Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of ...stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients.
In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically ‘fit’ (n=123) or ‘unfit’ (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT.
GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls.
Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome.
Trial registry: UK NIHR CRN 7285, ISRCTN 14680495.
http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285.
Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure ...with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.
An understanding of the role of autophagic processes in the management of cardiac metabolic stress responses is advancing rapidly and progressing beyond a conceptualization of the autophagosome as a ...simple cell recycling depot. The importance of autophagy dysregulation in diabetic cardiomyopathy and in ischemic heart disease - both conditions comprising the majority of cardiac disease burden - has now become apparent. New findings have revealed that specific autophagic processes may operate in the cardiomyocyte, specialized for selective recognition and management of mitochondria and glycogen particles in addition to protein macromolecular structures. Thus mitophagy, glycophagy, and macroautophagy regulatory pathways have become the focus of intensive experimental effort, and delineating the signaling pathways involved in these processes offers potential for targeted therapeutic intervention. Chronically elevated macroautophagic activity in the diabetic myocardium is generally observed in association with structural and functional cardiomyopathy; yet there are also numerous reports of detrimental effect of autophagy suppression in diabetes. Autophagy induction has been identified as a key component of protective mechanisms that can be recruited to support the ischemic heart, but in this setting benefit may be mitigated by adverse downstream autophagic consequences. Recent report of glycophagy upregulation in diabetic cardiomyopathy opens up a novel area of investigation. Similarly, a role for glycogen management in ischemia protection through glycophagy initiation is an exciting prospect under investigation.
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•HFpEF is highly prevalent in women, with a gender distribution ratio of 2:1.•The aging female demographic confers an increased burden of disease in women.•Women with HFpEF have ...markedly increased incidence of diastolic dysfunction.•Sex-specific molecular understanding of diastolic dysfunction in HFpEF is required.•Discerning the mechanisms of HFpEF sex disparity will help identify new treatments.
We present results from a study of the nonlinear inter-modal coupling between different flexural vibrational modes of a single high-stress, doubly-clamped silicon nitride nanomechanical beam. Using ...the magnetomotive technique and working at 100 mK we explored the nonlinear behaviour and modal couplings of the first, third and fifth modes of a 25.5 μm long beam. We find very good agreement between our results and a simple analytical model which assumes that the different modes of the resonator are coupled to each other by displacement induced tension in the beam. The small size of our resonator leads to relatively strong nonlinear couplings, for example we find a shift of about 7 Hz in the third mode for a 1 nm displacement in the first mode and frequency shifts ∼ 20 times larger than the linewidth (130 Hz) are readily observed.
Summary
Reasons for performing study: Superficial digital flexor (SDF) tendinopathy is a common injury in Thoroughbred horses racing over hurdles. Identification of risk factors may allow the ...introduction of measures to minimise the incidence of this injury.
Objective: To identify risk factors for SDF tendinopathy in Thoroughbred horses in hurdle races in the UK.
Methods: Potential risk factors for SDF tendinopathy were studied between 1 January 2001 and 31 December 2009 using a retrospective cohort study design with 1031 case starts and 168,637 control starts. Potential risk factors were screened using univariable logistic regression prior to multivariable model building.
Results: In the final multivariable model, 20 statistically significant risk factors were identified. Variables found to be associated with increased odds of SDF tendinopathy included: firmer going; increased horse age at first race; having had a previous SDFT injury; and racing in the summer compared to other seasons. Variables found to be associated with decreased odds included: being trained by a more successful trainer; and having raced more frequently in the preceding 9–12 months.
Conclusions: This study identified multiple risk factors associated with SDF tendinopathy, some of which are difficult to explain with the current data source. Factors resulting in increased cumulative horse and tendon fatigue (increased years in racing; carrying increased weight; and racing over longer distances), firm ground, and the presence of previous tendon injury should be considered when attempting to reduce the likelihood of sustaining SDF tendinopathy.
Potential relevance: The results will facilitate the development of strategies to improve the overall safety of horses in hurdle racing in the UK.
The benefits of stroke volume optimization during surgery are unclear, with recent data not replicating the positive effects of earlier studies.
This was a randomized controlled trial of standard ...fluid therapy with or without supplementary blinded intraoperative stroke volume optimization in 220 patients having major elective rectal resection or cystectomy with ileal conduit. All patients were treated using a contemporary enhanced recovery pathway. Interventional fluid challenges used Gelofusine (B Braun, Germany), guided by stoke volume variability measured by LiDCOrapid (LiDCO, UK). Participants were stratified by aerobic fitness (characterized by preoperative cardiopulmonary exercise test), surgical specialty, and intended surgical approach (open or laparoscopic). The primary outcome was the prevalence of moderate or severe complications on day 5 after surgery, defined using the postoperative morbidity survey (POMS) criteria.
Patients received ∼13 ml kg−1 h−1 of i.v. fluids during surgery. The intervention group received an additional mean (sd) 956 (896) ml Gelofusine. There were no statistically significant differences between groups in any primary or secondary end point. A positive POMS on postoperative day 5 was noted in 54 of 111 control subjects (48.6%) and 55 of 109 participants in the intervention group 50.5%; adjusted odds ratio 0.90 (95% confidence interval 0.52–1.57), P=0.717. Mean (sd) hospital length of stay was 9.6 (6.8) days in the control group and 11.8 (11.5) days in the intervention group (adjusted difference −2.1 (−4.6 to 0.3) days, P=0.091). There was no statistical interaction between stroke volume optimization and aerobic fitness in terms of rate of complications or length of stay.
Algorithm-driven stroke volume optimization is of no benefit when superimposed on a liberal baseline fluid regimen in patients having elective major abdominal surgery, when stratified to minimize differences in fitness and surgical approach between groups.
ISRCTN21597243.
The process by which societies adapt to increasing knowledge about the mental and physical capacities of animals and the ways in which they are affected by human activities has been described as a ...journey. Different countries and regions are at various stages of this journey, and will take a unique path, depending on their specific social and cultural dynamics. However, all participants are unified by an increasing awareness of, and concern for, animal welfare. This journey has been characterised by a number of landmark events, one of which was the release of the Five Freedoms concept. Although aspirational and abstract, as it did not outline specific practical goals, nonetheless this concept became a catalyst for moving animal welfare thinking in a new direction, and set up a number of important targets for research. This eventually led to a key shift in thinking from a focus on biological functioning and resources, to ways of assessing welfare outcomes in terms of animals' experiences, i.e. their affective states. Behaviour science played an important role in the interpretation of animals' affective experiences, receiving compelling support from parallel studies in affective neuroscience. An important aspect of our understanding of animal welfare is that affective states can be negative or positive. Enabling animals to perform specific behaviours at key times when they are needed is central to the achievement of positive affective states. Another important event has been the development of practical ways to shift the spectrum of affective states towards a positive balance and their incorporation into welfare codes and regulations. The recent focus on positive affective states does not mean that negative experiences should be given less attention. In fact, in those countries that are at the early stages of the journey, improving function and productivity may be the most effective way to promote some important aspects of animal welfare. For example, alleviating pain is a useful entry point. Finally, it is important that the pace of the journey, in terms of public awareness and shifts in understanding, be supported by high-quality science that is rigorously assessed and validated in its practical application to the management of animal welfare.
While recent work developing GaAsBi for opto-electronic applications has shown promise, it has also indicated that the large valence band offset of GaAsBi/GaAs may cause undesirable hole-trapping in ...GaAsBi quantum wells. In this work, hole-trapping is demonstrated to be the cause of the reduced depletion width of GaAsBi/GaAs multi-quantum well solar cell devices under illumination. Modelling of the quantum confinement energies in these devices shows how the carrier escape times vary as functions of temperature, providing a tool for the design for future GaAsBi based photovoltaic devices.
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