Awake tracheal intubation with the ProVu™ video stylet: a case series.

Management of the difficult airway is integral to peri-operative practice. The development of devices to simplify airway handling are changing our approach to tracheal intubation. We report a case series of three patients who underwent awake tracheal intubation with the ProVu™ video stylet (Flexicare Medical Ltd, Mountain Ash, UK). All three patients had predicted difficult airways, including: limited mouth opening secondary to radiotherapy; previous exenteration, hemi-maxillectomy and scapular free flap formation; and cervical fixation. Awake tracheal intubation was performed successfully in all three cases, with no complications reported. This is the first reported case series of the ProVu™ video stylet as an awake tracheal intubation device. The benefits and limitations of this video stylet are discussed.

Risks to healthcare workers following tracheal intubation of patients with COVID-19: a prospective international multicentre cohort study.

Healthcare workers involved in aerosol-generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID-19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID-19. Information on tracheal intubation episodes, personal protective equipment use and subsequent provider health status was collected via self-reporting. The primary endpoint was the incidence of laboratory-confirmed COVID-19 diagnosis or new symptoms requiring self-isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure-related factors and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow-up of 32 (18-48 [0-116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1% and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in women, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID-19 subsequently reported a COVID-19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID-19 transmission.

Characterising the nutritional status of children with primary ciliary dyskinesia.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, heterogeneous genetic disorder where impaired mucociliary clearance is caused by dysfunctional motile cilia leading to bronchiectasis. There is limited evidence characterising the nutritional status of children with PCD, although lower body mass index (BMI) z-score has been associated with worse lung function (FEV1). METHODS: All children (n = 43) with PCD, aged <16 years, from a single tertiary centre were prospectively enrolled. Information on clinical phenotype and nutritional status including bioelectrical impedance spectroscopy (BIS) phase-angle was collected. RESULTS: There was a weak positive association between height-for-age z-score (HAZ) and FEV1 z-score (n = 28, r = 0.4, p = 0.049). Those with a low fat free mass index (<-2 z scores) had a lower BMI z score (-1.3 ± 1.2 vs. 0.8 ± 0.7, p = 0.0002). BIS phase angle identified more patients at nutritional risk than using moderate malnutrition cut-offs of either HAZ or BMI ≤ -2 z scores alone (21% vs. 4.6% vs. 6.9% respectively). PCD patients had a higher incidence of vitamin D insufficiency (<50 nmoL/L) (54%) and deficiency (<30 nmoL/L) (26%) than healthy children. CONCLUSIONS: We have characterised the nutritional phenotype of a cohort of children with PCD. Monitoring vitamin D levels is important in PCD patients. There is a weak association between lung function and nutritional status, and measures of BIS phase-angle. The use of BIS phase-angle may allow for early identification of at risk children and may therefore be of benefit for nutritional assessments in the clinical setting. These findings will help inform a future nutritional intervention strategy in children with PCD.

Bioimpedance spectroscopy measurements of phase angle and height for age are predictive of outcome in children following surgery for congenital heart disease.

OBJECTIVE: Children with congenital heart disease (CHD) are often growth restricted (low weight- and/or height-for-age) which may increase risk of poor post operative resilience. Bioelectrical impedance spectroscopy (BIS) has been used to determine body composition in different clinical settings and has been shown to mark differences in nutritional state and clinical outcome. In disease conditions were fluid is not normally distributed it is proposed that raw impedance values and BIS derived phase-angle may serve as prognostic indicators of clinical outcome. We sought to describe the relationship between nutritional status, phase-angle and post-operative outcomes in children with congenital heart disease. DESIGN: Single centre prospective cohort study. SETTING: Paediatric Intensive Care Unit (PICU), Southampton Children's Hospital. PATIENTS: 122 children with CHD following cardiac surgery (March 2015-April 2016). Outcome variables included growth, mechanical-ventilation, PICU length of stay (PICU-LOS) and phase-angle at 50 Hz. MEASUREMENTS AND MAIN RESULTS: BIS measurements were taken before and on the day of surgery (day 0), day 2 post-operatively and on discharge from hospital. Pre-operative moderate malnutrition defined as height-for-age-z-score (HAZ) ≤-2 was observed in 28.5% of infants and 20.6% of children. Regression analysis was used to investigate the relationship between phase-angle, HAZ and clinical outcomes. Moderate-malnutrition (HAZ ≤-2) was associated with an increased PICU-LOS (odds ratios (OR) with 95% confidence interval: 1.8; 1.1-2.7, p = 0.008) whilst a low phase-angle (≤2.7° on day 2 was associated with longer PICU-LOS (OR 7.8; 2.7-22.45, p < 0.001)); When the model was adjusted for age, known risk factors and length of surgery, HAZ ≤-2 and phase-angle ≤2.7° on day 2 were associated with longer PICU-LOS (p = 0.001 and p = 0.04 respectively) and together explained 81.7% of the variability in PICU-LOS. CONCLUSIONS: Moderate malnutrition (HAZ ≤-2) in infants and children undergoing cardiac surgery is associated with longer PICU-LOS. Post-operative measures of BIS phase angle may further improve our ability to identifying hose children with an increased risk of prolonged PICU-LOS compared to using pre-operative anthropometry alone.

Duration of motor block with intrathecal ropivacaine versus bupivacaine for caesarean section: a meta-analysis.

BACKGROUND: Bupivacaine is a commonly used local anaesthetic for spinal anaesthesia for caesarean section, but may produce prolonged motor block, delaying discharge from the post-anaesthesia care unit. Ropivacaine may have a shorter time to recovery of motor function compared with bupivacaine. We performed a meta-analysis to assess the time difference in duration of motor block with intrathecal ropivacaine compared with bupivacaine for caesarean section. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases for randomised controlled trials comparing ropivacaine with bupivacaine in parturients undergoing elective caesarean section under spinal anaesthesia. The primary outcome was the duration of motor block. Secondary outcomes included the time to onset of sensory block, need for conversion to general anaesthesia and the incidence of hypotension. RESULTS: Thirteen trials comprising 743 spinal anaesthetics were included. Intrathecal ropivacaine resulted in a reduced duration of motor block, regressing 35.7min earlier compared with intrathecal bupivacaine (P<0.00001). There was no difference in the time to onset of sensory block (P=0.25) or the incidence of hypotension (P=0.10). Limited data suggested no difference in the rate of conversion to general anaesthesia, but an earlier request for postoperative analgesia with ropivacaine. CONCLUSIONS: Compared with bupivacaine, intrathecal ropivacaine is associated with more rapid recovery of motor block despite similar sensory properties and no increased rate of conversion to general anaesthesia. This may be useful in centres in which recovery of motor block is a criterion for discharge from the post-anaesthesia care unit. However, small numbers of trials and significant heterogeneity limit the interpretation of our results.

MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways.

The microRNA-200 (miR-200) family has a critical role in regulating epithelial-mesenchymal transition and cancer cell invasion through inhibition of the E-cadherin transcriptional repressors ZEB1 and ZEB2. Recent studies have indicated that the miR-200 family may exert their effects at distinct stages in the metastatic process, with an overall effect of enhancing metastasis in a syngeneic mouse breast cancer model. We find in a xenograft orthotopic model of breast cancer metastasis that ectopic expression of members of the miR-200b/200c/429, but not the miR-141/200a, functional groups limits tumour cell invasion and metastasis. Despite modulation of the ZEB1-E-cadherin axis, restoration of ZEB1 in miR-200b-expressing cells was not able to alter metastatic potential suggesting that other targets contribute to this process. Instead, we found that miR-200b repressed several actin-associated genes, with the knockdown of the ezrin-radixin-moesin family member moesin alone phenocopying the repression of cell invasion by miR-200b. Moesin was verified to be directly targeted by miR-200b, and restoration of moesin in miR-200b-expressing cells was sufficient to alleviate metastatic repression. In breast cancer cell lines and patient samples, the expression of moesin significantly inversely correlated with miR-200 expression, and high levels of moesin were associated with poor relapse-free survival. These findings highlight the context-dependent effects of miR-200 in breast cancer metastasis and demonstrate the existence of a moesin-dependent pathway, distinct from the ZEB1-E-cadherin axis, through which miR-200 can regulate tumour cell plasticity and metastasis.

Designed multiple ligands in metabolic disease research: from concept to platform.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs.

Clinical working postures of bachelor of oral health students.

OBJECTIVE: To observe and describe the clinical working postures of final-year Bachelor of Oral Health (BOH) students. DESIGN: Pilot observational study. SETTING: The University of Otago Faculty of Dentistry and School of Physiotherapy. METHODS: Eight final-year BOH students voluntarily participated in this study, where postural data were collected using a digital video camera during a standard clinical treatment session. The postural data were analysed using 3D Match biomechanical software. RESULTS: Final-year BOH students who work in the seated position are exposed to neck flexion of greater than 35 degrees, together with trunk flexion greater than 20 degrees and bilateral elbow flexion greater than 90 degrees. CONCLUSIONS: The findings of this study agree with the findings of previous postural studies of dental professionals. Dental hygiene students, together with their clinical supervisors, need to be aware of the importance of good working posture early in their careers, and pay particular attention to the degree of neck flexion occurring for prolonged periods.

LIN28B fosters colon cancer migration, invasion and transformation through let-7-dependent and -independent mechanisms.

Lin28b is an RNA-binding protein that inhibits biogenesis of let-7 microRNAs. LIN28B is overexpressed in diverse cancers, yet a specific role in the molecular pathogenesis of colon cancer has to be elucidated. We have determined that human colon tumors exhibit decreased levels of mature let-7 isoforms and increased expression of LIN28B. To determine LIN28B's mechanistic role in colon cancer, we expressed LIN28B in immortalized colonic epithelial cells and human colon cancer cell lines. We found that LIN28B promotes cell migration, invasion and transforms immortalized colonic epithelial cells. In addition, constitutive LIN28B expression increases expression of intestinal stem cell markers LGR5 and PROM1 in the presence of let-7 restoration. This may occur as a result of Lin28b protein binding LGR5 and PROM1 mRNA, suggesting that a subset of LIN28B functions is independent of its ability to repress let-7. Our findings establish a new role for LIN28B in human colon cancer pathogenesis, and suggest LIN28B post-transcriptionally regulates LGR5 and PROM1 through a let-7-independent mechanism.

Predictive blood glucose lowering efficacy by Glucokinase activators in high fat fed female Zucker rats.

BACKGROUND AND PURPOSE: Glucokinase (GK) is the rate-limiting enzyme of hepatic glucose metabolism and acts as a sensor for glucose-stimulated insulin release in beta-cells. Here we examine whether the lowering of blood glucose levels in the rat by small molecule glucokinase activators (GKAs) can be predicted from in vitro enzyme potencies and plasma compound exposure. EXPERIMENTAL APPROACH: We developed an insulin resistant and hyperinsulinemic animal model, the high fat fed female Zucker (fa/fa) rat (HFFZ), and measured the acute in vivo glucose-lowering efficacy of a number of GKAs in an oral glucose tolerance test. KEY RESULTS: Four GKAs (at 1 to 30 mg kg(-1)), with different in vitro enzyme potencies, dose-dependently improved oral glucose tolerance in HFFZ rats (10-40% decrease glucose area under the curve (AUC) from vehicle control). The extent of glucose lowering, or the pharmacodynamic (PD) effect, of a GKA was directly related to the total compound concentration in the plasma; the pharmacokinetic (PK) measurement. This PK-PD relationship was extended across a series of GKAs by accounting for differences in protein binding and in the in vitro potency. CONCLUSIONS AND IMPLICATIONS: When the unbound GKA compound level is greater than the in vitro enzyme potency there was significant blood glucose lowering in vivo. This latter relationship was upheld in non-diabetic Wistar rats orally dosed with a GKA. The robust and predictive nature of the PK-PD relationship for GKAs may prove of value in testing these agents in early human clinical studies.

Valuing river characteristics using combined site choice and participation travel cost models.

This paper presents new welfare measures for marginal changes in river quality in selected English rivers. The river quality indicators used include chemical, biological and habitat-level attributes. Economic values for recreational use of three types of river-upland, lowland and chalk-are presented. A survey of anglers was carried out and using these data, two travel cost models were estimated, one to predict the numbers of trips and the other to predict angling site choice. These models were then linked to estimate the welfare associated with marginal changes in river quality using the participation levels as estimated in the trip prediction model. The model results showed that higher flow rates, biological quality and nutrient pollution levels affect site choice and influence the likelihood of a fishing trip. Consumer surplus values per trip for a 10% change in river attributes range from pound 0.04 to pound 3.93 ( pound 2001) depending on the attribute.

Spinal cord stimulation: a seven-year audit.

OBJECTIVE: To evaluate the outcome and complications of spinal cord stimulation (SCS) for chronic neuropathic pain in an Australian population. MATERIALS AND METHODS: An independent researcher retrospectively examined the records of 138 patients trialing SCS between 1995 and 2002 at our institution. Information collected included pain relief, ability to perform activities of daily living (ADLs), return to work and reduction in opiate analgesia. Clinical, psychological, demographic and financial data were also collected. RESULTS: Of 138 patients who trialed SCS, 103 (74.7%) achieved a greater than 50% reduction in their pain and proceeded to permanent implantation. At 1 year following permanent implantation, 84.4% of these still had a reduction in their pain by greater than 50%. The majority of patients, 59.1%, stated that their analgesia was good (50-74% pain reduction). All patients required opiate analgesics prior to SCS implantation, but this fell to 54.6% after SCS implantation. Additionally, 73.6% had a significant improvement in their ability to perform ADLs and 24% of patients were able to return to work. CONCLUSION: SCS is an effective treatment in the control of chronic neuropathic pain, particularly in combination with comprehensive medical management within a multidisciplinary pain management centre.