Contrast-Enhanced Echocardiography Application in Patients Supported by Extracorporeal Membrane Oxygenation (ECMO): A Narrative Review.

Extracorporeal membrane oxygenation (ECMO) is a lifesaving intervention increasingly used to support patients with severe respiratory and cardiac dysfunction. Echocardiography is an important tool, aiding implantation and monitoring during ECMO therapy, but often its use is limited by poor acoustic windows. This limitation may be overcome by the use of echocardiography contrast agents to improve diagnostic yield and reduce the need for other imaging modalities that may require patient transfer, involve ionizing radiation and, occasionally, nephrotoxic radio-opaque contrast medium. In this article the authors review the literature addressing the use of contrast-enhanced echocardiography (CEE) in ECMO-supported patients. The authors discuss the role of CEE in guiding implantation of ECMO, cardiac assessment and diagnosis of complications during ECMO therapy, as well as the safety of ultrasound-enhancing agents in this cohort of patients.

Enhanced recovery for thoracic surgery in the elderly.

PURPOSE OF REVIEW: Both surgical workload and the age of those patients being considered for radial pulmonary resection are increasing. Enhanced recovery programmes are now well established in most surgical disciplines and are increasingly reported in thoracic procedures. This review will discuss the relevant principles of these programmes as applied to an increasing elderly population. RECENT FINDINGS: Elderly patients undergoing less radial surgical resections without lymphadenectomy have comparable outcomes to those undergoing classical curative treatment. Patients require careful assessment and self-reported quality of life metrics or function may be a better marker of outcome than static measures such as lung function. Hypotension, low values for bispectral index and low anaesthetic gas mean alveolar concentration values are common and independent predictors of mortality in the elderly. Paravertebral blockade is preferred to epidural anaesthesia because of a more favourable side-effect profile and comparable efficacy. As yet no robust work has examined the efficacy of an integrated enhanced recovery programme in thoracic surgery. SUMMARY: Elderly patients are suitable for enhanced recovery programmes but these must be tailored to individual circumstance. Further work is required to comprehensively assess their value in a modern healthcare setting.

Pharmacological Therapy for the Prevention and Treatment of Weakness After Critical Illness: A Systematic Review.

OBJECTIVES: ICU-acquired weakness is a common complication of critical illness and can have significant effects upon functional status and quality of life. As part of preliminary work to inform the design of a randomized trial of a complex intervention to improve recovery from critical illness, we sought to identify pharmacological interventions that may play a role in this area. DATA SOURCES: We systematically reviewed the published literature relating to pharmacological intervention for the treatment and prevention of ICU-acquired weakness. STUDY SELECTION: We searched MEDLINE, EMBASE, CINAHL+, Web of Science, and both U.S. and European trial registries up to July 2014 alongside reviews and reference lists from populations with no age or language restrictions. We included studies that reported a measure of muscle structure or physical function as an outcome measure. DATA EXTRACTION: We estimated pooled odds ratios and 95% CI using data extracted from published articles or where available, original data provided by the authors. Assessment of bias was performed using the Cochrane Collaboration's risk of bias tool. DATA SYNTHESIS: Ten studies met the inclusion criteria. The current body of evidence does not support the use of any pharmacological agent in this setting, although maintaining euglycemia may reduce the prevalence of critical illness polyneuropathy. CONCLUSIONS: At present, no pharmacological intervention can be recommended to prevent or treat ICU-acquired weakness. Further research is required into this field to include more novel agents such as myostatin inhibitors. Challenges in the conduct of research in this area are highlighted.

What's new in the management of traumatic brain injury on neuro ICU?

PURPOSE OF REVIEW: In recent years, we have begun to better understand how to monitor the injured brain, look for less common complications and importantly, reduce unnecessary and potentially harmful intervention. However, the lack of consensus regarding triggers for intervention, best neuromonitoring techniques and standardization of therapeutic approach is in need of more careful study. This review covers the most recent evidence within this exciting and dynamic field. RECENT FINDINGS: The role of intracranial pressure monitoring has been challenged; however, it still remains a cornerstone in the management of the severely brain-injured patient and should be used to compliment other techniques, such as clinical examination and serial imaging.The use of multimodal monitoring continues to be refined and it may be possible to use them to guide novel brain resuscitation techniques, such as the use of exogenous lactate supplementation in the future. SUMMARY: Neurocritical care management of traumatic brain injury continues to evolve. However, it is important not to use a 'one-treatment-fits-all' approach, and perhaps look to use targeted therapies to individualize treatment.

