Cancer by Sfakianakis Alexandros: 09/28/17

Πέμπτη 28 Σεπτεμβρίου 2017

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Hypertension and cataract surgery under loco-regional anaesthesia: not to be ignored?

The presence of sight-impairing opacification, cataract, is an age-related condition. Modern phacoemulsification procedures allow cataract removal safely and efficiently under loco-regional anaesthesia.¹ Increasing numbers of patients with comorbid conditions, including dementia, diabetes mellitus, cardiovascular disease on concurrent antithrombotics and hypertension, present for cataract surgery. The British Journal of Anaesthesia has recently addressed anaesthesia-related issues for ophthalmic surgery in patients with dementia,² diabetes mellitus³ and anticoagulation.⁴ This editorial addresses issues related specifically to hypertension. Hypertension impacts 1 billion adults across the globe affecting up to 80% of patients in the general population aged 60 yr and older.⁵ ⁶ Like the sensation of a fishbone stuck in the throat, the impact of hypertension on perioperative outcome after cataract surgery should not be ignored without meticulous interrogation.

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Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis

Abstract

Background

The assessment of intravascular volume status remains a challenge for clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the peripheral venous waveform that has been used to monitor volume status. We present a proof-of-concept study for evaluating the efficacy of PIVA in detecting changes in fluid volume.

Methods

We enrolled 37 hospitalized patients undergoing haemodialysis (HD) as a controlled model for intravascular volume loss. Respiratory rate (F₀) and pulse rate (F₁) frequencies were measured. PIVA signal was obtained by fast Fourier analysis of the venous waveform followed by weighing the magnitude of the amplitude of the pulse rate frequency. PIVA was compared with peripheral venous pressure and standard monitoring of vital signs.

Results

Regression analysis showed a linear correlation between volume loss and change in the PIVA signal (R²=0.77). Receiver operator curves demonstrated that the PIVA signal showed an area under the curve of 0.89 for detection of 20 ml kg⁻¹ change in volume. There was no correlation between volume loss and peripheral venous pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory rate were consistent with similar numbers derived from the bio-impedance and electrical signals from the electrocardiogram.

Conclusions

PIVA is a minimally invasive, novel modality for detecting changes in fluid volume status, respiratory rate and pulse rate in spontaneously breathing patients with peripheral i.v. cannulas.

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Lost in translation? Comparing the effectiveness of electronic-based and paper-based cognitive aids

It is now established that the use of cognitive aids, such as checklists and algorithms leads to improved technical¹ and team performance² during anaesthetic emergencies. The unpredictable nature of emergencies means that it is difficult to examine these outside of a simulation setting. Consequently, it is challenging to prove these observed behaviours translate to improved patient outcomes, although many anecdotal reports exist.³ ⁴ Research is now focused on the nature of these cognitive aids and how they can be integrated into the clinical setting, working with, rather than against the instincts of experienced practitioners.⁵

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SmartPilot ® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study

Abstract

Background

Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot^® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery.

Methods

This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45–60 and systolic arterial pressure of 80–140 mm Hg. Postoperative complications were recorded for one month in a blinded manner.

Results

Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0–40) vs 5 (0–116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2–20) vs 8 (2–60) days, P=0.017).

Conclusions

SmartPilot^® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients.

Clinical trial registration.

NCT 02556658.

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Does variable training lead to variable care?

Entrants to anaesthesia training programs in the developed world are broadly comparable in terms of readiness for specialist training as a result of global standards established by the World Federation for Medical Education. While the context of national health systems has undeniable significance, the competencies required to provide anaesthesia for patients undergoing surgery should also be broadly comparable. In this issue of the British Journal of Anaesthesia, Jonker and colleagues¹ report wide variability in anaesthesia training programmes across the European Union (EU), and variable certification processes. Could this potentially result in variable quality in patient care? Jonker and colleagues propose that variability of training and certification limits the easy movement of anaesthetists around the EU. National health systems around the world remain dependent on a mobile workforce, often trained in other jurisdictions. Determining if a foreign graduate is competent is a key concern for employers.

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Point-of-care paediatric gastric sonography: can antral cut-off values be used to diagnose an empty stomach?

Abstract

Background

Gastric sonography is emerging as a valuable clinical point-of-care tool to assess aspiration risk. A recent study proposed that a single cut-off cross-sectional area (CSA) in the supine position could diagnose an empty stomach in the parturient. This study establishes the sensitivity and specificity of a single CSA cut-off measurement in both supine and right lateral decubitus (RLD) positions in the diagnosis of an empty antrum in paediatric patients.

Methods

Following induction of anaesthesia, antral sonography was performed in supine and RLD positions in 100 fasted paediatric patients prior to upper endoscopic evaluation. Following upper endoscopy, any residual stomach content was suctioned under direct visualization and antral sonography was immediately performed. Antral CSA values were compared using Wilcoxon signed rank test. Receiver operator characteristic (ROC) curves were plotted to estimate the discriminating power of antral sonography position in the diagnosis of an empty antrum.

Results

Significant differences were found between pre-suctioned and post-suctioned CSA values in the RLD position. The cut-off CSAs of the empty antrum in the supine and RLD positions were 2.19 cm² (sensitivity 75%, specificity 36%) and 3.07 cm² (sensitivity 76%, specificity 67%), respectively.

Conclusions

The RLD position produces the most sensitive and specific CSA cut-off value where an antral CSA of ≤ 3.07 cm² in the RLD position presents with acceptable performance in the ability to discriminate an empty antrum in paediatric patients over 1 yr of age. As age increases, the sensitivity and specificity of this test increases in the RLD position.

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Use of a hand-held digital cognitive aid in simulated crises: the MAX randomized controlled trial

Abstract

Background

Cognitive aids improve the technical performance of individuals and teams dealing with high-stakes crises. Hand-held electronic cognitive aids have rarely been investigated. A randomized controlled trial was conducted to investigate the effects of a smartphone application, named MAX (for Medical Assistance eXpert), on the technical and non-technical performance of anaesthesia residents dealing with simulated crises.

Methods

This single-centre randomized, controlled, unblinded trial was conducted in the simulation centre at Lyon, France. Participants were anaesthesia residents with >1 yr of clinical experience. Each participant had to deal with two different simulated crises with and without the help of a digital cognitive aid. The primary outcome was technical performance, evaluated as adherence to guidelines. Two independent observers remotely assessed performance on video recordings.

Results

Fifty-two residents were included between July 2015 and February 2016. Six participants were excluded for technical issues; 46 participants were confronted with a total of 92 high-fidelity simulation scenarios (46 with MAX and 46 without). Mean (sd) age was 27 (1.8) yr and clinical experience 3.2 (1.0) yr. Inter-rater agreement was 0.89 (95% confidence interval 0.85–0.92). Mean technical scores were higher when residents used MAX [82 (11.9) vs 59 (10.8)%; P<0.001].

