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Validation of the NUn score as a predictor of anastomotic leak and major complications after Esophagectomy.
No full textPredicting major anastomotic leak (AL) and major complications (Clavien-Dindo 3-5) following esophagectomy improves postoperative management of patients. The role of the NUn score in their prediction is controversial. This study aims to evaluate the predictive ability of this simple score. Data were retrospectively collected for consecutive esophagectomies over a 10-year period, and NUn scores were retrospectively calculated for each patient from informatics data. A standardized definition of major AL was used, excluding minor asymptomatic, radiologically detected leaks. The predictive accuracy of the NUn score and its constituent parts, for major AL and major complications, was assessed using area under receiver operating characteristics curves (AUROCs). Of 382 patients, 48 (13%) developed major AL and 123 (32%) developed major complications. The NUn score calculated on postoperative day 4 was significantly predictive of both outcomes, with AUROCs of 0.77 and 0.71, respectively (both P < 0.001). A NUn score cut-off of 10 had a negative predictive value of 95% for major AL. The NUn score was predictive of major complications on multivariable analysis. The NUn score was found to be a significant predictor of major AL, suggesting that this is a useful early warning score for major AL. The score may also be useful in identifying patients that are the most likely to benefit from enhanced recovery protocols
Response Letter to the Editor from Chee et al.: "Prevention of Adrenal Crisis: Cortisol Response to Major Stress Compared to Stress Dose Hydrocortisone Delivery".
No full textComment on: British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: reply.
No full textComment on: Equal rights in autoimmunity: is Sjögren's syndrome ever 'secondary'?: reply.
No full textProtocol for a feasibility study of smoking cessation in the surgical pathway before major lung surgery: Project MURRAY.
No full textINTRODUCTION
Smoking prior to major thoracic surgery is the biggest risk factor for development of postoperative pulmonary complications, with one in five patients continuing to smoke before surgery. Current guidance is that all patients should stop smoking before elective surgery yet very few are offered specialist smoking cessation support. Patients would prefer support within the thoracic surgical pathway. No study has addressed the effectiveness of such an intervention in this setting on cessation. The overall aim is to determine in patients who undergo major elective thoracic surgery whether an intervention integrated (INT) into the surgical pathway improves smoking cessation rates compared with usual care (UC) of standard community/hospital based NHS smoking support. This pilot study will evaluate feasibility of a substantive trial.
METHODS AND ANALYSIS
Project MURRAY is a trial comparing the effectiveness of INT and UC on smoking cessation. INT is pharmacotherapy and a hybrid of behavioural support delivered by the trained healthcare practitioners (HCPs) in the thoracic surgical pathway and a complimentary web-based application. This pilot study will evaluate the feasibility of a substantive trial and study processes in five adult thoracic centres including the University Hospitals Birmingham NHS Foundation Trust. The primary objective is to establish the proportion of those eligible who agree to participate. Secondary objectives include evaluation of study processes. Analyses of feasibility and patient-reported outcomes will take the form of simple descriptive statistics and where appropriate, point estimates of effects sizes and associated 95% CIs.
ETHICS AND DISSEMINATION
The study has obtained ethical approval from NHS Research Ethics Committee (REC number 19/WM/0097). Dissemination plan includes informing patients and HCPs; engaging multidisciplinary professionals to support a proposal of a definitive trial and submission for a full application dependent on the success of the study.
TRIAL REGISTRATION NUMBER
NCT04190966
The Effect of Airway Management on CPR Quality in the Paramedic2 Randomised Controlled Trial.
No full textINTRODUCTION
Good quality basic life support (BLS) is associated with improved outcome from cardiac arrest. Chest compression fraction (CCF) is a BLS quality indicator, which may be influenced by the type of airway used. We aimed to assess CCF according to the airway strategy in the PARAMEDIC2 study: no advanced airway, supraglottic airway (SGA), tracheal intubation, or a combination of the two. Our hypothesis was that tracheal intubation was associated with a decrease in the CCF compared with alternative airway management strategies.
METHODS
PARAMEDIC2 was a multicentre double-blinded placebo-controlled trial of adrenaline vs placebo in out-of-hospital cardiac arrest. Data showing compression rate and ratio from patients recruited by London Ambulance Service (LAS) as part of this study was collated and analysed according to the advanced airway used during the resuscitation attempt.
RESULTS
CPR process data were available from 286/ 2058 (13.9%) of the total patients recruited by LAS. The mean compression rate for the first 5 min of data recording was the same in all groups (P = 0.272) and ranged from 104.2 (95%CI of mean: 100.5, 107.8) min to 108.0 (95%CI of mean: 105.1, 108.3) min. The mean compression fraction was also similar across all groups (P = 0.159) and ranged between 74.7% and 78.4%. There was no difference in the compression rates and fractions across the airway management groups, regardless of the duration of CPR.
CONCLUSION
There was no significant difference in the compression fraction associated with the airway management strategy
Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release.
