Management of adult mechanically ventilated patients: A UK-wide survey.

Background: Mechanical ventilation is a common and often lifesaving intervention that is utilised in intensive care. However, the practices can vary between centres. Through this national survey we aim to gain more information about different strategies adopted across the UK.

Intensive Care Management of Severe Hyponatraemia-An Observational Study.

Hyponatraemia is a common electrolyte disorder. For patients with severe hyponatraemia, intensive care unit (ICU) admission may be required. This will enable close monitoring and allow safe management of sodium levels effectively.

Characteristics, Management, and Outcomes of Acute Life-Threatening Asthma in Adult Intensive Care.

Background: There is limited evidence regarding the management of acute life-threatening asthma in intensive care units (ICUs), and few guidelines have details on this. We aimed to describe the characteristics, management, and outcomes of adults with life-threatening asthma requiring ICU admission.

Methods: In this single-centre retrospective observational study, we included consecutive adults with acute asthma requiring ICU admission between 1 January 2016 and 31 December 2023.

Particles in Exhaled Air (PExA): Clinical Uses and Future Implications.

Access to distal airway samples to assess respiratory diseases is not straightforward and requires invasive procedures such as bronchoscopy and bronchoalveolar lavage. The particles in exhaled air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles (PEx) sized around 0.5-7 μm and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening.

Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial).

Introduction: AZD7442 (tixagevimab/cilgavimab) comprises neutralising monoclonal antibodies (mAbs) that bind to distinct non-overlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Viral evolution during mAb therapy can select for variants with reduced neutralisation susceptibility. We examined treatment-emergent SARS-CoV-2 variants during TACKLE (NCT04723394), a phase 3 study of AZD7442 for early outpatient treatment of coronavirus disease 2019 (COVID-19).

Multiple Organ Dysfunction Secondary to Herpes Simplex Virus -1 Reactivation After Treatment With Dexamethasone and Sarilumab for Covid-19 Disease.

Introduction: The immunological response to the SARS-CoV-2 virus and the treatment of COVID-19 disease present a potential susceptibility to viral reactivation, particularly Herpes simplex virus-1 (HSV-1).

Case Presentation: A 49-year-old female presented to hospital with severe COVID-19 pneumonitis and was given sarilumab and dexamethasone. She was intubated and ventilated in the intensive care unit (ICU) and initially demonstrated biochemical and clinical evidence of improvement.

Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants.

Background: We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.

Methods: Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.

Results: At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases.

Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review.

Background: Greater occipital nerve (GON) blockade is a short-term preventive therapy for cluster headache (CH). We conducted a systematic review to evaluate the effectiveness and safety of GON blockade in patients with CH.

Methods: On 23 October 2020, we searched MEDLINE, Embase, Embase Classic, PsycINFO, CINAHL, CENTRAL and Web of Science databases from their inception date.

Qualification of a Biolayer Interferometry Assay to Support AZD7442 Resistance Monitoring.

AZD7442, a combination of two long-acting monoclonal antibodies (tixagevimab [AZD8895] and cilgavimab [AZD1061]), has been authorized for the prevention and treatment of coronavirus disease 2019 (COVID-19). The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants requires methods capable of quickly characterizing resistance to AZD7442. To support AZD7442 resistance monitoring, a biolayer interferometry (BLI) assay was developed to screen the binding of tixagevimab and cilgavimab to SARS-CoV-2 spike proteins to reduce the number of viral variants for neutralization susceptibility verification.

Feasibility of a Web-Based Intervention to Prevent Perinatal Depression and Promote Human Milk Feeding: Randomized Pilot Trial.

Background: Mothers who identify as Black or African American are more likely to report depressed moods in late pregnancy and early postpartum and have the lowest rates of human milk feeding compared with all other racial groups in the United States. Internet interventions offer the potential to extend preventative and supportive services as they address key barriers, particularly for those navigating the complex and vulnerable early postpartum period. However, there is limited evidence on the feasibility of such interventions for preventing perinatal mental health disorders and improving human milk feeding outcomes in Black mothers.

Endocrine dysregulation in aneurysmal subarachnoid haemorrhage.

Introduction: Aneurysmal Subarachnoid haemorrhage (aSAH) is one of the most common causes of neurocritical care admission. Consistent evidence has been suggestive of endocrine dysregulation in aSAH. This review aims to provide an up-to-date presentation of the available evidence regarding endocrine dysregulation in aneurysmal subarachnoid haemorrhage.

Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.

Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts an evolutionary pressure on cancers that can result in the outgrowth of resistant clones. Use of rational drug combinations can overcome resistance to targeted drugs, but resistance may eventually develop to combinatorial therapies.

Retrospective cause analysis of troponin I elevation in non-CAD patients: Special emphasis on sepsis.

Background: Troponin I is one of the most commonly tested biochemical markers in the emergency room (ER) and in the hospital setting. Besides coronary artery disease (CAD), demand ischemia with underlying tachycardia, anemia, hypertensive emergency, congestive heart failure, kidney disease, sepsis, and pulmonary embolism have also been reported to cause troponin I elevations. Few reports have excluded patients with CAD, and no study has summarized the proportion of these factors relative to an increased troponin I level.

Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases.

Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19.

Gene expression profiling identifies distinct molecular subgroups of leiomyosarcoma with clinical relevance.

Background: Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Although defined as a single group, they exhibit a wide range of clinical behaviour.

Habituation of Arctic ground squirrels (Urocitellus parryii) to handling and movement during torpor to prevent artificial arousal.

Hibernation is a unique physiological adaptation characterized by periods of torpor that consist of repeated, reversible, and dramatic reductions of body temperature, metabolism, and blood flow. External and internal triggers can induce arousal from torpor in the hibernator. Studies of hibernating animals often require that animals be handled or moved prior to sampling or euthanasia but this movement can induce changes in the hibernation status of the animal.

Laparoscopic ventral mesh rectopexy in the management of solitary rectal ulcer syndrome: a cause for optimism?

Aim: The treatment of solitary rectal ulcer syndrome (SRUS) is notoriously difficult. Laparoscopic ventral mesh rectopexy (LVMR) is a nonresectional technique for patients with full thickness external rectal prolapse and internal prolapse with obstructed defaecation syndrome (ODS), features associated in the pathogenesis of SRUS. Our aim was to assess the short- and long-term efficacy of LVMR in treating SRUS.

Laparoscopic cholecystectomy in a patient with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited defect in haem synthesis causing dangerous phototoxic reactions following exposure to wavelengths of light around 400nm. It can cause catastrophic post-operative complications following open surgery, in which environment various safety measures are now routinely employed. The dangers at laparoscopy have never been discussed in the literature, and nor have any specific precautions been recommended.

Nuclear overexpression of the E2F3 transcription factor in human lung cancer.

Background: The E2F3 transcription factor has an established role in controlling cell cycle progression. In previous studies we have provided evidence that nuclear E2F3 overexpression represents a mechanism that drives the development of human bladder cancer and that determines aggressiveness in human prostate cancer. We have proposed a model in which E2F3 overexpression co-operates with removal of the E2F inhibitor pRB to facilitate cancer development.

Family medicine patients' use of the Internet for health information: a MetroNet study.

We explored a diverse sample of family medicine patients' use of the internet for health information. Primary objectives were to determine the extent of access to the Internet, and among those with access, the types of health information sought; how they search for that information; and how they assess the accuracy of the information. We also surveyed the physicians' perceptions of their patients' use of the Internet for health information.