Facial muscle coordination in monkeys during rhythmic facial expressions and ingestive movements.

Evolutionary hypotheses regarding the origins of communication signals generally suggest, particularly for the case of primate orofacial signals, that they derive by ritualization of noncommunicative behaviors, notably including ingestive behaviors such as chewing and nursing. These theories are appealing in part because of the prominent periodicities in both types of behavior. Despite their intuitive appeal, however, there are little or no data with which to evaluate these theories because the coordination of muscles innervated by the facial nucleus has not been carefully compared between communicative and ingestive movements. Such data are especially crucial for reconciling neurophysiological assumptions regarding facial motor control in communication and ingestion. We here address this gap by contrasting the coordination of facial muscles during different types of rhythmic orofacial behavior in macaque monkeys, finding that the perioral muscles innervated by the facial nucleus are rhythmically coordinated during lipsmacks and that this coordination appears distinct from that observed during ingestion.

Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial.

BACKGROUND: Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. METHODS: We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. FINDINGS: 459 patients were randomly assigned (115 to each of groups A-C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3-7·5] vs 4·5 months [2·8-6·4]; hazard ratio 0·84, 95% CI 0·69-1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14-1·52), less widespread disease (1·51, 1·05-2·19), and use of oxaliplatin (0·57, 0·39-0·82) were predictive of better OTU. INTERPRETATION: FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. FUNDING: Cancer Research UK and the Medical Research Council.

Mirroring of attention by neurons in macaque parietal cortex.

Macaques, like humans, rapidly orient their attention in the direction other individuals are looking. Both cortical and subcortical pathways have been proposed as neural mediators of social gaze following, but neither pathway has been characterized electrophysiologically in behaving animals. To address this gap, we recorded the activity of single neurons in the lateral intraparietal area (LIP) of rhesus macaques to determine whether and how this area might contribute to gaze following. A subset of LIP neurons mirrored observed attention by firing both when the subject looked in the preferred direction of the neuron, and when observed monkeys looked in the preferred direction of the neuron, despite the irrelevance of the monkey images to the task. Importantly, the timing of these modulations matched the time course of gaze-following behavior. A second population of neurons was suppressed by social gaze cues, possibly subserving task demands by maintaining fixation on the observed face. These observations suggest that LIP contributes to sharing of observed attention and link mirror representations in parietal cortex to a well studied imitative behavior.

Updates in the management of intracranial pressure in traumatic brain injury.

PURPOSE OF REVIEW: Traumatic brain injury remains a common and often debilitating event across the world, producing significant burdens upon health and social care. Effective neurocritical care coupled with timely and appropriate neurosurgical intervention can produce significant improvements in patient outcome. There remains controversy about how best to manage intracranial pressure on the ICU; we review the recent literature addressing a number of key variables. RECENT FINDINGS: Treatment of elevations in intracranial pressure can begin at the roadside and end on the ICU unit via a number of routes. Prehospital physician-led care may produce significant benefits in outcome which extend beyond airway management. Routine use of cooling worsens the respiratory outcomes without large improvement in neurological endpoints. The use of brain tissue oxygen monitoring is extending and increasingly used to guide management. Decompressive craniectomy in refractory intracranial hypertension has been associated with poor functional outcomes; a large multicentre trial is currently comparing it against barbiturate coma. SUMMARY: The role of the neurointensivist in outcome for patients who suffer severe traumatic brain injury is key. Targeted therapies are allowing early detection and manipulation of brain ischaemia leading to more individualized treatment.

Bedside post-pyloric tube placement using direct visualisation in mechanically ventilated patients: A single centre case series.

INTRODUCTION: Post-pyloric feeding tubes are used for intensive care patients unable to tolerate gastric feeding. The Kangaroo Feeding Tube with IRIS Technology ('IRIS') uses real-time visualisation of anatomical markers to guide bedside placement, however limited studies currently explore post-pyloric insertions in mechanically ventilated patients. We describe a case series of 'IRIS' post-pyloric placements performed by trained intensivists and dietitians. METHODS: This was a prospective, single-centred clinical effectiveness study of mechanically ventilated adults referred for bedside post-pyloric tube placement between May 2020 and May 2021. The feasibility, success rates, anatomical visualisation using 'IRIS' and nutritional outcomes were documented. RESULTS: Twelve patients were included in total. The primary indication for post-pyloric placement was gastric feeding intolerance, with a median of 3.5 (IQR 0-6) days with inadequate nutrition prior to placement. All tubes were inserted within 24 h of referral as there was always a trained clinician available. Post-pyloric placement was successful for 9/12 patients (75%), as identified on the 'IRIS' console and X-ray confirmation. Only 3 (25%) patients required parenteral nutrition (mean duration 4 [SD 1] days). Respiratory misplacement occurred in 1 patient (8%) and was clearly differentiated from gastrointestinal anatomy, permitting early removal. Although duodenal placement was possible, no tubes reached the jejunum solely using the 'IRIS' method. CONCLUSION: Post-pyloric tube placement using 'IRIS' in mechanically ventilated patients was feasible, successful and safe, resulting in reduced durations with inadequate enteral nutrition. Further, larger-scale studies are required to confirm these findings and explore the effectiveness of 'IRIS' in achieving deep small-intestinal placement.

Cardiac Transplantation following Cobalt Cardiomyopathy from Bilateral Metal-on-Metal Hip Replacements.

A fifty-two-year-old man underwent heart transplantation at our centre after four years of developing progressive heart failure symptoms due to cobalt toxicity-related cardiomyopathy. Between the ages of forty and forty-two, he underwent bilateral metal-on-metal hip arthroplasties for early onset osteoarthritis. Six years later, he developed increasing fatigue and pericardial effusions. Following a prolonged period of deterioration without a clear cause, the diagnosis of cobalt toxicity-related cardiomyopathy due to cobalt-chromium alloy hip prostheses was eventually made. He underwent bilateral revision hip arthroplasties and was listed for heart transplantation. Metal-on-metal joint replacement is a rare cause of iatrogenic cobalt toxicity. Anaesthetists may encounter patients with unexplained symptoms of heart failure, having a high index of suspicion presenting an opportunity for early diagnosis and intervention before end-stage disease develops.

Animation supported communication on intensive care; a service improvement initiative.

Objective: COVID-19 has created unique challenges for families of patients admitted to intensive care units. Restricted visiting, language barriers and time constraints have limited communication, resulting in a lack of understanding and anxiety. We introduced digital animations to support communication and assessed the impact on families of patients admitted to intensive care. Methods: Multi-language animations explaining mechanical ventilation, (www.explainmyprocedure.com/icu) were introduced at two London intensive care units during the COVID-19 pandemic. Web-links were sent by email. Reported understanding of the treatment, its benefits, risks and alternatives was assessed among family contacts of 71 consecutive patients admitted to intensive care; 39 before the animations were introduced (no animation group) and 32 afterwards (animation group). Reported understanding in the two groups was assessed by telephone questionnaire and compared. Results: Following introduction, all relatives reported they had watched the animation. The proportions who reported complete understanding of mechanical ventilation, its benefits, risks and alternatives, in the no animation group (n = 39) were, respectively, 15%, 28%, 0% and 3% and in the animation group (n = 32), 94%, 97%, 84% and 66% (p < 0.0001 for all comparisons). Conclusion: Family use of online multi-language animations explaining mechanical ventilation is feasible, acceptable and associated with substantial improvement in understanding. The approach is not limited to mechanical ventilation, or to use in a pandemic, and has the potential to be applied to a wide range of treatment and recovery pathways on intensive care.

Eye-gaze and arrow cues influence elementary sound perception.

We report a novel effect in which the visual perception of eye-gaze and arrow cues change the way we perceive sound. In our experiments, subjects first saw an arrow or gazing face, and then heard a brief sound originating from one of six locations. Perceived sound origins were shifted in the direction indicated by the arrows or eye-gaze. This perceptual shift was equivalent for both arrows and gazing faces and was unaffected by facial expression, consistent with a generic, supramodal attentional influence by exogenous cues.

Warfarin thromboprophylaxis in cancer patients with central venous catheters (WARP): an open-label randomised trial.

BACKGROUND: The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters (CVCs) is controversial. We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect. METHODS: In 68 clinical centres in the UK, we randomly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin, fixed-dose warfarin 1 mg per day, or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0. Clinicians who were certain of the benefit of warfarin randomly assigned patients to fixed-dose or dose-adjusted warfarin groups. The primary outcome was the rate of radiologically proven, symptomatic catheter-related thrombosis. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN 50312145. FINDINGS: Compared with no warfarin (n=404), warfarin (n=408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter-related thromboses (24 [6%] vs 24 [6%]; relative risk 0.99, 95% CI 0.57-1.72, p=0.98). However, compared with fixed-dose warfarin (n=471), dose-adjusted warfarin (n=473) was superior in the prevention of catheter-related thromboses (13 [3%] vs 34 [7%]; 0.38, 0.20-0.71, p=0.002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p=0.07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison. INTERPRETATION: The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments. FUNDING: Medical Research Council and Cancer Research UK.

Role of central and mixed venous oxygen saturation measurement in perioperative care.

Complications after major surgery are a leading cause of morbidity and mortality. The etiology of postoperative complications is complex, but poor cardiorespiratory reserve appears to be a key factor. There is increasing interest in the use of central and mixed venous oxygen saturation to guide therapeutic interventions during the perioperative period. However, a detailed understanding of the physiologic principles of venous oximetry is essential for safe and effective use in clinical practice. Venous oxygen saturation reflects the balance between global oxygen delivery and oxygen consumption, which may be affected by a wide range of factors during the perioperative period. The purpose of this article is to describe the physiology and measurement of mixed and central venous oxygen saturation and to explore the findings of clinical investigations of their use in perioperative care.

Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial.

BACKGROUND: In the non-curative setting, the sequence in which anticancer agents are used, singly or in combination, may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects. We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer, who were regarded as not potentially curable irrespective of response. METHODS: We studied patients with advanced colorectal cancer, starting treatment with non-curative intent. 2135 unpretreated patients were randomly assigned to three treatment strategies in the ratio 1:1:1. Strategy A (control group) was single-agent fluorouracil (given with levofolinate over 48 h every 2 weeks) until failure, then single-agent irinotecan. Strategy B was fluorouracil until failure, then combination chemotherapy. Strategy C was combination chemotherapy from the outset. Within strategies B and C, patients were randomly assigned to receive, as the combination regimen, fluorouracil plus irinotecan (groups B-ir and C-ir) or fluorouracil plus oxaliplatin (groups B-ox and C-ox). The primary endpoint was overall survival, analysed by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 79877428. RESULTS: Median survival of patients allocated to control strategy A was 13.9 months. Median survival of each of the other groups was longer (B-ir 15.0, B-ox 15.2, C-ir 16.7, and C-ox 15.4 months). However, log-rank comparison of each group against control showed that only C-ir--the first-line combination strategy including irinotecan--satisfied the statistical test for superiority (p=0.01). Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less (HR=1.06, 90% CI 0.97-1.17). INTERPRETATION: Our data challenge the assumption that, in this non-curative setting, maximum tolerable treatment must necessarily be used first-line. The staged approach of initial single-agent treatment upgraded to combination when required is not worse than first-line combination, and is an alternative option for discussion with patients.

Functional Networks for Social Communication in the Macaque Monkey.