No full textKinase oxidation is a critical signalling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, type-1 protein kinase A (PKARIα) can be reversibly oxidized, forming interprotein disulfide bonds within the holoenzyme complex. However, the effect of PKARIα disulfide formation on downstream signaling in the heart, particularly under states of oxidative stress such as ischemia and reperfusion (I/R), remains unexplored. Atrial tissue obtained from patients before and after cardiopulmonary bypass and reperfusion and left ventricular (LV) tissue from mice subjected to I/R or sham surgery were used to assess PKARIα disulfide formation by immunoblot. To determine the impact of disulfide formation on PKARIα catalytic activity and sub-cellular localization, live-cell fluorescence imaging and stimulated emission depletion super-resolution microscopy were performed in prkar1 knock-out mouse embryonic fibroblasts, neonatal myocytes or adult LV myocytes isolated from 'redox dead' (Cys17Ser) PKARIα knock-in mice and their wild-type littermates. Comparison of intracellular calcium dynamics between genotypes was assessed in fura2-loaded LV myocytes whereas I/R-injury was assessed ex vivo. In both humans and mice, myocardial PKARIα disulfide formation was found to be significantly increased (2-fold in humans, p=0.023; 2.4-fold in mice, p<0.001) in response to I/R in vivo. In mouse LV cardiomyocytes, disulfide-containing PKARIα was not found to impact catalytic activity, but instead led to enhanced A-kinase-anchoring protein (AKAP) binding with preferential localization of the holoenzyme to the lysosome. Redox-dependent regulation of lysosomal two pore channels (TPC) by PKARIα was sufficient to prevent global calcium release from the sarcoplasmic reticulum in LV myocytes, without affecting intrinsic ryanodine receptor leak or phosphorylation. Absence of I/R-induced PKARIα disulfide formation in "redox dead" knock-in mouse hearts resulted in larger infarcts (2-fold, p<0.001) and a concomitant reduction in LV contractile recovery (1.6-fold, p<0.001), which was prevented by administering the lysosomal TPC inhibitor Ned-19 at the time of reperfusion. Disulfide-modification targets PKARIα to the lysosome where it acts as a gatekeeper for TPC-mediated triggering of global calcium release. In the post-ischemic heart, this regulatory mechanism is critical for protecting from extensive injury and offers a novel target for the design of cardioprotective therapeutics
Retroperitoneoscopic Standard or Hand-Assisted Versus Laparoscopic Standard or Hand-Assisted Donor Nephrectomy: A Systematic Review and the First Network Meta-Analysis.
No full textBackground
At the present four minimally invasive procedures namely retroperitoneoscopic (RPDN), laparoscopic (LPDN), hand-assisted retroperitoneoscopic (HARDN) and hand-assisted laparoscopic donor nephrectomy (HALDN) are used to perform donor nephrectomies. The current evidence based on retrospective studies and on pairwise only meta-analyses is inconclusive. Up to authors' best knowledge there is no so far network meta-analysis to compare all the above-mentioned procedures. Therefore, a network meta-analysis was conducted to compare the feasibility, safety and reproducibility of the four donor nephrectomies procedures.
Methods
Google Scholar, EMBASE, PubMed, and Cochrane library were used for a systematic literature search. Both updated pairwise and network meta-analyses were performed.
Results
Compared to LPDN there was evidence of significantly more right kidneys retrieved with RPDN; nonsignificant differences demonstrated both with HALDN and HARDN compared to LPDN. There was evidence that the operative time was significantly shorter by 77 min in RPDN compared to LPDN; on the other hand, HARDN and HALDN did not demonstrate significant differences when compared to LPDN.
Conclusions
The present study demonstrates that each approach can be applied safely in adequately selected patients. Moreover, retroperitoneoscopic is reliable, safe and easily reproducible alternative of LPDN for both left and right kidneys
Renal outcome in patients with newly diagnosed multiple myeloma: results from the UK NCRI Myeloma XI trial.
No full textRenal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were 1000 mg/L, and/or a free light chain response of >90%. It did not correlate with monoclonal-protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852
Development and validation of a follow-up methodology for a randomised controlled trial, utilising routine clinical data as an alternative to traditional designs: a pilot study to assess the feasibility of use for the BladderPath trial.
No full textBACKGROUND
Bladder cancer outcomes have not changed significantly in 30 years; the BladderPath trial (Image Directed Redesign of Bladder Cancer Treatment Pathway, ISRCTN35296862) proposes to evaluate a modified pathway for diagnosis and treatment ensuring appropriate pathways are undertaken earlier to improve outcomes. We are piloting a novel data collection technique based on routine National Health Service (NHS) data, with no traditional patient-Health Care Professional contact after recruitment, where trial data are traditionally collected on case report forms. Data will be collected from routine administrative sources and validated via data queries to sites. We report here the feasibility and pre-trial methodological development and validation of the schema proposed for BladderPath.
METHODS
Locally treated patient cohorts were utilised for routine data validation (hospital interactions data (HID) and administrative radiotherapy department data (RTD)). Single site events of interest were algorithmically extracted from the 2008-2018 HID and validated against reference datasets to determine detection sensitivity. Survival analysis was performed using RTD and HID data. Hazard ratios and survival statistics were calculated estimating treatment effects and further validating and assessing the scope of routine data.
RESULTS
Overall, 829/1042 (sensitivity 0.80) events of interest were identified in the HID, with varying levels of sensitivity; identifying, 202/206 (sensitivity 0.98; PPV 0.96) surgical events but only 391/568 (sensitivity 0.69; PPV 0.95) radiotherapy regimens. An overall temporal quality improvement trend was present: detecting 41/117 events (35%) in 2011 to 104/109 (95%) in 2017 (all event types). Using the RTD, 5-year survival rates were 43% (95% CI 25-59%) in the chemoradiotherapy group and 30% (95% CI 23-36%) in the radiotherapy group; using the HID, the 5-year radical cystectomy survival rate was 57% (95% CI 50-63%).
CONCLUSIONS
Routine data are a feasible method for trial data collection. As long as events of interest are pre-validated, very high sensitivities for trial conduct can be achieved and further improved with targeted data queries. Outcomes can also be produced comparable to clinical trial and national dataset results. Given the real-time, obligatory nature of the HID, which forms the Hospital Episode Statistics (HES) data, alongside other datasets, we believe routine data extraction and validation is a robust way of rapidly collecting datasets for trials