Conclusion

The use of a hand-held cognitive aid was associated with better technical performance of residents dealing with simulated crises. These findings could help digital cognitive aids to find their way into daily medical practice and improve the quality of health care when dealing with high-stakes crises.

Clinical trial registration

NCT02678819.

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Volumes of the spinal canal and caudal space in children zero to three years of age assessed by magnetic resonance imaging: implications for volume dosage of caudal blockade

Abstract

Background

The primary aim of this study was to objectively assess the different spinal and caudal volumes that are of interest for caudal block volume dosing.

Methods

Three directly assessed (volume of spinal canal/caudal space, volume of the dural sac and volume of spinal cord) and two derived volumes (volume of the epidural space and cerebrospinal fluid volume) were determined from magnetic resonance images (MRI) in 20 children (zero - three yr of age). The assessed volumes were correlated to age, height and weight. Furthermore, the volumes of the epidural space from caudal canal to three different clinically relevant target levels (L 1, Th 10 and Th 6) and the epidural volume of each individual spinal segment at the caudal, lumbar and thoracic levels were calculated.

Results

All volumes correlated in a linear manner to length and weight (R² 0.614 – 0.867) whereas a curvilinear correlation was associated with best curve fit for age (R² 0.696 – 0.883). The median volumes of the epidural space from caudal canal to L 1, Th 10 and Th 6 were 1.30 ml kg⁻¹ (95%CI 1.08-1.51), 1.57 ml kg⁻¹ (95%CI 1.29-1.81) and 1.78 ml kg⁻¹ (95%CI 1.52-2.08), respectively. The median volumes of the epidural space per vertebral segment were Thoracic: 0.60 ml (95%CI 0.38-0.75); Lumbar: 1.18 ml (95%CI 0.94-1.43) and Caudal: 0.85 ml (95%CI 0.56-1.18).

Conclusions

The spinal volumes of interest show a linear correlation to height and weight whereas a curvilinear correlation was found for age. The volume of the epidural space per segment was found to be significantly higher at the lumbar level compared with the caudal and thoracic levels.

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Heterogeneity of studies in anesthesiology systematic reviews: a meta-epidemiological review and proposal for evidence mapping

Abstract

Heterogeneity among the primary studies included in a systematic review (SR) is one of the most challenging considerations for systematic reviewers. Current practices in anaesthesiology SRs have not been evaluated, but traditional methods may not provide sufficient information to evaluate the true nature of these differences. We address these issues by examining the practices for evaluating heterogeneity in anesthesiology reviews. Also, we propose a mapping method for presenting heterogeneous aspects of the primary studies in SRs.We evaluated heterogeneity practices reported in SRs published in highly ranked anesthesiology journals and Cochrane reviews. Elements extracted from the SRs included heterogeneity tests, models used, analyses conducted, plots used, and I² values. Additionally, we selected a SR to develop an evidence map in order to display clinical heterogeneity.Our statistical analysis showed 150/207 SRs reporting a test for statistical heterogeneity. Plots were used in 138 reviews to display heterogeneity. Subgroup analyses were the most commonly reported analysis (54%). Meta-regression and sensitivity analyses were used sparingly (25%; 23% respectively). A random effects model was most commonly reported (33%). Heterogeneity statistics across meta-analyses suggested that, in our sample, the majority (55%) did not present sufficient heterogeneity to be of great concern. Cochrane reviews (n=58) were also analysed. Plots were used in 88% of Cochrane reviews. Subgroup analysis was used in 59% Cochrane reviews, while sensitivity analysis was used in 62%.Many reviews did not provide sufficient detail regarding heterogeneity. We are calling for improvement to reporting practices.

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Expression profiling of microRNAs in human bone tissue from postmenopausal women

Abstract

Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30–40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.

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Expression profiling of microRNAs in human bone tissue from postmenopausal women

Abstract

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Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract

Background

. Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia.

Methods

. Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h⁻¹ for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively.

Results

. A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min (P=0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine (P=0.009). At three months, no differences between groups were noted.

Conclusions

. Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up.

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Review: Brown’s Atlas of Regional Anesthesia . E Farag and L Mounir-Soliman (editors) & Brown’s Regional Anesthesia Review . E Farag and L Mounir-Soliman (editors)

Review: Brown's Atlas of Regional Anesthesia.FaragE and Mounir-SolimanL (editors), 5^th edn, 2017. Published by Elsevier. Pp. 376. Price $199.99. ISBN-13: 978-0323354905.

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Is the bougie redundant in direct laryngoscopic grade 3 intubations?

A 51-year-old woman presented for major elective colorectal surgery with predicted difficult intubation (Mallampati score 3, small mouth opening) and a video laryngoscope was prepared as a 'plan B'. After induction, the patient's lungs were easily ventilated with a bag valve mask. Direct laryngoscopy was performed that demonstrated a grade 3 view. An experienced operator intubated successfully using a bougie, which was carefully advanced in one attempt blindly behind the epiglottis into the trachea.

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In the October BJA …

This issue of the BJA contains a special section on pain medicine that includes articles on acute and chronic pain in the context of anaesthesia. The main section of the Journal includes a number of articles relevant to perioperative outcomes in sepsis and septic shock, and in cardiac, abdominal, and lung resection surgery. There are also articles on the impact of non-depolarising neuromuscular blocking agents, beta-blockers, and statins on perioperative outcomes. The Neurosciences and Neuroanaesthesia section features three articles and three editorials related to anaesthetic effects on neuronal network connectivity as it relates to unconsciousness. And the Quality and Patient Safety section features an article with an editorial on the impact of anaesthetist gender on communication in simulated crisis situations.

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The paradox in the current use of videolaryngoscopes in the UK

Editor—The recent national survey by Cook and Kelly¹ is the first to provide a comprehensive overview of the current usage and practices of videolaryngoscopes (VLs) in UK clinical practice. We feel we can add to this area and would like to present some of the results of a regional survey on VLs that we conducted to gain an understanding of current practices and decision-making in the use of VLs in general airway management in the operating theatre (OT). The survey was conducted electronically via SurveyMonkey (San Mateo, CA, USA) and was distributed to 10 departments of anaesthesia in the London Deanery (London, UK) in December 2016. There were 171 responses collected between December 2016 and January 2017 with a response rate of about 51%, including 44% consultants, 21% specialty Registrar (StR) yr 7–yr 5, 14% StR yr 4–yr 3, and 7% core trainees. Selected findings from the survey were as follows:

When asked whether VLs should be first line management strategy for anticipated difficult intubation (where bag mask ventilation was not predicted difficult), when given the choice between a VL and a Macintosh laryngoscope short/long blade +/–bougie, 51% of those surveyed preferred to use a VL.
When asked whether VLs should be used routinely for intubation in all patients, regardless of predicted difficulty of intubation, 14% of respondents thought that VLs should be used routinely.
When asked how many uses it approximately required to gain subjective competence in the use of any VL, 68% of respondents felt it required over 10 uses, 32% felt it required over 20 uses and 13% felt it required over 30 uses.
When asked whether anaesthetists should begin their core training with VLs alongside the Macintosh laryngoscope as first line for all intubations, 10% of respondents were of the opinion that this should be the case.

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Diastolic dysfunction and sepsis: the devil is in the detail

Diastolic dysfunction is the consequence of impaired left ventricular relaxation, decreased recoil and decreased ventricular compliance.¹ Before the era of tissue Doppler imaging (TDI), pulmonary vein Doppler imaging in conjunction with transmitral Doppler, was a major tool in identifying diastolic dysfunction, also in septic shock patients.² Pulmonary vein Doppler assessment with a systolic (S) < diastolic (D) flow velocity supports the finding of elevated left ventricular filling pressures in a euvolaemic patient.

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Preadmission statin use improves the outcome of less severe sepsis patients - a population-based propensity score matched cohort study

Abstract

Background

Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied.

Methods

We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications.

Results

We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78–0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78–0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission.

Conclusions

In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

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Readmission after surgery: are neuromuscular blocking drugs a cause?

Neuromuscular blocking drugs (NMBDs) play an integral role in balanced anaesthesia. They improve intubating conditions, reduce iatrogenic damage to the upper airway and decrease postoperative hoarseness.¹ They also improve surgical operating conditions.² But use of NMBDs always carries the risk of residual neuromuscular block postoperatively. About 30% of all patients who receive NMBDs intraoperatively show signs of residual neuromuscular block when arriving in the post-anaesthesia care unit.^3–5 It has been suggested that residual neuromuscular block can cause postoperative pulmonary complications.^6–8

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Tissue Doppler assessment of diastolic function and relationship with mortality in critically ill septic patients: a systematic review and meta-analysis

Abstract

Background

Myocardial dysfunction may contribute to circulatory failure in sepsis. There is growing evidence of an association between left ventricular diastolic dysfunction (LVDD) and mortality in septic patients. Utilizing echocardiography, we know that tissue Doppler imaging (TDI) variables e′ and E/e′ are reliable predictors of LVDD and are useful measurements to estimate left ventricular (LV) filling pressures.

Methods

We conducted a systematic review and meta-analysis to investigate the association of e′ and E/e′ with mortality of patients with severe sepsis or septic shock. In the primary analysis, we included studies providing transthoracic TDI data for e′ and E/e′ and their association with mortality. Subgroup analyses were conducted according to myocardial regional focus of TDI assessment (septal, lateral or averaged). Three secondary analyses were performed: one included data from a transoesophageal study, another excluded studies reporting data at a very early (<6 h) or late (>48 h) stage following diagnosis, and the third pooled data only from studies excluding patients with heart valve disease.

Results

The primary analysis included 16 studies with 1507 patients with severe sepsis and/or septic shock. A significant association was found between mortality and both lower e′ [standard mean difference (SMD) 0.33; 95% confidence interval (CI): 0.05, 0.62; P=0.02] and higher E/e′ (SMD –0.33; 95% CI: –0.57, –0.10; P=0.006). In the subgroup analyses, only the lateral TDI values showed significant association with mortality (lower e′ SMD 0.45; 95% CI: 0.11, 0.78; P=0.009; higher E/e′ SMD –0.49; 95% CI: –0.76, –0.22; P=0.0003). The findings of the primary analysis were confirmed by all secondary analyses.

Conclusions

There is a strong association between both lower e′ and higher E/e′ and mortality in septic patients.

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Age and inflammation after cardiac surgery

The cardiac surgical population is aging and these patients have increased expectations with respect to quantity and quality of postoperative survival. Some of the physiological changes related to aging that impact surgical outcomes are better understood than others, and recently we are also beginning to gain a better understanding of the impact of aging on immunity and the immune response to surgery.¹ ²

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An algorithm for suboptimally placed supraglottic airway devices: the choice of videolaryngoscope

Editor—We agree with Zundert and colleagues¹ that anaesthetists sometimes accept lower standards for supraglottic airway device (SAD) placement than for tracheal tube placement. They advocate the use of videolaryngoscopy to correct a suboptimal SAD position using an algorithm, however they do not make any specific recommendation about which type of videolaryngoscope to use. A variety of classifications of videolaryngoscopes exist,^2–5 and some classes (for example, channelled videolaryngoscopes) might prove to be very difficult to use in this situation; some may even cause trauma in the reduced space available when an SAD is present. Zundert and colleagues ⁶ have previously referenced the C-MAC videolaryngoscope (Karl Storz, Tuttlingen, Germany) in this situation, but presumably other Macintosh-type bladed scopes would be acceptable. We would be keen to learn whether they have experience of other videolaryngoscopes, and we also wondered whether they had considered the place of the optical stylet.

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Hierarchy in disruption of large-scale networks across altered arousal states

Understanding how anaesthetics act within neural circuits to induce altered arousal states that range from sedation to general anaesthesia is an important question in neuroscience. Studies in laboratory animals demonstrate that anaesthetics including propofol, ether derivatives, and dexmedetomidine induce activity patterns in brainstem arousal nuclei that are similar to natural sleep.^1–3 However, anaesthetic drug action in brainstem arousal nuclei may provide only a partial answer to explain the behavioural and neurophysiological distinctions between anaesthesia-induced states and sleep, because anaesthetics also significantly modulate neuronal activity in other brain regions such as the thalamus and cortex.⁴ ⁵ Insights into how anaesthetics disrupt networks that sustain consciousness have been constrained by the practical and ethical challenges involved in noninvasively studying human brain activity. Guldenmund and colleagues⁶ used human neuroimaging to study large-scale network disruptions that are associated with dexmedetomidine and propofol sedation, two anaesthetic drugs with different receptor level targets.

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Humour therapy intervention to reduce stress and anxiety in paediatric anaesthetic induction, a pilot study

Editor—Hospitalization is a particularly negative experience for the paediatric population. Infants experiencing surgery can develop problematic behaviour, such as preoperative anxiety (50–75%)¹ and postoperative negative behavioural changes (75%), sleep and eating disorders, cognitive alterations, enuresis and disobedience. These complications can persist for several months after the surgical procedure.² In addition, it is well known that stress slows the healing process, decreases inflammatory responses, and likewise increases fear and anxiety. From a pathophysiological point of view, the increase in levels of circulating cortisol, secondary to an increase in the production of corticotropin releasing hormone and the action of the autonomic nervous system, can create harmful effects in different organs and tissues.³ Salivary cortisol has been used in several studies to measure levels of stress in children, as an index of the amount in blood, but which is a noninvasive procedure ideal for use in the paediatric population.

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Fading whispers down the lane: signal propagation in anaesthetized cortical networks

An active area of enquiry in the neuroscientific investigation of general anaesthesia is the question of whether anaesthetic-induced unconsciousness is mediated by bottom-up or top-down mechanisms in the brain. Candidates for the bottom-up approach include suppression of arousal centres in the brainstem and diencephalon,¹ ² activation of sleep-promoting neurones or nuclei in similar locations,¹ ³ blockade of sensory information en route from the thalamus to the cortex,⁴ and a disabled thalamic conductor for the neuronal orchestra of the cortex.⁵ Candidates for the top-down approach include direct effects on long-latency activity in cortical networks,⁶ with a consequent disruption of higher-order information synthesis that occurs beyond the level of the primary sensory cortex.^7–9 This bottom-up vs top-down distinction is almost surely artificial given the integrated circuits required for the normal function of neural systems and the widespread effects of general anaesthetics on the brain. We recently proposed that anaesthetics alter the level of consciousness (e.g. awake vs somnolent) through bottom-up mechanisms while degrading the contents of consciousness (e.g. the particular qualities of experience) through top-down mechanisms.¹⁰ Developing a clearer understanding of these processes is important because it can inform (i) the neurobiology of consciousness, a fundamental question in science, and (ii) our approach to brain monitoring, a fundamental and unmet challenge in clinical anaesthesia. However, it is difficult to address this question by investigating individual brain areas or molecular targets in the laboratory and also difficult to distinguish cortical and subcortical mechanisms through human neuroimaging and neurophysiology. In this issue of the British Journal of Anaesthesia, Hentschke and colleagues¹¹ examine an intermediate level of neuroanatomy and neurophysiology in a cortical slice model, finding more profound effects of isoflurane on signal propagation through the cortex than to the cortex.

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Disruption of cortical network activity by the general anaesthetic isoflurane

Abstract

Background

Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear.

Methods

We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices.

Results

Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05–0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents.

Conclusions

Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.

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Speaking up: does anaesthetist gender influence teamwork and collaboration?

Speaking up can be defined as explicitly communicating observations or concerns, requesting clarification or explanation, or explicitly challenging a colleague's decision or action.¹ Speaking up provides an opportunity to intervene before patient harm occurs, or to mitigate actual harm, and is a key element in effective teamwork and collaboration.² The importance of speaking up is most evident in its absence, where colleagues remain silent or make ineffectual attempts at speaking up, and erroneous actions proceed to cause patient harm. There are many prominent examples where failing to speak up in an effective manner has contributed to accidents and catastrophes in aviation,³ space exploration⁴ and in healthcare.⁵

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Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis

Abstract

Background

To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain.

Methods

We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2–4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain.

Results

Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate.

Conclusions

Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.

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Special section on pain: progress in pain assessment and management

This issue of the British Journal of Anaesthesia has a special section on pain, featuring a number of editorials, reviews and original articles across a range of areas in pain medicine. The last BJA special issue on pain medicine was in July 2013, entitled "Managing pain: recent advances and new challenges", as summarized in the lead editorial of that issue.¹ A similar title could be used for this month's special section. Pain medicine continues to evolve, with advances in acute, chronic and cancer pain understanding and management. However, the challenges remain, and arguably, increase, as our population ages: Pain is one of the biggest causes of disability globally, with musculoskeletal pain being the leading cause of disability in most countries in 2015.² ³ Managing pain successfully - acute, chronic or cancer - is an area where there is potential major clinical benefit both at an individual and societal level.

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Response to: Emergency front-of-neck access: scalpel or cannula—and the parable of Buridan’s ass

Editor—I was interested to read the editorial by Greenland and colleagues¹ that contributes further to the debate that has raged for some time over whether a cannot intubate, cannot oxygenate (CICO) situation should be managed with a fine needle or scalpel cricothyroidotomy approach.

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Guidelines for perioperative pain management: need for re-evaluation

Optimal perioperative pain management facilitates postoperative ambulation and rehabilitation, and is considered a prerequisite to enhancing recovery after surgery.¹ ² Despite well-documented benefits, postoperative pain continues to be inadequately treated.³^–⁵ Although the reasons for the lack of appropriate pain management are not precisely known, conflicting and confusing evidence as well as lack of clear guidance could be contributing factors.

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Ascending upper limb lymphangitis

Description

A 7-year-old boy presented with ascending erythema of his left hand with erythematous extension to his axilla. At presentation, the boy was afebrile, well appearing and complained of itching and swelling of the hand, which started the evening prior. On examination, there were two insect bite marks on the index finger with erythematous, non-tender swelling inclusive of the index, middle fingers and dorsum of the hand with extension via a superficial fine erythematous line from the wrist to the axilla via the cubital fossa figures 1 and 2). A clinical diagnosis of lymphangitis was made. Treatment was commenced with flucloxacillin and immobilisation. Twenty-four hours later, the erythema had faded substantially. Lymphangitis is inflammation of the lymphatic channels that occur as a result of infection at a site distal to the channel and may spread within hours. Group A beta-haemolytic streptococci are the most common causes...

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False acute kidney injury alert due to model car fuel ingestion

We report a case of accidental ingestion of model car fuel (Optifuel) resulting in an apparent elevation of serum creatinine of 274 µmol/L (3.1 mg/dL) as measured by the Jaffe (alkaline picrate) reaction, which resulted in an acute kidney injury (AKI) stage 3 alert being reported. Optifuel contains nitromethane, which has been reported to interfere in the Jaffe reaction causing falsely high creatinine measurements. The laboratory staff were vigilant about this potential interfering substance so repeated the analysis of the creatinine using an enzymatic method that showed a markedly lower result of 47 µmol/L (0.5 mg/dL). This report highlights the ability of nitromethane to potentially mimic AKI and the importance of being aware of the limitations of biochemical tests to avoid misinterpretation of results and instigating inappropriate treatment.

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Typical carcinoid involving the main carina managed with arterial embolisation, endobronchial resection and ablation, ultimately followed by carinal resection

Bronchial carcinoids are uncommon pulmonary tumours, and the gold standard management is surgical resection. Their management is often complicated by their proximal location and propensity to bleed when manipulated. A 22-year-old man was found to have typical carcinoid tumour involving the carina and surgical resection was considered not feasible. We report our experience with a multimodality approach involving arterial embolisation, with subsequent endobronchial resection and ablation. Residual disease was found and managed with definitive carinal resection.

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Possible congenital dilatation of the pancreatic duct

The main pancreatic duct can become dilated in a number of conditions. We describe a patient with gross dilatation of the main pancreatic duct without evidence of causative underlying pathology suggesting congenital dilatation of the pancreatic duct. A 36-year-old man presented with signs of intestinal obstruction and a history of surgery for congenital pyloric stenosis. Incidental findings on CT showed a massively dilated main pancreatic duct. On MRI there was no duct irregularity or solid mural nodule, making a main duct intraductal papillary mucinous neoplasm unlikely. Endoscopic ultrasound findings were in keeping with those on MRI. Fine needle aspiration revealed a non-viscous fluid with a low carcinoembryonic antigen and high amylase concentration, consistent with normal pancreatic fluid levels rather than a mucinous collection. After 1 year, the cyst remains unchanged. This patient will be kept under surveillance with yearly MRI.

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Retroperitoneal teratoma simulating giant adrenal myelolipoma: a diagnostic puzzle

Teratoma is a germ-cell tumour that is common in para-axial regions. Retroperitoneal teratoma is rare and comprise only about 1% of all teratomas. We present a 21-year-old female who presented with a lump in the abdomen. After radiological investigations, she was diagnosed as case of adrenal myelolipoma which on excision turned out histologically to be retroperitoneal teratoma. Our case highlights the limitation of radiological investigations in preoperative diagnosis of teratoma.

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Acromegaly with hypophosphataemia: McCune-Albright syndrome

A 38-year-old man presented with excessive height gain and progressive enlargement of the extremities since childhood. This was compounded by lower limb deformities over the past 5 years. On examination, his height was 196 cm, he had macroglossia, acral enlargement, seborrhoea, hyperhidrosis—suggesting acrogigantism. He had facial asymmetry, wind-swept deformity of lower limbs and a café-au-lait macule over his trunk. Investigations revealed normal-sized pituitary gland with dysplastic cranial bones. Isotope bone scintigraphy was suggestive of polyostotic fibrous dysplasia. A diagnosis of McCune-Albright syndrome was made and trans-sphenoidal hypophysectomy was undertaken. He had persistent hypophosphataemia. Tubular reabsorption of phosphate adjusted for glomerular filtration rate was low and serum FGF-23 level was high. Ga-DOTATATE scintigraphy showed somatostatin-receptor expression in all the dysplastic lesions. FGF-23 produced by the bony lesions could counteract the phosphate-retaining effect of GH excess resulting in hypophosphataemia, which further worsened following hypophysectomy.

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Simultaneous combined complete tear of radial and ulnar collateral ligaments of thumb in an adolescent

Isolated tear of collateral ligaments of thumb are common but combined injuries of both radial and ulnar collateral ligaments are rare. These cases are reported in athletes involved in high-impact sports. Here, we report a case of a 15-year-old boy with pain at base of the thumb and instability following low-impact sporting activity. On subsequent clinicoradiological assessment, simultaneous combined complete tear of both radial and ulnar collateral ligaments of the thumb was noted. Delayed primary repair of both collateral ligaments was done. This case highlights the rarity of this type of injury in an adolescent and also the use of appropriate clinical tests and imaging modalities for early diagnosis of such injuries. Restoration of joint stability as early as possible either by repair or reconstruction of ligaments needs to be considered to prevent secondary osteoarthritis of metacarpophalangeal joint.

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HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining

Approximately 1%–10% of patients with HIV infection have been reported to have salivary gland enlargement. Parotid swelling in patients with HIV is often associated with salivary gland disease, including benign lymphoepithelial cysts (BLECs). The presence of BLEC can serve as an indicator of HIV infection, and the diagnosis of HIV-associated BLEC is usually based on clinical course, HIV confirmatory blood testing, such as western blot or viral detection, and imaging studies, but not on biopsies or immunostaining. To exclude other diseases such as tuberculosis and malignant lymphoma and to further improve the diagnostic accuracy of BLEC, the detection of the HIV-1 p24 antigen by immunohistochemistry is a useful diagnostic method. We report a case of a 65-year-old Japanese man with swelling of the parotid glands and HIV-associated BLEC confirmed via HIV-1 p24 immunohistochemical staining.

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Phelan-McDermid syndrome due to SHANK3 mutation in an intellectually disabled adult male: successful treatment with lithium

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the SHANK3 gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective. In addition to two elsewhere published adolescent patients, we here describe in detail the history of an adult male patient with PMS caused by a SHANK3 mutation in whom successive treatment regimens with antipsychotics and mood-stabilising anticonvulsants were all ineffective. Ultimately, addition of lithium to existing olanzapine therapy led to enduring stabilisation of mood and behaviour.

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Breast pseudoaneurysm arising from core needle biopsy should be left well alone

A 45-year-old woman previously fit and well, developed a pseudoaneurysm of the breast following core needle biopsy. She was ultimately reassured and discharged without further intervention. Pseudoaneurysm is a rare complication of core needle biopsy which, contrary to previously published cases, can be managed conservatively.

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Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma

Publication date: Available online 28 September 2017
Source:Cancer Cell
Author(s): Christian J. Braun, Monica Stanciu, Paul L. Boutz, Jesse C. Patterson, David Calligaris, Fumi Higuchi, Rachit Neupane, Silvia Fenoglio, Daniel P. Cahill, Hiroaki Wakimoto, Nathalie Y.R. Agar, Michael B. Yaffe, Phillip A. Sharp, Michael T. Hemann, Jacqueline A. Lees
Glioblastoma (GBM) is a devastating malignancy with few therapeutic options. We identify PRMT5 in an in vivo GBM shRNA screen and show that PRMT5 knockdown or inhibition potently suppresses in vivo GBM tumors, including patient-derived xenografts. Pathway analysis implicates splicing in cellular PRMT5 dependency, and we identify a biomarker that predicts sensitivity to PRMT5 inhibition. We find that PRMT5 deficiency primarily disrupts the removal of detained introns (DIs). This impaired DI splicing affects proliferation genes, whose downregulation coincides with cell cycle defects, senescence and/or apoptosis. We further show that DI programs are evolutionarily conserved and operate during neurogenesis, suggesting that they represent a physiological regulatory mechanism. Collectively, these findings reveal a PRMT5-regulated DI-splicing program as an exploitable cancer vulnerability.

Graphical abstract

Teaser

Braun et al. show that glioblastoma is selectively sensitive to the inhibition of PRMT5 and identify a predictive biomarker for this sensitivity. PRMT5 inhibition primarily disrupts the removal of detained introns, which results in the reduction of functional transcripts of mainly proliferation-associated genes.

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Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

Publication date: Available online 28 September 2017
Source:Cancer Cell
Author(s): Alan Mackay, Anna Burford, Diana Carvalho, Elisa Izquierdo, Janat Fazal-Salom, Kathryn R. Taylor, Lynn Bjerke, Matthew Clarke, Mara Vinci, Meera Nandhabalan, Sara Temelso, Sergey Popov, Valeria Molinari, Pichai Raman, Angela J. Waanders, Harry J. Han, Saumya Gupta, Lynley Marshall, Stergios Zacharoulis, Sucheta Vaidya, Henry C. Mandeville, Leslie R. Bridges, Andrew J. Martin, Safa Al-Sarraj, Christopher Chandler, Ho-Keung Ng, Xingang Li, Kun Mu, Saoussen Trabelsi, Dorra H'mida-Ben Brahim, Alexei N. Kisljakov, Dmitry M. Konovalov, Andrew S. Moore, Angel Montero Carcaboso, Mariona Sunol, Carmen de Torres, Ofelia Cruz, Jaume Mora, Ludmila I. Shats, João N. Stavale, Lucas T. Bidinotto, Rui M. Reis, Natacha Entz-Werle, Michael Farrell, Jane Cryan, Darach Crimmins, John Caird, Jane Pears, Michelle Monje, Marie-Anne Debily, David Castel, Jacques Grill, Cynthia Hawkins, Hamid Nikbakht, Nada Jabado, Suzanne J. Baker, Stefan M. Pfister, David T.W. Jones, Maryam Fouladi, André O. von Bueren, Michael Baudis, Adam Resnick, Chris Jones
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.

Graphical abstract

Teaser

Mackay et al. perform an integrated analysis of >1,000 cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma. They identify co-segregating mutations in histone-mutant subgroups and show that histone wild-type subgroups are molecularly more similar to lower-grade tumors.

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Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma

Graphical abstract

Teaser

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma

Graphical abstract

Teaser

Quality indicators in breast cancer care: An update from the EUSOMA working group

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Laura Biganzoli, Lorenza Marotti, Christopher D. Hart, Luigi Cataliotti, Bruno Cutuli, Thorsten Kühn, Robert E. Mansel, Antonio Ponti, Philip Poortmans, Peter Regitnig, Jos A. van der Hage, Yvonne Wengström, Marco Rosselli Del Turco
In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.

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Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): X. Pivot, S. Verma, L. Fallowfield, V. Müller, M. Lichinitser, V. Jenkins, A. Sánchez Muñoz, Z. Machackova, S. Osborne, J. Gligorov
AimTo assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166).Patients and methodsPost surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin^® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin^® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation.ResultsA total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients).ConclusionsThree-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected.

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Heart rate variability: implications for perioperative anesthesia care.

Purpose of review: Heart rate variability (HRV) is a measure of the balance between both the parasympathetic and sympathetic nervous system and may provide useful information for anesthesia care providers. HRV may offer predictive information about critically ill and operative patients. Further, HRV collection provides real-time information of patient autonomic nervous system status and may allow tailoring of the analgesia for patients in the ICU and operating room. Recent findings: Reduced and abnormal resting HRV predict sudden and nonsudden cardiac death. Recent evidence shows that decreased HRV correlates with worsened outcomes in both trauma patients and patients with sepsis, as well as the risk of developing hypotension after induction of general anesthesia and placement of intrathecal local anesthesia. In addition, HRV appears to provide an accurate assessment of the nociception-analgesia balance in deeply sedated ICU patients and those under general anesthesia. Summary: No study has assessed the prognostic value of preoperative HRV in patients presenting for surgery. Use of HRV for patient risk stratification and intraoperative analgesia management may allow tailored perioperative care and improved outcomes. If intraoperative HRV data leads to decreased perioperative opioid use, opioid-related adverse events, a serious perioperative issue, may be decreased. Clinical Trials Registration: Not applicable Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Difficult airway management and training: simulation, communication, and feedback.

Purpose of review: Successful and sustainable training and learning of the management of difficult and normal airway is essential for all clinically active anesthesiologists. We emphasize the importance of a continuously updated learning and training environment based on actual knowledge, best available equipment, standardized procedures, and educational theory. Recent findings: In the past, most of the training were based on 'learning by doing' under the supervision of superiors or experienced colleagues. This has been recognized as insufficient and training has evolved to its recent level by structuring it into technical, methodological, and behavioral components. Additionally, a large part of it has been shifted away from learning on patients to simulated scenarios in designated environments. The contents, structure, components, and succession of components have been refined according to the steadily evolving and available instruments. Increasingly, team interaction and behavioral aspects gained more attention and became part of standardized education units that are tailored to the learners' clinical role and level of experience. Summary: We present the details of the Zurich Airway Training and Simulation program, which has been constantly updated to the actual state of knowledge and available equipment. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative management of cardiac rhythm assist devices in ambulatory surgery and nonoperating room anesthesia.

Purpose of review: Patients with cardiac implantable electronic devices (CIEDs) frequently undergo various surgical procedures and in the past perioperative management involved only placing magnet over the device. New programming features, development of implantable cardiac defibrillator (ICD), cardiac resynchronization therapy, and increasing complexity of the operating room equipment have led to new sources of electromagnetic interference (EMI). A comprehensive understanding of the CIED is necessary to provide a timely and optimal care to the patients. Recent findings: Technological advancements and direct implantation of the transvenous implantable cardiac defibrillators into the heart have led to less clear lines between the pacemakers and the ICD. Subcutaneous ICD as well as the leadless transcatheter deployed intracardiac pacemaker development has complicated the issue further. Summary: Rapidly developing technologies and increasing number of patients with these devices coming for noncardiac surgeries necessitate continuous education of the anesthesia team regarding perioperative management of such devices. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The role of nitric oxide in melanoma

Publication date: Available online 27 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Keerthi Yarlagadda, John Hassani, Isaac P. Foote, Joseph Markowitz
Nitric oxide (NO) is a small gaseous signaling molecule that mediates its effects in melanoma through free radical formation and enzymatic processes. Investigations have demonstrated multiple roles for NO in melanoma pathology via immune surveillance, apoptosis, angiogenesis, melanogenesis, and on the melanoma cell itself. In general, elevated levels of NO prognosticate a poor outcome for melanoma patients. However, there are processes where the relative concentration of NO in different environments may also serve to limit melanoma proliferation. This review serves to outline the roles of NO in melanoma development and proliferation. As demonstrated by multiple in vivo murine models and observations from human tissue, NO may promote melanoma formation and proliferation through its interaction via inhibitory immune cells, inhibition of apoptosis, stimulation of pro-tumorigenic cytokines, activation of tumor associated macrophages, alteration of angiogenic processes, and stimulation of melanoma formation itself.

