30-day mortality among very old patients admitted to European intensive care units for major trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit. Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided with the use of organ dysfunction scores of both the acute condition (e.g. Sequential Organ Failure Assessment (SOFA) score) and chronic health issues (e.g. clinical frailty scale, (CFS)). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the VIP-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided and outcome (ICU and 30-day mortality) were summarised. Uni- and multi- variable regression analysis were undertaken to determine associations between CFS and SOFA score in the first 24-hours, type of major trauma and outcomes. RESULTS: Of the 8062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years; median SOFA score was 6 (IQR 3,9) and median CFS was 3 (IQR 2,5). Survival to 30-days was 54%. Median and inter-quartile range of CFS was the same in survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p<0.001) and trauma with head injury (p<0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

The value of right ventricular to pulmonary arterial coupling in the critically ill: a National Echocardiography Database of Australia (NEDA) substudy.

BACKGROUND: Right ventricular (RV) function is tightly coupled to afterload, yet echocardiographic indices of RV function are frequently assessed in isolation. Normalizing RV function for afterload (RV-PA coupling) using a simplified ratio of tricuspid annular plane systolic excursion (TAPSE)/ tricuspid regurgitant velocity (TRV) could help to identify RV decompensation and improve risk stratification in critically ill patients. This is the first study to explore the distribution of TAPSE/TRV ratio and its prognostic relevance in a large general critical care cohort. METHODS: We undertook retrospective analysis of echocardiographic, clinical, and mortality data of intensive care unit (ICU) patients between January 2012 and May 2017. A total of 1077 patients were included and stratified into tertile groups based on TAPSE/TRV ratio: low (< 5.9 mm.(m/s)-1), middle (≥ 5.9-8.02 mm.(m/s)-1), and high (≥ 8.03 mm.(m/s)-1). The distribution of the TAPSE/TRV ratio across ventricular function subtypes of normal, isolated left ventricular (LV), isolated RV, and biventricular dysfunction was explored. The overall prognostic relevance of the TAPSE/TRV ratio was tested, including distribution across septic, cardiovascular, respiratory, and neurological subgroups. RESULTS: Higher proportions of ventricular dysfunctions were seen in low TAPSE/TRV tertiles. TAPSE/TRV ratio is impacted by LV systolic function but to a lesser extent than RV dysfunction or biventricular dysfunction. There was a strong inverse relationship between TAPSE/TRV ratio and survival. After multivariate analysis, higher TAPSE/TRV ratios (indicating better RV-PA coupling) were independently associated with lower risk of death in ICU (HR 0.927 [0.872-0.985], p < 0.05). Kaplan-Meier analysis demonstrated higher overall survival in middle and high tertiles compared to low tertiles (log rank p < 0.0001). The prognostic relevance of TAPSE/TRV ratio was strongest in respiratory and sepsis subgroups. Patients with TAPSE/TRV < 5.9 mm (m/s)-1 had a significantly worse prognosis than those with higher TAPSE/TRV ratios. CONCLUSION: The TAPSE/TRV ratio has prognostic relevance in critically ill patients. The prognostic power may be stronger in respiratory and septic subgroups. Larger prospective studies are needed to investigate the role of TAPSE/TRV in pre-specified subgroups including its role in clinical decision-making.

Dominance loss and tenure maintenance in Kalahari meerkats.

In many social species, both the acquisition of dominance and the duration that individuals maintain their status are important determinants of breeding tenure and lifetime reproductive success. However, few studies have yet examined the extent and causes of variation in dominance tenure and the duration of breeding lifespans. Here, we investigate the processes that terminate dominance tenures and examine how they differ between the sexes in wild Kalahari meerkats (Suricata suricatta), a cooperative breeder where a dominant breeding pair produces most of the young recruited into each group. Mortality and displacement by resident subordinate competitors were important forms of dominance loss for both sexes. However, dominant males (but rarely females) were also at risk of takeovers by extra-group invading males. Dominant males also differed from dominant females in that they abandoned their group after the death of their breeding partner, when no other breeding opportunities were present, whereas dominant females that lost their partner remained and continued to breed in the same group. We show that a larger number of processes can terminate dominance tenure in males with the result that the average male tenure of breeding positions was shorter than that of females, which contributes to the reduced variance in the lifetime reproductive success in males compared to females. Our analysis suggests that sex differences in emigration and immigration may often have downstream consequences for sex differences in reproductive variance and for the selection pressures operating on females and males.

Mitral regurgitation in the critically ill: the devil is in the detail.

Mitral regurgitation (MR) is common in the critically unwell and encompasses a heterogenous group of conditions with diverging therapeutic strategies. MR may present acutely with haemodynamic instability or more insidiously with failure to wean from mechanical ventilation. Critical illness is associated with marked physiological stress and haemodynamic changes that dynamically influence the severity and implication of MR. The expanding role of critical care echocardiography uniquely positions the intensivist to apply advanced bedside valvular assessment to recognise haemodynanically significant MR, manipulate and optimise cardiopulmonary physiology and identify patients requiring urgent cardiology and surgical referral. This review will consider common clinical scenarios, therapeutic strategies and the pearls and pitfalls of echocardiographic assessment and quantification in the critically unwell.

A National Network of Safe Havens: Scottish Perspective.

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network's capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale.

Diagnostic Challenges in Sepsis.