All primates communicate. To dissect the neural circuits of social communication, we used fMRI to map non-human primate brain regions for social perception, second-person (interactive) social cognition, and orofacial movement generation. Face perception, second-person cognition, and face motor networks were largely non-overlapping and acted as distinct functional units rather than an integrated feedforward-processing pipeline. Whereas second-person context selectively engaged a region of medial prefrontal cortex, production of orofacial movements recruited distributed subcortical and cortical areas in medial and lateral frontal and insular cortex. These areas exhibited some specialization, but not dissociation, of function along the medio-lateral axis. Production of lipsmack movements recruited areas including putative homologs of Broca's area. These findings provide a new view of the neural architecture for social communication and suggest expressive orofacial movements generated by lateral premotor cortex as a putative evolutionary precursor to human speech.

Primate social attention: Species differences and effects of individual experience in humans, great apes, and macaques.

When viewing social scenes, humans and nonhuman primates focus on particular features, such as the models' eyes, mouth, and action targets. Previous studies reported that such viewing patterns vary significantly across individuals in humans, and also across closely-related primate species. However, the nature of these individual and species differences remains unclear, particularly among nonhuman primates. In large samples of human and nonhuman primates, we examined species differences and the effects of experience on patterns of gaze toward social movies. Experiment 1 examined the species differences across rhesus macaques, nonhuman apes (bonobos, chimpanzees, and orangutans), and humans while they viewed movies of various animals' species-typical behaviors. We found that each species had distinct viewing patterns of the models' faces, eyes, mouths, and action targets. Experiment 2 tested the effect of individuals' experience on chimpanzee and human viewing patterns. We presented movies depicting natural behaviors of chimpanzees to three groups of chimpanzees (individuals from a zoo, a sanctuary, and a research institute) differing in their early social and physical experiences. We also presented the same movies to human adults and children differing in their expertise with chimpanzees (experts vs. novices) or movie-viewing generally (adults vs. preschoolers). Individuals varied within each species in their patterns of gaze toward models' faces, eyes, mouths, and action targets depending on their unique individual experiences. We thus found that the viewing patterns for social stimuli are both individual- and species-specific in these closely-related primates. Such individual/species-specificities are likely related to both individual experience and species-typical temperament, suggesting that primate individuals acquire their unique attentional biases through both ontogeny and evolution. Such unique attentional biases may help them learn efficiently about their particular social environments.

Fatal cardiovascular instability secondary to hypercalcaemia and intracellular calcium deposition complicating T-cell leukaemia-lymphoma.

Adult T-cell leukaemia-lymphoma is a rare haematological malignancy, which can cause severe hypercalcaemia and metastatic calcification resulting in life-threatening arrhythmias.

Availability and use of capnography for in-hospital cardiac arrests in the United Kingdom.

BACKGROUND: Airway complications occur more frequently outside the operating theatre and in emergency situations. Capnography remains the gold standard for confirming correct endotracheal tube placement, retaining high sensitivity and specificity in cardiac arrest. The 2010 European Resuscitation Council guidelines for adult advanced life support recommended waveform capnography in this setting. We investigated current UK practice relating to the availability and use of this technology during cardiac arrest. METHODS: Between June and November 2014, a study was conducted of all UK acute hospitals with both a level three adult intensive care unit (ICU) and an emergency department (ED). A telephone questionnaire was administered examining intubation practice and utilisation of capnography within the ED, ICU and general wards. RESULTS: Two hundred and eleven hospitals met the inclusion criteria. The response rate was 100%. Arrests were mainly attended by anaesthesia (48%) and ICU physicians (38%) of registrar grade (56%). The ability to measure end tidal carbon dioxide (ETCO2) was available in all but 4 EDs; most used in waveform devices. Most ICUs were similar. However, in 67% of hospitals surveyed, it was not possible to measure ETCO2 in general wards. Where available, 87% used capnography to confirm ETT placement with less than 50% using ETCO2 to determine CPR effectiveness and 8% to prognosticate. CONCLUSIONS: We believe this is the first study of its kind to fully investigate the availability and use of capnography during cardiac arrest throughout the hospital. Whilst equipment provision appears adequate in critical care areas, it is insufficient in general wards.