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Evidence for Arrhythmogenic Effects of A-Adenosine Receptors.
No full textAdenosine can be released from the heart and may stimulate four different cardiac adenosine receptors. A receptor subtype that couples to the generation of cyclic adenosine monophosphate (cAMP) is the A-adenosine receptor (A-AR). To better understand its role in cardiac function, we studied mechanical and electrophysiological effects in transgenic mice that overexpress the human A-AR in cardiomyocytes (A-TG). We used isolated preparations from the left atrium, the right atrium, isolated perfused hearts with surface electrocardiogram (ECG) recording, and surface body ECG recordings of living mice. The hypothesized arrhythmogenic effects of transgenicity per se and A-AR stimulation were studied. We noted an increase in the incidence of supraventricular and ventricular arrhythmias under these conditions in A-TG. Moreover, we noted that the A-AR agonist CGS 21680 exerted positive inotropic effect in isolated human electrically driven (1 Hz) right atrial trabeculae carneae. We conclude that A-ARs are functional not only in A-TG but also in isolated human atrial preparations. A-ARs in A-TG per se and their stimulation can lead to cardiac arrhythmias not only in isolated cardiac preparations from A-TG but also in living A-TG
Plasma renin measurements are unrelated to mineralocorticoid replacement dose in patients with primary adrenal insufficiency.
No full textCONTEXT
No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency.
OBJECTIVE
To explore the relationship between mineralocorticoid replacement dose, plasma renin concentration (PRC) and clinically important variables to determine which are most helpful in guiding mineralocorticoid dose titration in primary adrenal insufficiency.
DESIGN
Observational, retrospective, longitudinal analysis.
PATIENTS
280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (SW-CAH) (149 adults and 55 children) and 39 adult patients with Addison's disease (AD) were analysed.
MAIN OUTCOME MEASURES
PRC, electrolytes, blood pressure (BP) and anthropometric parameters were used to predict their utility in optimizing MC replacement dose.
RESULTS
PRC was low, normal or high in 19%, 36% and 44% of patients, respectively, with wide variability in mineralocorticoid dose and PRC. Univariate analysis demonstrated a direct positive relationship between mineralocorticoid dose and PRC in adults and children. There was no relationship between mineralocorticoid dose and BP in adults, while BP increased with increasing mineralocorticoid dose in children. Using multiple regression modelling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in mineralocorticoid dose was able to predict potassium, but not BP or PRC.
CONCLUSIONS
The relationship between mineralocorticoid dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last mineralocorticoid dose, adherence and concomitant medications. Our data suggests that mineralocorticoid titration should not primarily be based only on PRC normalization, but also on clinical parameters as BP and electrolyte concentration
Results of flap reconstruction: categorisation to reflect outcomes and process in the management of head and neck defects.
No full textThe reporting of the outcomes of flap reconstruction is often based on numerical success rates. Whilst this remains a useful variable with which to measure success, it is limited in its ability to reflect the complex processes involved. The lack of consistency in the categorisation of outcomes of flap reconstruction in the head and neck could potentially lead us to lose the opportunity to fully capture the implications of its success or failure, or both. We propose a classification that moves away from primarily reporting the results of its binary nature, and focuses more on the process of reconstruction, particularly in the head and neck
Prospective Audit to Study urokinaSe use to restore Patency in Occluded centRal venous caTheters (PASSPORT 1).
No full textOBJECTIVES
Tunnelled central venous catheters dysfunction can be defined as failure to provide blood flow above 200 mL/min during dialysis often caused by thrombosis. Although urokinase is used routinely for thrombolysis, there is wide variation in dose regimens. A multidisciplinary group was formed to address this issue and offer guidance.
METHODS
Dialysis centres that used urokinase in the United Kingdom took part in a prospective study to determine the safety and outcomes of thrombolysis using agreed protocols. Data were collected anonymously from September 2017 until February 2018. Catheter blood flow was measured before and after the following interventions: catheter dwell or push locks with 12,500-50,000 IU or catheter infusion with 100,000-250,000 IU of urokinase. Interventions were repeated if the blood flow remained below 200 mL/min.
