivators.

New insights into the unique nature of colorectal cancer peritoneal metastases-rethinking HIPEC.

Colorectal peritoneal metastases (CRPM) can be resistant to the chemotherapy agent (oxaliplatin) most employed, up until recently, as hyperthermic intraperitoneal chemotherapy (HIPEC). Glutathione-mediated inactivation of oxaliplatin can be substantially reduced by genomic deletion of the gene or pharmacological inhibition of glutamate-cysteine ligase in CRPM tumouroids. These discoveries may rekindle the enthusiasm for HIPEC in concert with cytoreductive surgery, which has been employed to manage patients with this once-nihilistic form of stage-IV disease.

Effect of Surgical Humidification on Inflammation and Peritoneal Trauma in Colorectal Cancer Surgery: A Randomized Controlled Trial.

Background: Pre-clinical studies indicate that dry-cold-carbon-dioxide (DC-CO2) insufflation leads to more peritoneal damage, inflammation and hypothermia compared with humidified-warm-CO (HW-CO2). Peritoneum and core temperature in patients undergoing colorectal cancer (CRC) surgery were compared.

Methods: Sixty-six patients were randomized into laparoscopic groups; those insufflated with DC-CO2 or HW-CO2.

The impact of molecular and mismatch repair status on the survival outcomes of surgically treated patients with colorectal peritoneal metastases.

Background: Stratification of patients with colorectal peritoneal metastases (CRPM) using RAS/BRAF mutational status may refine patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to analyse the association of RAS/BRAF status and their variants, with clinicopathological variables and survival outcomes in patients who have undergone CRS ± HIPEC.

Methods: A single centre, peritonectomy database was interrogated for patients with CRPM who underwent peritonectomy procedures between 2010 and 2020.

Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial.

Objective: Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) antiseizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh the benefits. Novel treatments are needed to stop and durably control RSE without escalation to IV anesthetics.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases in an elderly population: outcomes from a single centre.

Background: The prevalence of elderly patients with resectable colorectal peritoneal metastases (CRPM) is increasing. This study aimed to compare short and long-term outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPM in patients above and below 70 years of age.

Methods: This was a retrospective, 10-year analysis of 90-day major morbidity and mortality, and long-term survival.

Real-world clinical and cost-effectiveness of community clozapine initiation: mirror cohort study.

Background: Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.

Aims: The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.

Method: This was a naturalistic study of community patients recommended for clozapine treatment.

The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis.

Background: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial.

Methods: A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC.

Warm humidified CO2 insufflation improves pericardial integrity for cardiac surgery: a randomized control study.

Background: Flooding the surgical field with dry cold CO2 during open-chamber cardiac surgery has been used to mitigate air entrainment into the systemic circulation. However, exposing epithelial surfaces to cold, dry gas causes tissue desiccation. This randomized controlled study was designed to investigate whether the use of humidified warm CO2 insufflation into the cardiac cavity could reduce pericardial tissue damage and the incidence of micro-emboli when compared to dry cold CO2 insufflation.

Diagnostic performance of positron emission tomography in the staging of pseudomyxoma peritonei.

Background: Pseudomyxoma peritonei (PMP) is a rare clinical entity, commonly derived from a mucin-producing tumour of the appendix. International consensus is unclear on the role of positron emission tomography (PET) in preoperative staging. This study aimed to assess the ability of preoperative PET in predicting the histological grade of PMP.

Primary and metastatic peritoneal surface malignancies.

Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis).