Preoperative and postoperative optimisation of patients undergoing thyroid surgery: a multicentre quality improvement project at Barts Health NHS Trust.

Hypocalcaemia following thyroid surgery can occur in up to 38% of patients. With over 7100 thyroid surgeries performed in 2018 in the UK, this is a common postoperative complication. Undertreated hypocalcaemia can result in cardiac arrhythmias and death.

Emerging Therapeutic Strategies for Fragile X Syndrome: Q&A.

Understanding how best to treat aspects of Fragile X syndrome has the potential to improve the quality of life of affected individuals. Such an effective therapy has, as yet, remained elusive. In this article, we ask those researching or affected by Fragile X syndrome their views on the current state of research and from where they feel the most likely therapy may emerge.

Sinonasal carcinosarcoma with cartilaginous and rhabdomyoblastic components: A previously undescribed entity.

Carcinosarcomas are rare, aggressive tumors seldom found in the sinonasal region. They classically consist of sarcomatous spindle cell and carcinomatous squamous cell elements. A 61-year-old woman presented reporting right-sided nasal discharge and obstruction.

Dysregulated Maresin Concentrations in Plasma and Nasal Secretions From Patients With Chronic Rhinosinusitis.

The mechanisms that lead to disease onset and propagation in patients with chronic rhinosinusitis (CRS) are not fully elucidated. Maresins (MaR) are a family of essential fatty acid-derived lipid mediators that play a central role in the regulation of inflammation with several studies demonstrating that these mediators display protective activities in airway inflammation. Therefore, in the present studies we evaluated whether concentrations of these mediators were altered in both peripheral blood and nasal secretions from CRS patients.

Disrupted Resolution Mechanisms Favor Altered Phagocyte Responses in COVID-19.

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The molecular march of primary and recurrent nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) results from the aberrant and uncontrolled growth of the nasopharyngeal epithelium. It is highly associated with the Epstein-Barr virus, especially in regions where it is endemic. In the last decade, significant advances in genetic sequencing techniques have allowed the discovery of many new abnormal molecular processes that undoubtedly contribute to the establishment, growth and spread of this deadly disease.

A new oncolytic augments antitumor immune responses to prevent tumor recurrence and metastasis after surgery.

Background: Local recurrence and remote metastasis are major challenges to overcome in order to improve the survival of patients with cancer after surgery. Oncolytic viruses are a particularly attractive option for prevention of postsurgical disease as they offer a non-toxic treatment option that can directly target residual tumor deposits and beneficially modulate the systemic immune environment that is suppressed post surgery and allows residual disease escape from control. Here, we report that a novel (VV), VVΔTKΔN1L (with deletion of both thymidine kinase (TK) and N1L genes) armed with interleukin 12 (IL-12), can prolong postoperative survival when used as a neoadjuvant treatment in different murine and hamster surgical models of cancer.

Transient Inhibition of PI3Kδ Enhances the Therapeutic Effect of Intravenous Delivery of Oncolytic Vaccinia Virus.

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors.

Long-term outcomes of children treated for Cushing's disease: a single center experience.

Purpose: Pediatric Cushing's disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients.

Methods: Retrospective review of 21 CD patients, mean age at diagnosis 12.

Vaccinia virus, a promising new therapeutic agent for pancreatic cancer.

The poor prognosis of pancreatic cancer patients signifies a need for radically new therapeutic strategies. Tumor-targeted oncolytic viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability to specifically target and lyse tumor cells as well as induce antitumor effects by multiple action mechanisms. Vaccinia virus has several inherent features that make it particularly suitable for use as an oncolytic agent.

A surprising cause of unilateral nasal obstruction and epistaxis: nasal septal schwannoma.

Schwannomas of the head and neck are the most common form of benign nerve sheath tumours, most commonly arising in the form of vestibular schwannomas. Schwannoma of the nasal cavity is an uncommon presentation of this pathology and specifically Schwannoma of the nasal septum is a rare presentation of this well understood disease process. We present the case of a 31-year-old Eastern European male who presented with unilateral nasal obstruction, congestion and epistaxis of 3 months duration.

Characterization of SNARE proteins in human pituitary adenomas: targeted secretion inhibitors as a new strategy for the treatment of acromegaly?

Context: Targeted secretion inhibitors (TSIs), a new class of recombinant biotherapeutic proteins engineered from botulinum toxin, represent a novel approach for treating diseases with excess secretion. They inhibit hormone secretion from targeted cell types through cleavage of SNARE (soluble N-ethylmaleimide-sensitive factor-activating protein receptor) proteins. qGHRH-LH(N)/D is a TSI targeting pituitary somatotroph through binding to the GHRH-receptor and cleavage of the vesicle-associated membrane protein (VAMP) family of SNARE proteins.

Endonasal endoscopic transsphenoidal pituitary surgery: early experience and outcome in paediatric Cushing's disease.

Background: Selective adenomectomy remains the first-line treatment for Cushing's disease (CD), until recently by microscopic transsphenoidal pituitary surgery. Endonasal transsphenoidal endoscopic surgery (ETES) is emerging as a novel, less invasive treatment for pituitary adenomas and has become the optimal surgical approach.

Objective: There are no published series for the treatment of paediatric CD by ETES, and we report our centre's preliminary results.

A novel therapeutic regimen to eradicate established solid tumors with an effective induction of tumor-specific immunity.

Purpose: The efficacy of oncolytic viruses depends on multiple actions including direct tumor lysis, modulation of tumor perfusion, and stimulation of tumor-directed immune responses. In this study, we investigated whether a sequential combination of immunologically distinct viruses might enhance antitumor efficacy through the induction of tumor-specific immunity and circumvention or mitigation of antiviral immune responses.

Experimental Design: The Syrian hamster as an immune-competent model that supports replication of both adenovirus and vaccinia virus was evaluated in vitro and in vivo.

Combined blockade of signalling pathways shows marked anti-tumour potential in phaeochromocytoma cell lines.

Currently, there is no completely effective therapy available for metastatic phaeochromocytomas (PCCs) and paragangliomas. In this study, we explore new molecular targeted therapies for these tumours, using one more benign (mouse phaeochromocytoma cell (MPC)) and one more malignant (mouse tumour tissue (MTT)) mouse PCC cell line - both generated from heterozygous neurofibromin 1 knockout mice. Several PCC-promoting gene mutations have been associated with aberrant activation of PI3K/AKT, mTORC1 and RAS/RAF/ERK signalling.

Meta-analysis of minimally invasive video-assisted thyroidectomy.

Objectives: The aim of this study is to compare minimally invasive video-assisted thyroidectomy (MIVAT) to conventional thyroidectomy.

Study Design: A systematic review of the literature and meta-analysis.

Methods: All published prospective controlled trials that compared MIVAT to conventional thyroidectomy were identified.

Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene: an oncolytic virus superior to dl1520 (ONYX-015) for human head and neck cancer.

Oncolytic viral therapy represents a promising strategy for the treatment of head and neck squamous cell carcinoma (HNSCC), with dl1520 (ONYX-015) the most widely used oncolytic adenovirus in clinical trials. This study aimed to determine the effectiveness of the Lister vaccine strain of vaccinia virus as well as a vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapy for HNSCC and to compare them with dl1520. The potency and replication of the Lister strain and VVhEA and the expression and function of the fusion protein were determined in human HNSCC cells in vitro and in vivo.

Cancer-specific transgene expression mediated by systemic injection of nanoparticles.

The lack of safe and efficient systemic gene delivery vectors has largely reduced the potential of gene therapy in the clinic. Previously, we have reported that polypropylenimine dendrimer PPIG3/DNA nanoparticles are capable of tumor transfection upon systemic administration in tumor-bearing mice. To be safely applicable in the clinic, it is crucial to investigate the colloidal stability of nanoparticles and to monitor the exact biodistribution of gene transfer in the whole body of the live subject.

A head and neck cancer database for the 21st century.

A versatile, hand-held computerised database is described. Its use for general patient management, audit and as a tool for clinical governance is illustrated.