Mesothelin antigen density influences anti-mesothelin chimeric antigen receptor T cell cytotoxicity.

Background Aims: Several anti-mesothelin (MSLN) chimeric antigen receptor (CAR) T cells are in phase 1/2 clinical trials to treat solid-organ malignancies. The effect of MSLN antigen density on MSLN CAR cytotoxicity against tumor cells has not been examined previously, nor are there data regarding the effect of agents that increase MSLN antigen density on anti-MSLN CAR T cell efficacy.

Methods: MSLN antigen density was measured on a panel of pancreatic cancer and mesothelioma cell lines by flow cytometry.

Erratum: Six Nations: a clinical scenario comparison of systems for prisoners with psychosis in Australia, Bolivia and four European nations - ERRATUM.

[This corrects the article DOI: 10.1192/bji.2022.

RISK aversion in Italian forensic and non-forensic patients with schizophrenia spectrum disorders.

Background: Goal-directed decision-making is a central component of the broader reward and motivation system, and requires the ability to dynamically integrate both positive and negative feedback from the environment in order to maximize rewards and minimize losses over time. Altered decision-making processes, in which individuals fail to consider the negative consequences of their decisions on both themselves and others, may play a role in driving antisocial behaviour.

Aim: The main study aim was to investigate possible differences in loss and risk aversion across matched patients, all with a schizophrenia spectrum disorder (SSD), but who varied according to whether they had a history of serious interpersonal violence or not, and a sample of healthy controls with no history of violence.

Difference between forensic patients with schizophrenia spectrum disorders in Italy and other European countries: Results of the EU-VIORMED project.

Background: There has been a substantial change in the law on the provision of secure health services for offender-patients in Italy, a country currently with the lowest general psychiatry bed availability per head of the population in Europe, raising questions about possible differences in offender-patient admissions between European countries.

Aims: In this multicentre case-control study, our aim was to compare the socio-demographic, clinical and criminological characteristics of a sample of Italian forensic in-patients with schizophrenia or similar psychosis with patients in a similar diagnostic range in specialist in-patient services elsewhere in Europe.

Methods: Secure hospital unit in-patients with psychosis were recruited across five European countries (Italy, Austria, Germany, Poland and England).

Six nations: a clinical scenario comparison of systems for prisoners with psychosis in Australia, Bolivia and four European nations.

This paper compares across six nations the mental health systems available to prisoners with the highest acuity of psychosis and risk combined with the lowest level of insight into the need for treatment. Variations were observed within and between nations. Findings highlight the likely impact of factors such as mental health legislation and the prison mental health workforce on a nation's ability to deliver timely and effective treatment close to home for prisoners who lack capacity to consent to treatment for their severe mental illness.

Clinical and radiological presentation of parasellar ectopic pituitary adenomas: case series and systematic review of the literature.

Purpose: Parasellar ectopic pituitary adenomas (pEPAs) are extremely rare tumors located out of the sella turcica. PEPAs are heterogeneous entities in terms of anatomical localization and secretion of anterior pituitary hormones.

Methods: Multicenter retrospective study.

Hitting the Bull's-Eye: Mesothelin's Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options and poor prognosis. MPM originates from the mesothelial lining of the pleura. Mesothelin (MSLN) is a glycoprotein expressed at low levels in normal tissues and at high levels in MPM.

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective.

Background: First-generation somatostatin receptor ligands (fg-SRLs) represent the first-line medical treatment for acromegaly, recommended in patients with persistent disease after neurosurgery, or when surgical approach is not feasible. Despite the lack of strong recommendations from guidelines and consensus statements, data from national Registries report an increasing use of medical therapy as first-line treatment in acromegaly.

Objective: We retrospectively evaluated the potential role of a large number of clinical and radiological parameters in predicting the biochemical response to 6-month treatment with fg-SRLs, in a cohort of naïve acromegaly patients referred to a single tertiary center for pituitary diseases.

From High-Throughput Screening to Target Validation: Benzo[]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents.

Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a nonselective monovalent cation channel activated by intracellular Ca increase. Within the gastrointestinal system, TRPM5 is expressed in the stoma, small intestine, and colon. In the search for a selective agonist of TRPM5 possessing in vivo gastrointestinal prokinetic activity, a high-throughput screening was performed and compound was identified as a promising hit.

Anti-Mesothelin CAR T cell therapy for malignant mesothelioma.

Malignant mesothelioma (MM) is a treatment-resistant tumor originating in the mesothelial lining of the pleura or the abdominal cavity with very limited treatment options. More effective therapeutic approaches are urgently needed to improve the poor prognosis of MM patients. Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a novel potential treatment for this incurable solid tumor.

An unusual case of coma related to glutamate receptor 3 (GluR3) auto-antibodies after a traumatic spinal cord injury: Clinical and pathological aspects.