RESULTS
10 centres took part and recruited 200 patients; 45.5% were female and 54.5% were male with mean age of 63.6 (±15.2) years. The cumulative success rate for thrombolysis was 90.5% after first intervention, 97% after second intervention, and 99% after more than 2 interventions. Although there was trend towards benefit with dose increments, the success rate between push/dwell locks and high-dose infusion of urokinase was not significantly different (p = 0.069). Seventeen (8.5%) tunnelled central venous catheters were removed due to failure of treatment. No urokinase-related adverse events were reported.
CONCLUSION
In this study, urokinase was safe and efficacious; there was no difference between dwell and push locks. There was some benefit with high-dose infusion of urokinase compared to the dwell and push lock
PREVENTION OF PRESSURE ULCERS IN NASAL BRIDGE DURING NON-INVASIVE MECHANICAL VENTILATION. DISCUSSION OF RESULTS. AUTHORS' RESPONSE TO PEÑA-OTERO ET AL.
No full textThe impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver.
No full textINTRODUCTION
The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate.
METHODS
Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed.
RESULTS
The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups.
CONCLUSION
The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate-cold-to-warm MP-mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability
Exploring the views of female genital mutilation survivors, their male partners and healthcare professionals on the timing of deinfibulation surgery and NHS FGM care provision (the FGM Sister Study): protocol for a qualitative study.
No full textINTRODUCTION
Female genital mutilation (FGM) is a significant global health concern and is likely to become an increasingly important healthcare challenge in destination countries such as the UK owing to rising levels of migration from FGM-affected countries. Currently, there is no consensus on the optimal timing of deinfibulation (opening) surgery for women who have experienced type 3 FGM and care provision remains suboptimal in the UK. This qualitative study aims to explore the views of survivors, male partners and healthcare professionals (HCPs) on the timing of deinfibulation and delivery of NHS FGM services.
METHODS AND ANALYSIS
A qualitative study, informed by the Sound of Silence conceptual framework, will be undertaken via two work packages (WPs). WP1 will explore views on timing preferences for deinfibulation and NHS FGM services through interviews and discussion groups with FGM survivors (n~50), male partners (n~10) and HCPs (n~50). WP2 will use established techniques via two workshops (community (n~20-25 participants) and national stakeholder (n~30-35 participants)) to synthesise qualitative research findings and inform best practice and policy recommendations around the timing of deinfibulation and NHS FGM care provision. Supported by trained interpreters, data collection will be audio recorded and transcribed. Data will be analysed using the framework method to facilitate a systematic mapping and exploration of qualitative data from multiple sources.
ETHICS AND DISSEMINATION
The study has received ethical approval from the North West Greater Manchester East Research Ethics Committee (18/NW/0498). The outputs for this study will be recommendations for best practice and policy around FGM care provision that reflects the views and preferences of key stakeholders. The findings will be disseminated via conference presentations, peer-reviewed publications, patient groups, third sector organisations and social media.
TRIAL REGISTRATION NUMBER
ISRCTN 14710507
Novel Minimal Access Bone Anchored Hearing Implant Surgery and a New Surface Modified Titanium Implant, the Birmingham Experience.
No full textBACKGROUND
Bone anchored hearing implants (BAHI) are widely used and highly successful, accompanied with a high level of patient satisfaction across most techniques. A large UK teaching hospital switched from the previously used wide diameter titanium fixture and drilling system to the novel minimally invasive technique and laser ablated titanium implant. Before this change the rates of fixture failure and skin problems necessitating abutment change were 1% each.
METHODS
Retrospective case note review of consecutive BAHI patients drawn from an electronic database between January 2015 and October 2016.
RESULTS
Data from a total of 118 procedures were reviewed, with different combinations of surgical techniques and implant types. Sixty procedures were performed via the novel minimally invasive technique with 21 failures (35%). Fourty-eight modified minimally invasive technique procedures were performed with seven failures. In 64 of the procedures, laser ablated titanium fixtures were placed with 21 failures (32.8%). In 54 procedures wide diameter titanium fixtures were placed with eight failures (5%).
CONCLUSION
Initial experience with the novel minimally invasive technique and laser ablated titanium fixture showed significantly higher failure rates than expected. This prompted a change to an open technique and subsequent abandonment of the laser ablated titanium fixture and custom drilling solution in our institution
Long-term follow-up of normal and structural heart ventricular tachycardia catheter ablation: real-world experience from a UK tertiary centre.
No full textBackground
Ventricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures.
Objective
To evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting.
Methods
This is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock.
Results
Forty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129-468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%).
Conclusions
Our real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies