A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion.

Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality for cell-based immunotherapy. However, its application in immunologically "cold" tumors such as glioblastoma remains limited due to sparse T cell infiltration, antigenic heterogeneity, and a suppressive tumor microenvironment. To identify genomic and spatial determinants of TIL expandability, we performed integrated, multimodal profiling of high-grade gliomas using spectral flow cytometry, TCR sequencing, single-cell RNA-seq, Xenium transcriptomics, and CODEX spatial proteomics.

IL-7-mediated expansion of autologous lymphocytes increases CD8+ VLA-4 expression and accumulation in glioblastoma models.

The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused nonantigen specific autologous lymphocytes could accumulate in intracranial tumors. We observed that nonspecific autologous CD8+ ALT cells can indeed accumulate in this context, despite endogenous T cell sequestration in bone marrow.

A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion.

Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality for cell-based immunotherapy. However, its application in immunologically 'cold' tumors such as glioblastoma remains limited due to sparse T cell infiltration, antigenic heterogeneity, and a suppressive tumor microenvironment. To identify genomic and spatial determinants of TIL expandability, we performed integrated, multimodal profiling of high-grade gliomas using spectral flow cytometry, TCR sequencing, single-cell RNA-seq, Xenium in situ transcriptomics, and CODEX spatial proteomics.

Associations of Patients with Pericardial Effusion Secondary to Light-Chain or Transthyretin Amyloidosis- A Systematic Review.

Background: Pericardial effusion is associated with amyloidosis, specifically amyloid light chain (AL) and transthyretin (ATTR) subtypes. However, the patients might present with different clinical symptoms.

Objective: To determine the characteristics and associations of patients with pericardial effusion owing to either AL or ATTR amyloidosis.

Correcting the drug development paradigm for glioblastoma requires serial tissue sampling.

A breakthrough in drug discovery for glioblastoma requires serial collection of tissue from the central nervous system via window of opportunity trials

Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.

Glioblastoma is highly aggressive and remains difficult to treat despite being the most common malignant primary brain tumor in adults. Current standard-of-care treatment calls for maximum resection of the tumor mass followed by concurrent chemotherapy and radiotherapy and further adjuvant chemotherapy if necessary. Despite this regimen, prognosis remains grim.

Endovascular and surgical obliteration rates of spinal dural arteriovenous fistulae: a single UK Centre experience.

Objective: Endovascular treatment (EVT) of spinal dural arteriovenous fistulae (SDAVF) has become increasingly popular given its less invasive nature. This study aims to assess radiological obliteration rates after surgery and EVT for SDAVF in a major tertiary referral centre serving a population of 2.2 million.

For whom the T cells troll? Bispecific T-cell engagers in glioblastoma.

Glioblastoma is the the most common primary brain tumor in adults. Onset of disease is followed by a uniformly lethal prognosis and dismal overall survival. While immunotherapies have revolutionized treatment in other difficult-to-treat cancers, these have failed to demonstrate significant clinical benefit in patients with glioblastoma.

Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma.

Glioblastoma is an immunologically 'cold' tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present.

Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma.

Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach.

Targeting Immunometabolism in Glioblastoma.

We have only recently begun to understand how cancer metabolism affects antitumor responses and immunotherapy outcomes. Certain immunometabolic targets have been actively pursued in other tumor types, however, glioblastoma research has been slow to exploit the therapeutic vulnerabilities of immunometabolism. In this review, we highlight the pathways that are most relevant to glioblastoma and focus on how these immunometabolic pathways influence tumor growth and immune suppression.

Improving the surgical consenting process for patients with acute hip fractures: a pilot quality improvement project.

Background: Consenting patients for trauma procedures following hip fracture is a key stage in the treatment pathway from admission to the operating theatre. Errors in this process can result in delayed procedures which may negatively impact patient recovery. The aim of this project was to identify and reduce errors in our consenting process for patients with capacity.

Does time of surgery influence the rate of false-negative appendectomies? A retrospective observational study of 274 patients.

Background: Multiple disciplines have described an "after-hours effect" relating to worsened mortality and morbidity outside regular working hours. This retrospective observational study aimed to evaluate whether diagnostic accuracy of a common surgical condition worsened after regular hours.

Methods: Electronic operative records for all non-infant patients (age > 4 years) operated on at a single centre for presumed acute appendicitis were retrospectively reviewed over a 56-month period (06/17/2012-02/01/2017).

Xanthomatous hypophysitis causing hypogonadotropic hypogonadism resulting in delayed presentation of slipped capital femoral epiphysis.

An 18-year-old man who underwent bilateral pinning of his hip joints after a left unstable Slipped Capital Femoral Epiphysis (right pinned prophylactically) was noted to have delayed secondary sexual characteristics and post-operative diabetes insipidus. The patient also described a history of fatigue, headache and polydipsia for the past 4 years. Endocrine investigations revealed reduced androgen levels, hypocortisolism, a borderline normal Serum ACE and secondary hypothyroidism.

An unusual case of a grade I meningioma with perineural spread.

A 39-year-old lady with worsening intermittent diplopia and headaches was diagnosed with a WHO Grade I Meningothelial Meningioma with highly unusual perineural spread on imaging, making this the first reported case of this behaviour. Complete surgical resection was deemed too great a risk and the patient remains under observation. The process of perineural spread is not restricted to more aggressive brain tumours.

Improving access to Early Intervention in Psychosis (EIP): the 2-week wait for cancer comes to psychosis.

Early Intervention in Psychosis (EIP) services aim to rapidly initiate specialist packages of care for those people newly experiencing symptoms. The intention of such rapid engagement is to mitigate the negative effects of a prolonged duration of untreated psychosis. Aiming to achieve a 'parity of esteem' between mental and physical health, a new target was introduced by the National Health Service (NHS) England, where 50% of new referrals were expected to receive a concordant package of care within 2 weeks from the National Institute for Health and Care Excellence.