Management of antithrombotic therapy in patients undergoing dental procedures.

A growing number of patients receiving antithrombotic therapy require dental procedures. Dental interventions in these patients can be challenging, as the risk of bleeding from the continuation of antithrombotic therapy needs to be weighed against the thromboembolic risk associated with drug interruption or de-escalation. Most minor dental procedures, including simple dental cleaning and filling, pose minimal bleeding risk, and antiplatelet or anticoagulation therapy can be continued without interruption.

Intraoperative kidney replacement therapy in acute liver failure.

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes.

Simultaneous Focal Boost With Stereotactic Radiation Therapy for Localized Intermediate- to High-Risk Prostate Cancer: Primary Outcomes of the SPARC Phase 2 Trial.

Purpose: Dose-escalated radiation therapy is associated with better biochemical control at the expense of toxicity. Stereotactic body radiation therapy (SBRT) with dose escalation to the dominant intraprostatic lesion (DIL) provides a logical approach to improve outcomes in high-risk disease while limiting toxicity. This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer.

Paraquat ingestion in an adult with cystic fibrosis (CF): Diagnostic and management dilemmas.

N,N'-dimethyl-4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long-term sequelae of paraquat, namely osteonecrosis.

TSC2 S1365A mutation potently regulates CD8+ T cell function and differentiation and improves adoptive cellular cancer therapy.

MTORC1 integrates signaling from the immune microenvironment to regulate T cell activation, differentiation, and function. TSC2 in the tuberous sclerosis complex tightly regulates mTORC1 activation. CD8+ T cells lacking TSC2 have constitutively enhanced mTORC1 activity and generate robust effector T cells; however, sustained mTORC1 activation prevents generation of long-lived memory CD8+ T cells.

Intradermal delivery of a quadrivalent cell-based seasonal influenza vaccine using an adjuvanted skin patch vaccination platform.

All seasonal influenza vaccines for 2021-2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology.

Comparative Stiffness Characteristics of Ilizarov- and Hexapod-type External Frame Constructs.

Background: The Ilizarov method and fixator are clinically recognised for the treatment of fractures, limb salvage and deformity correction. There have been extensive studies determining the basic mechanism for fracture healing using this technique. It is generally accepted that circular frames optimise the mechanical environment by reducing shear strain across the fracture while maintaining axial micromotion so as to promote fracture healing.

Taste responsiveness of chimpanzees (Pan troglodytes) and black-handed spider monkeys (Ateles geoffroyi) to eight substances tasting sweet to humans.

Using a two-bottle choice test of short duration, we determined taste preference thresholds for eight substances tasting sweet to humans in three chimpanzees (Pan troglodytes) and four black-handed spider monkeys (Ateles geoffroyi). We found that the chimpanzees significantly preferred concentrations as low as 100-500 mM galactose, 250 mM sorbitol, 0.5-2 mM acesulfame K, 0.

Atrophy patterns in isolated subscapularis lesions.

Background: While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon.

Methods: Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane.

Remote Patient Monitoring Program for Hospital Discharged COVID-19 Patients.

Objective: We deployed a Remote Patient Monitoring (RPM) program to monitor patients with coronavirus disease 2019 (COVID-19) upon hospital discharge. We describe the patient characteristics, program characteristics, and clinical outcomes of patients in our RPM program.

Methods: We enrolled COVID-19 patients being discharged home from the hospital.

The V-shaped subscapularis tenotomy for anatomic total shoulder arthroplasty.

Purpose: Management of the subscapularis tendon during anatomic total shoulder arthroplasty (TSA) remains controversial. In our unit, subscapularis tenotomy is the preferred technique; however, the potential for tendon gapping and failure is recognised. The purpose of this study is to describe and provide early clinical results of a novel, laterally based V-shaped tenotomy (VT) technique hypothesised to provide greater initial repair strength and resistance to gapping than a transverse tenotomy (TT), with both clinically and radiologically satisfactory post-operative tendon healing and function.

Stereotactic radiotherapy with focal boost for intermediate and high-risk prostate cancer: Initial results of the SPARC trial.

Introduction: Dose escalation to dominant intraprostatic lesions (DILs) is a novel method to increase the therapeutic ratio in localised prostate cancer. The Stereotactic Prostate Augmented Radiotherapy with Cyberknife (SPARC) trial was designed to determine the feasibility of a focal boost defined with multiparametric magnetic resonance imaging (mpMRI) using stereotactic ablative body radiotherapy (SABR).

Materials And Methods: Patients were included with newly diagnosed intermediate to high risk prostate cancer with at least one of: Gleason score 4 + 3, stage T3a, or PSA > 20 ng/ml.

Cohort study of sleep quality in adult patients with acute pulmonary exacerbations of cystic fibrosis.

Background: The impact of an acute pulmonary exacerbation of cystic fibrosis (CF) on sleep quality has not been established. Patients have greater burden of symptoms, higher intensity of therapy and are often admitted to hospital outside of their usual sleeping environment.

Aims: To evaluate the prevalence of, and factors associated with, poor sleep quality in adult patients admitted to hospital with an acute exacerbation of CF lung disease.

VaxiPatch™, a novel vaccination system comprised of subunit antigens, adjuvants and microneedle skin delivery: An application to influenza B/Colorado/06/2017.

This work introduces VaxiPatch, a novel vaccination system comprised of subunit glycoprotein vaccine antigens, adjuvants and dermal delivery. For this study, rHA of influenza virus B/Colorado/06/2017 was incorporated into synthetic virosomes, and adjuvant liposomes were formed with QS-21 from Saponaria quillaja, with or without the synthetic TLR4 agonist 3D - (6-acyl) PHAD. These components were concentrated and co-formulated into trehalose with dye.

Cardiorespiratory fitness, sleep, and physiological responses to stress in women.

Epidemiological studies suggest that cardiorespiratory fitness (CRfitness) is associated with reduced risk of depression and anxiety in women, however, the mechanisms by which CRfitness may be protective against the development of these disorders are less clear. Because sleep problems are associated with both a higher risk for mental illness and altered physiological responses to stress, this study investigated whether sleep quality might influence the relationship between CRfitness and physiological stress responses in women. Thirty healthy women (18-45 y) who were medication-free, with regular menstrual cycles completed: (1) enrolment visit [including the assessment of CRfitness via maximal oxygen consumption during exercise]; (2) one-week sleep monitoring period including subjective (daily sleep diaries) and objective (wrist actigraphy) sleep measures; and (3) psychosocial stressor protocol (the Trier Social Stress Test; TSST) for the collection of heart rate (HR), blood pressure (BP), and salivary cortisol stress responses.

CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma.

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas and other cancers can hamper CAR T cells is through surface expression of inhibitory ligands such as programmed cell death ligand 1 (PD-L1). Using the CRIPSR-Cas9 system, we created universal CAR T cells resistant to PD-1 inhibition through multiplexed gene disruption of endogenous T-cell receptor (TRAC), beta-2 microglobulin (B2M) and PD-1 (PDCD1).

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.

Background: Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy.

Functional improvements in active elevation, external rotation, and internal rotation after reverse total shoulder arthroplasty with isolated latissimus dorsi transfer: surgical technique and midterm follow-up.

Hypothesis: This study investigated the hypothesis that reverse total shoulder arthroplasty (RSA) in combination with an isolated latissimus dorsi tendon (LDT) transfer in patients with pseudoparalysis of abduction and external rotation (combined loss of active elevation and external rotation [CLEER] syndrome) would demonstrate improved postoperative functional results.

Methods: This study was a retrospective single-surgeon case series of 13 consecutive patients with CLEER who underwent RSA without subscapularis repair and combined with an isolated LDT transfer. We reviewed 10 patients (77%), at a minimum of 2 years, with 3 cases lost to follow-up.

Utility of Multi-Parametric Quantitative Magnetic Resonance Imaging for Characterization and Radiotherapy Response Assessment in Soft-Tissue Sarcomas and Correlation With Histopathology.

To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the surgical specimens. Thirty patients with retroperitoneal sarcoma were imaged at baseline, of whom 27 also underwent a second baseline examination for repeatability assessment. 14/30 patients were treated with pre-operative radiotherapy and were imaged again after completing radiotherapy (50.

Locking nail versus locking plate for proximal humeral fracture fixation in an elderly population: a prospective randomised controlled trial.

Background: Proximal humeral fractures (PHFs) are the third most common fracture in older patients. The purpose of the study was to prospectively evaluate the outcomes of PHF fixation with a locking blade nail (LBN) or locking plate (PHILOS) osteosynthesis in a homogeneous elderly patient population.

Methods: Inclusion criteria were an age > 60 years and the capacity to give informed consent.

Dosimetric Implications of Computerised Tomography-Only versus Magnetic Resonance-Fusion Contouring in Stereotactic Body Radiotherapy for Prostate Cancer.

Magnetic resonance (MR)-fusion contouring is the standard of care in prostate stereotactic body radiotherapy (SBRT) for target volume localisation. However, the planning computerised tomography (CT) scan continues to be used for dose calculation and treatment planning and verification. Discrepancies between the planning MR and CT scans may negate the benefits of MR-fusion contouring and it adds a significant resource burden.

Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly.

X-linked Dystonia-Parkinsonism (XDP) is a Mendelian neurodegenerative disease that is endemic to the Philippines and is associated with a founder haplotype. We integrated multiple genome and transcriptome assembly technologies to narrow the causal mutation to the TAF1 locus, which included a SINE-VNTR-Alu (SVA) retrotransposition into intron 32 of the gene. Transcriptome analyses identified decreased expression of the canonical cTAF1 transcript among XDP probands, and de novo assembly across multiple pluripotent stem-cell-derived neuronal lineages discovered aberrant TAF1 transcription that involved alternative splicing and intron retention (IR) in proximity to the SVA that was anti-correlated with overall TAF1 expression.