We report the case of a 28-year-old patient with a history of post-traumatic epilepsy who, following a spinal cord injury and the onset of nosocomial infection, went into a deep coma. A brain MRI revealed non-specific findings, anti-Glutamate Receptor 3 (GluR3) auto-antibodies were detected in the liquor, and the patient's serum and immunomodulatory therapy proved ineffective. Autopsy and histological investigations led to the diagnosis of autoimmune encephalitis.

Exploring Needs and Quality of Life of Forensic Psychiatric Inpatients in the Reformed Italian System, Implications for Care and Safety.

The Italian forensic psychiatric system underwent drastic reforms. The newly developed facilities are inspired by psychiatric community services, embracing a recovery-oriented approach. Needs and quality of life are broader concepts that consider the more rehabilitative and humanitarian aspects of treatment.

Development of novel multipotent compounds modulating endocannabinoid and dopaminergic systems.

Polypharmacology approaches may help the discovery of pharmacological tools for the study or the potential treatment of complex and multifactorial diseases as well as for addictions and also smoke cessation. In this frame, following our interest in the development of molecules able to modulate either the endocannabinoid or the dopaminergic system, and given the multiple and reciprocal interconnections between them, we decided to merge the pharmacophoric elements of some of our early leads for identifying new molecules as tools able to modulate both systems. We herein describe the synthesis and biological characterization of compounds 5a-j inspired by the structure of our potent and selective fatty acid amide hydrolase (FAAH) inhibitors (3a-c) and ligands of dopamine D or D receptor subtypes (4a,b).

Unusual and Fatal Case of an Undiagnosed Intravascular Large B-cell Lymphoma: The Oncologist's Great Imitator.

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphomas that is characterized by the selective growth of neoplastic cells within the lumen of small vessels. Authors document the case of an unexpected death caused by an undiagnosed intravascular large B-cell lymphoma with multi-organ involvement, which had initially manifested as an infection and then as an unclarified central nervous system pathology. Histological examination showed a diffuse intravascular large B-cell brain lymphoma with prominent cerebral involvement.

The closing of forensic psychiatric hospitals in Italy: Determinants, current status and future perspectives. A scoping review.

Introduction: Italy is the only country in the world to have closed forensic psychiatric hospitals and converted to fully-residential services. The international interest around this reform has not been matched by research. This scoping review aims to report the determinants of the reform, the most updated information on how the system operates, its benefits and its challenges.

The Individual Experience of Aging Patients and the Current Service Provision in the Context of Italian Forensic Psychiatry: A Case Study.

Introduction: After the recent development of residential units for the execution of security measures managed by the National Health Service and the closing down of forensic psychiatric hospitals, no study has been conducted to investigate the individual experience of aging patients and to assess whether the new service is adequately meeting their needs. We aimed to explore the experience of the service of a sample of patients aged 50 years and above living in one of the Italian residential units for the execution of security measures.

Methods: We adopted a case study design and included a sample of five patients.

A fatal and unusual iatrogenic fourth right lumbar artery injury complicating wrong-level hemilaminectomy: a case report and literature review.

The authors describe an unusual case of a fatal iatrogenic fourth lumbar artery injury during left hemilaminectomy in a 38-year-old woman. At autopsy, gross inspection revealed hemoperitoneum with 1,800 ml of free blood and massive retroperitoneal extravasation. A laceration with irregular and jagged margins was detected on the wall of the fourth right lumbar artery.

Qualitative and quantitative analysis of PMN/T-cell interactions by InFlow and super-resolution microscopy.

Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis and/or NETosis. Apart from these conventional roles, PMN also have immune-regulatory functions. They can transdifferentiate and upregulate MHCII as well as ligands for costimulatory receptors which enables them to behave as antigen presenting cells (APC).

1,2,4-Triazolyl 5-Azaspiro[2.4]heptanes: Lead Identification and Early Lead Optimization of a New Series of Potent and Selective Dopamine D3 Receptor Antagonists.

A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases.

1,2,4-Triazolyl octahydropyrrolo[2,3-b]pyrroles: A new series of potent and selective dopamine D3 receptor antagonists.

A novel series of 1,2,4-triazolyl octahydropyrrolo[2,3-b]pyrroles showing high affinity and selectivity at the DA D3 receptor is reported here. Compounds endowed with high selectivity over the hERG channel were identified and their pharmacokinetic properties thoroughly analyzed. A few derivatives with appropriate developability characteristics were selected for further studies and progression along the screening cascade.

Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.

Intra-operative vertebroplasty combined with posterior cord decompression. A report of twelve cases.

Percutaneous vertebroplasty (VP) is a minimally invasive technique for the treatment of vertebral pathology providing early vertebral stabilization and pain relief. In cases of vertebral pathology complicated by spinal cord compression with associated neurological deficits, VP alone cannot be performed free of risks. We describe a combined approach in which decompressive laminectomy and intra-operative vertebroplasty (IVP) are performed during a single session.