PURPOSE OF REVIEW: Sepsis is a leading cause of death worldwide. Groundbreaking international collaborative efforts have culminated in the widely accepted surviving sepsis guidelines, with iterative improvements in management strategies and definitions providing important advances in care for patients. Key to the diagnosis of sepsis is identification of infection, and whilst the diagnostic criteria for sepsis is now clear, the diagnosis of infection remains a challenge and there is often discordance between clinician assessments for infection. RECENT FINDINGS: We review the utility of common biochemical, microbiological and radiological tools employed by clinicians to diagnose infection and explore the difficulty of making a diagnosis of infection in severe inflammatory states through illustrative case reports. Finally, we discuss some of the novel and emerging approaches in diagnosis of infection and sepsis. SUMMARY: While prompt diagnosis and treatment of sepsis is essential to improve outcomes in sepsis, there remains no single tool to reliably identify or exclude infection. This contributes to unnecessary antimicrobial use that is harmful to individuals and populations. There is therefore a pressing need for novel solutions. Machine learning approaches using multiple diagnostic and clinical inputs may offer a potential solution but as yet these approaches remain experimental.

Decline and fall: The causes of group failure in cooperatively breeding meerkats.

In many social vertebrates, variation in group persistence exerts an important effect on individual fitness and population demography. However, few studies have been able to investigate the failure of groups or the causes of the variation in their longevity. We use data from a long-term study of cooperatively breeding meerkats, Suricata suricatta, to investigate the different causes of group failure and the factors that drive these processes. Many newly formed groups failed within a year of formation, and smaller groups were more likely to fail. Groups that bred successfully and increased their size could persist for several years, even decades. Long-lived groups principally failed in association with the development of clinical tuberculosis, Mycobacterium suricattae, a disease that can spread throughout the group and be fatal for group members. Clinical tuberculosis was more likely to occur in groups that had smaller group sizes and that had experienced immigration.

The Evolution of Indiscriminate Altruism in a Cooperatively Breeding Mammal.

Kin selection theory suggests that altruistic behaviors can increase the fitness of altruists when recipients are genetic relatives. Although selection can favor the ability of organisms to preferentially cooperate with close kin, indiscriminately helping all group mates may yield comparable fitness returns if relatedness within groups is very high. Here, we show that meerkats (Suricata suricatta) are largely indiscriminate altruists who do not alter the amount of help provided to pups or group mates in response to their relatedness to them. We present a model showing that indiscriminate altruism may yield greater fitness payoffs than kin discrimination where most group members are close relatives and errors occur in the estimation of relatedness. The presence of errors in the estimation of relatedness provides a feasible explanation for associations between kin discriminative helping and group relatedness in eusocial and cooperatively breeding animals.

The development of individual differences in cooperative behaviour: maternal glucocorticoid hormones alter helping behaviour of offspring in wild meerkats.

The phenotype of parents can have long-lasting effects on the development of offspring as well as on their behaviour, physiology and morphology as adults. In some cases, these changes may increase offspring fitness but, in others, they can elevate parental fitness at a cost to the fitness of their offspring. We show that in Kalahari meerkats ( Suricata suricatta), the circulating glucocorticoid (GC) hormones of pregnant females affect the growth and cooperative behaviour of their offspring. We performed a 3-year experiment in wild meerkats to test the hypothesis that GC-mediated maternal effects reduce the potential for offspring to reproduce directly and therefore cause them to exhibit more cooperative behaviour. Daughters (but not sons) born to mothers treated with cortisol during pregnancy grew more slowly early in life and exhibited significantly more of two types of cooperative behaviour (pup rearing and feeding) once they were adults compared to offspring from control mothers. They also had lower measures of GCs as they aged, which could explain the observed increases in cooperative behaviour. Because early life growth is a crucial determinant of fitness in female meerkats, our results indicate that GC-mediated maternal effects may reduce the fitness of offspring, but may elevate parental fitness as a consequence of increasing the cooperative behaviour of their daughters. This article is part of the theme issue 'Developing differences: early-life effects and evolutionary medicine'.

Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma.

Glioblastoma is universally fatal because of its propensity for rapid recurrence due to highly migratory tumor cells. Unraveling the genomic complexity that underlies this migratory characteristic could provide therapeutic targets that would greatly complement current surgical therapy. Using multiple high-resolution genomic screening methods, we identified a single locus, adherens junctional associated protein 1 (AJAP1) on chromosome 1p36 that is lost or epigenetically silenced in many glioblastomas. We found AJAP1 expression absent or reduced in 86% and 100% of primary glioblastoma tumors and cell lines, respectively, and the loss of expression correlates with AJAP1 methylation. Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in glioblastoma cell lines. This work shows the significant loss of expression of AJAP1 in glioblastoma and provides evidence of its role in the highly migratory characteristic of these tumors.

The environmental history of Chatthin Wildlife Sanctuary, a protected area in Myanmar (Burma).

We reconstructed the history of Chatthin Wildlife Sanctuary (CWS) to understand how social and economic events, and policy changes affected the sanctuary's condition. We surveyed 25 villages surrounding CWS to evaluate past and present ecological conditions, compare the results with historical accounts and identify causal relationships. During the first half of the 20th century, the primary threat was the government's reduction of old growth forest to supply fuel wood for the British-built railway. The railroad opened the area to colonization, but the villagers' impact on timber and wildlife was low. From 1945 to 1988, villagers became the primary force of landscape degradation. The post-war windfall of firearms increased hunting pressure, and populations of large mammal started to decline. With the economic decline of the 1970s and 1980s, the community's demand for game and forest products intensified, and the large mammal fauna was reduced from eleven to four species. From 1988-2003, the forests surrounding the sanctuary were fragmented and degraded. The absence of large predators rendered the park safe for livestock, and the combined effects of grazing and removal of forest products seriously degraded habitat within CWS. Major threats to CWS during the past two decades have resulted from land use decisions in which government-planned economic enterprises caused encroachment by villagers. Stabilization and recovery of this sanctuary will require management compatible with human needs, including expanded buffer zones, better core area protection, community forestry projects, and probably relocation of villages within the park.