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Corrigendum to “The vicious circle of treatment-induced toxicities in locally advanced head and neck cancer and the impact on treatment intensity” [Crit. Rev. Oncol./Hematol. 116 (2017) 82–88]

Publication date: November 2017
Source:Critical Reviews in Oncology/Hematology, Volume 119
Author(s): Paolo Bossi, Maria Cossu Rocca, Renzo Corvò, Roberta Depenni, Vittorio Guardamagna, Franco Marinangeli, Francesco Miccichè, Fabio Trippa

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Systematic literature review of health-related quality of life in locally-advanced non-small cell lung cancer: has it yet become state-of-the-art?

Publication date: Available online 28 September 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Lotte van der Weijst, Veerle Surmont, Wim Schrauwen, Yolande Lievens
Lung cancer and its treatment have an important impact on the patients' health-related quality-of-life (HRQoL). A systematic literature review of prospective clinical studies published since 2005 and measuring HRQoL in patients with locally-advanced non-small cell lung cancer (LA- NSCLC) was performed. Besides reviewing the HRQoL impact of LA-NSCLC treatment, it critically examined the frequency, methodology and quality of HRQoL data collection and analysis in LA-NSCLC clinical studies. Out of 814 potentially eligible publications, only 27 (representing 19 individual studies) met the inclusion criteria. Eight studies documented an impact on HRQoL. Large variability in use of HRQoL instruments, statistical analysis and methodological quality was observed. Reporting of HRQoL data lacks standardization, but recent initiatives establishing recommendations to standardize the analysis and reporting of HRQoL in cancer trials are expected to address these issues. Overall, more research is needed to evaluate the treatment impact on HRQoL in both clinical trials and daily care.

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Corrigendum to “The vicious circle of treatment-induced toxicities in locally advanced head and neck cancer and the impact on treatment intensity” [Crit. Rev. Oncol./Hematol. 116 (2017) 82–88]

Systematic literature review of health-related quality of life in locally-advanced non-small cell lung cancer: has it yet become state-of-the-art?

Gemtuzumab Receives New FDA Approval for Acute Myeloid Leukemia

FDA has approved gemtuzumab ozogamicin (Mylotarg™) for adults with newly diagnosed CD33-positive AML and patients 2 years and older with CD33-positive AML who have experienced a relapse or whose disease has not responded to initial treatment.

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Gemtuzumab Receives New FDA Approval for Acute Myeloid Leukemia

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The effect of agomelatine and melatonin on sleep-related eating: a case report

Sleep-related eating may occur in the context of mental illness, sleep disorders, or psychopharmacological treatment. Frequently, sleep-related eating leads to severe weight gain and, so far, there are no trea...

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Application of microscope-based scanning software (Panoptiq) for the interpretation of cervicovaginal cytology specimens

BACKGROUND

Digital pathology increasingly has been gaining the attention of pathologists worldwide. However, the application of digital cytology by Panoptiq (ViewsIQ, Vancouver, Canada) microscope-based scanning software is relatively unexplored. Panoptiq enables the operator to combine low-power panoramic digital images with z-stacks at regions of interest with a significantly smaller image size than that obtained by whole-slide scanning. The current study aimed to evaluate the feasibility of the use of Panoptiq in the digital interpretation of cervicovaginal cytology specimens in comparison with conventional light microscopy.

METHODS

A total of 100 liquid-based cytology slides were selected sequentially. The dotted slides were reviewed and scanned, in which all dotted areas were scanned further by the ×20 objective with z-stacks. The cases were reviewed by 4 pathologists and a cytotechnologist using conventional light microscopy and digital cytology images acquired by Panoptiq and interpreted based on the Bethesda classification system. The washout time was set as 3 weeks. The Cohen kappa coefficient was calculated to measure the agreement between the 2 modalities.

RESULTS

Digital cytology demonstrated an intermodality agreement among 3 observers who had sufficient training in digital pathology at concordance rates between 81% and 90% with kappa values between 0.76 and 0.86, whereas the other 2 observers who did not have sufficient training in digital pathology had lower agreement at a concordance rate of between 56% and 57%, with kappa values between 0.41 and 0.44.

CONCLUSIONS

Panoptiq appears to be feasible for the interpretation of cervicovaginal cytology specimens but requires adequate training in digital pathology. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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Application of microscope-based scanning software (Panoptiq) for the interpretation of cervicovaginal cytology specimens

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

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Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for patients with acute myeloid leukemia (AML). During transplantation, patients undergo a period of severe neutropenia, which puts them at high risk for infectious complications. However, the impact of patient colonization with multidrug-resistant organisms (MDRO) on overall survival remains unclear.

METHODS

In this retrospective, single-center study, the authors analyzed data from 264 patients with AML who underwent a first allo-HSCT between January 2006 and March 2016 at their institution. Primary endpoints were overall survival and nonrelapse-related mortality.

RESULTS

One hundred forty-two of 264 patients (53.8%) were colonized by at least 1 MDRO, mainly with vancomycin-resistant Enterococcus faecalis/faecium (n = 122). The characteristics of colonized patients did not differ from those of MDRO-negative patients with respect to median age (53.5 vs 53 years), cytogenetic risk according to European LeukemiaNet criteria, remission status before allo-HSCT (first or second complete remission: 55.7% vs 60.7%, respectively; active disease: 44.4% vs 39.3%, respectively), donor type, or hematopoietic cell transplantation-comorbidity index (HCT-CI). Compared with noncolonized patients, MDRO-positive patients had an inferior probability of survival at 5 years (43.3% vs 65.5%; P = .002), primarily because of a higher cumulative incidence of nonrelapse-related mortality (33.9% vs 9.4%; P < .001). Death caused by infections occurred in 15.5% of colonized patients versus 4.9% of noncolonized patients. There was no difference in the cumulative incidence of relapse in MDRO-positive versus MDRO-negative patients (33.8% vs 42.1%, respectively; P = .798).

CONCLUSIONS

The current data emphasize the importance of regular MDRO screenings and prompt further investigations into the impact of colonization with MDRO on the immune system after allo-HSCT. Cancer 2017. © 2017 American Cancer Society.

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Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature

BACKGROUND

Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.

METHODS

An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups.

RESULTS

A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD-1 group and 2460 patients in the PD-L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD-L1 (32% vs 25%; P = .6). There was no difference in response rate noted between PD-1 (19%) and PD-L1 (18.6%) inhibitors (P = .17). The incidence of overall adverse events (AEs) was comparable between the PD-1 and PD-L1 inhibitors (64% [95% confidence interval (95% CI), 63%-66%] vs 66% [95% CI, 65%-69%]; P = .8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P = .07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P = .01) compared with patients who received PD-L1 inhibitors.

CONCLUSIONS

In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2017. © 2017 American Cancer Society.

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Cabozantinib is well tolerated in acute myeloid leukemia and effectively inhibits the resistance-conferring FLT3/tyrosine kinase domain/F691 mutation

BACKGROUND

Cabozantinib, a tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 (FLT3), MET, AXL, vascular endothelial growth factor receptor, and KIT, is approved for use in multiple malignancies. We assessed the safety and tolerability of cabozantinib in AML, given up-regulation of multiple relevant pathways.

METHODS

Adults were eligible if they were 18 years old or older with relapsed/refractory AML or if they were 70 years old or older with newly diagnosed AML but were ineligible for conventional therapy. Cabozantinib was administered in 28-day cycles, and dose escalation occurred via cohorts. A pharmacodynamic evaluation of serial plasma samples via a plasma inhibitory assay (PIA) was used to assess FLT3-inhibitory activity in FLT3-mutant cell lines.

RESULTS

Among 18 patients enrolled, 5 were found to harbor FLT3/ITD mutations. Sixteen patients (89%) had relapsed/refractory AML, and most were treated with 2 or more lines of prior treatment. No dose-limiting toxicities (DLTs) were detected at the first dose level (40 mg daily), but 2 patients experienced DLTs at the next level (60 mg daily). The remaining patients were then dosed at 40 mg daily, the maximum tolerated dose (MTD). Additional grade 2 or higher toxicities, possibly/probably related to cabozantinib, included fatigue, nausea, transaminitis, and electrolyte imbalance. No patients had a marrow response according to formal criteria, but 4 had peripheral blast reductions; 2 of these 4 patients transiently cleared circulating blasts. One patient experienced a reduction in marrow blasts, and 1 had stable disease. The FLT3-inhibitory activity of plasma samples, as assessed with the PIA, revealed potent and sustained inhibition in FLT3/ITD and, notably, F691 tyrosine kinase domain (TKD)–mutant cells.

CONCLUSIONS

Cabozantinib is well tolerated in AML patients at an MTD of 40 mg daily and is a potent inhibitor of FLT3/ITD- and F691 TKD–altered tyrosine kinases. Cancer 2017. © 2017 American Cancer Society.

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Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ

BACKGROUND

The current study was conducted to examine the association between ipsilateral breast tumor recurrence (IBTR) and the timing of radiotherapy (RT) in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS).

METHODS

Women with DCIS who were treated with BCS and RT from 1980 through 2010 were identified from a prospectively maintained database. IBTR rates, measured from the time of RT completion, were compared between those who initiated RT ≤8 weeks, >8 to 12 weeks, and >12 weeks after the completion of surgery. The association between RT timing and IBTR was evaluated by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis.

RESULTS

A total of 1323 women met the inclusion criteria. The median follow-up was 6.6 years, with 311 patients followed for ≥10 years. A total of 126 IBTR events occurred. Patients were categorized by RT timing: 806 patients (61%) with timing of ≤8 weeks, 386 patients (29%) with timing of >8 to 12 weeks, and 131 patients (10%) with timing >12 weeks. The 5-year and 10-year IBTR rates were 5.8% and 13.0%, respectively, for RT starting ≤8 weeks after surgery; 3.8% and 7.6%, respectively, for RT starting >8 to 12 weeks after surgery; and 8.8% and 23.0%, respectively, for an RT delay >12 weeks after surgery (P = .004). On multivariable analysis, menopause (hazard ratio [HR], 0.54; P = .0009) and endocrine therapy (HR, 0.45; P = .002) were found to be protective against IBTR, whereas a delay in RT >12 weeks compared with ≤8 weeks was associated with a higher risk of IBTR (HR, 1.92; P = .014). There was no difference in IBTR noted between RT initiation at ≤8 weeks and initiation at >8 to 12 weeks after BCS (P = .3).

CONCLUSIONS

A delay in RT >12 weeks is associated with a significantly higher risk of IBTR in women undergoing BCS for DCIS. Efforts should be made to avoid delays in starting RT to minimize the risk of disease recurrence. Cancer 2017. © 2017 American Cancer Society.

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Clinical impact of colonization with multidrug-resistant organisms on outcome after allogeneic stem cell transplantation in patients with acute myeloid leukemia

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

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Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2017. © 2017 American Cancer Society.

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Cabozantinib is well tolerated in acute myeloid leukemia and effectively inhibits the resistance-conferring FLT3/tyrosine kinase domain/F691 mutation

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

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Delay in radiotherapy is associated with an increased risk of disease recurrence in women with ductal carcinoma in situ

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

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The Floor Is Not Stable

When you get cancer, you will seek the silver linings.

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Association of pN Staging With Survival in Non–Small Cell Lung Cancer

This study determines whether survival was affected by more stringent definitions of pathologic nodal staging quality in a cohort of patients with non–small cell lung cancer who underwent resection with curative intent.

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Survival of N Category–Stratified Non–Small Cell Lung Cancer

Lymph node staging is one of the most important factors determining the prognosis of resected non–small cell lung cancer (NSCLC), the other being an R0 resection. Pathologic lymph node (pN) assessment is more accurate than clinical assessment, and the thoroughness of pN examination affects the prognostic value. As Asamura et al point out, the International Association for the Study of Lung Cancer noted differences in prognosis for pN classification depending on geographic location. No universally accepted guidelines exist for what constitutes an adequate (thorough) pN examination. The National Comprehensive Cancer Network recommends a minimum of 3 or more mediastinal nodal stations, the American College of Surgeons Commission on Cancer recommends 10 total lymph nodes regardless of station, and the Union for International Cancer Control seventh edition recommends 6 total nodes, 3 from N1 and 3 from N2 stations.

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Propranolol for Off-Label Treatment of Patients With Melanoma

This study compares rates of disease progression and overall survival in patients with melanoma treated with propranolol vs not treated with propranolol.

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Immunoglobulin G Fragment C Receptor Polymorphisms in Solid Tumors

To the EditorFCGR3A and FCGR2A gene polymorphisms have been associated with differential binding affinity to IgG and with prediction of response to monoclonal antibody (mAb) therapy. Gavin and colleagues performed a retrospective evaluation of these polymorphisms in a randomized trial of adjuvant chemotherapy with or without trastuzumab (anti-ERBB2/HER2 mAb) in patients with surgically resected node-positive, HER2-positive breast cancer. As expected, they observed that homozygous low-affinity FCGR3A-158 phenylalanine/phenylalanine (F/F) patients received less benefit from trastuzumab than patients with higher-affinity alleles (valine [V]/F or V/V). However, in an exploratory analysis in the nontrastuzumab control arm, patients with FCGR3A-158 V/F or V/V had worse prognosis than patients with F/F. The authors moreover suggested that the differential binding affinity of FCGR proteins to intrinsic antibodies may result in differential benefit from chemotherapy alone.

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